ergoline and Pituitary-Neoplasms

Resistance to dopamine agonists is not uncommonly seen in prolactinomas. However, development of resistance to dopamine agonists after an initial period of robust treatment response is rare, and only 39 cases have been reported in the past four decades. We describe a Chinese man with this rare condition and explored the postulated mechanisms that may explain this phenomenon. We compiled similar cases that were previously reported and compared their etiology, progress, and response to treatment. On the basis of these cases, we derived a list of differential diagnoses to consider in patients with secondary resistance to dopamine agonists.. A 63-year-old Chinese man presented with blurred vision and was subsequently diagnosed with a macroprolactinoma. He had initial response to cabergoline but developed secondary resistance to it after 5 years. The prolactinoma continued to grow, and his serum prolactin remained markedly elevated despite adherence to escalating dosages of cabergoline up to 6 mg/week. The patient finally underwent transsphenoidal surgery and was found to have a sparsely granulated lactotroph tumor with Ki-67 index of 5%. Postoperatively, there was improvement in his serum prolactin level, although he still required treatment with cabergoline at 6 mg/week.. Surgery can facilitate disease control in patients with prolactinomas that develop secondary resistance to dopamine agonists. Malignant prolactinoma is an important differential diagnosis in this group of patients, especially when serum prolactin remains markedly elevated despite resolution or stability of the primary pituitary lesion, suggesting a metastatic source of prolactin secretion.

Topics: Cabergoline; Dopamine Agonists; Ergolines; Humans; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma

Prolactinomas are the most common pituitary tumor histotype, with microprolactinomas being prevalent in women and macroprolactinomas in men. Hyperprolactinemia is among the most common causes of hypogonadotropic hypogonadism in both sexes, prompting medical advice for hypogonadism (infertility, oligo-amenorrhea, impotence, osteoporosis/osteopenia) in both sexes, and for signs and symptoms of mass effects (hypopituitarism, visual loss, optic chiasm compression, cranial nerve deficits, headaches) predominantly in men. Diagnostic workup involves a single prolactin measurement and pituitary imaging, but some laboratory artifacts (ie, the "hook effect" and macroprolactin) can complicate or delay the diagnosis. The treatment of choice for prolactinomas is represented by dopamine agonists, mainly cabergoline, which are able to induce disease control, restore fertility in both sexes, and definitively cure one-third of patients, thus permitting treatment discontinuation. Pregnancy and menopause may promote spontaneous prolactin decline and anticipate cabergoline discontinuation in women. Surgery and/or radiotherapy are indicated in case of resistance to cabergoline not overcome by the increase in drug dose up to the maximally tolerated or the patient's personal choice of surgery. The evidence of resistance to cabergoline in invasive and proliferative tumors may indicate biological aggressiveness, thus requiring alternative therapeutic approaches mainly based on temozolomide use as monotherapy or combined with radiotherapy. In uncontrolled patients, new medical approaches (alternative hormonal treatments, cytotoxic drugs, peptide receptor radionuclide therapy, mTOR/Akt inhibitors, tyrosine kinase inhibitors, or immunotherapy) may be offered but the experience collected to date is still very scant. This article reviews different facets of prolactinomas and discusses approaches to the condition in more common clinical situations.

Topics: Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Hypogonadism; Male; Pituitary Neoplasms; Pregnancy; Prolactin; Prolactinoma

Dopamine agonists (DA) are the gold-standard for prolactinoma and hyperprolactinemia treatment. Intolerance to DA leading to drug drop out occurs in 3 to 12% of cases. We provide here a review of published data about DA intolerance and present a case report concerning the use of intravaginal cabergoline.. We review the literature on the definition, the pathogenesis, frequency and management of DA intolerance. In addition, the review provides strategies to enhance tolerability and avoid precocious clinical treatment withdrawal.. Cabergoline is often cited as the most tolerable DA and its side effects tend to ameliorate within days to weeks. Restarting the same drug at a lower dose or switching to another DA can be used in cases of intolerance. The vaginal route can be tried specifically if there are gastrointestinal side effects in the oral administration. Symptomatic treatment could be attempted, although mainly based on a strategy used in other diseases.. Due to limited data, no guidelines have been developed for the management of intolerance in DA treatment. The most frequent management is to perform transsphenoidal surgery. Nevertheless, this manuscript provides data derived from published literature and expert opinion, suggesting new approaches to this clinical issue.

Topics: Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactinoma

Paediatric prolactinomas are rare. The aim of this study was to investigate the clinical features and outcome of paediatric patients with prolactinomas.. In this single-centre retrospective analysis, clinical, biochemical, and radiological features of all paediatric patients with pituitary adenomas diagnosed between 2000 and 2016 were evaluated.. Among 21 patients with pituitary adenomas, 12 patients with prolactinomas (median age 14.2 years, range 11-16.6 years, 8 females, 4 males) were identified (7 macro- and 5 microprolactinomas). The most common clinical symptoms were headaches (67%) and pubertal delay (67%). All patients with macroprolactinomas with prolactin concentrations >10,000 mU/L had at least 1 pituitary hormone deficiency. Cabergoline as first-line treatment (n = 11, median follow-up of 37 months, range 12-89 months) induced normoprolactinemia (n = 8), reduced the mean tumour volume by 80%, and ameliorated headaches (p = 0.016) and pubertal delay (p = 0.031), whereas intermittent moderate side effects occurred in 55%.. Adolescents with headaches and pubertal delay should be investigated for prolactinomas. Treatment with cabergoline is well tolerated and effective in reducing clinical symptoms and prolactin concentrations was well as inducing tumour shrinkage. Further clinical prospective studies are needed to standardize paediatric treatment modalities.

Topics: Adolescent; Antineoplastic Agents; Cabergoline; Child; Ergolines; Female; Germany; Humans; Male; Pituitary Neoplasms; Prolactinoma; Retrospective Studies

Acromegaly, a rare disease due to growth hormone (GH) hypersecretion by a pituitary adenoma, is associated with severe comorbidity and premature death if not adequately treated. The usual first-line treatment is surgery. Various drugs, including somatostatin receptor ligands, dopamine agonists and GH receptor antagonists, are now available for use if surgery fails to suppress GH/IGF-I hypersecretion. Cabergoline, now the preferred dopamine agonist for treating hyperprolactinemia, is also used off-label for treating acromegaly. Cabergoline monotherapy is reported to normalize IGF-I levels in more than one-third of patients with acromegaly. When a somatostatin receptor ligand proves ineffective, cabergoline add-on therapy normalizes the IGF-I level in 40-50% of patients. Finally, when combined with the GH receptor antagonist pegvisomant in patients with mild uncontrolled disease, cabergoline helps to achieve normal IGF-I levels while avoiding the need for high-dose pegvisomant. Cabergoline is also inexpensive and well tolerated; in particular, it does not appear to promote heart valve disease.

Topics: Acromegaly; Cabergoline; Dopamine Agonists; Ergolines; Human Growth Hormone; Humans; Pituitary Neoplasms; Receptors, Somatostatin

Prolactinomas are the most common hormone-secreting pituitary tumors, accounting for approximately 40% of all pituitary tumors. Infertility, gonadal and sexual dysfunction are usually the most relevant clinical features in both sexes.. This review focuses on safety and tolerability of therapeutic approaches for prolactinomas. Complications from trans-sphenoidal surgery vary depending on tumor size, and mortality rate ranges 0.6%-31% for patients with microprolactinomas and macroprolactinoms, respectively. More than 50% of patients receiving pituitary radiotherapy will develop at least one hormone deficiency within the following decade, whereas cerebrovascular accidents, second brain tumors and optic neuropathy rarely occur. Nowadays, treatment of prolactinomas is based on dopamine-agonists (DA), mainly cabergoline (CAB). Whether CAB is associated with an increased risk of clinically relevant cardiac valvulopathy in patients with prolactinomas as in those with Parkinson's disease (PD), is still debated. In most studies, CAB has been found not to be associated with an increased risk of significant valvulopathy in prolactinomas, and no correlation has been shown between valvular abnormalities and CAB duration or cumulative dose.. DA are safe and well tolerated, and the main safety concerns are related to the potential risk of clinically relevant valvulopathy following treatment with CAB, rarely occurring in patients with prolactinomas.

Topics: Animals; Antineoplastic Agents; Cabergoline; Dopamine Agonists; Drug-Related Side Effects and Adverse Reactions; Ergolines; Humans; Pituitary Neoplasms; Prolactinoma; Safety

Present recommendations by the US Food and Drug Administration advise that patients with prolactinoma treated with cabergoline should have an annual echocardiogram to screen for valvular heart disease. Here, we present new clinical data and a systematic review of the scientific literature showing that the prevalence of cabergoline-associated valvulopathy is very low. We prospectively assessed 40 patients with prolactinoma taking cabergoline. Cardiovascular examination before echocardiography detected an audible systolic murmur in 10% of cases (all were functional murmurs), and no clinically significant valvular lesion was shown on echocardiogram in the 90% of patients without a murmur. Our systematic review identified 21 studies that assessed the presence of valvular abnormalities in patients with prolactinoma treated with cabergoline. Including our new clinical data, only two (0·11%) of 1811 patients were confirmed to have cabergoline-associated valvulopathy (three [0·17%] if possible cases were included). The probability of clinically significant valvular heart disease is low in the absence of a murmur. On the basis of these findings, we challenge the present recommendations to do routine echocardiography in all patients taking cabergoline for prolactinoma every 12 months. We propose that such patients should be screened by a clinical cardiovascular examination and that echocardiogram should be reserved for those patients with an audible murmur, those treated for more than 5 years at a dose of more than 3 mg per week, or those who maintain cabergoline treatment after the age of 50 years.

Topics: Adult; Antineoplastic Agents; Cabergoline; Dopamine Agonists; Echocardiography; Ergolines; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma

Cabergoline is a recommended first-line dopamine agonist for prolactinoma treatment, which is withdrawable for some cases. However, the optimal withdrawal strategy and the accurate recurrence rate associated with cabergoline withdrawal remains uncertain.. To assess the current recurrence rate of hyperprolactinemia and possible favorable factors associated with cabergoline withdrawal in prolactinoma patients.. The databases of PubMed, EMBASE, and Web of Science were searched up to May 2014 to identify studies containing data of recurrent hyperprolactinemia in prolactinoma patients after cabergoline withdrawal. Meta-analysis, including sensitivity analysis, meta-regression analysis, and subgroup analysis were performed.. When the patients who received cabergoline withdrawal were pooled, it was found that the hyperprolactinemia recurrence rate was 65% by a random effects meta-analysis [95% confidence interval 55-74%]. In a random effects meta-regression adjusting for optimal withdrawal strategies, CAB dose reduced to the lowest level before withdrawal was associated with treatment success (p = 0.006), whereas CAB treatment longer than 2 years showed no trend of effect (p = 0.587). Patients who received the lowest CAB dose and presented a significant reduction in tumor size before withdrawal were more likely to achieve the best success (p < 0.001).. Our meta-analysis shows that hyperprolactinemia recurs after cabergoline withdrawal in a majority of patients. The probability of success favors patients who have achieved normoprolactinemia and considerable reduction in tumor size by low dose of cabergoline treatment. In addition, our study further suggests that a beneficial strategy is associated with tapering CAB dose before withdrawal but not with CAB treatment duration longer than 2 years.

Topics: Biomarkers, Tumor; Cabergoline; Dopamine Agonists; Drug Administration Schedule; Ergolines; Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactin; Prolactinoma; Recurrence; Time Factors; Treatment Outcome; Tumor Burden

Cabergoline (CAB) is widely used for the medical treatment of pituitary tumors, particularly those associated with hormone hypersecretion. Whether treatment with CAB is associated with an increased risk of clinically relevant cardiac valve disease in patients with pituitary tumors is still debated. In most studies, CAB has been found not associated with an increased risk of significant valvulopathy, and no correlation has been shown between valvular abnormalities and CAB duration or cumulative dose. This review provides an overview of the studies reporting on the outcome of CAB in terms of cardiac valve disease in patients with pituitary tumors.

Topics: Acromegaly; Cabergoline; Dopamine Agonists; Ergolines; Heart Valve Diseases; Humans; Pituitary Neoplasms; Prolactinoma

The authors present an update on the various treatment modalities and discuss management strategies for prolactinomas. Prolactinomas are the most common type of functional pituitary tumor. Effective hyperprolactinemia treatment is of great importance, due to its potential deleterious effects including infertility, gonadal dysfunction and osteoporosis. Dopamine agonist therapy is the first line of treatment for prolactinomas because of its effectiveness in normalizing serum prolactin levels and shrinking tumor size. Though withdrawal of dopamine agonist treatment is safe and may be implemented following certain recommendations, recurrence of disease after cessation of the drug occurs in a substantial proportion of patients. Concerns regarding the safety of dopamine agonists have been raised, but its safety profile remains high, allowing its use during pregnancy. Surgery is typically indicated for patients who are resistant to medical therapy or intolerant of its adverse side effects, or are experiencing progressive tumor growth. Surgical resection can also be considered as a primary treatment for those with smaller focal tumors where a biochemical cure can be expected as an alternative to lifelong dopamine agonist treatment. Stereotactic radiosurgery also serves as an option for those refractory to medical and surgical therapy.

Topics: Bromocriptine; Cabergoline; Disease Management; Dopamine Agonists; Drug Administration Schedule; Drug Resistance, Neoplasm; Ergolines; Female; Humans; Hyperprolactinemia; Magnetic Resonance Imaging; Neoplasm Recurrence, Local; Neuroendoscopy; Pituitary Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Prolactin; Prolactinoma; Radiosurgery; Sphenoid Sinus

Hyperprolactinemia is associated with bone fragility. Traditionally attributed to prolactin-induced hypogonadism, recent studies have identified increased fracture rates independent of gonadal function.. We performed a systematic review to identify studies assessing fracture risk in patients with untreated hyperprolactinemia compared to those on dopamine agonists. MEDLINE, EMBASE, Cochrane, Web of Science and BIOSIS Previews databases were searched from inception to December 2013 for studies of hyperprolactinemia with fractures as an outcome. Two authors independently performed title and abstract searches, full-text searches, data abstraction, and quality assessment. A summary odds ratio (OR) was calculated using a random effects model.. Of the 197 articles identified, 2 met inclusion criteria. Both cross-sectional studies examined cabergoline use (or non-use) in patients with prolactin-secreting adenomas, with vertebral fractures as the primary outcome. For women, vertebral fractures were identified in 46% of untreated patients, vs. 20% of patients on cabergoline (OR: 0.29, 95% CI: 0.10-0.78). For men, the results were 67% in untreated, vs. 26% in cabergoline treated patients (OR: 0.18, CI: 0.03-0.94), with no difference between gonadal and hypogonadal men (p=0.8). Combining studies gave a summary odds ratio of 0.25 (CI: 0.11-0.59), I2=0%.. In the limited studies available, fracture prevalence was increased in patients with untreated hyperprolactinemia compared to those on treatment, independent of gonadal function. Further studies are needed to clarify if post-menopausal women, or high-risk men, with no other indication for treatment, should be on dopamine agonists to decrease fracture risk.

Topics: Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Hyperprolactinemia; Hypogonadism; Male; Odds Ratio; Osteoporotic Fractures; Pituitary Neoplasms; Prevalence; Prolactinoma; Sex Factors; Spinal Fractures

Meningitis is an uncommon complication of an untreated pituitary macroadenoma. Meningitis may occur in patients with macroadenomas who have undergone transsphenoidal surgery and radiotherapy and is usually associated with rhinorrhea. Less commonly, cerebrospinal fluid rhinorrhea has been reported as a complication of treatment of prolactinomas by dopamine agonists. Cerebrospinal fluid rhinorrhea in cases of untreated pituitary macroadenoma is reported only in isolated cases. Acute bacterial meningitis without rhinorrhea in patients with an untreated pituitary macroadenoma is an exceptional finding with only three previously reported cases.. A 31-year-old male was urgently admitted for headache, fever and visual loss. Neuroimaging disclosed an invasive pituitary lesion. Cerebrospinal fluid leakage was not clinically detected. Lumbar puncture showed acute meningitis. Blood tests revealed increased inflammatory markers, a serum prolactin of 9000 ng/ml (2.5-11 ng/ml) and panhypopituitarism. Intravenous antibiotics and hydrocortisone replacement therapy were initiated, leading to a favorable clinical outcome. An endoscopic transsphenoidal debulking procedure was performed, it showed that the sphenoid floor was destroyed and the sinus occluded by a massive tumor.. Meningitis should be ruled out in patients with a pituitary mass who present with headache and increased inflammatory tests, even in the absence of rhinorrhea.

Topics: Adult; Anti-Bacterial Agents; Blindness; Cabergoline; Combined Modality Therapy; Ergolines; Fever; Headache; Hormone Replacement Therapy; Humans; Hydrocortisone; Hypophysectomy; Hypopituitarism; Male; Meningitis, Aseptic; Neoplasm Invasiveness; Pituitary Neoplasms; Prolactinoma; Sella Turcica; Third Ventricle; Thyroxine

Hyperprolactinemia, frequently caused by a prolactinoma, is an important cause of infertility among young women. Dopamine agonists (DA) are the treatment of choice. Although cabergoline (CAB) is currently considered the gold standard DA, bromocriptine (BRC) remains the drug of choice for women desiring pregnancy, as it was proven to be safe in more than 6,000 pregnancies. The purpose of this review is to perform a critical evaluation of CAB safety in pregnancy, as it is used by most patients harboring prolactinomas. Although the number of CAB-induced pregnancies (about 800) is still reduced as compared with those under BRC treatment, data in the literature do not point to increase risk of preterm delivery or fetal malformations, comparing to pregnancies induced by BRC and those in the general population. Moreover, CAB use throughout pregnancy was reported in about ten cases, without evidence of any harm to fetal development. Therefore, even though BRC still remains the recommended DA drug for pregnancy induction or use during pregnancy in women with prolactinomas, increasing evidences point to the safety of CAB for this purpose.

Topics: Animals; Antineoplastic Agents; Cabergoline; Ergolines; Female; Fetal Development; Humans; Hyperprolactinemia; Infertility, Female; Pituitary Neoplasms; Pregnancy; Prolactinoma

Giant prolactinomas are an unusual subset of macroprolactinomas and are more commonly found in men. The goal of this review is to propose a giant prolactinoma definition and discuss the available therapeutic options for biochemical and tumour volume control.. A comprehensive search of all published studies was performed between April and November 2012 in electronic databases (PubMed and Ovid).. A giant prolactinoma should be defined as an adenoma with a maximum diameter of more than 4 cm that is associated with serum prolactin above 5300 mIU/l. Regarding treatment, cabergoline is the preferred dopamine agonist for medical management of giant prolactinomas because of its excellent efficacy and tolerability. Normalization of prolactin level and significant tumour reduction may be achieved in the majority of patients. Combined therapy, particularly cabergoline and surgery, may be necessary due to the large tumour load. Radiotherapy and temozolomide may be used for patients with aggressive giant prolactinomas in whom tumour volume control is not achieved with cabergoline and surgery.. There is a scarcity of large studies about the management of giant prolactinoma. Cabergoline is the first-line treatment. However, caution should be exercised when comparing efficacy rates among the different treatment modalities due to the variability in study design and data quality. In this scenario, a 'standard' definition for giant prolactinomas and larger series may be helpful to assess the real efficacy and safety of each therapeutic modality.

Topics: Cabergoline; Combined Modality Therapy; Dopamine Agonists; Ergolines; Humans; Pituitary Gland; Pituitary Neoplasms; Prolactin; Prolactinoma; Treatment Outcome; Tumor Burden

Prolonged overproduction of growth hormone, like insulin-like growth factor-1 hypersecretion leads to acromegaly in adults. This is associated with several co-morbidities and increased mortality. Despite typical clinical features and modern diagnostic tools, it often takes years to diagnose from the onset of the disease. The aims of the treatment are to reduce or control tumour growth, inhibit growth hormone hypersecretion, normalize insulin-like growth factor-1 levels, treat co-morbidities and, therefore, reduce mortality. There are three approaches for therapy: surgery, medical management (dopamine agonists, somatostatin analogues and growth hormone receptor antagonist), and radiotherapy. Efficient therapy of the disease is based on the appropriate multidisciplinary team management. The review provides a summary of medical treatment for acromegaly.. Az acromegalia a növekedési hormon, ennélfogva az inzulinszerű növekedési faktor-1 tartós túltermelése következtében kialakuló betegség felnőttekben, amely számos szövődménnyel jár és megfelelő kezelés nélkül a mortalitás növekedéséhez vezet. Jellegzetes tünetei ellenére, valamint a korszerű biokémiai és képalkotó diagnosztikai módszerek mellett is általában több év telik el a betegség kialakulásának kezdete és a diagnózis felállítása között. Terápiás lehetőségként sebészi beavatkozás, gyógyszeres (dopaminagonista, szomatosztatinanalóg és növekedésihormonreceptor-antagonista) kezelés és radioterápia áll rendelkezésre. A kezelés célja a biztonságos növekedési hormon- és inzulinszerű növekedési faktor-1-szintek elérése, a tumor eltávolítása vagy méretének csökkentése, valamint a betegség szövődményeinek kezelése, végső fokon a mortalitás csökkentése. Az eredményes kezelés több különböző diszciplína képviselőjének megfelelő együttműködésén alapszik. A közleményben a szerző az acromegalia gyógyszeres kezelési lehetőségeit tekinti át. Orv. Hetil., 2013, 154, 1527–1534.

Topics: Acromegaly; Aminoquinolines; Antineoplastic Agents, Hormonal; Bromocriptine; Cabergoline; Dopamine Agonists; Drug Administration Schedule; Drug Therapy, Combination; Ergolines; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Interdisciplinary Communication; Membrane Proteins; Octreotide; Patient Care Team; Peptides, Cyclic; Pituitary Neoplasms; Somatostatin

Pituitary apoplexy is a rare medical emergency which results from hemorrhage or infarction in the pituitary gland. One of the predisposing factors is treatment with dopamine agonists, especially bromocriptine. We report a 20-year-old Chinese man with prolactinoma who developed pituitary apoplexy 6 weeks after initiation of cabergoline. He was treated conservatively with supportive therapy, and recovered well with no loss of pituitary function. A literature search was conducted and a review of the reported patients with pituitary apoplexy during treatment with dopamine agonists is discussed.

Topics: Antineoplastic Agents; Cabergoline; Dopamine Agonists; Ergolines; Humans; Male; Pituitary Apoplexy; Pituitary Neoplasms; Prolactinoma; Young Adult

Somatostatin analogues are the cornerstone in the first-line and adjuvant (postsurgical) therapy in patients with acromegaly. These drugs highly effectively decrease serum concentrations of growth hormone (GH) and insulin-like growth factor type I (IGF-I), as well as pituitary adenoma size. However, in approximately one third of patients response to these agents is unsatisfactory. The optimization of the medical therapy for acromegaly can be accomplished by modifying the dose or the interval of administration of somatostatin analogues or by combining other pharmacological agents. Increasing the dose or frequency of administration is followed by an additional decrease in GH and IGF-I levels in a significant percentage of patients. These changes are not accompanied by a relevant increase in the number or severity of adverse events. Combined treatment with somatostatin analogues and pegvisomant has been shown to significantly reduce serum IGF-I levels in patients with inadequate control of disease activity. The addition of cabergoline to somatostatin analogue therapy is accompanied by a further decrease in IGF-I levels that is independent of serum prolactin concentrations.

Topics: Acromegaly; Cabergoline; Combined Modality Therapy; Dopamine Agonists; Dosage Forms; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Ergolines; Growth Hormone-Secreting Pituitary Adenoma; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Octreotide; Peptides, Cyclic; Pituitary Neoplasms; Randomized Controlled Trials as Topic; Receptors, Somatotropin; Somatostatin; Treatment Outcome

Double pituitary adenomas represent up to 2.6 % of pituitary adenomas in large surgical series and up to 3.3 % of patients with Cushing's disease have been found to have double or multiple pituitary adenomas. We report the case of a 60-year-old male patient whose medical history began in 2002 with erectile dysfunction; hyperprolactinemia was found and MRI showed a 6-mm area of delayed enhancement in the lateral portion of the right pituitary lobe. Treatment with cabergoline was started with normalization of prolactin levels; the following MRI, performed in 2005 and 2008, showed shrinkage of the pituitary lesion. In 2005, the patient began to manifest weight gain, hypertension, and facial plethora, but no further evaluations were done. In January 2010, the patient came to our attention and underwent multiple tests that suggested Cushing's disease. A new MRI was negative. Bilateral inferior petrosal sinus sampling showed significant pituitary-to-peripheral ratio and, in May 2010, the patient underwent exploratory pituitary surgery with evidence of a 1-2-mm white-coloured midline area compatible with pituitary adenoma that was surgically removed. Post-operatively, the patient's clinical conditions improved with onset of secondary hypoadrenalism. The histologic examination confirmed a pituitary adenoma (immunostaining was found to be positive for ACTH and negative for prolactin). We report the case of an ACTH-producing microadenoma metachronous to a prolactin secreting microadenoma although not confirmed histologically, shrunk by medical treatment. A review of data in the literature regarding double or multiple pituitary adenomas has also been done.

Topics: Adenoma; Antineoplastic Agents; Cabergoline; Combined Modality Therapy; Comorbidity; Ergolines; Humans; Male; Middle Aged; Neoplasms, Multiple Primary; Neurosurgical Procedures; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Treatment Outcome

New information has been provided over the last years regarding treatment of prolactinomas and will be reviewed in this update. Medical treatment with a dopamine agonist (DA) remains the cornerstone of therapy and cabergoline is the first choice, due to its high efficacy and good tolerability profile. Prolonged remission after discontinuation of DA may be observed if treatment has been given for at least two years, normal prolactin has been obtained with a low dose and tumoral diameter has been reduced by at least 50%. Although the risk of restrictive cardiac valve disease is low at the standard doses of cabergoline used for the treatment of hyperprolactinaemia, long-term echocardiographic surveillance is however indicated, in particular in resistant patients who need higher doses of cabergoline (2.0 mg/week or more). Neurosurgical treatment of prolactinomas is less effective than medical therapy and recurrence of hyperprolactinaemia is frequent. Besides classical indications such as drug intolerance, resistance or acute complications, new indications have emerged such as young patients with a high likelihood of complete tumour resection and who do not wish to take prolonged medical treatment, or patients who require high doses of cabergoline, in whom surgical debulking may significantly improve postoperative hormonal control. Finally, recent data indicate that cabergoline is safe for the developing foetus and for the mother, and therefore should not be preventively withdrawn in a young woman wishing to become pregnant.

Topics: Cabergoline; Contraindications; Dopamine Agonists; Endocrinology; Ergolines; Female; Humans; Magnetic Resonance Imaging; Male; Neurosurgical Procedures; Pituitary Neoplasms; Pregnancy; Prolactin; Prolactinoma

Hyperprolactinemia is a condition characterised by an increase of prolactin blood levels (more than 100-200 ng/ml). It is the most common endocrine disorder of the hypothalamic-pituitary axis. The clinical characteristics of the headache-hyperprolactinemia-hypophyseal-adenoma association are discussed, the various diagnostic and treatment possibilities are explored and the etiology of the headache is considered in the light of several pathogenetic possibilities. We present two cases. (1) A 35-year-old woman suffering from chronic tension-type headache interspersed with occasional episodes of migraine without aura (as defined by the International Headache Society criteria). She had also suffered menstrual cycle alterations since the age of 16. At the age of 30 she developed amenorrhea with hyperprolactinemia. Computed tomography (CT) and magnetic resonance imaging (MRI) scans revealed a median-left intrasellar mass. Treatment with cabergoline resulted in complete resolution of both types of headache and the menstrual cycle and prolactin levels returned to normal. The therapy also reduced the volume of the tumour. (2) The second case relates to a 47-year-old man who had been suffering from tension-type headaches for almost 3 months. The patient had never previously suffered from headaches. CT and MRI scans showed a large sellar and suprasellar lesion with raised serum prolactin levels. Treatment with cabergoline had significantly reduced the prolactin levels and had also improved the patient's headaches. High-resolution CT, with and without contrast, or MRI is necessary to visualise microprolactinomas (and other sellar lesions) and confirm the diagnosis.

Topics: Adult; Amenorrhea; Antineoplastic Agents; Cabergoline; Ergolines; Female; Humans; Hyperprolactinemia; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Tension-Type Headache; Tomography, X-Ray Computed; Treatment Outcome

Hypercortisolism induced by Cushing disease causes high morbidity and mortality. The treatment of choice is pituitary surgery, but it often fails to achieve cure, and other treatment modalities (radiotherapy, bilateral adrenalectomy) may therefore be required. If these treatments are not effective or while waiting for their results, hypercortisolism should be controlled with drugs. The classical drug treatments are those that act by inhibiting cortisol secretion by the adrenal gland (ketoconazole, metyrapone, mitotane, etomidate). The preliminary results of a new drug (LCI699) which is a potent enzyme inhibitor of cortisol secretion have been reported. A clinical trial of the safety and efficacy of mifepristone, a glucocorticoid receptor antagonist, has just been published. The drugs deserving more attention today are those with a direct action on the tumor by inhibiting ACTH secretion: somatostatin analogues (pasireotide), dopamine agonists (cabergoline), PPAR-γ, and retinoic acid. A special review is made of the available clinical trials with pasireotide and cabergoline.

Topics: Adenoma; Adrenocorticotropic Hormone; Animals; Cabergoline; Clinical Trials as Topic; Clinical Trials, Phase III as Topic; Drug Evaluation, Preclinical; Ergolines; Etomidate; Humans; Hydrocortisone; Imidazoles; Ketoconazole; Metyrapone; Mice; Mifepristone; Mitotane; Multicenter Studies as Topic; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; PPAR gamma; Pyridines; Rats; Somatostatin; Therapies, Investigational; Tretinoin

Primary resistance to dopamine agonists occurs in 10-15% of prolactinomas but secondary resistance following initial biochemical and anti-proliferative response is very rare and has only been hitherto described in four previous cases, two with bromocriptine and two with cabergoline. We describe a case of a 57-year-old woman who presented with a large macroprolactinoma with suprasellar extension. She was initially treated with bromocriptine therapy with a resolution of symptoms, marked reduction in prolactin concentration and complete tumour shrinkage; a response which was subsequently maintained on cabergoline. After 8 years of dopamine agonist therapy, her prolactin concentration began to rise and there was symptomatic recurrence of her tumour despite escalating doses of cabergoline up to 6 mg weekly. Non-compliance was outruled by observed inpatient drug administration. The patient underwent surgical debulking followed by radiotherapy with good response. This case adds to the previous two cases of secondary resistance to cabergoline therapy in prolactinomas a marked initial response. While the mechanism of secondary resistance remains unknown and not possible to predict, close observation of prolactinoma patients on treatment is necessary.

Topics: Antineoplastic Agents; Cabergoline; Drug Resistance, Neoplasm; Drug Tolerance; Ergolines; Female; Humans; Middle Aged; Pituitary Neoplasms; Prolactinoma

Prolactinomas are the most common pituitary adenomas in children and adolescents followed by adrenocorticotropic hormone-secreting and growth hormone-secreting adenomas. Females are slightly more affected than males (who have macroadenomas more frequently). Compared with the adult setting, in children macroadenomas are more frequent than microadenomas. Diagnosis is generally based on clinical symptoms of primary or secondary gonadal failure, growth delay and/or tumor compressive symptoms. Treatment is based on medical therapy with dopamine agonists, to control prolactin levels and reduce tumor size. Surgery is indicated in patients with tumors resistant to dopamine agonists as well as in those showing severe neurological symptoms at diagnosis. Radiotherapy should be limited to the cases with aggressive tumors, nonresponsive to dopamine agonists, because of the risk of neurological damage and hypopituitarism later in the lives of these patients.

Topics: Adolescent; Antineoplastic Agents; Cabergoline; Child; Combined Modality Therapy; Ergolines; Growth; Growth Disorders; Humans; Pituitary Neoplasms; Prolactinoma

Topics: Adult; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Neoplastic; Prolactin; Prolactinoma; Visual Fields

Aggressive pituitary adenomas are notoriously difficult to manage due to their size, invasiveness, speed of growth and high frequency of recurrence. Except for prolactinomas, surgery (usually transsphenoidal but sometimes transcranial) is the first-line option, but re-growth of aggressive tumors is almost inevitable and monitoring and repeat surgery is required to control symptoms. In prolactinomas, dopamine agonists are the first-line treatment and they normalize prolactin levels in most patients even with macroprolactinomas. Somatostatin analogues offer another pharmacotherapy for pituitary adenomas either for primary therapy, pre-operatively to reduce the tumor volume and make it more amenable to surgical removal, or post-surgery to control re-expansion. When surgery and pharmacotherapy fail, radiotherapy is a useful third-line strategy that reduces recurrence, while extreme pituitary adenomas with metastases may potentially be managed with chemotherapy (although more data are needed). A combination of these therapies will be required for aggressive pituitary adenomas and careful follow-up is essential.

Topics: Cabergoline; Dacarbazine; Dopamine Agonists; Ergolines; Female; Humans; Male; Pituitary Neoplasms; Somatostatin; Temozolomide

Recent molecular pathological investigations have elucidated the cytodifferentiation of pituitary cells and identified several transcriptional factors that regulate this cytodifferentiation of pituitary cells. The patterns of cytodifferentiation are closely related to the pathogenesis of pituitary adenomas. Meanwhile, the role of hypothalamic hormones in the development of pituitary adenomas has recently attracted the attention of investigators. The expression of growth hormone-releasing hormone and corticotrophin releasing hormone in corticotroph adenomas have been demonstrated in somatotroph adenomas and corticotropin adenomas, respectively. This finding indicates that the endogenous expression of hypothalamic hormones and their receptors in human pituitary adenoma cells has ample significance in the autocrine or paracrine regulation of pituitary hormone production and tumor extension induced by hypothalamic hormones produced by adenoma cells. The recent progress in surgical techniques for treatment of pituitary adenomas has provided several alternatives: transsphenoidal surgery vs. transcranial surgery, sublabial approach vs. endonasal approach, and microsurgery vs. endoscopic surgery. There have also been developments in the medical treatment of pituitary adenomas. The frequently used dopamine agonist, cabergoline, is very effective for treating prolactin-producing adenoma. Long-acting octreotide and pegvisomant are now available for the treatment of growth hormone producing adenoma. Cabergoline is also used for growth hormone producing adenoma. Temozolomide has recently been used for atypical adenomas or pituitary carcinomas. Adult growth hormone deficiency sometimes occurs in postoperative patients with pituitary adenomas. Growth hormone replacement is recommended to maintain the quality of life of these patients.

Topics: Adenoma; Antineoplastic Agents; Cabergoline; Corticotropin-Releasing Hormone; Dacarbazine; Ergolines; Growth Hormone-Releasing Hormone; Human Growth Hormone; Humans; Hypothalamic Hormones; Incidental Findings; Neurosurgical Procedures; Octreotide; Pituitary Neoplasms; Prolactinoma; Receptors, Neuropeptide; Receptors, Pituitary Hormone-Regulating Hormone; Temozolomide

Cushing's syndrome is a complex endocrine condition with potential serious complications if untreated or inadequately treated. Transsphenoidal surgery with resection of a pituitary adenoma is successful in 75 - 80% of patients, but approximately 20 - 25% show persistence of Cushing's, and a similar proportion may experience recurrence within 2 - 4 years post-op. When surgery fails, medical treatment can temporarily suppress excessive cortisol production and ameliorate its clinical manifestations while more definitive therapy becomes effective. We describe pharmacological approaches to the treatment of Cushing's syndrome. Drugs used to suppress cortisol secretion are mostly inhibitors of steroidogenesis. Ketoconazole, fluconazole aminoglutethimide, metyrapone, mitotane and etomidate are in that category. Ketoconazole is in current use while other drugs, although mostly available in the past, continue to have a potential role either alone or in combination. Drugs that suppress adrenocorticotropic hormone (ACTH) secretion are less popular as standard treatment and include cyproheptadine, valproic acid, cabergoline, somatostatin analogs, PPAR-gamma agonists, vasopressin antagonists. Some of these drugs have been tested in limited clinical trials but there is potential therapeutic benefit in analogs with better specificity for the class of receptors present in ACTH-secreting tumors. A third category of drugs is glucocorticoid receptor antagonists. Mifepristone is currently being tested in clinical trials in patients with persistent or recurrent Cushing's disease and in patients with metastatic adrenal cortical carcinoma or ectopic ACTH syndrome not amenable to surgery. We also review replacement therapy after surgery and non-specific drugs to treat complications in patients with severe hypercortisol. The review provides a complete survey of the drugs used in the medical treatment of Cushing's, and new advances in the development of pituitary-active drugs as well as receptor blockers of glucocorticoid action. It also provides avenues for exploration of new drugs active on somatostatin, dopamine and vasopressin receptors. There are effective pharmacological agents capable of chronically reversing biochemical and clinical manifestations of hypercortisolemia in Cushing's syndrome but new drugs are needed with action at the pituitary level.

Topics: Adrenal Cortex Neoplasms; Adrenocorticotropic Hormone; Antiparkinson Agents; Cabergoline; Cushing Syndrome; Ergolines; Human Growth Hormone; Humans; Hydrocortisone; Ketoconazole; Metyrapone; Pituitary Hormones; Pituitary Neoplasms

High-dose cabergoline therapy has been related to cardiac valve regurgitation in patients with Parkinson's disease.. To perform a systematic analysis of reports on low-dose cabergoline treatment in hyperprolactinemia and its effect on the cardiac valves.. None of the seven reports analyzed, including 463 patients in total, found clinically significant valve regurgitation. Only one report found moderate tricuspid valve regurgitation, and other two reports found mild tricuspid valve regurgitation. An increase in the mitral tenting area was documented in only one of two reports. Valve thickening and calcifications were found in only one study.. Cabergoline seems to be safe at the doses employed in hyperprolactinemic patients. There is a higher prevalence of tricuspid regurgitation, detected by systematic echocardiography, but this abnormality is asymptomatic. Although prospective longitudinal studies are needed, vigilance of these patients is recommended, especially those treated with high-dose cabergoline.

Topics: Adult; Aged; Antiparkinson Agents; Cabergoline; Case-Control Studies; Dopamine Agonists; Ergolines; Female; Heart Valve Diseases; Humans; Hyperprolactinemia; Male; Middle Aged; Pituitary Neoplasms; Prevalence; Prolactin; Prolactinoma; Ultrasonography

The increased risk of cardiac valve disease in patients treated for Parkinson's disease with cabergoline has raised concerns about the safety of treatment with ergot-derived dopamine agonists in patients with endocrine diseases, especially prolactinoma. Six cross-sectional studies have been published recently, of which five studies do not show an association between the treatment of prolactinoma with cabergoline during 45-79 months and clinically relevant valvular regurgitation in a total of 413 patients. Nonetheless, concern is raised because the use of cabergoline was associated in one study with an increased prevalence of moderate tricuspid regurgitation, and in two other studies with mild tricuspid regurgitation. Furthermore, the use of cabergoline was associated with increased frequencies of valvular thickening, calcifications and increased mitral tenting area. At present, the clinical relevance of these findings is still uncertain, but concern is raised with respect to the safety of the use of cabergoline in the long-term treatment of prolactinomas. Echocardiographic evaluation should be considered in patients, who require long-term treatment with cabergoline, especially in high doses. There is a need for larger, preferably prospective, studies with careful echocardiographic assessment and with longer durations of follow-up than the currently available studies.

Topics: Cabergoline; Clinical Trials as Topic; Dopamine Agonists; Ergolines; Heart Valve Diseases; Humans; Pituitary Neoplasms; Prolactinoma

Any process interfering with dopamine synthesis, its transport to the pituitary gland, or its action at the level of lactotroph dopamine receptors can cause hyperprolactinemia. As described in this article, considering the complexity of prolactin regulation, many factors could cause hyperprolactinemia, and hyperprolactinemia can have clinical effects not only on the reproductive axis. Once any drug effects are excluded, prolactinomas are the most common cause of hyperprolactinemia. The most frequent symptom is hypogonadism in both genders. Medical and surgical therapies generally have excellent results, and most prolactinomas are well controlled or even cured in some cases.

Topics: Bromocriptine; Dopamine Agonists; Ergolines; Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactinoma

Dopamine and somatostatin are both involved in the negative control of normal pituitary cells. Dopamine subtype 2 receptor (D2DR) and somatostatin receptor (sst) agonists, mainly directed to sst2, are used in the treatment of pituitary adenomas. Nevertheless, a majority of corticotroph and gonadotroph adenomas and a third of somatotroph adenomas are still not sufficiently controlled by these treatments. D2DR and sst1, 2, 3 and 5 are present in most pituitary adenomas. These receptors may interact by heterodimerization as shown for sst1-sst5, sst5-D2DR, sst2-sst3 and sst2-D2DR suggesting possible additive effects. D2DR and sst2 agonist cotreatment showed limited additivity on GH secretion in acromegaly. Moreover, new chimeric compounds with sst2, D2DR and sst5 affinity have shown an increased control of secretion and/or proliferation of different types of pituitary adenomas in cell culture. Together with the multi-sst ligand drugs recently developed, these dopamine-somatostatin ligands represent a new opportunity in the combinatory treatment of pituitary adenomas.

Topics: Adenoma; Antineoplastic Agents, Hormonal; Cabergoline; Cell Proliferation; Dopamine; Ergolines; Growth Hormone-Secreting Pituitary Adenoma; Human Growth Hormone; Humans; Octreotide; Pituitary Neoplasms; Protein Multimerization; Receptors, Dopamine D2; Receptors, Somatostatin; Somatostatin; Tumor Cells, Cultured

High prolactin levels can occur as a physiological condition in females who are pregnant or lactating. As a pathological condition, hyperprolactinaemia is associated with gonadal dysfunction, infertility and an increased risk of long-term complications including osteoporosis. The most frequent cause of persistent hyperprolactinaemia is the presence of a micro- (<10mm diameter) or macroprolactinoma (>/=10mm). These pituitary tumours may produce an excessive amount of prolactin or disrupt the normal delivery of dopamine from the hypothalamus to the pituitary; prolactin secretion from the pituitary is inhibited by dopamine released from neurones in the hypothalamus. Medications including anti-psychotics can induce hyperprolactinaemia, while idiopathic hyperprolactinaemia accounts for 30-40% of cases. The prevalence of hyperprolactinaemia is difficult to establish as not all sufferers are symptomatic or concerned by their symptoms and may remain undiagnosed. Symptoms of hyperprolactinaemia include signs of hypogonadism, with oligomenorrhoea, amenorrhoea and galactorrhoea frequently observed. Pharmacological intervention should be considered the first line therapy and involves the use of dopamine agonists to reduce tumour size and prolactin levels. Bromocriptine has the longest history of use and is a well-established, inexpensive, safe and effective therapy option. However, bromocriptine requires multiple daily dosing and some patients are resistant or intolerant to this therapy. The two newer dopamine agonists, quinagolide and cabergoline, provide more effective and better tolerated treatments compared with bromocriptine and may offer effective therapies for bromocriptine-resistant or intolerant patients. Quinagolide can be used until pregnancy is confirmed and may result in improved compliance in females wishing to become pregnant. For patients with hyperprolactinaemia, pregnancy is safe and can frequently be beneficial, inducing a decrease in prolactin levels. There does not appear to be any increased risk of abortion, malformations or multiple births in pregnancies achieved with bromocriptine and this dopamine agonist can be used safely during pregnancy. Surgery should be considered only in certain circumstances, and for the majority of patients, dopamine agonists will be sufficient to alleviate symptoms and restore normal prolactin levels.

Topics: Aminoquinolines; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Hyperprolactinemia; Male; Pituitary Neoplasms; Pregnancy; Prolactinoma

The neurotransmitter/neuromodulator dopamine plays an important role in both the central nervous system and the periphery. In the hypothalamopituitary system its function is a dominant and tonic inhibitory regulation of pituitary hormone secretion including prolactin- and proopiomelanocortin-derived hormones. It is well known that dopamine agonists, such as bromocriptine, pergolide, quinagolide, cabergoline, and lisuride, can inhibit PRL secretion by binding to the D(2) dopamine receptors located on normal as well as tumorous pituitary cells. Moreover, they can effectively decrease excessive PRL secretion as well as the size of the tumor in patients having prolactinoma. Furthermore, dopamine agonists can also be used in other pituitary tumors. The major requirement for its use is that the tumor cells should express D(2) receptors. Therefore, in addition to prolactinomas, targets of dopamine agonist therapy are somatotroph tumors, nonfunctioning pituitary tumors, corticotroph pituitary tumors, Nelson's syndrome, gonadotropinomas, and thyrotropin-secreting pituitary tumors. It is also an option for the treatment of pituitary disease during pregnancy. Differences between the effectiveness and the resistance of different dopaminergic agents as well as the future perspectives of them in the therapy of pituitary tumors are discussed.

Topics: Adenoma; Bromocriptine; Cabergoline; Dopamine; Dopamine Agonists; Ergolines; Humans; Pituitary Neoplasms; Receptors, Dopamine

Prolactinomas are the most frequent pituitary tumors. Treatment of infertility in such tumors usually is very successful. On the other hand, reports of pituitary tumor growth during pregnancy have been described since bromocriptine started to be used. Since then, dopamine agonists (DA) have been increasingly used as the first-choice treatment of prolactinomas, with surgery being reserved for resistance or persistent intolerance to DA or for special situations. More recently other DA, such as quinagolide and cabergoline have shown better tolerance than bromocriptine with similar or greater efficacy. Cabergoline is now the first choice drug but its use in pregnancy is still under evaluation. We followed 71 term pregnancies in women bearing microprolactinomas. Of the 22 patients with previous surgery, none presented symptoms of tumor growth. Of the 41 pregnant patients treated with bromocriptine alone, only one (2.4%) presented with headaches, which regressed with drug reintroduction. Fifty one term pregnancies in patients with macroprolactinomas were followed by us. Of those, 21 were in patients with previous surgery and none of them presented clinical evidence of tumor growth. On the other hand, of the 30 patients treated only with pre-gestational bromocriptine, 11 (37%) manifested complaints related to tumor growth. A non-hormonal contraceptive should be the use along with a DA drug until tumor shrinkage within sellar boundaries has been evidenced. After pregnancy has been confirmed, the DA can be withdrawn and the patient must be closely followed. If tumor expansion is suspected, confirmation can be made through MRI and by visual field testing. Reintroduction of bromocriptine in such cases can lead to tumor reduction and clinical improvement. Surgery can also be employed as treatment for symptomatic tumor growth in pregnancy.

Topics: Aminoquinolines; Bromocriptine; Cabergoline; Child; Dopamine Agonists; Ergolines; Female; Humans; Magnetic Resonance Imaging; Pituitary Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Prolactinoma

Prolactinomas are the most frequent pituitary tumors and their frequency varies with age and sex, occurring most frequently in females between 20-50 yr-old. In men, hyperprolactinaemia is often present for many years without symptoms, as generally the most important symptoms are the decrease in libido and/or sexual potency both underestimated by the majority of the patients. Prolactin (PRL) plays a role in the process of spermatogenesis, and normal serum PRL levels are required for normal testicular function. On the other hand, hyperprolactinaemia has multiple negative effects on the gonadal axis. As a consequences hyperprolactinemic males show alteration of sexual potency and seminal fluid quality. Cabergoline treatments is able to induce normalization of PRL levels and a reduction of tumor mass in the majority of patients and consequently restoring the normal semen quality and ameliorating the quality of life of men with pituitary PRL-secreting adenoma.

Topics: Age Factors; Cabergoline; Dopamine Agonists; Ergolines; Humans; Libido; Male; Pituitary Neoplasms; Prevalence; Prolactin; Prolactinoma; Prostatic Hyperplasia; Semen; Sex Factors; Spermatogenesis; Testis

Pharmacologic resistance to dopamine agonists is defined here as failure to normalize PRL levels and failure to decrease macroprolactinoma size by >or=50%. Failure to normalize PRL levels is found in about one-quarter of patients treated with bromocriptine and 10-15% of those treated with pergolide or cabergoline. Failure to achieve at least a 50% reduction in tumor size occurs in about one-third of those treated with bromocriptine and 10-15% of those treated with pergolide or cabergoline. The cause of dopamine resistance is primarily a decrease in D(2) receptors but the receptors have normal affinity for dopamine. Treatment approaches for patients resistant to dopamine agonists include changing to another dopamine agonist and increasing the dose of the drug as long as there is continued response to the dose increases and no adverse effects with higher doses. Transsphenoidal surgery is also an option. Clomiphene, gonadotropins, and GnRH can be used if fertility is desired. For those not desiring fertility, estrogen replacement may be used unless there is a macroadenoma, in which case control of tumor growth is also an issue and dopamine agonists are generally necessary. In many patients modest or even no reduction in tumor size may be acceptable as long as there is not tumor growth. Hormone replacement (estrogen or testosterone) may cause a decrease in efficacy of the dopamine agonist so that it must be carried out cautiously. Reduction of endogenous estrogen, use of selective estrogen receptor modulators, and aromatase inhibitors are potential experimental approaches.

Topics: Bromocriptine; Cabergoline; Cell Proliferation; Dopamine Agonists; Dose-Response Relationship, Drug; Drug Resistance; Ergolines; Estrogens; Female; Humans; Male; Pergolide; Pituitary Neoplasms; Prolactin; Prolactinoma; Receptors, Dopamine D2

Prolactin-secreting pituitary adenomas--prolactinomas--are the most common type of functional pituitary tumor. Treatment of hyperprolactinemia is indicated because of the consequences of infertility, gonadal dysfunction, and osteoporosis. Making the correct diagnosis is important because the first line of therapy is medical management with dopamine agonists. Medical therapy is effective in normalizing prolactin levels in more than 90% of patients, but longterm treatment may be required in some patients. Transsphenoidal surgery is usually indicated in those patients in whom medical therapy fails or cannot be tolerated, or in patients who harbor microprolactinomas. In experienced hands, a hormonal and oncological cure can be achieved in more than 90% of patients after transsphenoidal removal of microprolactinomas with minimal risks. Thus, surgery may be an option for microprolactinomas in a young patient who desires restoration of fertility and avoidance of long-term medical therapy. The authors review the diagnosis and management of prolactinomas, including medical therapy, surgical therapy, and stereotactic radiosurgery.

Topics: Bromocriptine; Cabergoline; Contraindications; Diagnosis, Differential; Ergolines; Female; Humans; Hypophysectomy; Magnetic Resonance Imaging; Male; Pituitary Diseases; Pituitary Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Prolactin; Prolactinoma; Radiosurgery; Remission Induction

Topics: Aminoquinolines; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Pituitary Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Prolactinoma

Resistance to dopamine agonists can be defined with respect to failure to normalize PRL levels and failure to decrease tumor size by > or = 50%. Using these definitions, failure to normalize PRL levels is seen in 24% of those treated with bromocriptine, 13% of those treated with pergolide and 11% of those treated with cabergoline. Failure to achieve at least a 50% reduction in tumor size occurs in about one-third of those treated with bromocriptine and 10-15% of those treated with pergolide or cabergoline. Studies of in vitro cell preparations show that the D2 receptors of resistant tumors are decreased in number but have normal affinity. Treatment approaches for resistant patients include switching to another dopamine agonist and raising the dose of the drug as long as there is continued response to the dose increases and no adverse effects. Transsphenoidal surgery can also be done. If fertility is desired, clomiphene, gonadotropins, and GnRH are also options. If fertility is not desired, estrogen replacement may be used unless there is a macroadenoma, in which case control of tumor growth is also an issue and dopamine agonists are generally necessary. However, in many cases modest or even no reduction may be acceptable long-term as long as there is not tumor growth. Hormone replacement (estrogen or testosterone) may cause a decrease in efficacy of the dopamine agonist so that it must be carried out cautiously. Reduction of endogenous estrogen, use of selective estrogen receptor modulators, and aromatase inhibitors are potential experimental approaches.

Topics: Bromocriptine; Cabergoline; Dopamine Agonists; Drug Resistance; Ergolines; Humans; Pituitary Neoplasms; Prolactinoma

Hyperprolactinemia is commonly found in both female and male patients with abnormal sexual and/or reproductive function or with galactorrhea. If serum prolactin levels are above 200 microg/L, a prolactin-secreting pituitary adenoma (prolactinoma) is the underlying cause, but if levels are lower, differential diagnoses include the intake of various drugs, compression of the pituitary stalk by other pathology, hypothyroidism, renal failure, cirrhosis, chest wall lesions, or idiopathic hyperprolactinemia. When a pituitary tumor is present, patients often have pressure symptoms in addition to endocrine dysfunction, such as headaches, visual field defects, or cranial nerve deficits. The large majority of patients with prolactinomas, both micro- and macroprolactinomas, can be successfully treated with dopaminergic drugs as first-line treatment, with normalization of prolactin secretion and gonadal function, and with significant tumor shrinkage in a high percentage of cases. Surgical resection of the prolactinoma is the option for patients who may refuse or do not respond to long-term pharmacological therapy. Radiotherapy and/or estrogens are also reasonable choices if surgery fails. In patients with asymptomatic microprolactinoma no treatment needs to be given and a regular follow-up with serial prolactin measurements and pituitary imaging should be organized. Currently, the most commonly used dopamine agonists are bromocriptine, pergolide, quinagolide and cabergoline. When comparing the plasma half-life, efficacy and tolerability of these drugs, cabergoline seems to have the most favorable profile, followed by quinagolide. Ifprolactin levels are well controlled with dopamine agonist therapy, gradual tapering of the dose to the lowest effective amount is recommended, and in a number of cases medication can be stopped after several years. Evidence to date suggests that cabergoline and quinagolide appear to have a good safety profile for women who wish to conceive, but hard evidence proving that dopamine agonists do not provoke congenital malformations when taken during early pregnancy is currently only available for bromocriptine. Once pregnant, dopamine agonist therapy should be immediately stopped, unless growth of a macroprolactinoma is likely or pressure symptoms occur. At our institution patients with symptomatic prolactinomas, both micro- and macroadenomas, are treated with cabergoline as the first-line aproach. In the small group of patients who do not re

Topics: Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Estrogens; Female; Humans; Hyperprolactinemia; Male; Pergolide; Pituitary Neoplasms; Pregnancy; Prolactin; Prolactinoma; Radiotherapy; Surgical Procedures, Operative

Prolactinomas are the most common hormone-secreting pituitary tumours and cause infertility and gonadal and sexual dysfunction in both sexes. The approach to prolactinomas has changed in the last 25 years thanks to the availability of dopaminergic drugs characterised by a potent prolactin-inhibitory effect, a tumour shrinking effect associated with a satisfactory tolerability. In more recent years, cabergoline 1-[(6-allelylergolin-8beta-yl)carbonyl]-1-[3-(dimethylamino) propyl]-3-ethyl-urea an ergoline derivative with potent, selective and long-lasting inhibitory activity on prolactin release, has been used to suppress prolactin secretion in women with hyperprolactinaemia. Cabergoline was shown to be significantly more effective than bromocriptine in inducing a complete biochemical response and clinical efficacy and was better tolerated than bromocriptine in the majority of patients. Notable tumour shrinkage until tumour disappearance was observed during cabergoline treatment in most patients with macroprolactinoma and it was also proven effective in patients resistant to or with a poor response to bromocriptine. In view of the limited data on cabergoline-associated pregnancies and the long half-life of the drug, it is currently recommended that women hoping to become pregnant, once ovulatory cycles have been established, should discontinue cabergoline therapy 1 month before they intend to conceive. However, no data concerning negative effects on pregnancy or offspring have been reported. The great efficacy of this compound together with its excellent tolerability makes this drug the current treatment of choice for the majority of patients with hyperprolactinaemic disorders.

Topics: Aminoquinolines; Animals; Bromocriptine; Cabergoline; Dopamine Agonists; Drug Resistance, Neoplasm; Ergolines; Ergot Alkaloids; Female; Humans; Pergolide; Pituitary Neoplasms; Pregnancy; Prolactin; Prolactinoma

The primary aim of therapy should be to remove symptoms, reduce tumor bulk, prevent relapse, and improve long-term outcome. Surgery, radiotherapy and medical therapies are used to achieve these aims. Post-treatment mean "safe" serum growth hormone values of < 2.5 ng/ml should be the therapeutic goal. Transsphenoidal surgery remains the first line treatment for acromegaly. Patients with microadenoma can expect 85%, while those with macroadenoma 50% chance to achieve safe serum growth hormone levels. Less than 20% of acromegalics respond to treatment with bromocriptine, while quinagolide and cabergoline may show better clinical response; the success rate is higher for tumors secreting both growth hormone and prolactin. Dopamine agonists may be considered either in combination with somatostatin-analogues or as monotherapy in selected patients, and in those with co-secretion of prolactin. Octreotide (Sandostatin, Novartis) is a synthetic somatostatin-analogue, which is administered subcutaneously in doses between 100 and 250 micrograms 3 times daily. Long-acting octreotide (Sandostatin LAR, Novartis) contains octreotide incorporated into microspheres of biodegradable polymer. To effectively lower serum growth hormone levels, monthly injections of 10-30 mg of long-acting octreotide are needed, serum growth hormone falls to 2.5 ng/ml in 70% of cases, and serum insulin-like growth factor I normalizes in 67%. Slow release lanreotide (Somatuline SR, Ipsen) is an alternative depot long-acting somatostatin-analogue, which is administered in a dose of 30 mg intramuscularly every 14, 10 or 7 days. Both compounds are equally, if not more, effective than subcutaneous octreotide, and significantly improve patient compliance. Pegvisomant (Sensus Drug Development Corporation) is a genetically engineered growth hormone receptor antagonist, which inhibits growth hormone action. When given subcutaneously in a dose of 20 mg/day, serum insulin-like growth factor I levels return to normal in 90% of patients. Theoretical concerns of tumor expansion have not been a problem to date, but long term studies are needed. Primary medical--somatostatin-analogue--therapy is recommended if surgery fails, if the patient refuses or unsuited for surgery and it may be also considered in patients with macroadenoma with extra--but not suprasellar extension, since the surgical "cure" rates of these tumors are low.

Topics: Acromegaly; Adenoma; Aminoquinolines; Antineoplastic Agents, Hormonal; Cabergoline; Dopamine Agonists; Drug Administration Schedule; Ergolines; Hormones; Human Growth Hormone; Humans; Octreotide; Peptides, Cyclic; Pituitary Neoplasms; Prolactin; Receptors, Somatotropin; Somatostatin

The management of CSF rhinorrhoea following dopamine agonist (DA) treatment for invasive prolactinomas is difficult and there is no clear consensus for its treatment. Our objective was therefore to investigate the different treatments for this condition.. We examined the case notes of five patients with invasive prolactinomas and CSF rhinorrhoea following DA treatment. The different ways in which this complication had been managed is detailed along with a review of the literature.. Five patients aged 24-67 years (3 male) with massive invasive prolactinomas (serum prolactin 95000-500000 mU/l) eroding the skull base were treated with dopamine agonists (3 bromocriptine, 1 cabergoline and 1 both). CSF rhinorrhoea developed in all patients between 1 week and 4 months after commencing dopamine agonist treatment. In two patients (cases 1 and 4), CSF rhinorrhoea ceased within a few days of stopping bromocriptine but restarted when treatment was resumed. One of these (case 4), a 67-year-old woman had no further treatment and CSF leakage stopped completely. She died of unrelated medical problems 3 years later. In one patient staphylococcus aureus meningitis and pneumocephalus developed as a complication of CSF rhinorrhoea. Three patients had endoscopic nasal surgery to repair the fistula using muscle grafts, and to decompress the pituitary tumour, with success in two. One patient had intracranial surgery and dural repair, which was successful in sealing the leak.. We suggest that surgery as soon as is feasible is the treatment of choice for the repair of a CSF leak following dopamine agonist treatment. An additional strategy is the withdrawal of dopamine agonist to allow tumour re-growth to stop the leak.

Topics: Adult; Bromocriptine; Cabergoline; Cerebrospinal Fluid Rhinorrhea; Dopamine Agonists; Ergolines; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma; Tomography, X-Ray Computed

We report the case of a 45-year-old male presenting with unilateral exophthalmos due to a large tumoral mass invading the skull base. Ophthalmologic examination did not show any visual field defects. Imaging techniques demonstrated extension of a huge tumor (approx. 8x8x8 cm) into the right orbit and nasopharynx. Endocrine work-up revealed grossly elevated serum prolactin (PRL) levels (26,466 microg/l, nl. < 12), pointing to a large, invasive macroprolactinoma. Stimulation tests indicated associated partial adrenal and growth hormone deficiencies. Planned surgery was abandoned, and the patient was instead treated with the long-acting dopamine agonist, cabergoline. Over a period of one year, serum PRL dropped to 131 microg/l, while the tumor mass shrank to less than 50% of its original volume (with 3.5 mg/week of cabergoline). The exophthalmos disappeared, and the patient did not develop rhinorrhea or any other side effects from treatment with cabergoline. The efficacy was maintained throughout the second year (ultimate serum PRL 74 microg/l, and final size less than 10% of the original). With reference to this case, we review other macroprolactinomas reported in the recent literature for associated exophthalmos, grossly elevated serum PRL levels (> or = 15,000 microg/l), and/or "giant" size (> or = 4 cm in maximum diameter). We highlight the use of dopamine agonists in the treatment of prolactinomas with such unusual characteristics.

Topics: Cabergoline; Dopamine Agonists; Ergolines; Exophthalmos; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma

Prolactinomas are benign, sporadic pituitary tumours that typically present with amenorrhoea and galactorrhoea in women, and hypogonadism and space-occupying effects in men. Hyperprolactinaemic hypogonadism in either sex is associated with reduced bone mineral density, which may be progressive and only partially reversible. For most microprolactinomas, dopamine agonists are the treatment of choice, achieving normoprolactinaemia and restoring gonadal function in 80-90% of cases. Trans-sphenoidal surgery is curative in 60%, but may be complicated by hypopituitarism and is usually reserved for patients with dopamine agonist intolerance or resistance. A subgroup of patients with small tumours, mild symptoms and normal gonadal function may be monitored without specific treatment--the risk of tumour expansion is small. Macroprolactinomas should be treated medically, dopamine agonists controlling prolactin secretion and achieving significant tumour shrinkage in 80% of cases, whereas surgery is curative in only a quarter. Cabergoline is the dopamine agonist of choice in most situations, being better tolerated and more effective than bromocriptine. Quinagolide is an effective alternative. Dopamine agonist withdrawal or dose reduction should be considered after 2-5 years therapy. Oestrogens may be used with caution in women with prolactinomas.

Topics: Bone Density; Cabergoline; Dopamine Agonists; Drug Resistance; Ergolines; Female; Humans; Hypogonadism; Male; Pituitary Neoplasms; Pregnancy; Prolactinoma

Among the various endocrine forms impotence associated with hyperprolactinaemia is discussed in this paper. A more relevant clinical picture is particularly due to prolactinoma. A marked reduction or suppression of libido and sexual power are mostly present; sometimes an altered spermatogenesis with oligospermia and infertility may be found; on the contrary galactorrhea and gynaecomastia are less frequent. Symptoms and signs of hypopituitarism or extrasellar growth may be found too. The main physiopathologic aspects as well as biochemical and instrumental diagnostic evaluation methods of prolactinoma in men are examined. The treatment may be pharmacological, surgical or radiant: indications and efficacy of each one are reported. A guide-line in case of macro- or microprolactinoma is explained too. With regard to pharmacological treatment, dopaminergic agonists have been available for more than twenty years and there is a wide experience with bromocriptine. Among the latest dopaminergic agonists, cabergoline is very interesting because it is effective, selective and long-term active; its pharmacological features are mentioned. At last, personal experience in three men, one suffering from micro- and two from macroprolactinoma recently treated with cabergoline is reported. Clinical aspects and hormonal and instrumental data before treatment are presented. Clinical and hormonal evaluations have been made after 2, 3 and 6 months of therapy and TAC control after the sixth month. The results allowed to verify the effectiveness of the drug.

Topics: Cabergoline; Cranial Irradiation; Dopamine Agonists; Erectile Dysfunction; Ergolines; Galactorrhea; Gynecomastia; Humans; Hyperprolactinemia; Hypophysectomy; Infertility, Male; Libido; Male; Pituitary Neoplasms; Prolactinoma; Treatment Outcome

The current status of treatments designed to treat prolactinoma and other hyperprolactinaemic disorders is reviewed. The use of ergoline derivatives is described to correct prolactin levels, restore reproductive dysfunctions and reduce the size of prolactinomas. Side effects are minimal but withdrawal is almost always followed by a recurrence of the original condition. Radiation therapy is less effective and surgical resection of prolactinomas is effective, but the condition may recur. The authors recommend that dopaminergic drugs should be the primary therapies for prolactin-secreting adenomas and idiopathic hyperprolactinaemia, and surgery should be reserved for dopamine-resistant conditions.

Topics: Acromegaly; Bromocriptine; Delayed-Action Preparations; Dopamine; Ergolines; Female; Humans; Hyperprolactinemia; Lisuride; Pergolide; Pituitary Neoplasms; Pregnancy; Prolactin; Psychoses, Substance-Induced; Tamoxifen

Topics: Adenoma; Adrenocorticotropic Hormone; Bromocriptine; Dihydroergotoxine; Dopamine; Drug Administration Schedule; Ergolines; Growth Hormone; Levodopa; Lisuride; Metergoline; Methysergide; Pergolide; Pituitary Neoplasms; Prolactin; Tomography, X-Ray Computed

Topics: Adenoma; Adult; Diagnosis, Differential; Ergolines; Female; Follow-Up Studies; Galactorrhea; Genital Diseases, Female; Humans; Hypophysectomy; Hypothyroidism; Infertility, Female; Pergolide; Pituitary Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Prolactin; Sella Turcica; Tomography, X-Ray Computed; Visual Field Tests

Topics: Adrenergic alpha-Antagonists; Adrenocorticotropic Hormone; Amenorrhea; Antineoplastic Agents; Bromocriptine; Cyproheptadine; Ergolines; Estrogens; Female; Galactorrhea; Growth Hormone; Humans; Hypothalamus; Levodopa; Pituitary Gland; Pituitary Neoplasms; Pregnancy; Prolactin

Cabergoline (CAB) has been found to be associated with increased risk of cardiac valve regurgitation in Parkinson's disease, whereas several retrospective analyses failed to detect a similar relation in hyperprolactinemic patients. The current study aimed at investigating cardiac valve disease before and after 24 and 60 months of continuous treatment with CAB only in patients with hyperprolactinemia.. Forty patients (11 men and 29 women, aged 38.7 ± 12.5 years) newly diagnosed with hyperprolactinemia entered the study. Cumulative CAB dose ranged from 12 to 588 mg (median 48 mg) at 24 months and 48-1260 mg (median 149 mg) at 60 months. All patients underwent a complete trans-thoracic echocardiographic examination. Valve regurgitation was assessed according to the American Society of Echocardiography.. At baseline, the prevalence of trace mitral, aortic, pulmonic, and tricuspid regurgitations was 20, 2.5, 10, and 40% respectively, with no patient showing clinically relevant valvulopathy. After 24 months, no change in the prevalence of trace mitral (P=0.78) and pulmonic (P=0.89) regurgitations and of mild aortic (P=0.89) and tricuspid (P=0.89) regurgitations was found when compared with baseline. After 60 months, the prevalence of trace tricuspid regurgitation was only slightly increased when compared with that after 24 months (37.5%; P=0.82), but none of the patients developed significant valvulopathy. No correlation was found between cumulative dose and prevalence or grade of valve regurgitation at both evaluations. Prolactin levels normalized in all patients but one.. CAB does not increase the risk of significant cardiac valve regurgitation in prolactinomas after the first 5 years of treatment.

Topics: Adult; Antineoplastic Agents; Cabergoline; Cohort Studies; Dopamine Agonists; Drug Monitoring; Early Diagnosis; Ergolines; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valves; Humans; Italy; Male; Middle Aged; Pituitary Neoplasms; Prevalence; Prolactinoma; Severity of Illness Index; Time Factors; Ultrasonography

The frequency and the degree of recovery of anterior pituitary hormone deficits in patients with macroprolactinoma responsive to cabergoline are not clear. Our aim was to evaluate pituitary function in these patients with particular reference to an assessment of the possible restoration of pituitary deficits.. The records of all subjects prospectively presenting to our Department with macroprolactinomas treated with cabergoline over a 2-year period were reviewed. Pituitary function was assessed at diagnosis and, if abnormal, for three consecutive years for the GH, FSH/LH and ACTH axes, and at 3 years for the TSH axis.. Twelve patients were included. Severe GH deficiency was found in 83% at diagnosis and did not resolve in any patient at last assessment. Gonadotrophin deficiency was found in 90% at diagnosis and in 50% at last evaluation (showing reversal in 44% of deficient patients, all achieved within 1 year). ACTH deficiency was found in 17% at diagnosis and it did not reverse in any patient at last assessment. TSH deficiency was found in 36% at diagnosis and in 27% at last assessment (reversal in 25% of deficient patients).. In our study, in a group of patients with macroprolactinoma systematically assessed at intervals, pituitary dysfunction in response to cabergoline was found to be mostly irreversible, except for the gonadotroph axis which showed restoration in a subset of subjects following achievement of normoprolactinaemia. It would appear that the reversibility of pituitary axes may be less common than previously thought.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Hypopituitarism; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Prospective Studies

The aim of this study was to evaluate the effect of Cabergoline on insulin sensitivity, inflammatory markers, and carotid intima media thickness in prolactinoma patients. Twenty-one female, newly diagnosed patients with prolactinoma were included in the study. None of the patients were treated previously. Cabergoline was given as treatment, starting with 0.5 mg/day and tapered necessarily. Blood samples were taken for prolactin, highly sensitive C-reactive protein, homocysteine, total cholesterol, low density lipoprotein (LDL) cholesterol, fasting glucose, insulin, and HOMA (homeostasis model assessment of insulin resistance) score was calculated, prior to and 6 months after starting treatment. The body mass index (BMI) was measured and carotid intima media thickness (CIMT) was evaluated for each patient prior to and 6 months after the treatment. The prolactin levels and LDL decreased significantly after cabergoline treatment. Insulin sensitivity improved independently from the decrease in prolactin levels and BMI. The significant decrease in homocysteine and hs-CRP was not related with the decrease in prolactin levels. The significant decrease in CIMT was independent from the decrease in prolactin levels, HOMA score, and BMI. Our data suggest that cabergoline treatment causes an improvement in insulin sensitivity and inflammatory markers and causes a decrease in CIMT independent from the decrease in prolactin, LDL cholesterol, and BMI. We conclude that short term cabergoline treatment can improve endothelial function independently from the changes in metabolic disturbances and inflammatory markers.

Topics: Adolescent; Adult; Antineoplastic Agents, Hormonal; Biomarkers; Cabergoline; Carotid Intima-Media Thickness; Ergolines; Female; Glucose Tolerance Test; Humans; Inflammation; Insulin Resistance; Middle Aged; Pituitary Neoplasms; Prolactinoma; Young Adult

Intensive treatment with cabergoline may lead to earlier reduction in prolactin and tumour volume in comparison to conventional schedule.. To compare the efficacy and safety of two different dosing schedules of cabergoline in patients with macroprolactinoma.. Prospective, randomized trial in drug naive patients assigned to conventional (4 weekly escalation by 0·5 mg per week, group A) or intensive (weekly increase by 1 mg per week followed by 4 weekly escalation, group B) treatment with cabergoline.. The duration required to achieve normoprolactinemia and tumour shrinkage of >50% as a composite end-point.. 38 patients (19 in each group) completed the study with a mean follow-up of 64·3 ± 24·9 weeks. More subjects (22%) achieved the composite end-point in group B (18/19) as compared to the group A (14/19) (P = 0·18). The duration of cabergoline treatment required to achieve the composite end-point was 13·1 ± 9·5 weeks vs 19·3 ± 15·7 weeks (P = 0·34) in the group A and B, respectively. A reduction in prolactin of ≥90% by the fourth week of cabergoline therapy predicted subsequent normalization of prolactin (AUC 0·78; P = 0·04). A further increase in cabergoline dosage after normalization of prolactin in patients with tumour reduction of <50%, led to further tumour shrinkage by 31·2% in an additional 26·3% of patients.. Intensive treatment with cabergoline is not superior to the conventional recommended dosage schedule in respect to the time necessary to achieve normoprolactinemia and ≥50% tumour shrinkage.. NCT 01143584.

Topics: Adult; Antineoplastic Agents; Cabergoline; Drug Administration Schedule; Echocardiography; Ergolines; Female; Humans; Luminescence; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma; Prospective Studies; ROC Curve; Treatment Outcome; Young Adult

Chronic low-dose cabergoline treatment for microprolactinoma may cause cardiac valve pathology, but the evidence is contradictory. We investigated whether the expectation of the echocardiographer could influence the report.. Transthoracic echocardiograms from 40 patients aged 49·3 ± 9·6 (mean ± SD) years (Men:Women 7:33) on long-term cabergoline and bromocriptine therapy (duration 9·94 ± 4·5 years) were randomly assigned to two groups of echocardiographers so that each echocardiogram was reported twice. One group was told that 'the patients were control subjects' (Group A) and the other that 'the patients were on dopamine agonist therapy which is known to cause valve disease' (Group B). An observer who was blind to the group scored the reports for regurgitation at each valve (scores 0-4; max 16 per case).. Mean total regurgitation score was significantly higher in Group B (1·43 ± 1·28; P = 0·014) than in Group A (0·73 ± 1·30). The difference was mainly from reporting trivial regurgitation: (mitral 16 vs 5, P = 0·005; tricuspid 17 vs 6, P = 0·007 and pulmonary 8 vs 1, P = 0·013). Mild regurgitation was uncommon (mitral 1 vs 1 and tricuspid 3 vs 6). Moderate regurgitation occurred in only one case and was associated with restriction of the leaflets consistent with the effects of cabergoline. Valve thickening was not reported in Group A, but in 9 (23%) mitral and 4 (10%) aortic valves in Group B.. Long-term, low-dose dopamine agonist therapy rarely causes cardiac valve disease, but operator bias can lead to over-reporting of both valve thickening and trivial regurgitation.

Topics: Adult; Antineoplastic Agents; Artifacts; Bias; Cabergoline; Dopamine Agonists; Echocardiography; Ergolines; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Pituitary Neoplasms; Prolactinoma; Tricuspid Valve Insufficiency

This study aimed to determine the effectiveness of short-term maintenance treatment with cabergoline and to find out minimum effective dosage of cabergoline during maintenance treatment for patients with microadenoma-related and idiopathic hyperprolactinemia.. Cabergoline was administered orally at a dose of 0.5 mg twice per week to 164 de novo hyperprolactinemic patients until serum prolactin level normalized. After this initial treatment phase, patients started on maintenance phase for which they were previously randomized. No maintenance treatment (Group I, n = 36) or cabergoline 0.5 mg (Group II, n = 46), 0.25 mg (Group III, n = 39), 0.125 mg (Group IV, n = 43) was administered twice per week for 8 weeks as maintenance treatment. Then, maintenance phase was finalized and patients were followed up for 6 months. Mean serum prolactin levels through maintenance treatment phase and follow-up period were assessed between groups and within groups.. Except for group I, all the groups showed a similar pattern with fast decrease of serum prolactine level during maintenance phase and slower increase during the follow-up period. Notably, the average prolactin level was significantly lower at the last follow-up visit than at the diagnosis time in all of the groups. Stable normoprolactinemia of the groups at the end of follow-up period were 47.2, 37, 48.7, and 34.9%, respectively.. The results indicate that short maintenance treatment in idiopathic and microadenoma-related hyperprolactinemia seems as effective as long maintenance treatment in the present study. But, further studies with larger study population and longer follow-up period are needed to make a decision about early treatment withdrawal. Also, during the maintenance treatment administration of medicine to patients should be tapered down to the lowest dose that will maintain prolactin levels normal.

Topics: Adolescent; Adult; Cabergoline; Chi-Square Distribution; Dopamine Agonists; Dose-Response Relationship, Drug; Ergolines; Female; Humans; Hyperprolactinemia; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Young Adult

Cabergoline fails to normalize hyperprolactinemia in a considerable proportion of prolactinomas, especially macroadenomas.. We examined the effect of individualized high-dose cabergoline treatment on hyperprolactinemia in prolactinomas.. The study included 122 women and 28 men (93 microadenomas and 57 macroadenomas). Forty-seven had undergone transsphenoidal surgery. According to the preceding medical treatment, the participants were separated into untreated (group U; n = 60), intolerant (group I; n = 64), and resistant (group R; n = 26) groups.. We promptly increased cabergoline dose on the basis of individual prolactin levels. Length of treatment was 1 yr.. Cabergoline normalized hyperprolactinemia in all patients except one. The proportion of prolactin normalization in both groups U and I was 83% at 3 months and 95% at 6 months. By contrast, that in group R was 35% at 3 months and 58% at 6 months. Mean cabergoline dose in milligrams per week at the time of prolactin normalization was 2.0 +/- 0.3 in group U, 0.9 +/- 0.1 in group I, and 5.2 +/- 0.6 in group R. Prolactin normalization rate at the 3 mg/wk dose was 84% overall but only 35% in group R. Serum progesterone or testosterone levels, diminished in 122 women or 16 men, respectively, were recovered in all except one resistant and four postmenopausal or panhypopituitary patients.. Individualized high-dose cabergoline treatment can normalize hyperprolactinemia and hypogonadism in nearly all prolactinomas irrespective of tumor size or preceding treatments. Hyperprolactinemia could be controlled in poor responders within 1 yr with doses higher than 3 mg/wk.

Topics: Adult; Aged; Antineoplastic Agents; Cabergoline; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Resistance; Ergolines; Female; Humans; Male; Middle Aged; Neurosurgical Procedures; Pituitary Neoplasms; Prolactin; Prolactinoma; Prospective Studies; Young Adult

To evaluate QOL in women with microprolactinomas treated with dopamine agonists, comparing the patients with normal versus those with elevated prolactin levels, and to identify clinical and biochemical influences on patients' QOL.. A cross-sectional evaluation was performed in two University referral centers. Fifty women with microprolactinoma answered the SF-36 questionnaire by the time of their clinical evaluation. Their biochemical analysis included PRL, estradiol, testosterone, and SHBG. Fifty women of similar age distribution served as controls.. Patients had lower scores than controls in all SF-36 categories: physical functioning, physical role, pain, general health, vitality, social functioning, emotional aspect, and mental health. Within the patients' group, the ones with normal PRL levels had higher scores than those with high PRL levels in all categories but the physical role. The physical functioning score correlated with the free androgen index, while the pain, vitality, social functioning, emotional aspect, and mental health scores were associated with the prolactin levels obtained at study entry.. QOL is impaired in women with microprolactinoma treated with dopamine agonists, and was inversely associated with the PRL levels. This latter finding reinforces the importance of providing adequate disease control for these patients in order to avoid the adverse consequences of hyperprolactinemia on QOL.

Topics: Adult; Antineoplastic Agents; Brazil; Bromocriptine; Cabergoline; Case-Control Studies; Cross-Sectional Studies; Dopamine Agonists; Ergolines; Female; Health Status Indicators; Humans; Hyperprolactinemia; Middle Aged; Multivariate Analysis; Pituitary Neoplasms; Prolactin; Prolactinoma; Quality of Life; Reproducibility of Results; Surveys and Questionnaires; Treatment Outcome

The effectiveness of treatment of hyperprolactinemia (of functional and organic genesis) with dophamin agonists was studied in 97 women aged 18-32. The effectiveness was evaluated by normalization of the laboratory indices of prolactin level, and the clinical parameters: restoration of the regularity of the menstrual cycle; resumption of ovulation; becoming pregnant; stopping of galactorrhea. Dophamin agonists of the I generation, parlodel, and of the III generation, dostinex, were prescribed. The doses were selected individually, in accordance with the monthly indices of the prolactin level. The duration of treatment was 6 months with a subsequent 6-month follow-up. At micro- and macroadenomas of hypophysis, dostinex proved most effective and highly durable. Dostinex is characterized by infrequent occurrence of side effects; is particularly recommended in cases of parlodel resistance or intolerance. Parlodel may be a preparation of choice for treating all kinds of hyperprolactinemia conditions; no contraindication at becoming pregnant.

Topics: Adenoma; Adolescent; Adult; Bromocriptine; Cabergoline; Dopamine Agonists; Drug Administration Schedule; Ergolines; Female; Humans; Hyperprolactinemia; Ovulation; Pituitary Neoplasms; Treatment Outcome

We report the comparative efficacy of octreotide, cabergoline and multiple ligands directed towards the different somatostatin subtypes (ssts), such as BIM-23A779 and SOM-230, and of chimeric analogs which bind both somatostatin and the dopamine D2 receptors (D2R), such as BIM-23A760 and BIM-23A781, in cell cultures from human growth hormone (GH)-secreting pituitary adenomas.. RT-PCR analysis of the quantitative expression of the different ssts and D2R mRNAs was performed on tumor fragments of 22 GH-secreting adenomas collected after surgery. Pharmacological studies, using the different ligands, were performed on cell cultures of such tumors.. sst2, sst5 and D2R were constantly coexpressed in all tumors, in variable amounts. The levels of expression of sst2 and D2R mRNAs were significantly correlated with the maximal GH suppression by either octreotide or cabergoline (p < 0.001). In each tumor tested, 3 patterns of response, in terms of GH suppression, were observed. GH secretion was preferentially inhibited by the sst2 preferential compound octreotide in 61% of the tumors. In 19% of the tumors, the maximal inhibition of GH release was achieved with the sst5 preferential compound BIM-23268. The dopamine analog cabergoline was the most effective inhibitor of GH secretion in 21% of cases. Among the compounds tested, the most potent inhibitors of GH secretion were the sst2, sst5, D2R chimeric compound BIM-23A760, followed by the sst universal ligand SOM-230.. The variable patterns of response to sst2, sst5 and dopamine D2 analogs may explain the greater efficacy of drugs which bind to the 3 receptors in suppressing GH secretion. The biological potency (EC50) and efficacy of the chimeric compound BIM-23A760 on GH secretion can be partly explained by its high affinity for sst2. The effect of multiple receptor activation on the functions of other pituitary tumor types, such as prolactinomas and corticotropinomas, is not presently analyzed, and the efficacy of multireceptor ligands remains to be elucidated.

Topics: Adenoma; Adult; Antineoplastic Agents, Hormonal; Cabergoline; Dopamine; Drug Screening Assays, Antitumor; Ergolines; Female; Human Growth Hormone; Humans; Ligands; Male; Octreotide; Pituitary Neoplasms; Receptors, Dopamine D2; Receptors, Somatostatin; Recombinant Fusion Proteins; RNA, Messenger; Somatostatin; Tumor Cells, Cultured

First choice therapy of microprolactinoma is drug treatment with dopamine agonists. Cabergoline is widely accepted in clinical practice as a first line therapy for tumor-induced pituitary hyperprolactinemia. This study assessed serum prolactin levels, tumor size and adverse events in 22 women treated with cabergoline for one year (mean age 43.5 +/- 6.6 years). Serum prolactin levels changed from a baseline mean of 1417 +/- 347 UI/L to 489 +/- 102 UI/L at study end (in the normal range). Tumor size reduction to tumor disappearance was found in 18 women (from a mean of 7.2 mm to 5.5 mm), and was absent in 4 participants. Adverse events were reported in 2 women. In conclusion, the excellent therapeutic efficacy and the lack of adverse events with Cabergoline promotes its use as a first line therapy of hyperprolactinemia due to pituitary microadenoma.

Topics: Adenoma; Adult; Antineoplastic Agents; Cabergoline; Ergolines; Female; Humans; Hyperprolactinemia; Middle Aged; Pituitary Neoplasms; Prolactin; Treatment Outcome; Tumor Burden

The outcome of 24 months of cabergoline treatment on prolactin (PRL) normalization, tumor shrinkage, restoration of pituitary function, and semen alterations was prospectively investigated in 41 men with macro- (age 17-70 yr) and 10 with microprolactinoma (age 18-53 yr). Fifty-one age-matched men served as controls for semen analysis. At study entry, of the 41 patients with macroprolactinoma, 17 (41.4%) had visual field defects, 14 (34.1%) had headache, eight (19.5%) had galactorrhea, 22 (53.6%) had hypopituitarism apart from hypogonadism, and 30 (73.2%) had low testosterone levels; of the 10 patients with microprolactinoma, none had visual field defects, galactorrhea, or hypopituitarism apart from hypogonadism, two had headache (20%), and five had low testosterone levels (50%; P = 0.3). After 24 months of therapy, 1) PRL levels normalized in 31 patients with macro- (75.6%) and in eight with microprolactinoma (80%; P = 0.9), and galactorrhea disappeared in all patients; 2) maximal tumor diameter reduced by 73.7 +/- 22.6% in macro- and 72.8 +/- 28.3% in microprolactinomas (P = 0.91), and 15 macro- (30%) and seven microprolactinomas (46.7%; P = 0.37) disappeared; 3) visual field defects disappeared in 15 (75%) patients with macroprolactinoma, and headache disappeared in 15 (83%) patients with macro- and in one with microprolactinoma (50%); 4) GH secretion recovered in 62.5% and ACTH secretion in 60% of patients; 5) testosterone levels normalized in 25 patients with macro- (60.9%) and six with microprolactinoma (60%) after 6 months, and 20 patients required testosterone or gonadotropin replacement (in 14 or six patients, respectively); and 6) sperm volume and count normalized in all patients who normalized testosterone levels, whereas motility normalized in more than 80%. Cabergoline therapy was well tolerated; only 4.5% of patients had side effects at high doses. These data demonstrate that cabergoline treatment is as effective and safe in men as in women with prolactinoma and can be successfully used as primary therapy even in men bearing large macroprolactinomas.

Topics: Adolescent; Adult; Aged; Cabergoline; Dopamine Agonists; Drug Administration Schedule; Ergolines; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Prolactin; Prolactinoma; Semen; Treatment Outcome

In experimental models, prolactin (PRL) displays independent hypertrophic effects on the prostate. To investigate whether hyperprolactinemia is associated with prostate enlargement in humans, we designed this open, prospective, case-control study enrolling 20 men with prolactinoma (aged 34 +/- 10 yr) and 20 age-matched healthy men. The endocrine profile and prostate transrectal ultrasonography were performed before and after 12 and 24 months of cabergoline treatment in the patients and at study entry and after 24 months in the controls. The patients had lower serum testosterone, dihydrotestosterone (DHT), and IGF-I levels and prostate volume (15.4 +/- 3.5 vs. 19.6 +/- 5.1 ml; P < 0.001) and higher PRL levels and prostate-specific antigen density than controls. There was no difference in prostate and transitional zone volumes between patients with normoandrogenemia (n = 8) or hypoandrogenemia (n = 12). After 12 and 24 months of treatment, PRL, testosterone, and DHT levels were normal in all cases, as were IGF-I and IGF-binding protein-3 levels. After 24 months, prostate volume was comparable to that in controls (21.7 +/- 4.5 vs. 22.5 +/- 4.7 ml). There were no changes in prostate structure throughout the study period in either the patients or the controls. In conclusion, in young men with prolactinoma PRL excess is unlikely to have effects on the prostate per se, because it is accompanied by low testosterone and DHT levels that produce the major effects.

Topics: Adult; Cabergoline; Case-Control Studies; Dihydrotestosterone; Dopamine Agonists; Ergolines; Humans; Male; Middle Aged; Pilot Projects; Pituitary Neoplasms; Prolactin; Prolactinoma; Prospective Studies; Prostate; Prostatic Hyperplasia; Testosterone; Ultrasonography

Gender differences in tumor size are supposed to exist in hyperprolactinemia since microadenomas are more commonly found in women and macroadenomas in men. Whether this reflects only a delay in diagnosis in men or a true gender difference in tumor pathogenesis is still unclear.. To prospectively analyze gender differences in the presentation and response to cabergoline treatment in 219 consecutive newly diagnosed patients with hyperprolactinemia.. An open prospective design.. Of the 219 patients of which 145 were women; 107 patients had macroprolactinoma, 97 had microprolactinoma, and 15 had non-tumoral hyperprolactinemia.. Presenting clinical symptoms, prolactin levels and tumor size at magnetic resonance imaging were measured before and 3-6 Months after cabergoline therapy.. Prevalence of microprolactinomas (56% vs 22%, P=<0.0001) and non-tumoral hyperprolactinemia (10% vs 0%, P=0.01) was higher in women than in men. Men and women were of similar age (median 32 vs 29 Years; P=0.2) and a similar number had gonadal/sexual dysfunction (85 vs 83%, P=0.6); weight gain (70 vs 46%; P=<0.0001) and galactorrhea (52 vs 19%; P=<0.0001) were more common in women. Prolactin levels were higher in men than in women, whether exhibiting macro- (2848+/-2954 vs 1132+/-2351 microg/l, P=<0.0001) or microadenomas (187.8+/-51.8 vs 135.4+/-60.5 microg/l, P=0.009) and the size of the adenoma was larger in men than in women irrespective of macro- (25.8+/-12.4 vs 17.2+/-7.2 mm, P=<0.0001) or microadenoma diagnosis (8.0+/-1.4 vs 7.1+/-1.6 mm, P=0.04). After treatment, prolactin levels decreased by 89.2-96.4% in all groups, and normalized more frequently in micro- than in macroadenoma patients (86 vs 64%, P<0.0001), regardless of gender (70% vs 69%, P=0.9). Menses resumed in 82% of women, libido disturbances improved in 57% of men. Tumor size was reduced by 45+/-25% and 52+/-24% in macroprolactinoma patients and by 44+/-31 and 38+/-29% in microprolactinoma patients in women and men respectively. Visual field defects disappeared in 61% of women and in 71% of men (P=0.6).. Prevalence of macroprolactinomas was similar in men and women; microprolactinomas and non-tumoral hyperprolactinemia were more frequent in women. Clinical symptoms at presentation differed according to gender, with galactorrhea and weight gain more frequent in women. The successful response to cabergoline treatment for 6 Months was higher in micro- than in macroprolactinoma patients and was similar in women and men.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Cabergoline; Ergolines; Female; Follow-Up Studies; Galactose; Humans; Hyperprolactinemia; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Prospective Studies; Sex Characteristics; Sexual Dysfunction, Physiological; Treatment Outcome; Visual Fields; Weight Gain

Prolactinoma is the most frequent type of secreting pituitary tumours. In the treatment, pharmacotherapy with dopamine agonists is considered the first-line option. For many years bromocriptine, a D1 and D2 dopamine receptor agonist, has been the standard medicine for hyperprolactinemic patients. However, the treatment is frequently associated with intolerance or resistance. Recently cabergoline, a long acting, ergoline-derived, selective D2 agonist has become available and has been promoted as the initial treatment. Therefore the object of four studies was to assess the efficacy and tolerability of cabergoline in patients with prolactin-secreting pituitary adenomas. 17 patients, 13 women at the age of 21-55 years (average 37.1) and 4 men at the age of 29-45 years (average 36.3), with pathological hyperprolactinemia due to pituitary tumours were involved in the study. In all patients the increased pretreatment concentration of PRL was observed, ranging from 1047 to 1678 mlU/ml (mean 1369 mlU/ml). MRI scans revealed microprolactinomas in 11 (64.7%) cases and macroadenomas in 6 (35.3%) cases. None of the patients had previously undergone pituitary surgery and all of them were newly diagnosed, previously untreated. The patients were treated with cabergoline for 6 months. Cabergoline therapy was started at a dose of 0.5 mg twice a week for the first two months, then the dose was decreased to a 0.25 mg twice a week and finally maintained at 0.25 mg a week. After 6 months of the therapy, the normalization of serum PRL concentrations (from mean 1358 mlU/ml to mean 420 mlU/ml; p < 0.001) was achieved in 13 (76.5%) patients (8 with microprolactinoma and 5 with macroprolactinoma). In the remaining 4 patients PRL levels remained elevated but were decreased from mean 1403 mIU/ml to mean 812 mIU/ml. There were no differences, regarding CAB efficacy in lowering PRL levels, between patients with micro- and macroadenomas (p > 0.05). About 90% women resumed menstrual cycles in our study. All the other clinical pretreatment symptoms disappear in the course of the therapy. The tumour shrinkage, confirmed by control MRI was noted in 2 patients (33%) with macroprolactinoma. Cabergoline was tolerated satisfactorily by all our patients. The results have confirmed a high efficacy and a very good tolerability of CAB in the treatment of patients with pituitary adenomas. Together with a very convenient administration, such therapy can provide a very good patient compliance thus sho

Topics: Adult; Cabergoline; Dopamine Agonists; Drug Tolerance; Ergolines; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma; Receptors, Dopamine D2

The aim of the study was to evaluate circulating nitric oxide (NO) levels throughout ovulatory cycles in healthy women and women under long-term treatment with dopamine agonists. Fifty women (aged 32.5 +/- 1.2 years) affected by pathological hyperprolactinemia (prolactin (PRL)-secreting microadenoma, 63%; idiopathic, 19%; 'empty sella', 12%; and PRL-secreting macroadenoma, 6%) and on dopamine-agonist therapy (range 1-10 years) were studied; 37 healthy women (aged 30.4 +/- 1.4 years) served as a control group. Blood samples were collected on days 7, 14 and 21 of the menstrual cycle in order to assay NO, PRL, 17 beta-estradiol and progesterone. In all subjects, ovulatory cycles were recorded. PRL levels were comparable between the two groups and significantly rose during the luteal phase. NO levels recorded throughout the menstrual cycles of healthy controls were significantly higher than those recorded in subjects treated with dopamine-agonist; NO levels in the latter were no different from those recorded in non-treated, non-ovulatory hyperprolactinemic women. However, in both healthy controls and dopamine-agonist-treated women, NO was negatively correlated with progesterone concentration and significantly reduced on day 21. In dopamine-treated patients, NO levels did not correlate with the dose or the duration of dopamine-agonist therapy. We conclude that, in our hyperprolactinemic women on therapy, physiological NO secretion is not fully restored, despite restoration of ovulatory cycles by dopamine-agonist therapy.

Topics: Adult; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Estradiol; Female; Humans; Hyperprolactinemia; Luteal Phase; Menstrual Cycle; Nitric Oxide; Ovulation; Pituitary Neoplasms; Progesterone; Prolactinoma; Reference Values

Hyperprolactinaemia frequently causes secondary hypogonadism through central suppression of gonadotropin secretion. Macroprolactinomas (> 1 cm diameter) are more common in males and may additionally cause more generalised hypopituitarism. Recovery of the thyrotropic and/or corticotropic axes is well described following selective adenomectomy, but remains poorly defined in relation to medical (dopamine-agonist) therapy of macroprolactinomas. We therefore performed a retrospective examination of case records of male patients who had received medical therapy alone for macroprolactinoma between 1980-2001 (n = 35) and in whom tumor shrinkage was documented by interval pituitary imaging (reported throughout by a single neuroradiologist). Mean prolactin level at baseline was 59,932 mU/L (median 31,400; range 3,215-332,000); mean period of follow up was 4.2 years (median 2.6; range: 1.0-15). Defects of the following axes were evident at diagnosis: LH/FSH-testosterone (n = 27; 77%), TSH-T4 (n = 14; 41%-not including one case with pre-existing 1 degress hypothyroidism), ACTH-cortisol (n = 8; 23%). Overall, 14 men (40%) were deficient in 1 axis, seven (20%) in 2 axes and seven (20%) in 3 axes. Growth hormone secretory status was not systematically evaluated. In all but 6 patients, prolactin levels fell to normal or near-normal levels (mean 764 mU/L; median 260; range: < 10-4,833). Of the patients in whom adequate reassessment had been performed, thyrotroph function recovered in 4/9, corticotroph function in 4/6 and gonadotroph function in 16/26 cases. In four cases (11%) previously described, development of visual impairment as a result of the chiasmal traction syndrome necessitated a dose reduction in medical therapy to allow a degree of controlled tumor re-expansion. The prevalence at diagnosis of TSH and ACTH deficiency in men with macroprolactinomas was 41% and 23%, respectively. Among eight patients with insufficiency of TSH and/or ACTH secretion who underwent complete interval reassessment over several years of treatment, recovery of at least one axis occurred in six cases (75%). This study highlights the importance of screening ACTH- and/or TSH-deficient men during dopamine agonist therapy in order to identify cases where hypopituitarism has resolved.

Topics: Adrenocorticotropic Hormone; Adult; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Follicle Stimulating Hormone; Humans; Hypopituitarism; Luteinizing Hormone; Male; Middle Aged; Pergolide; Pituitary Function Tests; Pituitary Gland; Pituitary Neoplasms; Prolactin; Prolactinoma; Testosterone; Thyrotropin

The purpose of this study was to define safety and efficacy of medical therapy in the treatment of nonfunctioning pituitary tumours.. We studied thirteen patients with a clinically nonfunctioning pituitary macroadenoma for response to cabergoline treatment for 1 year. Twelve/13 patients were already operated and had residual or recurrent tumours.. We determined the outcome of treatment by visual perimetry, computed tumour size measurement in MRI and hormonal response (changes in pituitary function, reduction of alpha-subunit).. Seven/13 patients on cabergoline had a tumour shrinkage above 10% of the initial tumour volume. In 4 patients, this tumour shrinkage was correlated to an increasing distance of the tumour to the optic chiasm. Only 2/9 patients with visual field defects before therapy showed improvements in visual acuity under cabergoline. No significant side effects of the therapeutical regimens were observed. Neither LH and/or FSH expression in the tumour cells nor the reduction of the alpha-subunit serum levels by medical therapy was correlated to tumour shrinkage.. Given that these patients had advanced disease which makes it difficult to find significant therapeutic effects, medical therapy with potent dopamine agonists such as cabergoline may evolve as a novel therapeutic option in a subgroup of patients with clinically nonfunctioning tumours declining operation and radiotherapy.

Topics: Adenoma; Aged; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Treatment Outcome; Visual Acuity

It is well known that bromocriptine has a suppressive effect on the prolactin release in hyperprolactinemic patients. But it also has some adverse effects. The new, long-acting dopaminergic drug, cabergoline, has been reported to be an effective agent in these patients. However, there are relatively few reports comparing the beneficial and adverse effects of these drugs in the treatment of hyperprolactinemic patients. Therefore, here we studied and compared the efficacy and tolerability of cabergoline with bromocriptine in hyperprolactinemic patients.. Seventeen patients (7 with microprolactinoma, 4 with macroprolactinoma, 6 with idiopathic hyperprolactinemia) were given bromocriptine at a dose of 2.5 mg (or 5 mg for macroprolactinomas) twice daily, and 17 patients (8 with microprolactinoma, 4 with macroprolactinoma, 5 with idiopathic hyperprolactinemia) were given cabergoline at a dose of 0.5 mg twice weekly for 12 weeks.. At the end of the study, the prolactin reduction was significantly greater in the cabergoline group than in the bromocriptine group (-93 vs. -87.5 %, respectively, p < 0.05). Normalization of prolactin levels was achieved in 10 of 17 patients (59%) in the bromocriptine group, and in 14 of 17 patients (82%) in the cabergoline group (p = 0.13). Two patients (50%) with macroprolactinoma in the bromocriptine group and three patients (75%) with macroprolactinoma in the cabergoline group demonstrated a normalization of their serum prolactin levels. Adverse events were noted in 53% of bromocriptine patients and in 12% of cabergoline patients (p < 0.01).. These data indicate that cabergoline is a very effective agent for lowering the prolactin levels in hyperprolactinemic patients and that it appears to offer considerable advantage over bromocriptine in terms of efficacy and tolerability.

Topics: Adult; Antineoplastic Agents, Hormonal; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Female; Hormone Antagonists; Humans; Hyperprolactinemia; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Treatment Outcome

To evaluate the prevalence of resistance to cabergoline treatment, we studied 120 consecutive de novo patients (56 macroadenoma, 60 microadenoma, 4 nontumoral hyperprolactinemia) treated with cabergoline (CAB) compared with 87 consecutive de novo patients (28 macroadenoma, 44 microadenoma, 15 nontumoral hyperprolactinemia) treated with bromocriptine (BRC) for 24 months. Resistance was evaluated as inability to normalize serum PRL levels (first end point) and to induce tumor shrinkage (second end point). After 24 months, PRL normalization and tumor shrinkage after CAB and BRC treatments, respectively, were obtained in 82.1% and 46.4% of macroprolactinomas (P < 0.001) and in 90% vs. 56.8% of microprolactinomas (P < 0.001). The median doses of CAB and BRC able to fulfill the two criteria of treatment success were 1 mg/wk and 7.5 mg/d in macroprolactinomas, 1 mg/wk and 5 mg/d in microprolactinomas, and 0.5 mg/wk and 3.75 mg/d in nontumoral hyperprolactinemia. Hyperprolactinemia persisted in 17.8% of macroprolactinomas, 10% of microprolactinomas, and after CAB at doses of 5-7 mg/wk and in 53.6% of macroprolactinomas, 43.2% of microprolactinomas, and 20% of nontumoral hyperprolactinemic patients, after BRC at doses of 15-20 mg/d. In these resistant macro- and microprolactinomas, the maximal tumor diameter was reduced by 43.7 +/- 3.6% and 22.1 +/- 3.7% and by 59.3 +/- 7.1% and 4.3 +/- 2.1% after CAB and BRC, respectively (P < 0.001). In conclusion, long-term CAB treatment induced the successful control of hyperprolactinemia associated with tumor shrinkage in a higher proportion of patients than did BRC treatment. In a small number of patients (i.e. 17.8% of macroprolactinomas and 10% of microprolactinomas), however, CAB treatment did not normalize serum PRL levels despite reducing tumor mass, even at very high doses. Therefore, an absence of tumor shrinkage cannot be considered as end point to indicate resistance to CAB, and increasing the dose of CAB higher than 3 mg/wk does not seem to be helpful in controlling PRL hypersecretion.

Topics: Adenoma; Adolescent; Adult; Aged; Bromocriptine; Cabergoline; Dopamine Agonists; Drug Resistance; Ergolines; Female; Hormone Antagonists; Humans; Hyperprolactinemia; Hypopituitarism; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Radioimmunoassay; Retrospective Studies

Dopamine agonists are indicated as primary therapy for PRL-secreting pituitary adenomas, while controversial results have been reported in nonfunctioning adenomas (NFA).. To evaluate whether the in vivo visualization of dopamine D2 receptor expression detected by pituitary scintigraphy using 123I-methoxybenzamide (123I-IBZM) was correlated with the response to chronic treatment with quinagolide or cabergoline.. 10 patients affected with NFA (5 men and 5 women, age ranging between 25 and 50 years), and 10 with PRL-secreting naive macroadenomas (3 men and 7 women, age ranging between 22 and 59 years), serving as control.. All patients underwent an acute test with quinagolide: at 3-day intervals and in random order all patients received the drug (0.075 mg at 0800 h), or placebo. Blood samples were taken 15 and 5 minutes before and every 30 minutes for 6 h after drug or placebo administration. The test was considered positive when PRL and/or alpha-subunit levels decreased >/=50% as compared to baseline levels. After 6 months of treatment, 10 patients were randomised to continue the treatment with quinagolide and the remaining 10 received cabergoline for the remaining 6 months. The doses of quinagolide and cabergoline ranged from 0.075 to 0.6 mg/day and from 0.5 to 3 mg/week, respectively. At study entry, a magnetic resonance imaging (MR) study of the pituitary region and 123I-IBZM pituitary scintigraphy were performed. MR was repeated after 12 months of treatment to evaluate tumour shrinkage: reduction of tumour volume = 80% in prolactinomas and = 50% in NFA was considered significant. Basal PRL levels were 9495.0 +/- 1131.6 mU/l in prolactinomas and 602.4 +/- 50.5 mU/l in NFA.. The scintigraphy was negative in 6 out of 10 patients with NFA. Moderate uptake was observed in 3 patients with prolactinoma and 2 patients with NFA whereas intense uptake was observed in the remaining 7 patients with prolactinoma and 2 patients with NFA. Among the 8 patients with NFA and high circulating alpha-subunit levels, the acute test was negative in 5 while it was positive in the remaining 3 patients. The acute test was positive in all 10 patients with prolactinoma. After 12 months of treatment with quinagolide and cabergoline, circulating PRL levels were decreased in all 10 patients with prolactinoma (571.8 +/- 255.9 mU/l), being normalized in 7 patients. Suppression of PRL levels was found in all 10 patients with NFA (89.5 +/- 2.3 mU/l). A significant reduction of alpha-subunit levels was obtained in 9 out of 10 patients with NFA: in 4 out of 8 patients alpha-subunit levels were normalized. Significant adenoma shrinkage was recorded in 4 patients with prolactinoma among the 7 with intense pituitary uptake of 123I-IBZM. Significant adenoma shrinkage was recorded only in the 2 out of 10 patients with NFA with intense pituitary uptake of 123I-IBZM. A significant positive correlation was found between the degree of uptake (considered as score) and the response to quinagolide or cabergoline treatment (considered as percent hormone suppression) either in patients affected with PRL-secreting adenoma (r = 0.856, P < 0.005) or in those affected with NFA (r = 0.787, P < 0.05).. An intense 123I-IBZM uptake in patients with non-functioning adenomas was predictive of a good response to a chronic treatment with quinagolide and cabergoline. This result suggests that a pituitary 123I-IBZM scintigraphy could be considered in selected patients with non-functioning adenomas before starting medical treatment with dopamine agonists.

Topics: Adenoma; Adult; Aminoquinolines; Benzamides; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Middle Aged; Patient Selection; Pituitary Neoplasms; Predictive Value of Tests; Prolactin; Prolactinoma; Radionuclide Imaging

To investigate whether previous treatment with bromocriptine (BRC) or quinagolide (CV) impairs a subsequent response to long-term cabergoline (CAB) treatment, we prospectively studied 110 patients with macroprolactinoma. Four groups of patients were considered: 1) naive: 26 untreated patients with a mean serum PRL levels of 1013.4 +/- 277.7 microg/L (+/- SEM; range, 185.5-5611 microg/L); 2) intolerant: 19 patients previously shown to be intolerant of BRC treatment with a mean serum PRL level of 539.4 +/- 172.2 microg/L (range, 174-3564 microg/L); 3) resistant: 37 patients shown to be resistant/hyporesponsive to BRC, CV, or both, with a mean serum PRL level of 602.6 +/- 136.8 microg/L (range, 148-3511 microg/L); and 4) responsive: 28 patients previously treated with BRC or CV for 1-5 yr, achieving normoprolactinemia and restoration of gonadal function, but no longer treated with BRC or CV because of poor compliance or because the drug was not available. After a 15- to 30-day washout period, the serum PRL level was 397 +/- 43.1 microg/L (140-978 microg/L). CAB treatment was given at doses ranging 0.25-3.5 mg weekly for 1 yr to 110 patients, for 2 yr to 104 patients, and for 3 yr to 81 patients. Magnetic resonance imaging was performed before and after 12, 24, and 36 months of CAB treatment to evaluate significant tumor shrinkage (>80% reduction of pretreatment tumor volume). Among the 26 naive patients, normoprolactinemia was achieved in 21 (80.8%) after 1-6 months at 0.25-2 mg/week and in 5 patients after 24 months at 0.5-3 mg/week. Tumor volume was reduced from 1431.5 +/- 310.3 to 47.2 +/- 21.5 mm3 (P < 0.0001); average tumor shrinkage was 92.1 +/- 2.9%; significant tumor shrinkage was observed in 92.3% of patients, and tumor mass completely disappeared in 16 patients (61.5%). Among the 19 intolerant patients, normoprolactinemia was achieved in 18 (94.7%) after 1-6 months of CAB treatment at 0.25-1 mg/week. One patient remained mildly hyperprolactinemic. Tumor volume was reduced from 1925 +/- 423.1 to 842.0 +/- 330.7 mm3 (P < 0.001); average tumor shrinkage was 66.2 +/- 6.4%; significant tumor shrinkage was obtained in 42.1% of patients, and tumor mass completely disappeared in 4 patients (21%). Among the 37 resistant patients, normoprolactinemia was achieved in 19 (51.3%) after 6-12 months at 1-2 mg/week and in the remaining 18 patients after 18-24 months at 3-3.5 mg/week. Tumor volume was reduced from 1208.0 +/- 173.7 to 471.2 +/- 87.3 mm3 (P < 0.005);

Topics: Adolescent; Adult; Aged; Cabergoline; Dopamine Agonists; Drug Resistance; Ergolines; Female; Humans; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Prospective Studies; Treatment Outcome

To compare effectiveness and tolerability of quinagolide (CV 205-502) and cabergoline (CAB) treatments in 39 patients with prolactinoma.. All 39 patients were treated first with quinagolide for 12 months and then with cabergoline for 12 months. A wash-out period was performed in all patients after 12 months of both treatments in order to evaluate recurrence of hyperprolactinaemia.. Twenty-three patients with microprolactinoma (basal serum PRL levels 1620-18750 mU/l) and 16 patients with macroprolactinoma (basal serum PRL levels 4110-111000 mU/l), previously shown to be intolerant of bromocriptine. All patients had gonadal failure and 11 patients with macroprolactinoma had visual field defects. Five patients with macro- and one with microprolactinoma had previously undergone surgery.. The starting doses of quinagolide and CAB were 0.075 mg/day and 0.5 mg/week, respectively, subsequently increased up to 0.6 mg once daily and 1.5 mg twice weekly, respectively. Serum PRL levels were measured monthly for the first 3 months and then quarterly for 12 months. PRL levels were assayed weekly for the first month and then monthly during the wash-out period. Tumour shrinkage was evaluated by serial magnetic resonance imaging (MRI) studies of the hypothalamus-pituitary region at study entry and after 6 and 12 months of both treatments in micro- and macroprolactinomas.. After 12 months of quinagolide treatment, serum PRL levels normalized in all 23 patients with microprolactinoma (100%) and in 14 out of 16 with macroprolactinoma (87.5%). A tumour volume reduction of greater than 80% was documented by MRI studies in five of 23 (21.7%) patients with microprolactinoma and in four of 16 (25%) with macroprolactinoma. All patients had recurrence of hyperprolactinaemia after 15-60 days withdrawal of quinagolide treatment. However, before starting CAB treatment basal PRL levels were significantly lower than before quinagolide treatment both in microprolactinomas (4667.4 +/- 714.7 vs. 2636.1 +/- 262.3 mU/l, P = 0.006) and in macroprolactinomas (24853.1 +/- 7566.7 vs. 3576.6 +/- 413.0 mU/l, P = 0.013). After 12 months of CAB treatment, serum PRL levels normalized in 22 out of 23 patients with microprolactinoma (95.6%) and in 14 out of 16 with macroprolactinoma (87.5%). No difference in PRL nadir was found after quinagolide and CAB treatments both in micro 174.6 +/- 30.6 vs. 169.8 +/- 37.9 mU/l, P = 0.5) and in macroprolactinomas (277.5 +/- 68.4 vs. 341.8 +/- 95.2 mU/l, P = 0.6). A tumour volume reduction of greater than 80% was documented by MRI studies in seven other patients with microprolactinoma (30.4%) and in five other patients with macroprolactinoma (31.2%). After CAB treatment, further tumour shrinkage ranging 4-40% and 2-70% was observed in 12 micro- and seven macroprolactinomas, respectively. The percentage of tumour shrinkage after CAB was significantly higher than that observed after quinagolide in microprolactinomas (48.6 +/- 9.5 vs. 26.7 +/- 4. 5%, P = 0.046) but not in macroprolactinomas (47.0 +/- 10.6 vs. 26.8 +/- 8.4%, P = 0.2). The withdrawal from CAB treatment, induced an increase in serum PRL levels in all macroprolactinomas between 15 and 30 days, in 15 out of 23 microprolactinoma after 30 days, and in four patients after 2-4 months. In the remaining four patients serum PRL levels remained normal after 12 months of CAB withdrawal. Both compounds were tolerated satisfactorily by all patients. In the first week of quinagolide treatment, 12 patients reported nausea and postural hypotension, which spontaneously disappeared during the second-third week of treatment. None of the 39 patients reported side-effects during CAB treatment.. Both quinagolide and CAB treatments, induced the normalization of serum PRL levels in the great majority of patients with prolactinoma. Tumour shrinkage was recorded in 22-25% of patients after quinagolide and in 30-31% after CAB treatment

Topics: Adult; Aminoquinolines; Cabergoline; Cross-Over Studies; Dopamine Agonists; Ergolines; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Receptors, Dopamine D2; Treatment Outcome

There are few long-term studies of cabergoline (CAB) administration in patients with macroprolactinomas. All of these studies included different type of patients, such as patients with idiopathic hyperprolactinemia, microprolactinomas and previously treated or untreated macroprolactinomas. We report a study of CAB treatment conducted exclusively in patients with newly diagnosed, untreated, macroprolactinomas. Twelve patients (6 M, 6 F) with macropolactinomas were investigated prospectively for 12 months to determine the effects of prolonged treatment with CAB on serum PRL levels, tumor size, visual fields and prevalence of side effects. Nine of these patients continued therapy and follow-up for 6 or more additional months of CAB administration. Our results demonstrated that CAB decreased the volume of the tumor in all patients investigated 3 months after the initiation of treatment. Specifically, mean tumor volume was 11,327 +/- 25,187 mm3 before the study and decreased to 4281 +/- 8465 mm3 and 1544 +/- 2118 mm3 in the second and last measurement, respectively. However, these changes were not statistically significant, most probably due to the very high SD. As far as the maximum diameter is concerned, mean values was 22.8 +/- 16.9 mm before the study and decreased to 16.6 +/- 10.9 mm and 13.4 +/- 7.5 mm in the 3 months and last examination, respectively. These changes were statistically significant (p = 0.005 and p = 0.007). The mean percentage decrease of the tumor volume and maximum tumor diameter was 42.4 +/- 14.0% and 24.7 +/- 4.8% respectively in the third month and 67.2 +/- 17.3% and 35.9 +/- 11.8% in the last estimation. These differences were statistically significant, (p < 0.01 and p < 0.001, respectively). The same was also true for PRL levels, the mean of which was 14,719 +/- 20,616 before treatment and became normal in the third month (153.3 +/- 63.4) and continued to be throughout the study. Four patients had visual field defects, which improved or even completely resolved during the treatment period. Finally, the CAB doses used were particularly small, i.e., 0.5-2 mg per week. All the patients recovered from their clinical problems and symptoms. This remarkable improvement was associated with an excellent tolerability of the long-term treatment due to the low incidence of side effects. In conclusion, the results of the present study demonstrated that CAB produced tumor shrinkage and normalized PRL levels in all the patients studied. Also, cl

Topics: Adolescent; Adult; Antineoplastic Agents; Cabergoline; Child; Ergolines; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Time Factors; Visual Fields

Cabergoline (CAB) treatment is an effective, safe and well tolerated approach for hyperprolactinemia. We investigated the efficacy of 24-month treatment with CAB in 37 patients with previously untreated PRL-secreting pituitary adenoma and evaluated the hormonal and neuroradiological changes after the discontinuation of long-term therapy. Eleven patients with macroprolactinoma (1M/10F) and 26 with microprolactinoma (4M/22F) started treatment taking 0.25 mg CAB twice a week for 4 weeks. The dose was increased stepwise in 0.5 mg increments until reaching lowest maximally effective and tolerated dose. CAB was withdrawn before the end of the study in 6 women who became pregnant and in one patient who showed a slight increase of the macroadenoma at MRI. During treatment, PRL levels decreased significantly in macro (11.1+/-1.1 vs 407.8+/-98.3 microg/l, p<0.001) and microprolactinomas (11.1+/-1.6 vs 193.8+/-23.4 microg/l, p<0.05) and normalized in all macro and in 23/26 microprolactinomas. In 3 cases PRL levels decreased but did not normalize because the appearance of side effects, such as nausea or hypotension, prevented the increase of the dose of CAB. The effective dose of drug correlated significantly with basal serum PRL levels (p<0.05) and with the pituitary tumor size (p<0.05). A significant decrease of the mean adenoma size was evident for macro (6.9+/-1.8 vs 16.0+/-1.8 mm, p<0.001) and microprolactinomas (3.0+/-0.5 vs 6.5+/-0.4 mm, p<0.001) at MRI. The tumor disappeared in 4 macroadenomas and in 11 microadenomas after 12 months of treatment. CAB withdrawal was followed by serum PRL increase in 13 cases after 3 months, in 6 after 6 months, in 2 after 9 months, and in one patient at the 12th month. Five patients showed normoprolactinemia with negative MRI after one year. Regular menses were restored in 7/10 macroprolactinomas and in all oligo-amenorrhoic patients with microadenoma; serum testosterone levels normalized in 2/3 hypogonadic men. Five out of 6 women become pregnant and had uneventful pregnancies which resulted in deliveries of normal babies. In conclusion, this study confirms the effectiveness and safety of CAB for patients with PRL-secreting pituitary adenoma and suggests that it can be considered a first choice treatment.

Topics: Adolescent; Adult; Antineoplastic Agents; Cabergoline; Ergolines; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Prolactin; Prolactinoma; Treatment Outcome

Cabergoline is a new, long acting, dopamine agonist that is more effective and better tolerated than bromocriptine in patients with hyperprolactinemia. Because dopamine agonists still have a place in the medical management of acromegaly, cabergoline might be a useful treatment. We, therefore, evaluated the effect of long term administration of cabergoline in a large group of unselected acromegalic patients. Sixty-four patients were included in a multicenter, prospective, open labeled study. A subgroup of 16 patients had GH-/PRL-cosecreting pituitary adenomas. Cabergoline was started at a dose of 1.0 mg/week and was gradually increased until normalization of plasma insulin-like growth factor I (IGF-I) levels, occurrence of unacceptable side-effects, or a maximal weekly dose of 3.5 mg (7.0 mg in 1 case) was reached. Treatment with cabergoline suppressed plasma IGF-I below 300 micrograms/L in 39% of cases and between 300-450 micrograms/L in another 28%. With pretreatment plasma IGF-I concentrations less than 750 micrograms/L, a suppression of IGF-I below 300 micrograms/L was obtained in 53% of cases, and a suppression between 300-450 micrograms/L was obtained in another 32%. By contrast, with pretreatment plasma IGF-I concentrations above 750 micrograms/L, only 17% of cases showed a suppression of IGF-I below 300 micrograms/L, and there was IGF-I suppression between 300-450 micrograms/L in another 21%. In GH-/PRL-cosecreting adenomas, 50% of cases suppressed plasma IGF-I levels below 300 micrograms/L, and another 31% did so between 300-450 micrograms/L, in contrast to only 35% and 27%, respectively in GH-secreting adenomas. Similar results were obtained concerning the secretion of GH. Tumor shrinkage was demonstrated in 13 of 21 patients, with a mass reduction by more than half in 5 GH-/PRL-cosecreting adenomas. Except for slight gastrointestinal discomfort and orthostatic hypotension in a few patients at the beginning of therapy, cabergoline treatment was well tolerated. Only 2 patients stopped medication because of nausea. The weekly dose of cabergoline ranged between 1.0-1.75 mg. A further increase in the dose was only effective in 1 GH-/PRL-cosecreting adenoma. The results of this study suggest that cabergoline is an effective, well tolerated therapy that should be considered in the management of acromegaly, especially if the pituitary adenoma cosecretes GH and PRL or if pretreatment plasma IGF-I levels are below 750 micrograms/L.

Topics: Acromegaly; Adenoma; Adolescent; Adult; Aged; Cabergoline; Dopamine Agonists; Ergolines; Female; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prospective Studies

Eighteen active acromegalics entered a prospective open study with cabergoline (CAB), a dopaminergic drug much more potent than bromocriptine (Br).. CAB was administered for 6 months at doses ranging between 0.5 mg twice weekly and 0.5 mg/day. Clinical-anamnestic characteristics of the patients were: (i) sensitivity to dopamine agonist drugs (10 patients); (ii) resistance to somatostatin analogs (SAs) (8 patients): (iii) intolerance to SA (3 patients). In 2 patients marked hyperprolactinemia was present.. Basal GH was 6.6 microg/l (2.2-50) (median (range)), and on treatment it was 3.5 microg/l (1.2-34) (P=0.013). The corresponding IGF-I values were 720 microg/l (410-1438) and 375 microg/l (167-1260) respectively (P=0.00001). Individual GH levels decreased below 2 microg/l in 5 patients, and between 2 and 5 microg/l in another 5 patients. IGF-I levels were suppressed below 50% of baseline in 8 patients and normal age-adjusted IGF-I values were reached in 5 patients (27% of the series). The retrospective comparison with previous chronic treatment with Br in the 10 suitable patients showed a greater effectiveness of CAB (IGF-I decrease on CAB treatment, 46.8%, on Br treatment, 31%, P=0.02). Adenoma shrank in the 3 patients whose pituitary imaging was repeated during CAB.. These results envisage that CAB may represent a worthy therapeutic tool in acromegalic patients, inducing a degree of IGF-I and GH suppression comparable to SAs, administered by the oral route and much less expensive.

Topics: Acromegaly; Adenoma; Adult; Aged; Cabergoline; Dopamine Agonists; Ergolines; Female; Growth Hormone; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Pituitary Neoplasms; Prolactin

Cabergoline (CAB), a long-lasting dopamine-agonist, specific for the D2 receptor, is effective in normalizing serum PRL levels in most patients with microprolactinoma or idiopathic hyperprolactinemia. Because few data are presently available on the effects of CAB treatment in macroprolactinomas, the aim of this open-label study was to investigate whether this drug was effective in producing tumor shrinkage, as well as in normalizing PRL levels. Twenty-three patients with macroprolactinoma entered this study 15 patients had had no treatment, whereas the remaining 8 patients had been previously treated with bromocriptine, which was with-drawn because of intolerance. Three of 23 patients had undergone unsuccessful surgery. Pretreatment serum PRL levels ranged from 100-3860 micrograms/L. CAB was administered at a dose of 0.5-3 mg once or twice a week for 12-24 months. Magnetic resonance imaging (MRI) scans were performed before and 3, 6, 12, and 24 months after the beginning of treatment, to evaluate tumor shrinkage, defined as a decrease of at least 80% of baseline tumor volume. After 3-6 months of treatment with a low dose (0.5-1 mg/week), serum PRL levels normalized in 18 patients. In the remaining 5 patients, whose serum PRL levels were not normalized, the dose was increased to 2-3 mg/week. This schedule caused the normalization of PRL levels in 1 patient, whereas in the remaining 4 patients, PRL levels were reduced to 30-82 micrograms/L. A tumor volume reduction greater than 80% at MRI occurred in 14 of 23 patients (61%) after CAB treatment (from 2609.4 +/- 534.7 to 530.1 +/- 141.3 mm3 at the 12-24th month follow-up, P < 0.001). A volume reduction of 41.8 +/- 3.4% was already evident after 3 months (1436 +/- 285.9 mm3; P < 0.001). The complete disappearance of the tumor mass at MRI occurred after 6 months of treatment with CAB in 1 patient, and in 5 patients after 1 yr of treatment. An improvement of visual field defects was obtained in 9 of the 10 patients presenting visual impairment before CAB treatment. The drug was tolerated well by all patients. Only 1 patient experienced mild nausea, which disappeared spontaneously after the 2nd day of treatment. Long-term, a low dose of the D2 receptor agonist CAB significantly reduced tumor volume and normalized serum PRL levels in a great majority of patients bearing macroprolactinoma. This treatment met with excellent patient compliance. This study suggests that CAB can be used as a first choice drug treatment

Topics: Adolescent; Adult; Antineoplastic Agents; Cabergoline; Ergolines; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Time Factors; Treatment Outcome; Visual Field Tests

Cabergoline (Cab), a very potent and long-lasting dopaminergic compound, was administered to 26 women with pituitary microprolactinoma [mean serum PRL levels: 124.8 +/- 11.3 micrograms/l (+/- SE), range 62-300 micrograms/l] and 3 patients with GH-secreting pituitary adenoma (2 with associated PRL hypersecretion) for 12 and 24 months, respectively. In microprolactinomas, a stable normoprolactinemia was achieved in 96.1% of cases: in 13 women (50%) with the lowest dose of the drug (0.5 mg/week), and in other 12 patients (46.1%) with increasing doses up to 3 mg/week. All the oligomenorrheic/amenorrheic women, except one, restored regular and ovulatory menses. Two patients became pregnant. Pituitary abnormalities at high resolution-CT (HR-CT) scan disappeared in 13 of 19 patients (68.4%) after 12 months of therapy and this feature persisted in 8/13 cases (61.5%) 12 months after drug withdrawal. During Cab discontinuation (range: 3-60 months), mean serum PRL levels remained significantly lower than the basal ones. Six of 25 women are still without therapy. In 2 patients, normoprolactinemia persisted up to 38 and 60 months, respectively. Cab treatment was re-instituted in 13 patients because of the recurrence of hyperprolactinemia. Five patients were lost at follow up. In all the acromegalic patients, Cab (1-3 mg/week) normalized serum GH, IGF-I and PRL levels. A clear improvement in clinical symptoms was observed in all patients, but neuroradiological improvement in only one. Cab therapy was very well tolerated, as only seven patients complained of mild and transient side-effects and none had to stop treatment. In conclusion, Cab is an effective, safe, and well tolerated dopaminergic compound for the treatment of hyperprolactinemic disorders and the control of the clinical and hormonal features of dopamine-sensitive acromegalic patients.

Topics: Acromegaly; Adenoma; Adult; Cabergoline; Dopamine Agonists; Ergolines; Female; Human Growth Hormone; Humans; Hyperprolactinemia; Insulin-Like Growth Factor I; Middle Aged; Pituitary Neoplasms; Pregnancy; Prolactin

Cabergoline is a new long-acting crgoline derivative used to treat hyperprolactinaemia. Its effect was assessed in 10 patients (eight women and two men) with prolactinoma who were intolerant (group I: N = 7) or resistant (group II: N = 3) to bromocriptine. In group I, no side effect was observed on cabergoline therapy; two patients became pregnant and normoprolactinaemia was achieved in the live others. In group II, cabergoline was active and well-tolerated in two out of the three patients: one woman had three consecutive pregnancies: in another patient normoprolactinaemia was restored and the tumour shrank by 60%; in the third patient cabergoline was discontinued because of side effects and inefficacy. Thus, cabergoline appears to be an alternative of choice as treatment of hyperprolactinaemic patients who are intolerant or resistant to bromocriptine.

Topics: Adult; Antineoplastic Agents; Bromocriptine; Cabergoline; Dopamine Agonists; Drug Resistance, Neoplasm; Ergolines; Female; Humans; Male; Middle Aged; Pituitary Neoplasms; Pregnancy; Prolactinoma

Hyperprolactinemia can successfully be treated by dopaminagonists such as bromocriptin or lisuride. About 10% of patients complain about side effects like orthostatic hypotension, nausea or vomiting, which may lead to discontinuation of treatment. We therefore conducted a study using terguride--a new dopaminagonist--in 5 patients with hyperprolactinemia and intolerable side effects under conventional treatment. Terguride is the transdihydroderivative of lisuride (Dopergin). We treated 5 patients, 2 men with macroprolactinoma and 3 women with microprolactinoma with terguride. The mean duration of treatment was 15.6 months (7-37 months). Patients were treated with up to 5 mg terguride daily. All 5 patients had a marked initial decrease of elevated prolactin levels 8 h after administration of 0.25 mg terguride orally. Three patients became normoprolactinemic after sufficient increase of the dose of terguride, 2 female patients with a microprolactinoma got eumenorrhoeic thereafter. The treatment with terguride was tolerated without side effects by all patients. There were no significant changes of the examined parameters of clinical chemistry nor the other pituitary hormones. Results of cranial computertomography did not change in 4 patients, one patient had tumor progression. Tergurid as a dopaminagonist is an effective inhibitor of prolactin with little side effects and thus a useful drug in the treatment of hyperprolactinemia.

Topics: Adult; Clinical Trials as Topic; Dose-Response Relationship, Drug; Ergolines; Female; Follow-Up Studies; Humans; Hyperprolactinemia; Lisuride; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Prospective Studies

Cabergoline, a new orally active dopaminergic drug with an extremely long-lasting PRL-lowering effect, was given to 48 hyperprolactinemic women for 3-18 months (median, 8 months) at doses varying between 0.2-3 mg/week administered one to three times weekly. Serum PRL levels declined to normal in 41 women, 30 of whom received 0.2-1 mg cabergoline once weekly, 8 received 0.2-0.5 mg twice weekly, and 3 received 0.4-0.6 mg 3 times weekly. Five women had slightly supranormal serum PRL levels while receiving 0.3-0.6 mg once weekly, but the dose was not increased because the lower dose had produced the desired clinical benefit. Two women had 50% reductions in their serum PRL levels, but remained hyperprolactinemic while receiving 2-3 mg cabergoline weekly. Among 30 amenorrheic women, 28 had resumption of menses, the exceptions being 2 hypopituitary women, presumptive evidence of ovulation was available in 21. Marked tumor shrinkage occurred after 3-month treatment in 5 of the 6 women who had macroprolactinomas. Only 4 women had side-effects during the first weeks of treatment, and these vanished despite continued cabergoline administration at the same or reduced, but still effective, doses. In a short term, double blind study, cabergoline at 3 different schedules (0.4 mg twice weekly, 0.2 mg 4 times weekly, and 0.4 mg 3 times weekly for 3 weeks, followed by 0.4 mg twice weekly) or placebo was given to a total of 24 hyperprolactinemic women (6 in each subgroup) for 8 weeks, with weekly evaluation of serum PRL levels and side-effects. All 3 cabergoline schedules, but not placebo, induced significant reductions in serum PRL concentrations during the 8-week treatment period. Mild transient side-effects occurred in 7 drug-treated patients (nausea in 5; dizziness in 3). We conclude that cabergoline is effective treatment for hyperprolactinemia. Its efficacy, tolerability, and long duration of action may make it the drug of choice for patients with hyperprolactinemia.

Topics: Administration, Oral; Adolescent; Adult; Cabergoline; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Ergolines; Female; Humans; Hyperprolactinemia; Middle Aged; Pituitary Neoplasms; Placebos; Prolactin; Prolactinoma; Radiography

CU 38085 (mesulergin) was given at doses ranging from 0.5 to 5 mg/day to 37 patients with pathological hyperprolactinaemia of varying aetiology. The effectiveness of this drug on the suppression of hyperprolactinaemia and on the recovery of gonadal functions was equivalent to that of bromocriptine previously given to a different group of 83 hyperprolactinaemic patients. Tumour shrinkage during treatment with CU 32085 was ascertained in two cases of macroprolactinoma. Histological examination after adenomectomy revealed extensive peri-vascular fibrosis in both cases. In most patients, the efficient doses of CU 32085 were 5-fold lower than those of bromocriptine. After acute oral administration in 10 previously untreated patients, 0.5 mg of CU 32085 had a more prolonged suppressive effect on Prl levels than 2.5 mg of bromocriptine (approximately 18 vs 12 h). According to this, 0.5 mg CU 32085 once a day was sufficient to maintain Prl levels within the normal range in 16 patients. Side-effects were similar in nature and frequency to those induced by bromocriptine and seemed to be dose-dependent. They can be avoided by slowly increases of dose at initiation of treatment.

Topics: Administration, Oral; Adolescent; Adult; Aged; Bromocriptine; Clinical Trials as Topic; Ergolines; Female; Gonads; Humans; Hyperprolactinemia; Male; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Prolactin; Receptors, Dopamine; Tomography, X-Ray Computed

Thirty-one patients with hyperprolactinemia were admitted for protocol study. Twenty-one of these patients had no findings of prolactinoma by computerized axial tomography (CAT) scanning; 10 had documented tumor by CAT scan. The patients were assigned to either Parlodel or Pergolide treatment on the basis of random numbers tables. They were treated for 6 months continuously and followed during this time with radiologic survey, hormonal evaluation, and blood chemistry determinations. Patients in both groups showed a decrease in prolactin levels, whether they were treated with Parlodel or Pergolide. The response was similar whether patients had hyperplasia or pituitary tumors. Patients with pituitary tumors tended to have a diminution in the size of their lesions regardless of the dopamine agonist used. The types of side effects experienced by various groups were similar regardless of the treatment. It is concluded that both Pergolide and Parlodel are useful in the treatment of hyperprolactinemic syndromes, although neither one appears to be superior to the other.

Topics: Adolescent; Adult; Aged; Amenorrhea; Bromocriptine; Clinical Trials as Topic; Dopamine; Ergolines; Female; Galactorrhea; Humans; Middle Aged; Pergolide; Pituitary Neoplasms; Pregnancy; Prolactin; Random Allocation

Ectopic prolactin-secreting microadenomas are rare and management is often surgical in contrast to intrasellar pituitary prolactin-secreting microadenomas. We present a case of ectopic dopamine-resistant microprolactinoma treated with cabergoline which led to symptom resolution, hormonal remission, and cystic degeneration of the tumor. A 30-year-old active duty male presented with a chief complaint of inability to maintain an erection for 6 months. Initial workup revealed suppressed serum testosterone of 128.60 ng/ml with an elevated prolactin level at 275.10 ng/ml. Pituitary magnetic resonance imaging showed a small mass measuring 9 mm in the left cavernous sinus. Medical management was initiated with cabergoline, which was titrated over the course of a year from 0.5 mg a week to 3.5 mg a week at its peak before being weaned off completely at 54 months. After treatment, the patient's symptoms resolved, his prolactin decreased to 29.5 ng/ml, near-normal, and his tumor had decreased size with cystic degeneration. Management for any prolactinoma has three primary goals: remittance of symptoms, decrease in prolactin levels, and decrease in tumor size. These are achieved through primarily medical management or surgery. Even though ectopic microprolactinomas are still frequently addressed surgically, this case shows that medical therapy can successfully treat ectopic prolactin-secreting pituitary microadenomas even in cases of dopamine resistance.

Topics: Adult; Cabergoline; Cavernous Sinus; Dopamine; Ergolines; Humans; Male; Pituitary Neoplasms; Prolactin; Prolactinoma

A 60-year-old patient, professor of physics, presented in 1999 with sudden-onset vitiligo associated with hyperprolactinemia and a prolactinoma. Fearful of potential surgical complications at the peak of his career, the patient declined surgery and opted for medical management with bromocriptine. The decreasing effectiveness of bromocriptine after 5 years required a switch to cabergoline. After a 15-year-course of cabergoline therapy with a cumulative dose of 572 mg, echocardiographic monitoring demonstrated aortic and mitral valve thickening and regurgitation. An additional 3 years of cabergoline treatment (cumulative dose: 649 mg) resulted in worsening valve thickening and regurgitation. It is well-recognized that such valvular changes may occur with high-dose cabergoline treatment. We report a case of mitral and aortic vavulopathy in a patient who was treated with long-term (18 years) low-dosage (.5-1 mg weekly) cabergoline. cabergoline, echocardiography, valvulopathy.

Topics: Bromocriptine; Cabergoline; Ergolines; Heart Valve Diseases; Humans; Middle Aged; Pituitary Neoplasms

Knockout prolactin receptor gene (PRL-R) mice are animal models for prolactinomas and PRL acts via autocrine/paracrine inhibiting lactotroph proliferation. Recently, variants of the PRL-R were identified in prolactinoma patients and their frequency was higher compared to individuals from the genomic database.. We analyzed PRL-R variants frequency in an extensive cohort of prolactinoma patients and evaluated their association with clinical, laboratorial, and imaging characteristics and hormonal response to cabergoline.. Observational, retrospective, and cross-sectional study.. This study took place at the Neuroendocrinology Unit of Clinics Hospital, Medical School of University of São Paulo, Brazil, a tertiary referral center.. Study participants included adults with sporadic prolactinomas treated with cabergoline, where response to therapy was defined by prolactin normalization with up to 3 mg/week doses. DNA was extracted from blood samples and the PRL-R was analyzed by polymerase chain reaction techniques and automatic sequencing. The association of PRL-R variants with serum prolactin levels, maximal tumor diameter, tumor parasellar invasiveness, and response to cabergoline was analyzed.. We found 6 PRL-R variants: p.Ile100(76)Val, p.Ile170(146)Leu, p.Glu400(376)Gln/p.Asn516(492)Ile, p.Glu470Asp e p.Ala591Pro; the last 2 are newly described in prolactinomas' patients. The variants p.Glu400(376)Gln/p.Asn516(492)Ile and p.Ala591Pro were more frequent amongst patients compared to genomic databases, and the p.Asn516(492)Ile showed pathogenic potential using in silico analysis as previously described. PRL-R variants were associated with male sex (P = 0.015), higher serum PRL levels (P = 0.007), larger tumors (P = 0.001), and cabergoline resistance (P < 0.001).. The prolactin/prolactin receptor system seems to be related to prolactinoma tumorigenesis and cabergoline resistance. Additional studies are needed to better understand the PRL-R variants' role and their potential as therapeutic targets.

Topics: Animals; Cabergoline; Cross-Sectional Studies; Dopamine Agonists; Ergolines; Humans; Male; Mice; Mice, Knockout; Pituitary Neoplasms; Prolactin; Prolactinoma; Receptors, Prolactin; Retrospective Studies

This guideline (GL) is aimed at providing a reference for the management of prolactin (PRL)-secreting pituitary adenoma in adults. However, pregnancy is not considered.. This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinologi (AME) has identified potentially relevant outcomes, which have then been rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" have been considered in the systematic review of evidence and only those classified as "critical" have been considered in the formulation of recommendations.. The present GL provides recommendations regarding the role of pharmacological and neurosurgical treatment in the management of prolactinomas. We recommend cabergoline (Cab) vs. bromocriptine (Br) as the firstchoice pharmacological treatment to be employed at the minimal effective dose capable of achieving the regression of the clinical picture. We suggest that medication and surgery are offered as suitable alternative first-line treatments to patients with non-invasive PRL-secreting adenoma, regardless of size. We suggest Br as an alternative drug in patients who are intolerant to Cab and are not candidates for surgery. We recommend pituitary tumor resection in patients 1) without any significant neuro-ophthalmologic improvement within two weeks from the start of Cab, 2) who are resistant or do not tolerate Cab or other dopamine-agonist drugs (DA), 3) who escape from previous efficacy of DA, and 4) who are unwilling to undergo a chronic DA treatment. We recommend that patients with progressive disease notwithstanding previous tumor resection and ongoing DA should be managed by a multidisciplinary team with specific expertise in pituitary diseases using a multimodal approach that includes repeated surgery, radiotherapy, DA, and possibly, the use of temozolomide.. The present GL is directed to endocrinologists, neurosurgeons, and gynecologists working in hospitals, in territorial services or private practice, and to general practitioners and patients.

Topics: Adult; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Humans; Pituitary Neoplasms; Prolactin; Prolactinoma

Giant prolactinomas (GP) are rare tumors accounting for 4.3% of prolactinomas, with paucity of literature from India. We aim to describe clinical, biochemical, radiological, and treatment outcomes in a large series of Asian-Indian patients with GP.. A single-center retrospective analysis of GPs (n=84), age-based (adults: 66 versus pediatric: 18) and gender-based (males: 64 versus females: 20) comparison was done.. The mean age at presentation was 34.1±13years, and 64 (76.2%) were males. Males were younger at presentation (32.1±12.2 versus 40.1±13.8years, P: 0.01). The majority presented with mass-effect-related manifestations (visual disturbances: 91.6%, headache: 84.5%) and/or hypogonadism (98.7%). At baseline, largest tumor dimension was 5.3±1.0cm, and serum prolactin was 8343 (3865.5-12,306) ng/mL; most (94.6%) had gonadal axis involvement. Dopamine-agonist (DA) as first-line therapy (45/67, 67.2%) achieved normoprolactinemia (maximum cabergoline dose: 2.0±1.2mg/week) in 36/45 (80%) and tumor response (≥50% reduction) in 36/37 (97.3%) patients at the last follow-up (median duration: 33 [14.5-53.5]months). Notably, gonadal axis recovery was poor (6/30, 20%) despite normoprolactinemia post-DA monotherapy. At latest follow-up, secondary hypothyroidism (32.5% versus 82.6%, P: 0.001) and central hypocortisolism (5.6% versus 42.9%, P: 0.007) were less frequent in DA monotherapy (n=43) than in multimodal therapy group (n=23). The proportion of males (94.4% versus 71.2%, P: 0.04) was higher in the pediatric age group, with DA-induced (first-line) normoprolactinemia observed in 66.7% of them.. GP has male predominance, DA as first-line therapy normalized prolactin in four-fifths of patients with better preservation of HPT and HPA axes in patients with DA monotherapy.

Topics: Adult; Child; Dopamine Agonists; Ergolines; Female; Humans; Male; Pituitary Neoplasms; Prolactin; Prolactinoma; Retrospective Studies

Prolactin (PRL)-secreting tumors are the most common functional pituitary adenomas. They usually respond to dopamine agonist (DA) treatment, with PRL normalization and adenoma shrinkage. Our aim was to characterize patients with prolactinoma resistant to DA treatment.. This retrospective case series included patients diagnosed with DA-resistant prolactinomas between 1993-2017 in three medical centers. Resistance was defined as PRL levels above three times the upper limit of normal (ULN) despite a weekly dose of ≥2 mg cabergoline (CAB). Clinical and biochemical information, and response to treatment, were retrieved from medical records.. Twenty-six patients were identified; 20 males. Of 25 macroadenomas, three were giant tumors (>40 mm) and 15 (57.7%) were invasive. The mean age at diagnosis was 31.8 ± 14.9 years (range: 13-62). The median maximal CAB dose was 3.5 mg/week (IQR, 2.5-5). Half the patients received only CAB in escalating doses, nine received CAB and underwent transsphenoidal surgery, and four underwent surgery and radiotherapy in addition to CAB treatment. PRL levels at baseline between patients treated only with CAB and those operated were (91.6 [51.1-296.7] vs. 73.1 [22.6-170.9] XULN p = 0.355), and under maximal CAB dose PRL levels between patients treated only with CAB and those operated were similar (5.77 [1.27-11.27] vs 5.27 (2.9-26) XULN p = 0.317). At the last visit patients who received combined therapy achieved lower PRL levels than those treated with DA only (5.22 [1.7-21.6] vs 1.1 [0.44-3.99] XULN p = 0.017) PRL normalization was attained in seven patients and levels below 3 × ULN in fourteen patients; the overall response was 56%.. Resistant prolactinomas usually require a multi-modal treatment strategy. We were able to control 14/25 (56%) of resistant tumors.

Topics: Adenoma; Adolescent; Adult; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Retrospective Studies; Young Adult

Prolactinomas are rare in children and adolescents. As in adults, dopamine agonists (DAs) are the treatment of choice in the majority of patients. However, at what point children should be taken off of therapy and what the recurrence risk of hyperprolactinemia is following treatment withdrawal is not well described.. Our objective was to systematically review our experience with DA treatment withdrawal in children and adolescents with prolactinomas.. A retrospective review of patients followed for prolactinomas during the last 12 years was conducted. Variables analyzed included age, gender, initial serum prolactin levels, tumor characteristics, cabergoline dose, and results of treatment withdrawal. Clinical characteristics of patients who met eligibility criteria for DA withdrawal were compared with those who did not. Patients who underwent surgery were excluded.. Of 47 patients identified, 42 were included in the study. Of those, DA withdrawal was attempted in 13 (31%) and was initially successful in 3 (21%). Patients who did not meet eligibility criteria for treatment withdrawal had higher baseline prolactin levels (p = 0.018) as well as larger (p = 0.03) and more invasive (p = 0.002) tumors.. Less than half of our patients were eligible for DA treatment withdrawal and less than one-fourth achieved remission of hyperprolactinemia following cessation of therapy. This suggests that the overall recurrence rate of prolactinomas in pediatric patients may be higher than has been reported in adults.

Topics: Adolescent; Child; Dopamine Agonists; Ergolines; Female; Humans; Hyperprolactinemia; Male; Pituitary Neoplasms; Prolactin; Prolactinoma; Treatment Outcome

Hypogonadism is the most common form of hypopituitarism in men with macroprolactinoma. However, evidence on factors related to hypogonadism recovery is limited.. We estimated the proportion of hypogonadism in men with macroprolactinoma exclusively treated with dopamine agonists, and we assessed the factors predicting hypogonadism recovery.. This was a multicenter retrospective study of men with macroprolactinoma identified using ICD 9 and 10 codes and treated between 2009 and 2019 in five centers in the United Arab Emirates and Saudi Arabia. We evaluated hypogonadism, defined as low total testosterone (TT) level with normal or low gonadotropins on presentation and during the last clinic visit.. A total of 79 patients (median age 32 years) were included in the study. The most common symptoms at presentation were headache (73.7%), erectile dysfunction (55.4%), and low libido (54.3%). The median tumor size was 2.9 cm (1.0-9.7) at diagnosis. Sixty-three patients (79.7%) had hypogonadism at baseline. Growth hormone deficiency (GHD) and hypothyroidism were present in 34.4% and 32.9% of patients, respectively. The median serum prolactin (PRL) level was 20,175 (min-max 2254 - 500,000) mIU/l with a median serum TT of 4.5 (min-max 0.4-28.2) nmol/l. Most patients were treated with cabergoline (n = 77, 97.5%) with a median of 6 (min-max 0.6-22) years. At follow-up, 65% of patients recovered their pituitary-testicular axis. Patients with recovered hypogonadism had smaller median tumor size (2.4 [1-5.4] vs. 4.3 [1.6-9.7], p = 0.003), lower PRL level (18, 277 [2254 - 274, 250] vs. 63,703 [ 3,365-500,000], p = 0.008 ), higher TT level (4.6 [0.6-9.2] vs. 2.3 [0.5-7.3], p = 0.008), lower PRL normalization time on medical therapy (8 months (0.7-72) vs. 24 (3-120), p = 0.009) as well as lower frequency of GHD (17.1% vs. 60%, p = 0.006) and secondary hypothyroidism (17.9% vs. 57.1%, p = 0.003) compared with those with persistent hypogonadism respectively. Age at diagnosis, presenting symptoms and duration of medical therapy did not predict hypogonadism recovery.. About two-thirds of men with macroprolactinoma recover from hypogonadism, mostly with 24 months of therapy. Smaller adenoma size, lower prolactin level, earlier prolactin normalization, and higher testosterone patients were related to testosterone normalization.

Topics: Adult; Dopamine Agonists; Ergolines; Humans; Hypogonadism; Hypothyroidism; Male; Pituitary Neoplasms; Prolactin; Prolactinoma; Retrospective Studies; Testosterone

A 22-year-old man complaining erectile dysfunction underwent transsphenoidal surgery for a 2.7 cm sellar mass with total resection and was confirmed at pathology to have a lactotroph pituitary neuroendocrine tumor (PiNET). Postoperatively, the patient's PRL remained at high level and therefore accepted high-dose dopamine receptor agonist (DA) therapy. After over 3 months of bromocriptine (BRC) (15mg/day) and over 3 years of cabergoline (CAB) (3mg/week) therapy, the patient's prolactin (PRL) never achieved long-term normalization. He was diagnosed with DA-resistant lactotroph PitNET.. In this study, the patient was given hydroxychloroquine (HCQ) (200 mg/d) and CAB (3 mg/w) in combination for four months. His PRL level was tested by blood test every month.. Taking the combination therapy of HCQ and CAB, the patient's uncontrolled PRL level was normalized within one month and was maintained at the normal level thereafter. Pituitary magnetic resonance imaging (MRI) images with enhancement showed no recurrence. The patient also regained normal sexual function.. This is the first report on the combination of HCQ with CAB for the effective treatment of DA-resistant lactotroph pituitary neuroendocrine tumor in a patient, which might provide a novel treatment strategy for clinical management.

Topics: Adult; Cabergoline; Ergolines; Humans; Hydroxychloroquine; Lactotrophs; Male; Neuroendocrine Tumors; Pituitary Neoplasms; Prolactin; Prolactinoma; Young Adult

Cabergoline (CAB) therapy for prolactinomas has been associated with serum IGF-1 levels modifications, with recent reports indicating a paradoxical increase of IGF-1 levels during ongoing therapy. As a result, IGF-1 measurement has been proposed not only at diagnosis of a prolactinoma, but also during follow-up. In this follow-up study on prolactinoma patients with chronic CAB therapy, we investigated whether there are long-term changes in IGF-1 levels that necessitate continuous monitoring.. We reviewed our institutional database on prolactinoma patients with long-term CAB therapy, in whom IGF-1 levels were measured at baseline, at 3-months follow-up and in the long term.. Chronic CAB therapy was noted in 20 patients (13 men, 7 women). Median (±SD) age was 43.5 ± 12.6 years. 17 (85%) patients presented with a macroprolactinoma. Median CAB treatment time was 75 ± 43 months (range 24-187). Median IGF-1 levels increased at last follow-up, though not significantly; from 122 ± 37 ng/ml (IQR 104-160 ng/ml) to 133 ± 54 (IQR 121-162 ng/ml), p = 0.10. Thereby, 18 (90%) patients showed normal serum IGF-1 levels adjusted for age, one (5%) patient above (1.05 × ULN) and 1 (5%) patient below the normal range (0.34 × ULN). No patient was or became symptomatic of acromegaly.. Our long-term results indicate that chronic treatment with CAB in prolactinoma patients does not significantly modify serum IGF-1 levels. Bearing in mind the sample size of this study, continuing IGF-1 monitoring is not indicated in prolactinoma patients with long-term CAB therapy.

Topics: Adult; Cabergoline; Dopamine Agonists; Ergolines; Female; Follow-Up Studies; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma

Topics: Cabergoline; Ergolines; Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactinoma

Topics: Cabergoline; Ergolines; Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactinoma

To study the outcome of men with macroprolactinoma following cabergoline treatment based on tumour size.. Retrospective cohort study.. The study included 94 men, divided into three groups according to adenoma diameter: 10-19 mm (Group A, n = 36); 20-39 mm (Group B, n = 41); or ≥40 mm (Group C, giant prolactinomas, n = 17). Patients were followed for a mean of 7.5 years with sellar magnetic resonance imaging, visual fields and hormone measurements.. Mean baseline prolactin was 767, 2090 and 24,806 ng/ml in Groups A, B and C, respectively (p < .01). Prolactin suppression below three times the upper limit of normal (ULN) was achieved in 34 (94%; mean weekly cabergoline dose of 1.2 mg), 37 (90%; cabergoline dose, 2.1 mg) and 15 (88%; cabergoline dose, 2.8 mg) men (p = .31) in each group. After excluding patients who underwent surgery and radiotherapy, cabergoline suppressed prolactin below three times ULN in 32/35 (91%), 29/37 (78%) and 11/14 (79%) men in Groups A, B and C, respectively (p = .27). Visual deficits were observed in 5 (14%), 12 (29%) and 10 (59%) patients (p < .01); improvement was achieved in 5/5 (100%), 11/12 (92%) and 10/10 (100%) of men in Groups A, B and C. Low baseline testosterone was measured in 26 (72%), 39 (95%) and 17 (100%) patients in the three groups (p < .01). Following multi-modal treatment, hypogonadism persisted in 3 (8%), 5 (12%) and 2 (12%) men, respectively (p = .85).. Macroprolactinomas in men were controlled with cabergoline in 84% of cases, independent of tumour size. Pituitary surgery and adjuvant radiotherapy further improved long-term response to 91%.

Topics: Cabergoline; Dopamine Agonists; Ergolines; Humans; Male; Pituitary Neoplasms; Prolactin; Prolactinoma; Retrospective Studies; Treatment Outcome

Prolactin-secreting adenoma (PRLoma) can present as large and invasive neoplasm, with increased markers of cellular proliferation. First-line approach is Dopamine Agonists (DAs) treatment; however, DA-resistance has been reported, especially in male patients. Estrogens induce lactotroph cell replication and PRL secretion: the use of anti-estrogen treatment in patients with PRLoma have been described in few cases. We reported our experience regarding treatment with the aromatase inhibitor anastrozole (ANA) as add-on therapy for male patients with DA resistant PRLoma.. We describe four male patients (26, 38, 29 and 19 years old at diagnosis), with PRLoma (median diameter 26 mm, PRL 7730 μg/L). They were resistant to cabergoline (CAB, > 2 mg/week) in terms of PRL secretion and tumor size reduction. ANA 1 mg/day was added to the maximum tolerated dose of CAB for at least 1 year. Magnetic Resonance was performed at baseline, after 6 months of CAB + ANA combination and every 12 months afterward.. PRL levels decreased in all patients after CAB + ANA (mean - 70%, range - 44/- 97%), achieving a normalization of PRL levels in one case. Tumor size decreased in all cases (mean - 47%, range - 24.5/- 68%). No severe adverse effects have been reported, a moderate weight gain has been observed in two cases.. Addition of an aromatase inhibitor (ANA) to the dopamine agonist therapy improved the control of prolactin levels and induced tumour regression.

Topics: Anastrozole; Cabergoline; Dopamine Agonists; Ergolines; Humans; Male; Pituitary Neoplasms; Prolactin; Prolactinoma

Topics: Cabergoline; Dopamine Agonists; Ergolines; Humans; Insulin-Like Growth Factor I; Pituitary Neoplasms; Prolactinoma

Treatment with dopamine agonists (DA) is highly effective in patients with prolactinomas. In selected patients, discontinuation of DA after several years of successful treatment is possible, however, hyperprolactinemia recurs in 60-80% of them. It is unclear what is the clinical significance of these recurrences and hence, whether or not reinitiation of therapy is necessary.. To evaluate the recurrence rate in prolactinoma patients after DA withdrawal and the necessity to restart treatment.. Patients with >2 years of treatment with cabergoline (CBG) who achieved normoprolactinemia and a > 50% reduction in tumor size were included. DA dose was down titrated until withdrawal. Basal tumor size, as well as PRL and gonadal steroid levels were recorded at diagnosis, at withdrawal of DA and every 3-6 months for 1-3 years.. Fifty patients were included (38 women, 34 macroprolactinomas). After withdrawal, 34 (68%) presented recurrence of hyperprolactinemia. PRL levels <5 ng/mL at the time of withdrawal predicted remission (sensitivity 76%, specificity of 63%). CBG was restarted in eight patients (23%) because of the presence of hypogonadism. CBG was withheld in the remaining 26, based on the following arguments: (1) premenopausal women without biochemical hypogonadism, (54%); (2) asymptomatic men under 65 without biochemical hypogonadism (19%); (3) asymptomatic postmenopausal women (19%); (4) asymptomatic men over 65 (8%). After a median follow-up of 30 months, no increase in PRL levels or tumor growth was documented.. Biochemical recurrence in prolactinomas is very frequent, however, in only a few of these patients reinitiation of DA is necessary.

Topics: Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Male; Neoplasm Recurrence, Local; Pituitary Neoplasms; Prolactin; Prolactinoma

Currently, cabergoline therapy is the main method of treatment with prolactin. The use of the drug in most cases leads to tumor regression, normalization of prolactin levels and restoration of gonadotropic function. The mechanism of its impact on tumor cells in vivo, which is dynamically traced in the same human tumor, is the case of considerable interest. We observed a 30-year-old patient who was operated on twice for a giant prolactinoma before and on treatment by cabergoline. The morphological study after the first surgery (before introducing of cabergoline therapy) revealed a prolactin-positive pituitary tumor with a Ki-67 labeling index of 8% and with strong expression of dopamine type 2 receptors (D2R), CD31 and CD34. After 4 months, during which the patient received cabergoline at a dose starting from 0.5 mg to 1.5 mg per week, a second transsphenoidal surgery was performed with subtotal removal of residual tumor tissue. During the morphological study of the second biopsy sample, the tumor retained a pronounced immunopositivity to prolactin and D2R, with a decrease in the labeling index Ki-67 to 2%, as well as a decrease in the expression of CD31 and CD34. Subsequent cabergoline therapyresulted in persistent normoprolactinemia, restoration of androgen (and reproductive) status, and no tumor recurrence over a 10-year period on cabergoline treatment. Thus, one of the mechanisms of effect of cabergoline that leads to tumor regression is a decrease in the proliferative index and angiogenesis of the tumor.

Topics: Adult; Cabergoline; Dopamine Agonists; Ergolines; Humans; Neoplasm Recurrence, Local; Pituitary Neoplasms; Prolactinoma

Prolactinomas are pituitary tumors with a very low prevalence in childhood and adolescence compared to adulthood. This condition is preferentially treated with dopamine agonists. Resistance to these drugs is rare.. We describe the case of a boy diagnosed with macroadenoma at the age of 9 and followed up for 21 years. He did not fully respond to treatment with dopamine agonists. His initial prolactin level was 2,400 ng/mL (in males, normal values are <16.0 ng/mL) and never normalized. At the last assessment, his prolactin level was 21.5 ng/mL, recorded after 21 years of treatment with the dopamine agonist cabergoline at a dose as high as 4.5 mg per week. Although the prolactin level remained elevated throughout the follow-up period, the patient never presented a low testosterone level and had normal pubertal development. An MRI of the sella turcica showed that the tumor became progressively cystic and disappeared, but a normal pituitary gland was observed. The pituitary gland retained its normal functions despite a partially empty sella.. Long-term treatment with high doses of cabergoline may cause cystic degeneration of a prolactinoma considered to be resistant to this treatment, but we cannot rule out the possibility that this outcome represents the natural development of the tumor.

Topics: Cabergoline; Child; Dopamine Agonists; Drug Resistance, Neoplasm; Ergolines; Follow-Up Studies; Humans; Male; Pituitary Neoplasms; Prolactin; Prolactinoma

Prolactinomas may rarely present with meningitis and cerebrospinal fluid (CSF) rhinorrhea secondary to erosion of the wall of the sella turcica. It is even more uncommon for this abnormal communication to be caused by an ectopic prolactinoma arising from the sphenoid sinus and eroding into the sella. This atypical growth pattern makes diagnosis very difficult because there may be no displacement of the normal pituitary gland. The first reported case of a patient with an ectopic prolactinoma originating within the sphenoid sinus presenting primarily with meningitis is presented, and the management strategy and surgical and nonsurgical treatment options are discussed.. A 48-year-old woman presented with confusion, low-pressure headache, and fever. A lumbar puncture revealed Streptococcus pneumoniae meningitis, and she was placed on intravenous penicillin G. After initiation of antibiotics, she noticed salty tasting postnasal fluid leakage. Imaging was remarkable for bony erosion of the sphenoid sinus wall by a soft tissue mass growing from within the sinus, with no disruption of the normal pituitary gland. A biopsy was then performed with an endoscopic transnasal transsphenoidal approach, and the CSF leak was repaired with a pedicled nasoseptal flap. The final pathology was prolactinoma, and she was placed on cabergoline.. Ectopic prolactinomas may rarely present as meningitis secondary to retrograde transmission of bacteria through a bony defect in the sphenoid sinus, and must be included in the differential diagnosis of any sphenoid sinus mass. Management should first address the infection, followed by surgical repair of the bony defect.

Topics: Cabergoline; Cerebrospinal Fluid Rhinorrhea; Diagnosis, Differential; Dopamine Agonists; Ergolines; Female; Humans; Meningitis, Bacterial; Middle Aged; Penicillin G; Pituitary Neoplasms; Prolactinoma; Streptococcus pneumoniae; Treatment Outcome

Prolactinomas are typically treated nonsurgically with a dopamine agonist. Once the tumor shrinks, adjacent eloquent structures, such as the optic apparatus, can become skeletonized and herniate into the dilated parasellar space.. A 48-year-old man with a prolactin-secreting macroadenoma treated with cabergoline presented with progressive bitemporal hemianopsia. Magnetic resonance imaging showed no recurrence of disease and a stretched optic chiasm herniating into an empty sella. Elevation of the optic chiasm via a transnasal transsphenoidal approach with ALLODERM graft and septal cartilage strut was performed. The patient was discharged home the next day with significant improvement in vision; magnetic resonance imaging showed interval elevation of the optic chiasm.. We review secondary empty sella syndrome and discuss surgical strategies for optic chiasmapexy.

Topics: Cabergoline; Dopamine Agonists; Empty Sella Syndrome; Ergolines; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neurosurgical Procedures; Optic Chiasm; Pituitary Neoplasms; Prolactinoma; Treatment Outcome

Dopamine agonists such as bromocriptine and cabergoline have been successfully used in the treatment of pituitary prolactinomas and other neuroendocrine tumors. However, their therapeutic mechanisms are not fully understood. In this study we demonstrated that DRD5 (dopamine receptor D5) agonists were potent inhibitors of pituitary tumor growth. We further found that DRD5 activation increased production of reactive oxygen species (ROS), inhibited the MTOR pathway, induced macroautophagy/autophagy, and led to autophagic cell death (ACD) in vitro and in vivo. In addition, DRD5 protein was highly expressed in the majority of human pituitary adenomas, and treatment of different human pituitary tumor cell cultures with the DRD5 agonist SKF83959 resulted in growth suppression, and the efficacy was correlated with the expression levels of DRD5 in the tumors. Furthermore, we found that DRD5 was expressed in other human cancer cells such as glioblastomas, colon cancer, and gastric cancer. DRD5 activation in these cell lines suppressed their growth, inhibited MTOR activity, and induced autophagy. Finally, in vivo SKF83959 also inhibited human gastric cancer cell growth in nude mice. Our studies revealed novel mechanisms for the tumor suppressive effects of DRD5 agonists, and suggested a potential use of DRD5 agonists as a novel therapeutic approach in the treatment of different human tumors and cancers.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Animals; Autophagosomes; Autophagy; Cabergoline; Cell Line, Tumor; Cell Proliferation; Ergolines; Humans; Mice, Nude; Pituitary Neoplasms; Rats; Reactive Oxygen Species; Receptors, Dopamine D5; Superoxide Dismutase; TOR Serine-Threonine Kinases

Topics: 14-alpha Demethylase Inhibitors; Adenoma; Cabergoline; Cushing Syndrome; Dopamine Agonists; Ergolines; Female; Humans; Hypokalemia; Ketoconazole; Middle Aged; Pituitary ACTH Hypersecretion; Pituitary Neoplasms

Topics: Adult; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Hyperprolactinemia; Outcome Assessment, Health Care; Pituitary Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Prolactinoma; Retrospective Studies; Young Adult

A 23-year-old man presenting with florid Cushing's syndrome was found to have high plasma ACTH and very high serum prolactin. Pituitary MRI showed a large invasive macroadenoma. Low-dose cabergoline promptly suppressed both ACTH and prolactin levels within 2 weeks, with unexpected clinical and biochemical hypocortisolism requiring hydrocortisone replacement. Secondary hypogonadism was reversed. Clinical and biochemical remission of his Cushing's syndrome together with significant shrinkage of his macroadenoma has been maintained for 1 year on cabergoline 0.5 mg twice weekly. Reduction in pituitary tumour volume and brisk fall in serum prolactin in response to low-dose cabergoline is regularly observed in patients with macroprolactinomas, but the concurrent fall in the plasma ACTH level and hypocortisolism was a pleasant surprise. We assume that he most likely has a single bihormonal adenoma that is enriched with dopamine-2 receptors.

Topics: ACTH-Secreting Pituitary Adenoma; Adenoma; Antineoplastic Agents; Cabergoline; Cushing Syndrome; Ergolines; Humans; Male; Pituitary Neoplasms; Prolactinoma; Young Adult

A 12-year-old male Yorkshire Terrier was presented because of decreased appetite. Physical examination revealed mammary gland swelling and galactorrhea. Contrast-enhanced computed tomographic scanning of the skull indicated an enlarged pituitary gland, compatible with a pituitary tumor. The serum prolactin concentration was markedly elevated. One week after the start of treatment with the dopamine agonist cabergoline, the serum prolactin concentration normalized and the galactorrhea resolved. Cabergoline was administered for approximately 4 months and then discontinued. Subsequently, serum prolactin concentration increased again, and mammary gland swelling and galactorrhea reappeared. The dog was euthanized 10 months after the first detection of the galactorrhea because of problems not directly related to pituitary disease. Postmortem examination revealed an infiltrative adenoma of the pituitary gland with immunolabeling for prolactin. The clinical and histopathologic findings indicated the diagnosis of a functional prolactinoma in a male dog.

Topics: Adenoma; Animals; Cabergoline; Dogs; Dopamine Agonists; Ergolines; Fatal Outcome; Male; Pituitary Neoplasms; Prolactin; Prolactinoma; Tomography Scanners, X-Ray Computed

Galactocele is a rare cystic formation, a benign breast lesion, occurring when breast duct is blocked and engorged. It generally affects postpartum women, either breastfeeding or not. Only a few cases have been reported in the literature and they were not related to lactation, as in the case of postmenopausal women or of men; moreover, their relationship to the overproduction of prolactin, a growth factor stimulating mammary epithelial cells, is not very well defined at this time. We here report the unusual case of a 30-year old patient with no personal history of childbirth or abortion. She was treated in the Division of Endocrinology for pituitary microadenoma with Cabergoline, that she stopped for 1 year. Even taking into account this rare association, it is important to emphasize the role of hormones in the progression of breast anatomy.

Topics: Adult; Antineoplastic Agents; Breast Cyst; Cabergoline; Ergolines; Female; Humans; Pituitary Neoplasms; Prolactinoma

The dopamine agonist cabergoline (CAB) has been used widely in the treatment of prolactinomas and other types of pituitary adenomas, but its clinical use is hampered by intolerance in some patients with prolactinoma and lack of effectiveness in other pituitary tumor types. Chloroquine (CQ) is an old drug widely used to treat malaria. Recent studies, including our own, have revealed that CAB and CQ are involved in induction of autophagy and activation of autophagic cell death.. To test whether CAB and CQ can function cooperatively to suppress growth of pituitary adenomas as well as other cancers.. In vitro studies using the rat pituitary tumor cell lines MMQ and GH3, human pituitary tumor cell primary cultures, and several human cancer cell lines showed that CQ enhanced suppression of cell proliferation by CAB. These results were confirmed in in vivo xenograft models in nude mice and estrogen-induced rat prolactinomas. To understand the mechanism of combined CAB and CQ action, we established a low-CAB-dose condition in which CAB was able to induce autophagy but failed to suppress cell growth. Addition of CQ to low-dose CAB blocked normal autophagic cycles and induced apoptosis, evidenced by the further accumulation of p62/caspase-8/LC3-II.. The data suggest that combined use of CAB and CQ may increase clinical effectiveness in treatment of human pituitary adenomas, as well as other cancers, making it an attractive option in tumor and cancer therapies.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cabergoline; Cell Death; Cells, Cultured; Chloroquine; Ergolines; Female; Hep G2 Cells; Humans; Mice; Mice, Nude; Pituitary Neoplasms; Prolactinoma; Rats; Rats, Inbred F344; Xenograft Model Antitumor Assays

Topics: Acromegaly; Adult; Antineoplastic Agents; Cabergoline; Central Nervous System Cysts; Ergolines; Female; Human Growth Hormone; Humans; Magnetic Resonance Imaging; Neurofibromatosis 1; Pituitary Gland; Pituitary Neoplasms

Presently, the standard of care for prolactinomas, a type of pituitary adenoma, is dopaminergic agents such as bromocriptine and cabergoline. However, dopaminergic agents may induce fibrosis of cardiac valves leading to valvular insufficiency, necessitating surgical treatment of prolactinoma. Fibrosis of prolactinoma can be induced by prolonged medical treatment with bromocriptine, and this usually occurs after years of treatment. In comparison to bromocriptine, there have been no reports of cabergoline-induced fibrosis of prolactinoma. There is a potential for greater emphasis to be placed on assessing the tumour consistency from preoperative MRI scans, or even preoperative contrast-enhanced 3D Fast Imaging Employing Steady-state Acquisition imaging to allow better planning of the surgery. We report a rare case of fibrosis of prolactinoma after cabergoline treatment resulting in its subsequent difficult surgical removal. This patient had early MRI changes of fibrosis of prolactinoma after a short period of 6 months of cabergoline treatment.

Topics: Adult; Antineoplastic Agents; Cabergoline; Combined Modality Therapy; Diagnosis, Differential; Dopamine Agonists; Ergolines; Fibrosis; Humans; Hypogonadism; Hypothyroidism; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Prolactinoma; Thyroxine; Tricuspid Valve Insufficiency

Topics: Aged; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Bromocriptine; Cabergoline; Combined Modality Therapy; Dacarbazine; Drug Substitution; Ergolines; Fatal Outcome; Headache; Humans; Hyperprolactinemia; Liver Neoplasms; Male; Neoplasm Recurrence, Local; Pituitary Neoplasms; Prolactin; Prolactinoma; Proton Therapy; Temozolomide

Aneurysms of the cavernous segment of the internal carotid artery (ICA) are believed to have a low risk of subarachnoid haemorrhage (SAH), given the confines of the dural rings and the anterior clinoid process. The risk may be greater when the bony and dural protection has been eroded. We report a case of spontaneous SAH from rupture of a cavernous ICA aneurysm in a patient whose large prolactinoma had markedly decreased in size as the result of cabergoline treatment. After passing a balloon test occlusion, the patient underwent successful endovascular vessel deconstruction. This case suggests that an eroding skull base lesion may distort normal anterior cranial base anatomy and allow communication between the cavernous ICA and subarachnoid space. The potential for SAH due to cavernous ICA aneurysm rupture should be recognised in patients with previous pituitary or other skull base lesions adjacent to the cavernous sinus.

Topics: Aneurysm, Ruptured; Cabergoline; Carotid Artery Diseases; Carotid Artery, Internal; Cavernous Sinus; Ergolines; Humans; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma; Skull Base; Subarachnoid Hemorrhage; Treatment Outcome

Previous studies suggest that hyperprolactinaemia might have adverse effects on lipid and glucose metabolism. We therefore aimed to evaluate whether dopamine agonist treatment with cabergoline has significant effects on blood lipids, fasting glucose and HbA1c levels in patients with micro- or macroprolactinoma. In this retrospective observational study the main outcome measures are changes in parameters of glucose and lipid metabolism compared at hyperprolactinaemia and after achievement of normoprolactinaemia by cabergoline treatment. We enrolled 53 study participants (22 females; median [interquartile range] age: 40.0 [27.5 to 50.0] years), 22 (41.5 %) with micro-, and 31 (58.5 %) with macroprolactinomas. After a median follow-up of 9 months, prolactin levels decreased from 220.6 (80.7-913.4) to 11.2 (3.5-18.7) ng/mL (p < 0.001). There was a significant decrease in median levels of low-density lipoprotein (LDL) from 121.6 (±39.4) to 110.6 mg/dl (±37.6, p = 0.005) and total cholesterol from 191 (168.5-241) to 181 mg/dl (162-217, p < 0.001), but no change in high-density lipoprotein (HDL), triglycerides, fasting glucose and HbA1c. We observed a significant increase in testosterone in men and in oestradiol in women. In linear regression analyses using the change in total cholesterol or LDL as dependent, and the change in prolactin, oestradiol, and testosterone as independent variables, no significant predictor of the change in total cholesterol or LDL was identified. In patients with prolactinomas, normalisation of elevated prolactin levels by cabergoline treatment was accompanied by significant reductions in LDL and total cholesterol. Further studies are warranted to confirm our findings and to evaluate the clinical implications of lipid levels in the monitoring and treatment of patients with prolactinomas.

Topics: Adult; Cabergoline; Cholesterol; Dopamine Agonists; Ergolines; Female; Humans; Hyperprolactinemia; Lipoproteins, HDL; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma; Treatment Outcome

Dopamine agonists are the first line of therapy for prolactinomas, with high rates of biochemical control and tumour shrinkage. Toxicity is considered to be low and manageable by switching of agents and dose reduction. Dopamine agonist-induced impulse control disorders are well described in the neurology setting, but further data are required regarding this toxicity in prolactinoma patients. We performed a multicenter retrospective cohort study of eight men with prolactinomas and associated central hypogonadism. The eight men had no prior history of psychiatric disease, but each developed disruptive hypersexuality whilst on dopamine agonist therapy at various doses. Cabergoline, bromocriptine and quinagolide were all implicated. Hypersexuality had manifold consequences, including relationship discord, financial loss, reduced work performance, and illicit activity. We hypothesise that this phenomenon is due to synergy between reward pathway stimulation by dopamine agonists, together with rapid restoration of the eugonadal state after prolonged hypogonadism. We refer here to this distinct drug toxicity as 'dopa-testotoxicosis'. Given the profound impact in these patients and their families, cessation of dopamine agonists should be considered in men who develop hypersexuality, and pituitary surgery may be required to facilitate this. Awareness of this distinct impulse control disorder should enable further research into the prevalence, natural history and management of dopa-testotoxicosis. The condition is likely under-reported due to the highly personal nature of the symptoms and we suggest a simple written questionnaire to screen for hypersexuality and other behavioural symptoms within the first six months of dopamine agonist treatment.

Topics: Adult; Aged; Aminoquinolines; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Humans; Hypogonadism; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma; Retrospective Studies; Sexual Dysfunction, Physiological

Prolactinomas are primarily treated with medical therapy. Given the efficacy of dopamine agonists (DAs), surgery has remained a second-line treatment option. Despite medical therapy, some tumors display resistance and/or patients maybe intolerant of DA and require alternative treatment options. We examined the indications, efficacy, and safety of pituitary surgery for the treatment of prolactinomas.. We performed a retrospective analysis of all patients who had surgery for a prolactinoma at our institution from January 1993 to October 2014.. Seventy-eight patients (46 females, mean age 32 years) with a median follow-up of 12 months were analyzed. Macroprolactinomas accounted for 65% (51/78) of tumors. The most common indication for surgery in microprolactinomas was medication intolerance (37%, 10/27) and medication failure (33%, 17/51) in macroprolactinomas. DA therapy had been tried in 76% (59/78) patients prior to surgery. Following surgery, long-term remission was seen in 72% (18/25) of micro-adenomas and 20% (10/49) of macro-adenomas (32% [10/32] in those without cavernous sinus invasion). Despite persistent disease in those with macro-adenomas (34% [13/38]) were able to remain off medication. Early surgical failure was more common in males (P = .004) and those with large (P≤.001) or atypical (P = .003) adenomas.. Surgery can result in prolonged remission in 72% of microprolactinomas. Despite lower remission rates among macroprolactinomas, a third of patients with persistent disease did not require medical therapy. Therefore, surgery remains an alternative effective treatment option, particularly for those who are intolerant or resistant to medical therapy.. ACTH = adrenocorticotropic hormone CI = confidence interval CSF = cerebrospinal fluid DA = dopamine agonist IQR = interquartile range MIB-1 = methylation inhibiting binding protein-1 VF = visual field.

Topics: Adult; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neurosurgical Procedures; Pituitary Neoplasms; Prolactinoma; Remission Induction; Retrospective Studies; Treatment Failure; Treatment Outcome; Tumor Burden; Young Adult

While dopamine-agonists are the first-line approach in treating prolactinomas, surgery can be considered in selected cases besides non-responders or patients with dopamine-agonist intolerance. The aim of the present study was to compare the long-term outcome in women with prolactinomas treated primarily either surgically or medically who had not had prior dopamine-agonist treatment. Retrospective case-note study of all consecutive women with prolactinomas primarily managed with medical therapy or surgery in a tertiary referral centre. The clinical, biochemical, and radiological responses to first-line treatment at early and long-term follow-up were analysed. The primary therapeutic strategy was dopamine-agonists for 36 (34 %) and surgery for 71 (66 %) of the women. Baseline clinical and biochemical characteristics were not significantly different between the primary surgical and medical cohort. Median follow-up time was 90 months (range 13-408). Following primary treatment, prolactin level significantly decreased in both cohorts, on average to 13.5 µg/L (IQR 7-21; p < 0.001), and was within the normal range in 82 % of all patients. No women in the surgical cohort demonstrated permanent sequelae and morbidity was low. At final follow-up, control of hyperprolactinaemia required dopamine-agonist therapy in 64 % of women who had undergone primary medical therapy vs. 32 % of those who had primary surgical therapy (p = 0.003). Logistic regression revealed that the primary therapeutic strategy, but not adenoma size, was an independent risk factor for long-term dependence on dopamine-agonists. The present data indicate that in a dedicated tertiary referral centre, long-term control of hyperprolactinaemia in women with prolactinomas is high. In selected cases, a primary neurosurgical approach might at least be interdisciplinarily discussed with the primary goal of minimizing long-term dependence on dopamine-agonists.

Topics: Adult; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Female; Follow-Up Studies; Humans; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Prolactin; Prolactinoma; Retrospective Studies; Treatment Outcome; Young Adult

Since the 1990's cabergoline has been the treatment of choice in prolactinoma, as it permits rapid and effective hormonal and tumor control in most cases. Evidence of cardiac valvulopathy was demonstrated in Parkinson's disease patients treated with dopamine agonists. Retrospective studies in prolactinoma patients treated with cabergoline at lower doses did not show such an effect. However, few prospective data with long-term follow-up are available. The aim of this study was to assess the safety of cabergoline regarding cardiac valvular status during prospective follow-up in patients treated for prolactinoma or idiopathic hyperprolactinemia. We report here a series of 100 patients (71F; median age at diagnosis: 41.5 years) treated with cabergoline for endocrine diseases (prolactinoma n = 89, idiopathic hyperprolactinemia n = 11). All patients underwent complete transthoracic echocardiographic studies at baseline and during long-term prospective surveillance using the same equipment and performed by the same technicians. The median interval between baseline and last follow-up echocardiographic studies while on cabergoline was 62.5 months (interquartile range: 34.75-77.0). The median total duration of cabergoline treatment was 124.5 months (interquartile range: 80.75-188.75) and the median cumulative total dose of cabergoline was 277.8 mg (interquartile range : 121.4-437.8 mg) at last follow-up. We found no clinically relevant alterations in cardiac valve function or valvular calcifications with cabergoline treatment. Our data suggest that findings from retrospective analyses are correct and that cabergoline is a safe chronic treatment at the doses used typically in endocrinology.

Topics: Adult; Cabergoline; Dopamine Agonists; Echocardiography; Ergolines; Female; Heart Valve Diseases; Heart Valves; Humans; Hyperprolactinemia; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma; Prospective Studies; Treatment Outcome; Young Adult

Prolactinomas are the commonest functional tumors of the pituitary gland. There are still controversies regarding medical therapy in specific clinical situations. Patients may be managed by different specialists in the Middle East and North Africa (MENA) region and no data exist on patterns of clinical management.. To ascertain the diagnostic and therapeutic approaches to prolactinomas among relevant professionals from the MENA region.. An online survey of a large sample of physicians was conducted. The questionnaire covered various aspects of diagnosis and treatment of prolactinomas. 468 respondents were included; 36 % were endocrinologists; 49 % worked in public facilities and 81 % graduated more than 10 years. 40 and 30 % would have seen 1-5 and more than 5 suspected or confirmed prolactinomas over a 6 months period, respectively.. Regarding the diagnosis, 30 % of the respondents considered that prolactin levels <100 ng/ml exclude the presence of a prolactinoma. 21 % of respondents considered prolactin levels >250 ng/ml compatible with macroprolactinomas only, whereas others accepted this to be compatible also with microprolactinomas, macroprolactinaemia and drug-induced hyperprolactinemia (50, 42 and 36 % respectively). 71 % of respondents favored the screening for macroprolactin in asymptomatic individuals with hyperprolactinemia. Regarding the treatment, 84 % of respondents would treat microprolactinomas even in the absence of symptoms whereas 72 % of the respondents would treat microprolactinomas only if symptoms exist. 60 and 49 % of the respondents chose cabergoline as the drug of choice to treat macroprolactinomas and microprolactinomas respectively. Similar proportions had no preference of either cabergoline or bromocriptine as the best treatment for macroprolactinoma (27 %) and microprolactinomas (32 %). 46 and 75 % of respondents favored treatment withdrawal 2-3 years after prolactin normalization in patients with macroprolactinomas and microprolactinomas, respectively whereas 10 % of respondents withdraw treatment after menopause in either case. 94 % of respondents considered medical therapy as the primary treatment for microprolactinomas. In case of pregnancy, 49 % considered bromocriptine as the drug of choice for women who wish to become pregnant. 65 and 38 % of respondents advocated discontinuation of treatment with dopamine agonists in patients with microprolactinomas and macroprolactinomas, respectively. Finally, 48 % would allow breast-feeding without restriction, 28 % would restrict it to patients with microprolactinomas and 25 % would not recommend it for women with prolactinomas.. This is the first study of the clinical management of prolactinomas in the MENA region. Some of the practices are not in line with the latest Endocrine and Pituitary Societies guidelines. These warrant further discussions of contemporary guidelines in regional forums.

Topics: Adult; Africa, Northern; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Middle East; Physicians; Pituitary Neoplasms; Pregnancy; Prolactin; Prolactinoma; Surveys and Questionnaires

The aim of this study to was to evaluate the effect of fibroblast growth factor-23 (FGF-23), osteoprotegerin (OPG), receptor activator nuclear κB ligand (RANKL), and vitamin D hormones on bone loss in patients with hyperprolactinemia due to pituitary prolactinoma.. We recruited 46 premenopausal female patients with prolactinoma and age and sex-matched healthy controls (Group 3, n = 20) for this cross-sectional study. Prolactinoma patients were divided into 2 groups as patients newly diagnosed (Group 1, n = 26) and those under cabergoline treatment (Group 2, n = 20). Anthropometric and metabolic variables; hormonal profiles; and osteocalcin, deoxypyridinoline (DOP), and bone mineral density measurements were performed for all participants. FGF-23, OPG, and RANKL levels were analyzed in all groups.. FGF-23, OPG, calcium, phosphorus, and parathormone levels were similar between all groups despite significantly higher levels in the control group in terms of vitamin D and RANKL levels than in patients. Bone loss was found more in Group 2, particularly observed in Z scores of femur and spinal bone (P<.05). Correlation analysis revealed a negative correlation between FGF-23 and femur neck T score (r = -0.0433, P = .05) in patients with active prolactinoma. A positive correlation was also observed between parameters of DOP and OPG (r = 0.673, P = .02). In patients with remission there were a negative correlation between prolactin and luteinizing hormone (r = -600, P = .08). Additionally, a negative correlation was found between osteocalcin and osteoprotegerin in patients in remission (r = -0.73, P = .01).. Our data indicated that FGF-23 and OPG levels do not play a critical role on the development of bone decrease in patients with hyperprolactinemia. However, further prospective studies in larger numbers of participants should be designed to clarify this issue.. BFP = body fat percentage BMD = bone mineral density BMI = body mass index CV = coefficient of variation DOP = deoxypyridinoline ELISA = enzyme-linked immunosorbent assay FGF-23 = fibroblast growth factor-23 HOMA-IR = homeostatic model assessment of insulin resistance OPG = osteoprotegerin RANKL = receptor activator nuclear κB ligand.

Topics: Adult; Amino Acids; Antineoplastic Agents; Biomarkers, Tumor; Bone Density; Cabergoline; Cross-Sectional Studies; Ergolines; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Middle Aged; Osteocalcin; Osteoprotegerin; Pituitary Neoplasms; Prolactinoma; Prospective Studies; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Vitamin D

Hyperprolactinemia and prolactinomas cause infertility in significant number of women. But, pregnancy may lead to post-partum remission of hyperprolactinemia. The data on pregnancy and tumor outcome in women with macroprolactinoma conceiving on Cabergoline (CAB) therapy is increasing but still less than with Bromocriptine. We studied the incidence of fetal malformations, hyperprolactinemia and tumor course after gestation in infertile women harboring macroprolactinoma, who conceived on CAB therapy during the year 2005-2015. The cohort was divided into two groups based on the continuation of CAB therapy during gestation (Group A) or not (Group B). Forty-eight pregnancies in 33 women were recorded. CAB was continued throughout gestation in 25 pregnancies (Group A). The incidence of missed abortion (8.3%), still birth (4.2%) and low birth weight (7.7%) were not different in two groups. Neural tube defects were observed in 3 pregnancies (all in Group A). Post-partum, recurrence of hyperprolactinemia was observed in 64.6% and 60.9% (p = 0.8) of women in group A and B, respectively. Cabergoline was restarted after 60% and 60.9% (p = 0.9) pregnancies in the two groups in view of symptomatic hyperprolactinemia and/or persistence of macroadenoma. Post-partum, recurrence of hyperprolactinemia is common in spite of significant tumor reduction in infertile women with macroprolactinoma. Continuation of CAB during gestation does not influence the post-pregnancy recurrence of hyperprolactinemia or tumor remission.

Topics: Adult; Antineoplastic Agents; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Infertility, Female; Pituitary Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Prolactinoma; Treatment Outcome; Young Adult

To examine the monitoring, management, and outcomes of pituitary tumors in pregnancy.. A national, prospective, observational, population-based case series study was conducted in all U.K. consultant-led obstetric units over 3 years using the U.K. Obstetric Surveillance System. To evaluate rates of adverse pregnancy outcomes, women with a macroprolactinoma (10 mm or greater) or nonfunctioning pituitary adenoma, diagnosed before or during pregnancy, were compared with two comparison groups: 1) a U.K. Obstetric Surveillance System cohort with singleton (n=2,205) or twin (n=27) pregnancy; and 2) data from the Office of National Statistics (n=2,703,102). Main outcome measures were the incidence, management, and frequency of adverse maternal and offspring outcomes of pituitary tumors in pregnancy.. There were 71 confirmed cases of pituitary tumors in pregnancy (49 macrolactinoma, 16 nonfunctioning adenomas, three acromegaly, three Cushing's disease). The women with pituitary tumors were 4 years older than comparison women (P<.001). None of the nine women treated with surgery or radiotherapy before pregnancy had symptomatic tumor expansion. This occurred in 6 of 40 women with macroprolactinomas and one of seven nonfunctioning adenomas diagnosed before conception and in three of five women with nonfunctioning adenomas diagnosed in pregnancy. Two women had pituitary apoplexy, both of whom also had symptoms of expansion of tumor or surrounding pituitary tissue. To within the level of accuracy possible, there was no evidence that pituitary tumors were associated with adverse pregnancy outcomes (pregnancy-induced hypertension, preeclampsia, preterm labor, stillbirth). Women with nonfunctioning adenomas were more likely to have cesarean delivery compared with women in a control group (relative risk 2.06, confidence interval 1.26-3.36, P=.035).. The majority of women with macroprolactinomas and nonfunctioning adenomas have good pregnancy outcomes. Nonfunctioning pituitary adenomas occur more commonly in pregnancy than previously thought and can present de novo with symptoms of pituitary expansion in pregnancy.

Topics: Adenoma; Adult; Amenorrhea; Antineoplastic Agents; Bromocriptine; Cabergoline; Case-Control Studies; Cesarean Section; Dopamine Agonists; Ergolines; Female; Galactorrhea; Humans; Incidence; Pituitary Neoplasms; Pre-Eclampsia; Preconception Care; Pregnancy; Pregnancy Complications, Neoplastic; Premature Birth; Prolactinoma; Prospective Studies; Stillbirth; United Kingdom; Vision Disorders; Young Adult

Both antitumor and antisecretory efficacies of dopamine agonists (DA) make them the first-line treatment of macroprolactinomas. However, there is no guideline for MRI follow-up once prolactin is controlled. The aim of our study was to determine whether a regular MRI follow-up was necessary in patients with long-term normal prolactin levels under DA.. We conducted a retrospective multicenter study (Marseille, Paris La Pitie Salpetriere and Nancy, France; Liege, Belgium) including patients with macroprolactinomas (largest diameter: >10 mm and baseline prolactin level: >100 ng/mL) treated by dopamine agonists, and regularly followed (pituitary MRI and prolactin levels) during at least 48 months once normal prolactin level was obtained.. In total, 115 patients were included (63 men and 52 women; mean age at diagnosis: 36.3 years). Mean baseline prolactin level was 2224 ± 6839 ng/mL. No significant increase of tumor volume was observed during the follow-up. Of the 21 patients (18%) who presented asymptomatic hemorrhagic changes of the macroprolactinoma on MRI, 2 had a tumor increase (2 and 7 mm in the largest size). Both were treated by cabergoline (1 mg/week) with normal prolactin levels obtained for 6 and 24 months. For both patients, no further growth was observed on MRI during follow-up at the same dose of cabergoline.. No significant increase of tumor size was observed in our patients with controlled prolactin levels on DA. MRI follow-up thus appears unnecessary in patients with biologically controlled macroprolactinomas.

Topics: Adult; Aminoquinolines; Belgium; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Female; Follow-Up Studies; France; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Retrospective Studies

Prolactinomas are the most common hormone-secreting pituitary tumors\ and represents approximately 40% of all pituitary adenomas. Pharmacology\ therapy with dopamine agonists is the mainstay treatment for prolactinomas.\ Usually, patients respond to these drugs with decreased level of the serum\ prolactin and with time, by tumor shrinkage. Less than 10% of patients\ with prolactinomas exhibit resistance to the action of dopamine agonists, as\ defined by the lack of normalization of the serum prolactin levels despite long-\ term treatment at high doses of these drugs. However secondary resistance\ to dopamine agonists therapy has also been described in patients who were\ initially responsive to treatment, either with Cabergoline or Bromocriptine\ but later develop dopamine agonist resistance, with elevated prolactin levels\ and sometimes an enlarging tumor volume several years afterwards. We\ report a case of a male patient with prolactinoma who developed drug resistance\ 13 months after initial dopamine agonist therapy.

Topics: Adult; Cabergoline; Dopamine Agonists; Drug Resistance; Ergolines; Humans; Male; Pituitary Neoplasms; Prolactinoma; Time Factors

Although prolactinomas are treated effectively with dopamine agonists, some have proposed curative surgical resection for select cases of microprolactinomas to avoid life-long medical therapy. We performed a cost-effectiveness analysis comparing transsphenoidal surgery (either microsurgical or endoscopic) and medical therapy (either bromocriptine or cabergoline) with decision analysis modeling.. A 2-armed decision tree was created with TreeAge Pro Suite 2012 to compare upfront transsphenoidal surgery versus medical therapy. The economic perspective was that of the health care third-party payer. On the basis of a literature review, we assigned plausible distributions for costs and utilities to each potential outcome, taking into account medical and surgical costs and complications. Base-case analysis, sensitivity analysis, and Monte Carlo simulations were performed to determine the cost-effectiveness of each strategy at 5-year and 10-year time horizons.. In the base-case scenario, microscopic transsphenoidal surgery was the most cost-effective option at 5 years from the time of diagnosis; however, by the 10-year time horizon, endoscopic transsphenoidal surgery became the most cost-effective option. At both time horizons, medical therapy (both bromocriptine and cabergoline) were found to be more costly and less effective than transsphenoidal surgery (i.e., the medical arm was dominated by the surgical arm in this model). Two-way sensitivity analysis demonstrated that endoscopic resection would be the most cost-effective strategy if the cure rate from endoscopic surgery was greater than 90% and the complication rate was less than 1%. Monte Carlo simulation was performed for endoscopic surgery versus microscopic surgery at both time horizons. This analysis produced an incremental cost-effectiveness ratio of $80,235 per quality-adjusted life years at 5 years and $40,737 per quality-adjusted life years at 10 years, implying that with increasing time intervals, endoscopic transsphenoidal surgery is the more cost-effective treatment strategy.. On the basis of the results of our model, transsphenoidal surgical resection of microprolactinomas, either microsurgical or endoscopic, appears to be more cost-effective than life-long medical therapy in young patients with life expectancy greater than 10 years. We caution that surgical resection for microprolactinomas be performed only in select cases by experienced pituitary surgeons at high-volume centers with high biochemical cure rates and low complication rates.

Topics: Adult; Aged; Bromocriptine; Cabergoline; Cost-Benefit Analysis; Decision Support Techniques; Decision Trees; Ergolines; Female; Health Care Costs; Hormone Antagonists; Humans; Hyperprolactinemia; Life Expectancy; Male; Medicare; Microsurgery; Middle Aged; Monte Carlo Method; Neuroendoscopy; Pituitary Neoplasms; Prolactinoma; Quality-Adjusted Life Years; Sphenoid Sinus; Time Factors; Treatment Outcome; United States

Topics: Adult; Brain; Cabergoline; Dopamine Agonists; Erectile Dysfunction; Ergolines; Headache; Humans; Magnetic Resonance Imaging; Male; Nipple Discharge; Pituitary Neoplasms; Prolactinoma

The aim of the study was to determine whether atherosclerotic risk markers exist at the moment and after withdrawal of cabergoline (CAB) therapy in patients who had taken a suitable dose of CAB therapy for a suitable period of time before cessation of CAB.. This study was designed as prospective cross-sectional. Out of a total of 115 patients with prolactinoma, 42 non-obese women with microprolactinoma, who met the Pituitary Society criteria (2006) for the withdrawal of long-term CAB therapy, and 30 healthy patients participated in our study. The number of patients excluded from the study were as follows: 34 patients with tumor shrinkage of less than 50%; 10 who received DA treatments for less than 2 years; 9 who were treated with bromocriptine; and 20 who had diabetes mellitus, hypertension, hyperlipidemia, obesity, renal disease, coronary arterial disease, or were tobacco smokers. The patients were evaluated for anthropometric, metabolic, and inflammatory parameters at the time of cessation of CAB therapy and at the 3rd and 12th months after the withdrawal of CAB therapy. Endothelial dysfunction was determined by flow-mediated dilation (FMD) of the brachial artery and carotid intima media thickness (IMT), which were assessed by high resolution ultrasonography (USG) by the same practitioner.. At the moment of cessation of CAB therapy, the FMD percentage in patients with prolactinoma was worse than that in healthy controls (p=0.0029). After the withdrawal of CAB treatment, fibrinogen (p=0.036), mean platelet volume (MPV) (p<0.001), carotid IMT (p=0.041), and high-density lipoprotein cholesterol (HDL C) (p=0.048) were worse in the relapse patients than those in the remission patients. Furthermore, only MPV values were found to be significantly related to a relapse of hyperprolactinemia among all atherosclerotic risk markers [area under the curve: 0.830 (95% CI 0.685-0.974) (p<0.001)].. Unfavorable cardiovascular risk profiles are a problem for patients with prolactinoma during cessation and after CAB withdrawal.

Topics: Adolescent; Adult; Atherosclerosis; Brachial Artery; Cabergoline; Carotid Intima-Media Thickness; Cross-Sectional Studies; Ergolines; Female; Humans; Neoplasm Recurrence, Local; Pituitary Neoplasms; Prolactin; Prolactinoma; Prospective Studies; Young Adult

The aim of the study was to assess the effect of dopamine agonist (DA) withdrawal, the current recurrence rate of hyperprolactinemia, and possible factors that predict recurrence in patients with prolactinoma.. We evaluated DA withdrawal in 67 patients with prolactinoma (50 female/17 male) who received DA treatment for at least 2 years and showed normalization of prolactin (PRL) levels and tumor disappearance or ≥50 % tumor shrinkage, retrospectively. Accordingly, patients were divided into two groups as remission and recurrence groups, and factors that predict recurrence were evaluated.. The overall remission rate was 46 %; the remission ratios were 65 % in microprolactinomas and 36 % in macroprolactinomas. Remission rates were 39 % in the bromocriptine withdrawal group and 55 % in the cabergoline withdrawal group. The maximum tumor diameter and baseline PRL levels were significantly higher in the recurrence group (p = 0.001 and p = 0.003, respectively). The mean duration of DA therapy was significantly longer in the remission group (88.7 ± 48.1 and 66.7 ± 30.4 months, respectively, p = 0.026).The mean time to recurrence was 5.3 ± 3.2 months. The mean PRL levels at recurrence time were significantly lower than baseline PRL levels (p = 0.001).. The most important predictors of recurrence were maximum tumor diameter and baseline PRL levels in this study. The remission rate in our study group was higher, which was thought to be associated with the longer duration of DA treatment and that our patients were selected according to certain criteria. Despite these positive results, close monitoring is necessary for detection of early and late recurrence, especially within the first year after DA withdrawal.

Topics: Adolescent; Adult; Aged; Bromocriptine; Cabergoline; Deprescriptions; Dopamine Agonists; Ergolines; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Neoplasm Recurrence, Local; Patient Selection; Pituitary Neoplasms; Prolactin; Prolactinoma; Retrospective Studies; Time Factors; Tumor Burden; Young Adult

Prolactin is a multifunctional pituitary hormone. The effect of prolactin on platelet activation is not well understood. Prolactinomas are the most common type of pituitary adenomas, and they are medically responsive to dopamine agonists. Mean platelet volume (MPV) is a marker of platelet function and activation. The aim of this study was to evaluate MPV values before and 6 months of cabergoline treatment when normoprolactinemia was achieved.. A total of 101 newly diagnosed prolactinoma patients and 102 healthy control subjects were included in the study. Patients with hematological disorders that affect MPV and those on medications were excluded. Prolactin, platelet count and MPV levels were recorded before and 6 months after the initiation of cabergoline treatment (0.5 to 1 mg, two times a week).. There was no significant difference in platelet count and MPV before and after 6 months of treatment with cabergoline in patients with prolactinoma compared with the control group (p > 0.05).. Our results showed that MPV, a marker of platelet function, was unchanged in patients with prolactinoma.

Topics: Adolescent; Adult; Biomarkers, Tumor; Cabergoline; Case-Control Studies; Dopamine Agonists; Ergolines; Female; Humans; Male; Mean Platelet Volume; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Reference Values; Retrospective Studies; Time Factors; Treatment Outcome; Young Adult

The aim was to assess the evolution of tumor size and prolactin (PRL) levels in patients with micro and macroprolactinomas diagnosed and treated with dopamine agonists during fertile age, and the effects of suspension of drugs after menopause.. Retrospective study, 29 patients with prolactinomas, 22 microadenomas and 7 macroadenomas, diagnosed during their fertile age were studied in their menopause; treatment was stopped in this period. Age at menopause was 49 ± 3.6 years. The average time of treatment was 135 ± 79 months. The time of follow-up after treatment suspension was 4 to 192 months. Results: Pre-treatment PRL levels in micro and macroadenomas were 119 ± 57 ng/mL and 258 ± 225 ng/mL, respectively. During menopause after treatment suspension, and at the latest follow-up: in microadenomas PRL levels were 23 ± 13 ng/mL and 16 ± 5.7 ng/mL, respectively; in macroadenomas, PRL levels were 20 ± 6.6 ng/mL 5t5and 25 ± 18 ng/mL, respectively. In menopause after treatment suspension, the microadenomas had disappeared in 9/22 and had decreased in 13/22. In the group of patients whose tumor had decreased, in the latest follow-up, tumors disappeared in 7/13 and remained unchanged in 6/13. In macroadenomas, after treatment suspension 3/7 had disappeared, 3/7 decreased and 1/7 remained unchanged. In the latest control in the 3 patients whose tumor decreased, disappeared in 1/3, decreased in 1/3 and there was no change in the remaining.. Normal PRL levels and sustained reduction or disappearance of adenomas were achieved in most of patients, probably due to the decrease of estrogen levels. Dopamine agonists might be stopped after menopause in patients with prolactinomas.

Topics: Adenoma; Adult; Bromocriptine; Cabergoline; Disease Progression; Dopamine Agonists; Ergolines; Female; Humans; Menopause; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Retrospective Studies; Treatment Outcome; Withholding Treatment

Cluster headache is classified as a primary headache by definition not caused by an underlying pathology. However, symptomatic cases of otherwise typical cluster headache have been reported.. A 47-year-old male suffered from primary chronic cluster headache (CCH, ICHD-3 beta criteria fulfilled) since the age of 35 years. A magnetic resonance imaging (MRI) study of the brain in 2006 came back normal. He tried several prophylactic treatments but was never longer than 1 month without attacks. He was under chronic treatment with verapamil with only a limited effect on the attack frequency. Subcutaneous sumatriptan 6 mg injections were very effective in aborting attacks. By February 2014 the patient developed a continuous interictal pain ipsilateral to the right-sided cluster headache attacks. An indomethacin test (up to 225 mg/day orally) was negative. Because of the change in headache pattern we performed a new brain MRI, which showed a cystic structure in the pituitary gland. The differential diagnosis was between a Rathke cleft cyst and a cystic adenoma. Pituitary function tests showed an elevated serum prolactin level. A dopamine agonist (cabergoline) was started and the headache subsided completely. Potential pathophysiological mechanisms of pituitary tumor-associated headache are discussed.. Neuroimaging should be considered in all patients with CCH, especially those with an atypical presentation or evolution. Response to acute treatment does not exclude a secondary form of cluster headache. There may be shared pathophysiological mechanisms of primary and secondary cluster headache.

Topics: Adenoma; Cabergoline; Central Nervous System Cysts; Cluster Headache; Diagnosis, Differential; Dopamine Agonists; Ergolines; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Sumatriptan; Treatment Outcome; Verapamil

Bone metabolic disorders in patients with prolactinoma have not been fully characterized. The case presented herein illustrates potential causal associations between prolactinoma and osteopenia, with a reversal of the disorder by treatment with a dopamine agonist.. A 43-year-old male with macro-prolactinoma [PRL 7770 ng/mL] was referred to our hospital. He suffered was overweight [body mass index (BMI) 29.4 kg/m2] and had impaired glucose tolerance, hypertriglyceridemia, and osteopenia. The patient was administered cabergoline, a dopamine D2 receptor agonist, and the dose was gradually increased up to 9 mg/week over the period of 1 year. One year later, the patient's serum PRL levels decreased to within the normal range (19.1 ng/mL), and his pituitary tumor mass decreased to 1/4 of its initial size. His weight, dyslipidemia, and impaired glucose tolerance improved within 1 year. A marked increase in the bone mineral density (BMD) at the second to fourth lumbar spine (from 0.801 g/cm2 to 0.870 g/cm2, +8.6%) and at the femoral neck (from 0.785 g/cm2 to 0.864 g/cm2, +10.1%) were observed despite the presence of unresolved hypogonadism.. Treatments with dopamine agonists represent a beneficial strategy for patients with prolactinoma accompanied with bone loss, in addition to their established efficacy in shrinkage of the size of pituitary tumors, normalization of PRL levels, and improvement of metabolic disorders.

Topics: Adult; Bone Diseases, Metabolic; Cabergoline; Dopamine Agonists; Ergolines; Glucose Intolerance; Humans; Hypertriglyceridemia; Male; Overweight; Pituitary Neoplasms; Prolactinoma

A 38-year-old woman was admitted to our hospital because of amenorrhea, multiple bone fractures, and a Cushingoid appearance. Endocrinological investigations revealed that she had co-existing Cushing's disease and prolactinoma, with a serum level of prolactin (PRL) at 1,480 ng/mL, corticotropin (ACTH) at 81.3 pg/mL, and cortisol at 16.6 μg/dL. Due to the lack of indication for transsphenoidal surgery, cabergoline monotherapy was initiated. A 6-month course of treatment resulted in only subtle amelioration of hypercortisolism, while hyperprolactinemia was dramatically improved. In 5 cases of bihormonal (ACTH/PRL) pituitary macroadenoma reported in the English literature, 2 were initially treated with dopaminergic agonists with substantial effectiveness for both PRL and ACTH. We herein report an extremely rare case of bihormonal macroadenoma in which only PRL was responsive to treatment.

Topics: Adrenocorticotropic Hormone; Adult; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Hydrocortisone; Hyperprolactinemia; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Prolactin; Prolactinoma

Prolactin (PRL)-secreting macroadenomas usually measure between 10 and 40 mm. Giant (adenoma size ≥40 mm) PRL-tumors are not common, and larger prolactinomas (maximal diameter ≥60 mm) are rare, and their management outcomes have not been well characterized.. We have identified 18 subjects (16 men, 2 females) with giant PRL-adenomas (size ≥60 mm; PRL > 1000 ng/ml) and summarized their characteristics and response to treatment.. Mean age was 36.3 ± 13.5 years (range 12-59 years). Mean adenoma size was 71.8 ± 10.2 mm (60-92 mm). Complaints at presentation included headaches in 11 patients, visual deterioration in 9, sexual dysfunction in 9 males, and behavioral changes in two. Fourteen (78 %) had visual field defects. Mean PRL at presentation was 28,465 ng/ml (range 1300-270,000). All patients were treated with cabergoline (3.9 ± 2.0 mg/week), except for one who received bromocriptine. Treatment achieved PRL normalization in 11/18 patients within a median interval of 20 months. Visual improvement occurred in 12/14 patients with pre-treatment visual abnormalities. Nine patients underwent surgery (transsphenoidal, 7; transcranial, 2). None of the seven patients with elevated PRL before surgery achieved remission post-operatively. After a follow-up of 7.8 ± 5.1 years, 15/18 patients had significant adenoma shrinkage. Eleven patients are normoprolactinemic, 3 are partially controlled (PRL < 3 × ULN), and 4 remain with significantly elevated PRL. Most patients reported disappearance or improvement of their complaints.. These enormous PRL-adenomas are invasive but respond fairly well to medical treatment. Long-term therapy with high dose cabergoline together with a pituitary surgery in some patients was the key for their successful management, achieving biochemical and clinical remission in most patients.

Topics: Adolescent; Adult; Antineoplastic Agents; Bromocriptine; Cabergoline; Child; Ergolines; Female; Galactorrhea; Headache; Hormone Antagonists; Humans; Male; Middle Aged; Neurosurgical Procedures; Pituitary Neoplasms; Prolactinoma; Sexual Dysfunction, Physiological; Treatment Outcome; Tumor Burden; Vision Disorders; Young Adult

Clinically nonfunctioning pituitary adenoma (NFPA) remains the only pituitary tumor subtype for which no effective medical therapy is available or recommended. We evaluated dopamine agonist (DA) therapy for preventing growth of postsurgical pituitary tumor remnants.. The study design included historical cohort analysis of clinical results at two pituitary referral centers with different standard practices for postoperative NFPA management: DA therapy or conservative follow-up.. Seventy-nine patients followed for 8.8±6.5 years were treated with DA, initiated upon residual tumor detection on postoperative MRI (preventive treatment (PT) group, n=55), or when tumor growth was subsequently detected during follow-up (remedial treatment (RT) group, n=24). The control group (n=60) received no medication. Tumoral dopamine and estrogen receptor expression assessed by quantitative RT-PCR and immunostaining were correlated with response to treatment.. Tumor mass decreased, remained stable, or enlarged, respectively, in 38, 49, and 13% of patients in the PT group, and in 0, 53, and 47% of control subjects; shrinkage or stabilization was achieved in 58% of enlarging tumors in the RT group, P < 0.0001.Fifteen-year progression-free survival rate was 0.805, 0.24, and 0.04, respectively, for PT, RT, and control groups (P<0.001). About 42% of patients in the control group required additional surgery or radiotherapy, compared with 38 and 13% subjects in the RT and PT groups, respectively (P=0.002). Outcome measures were not related to NFPA D2R abundance.. Dopamine agonist therapy in patients with NFPA is associated with decreased prevalence of residual tumor enlargement after transsphenoidal surgical resection.

Topics: Adenoma; Adult; Aged; Bromocriptine; Cabergoline; Disease Progression; Dopamine Agonists; Ergolines; Female; Humans; Immunohistochemistry; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Receptors, Dopamine; Receptors, Estrogen; Treatment Outcome

The optimal duration of cabergoline (CAB) treatment of prolactinomas that minimizes recurrences is not well established. 2011 Endocrine Society Guidelines suggested that withdrawal may be safely undertaken after 2 years in patients achieving normoprolactinemia and tumor reduction.. We analyzed 74 patients (mean age = 46.9 ± 14.4, M/F = 19/55, macro/micro = 18/56) bearing a prolactinoma divided in 3 groups: group A (23) treated for 3 years, group B (23) for a period between 3 and 5 years, and group C (28) for a period >5 years. CAB therapy was interrupted according to Endocrine Society Guidelines. Prolactin (PRL) levels were measured 3, 6, 12 and 24 months after withdrawal. Recurrence was defined with PRL levels ≥30 ng/ml.. Groups did not differ in pretreatment PRL levels (123.2 ± 112.1, 120.9 ± 123.8, 176.6 ± 154.0), pituitary deficit (4, 17, 17 %), mean CAB weekly dose (0.7 ± 0.4, 0.6 ± 0.3, 0.7 ± 0.4) and PRL levels before withdrawal (17.1 ± 19.6, 11.4 ± 8.8, 13.8 ± 13.5). Recurrence occurred within 12 months in 34 patients (45.9 %), without significant differences among groups. Neuroradiological evaluation showed a significantly higher presence of macroadenoma in group C (13, 17 and 39 %, respectively). Recurrence rate of hyperprolactinemia did not depend on sex, tumor size or CAB dose but it was significantly correlated with PRL levels at diagnosis and before withdrawal (p = 0.03). Finally, patients with pituitary deficit at diagnosis showed a significantly higher recurrence rate (p = 0.03).. The study provides additional evidence that prolonging therapy for more than 3 years does not reduce recurrence rate. In particular, recurrence risk was similar in micro- and macroadenomas, and higher in patients with pituitary deficits at diagnosis.

Topics: Adult; Aged; Biomarkers; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Neoplasm Recurrence, Local; Pituitary Neoplasms; Prognosis; Prolactinoma; Tomography, X-Ray Computed; Withholding Treatment

Topics: Brain; Cabergoline; Central Nervous System Agents; Child; Dopamine Agonists; Ergolines; Fructose; Humans; Male; Migraine Disorders; Pituitary Neoplasms; Prolactinoma; Topiramate

Topics: Adult; Antineoplastic Agents; Biomarkers; Blood Glucose; Cabergoline; Cholesterol; Ergolines; Humans; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma; Retrospective Studies; Treatment Outcome; Triglycerides

The purpose of this case series is to report eight patients with giant prolactinomas emphasizing presentations and a treatment complication. The study group included six men and two women. The median age was 29 years (18-54 years); median serum prolactin level was 4,562 ng/ml (1,543-18,690 ng/ml); three patients (37.5%) had panhypopituitarism; median tumor diameter was 50 mm (41-60 mm). Five patients (62.5%) had visual field defects and three had improvement during treatment; six patients (75%) reached prolactin normalization, with a median time of 10.5 months (7-84 months) and median dose of 2.0 mg/week (1.0 to 3.0 mg/week). One patient presented as a true incidentaloma. One patient presented a cerebrospinal fluid leakage during medical treatment and refused surgery, however this resolved with conservative measures. This case series illustrate a rare subtype of macroprolactinomas, the importance of considering unusual presentations at the diagnosis, the effectiveness of pharmacological treatment and its possible complications.

Topics: Adolescent; Adult; Antineoplastic Agents; Cabergoline; Cerebrospinal Fluid Leak; Dopamine Agonists; Ergolines; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Sella Turcica; Time Factors; Treatment Outcome; Tumor Burden; Young Adult

Up to date, only a small evidence of psychosis induced by cabergoline is available in literature. Herein, the case of a 34-year-old bipolar patient treated with cabergoline has been described. Cabergoline is generally a safe and effective method of reducing prolactin levels and it may be associated with psychiatric side effects, including psychotic features.

Topics: Adult; Antineoplastic Agents; Bipolar Disorder; Cabergoline; Ergolines; Female; Humans; Pituitary Neoplasms; Prolactinoma; Psychoses, Substance-Induced

Pituitary manifestation of Wegener granulomatosis (WG) is extremely rare. When there is pituitary involvement, the granulomatous inflammatory lesions involving the pituitary gland may appear several months to years after the primary diagnosis.. We present a case of a 32-year-old woman who presented with galactorrhea, amenorrhea, and elevated serum prolactin levels. Imaging demonstrated a sellar lesion with characteristics of a pituitary macroadenoma. Treatment with cabergoline was initiated, but the tumor continued to grow during a 6-month period. Subsequent surgical exploration revealed a chronic inflammatory lesion; the patient subsequently was diagnosed with WG based on laboratory evaluation and further systemic manifestations. She had a favorable clinical and radiologic response with immunosuppressive doses of glucocorticoids and rituximab.. This case appears to be the first reported of a patient with unknown WG in whom the diagnosis was established after she presented with a sellar lesion mimicking a prolactin-secreting pituitary adenoma on initial presentation requiring surgical resection. The only endocrine abnormality discovered was moderate hyperprolactinemia. Sellar lesions with only moderate elevations in serum prolactin, particularly those that are refractory to medical management with a dopamine agonist, should prompt further investigation to confirm the diagnosis. WG should be part of the differential diagnosis of inflammatory lesions in the sella, the identification of which can facilitate early diagnosis and treatment of this systemic disease for optimal outcome.

Topics: Adult; Antineoplastic Agents; Cabergoline; Diagnosis, Differential; Drug Resistance, Neoplasm; Ergolines; Female; Glucocorticoids; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Pituitary Neoplasms; Prolactinoma; Rituximab; Sella Turcica

A gangliocytoma rarely coexists with a pituitary adenoma in a sellar lesion. Herein, we describe our experience in treating a mixed gangliocytoma and prolactinoma of the pituitary gland.. A 16-year-old male presented with severe headache and vomiting. Magnetic resonance imaging showed a large pituitary tumor with hydrocephalus. Because of the increased levels of serum prolactin (PRL), we treated the patient with cabergoline, which decreased the tumor size and improved the hydrocephalus. Six months after the treatment, the tumor began to increase in size, despite the normalization of the PRL level with cabergoline treatment. An endoscopic transsphenoidal resection was performed and the tumor was mostly removed. Microscopic examination of the resected tumor showed a mixture of prototypical pituitary adenoma cells and the proliferation of mature ganglion cells. Immunohistochemistry showed that the ganglion cells were positively stained for synaptophysin, NeuN, and PRL as shown in the adenomatous component. A few cells were immunostained with both PRL and NeuN, and a few cells were immunopositive for nestin, but not PRL or synaptophysin.. Our findings showed the existence of cells that are phenotypically intermediate between ganglion cells and adenoma cells, and the existence of stem cell-like cells, which support the hypothesis that adenoma cells can transform into ganglion cells or that both ganglion and adenoma cells derive from common stem cells. Furthermore, the ganglion cells seemed to grow rapidly and independently of dopamine, which is in contrast to prototypical prolactinoma cells.

Topics: Adolescent; Antineoplastic Agents; Cabergoline; Disease Progression; Drug Resistance, Neoplasm; Ergolines; Ganglioneuroma; Humans; Hydrocephalus; Magnetic Resonance Imaging; Male; Neoplasms, Complex and Mixed; Neuroendoscopy; Pituitary Neoplasms; Prolactinoma

Management of macroprolactinomas has dramatically changed in recent decades, from surgical to medical treatment as first-line therapy, with the development of dopamine agonists (DA). But few data exist on the long-term outcome of these patients.. Retrospective descriptive multicenter study of patients with macroprolactinoma followed for at least 5 years between 1973 and 2008 at the University Hospitals of Strasbourg and Marseille.. Forty-eight patients were included with 27 men, hypopituitarism in 33.3% of all patients and mean serum prolactin (PRL) level at diagnosis 2218.2±4154.7μg/L. Among the patients, 58.3% received medical treatment, 25% had additional surgery and 12.5% surgery and radiotherapy. The mean follow-up duration was 196±100 months. At the end of follow-up, 10 patients (20.8%) were cured (i.e. normal PRL level and normal imaging, no symptoms and withdrawal of DA≥1 year), 33 (68.8%) were controlled (i.e. normal PRL level, normal or abnormal imaging, no symptoms, DA in progress) and 5 (10.4%) were uncontrolled. Uncontrolled patients had significant higher baseline PRL level (P=0.0412) and cabergoline cumulative dose (P=0.0065) compared to the controlled group. There was no increase in frequency of hypopituitarism. Clinically significant valvular heart disease was found in 2 patients but screening was not systematic.. Macroprolactinoma is currently most often a chronic disease controlled with DA. However, uncertainty about the adverse effects associated with high cumulative doses and the lack of data on the prognosis at very long-term should incite to revisit current strategies, including the role of surgery combined to medical treatment.

Topics: Adolescent; Adult; Cabergoline; Dopamine Agonists; Ergolines; Female; France; Humans; Hyperprolactinemia; Hypopituitarism; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma; Retrospective Studies; Treatment Outcome; Young Adult

Topics: Cabergoline; Dopamine Agonists; Ergolines; Eunuchism; Hormone Replacement Therapy; Humans; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Testosterone

Pons herniation after cabergoline therapy for giant prolactinoma is a complication not documented in literature.. We report a medium aged patient who developed secondary hemiparesis after 18 months of medical treatment. MRI revealed pons herniation into the clivus. There was improvement with conservative treatment. Secuencial MRIs are presented showing the tumor at the moment of the diagnosis, tumor shrinkage and pons herniation.. Some studies have shown that a significant and rapid tumor shrinkage resulting from treatment with cabergoline can occur and it is thought that some complications are related with this tumor regression, as in the presented case.

Topics: Antineoplastic Agents; Cabergoline; Ergolines; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Pons; Prolactinoma

Male-to-female transsexual persons use oestrogens + antiandrogens to adapt their physical bodies to the female sex. Doses are usually somewhat higher than those used by hypogonadal women receiving oestrogen replacement. Particularly in cases of self-administration of cross-sex hormones, doses may be very high. Oestrogens are powerful stimulators of synthesis and release of prolactin and serum prolactin levels are usually somewhat increased following oestrogen treatment. Prolactinomas have been reported in male-to-female transsexual persons, both after use of high and conventional doses of oestrogens but remain rare events. We report two new cases of prolactinomas in male-to-female transsexual persons, one in a 41-year-old subject who had used nonsupervised high-dose oestrogen treatment since the age of 23 years and another one in a 42 year old who had initiated oestrogen treatment at the age of 17 years. Their serum prolactin levels were strongly increased, and the diagnosis of a pituitary tumour was confirmed by imaging techniques. Both cases responded well to treatment with cabergoline treatment whereupon serum prolactin normalised. Our two cases are added to the three cases of prolactinomas in the literature in persons who had used supraphysiological doses of oestrogens.

Topics: Adult; Antineoplastic Agents; Cabergoline; Ergolines; Estrogens; Female; Humans; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Prolactin; Prolactinoma; Transgender Persons

The management of giant prolactinomas remains a major challenge, despite dopamine agonists being the first line of treatment, owing to its efficacy to normalize prolactin levels and reduce tumor volume. The aim of this study is to characterize the therapeutic aspects, manifestations and outcomes of 16 cases of giant prolactinomas admitted at a single tertiary center in Riyadh, Saudi Arabia.. Retrospective data collection involving 16 Saudi patients diagnosed with giant prolactinoma at the Pituitary Clinic in King Fahad Medical City, Riyadh, Saudi Arabia between January 2006 and July 2012.. A total of 16 patients (ten males; six females) with age of diagnosis between 21 and 55 years (mean 34.9 years) were included in the analysis. The most common presenting features include headache, visual defects and sexual dysfunction. Baseline mean serum prolactin level were extremely high for both sexes which eventually decreased by as much as 97% after cabergoline treatment. Serum prolactin concentrations completely normalized in six patients and significantly decreased in five patients 3-5 times that of normal range. Tumor volume also decreased by an average of 86% for males and 87% for females. Two patients had no tumor size change with cabergoline and required surgery.. Findings indicate that cabergoline provides dramatic clinical improvements with excellent safety profile. Cabergoline should therefore be considered as the primary therapy for giant prolactinomas.

Topics: Adult; Antineoplastic Agents; Arabs; Biomarkers, Tumor; Cabergoline; Comorbidity; Ergolines; Female; Humans; Male; Middle Aged; Neurosurgical Procedures; Pituitary Neoplasms; Prolactin; Prolactinoma; Retrospective Studies; Saudi Arabia; Tertiary Care Centers; Time Factors; Treatment Outcome; Tumor Burden; Young Adult

Cabergoline is the treatment of choice for prolactin (PRL)-producing pituitary adenomas, because of its efficacy in normalizing PRL levels, and inducing tumor shrinkage. The clinical use of 3 T magnetic resonance imaging (MRI) for neuroimaging has rapidly expanded in recent years. In particular, T2-weighted imaging (T2WI) provides high anatomical and contrast resolution.. In this study, serial 3 T MRI with T2WI was utilized during cabergoline treatment of 10 patients with macroprolactinomas. Cabergoline was started at a standard weekly dosage and incrementally adjusted on individual posttreatment PRL values.. MRI confirmed tumor shrinkage in all patients during cabergoline treatment. Cabergoline normalized hyperprolactinemia in all but one patient. In six of 10 patients, distinct low-signal-intensity areas were evident throughout the adenomas on T2WI. In four of those six patients, massive low-signal-intensity areas appeared at 1-4 months, after which tumors decreased in size by over 80%. These findings in the early phase of prolactinoma treatment predicted pronounced regression or near-complete disappearance of the tumor. Reduction of T2 intensity possibly reflected dehydration due to diffuse hemorrhage in the adenomas.. T2-weighted 3 T MR images are valuable for assessing and monitoring cabergoline treatment of macroprolactinomas.

Topics: Adult; Aged; Antineoplastic Agents; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma; Young Adult

To determine the dopamine receptor subtype 2 (DR2) mRNA levels and protein expression and to evaluate the effect of adjuvant cabergoline therapy on tumour volume (TV) in patients with postoperative residual nonfunctioning pituitary adenoma (NFPA).. The mRNA expression was quantified by real-time RT-PCR (TaqMan(®)), and protein expression was evaluated by immunohistochemistry. Tumours were classified according to the percentage of immunostained cells for DR2 as scores 1 (<50% of stained cells) or 2 (≥50%). Cabergoline was started at least 6 months after surgery in nine patients with residual tumours (3 mg/week). The cabergoline effect was prospectively evaluated by magnetic resonance imaging using three-dimensional volume calculation. TV reduction >25% was considered significant.. The DR2 mRNA expression was variable but was observed in 100% of the samples (N = 20). DR2 protein expression was also observed in all the tumours (N = 34). Twenty-nine tumours (85%) were classified as score 2. The median DR2 mRNA expression was higher in the tumours classified as score 2 compared with score 1 (P = 0·007). TV reduction with cabergoline therapy was observed in 67% of the patients (6/9). The median TV before and after 6 months of treatment was 1·90 cm(3) (0·61-8·74) and 1·69 cm(3) (0·36-4·20) [P = 0·02], respectively.. In conclusion, DR2 is expressed in all adenomas and the majority of the patients in this study displayed tumour shrinkage on cabergoline (CAB) therapy. Thus, CAB might be useful in adjuvant therapy in NFPA patients with residual tumours after surgery.

Topics: Adenoma; Adult; Aged; Antineoplastic Agents; Cabergoline; Ergolines; Female; Gene Expression Regulation, Neoplastic; Humans; Ki-67 Antigen; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Receptors, Dopamine D2; RNA, Messenger; Treatment Outcome

Hyperprolactinemia and hypogonadism are reportedly associated with an impaired metabolic profile. The current study aimed at investigating the effects of testosterone replacement and cabergoline (CAB) treatment on the metabolic profile in male hyperprolactinemic patients.. Thirty-two men with prolactinomas, including 22 with total testosterone (TT) <8 nmol/l (HG, 69%) and 10 with TT >8 nmol/l (non-HG, 31%), were entered in the study. In all patients, metabolic parameters were assessed at diagnosis and after 12- and 24-month treatment.. Compared to non-HG patients, at baseline the HG patients had higher waist circumference (WC). TT significantly correlated with body mass index (BMI). Twelve-month CAB induced PRL normalization in 84%. HG prevalence significantly decreased (28%) and non-HG prevalence significantly increased (72%). Anthropometric and lipid parameters, fasting insulin (FI), insulin sensitivity index (ISI0), homeostatic model assessment of insulin secretion (HOMA-β) and homeostatic model assessment of insulin resistance (HOMA-IR) significantly improved compared to baseline. TT was the best predictor for FI. Percent change (Δ) of TT significantly correlated with ΔCholesterol, ΔWeight and ΔBMI. Compared to non-HG patients, the HG patients had a higher weight, BMI, WC and HOMA-β. In HG, testosterone replacement was started. After 24 months, PRL normalized in 97%. HG prevalence significantly decreased (6%) and non-HG prevalence significantly increased (94%). Anthropometric and lipid parameters, FI, ISI0, HOMA-β and HOMA-IR significantly improved compared to baseline, with FI, ISI0, HOMA-β and HOMA-IR further ameliorating compared to the 12-month evaluation. Compared to non-HG patients, the HG patients still had a higher weight, BMI and WC.. In hyperprolactinemic hypogonal men, proper testosterone replacement induces a significant improvement in the metabolic profile, even though the amelioration in the lipid profile might reflect the direct action of CAB.

Topics: Adult; Cabergoline; Dopamine Agonists; Ergolines; Hormone Replacement Therapy; Humans; Hyperprolactinemia; Male; Metabolome; Middle Aged; Pituitary Neoplasms; Prolactinoma; Testosterone

Topics: Adult; Bromocriptine; Cabergoline; Combined Modality Therapy; Contraindications; Dopamine Agonists; Drug Substitution; Ergolines; Female; Headache; Hormone Replacement Therapy; Humans; Hydrocortisone; Hypophysectomy; Infant, Newborn; Male; Pituitary Apoplexy; Pituitary Neoplasms; Pregnancy; Pregnancy Complications; Pregnancy Complications, Neoplastic; Prolactinoma; Thyroxine; Vision Disorders

Giant prolactinoma is a rare subset of macroadenomas. Limited studies demonstrated which therapy could be successfully used in the first-line therapy of giant prolactinoma. We presented a case with a 54 × 40 × 40 mm pituitary adenoma and optic chiasmatic compression with left sphenoid sinus invasion. The tumor caused a loss of visual field of the right side. Cabergoline treatment was started with dose of 1.5 mg/week. Fifteen days later, the clinical visual acuity examination showed a significant improvement in the patient with visual field defect. After the five years follow-up magnetic resonance imagining showed reduction of the adenoma size (17 × 12 mm) was significant. Our findings suggest that, cabergoline can be used as a first-line therapy in giant prolactinomas because tumoral shrinkage without a surgical procedure and rapid improvement in visual field defect is achieved with this medical treatment.

Topics: Adult; Antineoplastic Agents; Cabergoline; Ergolines; Follow-Up Studies; Humans; Male; Optic Chiasm; Pituitary Neoplasms; Prolactinoma; Treatment Outcome; Vision, Low

Topics: Antidepressive Agents; Antineoplastic Agents; Cabergoline; Depressive Disorder, Major; Electroconvulsive Therapy; Ergolines; Female; Humans; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma

To identify early follow-up measures that will predict the dynamics of prolactin (PRL) decrease and adenoma shrinkage in men harboring macroprolactinomas.. A single-center historical prospective study including a consecutive group of 71 men with pituitary macroadenomas (≥10 mm) and hyperprolactinemia (PRL >7 times the upper limit of normal [ULN]) treated medically with cabergoline. Comparisons of PRL normalization rates were performed according to PRL levels achieved at 6 months, maximal adenoma shrinkage during follow-up, and other patient characteristics. Correlations were analyzed to identify characteristics of PRL suppression dynamics.. PRL levels after 6 months of treatment correlated positively with current PRL levels (r = 0.74; P<.001), with time to PRL normalization (r = 0.75; P<.001), and with adenoma diameter following treatment (r = 0.38; P = .01). Adenoma shrinkage depicted by first magnetic resonance imaging on treatment correlated with maximal adenoma shrinkage during follow-up (r = 0.56; P = .006). Five patients had nadir PRL levels ≥3 times the ULN (51 ng/mL) and showed slower response to cabergoline treatment, with consistently higher PRL levels compared with responding patients throughout follow-up (mean 6-month PRL levels, 519 ± 403 ng/mL versus 59 ± 118 ng/mL; P<.001).. Six-month PRL level might serve as a surrogate marker for PRL normalization and adenoma shrinkage dynamics among men harboring macroprolactinomas.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Cabergoline; Cohort Studies; Down-Regulation; Ergolines; Humans; Hyperprolactinemia; Male; Middle Aged; Pituitary Neoplasms; Prognosis; Prolactin; Prolactinoma; Remission Induction; Time Factors; Tumor Burden; Young Adult

Topics: Adrenocorticotropic Hormone; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Hydrocortisone; Magnetic Resonance Imaging; Middle Aged; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Remission Induction; Tumor Burden

Genetic alterations explaining the clinical variability of prolactinomas still could not be clarified and dopamine D2 receptor (DRD2) polymorphism is a putative candidate for the variable response to dopaminergic treatment. The present study was conducted to investigate the influence of DRD2 TaqI A polymorphism on initial and follow-up characteristics of prolactinoma.. Seventy-two patients with prolactinoma and 98 age and gender matched control subjects were recruited to the case-control study. Serum prolactin levels were assessed by enzyme-linked immunosorbent assay and DRD2 polymorphism was determined by polymerase chain reaction and restriction length polymorphism analysis.. Decrease of prolactin levels and the tumor shrinkage after cabergoline treatment were 93.9±5.9% and 58.3±33.1% in microadenomas and 96.1±6.1% and 51.7±29.3 in macroadenomas (P=0.02 and P>0.05, respectively). We observed no significant difference for DRD2 genotypes and the alleles between the patients and healthy group (P>0.05). Prolactin levels before treatment were correlated with tumor diameter before and after treatment and the percentage of prolactin decrease with treatment (P<0.001 r=0.58, P<0.001 r=0.40 and P<0.001 r=0.47, respectively). Tumor diameter before the treatment was also correlated with the tumor diameter after the treatment (P<0.001 r=0.64) and the percentage of prolactin decrease (P=0.01 r=0.30). However, no significant association was found between characteristics of prolactinoma and DRD2 genotypes and alleles (P>0.05).. This study revealed that DRD2 TaqI A receptor polymorphism was not associated with the development of prolactinoma and its clinical characteristics. Future studies are needed to clarify the clinical implications of genetic alterations in prolactinoma.

Topics: Adult; Alleles; Antineoplastic Agents; Cabergoline; Case-Control Studies; Dopamine Agonists; Ergolines; Female; Genotype; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Prolactin; Prolactinoma; Receptors, Dopamine D2

Giant prolactinomas are rare pituitary tumours of which management can be a challenge. A 28-year-old man presented with headaches, visual impairment and behavioural changes. Clinically, the patient was found to have hypogonadism and bitemporal hemianopsia. A MRI demonstrated a pituitary tumour 76 mm in diameter and blood tests revealed a serum prolactin of 158,700 µU/mL (reference range 58-254). Initially, a craniotomy was performed. Immunohistochemistry of the tumour identified a prolactinoma with a high proliferative index and the patient was started on treatment with a dopamine agonist. A year later, neurological symptoms worsened due to regrowth of the lesion's cystic component, and so further surgery was performed. After 10 years of treatment with dopamine agonists, the prolactin levels decreased by 96.8%, there was an effective reduction in tumour size, and the neurological signs and symptoms resolved.

Topics: Adult; Craniotomy; Dopamine Agonists; Ergolines; Follow-Up Studies; Headache; Hemianopsia; Humans; Hypogonadism; Immunohistochemistry; Magnetic Resonance Imaging; Male; Pituitary Gland; Pituitary Neoplasms; Prolactin; Prolactinoma; Vision, Low

Amyloid deposition in the pituitary gland is a rare localised form of amyloidosis, and most commonly reported with prolactinoma. Macular amyloidosis is a rare form of localised cutaneous amyloidosis of obscure aetiology. In contrast to most localised amyloidosis, the precursor protein(s) of both macular amyloidosis and prolactinoma are unknown. A 35-year-old man with chronic headache (six years), blurring of vision (three years), and hyperpigmented macular lesion involving arms, legs, and back (two years) was diagnosed to have hyperprolactinaemia (8927 ng/mL) and secondary adrenal insufficiency. MRI revealed pituitary macroadenoma compressing the optic chiasma, encasing the right carotid artery and extending into the sphenoid sinus. A biopsy of skin from the right upper arm revealed thickened stratum corneum, acanthosis, and deposition of pale eosinophilic material in papillary dermis that gave a rose pink colour under methyl-violet and appeared congophilic with Congo red stain, which under polarised light showed green birefringence, diagnostic of macular amyloidosis. Headache, bitemporal haemianopia, and skin lesion improved following cabergoline therapy. Temporal profile of the disease characterised by symptoms of macroprolactinoma preceding onset of macular amyloidosis with resolution of symptoms of macroprolactinoma, accompanied by reductions in prolactin, and concomitant improvement in macular amyloidosis with cabergoline therapy may suggest some link between macroprolactinoma and macular amyloidosis. This report intends to highlight this novel association of macular amyloidosis and macroprolactinoma.

Topics: Adrenal Insufficiency; Adult; Amyloidosis, Familial; Antineoplastic Agents; Cabergoline; Ergolines; Humans; Hyperprolactinemia; Macula Lutea; Male; Pituitary Neoplasms; Prolactinoma; Retinal Diseases; Skin Diseases, Genetic

Pituitary gland adenomas producing prolactin are one of the commonest hormonally active tumours. Pharmacological treatment using of dopamine receptors agonists is the therapy of choice in a case of prolactinoma. Bromocriptine, which causes numerous side-effects is the most commonly used drug. Recently, good results of therapy have been achieved with cabergoline - a selective dopamine receptor agonist with prolonged time of action. The aim of the study was to evaluate therapy with cabergoline of men with macroprolactinoma based on clinical, hormonal and radiological examinations.. Ten men aged 18-65 (mean 41.9 ?15.01 years) with the presence of a pathological mass in the pituitary gland sized between 16.7 and 40.5 mm (mean 29.8 ± 9.38 mm) and an elevated prolactin (PRL) level of between 37.3 and 4700 ng/mL (mean 1608.2 ±1771.6 ng/mL) were included in the study. The PRL and other trophic hormones levels were evaluated after 1, 3, 6 and 12 months, and tumour size was evaluated by magnetic resonance imaging examination after 12 months of therapy with cabergoline. Results: Therapy with cabergoline led to remission of headaches, visual acuity correction, and a significant improvement in libido and erection in all patients. In 90% of patients, PRL normalisation was achieved, just the initial months of therapy. The mean PRL serum concentrations were before, and after 1, 3, 6 and 12 months of therapy respectively, 1608.2 ± 1771.6 ng/mL and 263.4 ± 223.4, 136.1 ± 244.7,91.31 ± 105.5 and 27.5 ± 57.7 ng/mL. A significant tumour size reduction was observed: from 29.8 ± 9.4 mm to 23.2 ± 9.4 mm, a mean reduction of about 6 mm, or 25.1% (from 4-48.5%). No significant correlation between the mean tumour size and PRL level was observed before or during the treatment. A decreased testosterone level before the therapy was proven, and its gradual increase during the treatment was observed, but after 12 months no normal mean testosterone concentration was achieved.. 1. The administration of cabergoline to patients with macroprolactinoma is effective in reaching PRL level normalisation as well as in tumour size reduction. 2. Therapy with cabergoline significantly decreases the clinical symptoms of hyperprolactinemia and neurological and ophtalmological changes associated with the presence of a pathological lesion in the pituitary gland. 3. Tumour size is not a predictive factor for the effectiveness of therapy with cabergoline.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Cabergoline; Ergolines; Humans; Male; Middle Aged; Pituitary Neoplasms; Poland; Prolactinoma; Young Adult

In men harboring prolactinoma the most common symptoms are related to hypogonadism, including decreased libido, erectile dysfunction, and gynecomastia. These men characteristically present with elevated serum prolactin (PRL) levels, suppressed gonadotropins, and low testosterone levels. We studied a group of 11 unique men with prolactinomas presenting with testosterone levels within the normal range (≥2.6 ng/ml; cohort A), and compared them to 11 prolactinoma men with borderline baseline testosterone (2.1-2.5 ng/ml; cohort B) and to a cohort of 34 prolactinoma patients with low testosterone levels (≤2 ng/ml; cohort C). Mean testosterone levels at presentation were 3.91 ± 0.9 ng/ml in cohort A (range, 2.6-5.2 ng/ml), 2.44 ± 0.16 ng/ml in cohort B and 0.96 ± 0.6 in cohort C (p < 0.001). Mean baseline PRL levels were >20 times above normal in cohort A compared to >100 times above normal in cohorts B and C. Symptoms of hypogonadism were present in 55, 64 and 76% of men in groups A, B and C, respectively. There was a trend towards a larger tumor size in the low testosterone group (p = 0.06). Visual fields defects at presentation were more prevalent in this cohort (C). With cabergoline, testosterone level increased from 3.91 to 6.42 ng/ml (Δ = 2.51 ng/ml) in cohort A, from 2.44 to 5.63 ng/ml (Δ = 3.19 ng/ml) in cohort B, and from 0.96 to 3.30 ng/ml (Δ = 2.34 ng/ml) in cohort C (p < 0.05 for each group). Symptoms of hypogonadism improved following treatment in 83% of symptomatic men in cohort A. Normal testosterone does not exclude the likelihood of prolactinoma in men. When treated with cabergoline, testosterone levels in these men can increase higher within the normal range together with clinical improvement.

Topics: Adult; Aged; Antineoplastic Agents; Cabergoline; Cohort Studies; Ergolines; Humans; Hypogonadism; Male; Middle Aged; Pituitary Neoplasms; Prognosis; Prolactinoma; Testosterone; Treatment Outcome

Prolactinomas are common pituitary tumors that can cause gonadal dysfunction and infertility related to hyperprolactinemia. Dopamine agonists are the first-line treatment in these patients. Cabergoline leads to significant reduction in serum prolactin levels and tumor size in patients with prolactinoma. Dopamine agonists have been associated with adverse effects such as nausea, vomiting and psychosis. We report here a case with cabergoline-induced immune hemolytic anemia. The patient had cabergoline treatment history for prolactinoma and presented with weakness, fatigue, nausea, and paleness. Laboratory findings revealed severe anemia-related immune hemolysis. There were no causes identified to explain hemolytic anemia except cabergoline. Therefore, cabergoline therapy was stopped and subsequently hemolytic anemia resolved and did not occur again. This is the first reported pediatric case with prolactinoma and cabergoline-induced hemolytic anemia. Clinicians should be watchful for this rare side effect induced by cabergoline.

Topics: Adolescent; Anemia, Hemolytic; Antineoplastic Agents; Cabergoline; Ergolines; Female; Humans; Pituitary Neoplasms; Prolactinoma

Primary pharmacological therapy may be the only viable treatment option for many patients with acromegaly, especially those presenting with advanced disease with large inoperable tumors. Long-acting somatostatin analogs are currently the first-line treatment of choice in this setting, where they provide biochemical control and reduce tumor size in a significant proportion of patients. We herein present a brief overview of the role of primary pharmacological therapy in the treatment of acromegaly within the context of Latin America and support this with a representative case study.. A 20 year old male presented with clinical and biochemical evidence of acromegaly. The glucose-suppressed growth hormone (GH) was 5.3 μg/L, his insulin-like growth factor-1(IGF-1) was 3.5 times the ULN and serum prolactin greater than 4,000 μg/L. Pituitary MRI revealed a large and invasive mass, extending superiorly into the optic chiasm and laterally into the left cavernous sinus. He was treated with a combination of octreotide and cabergoline with remarkable clinical improvement, normalization of GH and IGF-1 values and striking shrinkage of the adenoma.. This case illustrates how effective the pharmacological therapy of acromegaly can be and yet at the same time, raises several important issues such as the need for life-long treatment with costly medications such as the somatostatin analogs. Access to these agents may be limited in regions where resources are restricted and clinicians face challenges in order to make the most efficient use of available options.

Topics: Acromegaly; Adenoma; Cabergoline; Dopamine Agonists; Ergolines; Human Growth Hormone; Humans; Male; Octreotide; Pituitary Neoplasms; Somatostatin; Young Adult

Pituitary carcinomas, which are rare, generally present with craniospinal and systemic metastases. Although several treatments exist, the prognoses of patients with pituitary carcinomas are extremely poor to date. In this report, the authors describe the case of a 23-year-old male who had undergone trans-sphenoidal surgery and radiotherapy for an invasive prolactinoma. Seven years later, he presented with a new 4th ventricle metastasis from the pituitary lesion, and it was diagnosed with a pituitary carcinoma. He underwent resection and Gamma-knife radiosurgery (GKRS). The tumor has been well controlled for over 3 years. To our knowledge, there have been no reports of the effects of GKRS in patients with pituitary carcinomas. GKRS might have considerable effects in the treatment of pituitary carcinomas.

Topics: Cabergoline; Cerebral Ventricle Neoplasms; Dopamine Agonists; Ergolines; Fourth Ventricle; Humans; Male; Pituitary Hormones; Pituitary Neoplasms; Prolactinoma; Radiosurgery; Young Adult

The aim of this article is to investigate the phenotype and etiology of prolactinoma-associated headache as well as present and discuss the plausible pain-relieving effect of dopamine agonist treatment.. In this case-based audit we included 11 patients with prolactinomas and one patient with idiopathic hyperprolactinemia presenting with headache that subsequently improved or resolved after dopamine agonist treatment.. A significant ipsilateral location of tumor mass and reported headache symptoms was observed (p = 0.018). After dopamine agonist treatment seven out of 12 patients became pain free within 2.5 months; after one year of treatment 11 out of 12 reported headache improvement or resolution. Average tumor volume reduction after treatment was 47 ± 22% during 9.5 ± 8.4 months of follow-up. There was no significant association between headache relief and tumor shrinkage (p = 0.43) or normalization of serum prolactin (p = 1.00), respectively.. 1) The significant association between lateralization of tumor and headache suggests a mechanical origin of the headache, 2) headache responded to dopamine agonist treatment in most patients, and 3) our observations encourage future prospective controlled trials to investigate the role of hyperprolactinemia in the pathogenesis of headache as well as the therapeutic effects of dopamine agonists.

Topics: Adult; Aminoquinolines; Cabergoline; Case-Control Studies; Dopamine Agonists; Ergolines; Female; Headache; Humans; Hyperprolactinemia; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma; Recurrence; Substance Withdrawal Syndrome

In women, prolactinomas (mainly microprolactinomas) are commonly diagnosed between 20-40-year old. In postmenopausal women, prolactinomas are rarely encountered and usually do not present with hyperprolactinemia-related symptoms as these are dependent on intact ovarian function. Therefore, the true incidence of prolactin (PRL)-secreting adenomas in postmenopausal woman is unknown. Our study objective was to characterize these rare and unique pituitary tumors. A retrospective study including a consecutive group of postmenopausal women followed and treated at 3 Endocrine academic clinics. Baseline clinical characteristics (PRL and gonadotropins levels, other pituitary hormones, adenoma size and invasiveness, visual fields) and response to treatment are reported. The cohort included 14 postmenopausal women with prolactinomas (mean age at diagnosis, 63.6 ± 7.1 years; range, 54-75 years). Mean adenoma size at presentation was 25.6 ± 12.4 mm (range, 8-50 mm). Six out of the 14 women had significant visual fields damage. Mean baseline PRL level was 1,783 ng/ml, and median PRL was 827 ng/ml (range, 85-6,732 ng/ml). Medical treatment with cabergoline was given to twelve of the patients. Cabergoline normalized/near-normalized PRL in eleven women; one woman was dopamine agonist-resistant. Five of the six subjects with visual disturbances normalized or improved their vision, and a pre-treatment diplopia in another patient disappeared. Two large pituitary tumors disappeared on MRI following long-term dopamine agonist therapy. All other treated prolactinomas, except the resistant adenoma, shrank following medical treatment. Prolactinomas are rarely diagnosed in postmenopausal women. These women usually harbor large and invasive macroadenomas, secreting high PRL levels, and usually respond to dopamine agonist treatment.

Topics: Aged; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Female; Follicle Stimulating Hormone; Humans; Hyperprolactinemia; Luteinizing Hormone; Middle Aged; Pituitary Neoplasms; Postmenopause; Prolactin; Prolactinoma; Retrospective Studies; Treatment Outcome

Pseudoacromegaly is a extremely rare condition previously described and characterized by acromegaloid changes, tissue overgrowth, without elevations in insulin-like growth factor or growth hormone as seen in Acromegaly. We present the case of a young female seen initially with acromegaloid features and a pituitary microadenoma. After work-up the patient was diagnosed as insulin-mediated pseudoacromegaly. Only a few cases of pseudoacromegaly has been reported and should always be considered when evaluating patients for acromegaloid features with negative biochemical and hormonal levels.

Topics: Acanthosis Nigricans; Acromegaly; Adult; Bromocriptine; Cabergoline; Diagnosis, Differential; Ergolines; Female; Gastrointestinal Diseases; Hirsutism; Human Growth Hormone; Humans; Hyperprolactinemia; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Pituitary Neoplasms; Pregnancy; Pregnancy Complications; Pregnancy Complications, Neoplastic; Prognathism; Prolactinoma

Dopamine agonists are considered as the first line therapy in prolactin (PRL) secreting pituitary adenomas inducing a normalization of serum PRL and reduction of tumor size. It is known that serum PRL levels, obtained during treatment, are a predictor of tumor shrinkage. Whether PRL suppression below the lower limit of the normal range is related to a greater chance of tumor shrinkage than just its normalization has not been established. This retrospective cohort study was carried out in a tertiary center. Clinical records of 151 patients with PRL-secreting pituitary adenomas (73 micro-, 78 macroadenomas) treated with cabergoline for at least 24 months were analyzed. The adenoma size was analyzed by MRI before and after 24 months of treatment. PRL levels were evaluated every 6 months, assigning a score at each time point (PRL 0 = suppressed; 1 = normal; 2 = above normal). The total score, after 24 months of treatment, was expressed as the sum of the score at each time point and ranged between 0 and 8. A tumor shrinkage was observed in 102/151 patients (67.5%) and it was significantly associated to a lower PRL total score (p = 0.021, OR = 0.85, CI = 0.73-0.97), being significantly more frequent in patients with suppressed PRL than in those with normal PRL (p = 0.045, OR = 0.42, CI = 0.18-0.98) at 24 months. Cabergoline therapy with the goal of achieving PRL levels below the lower limit of normal range can increase the chance to obtain tumor shrinkage of PRL-secreting pituitary adenomas.

Topics: Adult; Cabergoline; Ergolines; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Pituitary Neoplasms; Prolactin; Prolactinoma; Treatment Outcome

Pituitary apoplexy occurs when a preexisting pituitary adenoma undergoes acute haemorrhage, infarct or both. The patho-genesis is not fully understood but macroadenomas and prolactinomas have been reported as being predisposed to apoplexy. Only a few cases are described in the paediatric population. We present a 17-year-old woman with secondary amenorrhoea, headache and blurred vision. An MRI showed a pituitary apoplexy in a preexisting macroadenoma. The majority of milder cases resolve spontaneously. Close monitoring of the pituitary function is important to detect pituitary insufficiency witch may need long-term hormone replacement therapy.

Topics: Adenoma; Adolescent; Antineoplastic Agents; Cabergoline; Ergolines; Female; Humans; Magnetic Resonance Imaging; Pituitary Apoplexy; Pituitary Neoplasms

We investigated surgical cure rate and surgical complications of patients with macroprolactinomas who desired pregnancy to evaluate the efficacy of transsphenoidal surgery.. Surgical cure rate was investigated in 138 female patients who were under 40 years old.. We found a significant correlation between serum prolactin levels and adenoma volume (r=0.004; p<0.0001), adenoma volume and age (r=-0.213; p<0.03), and proliferative index of the adenoma and age (r=-0.15; p<0.007). Seventy-seven out of 81 patients with enclosed macroadenoma were considered cured, and therefore the overall surgical cure rate was 95%. However, during long-term follow-up, recurrence of adenomas with hyperprolactinemia was seen in 5 out of 81 patients (6%), and the long-term cure rate in patients with enclosed macroadenomas was 89%. Adenomas that did not invade the cavernous sinus showed a significantly higher surgical curability and lower serum prolactin levels, and a smaller size than those adenomas that invaded the cavernous sinus.. The long-term surgical cure rate was found to be 89% and this success rate far surpasses the complication rate of 39% during pregnancy by dopamine agonist therapy. Thus, transsphenoidal surgery should be considered as a first-line treatment for female patients who desire pregnancy.

Topics: Adult; Cabergoline; Cavernous Sinus; Dopamine Agonists; Endoscopy; Ergolines; Female; Humans; Magnetic Resonance Imaging; Microsurgery; Neoplasm Recurrence, Local; Neurosurgical Procedures; Pituitary Neoplasms; Postoperative Complications; Pregnancy; Prolactin; Prolactinoma; Retrospective Studies; Sphenoid Bone; Treatment Outcome

Currently available studies that fully analyse the metabolic parameters in patients with prolactinoma are scarce and discordant. The aim of this study was to evaluate the metabolic effects of cabergoline (CAB) treatment in patients with newly diagnosed prolactinoma in relation to disease control and CAB dosage.. This is a retrospective clinical-based therapy analysis.. Forty-three patients with prolactinoma (eight men, 35 women), aged 33·65 ± 11·23 years, were evaluated metabolically at baseline and after 12 months of CAB treatment.. Body mass index (BMI), systolic and diastolic blood pressure, waist circumference (WC), lipid profile, haemoglobinA1c (HbA1c), glucose and insulin levels (and their areas under the curve, AUC) after an oral glucose tolerance test, homoeostasis model assessment of insulin resistance (Homa-IR) index, insulin sensitivity index (ISI) Matsuda, oral disposition index (DIo) and visceral adiposity index (VAI) were measured at baseline and after 12 months of treatment.. Twelve months of CAB reduced WC (P < 0·001), total (P = 0·001) and low-density lipoprotein \\terol (P < 0·001), triglycerides (P = 0·024), fasting insulin (P < 0·001), AUCINSULIN (P < 0·001), HbA1c (P = 0·022), Homa-IR (P < 0·001) and VAI (P < 0·001), with a concomitant increase in high-density lipoprotein cholesterol (P < 0·001) and in ISI Matsuda (P < 0·001), regardless of the degree of reduction in prolactin levels. The patients receiving higher doses (>0·50 mg/week) of CAB showed lower BMI (P = 0·009), fasting insulin (P = 0·001), Homa-IR (P < 0·001) and VAI (P = 0·018) and higher ISI Matsuda (P = 0·002) and DIo (P = 0·011), compared with those on lower doses.. A significant metabolic improvement was observed in patients with prolactinoma after 12 months of CAB treatment, especially when higher doses were used, highlighting the importance of considering the metabolic profile in these patients and the role of active treatment with high CAB doses.

Topics: Adiposity; Adult; Blood Glucose; Body Mass Index; Cabergoline; Dopamine Agonists; Dose-Response Relationship, Drug; Ergolines; Female; Humans; Insulin Resistance; Lipids; Male; Metabolome; Pituitary Neoplasms; Prolactin; Prolactinoma; Retrospective Studies; Waist Circumference; Young Adult

Topics: Adult; Cabergoline; Diagnosis, Differential; Dopamine Antagonists; Epistaxis; Ergolines; Headache Disorders; Hearing Loss, High-Frequency; Hearing Loss, Sensorineural; Hearing Loss, Unilateral; Humans; Magnetic Resonance Imaging; Male; Nasal Obstruction; Pituitary Neoplasms; Prolactinoma; Sinusitis; Tinnitus; Tomography, X-Ray Computed

Giant prolactinomas are extremely rare in the pediatric population. We describe the case of a giant prolactinoma in a girl aged 14 years and 9 months old presented with delayed puberty. Medical treatment with dopamine agonist cabergoline resulted in a rapid normalization of prolactine levels and an impressive shrinkage and liquefaction of the mass as illustrated in serial MRIs. The therapeutic dilemma regarding the type of treatment (medical versus surgical) has now been replaced by the dilemma regarding the optimal treatment strategy and duration. Initial, rather optimistic, estimations regarding the probability of treatment discontinuation without increased relapsing risk have now been replaced by guidelines with more strict criteria for selecting candidates for treatment discontinuation.

Topics: Adolescent; Antineoplastic Agents; Cabergoline; Ergolines; Female; Humans; Induction Chemotherapy; Menarche; Pituitary Neoplasms; Prolactinoma; Tumor Burden

Topics: Antineoplastic Agents, Hormonal; Biomarkers; Carotid Intima-Media Thickness; Ergolines; Female; Humans; Inflammation; Insulin Resistance; Pituitary Neoplasms; Prolactinoma

Carbohydrate metabolism (CHM) is impaired in over 50% of acromegalic patients. Natural history of acromegaly and treatment modalities may impact in a different way on CHM. We assessed CHM alterations in acromegaly and their relationship with clinical features and treatment options.. Retrospective study with 55 patients with acromegaly. Age, sex, body mass index (BMI), tumor size, insulin growth factor type 1 (IGF-1) levels and the presence of impaired fasting glucose (IFG) or diabetes mellitus (DM) were analyzed before and after surgery or medical treatment.. There were 30 men and 25 women. Mean age was 50 ± 17 years and mean BMI was 27.9 ± 3.8 Kg/m(2). Impaired CHM was found in 50.9% (n = 28) (DM in 27% and IFG in 24%). In diabetic patients, we found no differences in age, sex, BMI and IGF-1 levels between IFG/DM and patients without CHM impairment. However, IFG/DM patients had macroadenomas more commonly. In diabetic patients, glycosylated hemoglobin (HbA1c) decreased after surgery from 7.6 to 6.7% and after somatostatin analogues from 7.1 to 6.6%; in patients on pegvisomant we observed a significant reduction of HbA1c: from 9.8 to 5.6% (P < .005). Furthermore, only in the pegvisomant group, insulin and/or oral agents had to be lowered.. Up to 50% of patients with active acromegaly have CHM impairment which correlates with tumor size. Only pegvisomant is associated with significant improvement in glycemic control and a reduction in hypoglycemic treatment.

Topics: Acromegaly; Adult; Aged; Blood Glucose; Body Mass Index; Cabergoline; Combined Modality Therapy; Cranial Irradiation; Cross-Sectional Studies; Ergolines; Female; Glucose; Glycated Hemoglobin; Growth Hormone-Secreting Pituitary Adenoma; Human Growth Hormone; Humans; Hyperglycemia; Hypophysectomy; Insulin-Like Growth Factor I; Male; Middle Aged; Pituitary Neoplasms; Retrospective Studies; Somatostatin; Tumor Burden

The prevalence of pituitary adenoma is of 1/1000 and has been fora long time underestimated. Prolactinomas represent the most frequent subtype (60%). From the mid eighties, their treatment is usually simple and efficient, allowing clinical, biological and tumoral control in most cases. However, management of carcinoma or resistant prolactinoma can be challenging. In these particular cases, a multimodal therapy approach is needed. Recently, progress in genetics of pituitary adenoma has allowed a better understanding and management of these particular cases. In consequence, genetic evaluation is recommended in FIPA (Familial Isolated Pituitary Adenoma) cases and in young patients with macroprolactinomas.

Topics: Antineoplastic Agents; Cabergoline; Diagnosis, Differential; Ergolines; Humans; Pituitary Neoplasms; Prolactinoma; Radiotherapy, Adjuvant

Hyperthyroidism is an important inducing factor in patients with atrial fibrillation, and may trigger heart failure. Thyrotropin (thyroid stimulating hormone, TSH)-secreting pituitary tumors are rare causes of hyperthyroidism. Here, we report a 66-year-old man with a pituitary TSH-secreting tumor who presented with hyperthyroidism and congestive heart failure. Endonasal trans-sphenoidal pituitary adenomectomy was performed. After the operation, the symptoms of hyperthyroidism and congestive heart failure were relieved, associated with normalization of thyroid function tests. Unfortunately, hand tremor and progressively elevated free T4 and TSH concentrations recurred 5 months after surgery. A dopaminergic agonist, cabergoline was administered and euthyroidism was restored for at least 11 months.

Topics: Aged; Cabergoline; Dopamine Agonists; Ergolines; Follow-Up Studies; Heart Failure; Humans; Male; Pituitary Neoplasms; Thyrotropin

Hyperprolactinemia has been implicated in the pathogenesis of obesity and glucose intolerance and is reportedly associated with an impaired metabolic profile. The current study aimed at investigating the effects of 12- and 60-month treatment with cabergoline (CAB) on metabolic syndrome (MetS) in patients with prolactinomas.. 61 patients with prolactinomas (13 men, 48 women, 41 with microadenoma, 20 with macroadenoma), aged 34.4 ± 10.3 years, entered the study. In all patients, prolactin (PRL) and metabolic parameters were assessed at diagnosis and after 12 and 60 months of continuous CAB treatment. MetS was diagnosed according to NCEP-ATP III criteria.. Compared to baseline, CAB induced a significant decrease in PRL with complete normalization in 93% of patients after the 60-month treatment. At baseline, MetS prevalence was significantly higher in patients with PRL above (34.5%) than in those with PRL lower (12.5%) than the median (129 μg/l, p = 0.03). MetS prevalence significantly decreased after 12 (11.5%, p = 0.039) and 60 (5.0%, p = 0.001) months compared to baseline (28.0%). At both evaluations the lipid profile significantly improved compared to baseline. Fasting insulin and homeostatic model assessment of insulin resistance significantly decreased after 1 year of CAB (p = 0.012 and p = 0.002, respectively) and further improved after 60 months (p = 0.000). The visceral adiposity index significantly decreased after the 60-month treatment (p = 0.000) compared to baseline. At the 5-year evaluation CAB dose was the best predictor of percent decrease in fasting insulin (t = 2.35, p = 0.022).. CAB significantly reduces MetS prevalence and improves the adipose tissue dysfunction index. The improvement in PRL, insulin sensitivity and other metabolic parameters might reflect the direct effect of CAB.

Topics: Adiposity; Adult; Antineoplastic Agents; Cabergoline; Dose-Response Relationship, Drug; Ergolines; Fasting; Female; Humans; Hyperprolactinemia; Insulin; Insulin Resistance; Male; Metabolic Diseases; Metabolic Syndrome; Pituitary Neoplasms; Prevalence; Prognosis; Prolactin; Prolactinoma; Prospective Studies; Time Factors; Treatment Outcome

Bromocriptine and cabergoline, ergot derived dopamine receptor agonists used to treat Parkinson's disease and prolactinomas, have been associated with increased risk of cardiac valve disease. Here we present a case of iatrogenic symptomatic severe mitral regurgitation due to these drugs.

Topics: Antineoplastic Agents; Bromocriptine; Cabergoline; Drug Therapy, Combination; Ergolines; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hormone Antagonists; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Pituitary Neoplasms; Prolactinoma; Treatment Outcome

Topics: Adult; Antineoplastic Agents; Cabergoline; Diagnosis, Differential; Ergolines; Humans; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Prolactinoma; Skull Base Neoplasms

Dopamine (DA) therapy of non-functioning pituitary adenomas (NFA) can result in tumor stabilization and shrinkage. However, the mechanism of action is still unknown. Previous evidence showed that DA can inhibit pituitary vascular endothelial growth factor expression (VEGF), that may be involved in pituitary tumor growth. The aim of our study was to clarify whether VEGF secretion modulation might mediate the effects of DA agonists on cell proliferation in human NFA. We assessed DA receptor subtype 2 (DR2) expression in 20 NFA primary cultures, where we also investigated the effects of a selective DR2 agonist, cabergoline (Cab), on VEGF secretion and on cell viability. All NFA samples expressed α-subunit and DR2 was expressed in 11 samples. In DR2 expressing tumors, Cab significantly reduced cell viability (-25%; P < 0.05) and VEGF secretion (-20%; P < 0.05). These effects were counteracted by treatment with the DA antagonist sulpiride. Cab antiproliferative effects were blocked by VEGF. Our data demonstrate that Cab, via DR2, inhibits cell viability also by reducing VEGF secretion in a selected group of NFA, supporting that DA agonists can be useful in the medical therapy of DR2 expressing NFA.

Topics: Aged; Cabergoline; Cell Survival; Ergolines; Female; Humans; Male; Microscopy, Fluorescence; Middle Aged; Pituitary Neoplasms; Receptors, Dopamine; Tumor Cells, Cultured; Vascular Endothelial Growth Factor A

This study was carried out to evaluate the effectiveness of cabergoline in the treatment of nonfunctioning pituitary adenomas (NFPA), in a short-term follow-up period. Nineteen patients (10 men and 9 women) followed at the University Hospital of Brasilia and harboring nonfunctioning pituitary macroadenomas were enrolled in the study. Eleven patients were previously submitted to transsphenoidal surgery, and in 8 patients no previous treatment had been instituted. Their response to the use of cabergoline (2 mg/week) by 6 months was evaluated. Significant tumor shrinkage (above 25 % from baseline tumor volume) was observed in 6 (31.6 %) of the 19 patients, and no adverse effects were observed during treatment. In 9 patients (47.4 %), a reduction in tumor volume of at least 10 % was noted, whereas tumor growth was observed in four patients (increase above 25 % was only observed in one patient). Cabergoline (2 mg/week) can lead to significant tumor shrinkage in NFPA in a considerable number of patients, and this effect can be observed early (6 months after starting medication). Thus, this therapeutic strategy may be a low cost and safe alternative for treatment of NFPA in patients with remnant or recurrent tumor after transsphenoidal surgery or in those not operated by contraindications or refusal to surgical procedure.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cabergoline; Ergolines; Female; Humans; Male; Middle Aged; Pituitary Neoplasms; Treatment Outcome; Young Adult

The incidence of medical failure for prolactin (PRL)-secreting pituitary tumours is not well known. Object. The purpose of this study is to report clinical, radiographic and laboratory findings of PRL-secreting tumours that predict failed medical management.. An analysis of 92 consecutive patients was performed that met the inclusion criteria. Decision for surgery was made based on failure of dopamine agonists to either control clinical symptoms and normalise hormonal level or diminish mass effect on follow-up evaluation.. Of the 92 patients treated, 14 patients (15%) required trans-nasal, trans-sphenoidal pituitary surgery (TSS). One patient underwent surgery for repair of a skull defect and 13 patients (14%) required surgery after failed medical management. Higher initial PRL was statistically significant regarding the need for surgical intervention, but a persistently abnormal level after initiation of treatment was a more significant predictor (Fisher exact test, p = 0.005 vs. p < 0.001). Size was also a statistically significant factor (p = 0.014); macroadenomas had a relative risk of 9.27 (95% CI: 1.15-74.86) for needing surgery compared to microadenomas. In addition, macroadenomas with cavernous sinus (CS) extension and pre-operative visual field deficit demonstrated a strong tendency for surgical intervention.. Medical management remains the most effective treatment option for prolactinomas. A partial hormonal response to medical management seems to be the most significant predictive factor but adenomas > 20 mm, visual field deficit and invasion of the CS may help predict the need for surgery. We suggest a minimum trial period (at least 8 weeks) of medical treatment prior to the consideration of surgery.

Topics: Adult; Antineoplastic Agents; Bromocriptine; Cabergoline; Ergolines; Female; Hormone Antagonists; Humans; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Postmenopause; Premenopause; Prolactinoma; Prospective Studies; Retrospective Studies; Sphenoid Bone; Time Factors; Treatment Failure

The current survey study investigated the recurrence rate of hyperprolactinemia after cabergoline (CAB)-induced pregnancy and after lactation as well as safety of CAB exposure during early gestation.. From 1997-2008, 143 pregnancies were recorded in 91 patients with hyperprolactinemia (age 30.4 ± 4.7 yr, 76 microadenomas, 10 macroadenomas, and five nontumoral hyperprolactinemia). CAB therapy was discontinued within wk 6 of gestation in all. Pregnancies were monitored until delivery or termination, during and after lactation, twice yearly up to 60 months. The incidence of abortions, premature delivery, and fetal malformations was also analyzed.. Pregnancies resulted in 13 (9.1%) spontaneous abortions and 126 (88.1%) live births. No neonatal malformations and/or abnormalities were recorded. In 29 of 91 patients (three with macroadenomas), treatment with CAB had to be restarted within 6 months after lactation because of hyperprolactinemia recurrence, whereas in 68% of cases, no additional therapy was required up to 60 months. No tumor mass enlargement was observed. All patients but three were breastfeeding, 35 (38.5%) for less than 2 months and 56 (61.5%) for 2-6 months. Three months after cessation of lactation and 60 months after pregnancy, no difference in prolactin levels was found between patients nursing for less than 2 months and 2-6 months.. Fetal exposure to CAB at conception does not induce any increased risk of miscarriage or malformations. Pregnancy is associated with normalization of prolactin levels in 68% of patients. Breastfeeding does not increase the recurrence rate of hyperprolactinemia.

Topics: Adult; Antineoplastic Agents; Breast Feeding; Cabergoline; Data Collection; Dopamine Agonists; Ergolines; Female; Humans; Hyperprolactinemia; Infertility, Female; Lactation; Observation; Pituitary Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Prolactinoma; Puerperal Disorders; Recurrence; Time Factors

Prolactin has been proposed as a potent coactivator of platelet aggregation, possibly contributing to thromboembolic events. The objective of the study was to evaluate the relationship between prolactinoma and deep vein thrombosis (DVT), pulmonary embolism (PE), and cerebrovascular accident (CVA). Subjects were identified from a prospectively maintained pituitary database at the Cleveland Clinic. We retrospectively reviewed the charts of 544 subjects: 347 patients with prolactinomas (prolactinoma group) and 197 patients with nonfunctional pituitary adenomas (control group). Main outcome measures were DVT, PE and CVA. We found that 19 (5.5%) patients in the prolactinoma group and five (2.5%) patients in the control group had documented DVT, PE, or CVA, but this difference was not significant (p = 0.109). However, the mean initial prolactin level was higher at the time of diagnosis among prolactinoma patients than among controls (815.23 ng/ml vs. 15.90 ng/ml; p < 0.001). Among prolactinoma patients, 15 (5.5%) of 275 patients who underwent medical treatment (with cabergoline, bromocriptine, pergolide and/or other drug) and 4 (5.6%) of 72 patients who underwent transsphenoidal surgery had documented DVT, PE, or CVA, which suggests that dopaminergic therapy did not influence the risk of thromboembolic events. Hyperprolactinemia per se does not appear to predispose to a hypercoagulable state.

Topics: Adult; Antineoplastic Agents; Bromocriptine; Cabergoline; Ergolines; Female; Humans; Male; Middle Aged; Pergolide; Pituitary Neoplasms; Prolactin; Prolactinoma; Retrospective Studies; Thromboembolism; Young Adult

Topics: Adenoma; Adult; Cabergoline; Dopamine Agonists; Erectile Dysfunction; Ergolines; Humans; Hyperprolactinemia; Male; Pituitary Neoplasms; Treatment Outcome

Pituitary tumours that present with nasal symptoms are uncommon. Management can be difficult due to their aggressive nature, location and extension.. We report a series of three cases of prolactinomas that enlarged inferiorly presenting initially as nasal polyps.. Recurrence of symptoms (case 1) prompted testing for serum prolactin and examination of histology confirmed the presence of a prolactinoma. In cases 2 and 3, radiological evidence of a pituitary mass prompted testing for a prolactinoma. No patients exhibited clinical signs of hyperprolactinaemia. All three cases have residual tumour at 2-4 years after diagnosis, despite prolactin levels approaching the normal range on dopaminergic therapy.. Pituitary tumours that invade the nasal cavity are rare and clinicians should be aware of their existence. A prolactinoma should be considered in the differential diagnosis of nasopharyngeal tumours. Measurement of serum prolactin can expedite a diagnosis and prevent delay of treatment with dopamine agonists.

Topics: Adult; Antineoplastic Agents; Cabergoline; Diagnosis, Differential; Diagnostic Errors; Ergolines; Humans; Male; Middle Aged; Nasal Polyps; Neoplasm Recurrence, Local; Pituitary Neoplasms; Prolactin

First-line therapy for thyrotropin-secreting pituitary adenomas (TSHomas) is neurosurgery, while medical treatment rests mainly on somatostatin analogues. Clinically available sst(2) -preferring analogues, octreotide and lanreotide, induce normalization of hormone levels in approximately 90% of patients and tumour shrinkage in 45%.. We evaluated somatostatin 1, 2, 3 and 5 and dopamine D2 receptor expression in tumour samples from three TSHomas, and the relationships between receptor expression, in vitro antiproliferative response and clinical data, including octreotide test and three months of therapy with octreotide long-acting repeatable (LAR). TSHoma cell proliferation was tested in vitro using octreotide, cabergoline and two chimeric compounds, BIM-23A760 and BIM-23A387.. All patients showed significant TSH lowering to acute octreotide test, but a hormonal response to long-term treatment was observed in only two patients, showing a high sst(5) /sst(2) ratio. Patient 2, characterized by high expression of sst(2) and sst(1) and a relative lower expression of sst(5) , experienced tachyphylaxis after prolonged octreotide treatment. In vitro, the somatostatin/dopamine receptor agonist BIM-23A760 caused the highest antiproliferative effect among those tested. Combined treatment with octreotide and cabergoline displayed an additive effect of magnitude comparable to that of the other chimeric compound (BIM-23A387). Octreotide resistance was confirmed in cells isolated from the nonresponder patient, although it could be overcome by treatment with the chimeric compounds..   A high sst(5) /sst(2) ratio might be predictive of a positive outcome to long-term treatment with somatostatin analogues in TSHomas. Moreover, combined somatostatin and D(2) receptor targeting might be considered as a potential tool to improve the response rate in octreotide-resistant tumours.

Topics: Adenoma; Adult; Cabergoline; Cell Proliferation; Dopamine; Dopamine Agonists; Drug Synergism; Ergolines; Gene Expression; Humans; Immunohistochemistry; Male; Octreotide; Pituitary Neoplasms; Protein Isoforms; Receptors, Dopamine D2; Receptors, Somatostatin; Reverse Transcriptase Polymerase Chain Reaction; Somatostatin; Thyrotropin; Thyroxine; Treatment Outcome; Triiodothyronine; Tumor Cells, Cultured

Von Hippel-Lindau disease is an autosomal dominant disorder involving the development of specific tumours in multiple organs, both benign and malignant. In the CNS, the syndrome is characterized by haemangioblastomas of the retina, spinal cord and brain. We report the case of a 15-year-old boy with the diagnosis of aggressive GH-PRL pituitary macroadenoma and a family history of VHL disease. Pituitary resection was performed, although complete excision of the lesion could not be confirmed by the neurosurgeon. A control MRI was done 6 months after surgery and the pituitary lesion was similar to the presurgical image. A second operation allowed partial resection of the tumour followed by targeted radiotherapy. Pituitary adenomas are rare benign tumours in children with macroadenomas observed mainly in boys. These tumours in adolescents often occur in a familial setting or in the context of known genetic defects. Angiogenesis is an important feature of pituitary adenomas and a possible inhibitory role of pVHL in pituitary angiogenesis has been suggested. This GH-PRL pituitary macroadenoma with a VHL mutation might be of particular aggressiveness. Pituitary adenomas are not classically described in VHL syndrome and the medical community should be alerted to its rare occurrence in this location.

Topics: Adenoma; Adolescent; Antineoplastic Agents; Cabergoline; Ergolines; Human Growth Hormone; Humans; Magnetic Resonance Imaging; Male; Mutation; Pituitary Neoplasms; Prolactin; Somatostatin; Treatment Outcome; von Hippel-Lindau Disease; Von Hippel-Lindau Tumor Suppressor Protein

Hyperprolactinemia causes hypogonadotrophic hypogonadism. Hyperprolactinemia can be pre-existing in some patients with schizophrenia. Dopamine is the most important prolactin-inhibiting factor, and dopaminergic hyperactivity has been implicated in the pathophysiology of psychosis.. Since dopamine is a prolactin-inhibiting factor and dopamine imbalanced has been implicated in the pathophysiology of psychotic disorders, we investigated the probable relationship between hyperprolactinemia and the development of psychotic symptoms, in a patient with hypogonadism due to hyperprolactnemia and subsequent first episode of psychosis. Since dopamine is a prolactin-inhibiting factor and dopamine imbalance has been implicated in the pathophysiology of psychotic disorders, we investigated the probable relationship between hyperprolactinemia and the development of psychotic symptoms.. We present the case of a patient with hypogonadism secondary to chronic, untreated hyperprolactinemia who developed acute psychotic symptoms.. Psychotic symptoms resolved soon after treatment with aripiprazole in conjunction with cabergoline, with a concomitant decrease in serum prolactin level.. This is an interesting case illustrating a complicated relationship among hypogonadism secondary to a prolactinoma and dopamine and psychosis.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Cabergoline; Ergolines; Humans; Hyperprolactinemia; Hypogonadism; Male; Obesity, Morbid; Piperazines; Pituitary Neoplasms; Prolactin; Prolactinoma; Psychotic Disorders; Quinolones; Schizophrenia

As prolactinomas fail to respond to dopamine agonist (DA) in 10-20% of cases, we hypothesized that somatostatin subtype 2 receptor (sst2) overexpression in DA-resistant prolactinomas may enhance suppression of prolactine (PRL) using chimeric agonist (dopastatin) that simultaneously binds sst2 and the dopamine subtype 2 receptor (D2DR).. PRL suppression by octreotide, sst5 agonist, sst2-D2DR agonist (BIM-23A760 dopastatin) and cabergoline was assessed in primary cultures of seven DA-resistant prolactinomas overexpressing sst2.. sst2 was effectively overexpressed via adenoviral expression in prolactinomas (38.1±7.4 vs. 0.1±0.1 copy/copy β-Gus) and induced octreotide sst2-mediated PRL suppression that remained lower than that induced by DA. BIM-23A760 inhibited PRL similarly to cabergoline both in the control and sst2-expressing cells. Antagonist experiments confirmed predominant dopaminergic effect in dopastatin activity.. sst2 was successfully overexpressed in prolactinomas. However BIM-23A760 was unable to enhance PRL suppression underlining a predominant dopaminergic contribution in its action.

Topics: Adenoviridae; Adolescent; Adult; Cabergoline; Dopamine; Dopamine Agonists; Ergolines; Female; Genetic Vectors; Humans; Male; Octreotide; Pituitary Neoplasms; Primary Cell Culture; Prolactin; Prolactinoma; Receptors, Dopamine D2; Receptors, Somatostatin; Somatostatin; Transfection

Although spontaneous coronary artery dissection is a rare cause of acute coronary syndrome, it should be considered during the evaluation of patients who have chest pain. Coronary vasospasm can lead to spontaneous dissection. The dopamine agonist cabergoline is known to cause digital vasospasm. Herein, we report a case of spontaneous right coronary artery dissection in a 43-year-old woman who was taking cabergoline as therapy for prolactinoma. To our knowledge, this is the first report of an apparent relationship between cabergoline therapy and spontaneous coronary artery dissection. The possible association of cabergoline with coronary artery spasm and dissection should be considered in patients who present with chest pain while taking this medication.

Topics: Adult; Angina Pectoris; Antineoplastic Agents, Hormonal; Aortic Dissection; Cabergoline; Cardiovascular Agents; Coronary Aneurysm; Coronary Angiography; Coronary Vasospasm; Ergolines; Female; Humans; Pituitary Neoplasms; Predictive Value of Tests; Prolactinoma; Recurrence; Risk Factors; Time Factors; Treatment Outcome

In contrast to cabergoline, evidence-based information about a possible profibrotic effect of bromocriptine in prolactinoma patients is extremely limited.. To assess the prevalence of valvular lesions among patients on long-term bromocriptine or cabergoline therapy.. Case-control study.. A transthoracic echocardiographic evaluation was performed in 334 subjects divided into four groups: 103 cabergoline treated, 55 bromocriptine treated, 74 naïve patients, and 102 controls.. Clinically relevant valve regurgitations were equally prevalent in all investigated groups whereas subclinical valve fibrosis was significantly more frequent in both bromocriptine- and cabergoline-treated patients (40 vs 43.6 vs 21.6 vs 23.5%; P=0.004). The odds ratio (OR) for developing valvular fibrosis was 2.27 (95% CI 1.17-4.41; P=0.016) for cabergoline and 2.66 (95% CI 1.22-5.78; P=0.014) for bromocriptine groups compared with subjects not exposed to dopamine agonists (DAs). A significantly higher pulmonary arterial pressure corresponding to the longer treatment duration was observed among patients taking bromocriptine compared with cabergoline-treated subjects.. Long-term treatment with cabergoline and bromocriptine seems not to be associated with an increased risk of clinically significant valve disease but possible subclinical lesions should be expected. An echocardiographic examination is recommended at the beginning and periodically during therapy with DAs acting as full or partial agonists of 5-hydroxytrytamine 2B receptors (cabergoline and bromocriptine). Bromocriptine seems not to be a safe alternative for patients receiving cabergoline treatment who have preexisting or diagnosed abnormalities suggesting valvular, interstitial myocardial, or pulmonary fibrosis. Further studies are needed to investigate the possible impact of DA treatment on pulmonary arterial pressure.

Topics: Adult; Antineoplastic Agents; Bromocriptine; Cabergoline; Case-Control Studies; Dopamine Agonists; Echocardiography; Ergolines; Female; Fibrosis; Heart Valve Diseases; Heart Valves; Humans; Male; Middle Aged; Pituitary Neoplasms; Prevalence; Prolactinoma; Prospective Studies

Prolactinoma is the most common pituitary adenoma, and dopamine agonists( BRC, and CAB) is the primary therapy. Recently, the increased prevalance of cardiac valvular disease in patients treated with DAs for Parkinson's disease has raised concerns about the safety of this drug in patients with prolactinoma. CAB and pergolide are frequently reported to cause valvulopathy, there are very few studies showing this side effect in BRC administiration which has less potent agonism of 5-HT2B receptors. Male patients who are known to have higher prevalance of macroadenomas compared to women. The dosage of DAs administered were rarely evaluated.. We performed a retrospective chart to evaluate the medical management and treatment outcomes of male patients with macro/giant prolactinomas. We evaluated 22 patients with prolactinoma managed with DAs therapy alone for at least 1 year. All patients were followed for a mean of 61 months. Pretreatment echocardiographic examination were not available at that time.. None of them had any resistance or intolerance to DAs. The mean tumor shrinkage was 62%. In three patients the macroprolactinoma disappeared, in two patients the tumor shrinkage was 93% and 70%. The DAs therapy was discontinued in these patient. After a follow up neither MRI showed a recurrence or enlargement of the adenoma, nor prolactin levels showed any elevation. The echocardiography were performed at the last visit of each patient and no valvulopathy in any of the patients on DAs therapy were detected.. DAs are effective, and safe for valve morphology with mean cumulative doses of 155 mg CAB, and 7 301 mg BRC in patients with macroprolactinoma.

Topics: Adult; Aged; Bromocriptine; Cabergoline; Dopamine Agonists; Dose-Response Relationship, Drug; Ergolines; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Pituitary Neoplasms; Prevalence; Prolactinoma; Retrospective Studies; Risk Factors; Ultrasonography; Young Adult

Treatment with dopamine agonists in patients with prolactin (PRL) adenomas and Parkinson's disease is associated with central side effects. Central side effects may depend on a substance's ability to pass the blood-brain barrier, which can be actively controlled by transporter molecules such as the P-glycoprotein (P-gp) encoded by the ABCB1 gene.. We aimed to determine whether cabergoline is transported by the P-gp and whether polymorphisms of its encoding ABCB1 gene predict central side effects of cabergoline therapy in patients with PRL adenomas. i) In an experimental mouse model lacking the homologues of the human ABCB1 gene (Abcb1ab double knockout mouse model), we examined whether cabergoline is a substrate of the P-gp using eight mutant and eight wild-type mice. ii) In a human case-control study including 79 patients with PRL adenomas treated with cabergoline at the Max Planck Institute of Psychiatry in Munich, we investigated the association of four selected ABCB1 gene single nucleotide polymorphisms (SNPs) (rs1045642, rs2032582, rs2032583 and rs2235015), with the occurrence of central side effects under cabergoline therapy.. i) In the experimental mouse model, we observed that brain concentrations of cabergoline were tenfold higher in the mutant mice compared with their wild-type littermates, implying that cabergoline is indeed a substrate of the transporter P-gp at the blood-brain barrier level. ii) In the human study, we observed significant negative associations under cabergoline for the C-carriers and heterozygous CT individuals of SNP rs1045642 with two central side effects (frequency of fatigue and sleep disorders) and for the G-carriers of SNP rs2032582 with the enhancement of dizziness. For the SNPs rs2235015 and rs2032583, no associations with central side effects under cabergoline were found.. This is the first study demonstrating that individual ABCB1 gene polymorphisms, reflecting a different expression and function of the P-gp, could predict the occurrence of central side effects under cabergoline. Our findings can be viewed as a step into personalised therapy in PRL adenoma patients.

Topics: Adult; Aged; Animals; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily D, Member 1; ATP-Binding Cassette Transporters; Cabergoline; Case-Control Studies; Ergolines; Fatigue; Female; Headache; Humans; Male; Mice; Mice, Knockout; Middle Aged; Pituitary Neoplasms; Polymorphism, Single Nucleotide; Predictive Value of Tests; Prolactinoma; Treatment Outcome

Algorithms previously focused primarily on the testosterone level and its role when diagnosing and managing hypoactive sexual desire (HSD) in men. The importance of prolactin in male sexuality is recognized and should be taken into account when investigating more complex cases of HSD in men.

Topics: Adult; Antineoplastic Agents; Cabergoline; Ergolines; Humans; Hyperprolactinemia; Libido; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma; Sexual Dysfunction, Physiological

Cushing syndrome is associated with significant morbidity and mortality if left untreated because of associated metabolic and cardiovascular complications. An extremely ill patient with Cushing's syndrome caused by adrenocorticotropic hormone producing pituitary macro adenoma responded dramatically to ketoconazole and cabergoline treatment. His 4 month long medical treatment resulted in improvement of hypercotisolism clinically and biochemically and in complete disappearance of pituitary macro adenoma without any surgical intervention.

Topics: 14-alpha Demethylase Inhibitors; Adenoma; Adult; Antineoplastic Agents; Cabergoline; Cushing Syndrome; Diagnosis, Differential; Drug Therapy, Combination; Ergolines; Humans; Ketoconazole; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Severity of Illness Index; Tomography, X-Ray Computed

Topics: Adult; Antineoplastic Agents; Cabergoline; Ergolines; Female; Humans; Pituitary Neoplasms; Pneumocephalus; Prolactinoma

Dopamine agonist resistance in prolactinoma is an infrequent phenomenon. Doses of cabergoline (CAB) of up to 2.0 mg/week are usually effective in controlling prolactin (PRL) secretion and reducing tumor size in prolactinomas. The clinical presentation, management, and outcome of patients that are not well controlled by such commonly used doses of CAB-resistant patients are poorly understood.. A multicenter retrospective study was designed to collect a large series of resistant prolactinoma patients, defined by uncontrolled hyperprolactinemia on CAB ≥2.0 mg weekly.. Ninety-two patients (50 F, 42 M) were analyzed. At diagnosis, most had macroprolactinomas (82.6%); males were significantly older than females (P=0.0003) and presented with a more aggressive disease. A genetic basis was identified in 12 patients. Thirty-six patients (39.1%) received only medical therapy, most underwent surgery (60.9%, including multiple interventions in 10.9%), and 14.1% received postoperative radiotherapy. Eight patients developed late CAB resistance (8.7%). The median maximal weekly dose of CAB (CAB(max/w)) was 3.5 mg (2.0-10.5). Despite a higher CAB(max/w) in patients treated with multimodal therapy (P=0.003 vs exclusive pharmacological treatment), a debulking effect of surgery was shown in 14 patients, with a higher rate of PRL control (P=0.006) and a significant reduction in CAB(max/w) (P=0.001) postoperatively. At last follow-up (median 88 months), PRL normalization and tumor disappearance were achieved in 28 and 19.9% of the patients respectively, with no significant sex-related difference observed in CAB(max/w) or disease control. Mortality was 4.8%, with four patients developing aggressive tumors (4.3%) and three a pituitary carcinoma (3.3%).. CAB-resistant prolactinomas remain a serious concern. Surgical debulking, newer therapeutic strategies, and early diagnosis of genetic forms could help to improve their outcome.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Cabergoline; Chemotherapy, Adjuvant; Child; Drug Administration Schedule; Drug Resistance, Neoplasm; Ergolines; Female; Humans; Hyperprolactinemia; Intracellular Signaling Peptides and Proteins; Male; Middle Aged; Mutation; Pituitary Neoplasms; Prolactinoma; Proto-Oncogene Proteins; Retrospective Studies; Treatment Failure

We assessed the safety of Cabergoline therapy during pregnancy in a lady with hyperprolactinemia intolerant to Bromocriptine.. We report the case of a 31 year old lady who presented to us with uncontrolled hyperprolactinemia. A pituitary Macroadenoma was demonstrated by MRI. Due to intolerance to Bromocriptine, Cabergoline was started. The patient improved and subsequently conceived. MRI in the second trimester demonstrated further reduction in the tumor size. It was decided to continue Cabergoline throughout pregnancy to ensure further reduction in tumor size until delivery and to hold Cabergoline during postpartum period to allow for an adequate interval of breastfeeding. At 37 weeks of gestation, the patient delivered a healthy baby.. We were able to safely treat macroprolactinemia in our patient during pregnancy with cabergoline. This case report contributes to the relatively meager data available which advocates the safety of cabergoline therapy in pregnant hyperprolactinemic patients.

Topics: Adult; Antineoplastic Agents; Cabergoline; Ergolines; Female; Humans; Hyperprolactinemia; Pituitary Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Prolactin; Prolactinoma

Topics: Adult; Cabergoline; Depressive Disorder; Ergolines; Female; Humans; Pituitary Neoplasms; Prolactinoma; Psychoses, Substance-Induced

We report the case of a 13-year-old prepubertal boy who presented with a left-sided proptosis, bilateral papilloedema and hydrocephalus who was subsequently diagnosed with a giant prolactinoma invading the left orbit. He was commenced on dopamine receptor agonists in the form of quinagolide and cabergoline, and made an excellent response to medical therapy alone, with resolution of hydrocephalus, restoration of normal vision and a 98% reduction in serum prolactin. The rapid improvement achieved negated the requirement for surgery and this highlights the efficacy of the dopamine agonists in the management of giant prolactinomas, even in the presence of neurological symptoms.

Topics: Adolescent; Aminoquinolines; Cabergoline; Dopamine Agonists; Ergolines; Exophthalmos; Humans; Hydrocephalus; Male; Pituitary Neoplasms; Prolactin; Prolactinoma

Hyperprolactinemia is a rare endocrine disorder in childhood, which may result from hypophyseal adenoma. We aimed to review the etiologic reasons and clinical features in hyperprolactinemia patients retrospectively. The mean age of 11 female patients at diagnosis was 14.2 ± 1.3 years. Five patients had microadenoma, four patients had macroadenoma, and two patients were diagnosed with idiopathic hyperprolactinemia. The most frequent symptoms were menstrual disorders, headache, and galactorrhea, and one-third of the patients had obesity at diagnosis. There was no anterior pituitary hormone deficiency. All patients received bromocriptine as initial therapy; only two patients with macroadenoma and one patient with microadenoma were switched to cabergoline. Transsphenoidal surgery was performed for a patient with macroadenoma, who had cavernous sinus invasion and visual field defect. Medical treatment should be the first-line treatment option in both microadenoma and macroadenoma cases without any neurological signs. Surgery should be employed with limited indications.

Topics: Adolescent; Bromocriptine; Cabergoline; Child; Combined Modality Therapy; Ergolines; Female; Hormone Antagonists; Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactinoma; Retrospective Studies; Treatment Outcome

Prolactinomas in males can be voluminous macroadenomas invading the surrounding structures. Medical therapy with dopamine agonists (the treatment of choice for these tumours) may be ineffective in the case of pharmacological resistance. In such cases, even surgical and/or radiation therapy cannot be curative due to the invasive potential of the adenoma. Hence, the appropriate therapeutic approach for these tumours is still a relevant clinical problem for endocrinologists. We report the history of an adolescent male who was diagnosed with a large invasive macroprolactinoma in 2002. He had severe bitemporal hemianopsia and hypopituitarism; prolactin levels at diagnosis were higher than 8,000 ng/ml. Medical therapy with cabergoline was initiated and resulted in decreased prolactin levels but not complete normalisation (maximal tolerated dose 3 mg/day). However, due to the worsening of the visual defect, the patient was operated in July 2004 through the trans-nasal approach and 2 years later through both the transcranial and the transphenoidal approaches. After the second surgery, a significant reduction of tumour mass was obtained. Immunohistochemistry for somatostatin receptors (sstr) subtypes showed a positive staining with the anti-sstr5 antibody. A scintigraphy with 111In-pentetreotide (Octreoscan) revealed a very intense tracer uptake in the sellar region. The administration of long-acting octreotide was initiated. After 12 months of therapy, prolactin levels normalised for the first time. Pituitary MRI did not reveal any tumor progression during a 2-year follow-up. This is a case of an invasive dopamine-resistant macroprolactinoma that was successfully controlled by extensive surgery and combined treatment with cabergoline and octreotide. The expression and functionality of sstr should be investigated in these tumours since a combined therapy with cabergoline and octreotide may be a good therapeutic course of action for select cases.

Topics: Adolescent; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Cabergoline; Dopamine Agonists; Drug Resistance, Neoplasm; Ergolines; Humans; Male; Octreotide; Pituitary Neoplasms; Prolactinoma; Treatment Outcome

Optic chiasmal herniation following dopamine agonist therapy is a rare complication in patients with giant prolactinomas. But there are a few case reports of brain and chiasmal herniation following medical therapy in such cases. We report a young man who developed secondary visual loss and seizures after 6 months of medical treatment with cabergoline for giant prolactinoma. Magnetic resonance imaging of hypothalamic pituitary region revealed optic chiasmal and frontal lobe herniation into sella. There was marginal improvement in his vision after cabergoline dose reduction. The present case report highlights frontal lobe herniation in conjunction with optic chiasmal herniation as a very rare complication of medical therapy of giant prolactinoma. Different treatment options of this condition are being discussed.

Topics: Adult; Cabergoline; Dopamine Agonists; Encephalocele; Ergolines; Humans; Male; Optic Chiasm; Pituitary Neoplasms; Prolactinoma; Sella Turcica; Tumor Burden

It has been reported that prolactinomas treated with Bromocriptine (BROM) show fibrosis that may interfere with complete surgical resection. The same has not been reported for Cabergoline (CAB). We retrospectively studied 24 consecutive patients (13 females, mean age 40 years, range 16-60) with histopathologically confirmed prolactinomas undergoing surgical resection at Johns Hopkins Hospital between 1992 and 2009. We compared these prolactinomas to 34 patients (22 females, mean age 42.9 years, range 15-75) with GH-secreting adenoma. The operative notes from 7 different neurosurgeons were reviewed to catalog the tumors as fibrous or not fibrous. Of the 24 prolactinomas, 21 (87.5%) were previously treated with DA. Indication for surgery was: DA resistance (n.5), DA intolerance (n.6), persistent mass effect (n.7) and CSF leak (n.3). Five (14.7%) of GH-secreting adenomas, were exposed to DA and/or somatostatin analogs. We found that 54% of prolactinomas and only 6% of GH-secreting adenomas were described as fibrous. 10/12 (77%) of prolactinomas exposed to BROM for at least 1 month, 2/9 (22%) exposed to CAB only, and 1/3 (33%) not previously treated were fibrous (P < 0.05). The mean BROM cumulative dose was 406 mg (range 75-1,375), while CAB dose was 28 mg (range 6-70). Only 18% of non-fibrous prolactinomas had been exposed to BROM. Only 3 patients had persistent biochemical remission (2 treated with CAB and 1 not treated). Patients exposed to BROM for at least 1 month are more likely to have tumor fibrosis than patients that are untreated or treated with CAB.

Topics: Adenoma; Adolescent; Adult; Aged; Bromocriptine; Cabergoline; Child; Dopamine Agents; Ergolines; Female; Humans; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma; Retrospective Studies; Young Adult

Topics: Antineoplastic Agents; Bromocriptine; Cabergoline; Ergolines; Humans; Meta-Analysis as Topic; Pituitary Neoplasms; Treatment Outcome

Prolactinomas are common secretory pituitary tumours, usually managed with dopamine agonists. There have previously been case reports of rarer giant prolactinomas causing invasion of surrounding structures. We describe a case report of an exceptionally aggressive giant prolactinoma that eroded the occipital condyles causing cranio-cervical joint instability mandating surgical fixation.

Topics: Adult; Antineoplastic Agents; Arthrodesis; Cabergoline; Cervical Vertebrae; Cranial Fossa, Posterior; Cranial Nerve Diseases; Craniotomy; Ergolines; Humans; Hyperprolactinemia; Joint Instability; Magnetic Resonance Imaging; Male; Neoplasm Invasiveness; Occipital Bone; Orthotic Devices; Pituitary Neoplasms; Prolactinoma; Recovery of Function; Treatment Outcome

Topics: Anemia; Antineoplastic Agents; Biomarkers, Tumor; Cabergoline; Chronic Disease; Dopamine Agonists; Drug Therapy, Combination; Early Detection of Cancer; Ergolines; Hematocrit; Hemoglobins; Hormone Replacement Therapy; Humans; Hydrocortisone; Hypogonadism; Hypopituitarism; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Testosterone; Thyroxine; Treatment Outcome

Treatment of prolactin-secreting pituitary adenomas by dopamine agonists is highly effective and currently is used as basic treatment in most cases, however, literature sources practically do not contain data about possible complications of this therapy. We described a total of 11 cases of deterioration due to primary treatment of macroprolactinomas by cabergoline in the series of 176 patients. The first group included patients with enlargement of the tumor producing deterioration of the symptoms (onset of visual disorders and/or cephalgia). This occurred in 3 (1.7%) cases due to intratumoral hemorrhage or cystic transformation, and in 1 (0.6%) case as a result of growth of cabergoline-resistant tumor. The second group was made up of 6 (3.4%) cases of nasal CSF leak which developed within 3 to 6 weeks after start of treatment. All patients with CSF leak had adenomas with high sensitivity to the drug which produced rapid and significant shrinking of the tumor. The third group was presented by the single case (0.6%) of visual deterioration due to development of empty sella syndrome with dislocation of chiasm and optic nerves into sellar cavity.

Topics: Adolescent; Adult; Cabergoline; Cerebrospinal Fluid Rhinorrhea; Dopamine Agonists; Ergolines; Humans; Intracranial Hemorrhages; Male; Middle Aged; Neurosurgical Procedures; Pituitary Neoplasms; Prolactinoma; Radiography; Treatment Outcome; Vision Disorders; Young Adult

Problems with impulse control and pathological gambling are known as possible side effects of dopaminergic therapy in patients with Parkinson's disease. We report 2 cases of pathological gambling induced by dopamine agonists in patients without Parkinson's disease. The first patient, a 46-year-old man, was treated with ropinirole for restless legs syndrome and had lost huge amounts of money in the context of internet-based poker game. Another 46-year-old male patient developed pathological gambling under treatment with cabergoline administered for prolactinoma. The two cases implicate pathological gambling as a possible consequence of dopaminergic treatment and support the increasing evidence regarding pathological gambling as an adverse drug reaction of dopaminergic treatment, also in patients who do not suffer from Parkinson's disease.

Topics: Antiparkinson Agents; Cabergoline; Dopamine Agonists; Ergolines; Gambling; Humans; Indoles; International Classification of Diseases; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma; Restless Legs Syndrome

A 0.65-kg (1.43-lb) 24-month-old sexually intact male albino pet rat was examined because of a 3-week history of hypodipsia, apparent blindness, and sudden change in behavior.. The rat was able to move around its cage but appeared unaware of its surroundings, was visually unresponsive, and seemed unusually aggressive. The rat's hind limbs appeared mildly paretic, and it had sporadic difficulty placing its hind limbs on a flat surface. Given the rat's age, history, and physical examination findings, the primary differential diagnosis was a pituitary tumor. Magnetic resonance imaging (MRI) of the rat's brain was performed and revealed a large pituitary mass, which was indicative of a tumor.. Cabergoline (0.6 mg/kg [0.27 mg/lb], PO, q 72 h) was administered. On follow-up MRI 2 months later, the pituitary mass had substantially decreased in size. For 6 months following the second MRI study, the rat continued to receive the same dosage of cabergoline and had no clinical signs of disease or unusual behavior. However, at 8.5 months after the start of the treatment, the rat was in poor condition and had clinical signs similar to those initially. A third MRI study was performed and revealed substantial regrowth of the mass. The rat was euthanized and a necropsy was performed; a histopathologic diagnosis of pituitary adenoma was made.. Pituitary adenomas have long been recognized as a common finding in geriatric rats (> 18 months old). Affected rats may respond favorably to oral administration of cabergoline.

Topics: Adenoma; Animals; Antineoplastic Agents; Cabergoline; Ergolines; Male; Pets; Pituitary Neoplasms; Rats; Rodent Diseases

Hyperprolactinaemia affects testicular functions by influencing hypothalamo-pituitary-testicular (HPT) axis at various levels. Available literature on the level of defect, time course of improvement of gonadal functions and its relation with decline in prolactin levels is scanty. We carried out this study to evaluate the HPT axis in patients with macroprolactinomas, before and six months after cabergoline therapy.. Fifteen men with macroprolactinomas underwent gonadotropin and testosterone response to their respective stimuli before and after six months of cabergoline therapy.. Serum prolactin levels decreased after six months of therapy. Pretreatment, mean lutenizing and follicle stimulating hormones (LH and FSH) levels were 2.0 ± 0.4 and 1.4 ± 0.2 IU/l, respectively. However, LH and FSH responses to GnRH were preserved in majority of the patients and LH peaked to 12.1 ± 2.3 IU/l (P<0.01), while FSH to 2.9 ± 0.4 IU/l suggesting the influence of hyperprolactinaemia at the level of hypothalamus with preserved gonadotrope reserve. After cabergoline therapy, there was an increase in basal as well as stimulated LH and FSH levels, though these were not statistically significant when compared to respective pretherapy levels. Basal testosterone (T) levels significantly improved after therapy, but peak T response to hCG was similar at both pre- and post treatment. A significant correlation was observed between peak LH and peak T at baseline (r=0.53, P<0.01) and it further strengthened after therapy (r=0.70, P<0.01). After cabergoline therapy, there was significant improvement in seminal volume, sperm count and motility and sperm count correlated with peak FSH response (r=0.53, P<0.05).. Hyperprolactinaemia affects testicular functions probably by influencing at the level of hypothalamus resulting in subnormal basal secretion of gonadotropins required for optimal testicular functions.

Topics: Analysis of Variance; Cabergoline; Enzyme-Linked Immunosorbent Assay; Ergolines; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hypothalamo-Hypophyseal System; Luteinizing Hormone; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Prolactin; Prolactinoma; Radioimmunoassay; Sperm Count; Sperm Motility; Testis; Testosterone; Time Factors

The aim of our study is to report the most adequate therapy for prolactinoma in the cabergoline era. From 2003 to 2009, 27 patients with prolactinoma were treated at our hospital. Patients are categorized into 2 groups. The Cabergoline Group: Cabergoline was administered for 5 years and discontinued. Using this protocol, the case with normal prolactin level in addition to having no visible tumor more than 24 months after the discontinuation of cabergoline was judged as cured. The Operation Group: Transsphenoidal surgery (TSS) was performed first. In the Cabergoline group, 12 cases were cured with 5 years cabergoline treatment (Cure) and 6 cases were not cured (Not cure). We compared the pretreatment prolactin level, the normalization of the serum level of prolactin, the degree of invasiveness on MRI, regression of the tumor during treatment on MRI, max dose of cabergoline, degree of pituitary hormone replacement, frequency of pregnancy, and follow up periods between the Cabergoline-cure group, the Cabergoline-not-cure group, and the Operation group. Normalization rate in serum level of prolactin and cure rate were 91% and 63% in the Cabergoline group. Pretreatment prolactine level and the frequency of tumor invasiveness on initial MRI were significantly higher in the Cabergoline-not-cure group compared to the Cabergoline-cure group. All of the five woman accompanied with pregnancy after the treatment belonged to the Cabergoline-cure group. In the Operation group, all 4 cases achieved normalization of serum prolactin level without visible tumor and with normal pituitary function. Cabergoline for prolactinoma is effective, but the cure rate by continuous usage of cabergoline for 5 years was 67%. The factors that cabergoline and / or TSS can cure prolactinoma are non-invasive tumor and prolactin level under 200 ng/mL at pretreatment.

Topics: Adolescent; Adult; Aged; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Pregnancy; Prolactin; Prolactinoma; Treatment Outcome

Treatment of patients with prolactinomas consists primarily of dopamine agonists (DA). When these drugs reduce the size of invasive prolactinomas, the intra- and extra-cranial spaces may be communicated. Pneumocephalus and cerebrospinal fluid leakage have been reported. A 56 year old male was admitted to the emergency unit with an intracranial hypertension syndrome. He had been treated for 2 weeks with cabergoline after an invasive prolactinoma was discovered. Brain CT showed frontal interhemispheric pneumocephalus on the previous tumor cavity, and bony defect on the sellar floor. Evacuation of pneumocephalus, reparation of cranial and meningeal defects and subtotal tumor removal were performed. The literature is reviewed looking for possible pathophysiological mechanism, prevention and treatment.

Topics: Antineoplastic Agents; Cabergoline; Ergolines; Humans; Male; Middle Aged; Pituitary Neoplasms; Pneumocephalus; Prolactinoma; Tomography, X-Ray Computed

Ergot-derived dopamine agonists are associated with increased risk of valvular dysfunction in Parkinson's disease. The risk of valvular disease associated with lower doses of cabergoline used to treat prolactinomas remains controversial.. To determine whether there is an association of cabergoline and valvular function in patients with hyperprolactinaemia according to gender.. Case-record retrospective study.. Outpatient neuroendocrine clinical centre at a tertiary care hospital.. One hundred patients (48 men and 52 women) with hyperprolactinaemia who had an echocardiogram while receiving cabergoline for at least 6 months.. One hundred controls (48 men and 52 women) selected from Massachusetts general hospital (MGH) database of echocardiograms without clinically significant findings, matched to patients for age, gender, body mass index (BMI) and hypertension.. Echocardiogram.. There were no significant differences in valvular function in patients compared with controls. However, women patients had a higher prevalence of mild tricuspid regurgitation (TR) than female controls (15.4%vs. 1.9%, P = 0.03). Among men only, patients had more trace TR than controls (68.8%vs. 45.8%, P = 0.02). The mild valvular regurgitation in patients was not clinically significant and did not correlate with dose, duration or cumulative dose.. Overall cabergoline was not associated with valvulopathy. However, subdivided by gender, hyperprolactinaemic men and women had higher prevalence of trace or mild TR, respectively, compared with gender matched controls. There may be gender differences in valvular dysfunction associated with cabergoline. Longer term, larger studies are necessary to evaluate definitively an effect of cabergoline on valvular function in hyperprolactinaemic patients.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Cabergoline; Case-Control Studies; Echocardiography; Ergolines; Female; Heart Valves; Hormone Antagonists; Humans; Hyperprolactinemia; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Retrospective Studies; Sex Characteristics; Young Adult

Pituitary adenomas can cause specific syndromes due to hormone excess and/or determine sellar mass symptoms. Pituitary cell growth can sometimes be influenced by medical therapy, such as for somatotroph adenomas treated with somatostatin analogs or prolactinomas treated with dopaminergic drugs. However, nonfunctioning pituitary adenomas (NFAs) are still orphans of medical therapy. Everolimus (RAD001), a derivative of rapamycin, is a well-known immunosuppressant drug, which has been recently shown to have antineoplastic activity in several human cancers.. The objective of the study was to investigate the possible antiproliferative effects of RAD001 in human NFAs.. We collected 40 NFAs that were dispersed in primary cultures, treated without or with 1 nm to 1 microm RAD001, 10 nm cabergoline, 10 nm SOM230 (a somatostatin receptor multiligand), and/or 50 nm IGF-I. Cell viability and apoptosis were evaluated after 48 h, and vascular endothelial growth factor (VEGF) secretion was assessed after an 8-h incubation. Somatostatin and dopamine subtype 2 receptor expression was investigated by quantitative PCR.. In 28 cultures (70%), Everolimus significantly reduced cell viability (by approximately 40%; P < 0.05 vs. control), promoted apoptosis (+30%; P < 0.05 vs. control), inhibited p70S6K activity (-20%), and blocked IGF-I proliferative and antiapoptotic effects. In selected tissues cotreatment with SOM230, but not cabergoline, exerted an additive effect. Everolimus did not affect VEGF secretion but blocked the stimulatory effects of IGF-I on this parameter.. Everolimus reduced NFA cell viability by inducing apoptosis, with a mechanism likely involving IGF-I signaling but not VEGF secretion, suggesting that it might represent a possible medical treatment of invasive/recurrent NFAs.

Topics: Adenoma; Aged; Apoptosis; Cabergoline; Cell Line, Tumor; Cell Survival; Ergolines; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Pituitary Neoplasms; Receptors, Somatostatin; Ribosomal Protein S6 Kinases, 70-kDa; Sirolimus; Somatostatin; Vascular Endothelial Growth Factor A

Dopamine agonists (DAs) are the first-line therapy for the treatment of hyperprolactinemia, with cabergoline, an ergot-derived selective D(2)-receptor agonist, being the preferred and most widely used drug. Recent studies reported cardiac valve regurgitations in patients with Parkinson's disease treated with high doses of DA, raising concerns about the safety of cabergoline in patients with hyperprolactinemia. To date, seven case-control studies have examined the potential association between cardiac valvular abnormalities and cabergoline therapy in patients with hyperprolactinemia. Overall, a total of 463 patients exposed to low doses of cabergoline (mean cumulative doses: 204-443 mg) for a mean duration of 45-79 months have been included in these studies. Patients in all the studies were asymptomatic without clinical signs of cardiac disease. Six studies did not show any association between cabergoline therapy and clinically relevant valvular regurgitation, whereas one study found an increased rate of moderate tricuspid regurgitation. In this report, we review and discuss the results of these studies and emphasize the limitations of the methodology used in the published literature. The clinical significance of the present findings has yet to be confirmed by future larger prospective studies with rigorous echocardiographic protocols and prolonged duration of follow-up.

Topics: Adult; Cabergoline; Case-Control Studies; Clinical Trials as Topic; Dopamine Agonists; Ergolines; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma; Receptors, Dopamine D2

A systematic review and meta-analysis by Dekkers et al. has assessed the effects of dopamine agonist withdrawal in patients with hyperprolactinemia. But not all dopamine agonists are the same, and much depends on the criteria for patient selection and the drug withdrawal strategy.

Topics: Antineoplastic Agents, Hormonal; Cabergoline; Dopamine Agonists; Ergolines; Humans; Hyperprolactinemia; Meta-Analysis as Topic; Pituitary Gland; Pituitary Neoplasms; Prolactinoma; Recurrence; Withholding Treatment

Cabergoline is effective for hyperprolactinemic hypogonadism. However, the rate of cabergoline-induced pregnancy in women with prolactinoma remains unknown. Also unknown is whether cabergoline can control tumor growth and thereby achieve successful pregnancy in patients with macroprolactinomas.. Eighty-five women with macroprolactinomas (n = 29) or microprolactinomas (n = 56) received prospective, high-dose cabergoline therapy for infertility based on individual prolactin suppression and/or tumor shrinkage. The patients included 31 bromocriptine-resistant, 32 bromocriptine-intolerant, and 22 previously untreated women. Conception was withheld until three regular cycles returned in women with microadenoma and until tumors shrank below 1.0 cm in height in women with macroadenoma. Cabergoline was withdrawn at the fourth gestational week.. Cabergoline normalized hyperprolactinemia and recovered the ovulatory cycle in all patients. All adenomas contracted, and 11 macroadenomas and 29 microadenomas disappeared. Eighty patients (94%) conceived 95 pregnancies, two of which were cabergoline-free second pregnancies. The dose of cabergoline at the first pregnancy was 0.25-9 mg/wk overall and 2-9 mg/wk in the resistant patients. Of the 93 pregnancies achieved on cabergoline, 86 resulted in 83 single live births, one stillbirth, and two abortions; the remaining seven were ongoing. All babies were born healthy, without any malformations. No mothers experienced impaired vision or headache suggestive of abnormal tumor reexpansion throughout pregnancy.. Cabergoline achieved a high pregnancy rate with uneventful outcomes in infertile women with prolactinoma, independent of tumor size and bromocriptine resistance or intolerance. Cabergoline monotherapy could substitute for the conventional combination therapy of pregestational surgery or irradiation plus bromocriptine in macroprolactinomas.

Topics: Adult; Birth Weight; Bromocriptine; Cabergoline; Cohort Studies; Dopamine Agonists; Drug Resistance; Ergolines; Female; Humans; Hyperprolactinemia; Infertility, Female; Magnetic Resonance Imaging; Pituitary Neoplasms; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Progesterone; Prolactin; Prolactinoma

Data concerning the safety for pregnancy of cabergoline treatment in hyperprolactinaemic women are still scarce.. To exclude a higher than normal risk for miscarriage and congenital malformation in pregnancies initiated under cabergoline treatment.. A retrospective study of 100 pregnancies in 72 hyperprolactinaemic women treated with cabergoline at the time of conception and follow-up of the 88 newborn children.. Cabergoline was interrupted in 99 pregnancies and continued in one case. Foetal exposure dose to cabergoline was calculated for each pregnancy. Complications of pregnancy and neonatal status were compared to those observed in an age-and delivery time-matched control group of 163 women.. The mean foetal exposure dose to cabergoline was 3.6 +/- 4.7 mg. The rate of spontaneous miscarriages was 10%. Three medical terminations of pregnancy were performed for a foetal malformation (3%). Minor to moderate complications were observed in 31% of the pregnancies, a figure similar to that found in the control group. An increase in tumour size (2-8 mm) was observed in 17/37 evaluated cases, needing reintroduction of cabergoline during pregnancy in five patients. The 84 deliveries resulted in 88 infants, three of them presenting with a malformation (3.4%). Neonatal status was comparable to the control group, where a malformation rate of 6.3% was observed. Postnatal development of the children was normal.. Cabergoline treatment at the time of conception appears to be safe for both the pregnancy and the neonate, although more data are still needed on a larger number of pregnancies.

Topics: Adult; Antineoplastic Agents; Cabergoline; Case-Control Studies; Dopamine Agonists; Ergolines; Female; Humans; Hyperprolactinemia; Infant, Newborn; Pituitary Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Prenatal Exposure Delayed Effects; Prolactinoma; Retrospective Studies

Topics: Aminoquinolines; Antineoplastic Agents; Cabergoline; Dopamine Agonists; Embryonic Development; Ergolines; Female; Humans; Pituitary Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Prolactinoma

Prolactinomas in men are usually macroprolactinomas and other investigators have attributed bigger size of tumors in men to delay in diagnosis. A retrospective study of 71 macroadenomas (42 men) was carried out. Parameters studied were age, signs and symptoms at presentation, time of onset of symptoms, basal prolactin, estradiol, and total testosterone levels, tumor size and Ki 67 expression in tumor tissue. Male patients were older. Visual defects were significantly more prevalent in men. Hardy 4 stage tumors were found only in men. We found no significant correlation between tumor size and the patients age nor between tumor size and the onset of symptoms. Whereas basal E2 levels (21.2+/-12.9 vs. 33.3+/-43.3 pg/ml, p=n.s.) were very similar in male and female patients, testosterone levels were significantly higher in men (0.6+/-0.5 vs. 1.8+/-1.2 ng/ml, p=0.02). The rate of cell proliferation represented by Ki 67 was significantly higher in tumors in men (3.5+/-1.2 vs. 1.5+/-0.5%, p=0.0001). This is the first study focused in macroprolactinomas that shows that they are clinically and biologically more aggressive in men. Hypogonadism in men could appear later in the progression of prolactinomas and this might explain why men were older at the time of diagnosis. Furthermore, testosterone could be a source for E2 in situ aromatization giving male tumors an advantage in cell proliferation.

Topics: Adult; Age Factors; Cabergoline; Ergolines; Estradiol; Female; Humans; Ki-67 Antigen; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Sex Characteristics

This report describes a case of prolactinoma that presented acutely with a third nerve palsy without evidence of apoplexy. The third nerve palsy resolved within 48 h on medical therapy. This is an atypical clinical presentation that highlights a successful and novel medical approach to treatment.

Topics: Adult; Antineoplastic Agents; Cabergoline; Ergolines; Humans; Male; Oculomotor Nerve; Oculomotor Nerve Diseases; Pituitary Neoplasms; Prolactinoma

Topics: Adult; Antineoplastic Agents; Cabergoline; Cerebrospinal Fluid Rhinorrhea; Ergolines; Humans; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Prolactinoma; Radiography; Treatment Outcome

Topics: Adenoma; Adult; Antineoplastic Agents; Cabergoline; Diagnosis, Differential; Diagnostic Errors; Ergolines; Female; Galactorrhea; Humans; Hyperprolactinemia; Magnetic Resonance Imaging; Menstruation Disturbances; Pituitary Neoplasms; Prolactin

The purpose of this study is to demonstrate the added value of intraoperative MRI in treating secondary empty sella syndrome.. We describe the case of a 66-year-old woman who was diagnosed with a prolactinoma stage IIIb. During treatment with cabergoline she presented with a secondary empty sella syndrome resulting in visual symptoms. We performed intraoperative MRI-guided packing of the secondary empty sella. We explain why this is useful in surgical treatment of secondary empty sella syndrome.. Intraoperative MRI helps to achieve adequate sellar packing while avoiding insufficient packing as well as overpacking.

Topics: Aged; Cabergoline; Empty Sella Syndrome; Ergolines; Female; Humans; Magnetic Resonance Imaging; Pituitary Neoplasms; Prolactinoma; Treatment Outcome; Visual Fields

During dopaminergic agonist treatment for macroprolactinoma, tumour shrinkage can be accompanied by secondary deterioration of the visual field in rare instances. The aim of the present study was to evaluate the incidence of symptomatic or asymptomatic delayed visual loss associated with chiasmal herniation during long-term cabergoline treatment of macroprolactinomas and to report our experience of its management.. The study included 28 patients (11 women and 17 men) aged 14-85 years treated for macroprolactinoma with cabergoline at our centre from 1997 to 2006.. Chiasmal herniation was observed at MRI in five out of the 28 cases. A systematic visual field evaluation revealed visual field worsening, during cabergoline treatment, in three out of these five patients. In two asymptomatic patients, secondary deterioration of visual field occurred 2.5 years and 4 years, respectively, after cabergoline treatment initiation. In the third case, cabergoline treatment resulted in a paradoxical worsening of an initial visual defect. In all three cases, visual fields improved after cabergoline withdrawal although chiasmal herniation persisted. Visual field remained normal in the two other patients.. Our results suggested that chiasmal herniation associated with delayed visual field defect is not a rare feature during cabergoline treatment of macroprolactinomas. It should be assessed by systematic visual field evaluation and treated by adaptation of medical treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Cabergoline; Dopamine Agonists; Dose-Response Relationship, Drug; Ergolines; Female; Humans; Male; Middle Aged; Optic Chiasm; Pituitary Neoplasms; Prolactinoma; Retrospective Studies; Vision Disorders; Visual Fields; Young Adult

Topics: Adult; Cabergoline; Ergolines; Female; Humans; Hyperprolactinemia; Infant, Newborn; Pituitary Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Prolactin; Prolactinoma

The present study reports the case of a 70-year-old Caucasian man who was referred to the Military Hospital of Buenos Aires for evaluation of a giant sellar-extrasellar mass with extension in the right temporal lobe and compression of the third ventricle. Patient was initially responsive to cabergoline with reduction of prolactin levels and shrinkage of tumor burden for at least 36 months. Thereafter, prolactin levels and tumor size increased even though cabergoline dosage was increased. Transcraneal surgery was performed at 56 months of treatment. Prolactin levels and tumor proliferation did not subside and the patient died 14 months later. High GH and IGF-I levels were observed in the late stages of tumor development, with no evidence of acromegalic features. Immunohistochemistry of the excised tumor revealed strong immunoreactivity for VEGF and FGF-2, two potent angiogenic factors, and CD31 (an endothelial marker) indicating high vascularization of the adenoma.

Topics: Aged; Antineoplastic Agents; Biomarkers, Tumor; Cabergoline; Drug Resistance, Neoplasm; Ergolines; Humans; Hypothyroidism; Immunohistochemistry; Magnetic Resonance Imaging; Male; Neovascularization, Pathologic; Pituitary Neoplasms; Prolactin; Prolactinoma

Macroprolactinomas poorly responsive to dopamine-agonists are often more aggressive and are usually termed 'resistant' but this clinical concept has always been defined empirically.. To define resistance to cabergoline (CAB) on the basis of a dose-response relationship established in a large series of macroprolactinoma patients and to assess the influence of gender and tumor invasiveness on the response to treatment.. Retrospective study.. One hundred and twenty-two patients (72 women and 50 men) primarily treated with CAB for at least 1 year were included. Main outcome measures were serum prolactin (PRL) and tumor size.. Normalization of PRL was obtained in 115 out of the 122 patients (94%). The majority of patients (96/115, 83%) were controlled with a CAB dose < or =1.5 mg/week. Most of the other patients (19/26) had only a partial resistance, responding to a further increase of the CAB dose. Beyond the dose of 3.5 mg/week, there was no clear advantage in further increasing the dose instead of continuing the treatment at the same dose. Most tumors (98/119 assessable cases, 82%) showed a significant shrinkage during CAB treatment. It was more likely to occur in cases of PRL normalization. Both cavernous sinus invasion and male gender were significantly and independently associated with partial or complete resistance to treatment.. Most macroprolactinomas primarily treated with CAB are adequately controlled with doses < or =1.5 mg/week. About 20% of patients, mainly men and/or those with invasive tumors will require a higher dose of CAB. We suggest defining such patients as resistant to CAB.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Cabergoline; Dose-Response Relationship, Drug; Down-Regulation; Drug Resistance, Neoplasm; Ergolines; Female; Humans; Male; Middle Aged; Neoplasm Invasiveness; Pituitary Neoplasms; Prolactin; Prolactinoma; Retrospective Studies; Treatment Failure; Young Adult

Topics: Antineoplastic Agents; Cabergoline; Ergolines; Gambling; Humans; Libido; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma

Recurrence of hyperprolactinemia after cabergoline withdrawal ranges widely from 36 to 80%. The Pituitary Society recommends withdrawal of cabergoline in selected patients.. Our aim was to evaluate recurrence of hyperprolactinemia in patients meeting The Pituitary Society guidelines.. Patients were followed from the date of discontinuation to either relapse of hyperprolactinemia or the day of last prolactin test.. We conducted the study at an academic medical center.. Forty-six patients meeting Pituitary Society criteria (normoprolactinemic and with tumor volume reduction after 2 or more years of treatment) participated in the study.. After withdrawal, if prolactin returned above reference range, another measurement was obtained within 1 month, symptoms were assessed by questionnaire, and magnetic resonance imaging was performed.. We measured risk of and time to recurrence estimates as well as clinical predictors of recurrence.. Mean age of patients was 50 +/- 13 yr, and 70% were women. Thirty-one patients had microprolactinomas, 11 had macroprolactinomas, and four had nontumoral hyperprolactinemia. The overall recurrence was 54%, and the estimated risk of recurrence by 18 months was 63%. The median time to recurrence was 3 months (range, 1-18 months), with 91% of recurrences occurring within 1 yr after discontinuation. Size of tumor remnant prior to withdrawal predicted recurrence [18% increase in risk for each millimeter (95% confidence interval, 3-35; P = 0.017)]. None of the tumors enlarged in the patients experiencing recurrence, and 28% had symptoms of hypogonadism.. Cabergoline withdrawal is practical and safe in a subset of patients as defined by The Pituitary Society guidelines; however, the average risk of long-term recurrence in our study was over 60%. Close follow-up remains important, especially within the first year.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Cabergoline; Ergolines; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Pituitary Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Prognosis; Prolactinoma; Recurrence; Retrospective Studies; Time Factors; Withholding Treatment; Young Adult

The use of drug therapy based on cabergoline, octreotide and long-acting release (LAR) octreotide has presented varying results in the treatment of GH excessive production in patients with McCune-Albright Syndrome.. We report the case of a 29 year-old female patient presenting McCune-Albright Syndrome and complaint of excessive bone growth.. The patient presented a pituitary adenoma involving the right internal carotid artery and excessive secretion of growth hormone (no GH suppression was observed after the oral glucose tolerance test). Due to the presence of diffuse thickness in skull base bones, surgical approach was not considered effective and the patient was submitted to drug therapy with octreotide LAR and cabergoline. At the one year follow-up, GH and IGF-1 levels were normal and no adverse effects were present.. The use of drug therapy based on the association of cabergoline and octreotide is safe and able to achieve complete hormonal control in the treatment of acromegaly for McCune-Albright patients.

Topics: Acromegaly; Adenoma; Adult; Antineoplastic Agents, Hormonal; Cabergoline; Ergolines; Facial Bones; Female; Fibrous Dysplasia, Polyostotic; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Octreotide; Pituitary Neoplasms; Skull

Topics: Brain Ischemia; Cabergoline; Dopamine Agonists; Dose-Response Relationship, Drug; Ergolines; Fatal Outcome; Fibrosis; Heart Valve Prosthesis Implantation; Humans; Intestinal Obstruction; Male; Middle Aged; Mitral Valve Insufficiency; Pituitary Neoplasms; Prolactinoma; Tricuspid Valve Insufficiency; Ventricular Dysfunction, Left

We report 3 cases of cabergoline resistance in adolescents with prolactinomas. All patients failed to respond to conventional doses of cabergoline. There are few reports on the management and outcome of dopamine agonist resistance in prolactinomas in the pediatric population, and our case series highlights the need for further research.

Topics: Adolescent; Antineoplastic Agents; Cabergoline; Drug Resistance, Neoplasm; Ergolines; Female; Humans; Male; Pituitary Neoplasms; Prolactinoma

Cystic prolactinomas are considered not amenable to dopamine agonist therapy. We present the results of dopamine agonist therapy in six patients with cystic prolactinomas. The inclusion criteria of patients were: (i) cystic macroadenomas with the cyst occupying more than 50% of the tumour volume; (ii) a serum prolactin value more than 150 ng/mL. All patients were males with a mean age of 35 years. The clinical presentations were erectile dysfunction in 66.6%, visual deficits in 50% and headache in 50% of patients. All patients were treated with bromocriptine only except one who was treated with both bromocriptine and cabergoline. The mean duration of follow up was 57.1 months. At the final follow-up 50% of patients had hormonal cure, 50% had radiological cure and 50% had reduction in the size of the tumour. Hence, it is appropriate to consider dopamine agonist therapy in patients with cystic prolactinomas before considering surgery.

Topics: Adult; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Follow-Up Studies; Gadolinium; Hormones; Humans; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Prolactinoma; Retrospective Studies; Young Adult

Although cabergoline is effective in the treatment of micro- and macro-prolactinoma, little is known about its efficacy in the treatment of invasive giant prolactinoma. We investigated the efficacy and safety of cabergoline in 10 male patients with invasive giant prolactinoma. Before treatment, mean serum prolactin level was 11,426 ng/mL (range, 1,450-33,200 ng/mL) and mean maximum tumor diameter was 51 mm (range, 40-77 mm). Three months after initiation of cabergoline treatment, serum prolactin concentrations decreased more than 97% in 9 patients; at last follow-up (mean treatment duration, 19 months), the mean decrease in serum prolactin concentrations was 98%, with 5 patients having normal serum prolactin levels. At first MRI follow-up (3-12 months after initiation of cabergoline), the mean reduction in tumor size was 85+/-4% (range, 57-98%). Cabergoline treatment for more than 12 months caused a greater reduction in tumor size compared to the treatment for less than 12 months (97+/-1% vs. 78+/-7%, P<0.05). These findings indicate that cabergoline treatment led to a significant and rapid reduction in serum prolactin concentrations and tumor size in patients with giant prolactinoma. Therefore, cabergoline represents an effective and well-tolerated treatment for invasive giant prolactinoma.

Topics: Adult; Antineoplastic Agents; Cabergoline; Ergolines; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Retrospective Studies

Dopamine D2 and somatostatin receptors (sstrs) were reported to affect non-functioning pituitary adenoma (NFPA) proliferation in vitro. However, the reported results differ according to the experimental conditions used. We established an experimental protocol allowing reproducible evaluation of NFPA cell proliferation in vitro, to test and compare the antiproliferative effects of dopamine and somatostatin analogs (alone or in combination) with the activity of the dopamine-somatostatin chimeric molecule BIM-23A760. The protocol was utilized by four independent laboratories, studying 38 fibroblast-deprived NFPA cell cultures. Cells were characterized for GH, POMC, sstr1-sstr5, total dopamine D2 receptor (D2R) (in all cases), and D2 receptor long and short isoforms (in 15 out of 38 cases) mRNA expression and for alpha-subunit, LH, and FSH release. D2R, sstr3, and sstr2 mRNAs were consistently observed, with the dominant expression of D2R (2.9+/-2.6 copy/copy beta-glucuronidase; mean+/-s.e.m.), when compared with sstr3 and sstr2 (0.6+/-1.0 and 0.3+/-0.6 respectively). BIM-23A760, a molecule with high affinity for D2R and sstr2, significantly inhibited [3H]thymidine incorporation in 23 out of 38 (60%) NFPA cultures (EC50=1.2 pM and Emax=-33.6+/-3.7%). BIM-23A760 effects were similar to those induced by the selective D2R agonist cabergoline that showed a statistically significant inhibition in 18 out of 27 tumors (compared with a significant inhibition obtained in 17 out of 27 tumors using BIM-23A760, in the same subgroup of adenomas analyzed), while octreotide was effective in 13 out of 27 cases. In conclusion, superimposable data generated in four independent laboratories using a standardized protocol demonstrate that, in vitro, chimeric dopamine/sstr agonists are effective in inhibiting cell proliferation in two-thirds of NFPAs.

Topics: Adenoma; Adult; Aged; Antineoplastic Agents, Hormonal; Cabergoline; Cell Division; Dopamine; Dopamine Antagonists; Dose-Response Relationship, Drug; Ergolines; Female; Fibroblasts; Humans; Male; Middle Aged; Octreotide; Pituitary Neoplasms; Receptors, Dopamine D2; Receptors, Somatostatin; RNA, Messenger; Somatostatin; Sulpiride; Thymidine; Tritium; Tumor Cells, Cultured

Treatment with ergot-derived dopamine agonists, pergolide, and cabergoline has been associated with an increased frequency of valvular heart disease in Parkinson's disease. The aim of the present study was to assess the prevalence of valvular heart disease in patients treated with dopamine agonists for prolactinomas.. This was a cross-sectional study.. We performed two-dimensional and Doppler echocardiography in 78 consecutive patients with prolactinoma (mean age 47 +/- 1.4 yr, 26% male, 31% macroprolactinoma) treated with dopamine agonists for at least 1 yr (mean 8 +/- 0.6 yr) and 78 control subjects. Patients were classified according to treatment: patients treated with cabergoline (group 1: n = 47) and patients not treated with cabergoline (group 2: n = 31).. Clinically relevant valvular heart disease was present in 12% of patients (nine of 78) vs. 17% of controls (13 of 78) (P = 0.141) and 17% (eight of 47) of patients treated with cabergoline vs. 3% (one of 31) of patients not treated with cabergoline (P = 0.062). Mild tricuspid regurgitation was present in 41% of patients vs. 26% of controls (P = 0.042), and aortic valve calcification was present in 40% of patients, compared with 18% of controls (P = 0.003). There was no relation between the cumulative dose of cabergoline and the presence of mild, moderate, or severe valve regurgitation.. Several years of dopamine agonist treatment in patients with prolactinomas is associated with increased prevalence of aortic valve calcification and mild tricuspid regurgitation but not with clinically relevant valvular heart disease. Therefore, additional studies on the adverse cardiac effects of dopaminergic drugs in prolactinoma are warranted, especially in patients with much longer use of these drugs.

Topics: Adult; Aortic Valve; Cabergoline; Calcinosis; Case-Control Studies; Cross-Sectional Studies; Disease Progression; Dopamine Agonists; Ergolines; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Pituitary Neoplasms; Prevalence; Prolactinoma; Time Factors; Tricuspid Valve Insufficiency

Cabergoline, a dopamine receptor-2 agonist used to treat prolactinomas, was associated with increased risk of cardiac valve disease in Parkinson's disease.. Our objective was to evaluate prevalence of cardiac valve regurgitation in cabergoline-treated patients with prolactinomas.. An observational, case-control study was conducted at a university hospital.. Fifty treated patients (44 women and six men) and 50 sex- and age-matched control subjects participated; 20 de novo patients were also studied.. In the treated patients, the last cabergoline dose was 1.3 +/- 1.3 mg/wk (<1 mg/wk in 44%, 1-3 mg/wk in 46%, and >3 mg/wk in 10%). Treatment duration was 12-60 months in 32% and more than 60 months in 68%. The cumulative (milligrams x months of treatment) dose of cabergoline ranged from 32-1938 mg (median 280 mg).. Valve regurgitation was assessed according to the recommendations of the American Society of Echocardiography.. In de novo patients, treated patients, and controls, the prevalence of mild regurgitation of mitral (35, 22, and 12%, P = 0.085), aortic (0, 4, and 2%, P = 0.59), tricuspid (55, 30, and 42%, P = 0.13) or pulmonic (20, 12, and 6%, P = 0.22) valves was similar. Conversely, the prevalence of moderate tricuspid regurgitation was higher in the treated patients (54%) than in de novo patients (0%) and controls (18%, P < 0.0001). Moderate tricuspid regurgitation was more frequent in patients receiving a cumulative dose above the median (72%) than in those receiving a lower dose (36%, P = 0.023). A higher systolic (P = 0.03) and diastolic blood pressure (P < 0.0001) was found in patients with than in those without moderate tricuspid regurgitation.. Moderate tricuspid regurgitation is more frequent in patients taking cabergoline (at higher cumulative doses) than in de novo patients and control subjects, but the clinical significance of this finding has not been established. A complete echocardiographic assessment is indicated in patients treated long term with cabergoline, particularly in those requiring elevated doses.

Topics: Adult; Antineoplastic Agents; Cabergoline; Case-Control Studies; Chronic Disease; Dose-Response Relationship, Drug; Ergolines; Female; Humans; Male; Middle Aged; Pituitary Neoplasms; Prevalence; Prolactinoma; Time Factors; Tricuspid Valve Insufficiency; Ultrasonography

To describe a patient who was misdiagnosed as having a nonfunctional pituitary tumor due to the hook effect on prolactin measurements.. A 45-year-old female was admitted with visual disturbances, panhypopituitarism and central diabetes insipidus due to pituitary tumor recurrence. She had been operated 4 times earlier and received cranial irradiation for a suspected nonfunctional pituitary adenoma. Serum prolactin was moderately elevated (164.5 ng/ml), but increased markedly after 1:100 dilution to 14,640 ng/ml. Diagnosis of a giant macroprolactinoma was made and cabergoline was started. Prolactin level normalized and a mild shrinkage of the tumor was achieved after 12 months of therapy.. The hook effect must be kept in mind while evaluating a giant pituitary adenoma with moderately elevated prolactin levels. This way unnecessary surgical procedures or irradiation may be avoided.

Topics: Antineoplastic Agents; Cabergoline; Diabetes Insipidus, Neurogenic; Diagnostic Errors; Ergolines; Female; Glucocorticoids; Humans; Hypopituitarism; Middle Aged; Neoplasm Recurrence, Local; Pituitary Neoplasms; Prednisolone; Prolactin; Prolactinoma; Thyroxine

A 61-year-old lady was admitted to hospital with sepsis due to a urinary tract infection. Three days after admission, she suddenly started to have severe headache with visual disturbance and right third nerve palsy. Urgent magnetic resonance angiography excluded internal carotid artery aneurysm but showed a large lesion extending superiorly from the clivus towards the right cerebral peduncle, which was confirmed by a CT scan of the brain. The lesion was initially thought to be a primary or a metastatic brain tumor. CT scans of the thorax, abdomen and pelvis showed no evidence of metastatic disease. MRI scan revealed a huge pituitary adenoma containing hemorrhage. Subsequent pituitary function tests indicated a grossly elevated serum prolactin level and hypopituitarism.. Magnetic resonance angiography of the head; CT scans of the brain, thorax, abdomen and pelvis; MRI scan of the pituitary gland; and baseline and dynamic anterior pituitary function testing.. Pituitary apoplexy within a macroprolactinoma.. Steroid replacement, careful control of fluid and electrolyte balance and conservative nonsurgical management with the dopamine agonist cabergoline resulted in resolution of the patient's headache, improvement of the third nerve palsy and subsequent normalization of the prolactin level, with reduction in size of the prolactinoma on MRI scan.

Topics: Antineoplastic Agents; Cabergoline; Diagnosis, Differential; Ergolines; Female; Humans; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Middle Aged; Pituitary Apoplexy; Pituitary Neoplasms; Prolactin; Prolactinoma; Tomography, X-Ray Computed

Topics: Aminoquinolines; Cabergoline; Diagnosis, Differential; Dopamine Agonists; Ergolines; Female; Humans; Hyperprolactinemia; Magnetic Resonance Imaging; Pituitary Gland; Pituitary Neoplasms; Pregnancy; Prolactin; Prolactinoma

Topics: Adult; Cabergoline; Dopamine Agonists; Drug Resistance; Echocardiography; Ergolines; Female; Heart Valve Diseases; Humans; Male; Pituitary Neoplasms; Prolactin; Prolactinoma; Receptors, Dopamine; Young Adult

Pituitary apoplexy is a rare and life-threatening clinical condition caused by hemorrhage and/or infarction of the pituitary gland or adenoma. Although pituitary apoplexy is usually spontaneous, it has been associated with numerous precipitating factors, such as bromocriptine use. However, reports of pituitary apoplexy during cabergoline therapy are scarce. We report three patients with cystic macroprolactinomas who developed pituitary apoplexy during cabergoline treatment.

Topics: Adolescent; Adult; Antineoplastic Agents; Cabergoline; Dopamine Agonists; Ergolines; Fatal Outcome; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Apoplexy; Pituitary Neoplasms; Prolactinoma; Tomography, X-Ray Computed

Juvenile cystinosis was diagnosed in a patient who presented with severe headache attacks and photophobia. Treatment with oral cysteamine and topical cysteamine eye drops was started. One-and-a-half years later, he developed unilateral gynecomastia and elevated prolactin and growth hormone levels. A pituitary macroprolactinoma was discovered and successfully treated with the dopamine agonist cabergoline. Increased serum growth hormone levels were attributed to enhanced growth hormone production by the prolactinoma and somatostatin inhibition by cysteamine. Although the occurrence of prolactinoma in this patient could be a simple coincidence, it might also be a rare yet unrecognised complication of cystinosis.

Topics: Administration, Oral; Administration, Topical; Body Height; Cabergoline; Child; Cysteamine; Cystinosis; Dopamine Agonists; Ergolines; Headache; Human Growth Hormone; Humans; Male; Ophthalmic Solutions; Pituitary Neoplasms; Prolactinoma; Radiation-Protective Agents; Treatment Outcome

We present the first case of successful non-surgical treatment of an internal carotid aneurysm, embedded within a macroprolactinoma. A 53 year old male, with a previous history of Non-Hodgkin's Lymphoma (NHL), presented with severe right sided frontal headache, decreased visual acuity, and ophthalmolplegia due to a third nerve palsy. A CT scan showed a 4.6 by 4.8 cm mass in the pituitary fossa with bony erosion. Initially, it was thought to be a cerebral recurrence of the Non-Hodgkin's disease. Direct questioning revealed a long history of erectile dysfunction with loss of libido. Prolactin at presentation was 537, 200 mU/l and a diagnosis of macroprolactinoma, with apoplexy was made. A subsequent MRI brain confirmed a large macroadenoma with an intra cavernous aneurysm encased by the tumour. A therapeutic dilemma ensued due to the need for urgent decompression of the visual pathways, preferably by surgery. However, in the presence of an intrasellar aneurysm, surgery would have been extremely hazardous. The patient was therefore commenced on cabergoline and rapidly titrated up to 4 mg per week. The aneurysm was treated by endovascular occlusion of the right carotid artery under radiological control. The combination of these therapies, without conventional surgical intervention, resulted in resolution of the third nerve palsy and recovery of visual acuity in the left eye. The diagnosis and management of this condition was challenging and the final outcome, with non-surgical treatment and carotid artery occlusion was satisfactory.

Topics: Angiography, Digital Subtraction; Antineoplastic Agents; Balloon Occlusion; Cabergoline; Carotid Artery, Internal; Dopamine Agonists; Ergolines; Headache; Humans; Intracranial Aneurysm; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Invasiveness; Ophthalmoplegia; Pituitary Apoplexy; Pituitary Neoplasms; Prolactinoma; Treatment Outcome; Vision Disorders

Cabergoline (CAB) has been proposed as the first-line treatment in the management of prolactin (PRL)-secreting tumors (prolactinoma [PRLoma]), including those resistant to standard dopamine agonist (DAA) therapy. The authors report remarkable effects of CAB in a case of huge PRLoma that had been resistant to a long-term, high-dose treatment with bromocriptine (BRC).. A 28-year-old man was originally presented with oculomotor paresis when he was 9 years old. After 2 partial resections, he was treated with a maximum 60-mg/d dose of BRC for 18 years. Nonetheless, the tumor grew up to more than 8 cm in diameter, serum PRL increased over 60000 ng/mL, and his visual acuity deteriorated. Cabergoline normalized serum PRL level, shrank the tumor mass remarkably, and caused marked improvement of visual acuity.. Prolactin normalization and significant tumor shrinkage could be achieved with CAB even in extremely BRC-resistant PRLomas. Surgical resection should be reserved only for patients who are resistant to cabergoline or who require urgent decompression in such emergency as massive intratumoral hemorrhage.

Topics: Adult; Antineoplastic Agents; Bromocriptine; Cabergoline; Dopamine Agonists; Drug Resistance, Neoplasm; Ergolines; Humans; Male; Pituitary Neoplasms; Prolactinoma; Treatment Outcome

Dopamine-agonist cabergoline (CB) reduces prolactin (PRL) secretion and tumor size in 80% of patients with prolactin-secreting adenomas (PRL-omas) by binding type 2 dopamine receptor (DRD2). The mechanisms responsible for resistance to CB remain largely unknown. To assess the association of DRD2 with sensitivity to CB, TaqI-A1/A2, TaqI-B1/B2, HphI-G/T and NcoI-C/T genotypes were determined in a cross-sectional retrospective study, including 203 patients with PRL-oma. DRD2 alleles frequencies did not differ between patients and 212 healthy subjects. Conversely, NcoI-T allele frequency was higher in resistant rather than responsive patients, considering both PRL normalization (56.6 vs 45.3%, P=0.038) and tumor shrinkage (70.4 vs 41.4%, P=0.006). Finally, [TaqI A1-/TaqI B1-/HphI T-/NcoI T-] haplotype was found in 34.5% of patients normalizing PRL with < or =3 mg/week of CB vs 11.3% of resistants (P=0.021). In conclusion, resistance to CB was associated with DRD2 NcoI-T+ allele, consistent with evidence suggesting that this variant may lead to reduction and instability of DRD2 mRNA or protein.

Topics: Adenoma; Adult; Alleles; Cabergoline; Cross-Sectional Studies; Dopamine Agonists; Ergolines; Female; Gene Frequency; Genotype; Humans; Male; Middle Aged; Pituitary Neoplasms; Polymorphism, Genetic; Prolactin; Receptors, Dopamine D2; Retrospective Studies

Ten percent of patients with prolactinoma fail to respond with normalization of prolactin (PRL) and tumor shrinkage under dopamine agonist (DA) therapy. The resistance to treatment is linked to a loss of dopamine receptor 2 (D2DR). Prolactinomas express somatostatin (SST) receptor subtypes, SSTR1, 2, and 5. The aim of this study was to determine whether different SST compounds could overcome the resistance to DA in prolactinomas.. The efficacy of SSTR1, SSTR2, and SSTR5 ligands; the universal SST ligand, SOM230; and the chimeric SST-DA compound, BIM-23A760, was compared with cabergoline in suppressing PRL secretion from primary cultures of ten prolactinomas (six DA responders and four DA resistant). Receptor mRNAs were assessed by quantitative PCR.. The mean mRNA levels for D2DR, SSTR1, SSTR2, and SSTR5 were 92.3+/-47.3, 2.2+/-1.4, 1.1+/-0.7, and 1.6+/-0.6 copy/copy beta-glucuronidase (beta-Gus) respectively. The SSTR1 agonist, BIM-23926, did not suppress PRL in prolactinomas. In a DA-resistant prolactinoma, it did not inhibit [(3)H]thymidine incorporation. The SSTR5 compound, BIM-23206, produced a dose-dependent inhibition of PRL release similar to that of cabergoline in three DA-sensitive prolactinomas. BIM-23A760 produced a maximal PRL inhibition superimposable to that obtained with cabergoline with a lower EC(50) (0.5+/-0.1 vs 2.5+/-1.5 pmol/l). In DA-resistant prolactinomas, BIM-23206 and SOM230 were ineffective. Cabergoline and BIM-23A760 produced a partial inhibition of PRL secretion (19+/-6 and 21+/-3% respectively).. Although the SSTRs are expressed in prolactinomas, the somatostatinergic ligands analyzed do not appear to be highly effective in suppressing PRL. D2DR remains the primary target for effective treatment of prolactinomas.

Topics: Adult; Antineoplastic Agents; Cabergoline; Dopamine; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Ergolines; Female; Growth Hormone-Secreting Pituitary Adenoma; Humans; Ligands; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma; Receptors, Dopamine D2; Receptors, Somatostatin; RNA, Messenger; Somatostatin; Tumor Cells, Cultured

We report for the first time a case of nephrotic-range proteinuria adequately controlled by using dopamine agonists. A 40-year-old man was studied because of persistent asymptomatic nephrotic proteinuria despite lifestyle modifications and treatment with converting enzyme inhibitors. The renal biopsy specimen did not show histopathologic changes. In the follow-up period, a giant prolactinoma was found by chance with extremely high prolactin (PRL) values. After establishing cabergoline therapy, we achieved a remarkable decrease in both serum PRL levels and tumor mass, and surprisingly, proteinuria disappeared. We discuss the possible pathogenic mechanisms of proteinuria that may correspond to PRL level in urine (prolactinuria) or another tumor-related protein.

Topics: Adult; Cabergoline; Dopamine Agonists; Ergolines; Humans; Hyperprolactinemia; Male; Pituitary Neoplasms; Prolactinoma; Proteinuria

TSH-secreting adenomas are rare tumors, representing only 0.5 to 2.5% of pituitary adenomas. Their main clinical characteristics include signs of thyrotoxicosis, diffuse goiter and a compressive syndrome. Biologically, free T4 and T3 serum levels are elevated, contrasting with inadequate serum TSH levels and increased alpha chains. Magnetic resonance (MR) imaging shows a pituitary tumor, the main differential diagnosis being resistance to thyroid hormones. Treatment is based on surgery, possibly associated with somatostatin analogs and radiotherapy. Though the long-term evolution of this rare pathology seems to have improved, some clinical situations are still a challenge to treat. We report one such case that was resistant to both stereotactic radiotherapy and somatostatin analogs, but surprisingly improved with cabergoline. We suggest that cabergoline should be considered as an alternative treatment in cases of pituitary adenomas that resist traditional treatments.

Topics: Adult; Antineoplastic Agents; Bone and Bones; Cabergoline; Ergolines; Humans; Male; Pituitary Neoplasms; Thyrotropin; Thyroxine; Triiodothyronine

Topics: Adult; Cabergoline; Disease Progression; Dopamine Agonists; Drug Resistance, Neoplasm; Ergolines; Female; Humans; Hyperprolactinemia; Middle Aged; Pituitary Neoplasms; Prolactinoma

Topics: Adenoma; Adult; Cabergoline; Dopamine Agonists; Ergolines; Face; Hair; Humans; Hydrocortisone; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Prolactin; Testosterone; Thyroxine

Short-lasting unilateral neuralgiform headache with conjuntival injection and tearing (SUNCT) syndrome is a rare trigeminal autonomic cephalalgia. We report a patient with prolactinoma and cabergoline-induced SUNCT attacks and the literature is reviewed for a better understanding of the pathophysiology.

Topics: Adult; Antineoplastic Agents; Cabergoline; Ergolines; Female; Humans; Pituitary Neoplasms; Prolactinoma; SUNCT Syndrome

To review our experience with cabergoline, a D2-selective dopamine agonist, for the treatment of giant prolactinomas.. A retrospective case series; descriptive statistics.. The study group included 12 men aged 24-52 years (mean 39.2 years) treated for giant prolactinoma at our centers from 1997 to 2006. Cabergoline was started at a dose of 0.5 mg/three times a week and progressively increased as necessary to up to 7 mg/week. Patients were followed by hormone measurements, sellar magnetic resonance imaging, and visual examinations.. In ten patients, cabergoline served as first-line therapy. The other two patients had previously undergone transsphenoidal partial tumor resection because of visual deterioration. Mean serum prolactin level before treatment was 14,393 +/- 14,579 ng/ml (range 2047-55,033 ng/ml; normal 5-17 ng/ml). Following treatment, levels normalized in ten men within 1-84 months (mean, 25.3 months) and decreased in the other two to 2-3 times of normal. Tumor diameter, which measured 40-70 mm at diagnosis, showed a mean maximal decrease of 47 +/- 21%; response was first noted about 6 months after the onset of treatment. Nine patients had visual field defects at diagnosis; vision returned to normal in three of them and improved in five. Testosterone levels, initially low in all patients, normalized in eight. There were no side effects of treatment.. Cabergoline therapy appears to be effective and safe in men with giant prolactinomas. These findings suggest that cabergoline should be the first-line therapy for aggressive prolactinomas, even in patients with visual field defects.

Topics: Adult; Antineoplastic Agents; Cabergoline; Ergolines; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Retrospective Studies; Time Factors; Treatment Outcome; Vision Disorders; Visual Fields

Prolactin hypersecretion from a pituitary adenoma usually results in a serum prolactin level less than 1,000 ng/ml. During therapy with a dopamine agonist, prolactin levels usually normalize and the tumors shrink substantially. In the past few years, we have seen three men who presented with serum prolactin levels greater than 10,000 ng/ml. All presented with large tumors, visual field deficits, and hypogonadotropic hypogonadism. All other pituitary hormones were normal. In all three patients, significant tumor shrinkage was achieved with improvement or resolution of headaches and visual field deficits. None of our patients has been able to achieve a normal prolactin or testosterone. A literature review identified 32 patients with prolactin levels of more than 10,000 ng/ml. Twenty-six (81%) were males. Most had large tumors, headaches and visual field defects. Even with the addition of surgery and/or radiation therapy to medical therapy, normalization of serum prolactin occurred in only six patients (19%) and only one man achieved a normal testosterone. We conclude that in patients with massive prolactin hypersecretion, therapy with a dopamine agonist will lead to tumor shrinkage and improvement of mass effects, but usually does not normalize prolactin or testosterone. Rather than waiting for maximal prolactin reduction, we would recommend early institution of testosterone replacement therapy.

Topics: Adult; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Humans; Hyperprolactinemia; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Prolactin; Prolactinoma; Testosterone

Criteria to define the response to somatostatin (SS) analogs (SSA) in acromegaly are based on biochemical control of the disease. However, the mechanisms of action of SSAs in inhibiting tumor growth and hormonal secretion are only partially understood, and the two effects may occur independently.. The objective of the study was to investigate the dissociation between antiproliferative and antisecretive effects of SSA in an octreotide-resistant patient displaying dramatic tumor shrinkage during primary therapy with octreotide LAR.. We characterized somatostatin and dopamine D(2) receptor expression by immunohistochemistry and real-time RT-PCR. The effects of different receptor-selective, bispecific analogs, and chimeric somatostatin/dopamine compounds on GH secretion and cell proliferation in primary cell cultures of the tumor were assessed.. The expression of SS receptor subtypes (sst)(5) and D(2) receptor was higher, compared with the other receptor subtypes. GH inhibition by SS-14 and the two chimeric somatostatin/dopamine compounds was scant but greater than subtype-selective and sst(2)/sst(5) bispecific agonists. Conversely, cell growth was potently inhibited by all test substances. However, SS-14, sst(2)/sst(5) bispecific agonist, and chimeric molecules were more potent than the other compounds.. The significant antiproliferative effect of octreotide seems to be related to the higher expression of sst(5) and the negligible antihormonal effect to the lower expression of sst(2). However, activation of multiple receptors by new analogs may produce better control of tumor cell activities. The dissociation between antisecretive and antiproliferative effects observed in vivo and in vitro confirms that SSAs may induce tumor shrinkage despite the lack of effect on GH secretion.

Topics: Acromegaly; Adenoma, Acidophil; Adult; Cabergoline; Cell Proliferation; Cells, Cultured; Delayed-Action Preparations; Ergolines; Human Growth Hormone; Humans; Immunohistochemistry; Insulin-Like Growth Factor I; Magnetic Resonance Imaging; Male; Microscopy, Electron; Octreotide; Pituitary Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Somatostatin; Thymidine

Limited data are available on clinical presentation and treatment strategy in patients with GH-secreting adenomas with onset in adolescence.. To report results of diagnosis and treatment in adolescents with GH and IGF-I excess.. Analytical, observational, retrospective.. Thirteen patients (five females and eight males, age 15-20 years) all with macroadenoma (two extrasellar, 11 invasive).. Height, body mass index (BMI), GH and IGF-I levels, tumour volume at diagnosis and after treatment.. Transsphenoidal surgery, octreotide subcutaneous (OCT, 0.3-0.8 mg/day), octreotide-LAR i.m. (LAR, 20-30 mg/q28 days), lanreotide i.m. (LAN, 60-90 mg/q28 days), bromocriptine (BRC, 5 mg/day), cabergoline (CAB, 1-2 mg/week).. Concomitant hyperprolactinaemia was found in eight patients (61.5%). All girls presented with amenorrhoea, which was associated with galactorrhoea in two patients; all boys presented with symptoms of tumour mass compression such as visual disturbance or headache; two girls also had these symptoms. Height at diagnosis was above the 97th centile in four of five girls and in six of eight boys. None of the patients had altered lipid profile while homeostasis model assessment of insulin resistance (HOMA-IR; 2.8 +/- 0.9) and beta-cell function (HOMA-beta, 207.6 +/- 98.1%) were higher than predicted (1% and 100%, respectively). First-line treatment was surgery in two patients and somatostatin analogues associated with dopaminergic drugs in 11 patients. None of the patients operated on were cured while six of 11 patients receiving pharmacotherapy (6-24 months) were controlled. In these six, tumour volume was reduced by 51.0 +/- 25.2% (median 51.5%). As second-line treatment, all the 11 patients treated with somatostatin analogues underwent surgical removal of their tumours. Surgery was successful in four patients and second-line pharmacotherapy in six patients. One patient was lost at follow-up and two patients maintained active acromegaly despite different treatment schedules; both patients were then treated with radiotherapy. At the last follow-up, there was a significant decrease in insulin levels, HOMA-IR and HOMA-beta without any change in lipid profile.. The clinical presentation of GH-secreting adenomas in adolescent girls is associated with menstrual disturbances and in boys with symptoms of mass effects; tall stature is characteristic in both. First-line treatment with depot somatostatin analogues followed by surgery and then by a second course of somatostatin analogues was successful and safe in 11 of 13 patients.

Topics: Adolescent; Adult; Antineoplastic Agents, Hormonal; Body Height; Body Mass Index; Bromocriptine; Cabergoline; Combined Modality Therapy; Ergolines; Female; Growth Hormone; Growth Hormone-Secreting Pituitary Adenoma; Headache; Hormone Antagonists; Humans; Insulin Resistance; Insulin-Like Growth Factor I; Male; Menstruation Disturbances; Octreotide; Peptides, Cyclic; Pituitary Neoplasms; Retrospective Studies; Somatostatin; Treatment Outcome

Topics: Administration, Oral; Adult; Antipsychotic Agents; Aripiprazole; Cabergoline; Clonazepam; Dopamine Agonists; Drug Therapy, Combination; Ergolines; Female; Follow-Up Studies; Humans; Patient Care Team; Piperazines; Pituitary Neoplasms; Prolactin; Prolactinoma; Quinolones; Schizophrenia

Dopamine agonists (DA) may act on prolactinoma size and secretion through additional effects on adenoma vascularity that can be visualized using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI).. We hypothesized that DAs may exert their effect through a change in tumour functional vascularity leading to a reduction of prolactin (PRL) levels and tumour size.. To investigate this, 23 subjects were studied comprising five with macroprolactinomas, 11 with microprolactinomas, seven with non-lesion hyperprolactinemia and 15 normal volunteers (including five females on oral contraceptive pills). Patients with macroprolactinomas were treated with cabergoline 4 mg weekly and microprolactinomas were treated with quinagolide 75 microg daily for the duration of study. DCE-MRI was performed immediately pre-treatment and at 3-4 days, 1 and 3-4 months after treatment. Normal volunteers took three 75 microg quinagolide doses and were scanned pre-treatment and at 3 days. Data were analysed using the Brix model, producing a measure of vascular permeability and leakage space.. PRL levels were significantly reduced in all patients and volunteers. Vascular parameters decreased significantly for four of five macroprolactinomas and all microprolactinomas which were maintained during the treatment period (p < 0.01). No changes were seen in normal volunteers or non-lesion hyperprolactinemia. One of five macroprolactinomas showed no change in either permeability or tumour size.. Functional prolactinoma vascularity differs from non-lesion hyperprolactinemic pituitary and normal pituitary, and is responsive to DA therapy. The reduction in vascular parameters precedes shrinkage in macroprolactinomas, and if not seen within days of treatment may indicate DA resistance requiring early surgery.

Topics: Adolescent; Adult; Aged; Aminoquinolines; Cabergoline; Contraceptives, Oral, Hormonal; Dopamine Agonists; Ergolines; Female; Humans; Immunoglobulin G; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Prolactin; Prolactinoma

Remission rates of 76, 69.5 and 64.3% have been reported in patients with nontumoural hyperprolactinaemia (NTH), microprolactinoma and macroprolactinoma, respectively, 2-5 years after cabergoline (CAB) withdrawal.. To report the estimated recurrence rate at 24-96 months after CAB withdrawal and indicate predictors of disease remission.. Observational, analytical, prospective.. Of 381 previously untreated de novo patients with hyperprolactinaemia, 221 (58%) (173 women, 48 men; 27 with NTH, 115 with micro-, and 79 with macroprolactinoma) were studied.. Using multiple regression analysis the diagnostic accuracy of nadir PRL levels (t = 7.6, P < 0.0001) and nadir maximal tumour diameter at CAB withdrawal (t = 3.9, P < 0.001) was analysed using receiver operating characteristic (ROC) curves.. The recurrence of hyperprolactinaemia was 25.9, 33.9 and 53.1% in patients with NTH, micro- or macroprolactinoma, respectively. To predict the last PRL level after withdrawal, the optimum cut-off of nadir PRL levels at withdrawal was 162 mU/l (5.4 microg/l) [sensitivity (95% CI) 76% (67-84%), specificity 65% (51-77%)] and that of nadir maximal tumour diameter was 3.1 mm [sensitivity 52% (41-63%), specificity 86% (79-91%)]. The patients achieving both nadir PRL levels

Topics: Adult; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Hyperprolactinemia; Kaplan-Meier Estimate; Male; Middle Aged; Pituitary Neoplasms; Predictive Value of Tests; Prolactinoma; Prospective Studies; Regression Analysis; Remission Induction; ROC Curve; Secondary Prevention; Sex Distribution; Time Factors; Young Adult

Topics: Adenoma; Bromocriptine; Cabergoline; Dopamine Agents; Dopamine Agonists; Ergolines; Humans; Pituitary Neoplasms; Prolactin

Topics: Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Pituitary Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Prolactinoma; Treatment Outcome

Pituitary gigantism, a condition of endogenous growth hormone (GH) hypersecretion prior to epiphyseal closure, is a rare condition. In the adult condition of GH excess, acromegaly, the occurrence of type 2 diabetes mellitus (T2DM) and diabetic ketoacidosis (DKA) have been reported, with resolution following normalization of GH levels. We report the case of a 16-year-old male with pituitary gigantism due to a large invasive suprasellar adenoma who presented with T2DM and DKA. Despite surgical de-bulking, radiotherapy and medical treatment with cabergoline and pegvisomant, GH and insulin-like growth factor-I (IGF-I) levels remained elevated. However, the T2DM and recurrent DKA were successfully managed with metformin and low-dose glargine insulin, respectively. We review the pathophysiology of T2DM and DKA in growth hormone excess and available treatment options.

Topics: Adenoma; Adolescent; Antineoplastic Agents; Cabergoline; Combined Modality Therapy; Diabetes Mellitus, Type 2; Ergolines; Gigantism; Human Growth Hormone; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Pituitary Neoplasms; Radiotherapy

Topics: Adenoma; Antineoplastic Agents; Cabergoline; Ergolines; Female; Gonadotropins; Humans; Neovascularization, Pathologic; Ovarian Hyperstimulation Syndrome; Pituitary Neoplasms; Polycystic Ovary Syndrome; Vascular Endothelial Growth Factor A

Pituitary carcinomas are very rare tumors, nearly always presenting as widely invasive masses, although the hallmark of these lesions is the finding of distant metastases. One third of reported cases are prolactin (PRL)-secreting tumors. We report the case of a fatal pituitary carcinoma evolving within 4 years from a PRL-secreting microadenoma. A 22-year-old woman presented because of galactorrhea. Evaluation of the patient disclosed slight hyperprolactinemia and magnetic resonance imaging (MRI) showed a 7-mm intrapituitary lesion, which responded to treatment with cabergoline. About 4 years after the first evaluation she developed sudden headache, ptosis, and diplopia in the right eye. MRI disclosed the growth of a large pituitary mass, invading the right cavernous sinus. Despite two trans-sphenoidal surgical procedures followed by gamma-knife radiosurgery, the patient showed rapid local progression of the tumor and the occurrence of new lung lesions, probably of metastatic nature. The patient died 7 months after the development of her first neurological symptoms because of tumor apoplexy and subsequent subarachnoid hemorrhage. This case represents the first documented rapid evolution from a microprolactinoma initially responding to dopamine agonists to a fatal pituitary carcinoma.

Topics: Adult; Cabergoline; Carcinoma; Combined Modality Therapy; Disease Progression; Dopamine Agonists; Drug Resistance; Ergolines; Fatal Outcome; Female; Humans; Octreotide; Pituitary Apoplexy; Pituitary Neoplasms; Prolactinoma; Radiosurgery; Subarachnoid Hemorrhage

Topics: Antidepressive Agents; Antineoplastic Agents; Cabergoline; Citalopram; Delusions; Depressive Disorder, Major; Ergolines; Female; Gambling; Humans; Middle Aged; Pituitary Neoplasms; Prolactinoma

Patients with large prolactin (PRL)-secreting pituitary adenoma often have symptoms due to varying degree of hypopituitarism and/or mass effect on visual structures, while presentation with hydrocephalus is extremely uncommon. Even more exceptional is the development of the syndrome of intracranial hypertension as a consequence of tumor obstruction of the cerebrospinal fluid circulation. In this report, we describe a 26-year-old man who was referred to the emergency department of our hospital because of headache, nausea, and vomiting. Clinical and radiological assessment led to the diagnosis of obstructive hydrocephalus caused by a giant macroprolactinoma. The patient received a temporary external ventricular drainage to relieve the symptoms of intracranial hypertension. The same day, after we received the result of the basal PRL level, medical treatment with cabergoline was initiated. A prompt response to the drug ensued with resolution of the obstructive hydrocephalus, which allowed removal of the external ventricular drainage. Initial shrinkage of the mass was already noted on a magnetic resonance imaging performed 12 days thereafter. Subsequent medical treatment led to progressive and marked shrinkage of the tumor. Eighteen months after presentation the patient was well while on cabergoline treatment and showed no symptom attributable to compression of the surrounding nervous structures. Our report confirms that, even in cases of giant sellar mass with neurological symptoms, a rapid hormonal evaluation is mandatory. If a macroprolactinoma is diagnosed, treatment with dopamine agonists can lead to prompt clinical amelioration and shrinkage of the tumor, with eventual resolution of neurological symptoms.

Topics: Adult; Cabergoline; Dopamine Agonists; Drainage; Ergolines; Humans; Hydrocephalus; Intracranial Hypertension; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Prolactinoma; Treatment Outcome

Alterations of sperm number and motility are found in hyperprolactinaemic men. Cabergoline treatment reverses alterations in semen. No information is currently available on the quality of seminal tests in hyperprolactinemia in response to cabergoline treatment.. To further investigate the effect of hyperprolactinaemia and its treatment with cabergoline on semen quality.. Forty-three men with hyperprolactinaemia (32 macro- and 11 micro-prolactinomas); 60 healthy men served as control.. Live spermatozoa count, sperm membrane function, kinetic index, nuclear DNA integrity, sperm curvilinear and linear velocity and amplitude of lateral movement of the sperm head were investigated before and after 6 and 24 months of treatment with cabergoline.. Open prospective.. At study entry, semen functional tests were severely and similarly impaired both in patients with macro- and micro-prolactinomas compared to controls. After 6 and 12 months of treatment there was a significant improvement of semen quality in patients achieving normalization of prolactin levels, although most of the parameters remained lower than in controls. After 24 months of treatment, seminal fluid characteristics were similar to the controls except for live spermatozoa count, sperm membrane function, sperm kinetic index and sperm nuclear DNA integrity, which remained abnormal in 9.3-53% of the patients.. Twenty-four months of cabergoline treatment restored gonadal function in 66.7% of men with hyperprolactinaemia.

Topics: Adult; Antineoplastic Agents; Cabergoline; Case-Control Studies; Drug Administration Schedule; Ergolines; Gonadotropins; Humans; Hyperprolactinemia; Male; Pituitary Neoplasms; Prolactin; Prolactinoma; Prospective Studies; Semen; Sperm Count; Spermatozoa; Testosterone; Time Factors; Treatment Outcome

The resistance of macroprolactinomas to dopamine agonist (DA) therapy, whether defined as an absence of PRL normalization or the lack of significant tumour shrinkage after prolonged treatment at high doses, is usually regarded as unpredictable. The aim of this retrospective study, conducted in a teaching hospital, was to determine whether cavernous sinus (CS) invasion assessed by magnetic resonance imaging (MRI) is associated with a higher rate of resistance to DA therapy.. Forty-nine patients with a macroprolactinoma were included in this study and classified into four groups according to the percentage of encasement of the intracavernous internal carotid artery (ICA) by the tumour. All patients received DA as the primary treatment, mainly cabergoline (CAB). PRL normalization and tumour shrinkage during treatment were evaluated as a function of CS invasion.. Tumours encasing more than three-quarters of the intracavernous ICA (group 4) were less responsive to DA therapy, exhibiting a lower rate of early (< or = 3 months) PRL normalization (8%vs. 69% in the others groups; P < 0.01) under a higher dose of CAB (median: 3.5 mg vs. 1.0 mg per week; P < 0.01). CS invasion was a strongly significant and independent predictor of hormonal resistance to CAB (P < 0.01). This hormonal resistance occurred in eight patients (16%), all but one belonging to group 4. Significant tumour shrinkage was observed in 31 out of 45 assessable cases (69%) and was more likely to occur in the case of PRL normalization (P < 0.01).. Parasellar extension of macroprolactinomas, assessed on the basis of strict MRI criteria, may predict a negative response to DA. The responsiveness of noninvasive macroprolactinomas (over 90%) is similar to that reported in microprolactinomas, whereas invasive tumours are resistant to treatment in more than 50% of cases.

Topics: Adult; Cabergoline; Carotid Artery, Internal; Dopamine Agonists; Ergolines; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Invasiveness; Pituitary Neoplasms; Prolactin; Prolactinoma; Retrospective Studies; Sphenoid Sinus; Treatment Outcome

The authors report a case of a patient with giant, invasive skull base tumor extending to the parasellar area discovered incidentally during the work-up for decreased memory. The patient's neurological exam was otherwise unremarkable. Endocrine evaluation performed at a local hospital showed a moderate hyperprolactinemia 103 ng/ml (normal up to 20 ng/ml). Given the large size of the tumor, the elevated prolactin (PRL) was interpreted to be secondary to stalk effect and patient underwent debulking surgery through a transcranial approach. Immunostaining of the excised tumor tissue was strongly positive for prolactin. His prolactin was found to be 13,144 ng/ml in our lab after surgery confirming the diagnosis of invasive giant prolactinoma. The patient developed a complete right third, fourth and sixth nerve palsy postoperatively. He was started on Cabergoline with normalization of his prolactin level and more than 50% decrease in residual tumor size over 9 months periods. There has been no clinically significant improvement in his right eye ophthalmoplegia since surgery. This case highlights the importance of 'Hook Effect' resulting in falsely low prolactin level, which may have significant therapeutic implication.

Topics: Abducens Nerve Diseases; Cabergoline; Diagnosis, Differential; Diagnostic Errors; Dopamine Agonists; Ergolines; Humans; Hyperprolactinemia; Magnetic Resonance Imaging; Male; Middle Aged; Neurosurgical Procedures; Oculomotor Nerve Diseases; Pituitary Neoplasms; Prolactin; Prolactinoma; Skull Base Neoplasms; Trochlear Nerve Diseases

Topics: Adolescent; Adult; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma

To report the effect of cabergoline on ovarian hyperstimulation syndrome associated with gonadotropin-secreting pituitary adenomas.. Case report.. Outpatient practice.. Two women with menstrual irregularity, enlarged ovaries, high E(2), and normal gonadotropin levels.. Cabergoline treatment and transsphenoidal surgery.. Estradiol levels, transvaginal ultrasonography, and pituitary magnetic resonance imaging. Transsphenoidal surgery showed pituitary adenoma staining for LH in both patients.. Cabergoline was effective in reducing E(2) levels and decreasing ovarian size but ineffective in shrinking the pituitary adenomas.. This is the first description of the effectiveness of cabergoline as the primary treatment of spontaneous ovarian hyperstimulation syndrome in patients with gonadotropin-producing pituitary adenomas.

Topics: Adenoma; Adult; Antineoplastic Agents; Cabergoline; Ergolines; Female; Gonadotropins; Humans; Ovarian Hyperstimulation Syndrome; Pituitary Neoplasms

Clinically non-functioning pituitary adenomas (NFPAs) can express functional dopamine D2 receptors. Therapy with dopamine (DA) agonists may result in a NFPA size reduction. However, DA agonist-sensitive and -resistant NFPAs are clinically indistinguishable. We have studied the correlation between in vivo imaging of D2 receptors using (123)I-epidepride and the radiological response of NFPA to DA in 18 patients.. Patients were treated with either cabergoline (1-2 mg/week) or quinagolide (150-300 mug/day) for a mean period of 89.7 months (range, 34-187 months).. Pituitary uptake of (123)I-epidepride varied from slight uptake classified as grade 0 to very high classified as grade 3. Grade 0 uptake was found in four patients; grade 1 in three; grade 2 in ten, and grade 3 in one. NFPA stabilization or shrinkage with DA agonist therapy showed no significant difference between grade 0, 1, and 2 tumors (mean tumor stabilization or shrinkage: 31, 30, and 36% respectively). However, when we considered a decrease in tumor size ranging from 0 to 20% as tumor stabilization and >20% decrease in tumor size as true shrinkage, one out of four NFPAs with grade 1 uptake, two out of three with grade 1 uptake, and eight out of ten with grade 2 uptake showed tumor shrinkage.. In conclusion, there is limited clinical usefulness of dopamine D2 receptor imaging for predicting the clinical efficacy of DA agonist in selected patients with NFPAs. DA agonist therapy in NFPAs can result in tumor stabilization and shrinkage.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Aminoquinolines; Benzamides; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Pyrrolidines; Receptors, Dopamine D2; Tomography, Emission-Computed, Single-Photon

The stimulatory role of testosterone in the production and release of prostate-specific antigen (PSA) has been well characterized. Testosterone production by the testes is dependent on a functional hypothalamic-pituitary-gonadal axis. High prolactin levels have been shown to disrupt this axis, resulting in decreases in gonadotropins and testosterone levels. We report a patient with prostate cancer and elevated PSA levels followed with "watchful waiting" for several years who experienced a precipitous decrease in PSA level over a 3 month period. The patient was found to have an asymptomatic prolactin-secreting pituitary macroadenoma.

Topics: Adenocarcinoma; Aged, 80 and over; Antineoplastic Agents; Cabergoline; Ergolines; Humans; Male; Neoplasms, Second Primary; Pituitary Neoplasms; Prolactinoma; Prostate-Specific Antigen; Prostatic Neoplasms

We present the case of a 60 year old male patient with incidentally detected visual abnormalities. Detailed personal history revealed a hypogonadism that had been present for several years. Further investigations established the diagnosis of an infiltrative macroadenoma. Medical treatment with cabergoline led to a rapid regression of ophthalmologic symptoms and, subsequently, of tumor size. In male subjects symptoms of hypogonadism are often reported only late in the course of the disease, thereby leading to a generally larger tumor size at the point of diagnosis. In contrast to other pituitary tumors that are mainly treated by surgery, medical treatment with dopamine agonists is the principal therapeutic option in prolactinomas.

Topics: Cabergoline; Diagnosis, Differential; Dopamine Agonists; Erectile Dysfunction; Ergolines; Humans; Hyperprolactinemia; Hypogonadism; Libido; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Compression Syndromes; Optic Nerve Diseases; Pituitary Neoplasms; Prolactinoma; Visual Fields

To evaluate our experience regarding the treatment of pituitary macroadenomas with cavernous sinus invasion in a series of 23 cases of transphenoidal resection.. Twenty two patients, fifteen males and seven females, with ages ranging from 27 to 75 (mean of 48), were operated under protocol by a single surgeon between May of 2002 and December of 2004. Preoperatively all lesions were diagnosed by MRI and staged according to the Knosp classification. All tumors had extension to one or both cavernous sinuses. Four patients were considered to be grade 1, two grade 2, one grade 3 and sixteen grade 4. Twenty three operations were performed on twenty-two patients. Twenty cases were the standard transsphenoidal approach, and three were endoscopic. Postoperatively, the excision was classified as Complete or Total, Subtotal or Partial. Mean follow up was 15 months. The variables considered for analysis include invasion and resection grades. All six patients with graded 1 and 2 lesions and two patients with grade 4 lesions underwent a complete resection. Subtotal (greater than 80%) excision was achieved in one patient with a grade 3 tumor and six patients with grade 4 tumors. The remaining seven patients with grade 4 adenomas had a Partial (less than 80%) excision. We compare de resection grade versus invasion grade with exact Fisher test. And there is not estadistical difference (p=0.12).. The Knosp classification alone cannot predict the behavior of these tumors. In our experience, despite tumor extension to the cavernous sinus, pituitary macroadenomas can be safely resected with low morbidity and mortality.

Topics: Adenoma; Adult; Aged; Antineoplastic Agents; Cabergoline; Cavernous Sinus; Combined Modality Therapy; Cranial Irradiation; Diabetes Insipidus, Neurogenic; Dose Fractionation, Radiation; Endoscopy; Ergolines; Female; Follow-Up Studies; Humans; Hypophysectomy; Magnetic Resonance Imaging; Male; Meningitis; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Pituitary Neoplasms; Postoperative Complications; Predictive Value of Tests; Prognosis; Prospective Studies; Radiography; Radiotherapy, Adjuvant; Somatostatin; Sphenoid Bone; Treatment Outcome

Treatment of patients with prolactinomas consists primarily of dopamine agonists (DA). Cerebrospinal fluid (CSF) leakage has sporadically been reported in patients with macroprolactinomas treated with short-acting DA such as bromocriptine. Little is known on the incidence of this complication in patients treated with the long-acting D2 specific DA cabergoline. We report three patients with CSF leakage shortly after initiation of cabergoline treatment for macroprolactinoma. All three patients responded rapidly to cabergoline (CAB) by shrinkage of the tumor and release of the optic chiasm compression. The CSF leakage occurred within 10 days after initiation of treatment. CAB treatment was not discontinued. In one patient the CSF leakage ceased spontaneously, with no additional therapy. The second patient had a surgical repair of the CSF fistula, permitting cabergoline to be continued without a recurrence of the CSF leakage. The third patient refused surgical repair of the sellar defect. In this patient the cabergoline dosage was temporarily decreased with no effect on the CSF leakage. Four years later, the CSF leakage is unchanged in this patient, whilst no other complications occurred during the follow-up. No infectious complications occurred in these three patients. In conclusion, patients with large, invasive macroprolactinomas are at risk of CSF leakage during medical treatment with CAB. It is advisable to warn these patients for occurrence of this complication and to monitor them closely especially during the first months of treatment.

Topics: Adult; Aged; Antineoplastic Agents; Cabergoline; Cerebrospinal Fluid Rhinorrhea; Dopamine Agonists; Ergolines; Female; Humans; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma

Prolactin-secreting pituitary adenomas are one of the most common causes of infertility in women. Prolactin plays an important role in lactation and is involved in producing some of the normal mammalian breeding and maternal behaviors. Elevated serum prolactin concentrations can adversely affect the reproductive cycle in females by inhibiting the normal lutenizing hormone surge that stimulates ovulation. A 17-year-old western lowland gorilla (Gorilla gorilla gorilla) presented with low fertility and hyperprolactinemia. An MRI confirmed a pituitary mass and treatment was initiated with cabergoline. Following 8 mo of treatment, mass size decreased and serum prolactin was within normal limits. The gorilla began to engage in normal breeding behavior, and within 6 mo of completing treatment, was pregnant. Hyperprolactinemia, secondary to presumed microprolactinoma, may be more common among breeding-age gorillas than is currently diagnosed and in humans is an easily diagnosed and treatable condition.

Topics: Animals; Antineoplastic Agents; Ape Diseases; Cabergoline; Ergolines; Female; Gorilla gorilla; Hyperprolactinemia; Pituitary Neoplasms; Prolactinoma; Reproduction; Treatment Outcome

The clinical characteristics of 84 patients with pituitary tumour who had troublesome headache were investigated. The patients presented with chronic (46%) and episodic (30%) migraine, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT; 5%), cluster headache (4%), hemicrania continua (1%) and primary stabbing headache (27%). It was not possible to classify the headache according to International Headache Society diagnostic criteria in six cases (7%). Cavernous sinus invasion was present in the minority of presentations (21%), but was present in two of three patients with cluster headache. SUNCT-like headache was only seen in patients with acromegaly and prolactinoma. Hypophysectomy improved headache in 49% and exacerbated headache in 15% of cases. Somatostatin analogues improved acromegaly-associated headache in 64% of cases, although rebound headache was described in three patients. Dopamine agonists improved headache in 25% and exacerbated headache in 21% of cases. In certain cases, severe exacerbations in headache were observed with dopamine agonists. Headache appears to be a significant problem in pituitary disease and is associated with a range of headache phenotypes. The presenting phenotype is likely to be governed by a combination of factors, including tumour activity, relationship to the cavernous sinus and patient predisposition to headache. A proposed modification of the current classification of pituitary-associated headache is given.

Topics: Adenoma; Adult; Aminoquinolines; Antineoplastic Agents, Hormonal; Bromocriptine; Cabergoline; Disability Evaluation; Dopamine Agonists; Ergolines; Female; Headache; Humans; Male; Migraine Disorders; Octreotide; Peptides, Cyclic; Pituitary Neoplasms; Severity of Illness Index; Somatostatin; Time Factors

A 17-year-old boy without a significant past medical history presented with recurrent cluster-like headaches induced by meals for 3 years. Magnetic resonance images showed a pituitary tumor. Just after starting treatment with cabergoline, the headaches resolved completely and the patient has been absolutely free from such headache attacks for 2 years.

Topics: Adolescent; Antineoplastic Agents; Cabergoline; Cluster Headache; Eating; Ergolines; Humans; Male; Pituitary Neoplasms; Prolactinoma; Recurrence; Treatment Outcome

Prolactinomas are rare in children and adolescents but well studied in adults. Dopamine agonists are the treatment of choice for all ages. Bromocriptine is the only agonist approved for use in pediatric patients by the FDA. Cabergoline, a second-generation ergot derivative with a longer half-life, has been used in resistant prolactinomas and as first-line treatment in adults. The authors describe an adolescent boy with a pituitary macroadenoma with an initial prolactin level of 73,777 ng/mL. After failing to respond to bromocriptine and standard-dose cabergoline, he responded well to very high daily doses of cabergoline (1.5 mg daily), with a current prolactin level of 726 ng/mL and notable reduction in tumor size. Escalating doses of cabergoline should be considered in pediatric patients with dopamine-resistant prolactinomas.

Topics: Bromocriptine; Cabergoline; Child; Dopamine Agonists; Ergolines; Humans; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Prolactinoma; Treatment Outcome

Reports suggest that up to 70% of patients with microprolactinomas treated with dopamine agonist therapy may achieve long-term normoprolactinaemic remission following drug withdrawal. Yet, there is no consensus on the duration of therapy nor is therapeutic interruption universally practised. We have assessed remission rates in a large cohort of treatment-naive subjects with microprolactinomas. Subjects received dopamine agonist (DA) therapy with either cabergoline or bromocriptine for a period of 2 to 3 years in the majority of cases, followed by a trial of treatment withdrawal.. Retrospective analysis of clinic records of 89 patients (mean age 32.7 +/- 8.4 years, 84 women and 5 men) who had received either cabergoline (n = 67) (0.5-3 mg weekly) or bromocriptine (n = 22) (2.5-10 mg daily) for a mean duration of 3.1 years.. Following withdrawal of therapy, 57 subjects developed recurrence (64%) and the mean time to recurrence was 9.6 months (range 1-44 months), while 32 subjects (36%) remained in remission beyond 1 year (mean 3.6 years, range 1-7 years). There was no difference in remission rates between subjects treated with cabergoline (n = 21) and bromocriptine (n = 11), but a direct relationship between pretreatment prolactin concentration and risk of recurrent symptomatic hyperprolactinaemia was observed. No subjects developed clinical features to suggest tumour expansion following therapeutic discontinuation.. This study confirms that abrupt withdrawal of chronic dopamine agonist therapy, following 2 to 3 years of treatment is safe and associated with long-term remission in 30-40% of subjects with microprolactinomas. This therapeutic strategy is convenient and applicable in clinical practice.

Topics: Adolescent; Adult; Antineoplastic Agents; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma; Recurrence; Remission Induction; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome

To study somatostatin/dopamine (SS/D) synergy in a human cell system constitutively expressing SS and D receptors (SSR and DR, respectively), we characterized the expression of SSR and DR subtypes in the non-small-cell lung cancer line Calu-6, and then we evaluated the effect on cell proliferation of SS/D chimeric molecules (BIM-23A387 and BIM-23A370), which bind with high affinity both sst(2) and D(2)R, and compared the results with those obtained by using SS-14 and subtype-selective SS analogs (SSA) and D agonists (DA). Because Calu-6 cells produce insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) peptides, which play a role in the autocrine/paracrine control of cell growth, we also investigated the effects of chimeric compounds on secretion and expression of IGF system components. Relative high levels of sst(2) and the long isoform of the D(2)R were detected by real-time RT-PCR and Western blot in Calu-6, together with sst(5) and to a lesser extent sst(3) and D(4)R. BIM-23A387 and BIM-23A370 significantly inhibited growth of Calu-6, whereas IGF-IGFBP secretion or expression was unaffected, suggesting a direct inhibitory effect. The inhibition of cell growth, measured by both [(3)H]thymidine incorporation and cell count, was significantly lower when individual SSA and DA control peptides or subtype-specific SSA and DA were tested. BIM-23A370 was more potent than BIM-23A387 (P < 0.001). These findings show that SS/D chimeras can inhibit Calu-6 proliferation in an IGF-independent manner and suggest that this enhanced potency might be because of the induction of SSR/DR dimerization. The Calu-6 cell line, constitutively expressing SSR and DR, provides a suitable model to elucidate the mechanism of action of SSA and DA on regulation of cell growth and to characterize the interaction between SSR and DR.

Topics: Acromegaly; Cabergoline; Cell Division; Cell Line, Tumor; Dopamine; Ergolines; Gene Expression; Humans; Insulin-Like Growth Factor Binding Protein 2; Insulin-Like Growth Factor II; Lung Neoplasms; Peptides, Cyclic; Pituitary Neoplasms; Receptors, Dopamine; Receptors, Somatostatin; Recombinant Fusion Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Somatostatin

Topics: Adult; Antineoplastic Agents; Cabergoline; Constriction, Pathologic; Ergolines; Female; Fingers; Humans; Peripheral Vascular Diseases; Pituitary Neoplasms; Prolactinoma

Surgery for prolactinoma patients is usually reserved for those who are intolerant of or have an inadequate response to medication. We report the results of surgical treatment in these patients.. We retrospectively analyzed a consecutive series of patients with histopathologically confirmed prolactinomas; two patients treated with craniotomy and 77 patients with prolactinomas treated by transsphenoidal surgery between 1993 and 2003. We evaluated symptomatic patients who did not tolerate or did not respond to dopamine agonist therapy (persistent hyperprolactinemia and/or no shrinkage of tumor mass). We report remission rates, prolactin levels, and medications either not tolerated or ineffective.. Eighteen patients were intolerant of medical therapy (nine with macroadenomas and nine with microadenomas). Postoperatively, 12 patients (67%) achieved normalization of prolactin and relief of symptoms from surgery alone. Sixty-one patients were resistant to dopamine agonist therapy (45 with macroadenomas and 16 with microadenomas). Forty-six patients had both elevated prolactin levels and no shrinkage. 22 patients (36%) achieved normal postoperative prolactin levels. Ten of the remaining 39 patients required adjunctive medical therapy to maintain normal prolactin levels and relief of symptoms.. Remission through surgery was achieved in 67% (12 of 18 patients, 4 macroadenomas and 8 microadenomas) of prolactinoma patients who fail medical therapy with dopamine agonists because of intolerance to medication. Remission was also achieved in 36% (22 of 61 patients, 12 macroadenomas and 10 microadenomas) of patients who demonstrated resistance to dopamine agonist medication.

Topics: Adult; Aged; Bromocriptine; Cabergoline; Dopamine Agonists; Drug Resistance; Ergolines; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Pergolide; Pituitary Neoplasms; Prolactin; Prolactinoma; Remission Induction; Retrospective Studies; Treatment Outcome

We report a case of a 10-y-old boy who presented with persistent headache and was found to have a giant prolactinoma. Laboratory evaluation revealed markedly elevated prolactin (PRL) level, thyroid-stimulating hormone (TSH) deficiency, and elevated insulin-like growth factor-I (IGF-I). He had normal random growth hormone (GH) but non-suppressible GH during oral glucose tolerance test (OGTT). Cabergoline treatment was initiated and was well tolerated. Therapy successfully reduced PRL levels, normalized IGF-I levels, and reduced tumor size.. Our patient presented with a GH-PRL-secreting tumor. Dopamine agonists are recommended as the treatment of choice for prolactinomas. However, there should be careful attention to GH status when treating GH-PRL-secreting tumor with dopamine agonists alone. IGF-I levels should be followed in all patients with prolactinoma, even in those with normal basal GH concentrations, because of the possibility of GH co-secretion.

Topics: Antineoplastic Agents; Cabergoline; Child; Ergolines; Glucose Tolerance Test; Humans; Hypothyroidism; Insulin-Like Growth Factor I; Male; Pituitary Neoplasms; Prolactinoma

Topics: Antineoplastic Agents; Cabergoline; Ergolines; Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactin; Prolactinoma; Withholding Treatment

Topics: Antineoplastic Agents; Cabergoline; Ergolines; Follow-Up Studies; Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactin; Prolactinoma; Recurrence; Withholding Treatment

Nerve growth factor (NGF) is known to play a role as a circulating neurokine, integrating signals from the neuro-immuno-endocrine system. The ability of NGF to activate the pituitary-adrenocortical axis, together with the increase of its serum concentration in pregnancy and lactation, supports the hypothesis that NGF is secreted by the pituitary gland and plays a role as modulator of endocrine functions. Evidence obtained both in vitro and in vivo in experimental animal models suggests that lactotroph cells secrete both prolactin (PRL) and NGF. Furthermore, in previous studies we demonstrate that cell lines derived from dopamine (DA)-sensitive human prolactinomas express high levels of NGF messenger RNA and protein. On these basis, we studied serum NGF concentrations in female patients with microprolactinoma (n = 4) and in control women (n = 5). PRL and NGF were measured at the diagnosis, during the thyrotropin releasing hormone (TRH) test and after the therapy with DA D2 receptor agonist cabergoline (0.25 mg, twice a week). Results obtained suggested that hyperprolactinemia (70.3+/-8.4 ng/ml) paralleled markedly higher NGF levels (58.4+/-18.7 pg/ml) compared to controls (PRL 8.7+/-3.2 ng/ml, NGF 8.4+/-1.3 pg/ml). Serum concentrations of NGF and PRL during the TRH test were closely associated (r = 0.943, p < 0.01). Cabergoline therapy normalized PRL (7.9+/-3.6 ng/ml) and induced a significant decrease of NGF levels (12.5+/-4.9 pg/ml). In conclusions, data reported here indicated that, in human microprolactinomas, NGF is released in the bloodstream paralleling PRL-secretion and it is modulated by a neurotransmitter-regulated mechanism, since the normalization of PRL elicited by the DA D2 receptor agonist cabergoline induced a significant decrease of serum NGF as well.

Topics: Adult; Cabergoline; Dopamine Antagonists; Ergolines; Female; Humans; Immunoenzyme Techniques; Nerve Growth Factor; Pituitary Neoplasms; Prolactin; Prolactinoma; Stimulation, Chemical; Thyrotropin-Releasing Hormone

The aim of this study was to correlate dopamine receptors and D(2) isoform expression with the cabergoline effect on alpha-subunit secretion in vitro and tumor mass in vivo in clinically nonfunctioning pituitary tumors. Eighteen patients were subjected to neurosurgery, and a tumor sample was used for dopamine receptor and D(2) isoform expression evaluation by RT-PCR and the in vitro functional studies. After neurosurgery, nine of 18 patients with persistent tumor were treated with cabergoline and tumor mass was evaluated before and after 1 yr treatment. D(2) receptor was expressed in 67% of cases. D(2long) was found in 50%, D(2short) in 17%, and both D(2) isoforms in 33% of cases. D(4) receptor was also expressed in 17% of cases. The in vitro inhibition of alpha-subunit concentration was found in 56% of cases and was associated with D(2) expression (chi(2) = 5.6; P < 0.05). After 1 yr of cabergoline treatment, tumor shrinkage was evident in 56% of patients and was associated with D(2) expression (chi(2) = 5.6; P < 0.05). The expression of D(2short) rather than D(2long) isoform is associated with the most favorable response of the tumor to cabergoline treatment. In conclusion, this study demonstrates D(2) receptor expression and function in nearly 70% of cases, suggesting a role of this drug in the treatment schedule of clinically nonfunctioning pituitary tumors.

Topics: Adult; Antineoplastic Agents; Cabergoline; Dopamine Agonists; Dose-Response Relationship, Drug; Ergolines; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Protein Isoforms; Protein Subunits; Receptors, Dopamine; Receptors, Dopamine D2; Receptors, Dopamine D4; Reverse Transcriptase Polymerase Chain Reaction; Treatment Outcome; Tumor Cells, Cultured; Visual Fields

Topics: Antineoplastic Combined Chemotherapy Protocols; Brain; Bromocriptine; Cabergoline; Carotid Arteries; Dopamine Agonists; Ergolines; Horner Syndrome; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Migraine Disorders; Neoplasm Recurrence, Local; p-Hydroxyamphetamine; Pituitary Neoplasms; Prolactin; Prolactinoma; Remission Induction

The role of dopamine agonist treatment in corticotroph pituitary tumors is controversial. The aim of this study was to evaluate D(2) receptor expression in 20 corticotroph pituitary tumors and to correlate it to the in vitro effect of dopamine agonists on ACTH secretion and the in vivo effect of short-term cabergoline treatment on cortisol secretion. D(2) expression was evaluated by receptor-ligand binding, immunohistochemistry, and RT-PCR. A 50% or more decrease in daily urinary cortisol levels was considered a significant clinical response. At receptor-ligand binding, specific binding of [(125)I]epidepride was found in 80% of cases. At immunohistochemistry, specific D(2) immunostaining was found in 75% of cases. D(2) expression was found in 83.3% of cases (D(2long) in 40%, D(2short) in 20%, and both in 40%) by RT-PCR. Significant in vitro inhibition of ACTH secretion was found in 100% of D(2)-positive cases, but not in 100% of D(2)-negative cases by either bromocriptine or cabergoline. A significant in vivo inhibition of cortisol secretion after 3-month cabergoline treatment was found in 60%, although a normalization of cortisol secretion was found in 40% of cases. All cabergoline-responsive cases were associated with D(2) expression, whereas all noncabergoline-responsive cases but one were not associated with D(2) expression. In conclusion, functional D(2) receptors were expressed in approximately 80% of corticotroph pituitary tumors. The effectiveness of cabergoline in normalizing cortisol secretion in 40% of cases supports its therapeutic use in the management of Cushing's disease.

Topics: Adenoma; Adrenocorticotropic Hormone; Adult; Antineoplastic Agents; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Immunoblotting; Immunohistochemistry; Male; Middle Aged; Pituitary Neoplasms; Radioligand Assay; Receptors, Dopamine D2; Reverse Transcriptase Polymerase Chain Reaction; Tumor Cells, Cultured

A 71-year-old man was referred because of memory loss. Magnetic resonance imaging showed a pituitary macroadenoma associated with hydrocephalus. Marked hyperprolactinaemia was present. After 2 months of cabergoline therapy, magnetic resonance imaging showed tumour shrinkage with resolution of the hydrocephalus. We report, for the first time, the adequate and rapid clinical response of a macroprolactinoma-induced symptomatic hydrocephalus in an elderly man to a low and once-a-week dose of cabergoline therapy. Medical therapy with this dopamine agonist in this particular patient was so effective that ventriculo-peritoneal shunting could be avoided.

Topics: Adenoma; Aged; Cabergoline; Dopamine Agonists; Ergolines; Humans; Hydrocephalus; Male; Pituitary Neoplasms; Prolactinoma

In 1970 a 20 year old woman presented with a pituitary chromophobe adenoma for which she underwent transfrontal pituitary surgery. In 1978 she had to be reoperated on because of local tumour recurrence, resulting in hypopituitarism. Bromocriptine (5 mg/day) was given for 15 years, but the plasma prolactin levels remained elevated. In 2000 the patient presented with signs and symptoms suggestive of a spinal cord lesion at the mid-thoracic level. A magnetic resonance imaging (MRI) scan showed an extensive leptomeningeal mass extending from the brainstem to L5, with a thoracic syringomyelia at the T7-T8 level. The plasma prolactin level was very high (5114 microg/l). A biopsy showed the presence of a metastasised prolactinoma. On administration of high dose cabergoline, 0.5 mg twice a day orally, the plasma prolactin levels decreased within one month and then normalised within 26 months. Tumour load reduced considerably but unfortunately, her signs and symptoms did not improve. This case illustrates that a high dose dopamine agonist might be an important therapeutic option in patients with a metastasised prolactinoma.

Topics: Adult; Antineoplastic Agents; Brain Stem Neoplasms; Cabergoline; Ergolines; Female; Humans; Hyperprolactinemia; Magnetic Resonance Imaging; Pituitary Neoplasms; Prolactinoma; Treatment Outcome

Topics: Antineoplastic Agents; Cabergoline; Dopamine Agonists; Ergolines; Humans; Neoplasm Recurrence, Local; Pituitary Neoplasms; Prolactin; Prolactinoma

A woman affected by Cushing's disease underwent bilateral adrenalectomy followed by radiotherapy of the hypothalamic-pituitary area when she was 18 years old. Thereafter, she used hydrocortisone acetate replacement therapy (35.5 mg divided into two daily doses). At the age of 26 years, the patient exhibited the clinical signs of the Nelson's syndrome, i.e. skin and gingival hyperpigmentation accompanied by amenorrhea, and elevated ACTH plasma levels (2,850 pg/ml, normal range 15-80 pg/ml). The magnetic resonance imaging (MRI) analysis of the sellar region evidenced a pituitary macroadenoma, measuring 14 x 13 mm. The patient was initially treated with cyproheptadine hydrochloride (12 mg/day) for 18 months. There was a partial improvement of the symptoms, with a reduction of the ACTH plasma levels to 112 pg/ml, but without any modification of the tumor mass. Due to sleepiness and weight gain, the cyproheptadine treatment was interrupted and substituted by a cabergoline (0.5 mg twice a week) therapy. Soon after cabergoline was applied an improvement of the clinical symptoms and signs was observed such as a regression of the tumor mass and the normalization of the ACTH plasma titers (38 pg/ml). Later, cabergoline was substituted by bromocriptine (7.5 mg/day) and the plasma levels of ACTH increased again (247 pg/ml), and headache and cutaneous hyperpigmentation were recorded. When cabergoline was reintroduced there was a clinical improvement and normalization of ACTH plasma levels (64 pg/ml). The MRI analysis of the sella region demonstrated a complete remission of the pituitary adenoma. The results obtained show for the first time that a long-term treatment with cabergoline also brings about a complete remission of Nelson's syndrome in the presence of a pituitary macroadenoma.

Topics: Adenoma; Adrenalectomy; Adrenocorticotropic Hormone; Adult; Bromocriptine; Cabergoline; Cyproheptadine; Dopamine Agonists; Ergolines; Female; Hormone Replacement Therapy; Humans; Magnetic Resonance Imaging; Nelson Syndrome; Pituitary Neoplasms

Dopamine agonists have been used as adjunctive therapy for acromegaly for many years, but relatively few studies have assessed the efficacy of a newer agonist, cabergoline. Some data suggest that cabergoline may be more effective than bromocriptine, in particular for those patients whose tumors secrete both growth hormone and prolactin. In order to assess this possibility further, we have evaluated the biochemical response to cabergoline therapy in patients with acromegaly at our center. We describe first an unusual patient who presented with a pituitary macroadenoma secreting both GH and prolactin. At presentation he had elevated levels of growth hormone 6.0 microg/L, IGF-I, 722 ng/ml, and prolactin, 6000 ng/ml. Cabergoline therapy alone was highly effective in this patient and normalized his levels of all three hormones and his gonadal function as well as produced significant shrinkage of his pituitary tumor. Fourteen other patients with more typical, active postoperative acromegaly were administered cabergoline in a 6-month, open label, dose-escalation study. Mean baseline GH was 1.3 +/- .23 ng/ml and fell to a nadir of 0.85 +/- .18 ng/ml on cabergoline therapy (p = 0.03). Mean baseline IGF-I was 520 +/- 45.2 ng/ml and fell to a mean nadir during cabergoline therapy of 368 +/- 29.8 ng/ml (p = 0.0013). At the completion of the cabergoline therapy study period, however, mean IGF-I was 453 +/- 46 ng/ml, not significantly lower than the baseline value (p = 0.11). No changes in tumor sizes occurred on cabergoline therapy. Eight of 14 patients achieved a normal IGF-I at some point during the 24 weeks study period, but the efficacy of cabergoline waned with time as only 3 of 14 (21%) of patients had a persistently normal IGF-I with up to 18 months of cabergoline therapy. Six patients had modest hyperprolactinemia at diagnosis (26-142 ng/ml) and 5 patients had positive immunohistochemical staining of their tumor for prolactin, but in neither of these small groups was cabergoline therapy more effective at normalizing IGF-I than in those patients with apparently pure GH secreting tumors. Three of 14 patients (21%) had side effects that limited therapy. A trial of cabergoline as adjunctive therapy may be considered in select patients with mild disease and small tumor residuals, but the expectation for biochemical control in these patients needs to be kept low, even for tumors that co-secrete GH and prolactin.

Topics: Acromegaly; Adult; Antineoplastic Agents; Biomarkers; Cabergoline; Ergolines; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Magnetic Resonance Imaging; Male; Pituitary Gland; Pituitary Neoplasms; Prolactin

The present case involves a 47-yr-old woman with Cushing's disease due to pituitary macroadenoma. The patient had suffered from hypertension and obesity for two yr. Her serum cortisol levels were moderately elevated throughout the observation period, and dexamethasone failed to suppress the cortisol secretion. Plasma ACTH levels were markedly high (>100 pg/ml) and did not respond to CRH provocation. Gel filtration analysis of the patient's plasma detected the existence of big ACTH molecules, which eluted with a peak of authentic 1-39 ACTH. Cranial magnetic resonance imaging (MRI) revealed a 3 cm pituitary tumor occupying the sellar region and right cavernous sinus with diffuse enhancement by gadolinium. The pituitary mass was removed by transsphenoidal surgery, and was pathologically identified as compatible to ACTH-producing pituitary adenoma by immunohistochemistry. RT-PCR analysis of total cellular RNA extracted from the resected adenoma revealed a relatively high expression level of dopamine D2 receptor (D2R) mRNA. Therefore, a long-acting D2R agonist, cabergoline (0.25 to 0.5 mg/week), was administered for the remnant adenoma, which gradually reduced ACTH levels in 90 days. In addition, cranial MRI exhibited shrinkage of the remnant pituitary mass after a 6-month treatment with cabergoline. This case demonstrates the efficacy of cabergoline to treat Cushing's disease caused by pituitary macroadenoma secreting aberrant ACTH molecules.

Topics: Adenoma; Adrenocorticotropic Hormone; Cabergoline; Dopamine Agonists; Ergolines; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Receptors, Dopamine D2; Treatment Outcome

Pituitary adenomas are rare in young patients. Prolactinomas are the most common type of pituitary adenomas in children older than 12 years, occurring more often in girls, at a 4.5:1 female-to-male ratio. The clinical presentation may vary according to the age and sex of the patient. Pituitary apoplexy is a rare life-threatening condition caused by a sudden infarction or hemorrhagic necrosis of the pituitary containing an adenoma. A wide variety of conditions can trigger apoplexy such as pituitary irradiation, general anesthesia, traumatic head injury, pituitary stimulatory tests and a wide variety of medications including bromocriptine. We report a case of a 16-year-old male patient with puberty arrest harboring a macroprolactinoma, who developed a sudden clinical picture of pituitary apoplexy during the 12th month of treatment with cabergoline.

Topics: Adenoma; Adolescent; Antineoplastic Agents; Cabergoline; Ergolines; Humans; Hypopituitarism; Magnetic Resonance Imaging; Male; Pituitary Diseases; Pituitary Neoplasms; Prolactin; Prolactinoma; Stroke

Dopamine agonists have been shown to reduce growth hormone secretion in some patients with acromegaly, but their effect on adenoma size has not been well appreciated. We describe a 69 year-old woman with acromegaly caused by a somatotroph macroadenoma who received primary treatment with the dopamine agonist cabergoline. Two months after beginning cabergoline, she experienced soft tissue regression and normalization of the serum IGF-1 concentration that persisted for the remainder of the 25 months of observation. By 13 months, the volume of the adenoma by MRI was 28% of its pretreatment size, and by 25 months it was 24%. This case demonstrates that when cabergoline decreases substantially the serum IGF-1 concentration of a patient with a somatotroph macroadenoma, the adenoma size may also decrease substantially. This demonstration, plus the ease of oral administration, suggests that it would be worthwhile to study systematically the effect of cabergoline on the size of somatotroph macroadenomas.

Topics: Adenoma; Aged; Antineoplastic Agents; Biomarkers, Tumor; Cabergoline; Ergolines; Female; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Pituitary Neoplasms; Treatment Outcome

To review clinical presentation, management and outcomes following different therapies in patients with pituitary apoplexy.. Retrospective analysis of case-records of patients with classical pituitary apoplexy treated in our hospitals between 1983-2004.. Forty-five patients (28 men; mean age 49 years, range 16-72 years) were identified. Only 8 (18%) were known to have pituitary adenomas at presentation. Thirty-four (81%) patients had hypopituitarism at presentation. CT and MRI identified pituitary apoplexy in 28% and 91% cases, respectively. Twenty-seven (60%) patients underwent surgical decompression, whilst 18 (40%) were managed conservatively. Median time from presentation to surgery was 6 days (range 1-121 days). Patients with visual field defects were more likely than those without these signs to be managed surgically (p = 0.01). Complete or near-complete resolution occurred in 93% (13/14), 94% (15/16) and 93% (13/14) of the surgically treated patients with reduced visual acuity, visual field deficit and ocular palsy, respectively. All patients with reduced visual acuity (4/4), visual field deficit (4/4) and ocular palsy (8/8) in the conservative group had complete or near-complete recovery. Only 5 (19%) patients in the surgical group and 2 (11%) in the conservative group had normal pituitary function at follow up. One (4%) patient in the surgical group and 4 (22%) in the conservative group had a recurrence of pituitary adenoma.. This large series suggests that the patients with classical pituitary apoplexy, who are without neuro-ophthalmic signs or exhibit mild and non-progressive signs, can be managed conservatively in the acute stage.

Topics: Acute Disease; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Cabergoline; Combined Modality Therapy; Decompression, Surgical; Ergolines; Female; Humans; Hypopituitarism; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Apoplexy; Pituitary Gland; Pituitary Neoplasms; Retrospective Studies; Tomography, X-Ray Computed; Treatment Outcome; Vision Disorders

Headache is a common problem in patients with pituitary tumours. Small pituitary lesions can cause debilitating headache, suggesting that the size of the pituitary tumour may not be the only causal factor in pituitary-related headache. We present two cases of prolactinoma-associated headache. The first case has a clinical diagnosis of short-lasting unilateral headache attacks with conjunctival injection and tearing (SUNCT). The second case has a clinical diagnosis of hemicrania continua and idiopathic stabbing headache. In each case, the administration of dopamine agonists has led to an exacerbation of symptoms. We review the relevant literature to understand the pathophysiological implications of these cases.

Topics: Adult; Amenorrhea; Anti-Inflammatory Agents, Non-Steroidal; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Female; Headache; Humans; Indomethacin; Magnetic Resonance Imaging; Pituitary Neoplasms; Prolactin; Prolactinoma; Radiography

Topics: Adult; Antineoplastic Agents; Cabergoline; Dopamine Agonists; Ergolines; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Prolactinoma; Time Factors

A 46-year-old woman was referred to the neurosurgery department for treatment of a macroadenoma of the pituitary. She had complained of recurrent galactorrhoea for 7 years; a hysterectomy was performed 4 years ago. The clinical investigation was unremarkable, except for a slight galactorrheoa on both sides.. The endocrinological work-up revealed a moderately elevated prolactin level of 3133 mU/l (147 ng/ml) with intact pituitary functions. She had no visual impairment and the MRI depicted a pituitary tumor with a maximal diameter of 1.9 cm and both intra- and suprasellar extension.. The diagnosis of a nonfunctioning macrodenoma with functional hyperprolactinemia was made and a selective transsphenoidal adenomectomy was performed. The primary histology showed a chromophobe adenoma. However, additional immunohistological investigations revealed distinct staining for prolactin. In the meantime, because of persistent galactorrhea and elevated prolactin levels, treatment with cabergolin 0.5 mg/week was started. This stopped galactorrhea and normalized the prolactin levels. A follow-up MRI after 3 months of treatment showed a significant shrinkage of the residual tumor.. This case demonstrates that the differential diagnosis of macroprolactinoma with low secretory activity and functional hyperprolactinemia is very difficult preoperatively in individual cases. This is relevant because macroprolactinomas with low secretory activity can also be treated successfully with dopamine agonists. We therefore suggest a drug treatment trial with dopamine agonists in all macroadenoms with hyperprolactinemia, particularly in those with prolactin levels above 2000 mU/l (100 ng/ml).

Topics: Cabergoline; Diagnosis, Differential; Ergolines; Female; Follow-Up Studies; Humans; Hyperprolactinemia; Magnetic Resonance Imaging; Middle Aged; Neoplasm, Residual; Pituitary Gland; Pituitary Neoplasms; Postoperative Complications; Prolactinoma

The term 'giant prolactinoma' can be used for tumours larger than 4 cm in diameter and/or with massive extrasellar extension. Cabergoline (CAB), a long-lasting dopamine agonist (DA), safe and well tolerated, is effective in normalizing PRL levels and inducing tumour shrinkage in micro- and macroprolactinomas. The purpose of this prospective study was to evaluate the efficacy and safety of CAB also for giant prolactinomas.. Ten men with giant prolactinomas with a median age of 44.8 years were treated with CAB. Before CAB, four patients had previously undergone transsphenoidal surgery without modifying the parasellar extension of the tumour or their visual defects. Pretreatment serum prolactin (PRL) levels ranged between 1230 and 22 916 micro g/l (mean +/- SEM: 5794 +/- 1996) and tumour volume was between 21.8 and 105.5 cm3 (mean +/- SEM: 50.7 +/- 8.8). CAB was administered at an initial low dose of 0.5 mg three times a week and, in five patients who did not achieve serum PRL normalization, the dose was progressively increased up to 10.5 mg/week. The duration of treatment was 13-68 months (mean 38.9). PRL levels and pituitary target organ hormones were assayed before, after 30 days and then every 3 months after the beginning of CAB treatment. Magnetic resonance imaging (MRI) was carried out before, after 1-3 months, after 6 months and then every 10-12 months to evaluate tumour shrinkage.. In every patient, a significant PRL decrease (P = 0.0086) of at least 96% of the pretreatment values occurred (from 5794 +/- 1996 to 77 +/- 38, mean +/- SEM); a persistent normalization of PRL levels was achieved in five out of 10 patients (50%) beginning from the first 3-6 months of CAB treatment (only one patient needed 12 months of therapy). A significant tumour shrinkage (P = 0.0003) was achieved after 12 months of therapy in nine out of 10 patients (90%), with a volume reduction greater than 95% in three, of 50% in four and 25% in two patients. Tumour volume decreased from 50.7 +/- 8.8 to 28.6 +/- 9.4 and then to 22.3 +/- 8.8 cm3 (mean +/- SEM) after 6 and 12 months of CAB treatment, respectively. An improvement of visual field defects (VFD) was obtained in six of the seven patients presenting visual impairment before CAB treatment. Among the eight patients presenting libido and potency (L-P) failure, five normalized their PRL levels. In two of these a complete restoration of libido and potency was observed. Three patients with secondary hypoadrenalism and a patient with secondary hypothyroidism were treated with substitutive therapy during all the study time. The drug was well tolerated by all patients and no one discontinued the therapy.. These data suggest that, in giant, aggressive prolactinomas, CAB represents a first-line therapy effective in reducing PRL levels and determining tumour shrinkage.

Topics: Adrenal Glands; Adult; Aged; Antineoplastic Agents; Cabergoline; Erectile Dysfunction; Ergolines; Humans; Hypothyroidism; Libido; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Prolactin; Prolactinoma; Vision Disorders

Whether the withdrawal of treatment in patients with nontumoral hyperprolactinemia, microprolactinomas, or macroprolactinomas is safe and effective has been unclear. We performed an observational, prospective study of cabergoline (a dopamine-receptor agonist) withdrawal in such patients.. The study population included 200 patients--25 patients with nontumoral hyperprolactinemia, 105 with microprolactinomas, and 70 with macroprolactinomas. Withdrawal of cabergoline was considered if prolactin levels were normal, magnetic resonance imaging (MRI) showed no tumor (or tumor reduction of 50 percent or more, with the tumor at a distance of more than 5 mm from the optic chiasm, and no invasion of the cavernous sinuses or other critical areas), and if follow-up after withdrawal could be continued for at least 24 months.. Recurrence rates two to five years after the withdrawal of cabergoline were 24 percent in patients with nontumoral hyperprolactinemia, 31 percent in patients with microprolactinomas, and 36 percent in patients; with macroprolactinomas. Renewed tumor growth did not occur in any patient; in 10 female patients (22 percent) and 7 male patients (39 percent) with recurrent hyperprolactinemia, gonadal dysfunction redeveloped. In all diagnostic groups, prolactin levels at the time of recurrence were significantly lower than at diagnosis (P<0.001). The Kaplan-Meier estimated rate of recurrence at five years was higher among patients with macroprolactinomas and those with microprolactinomas who had small remnant tumors visible on MRI at the time of treatment withdrawal than among patients whose MRI scans showed no evidence of tumor at the time of withdrawal (patients with macroprolactinomas, 78 percent vs. 33 percent, P=0.001; patients with microprolactinomas, 42 percent vs. 26 percent, P=0.02).. Cabergoline can be safely withdrawn in patients with normalized prolactin levels and no evidence of tumor. However, because the length of follow-up in our study was insufficient to rule out a delayed increase in the size of the tumor, we suggest that patients be closely monitored, particularly those with macroprolactinomas, in whom renewed growth of the tumor may compromise vision.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Hyperprolactinemia; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Prospective Studies; Recurrence; Withholding Treatment

Macroprolactinomas predominate in males in comparison to microprolactinomas, with greater trend to invasiveness than in females. The clinical treatment has been the first option to prolactinomas, in both macro and microadenomas, irrespective the sex. We compared clinical presentation, prolactin levels, neuroradiologic invasiveness and prolactinemia response of 23 men with prolactinomas subjected to clinical therapy (group 1) with 19 who went also through surgical and/or radiotherapeutic treatment (group 2). The statistical analysis was done by the tests of chi-square or exact of Fisher, in order to compare proportions, and by t of Student or Mann-Whitney, in order to compare means. The level of significance adopted was 5% (p<0.05). The two groups were similar regarding age (p=0.23), period between start of the first symptom and diagnosis (p=0.82), prolactin levels before treatment (p=0.41) and invasive macroadenomas proportion (p=0.096). There was significantly greater percentage of headache (p=0.009) and visual deficit (p=0.025) in group 2, as well as the drug usage (p=0.007) and observation (p=0.0005) periods were superior in this group. The variations of prolactin levels before and after therapy (p=0.49) as well as the percentage of prolactin normalization (p=0.20) did not show any significant difference when comparing the two groups. We conclude, emphasizing the relevance of precocious prolactinoma diagnostic in men, because of the demonstrated morbidity. We strengthen the use of dopamine agonist as the first therapeutic option irrespective the adenoma size.

Topics: Adolescent; Adult; Age of Onset; Biomarkers; Bromocriptine; Cabergoline; Chi-Square Distribution; Dopamine Agonists; Ergolines; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Staging; Pituitary Neoplasms; Prolactin; Prolactinoma; Statistics, Nonparametric; Treatment Outcome

We describe herein a 38 year old male who complained of persistent cephalalgias during six months which were associated to hyperprolactinemia and a pituitary macroprolactinoma shown by MRI. The patient was treated with cabergoline (0.5 mg/week) and remained asymptomatic for a year. The last MRI showed a normal pituitary.

Topics: Adult; Antineoplastic Agents; Cabergoline; Ergolines; Humans; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Prolactinoma

Most prolactinomas respond rapidly to low doses of dopamine agonists. Occasionally, stepwise increases in doses of these agents are needed to achieve gradual prolactin (PRL) reductions. Approximately 50% of treated men remain hypogonadal, yet testosterone replacement may stimulate hyperprolactinemia. A 34-yr-old male with a pituitary macroadenoma was found to have a PRL level of 10,362 micro g/liter and testosterone level of 3.5 nmol/liter. Eleven months of dopamine agonist therapy at standard doses lowered PRL levels to 299 micro g/liter. Subsequent stepwise increases in cabergoline (3 mg daily) further lowered PRL levels to 71 micro g/liter, but hypogonadism persisted. Initiation of testosterone replacement resulted in a rise and discontinuation in a fall of PRL levels. Aromatization of exogenous testosterone to estradiol and subsequent estrogen-stimulated PRL release was suspected. Concomitant use of cabergoline with the aromatase inhibitor anastrozole after resuming testosterone replacement resulted in the maintenance of testosterone levels and restoration of normal sexual function, without increasing PRL. Ultimately, further reduction in PRL on this therapy permitted endogenous testosterone production. Thus, novel pharmacological maneuvers may permit successful medical treatment of some patients with invasive macroprolactinomas.

Topics: Adult; Anastrozole; Aromatase Inhibitors; Bromocriptine; Cabergoline; Dopamine Agonists; Enzyme Inhibitors; Ergolines; Hormone Replacement Therapy; Humans; Magnetic Resonance Imaging; Male; Nitriles; Pituitary Neoplasms; Prolactin; Prolactinoma; Sexual Dysfunction, Physiological; Testosterone; Treatment Outcome; Triazoles

Topics: Cabergoline; Dopamine Agonists; Ergolines; Humans; Pituitary Neoplasms; Prolactinoma; Retrospective Studies; Thyrotropin; Thyroxine

McCune-Albright syndrome (MAS) is a disorder characterized by the triad of café-au-lait skin pigmentation, polyostotic fibrous dysplasia of bone, and hyperfunctioning endocrinopathies, including GH excess. The molecular etiology of the disease is postzygotic activating mutations of the GNAS1 gene product, G(s)alpha. The term gsp oncogene has been assigned to these mutations due to their association with certain neoplasms. The aim of this study was to estimate the prevalence of GH excess in MAS, characterize the clinical and endocrine manifestations, and describe the response to treatment. Fifty-eight patients with MAS were screened, and 22 with stigmata of acromegaly and/or elevated GH or IGF-I underwent oral glucose tolerance testing. Twelve patients (21%) had GH excess, based on failure to suppress serum GH on oral glucose tolerance test, and underwent a TRH test, serial GH sampling from 2000-0800 h, and magnetic resonance imaging of the sella. We found that vision and hearing deficits were more common in patients with GH excess (4 of 12, 33%) than those without (2 of 56, 4%). Of interest, patients with a history of precocious puberty and GH excess who had reached skeletal maturity achieved normal adult height despite a history of early epiphyseal fusion. All 9 patients tested had an increase in serum GH after TRH, 11 of 12 (92%) had hyperprolactinemia, and all 8 tested had detectable or elevated nighttime GH levels. Pituitary adenoma was detected in 4 of 12 (33%) patients. All patients with elevated IGF-I levels were treated with cabergoline (7 patients), long-acting octreotide (LAO; 8 patients), or a combination of cabergoline and LAO (4 patients). In six of the seven patients (86%) treated with cabergoline, serum IGF-I decreased, but not to the normal range. In the eight patients treated with LAO alone, IGF-I decreased, and, in four, returned to the normal range. The remaining 4 patients were treated with a combination of cabergoline and LAO. For them, symptoms of GH excess diminished, and IGF-I decreased further, but did not enter the normal range. GH excess is common in MAS and results in a distinct clinical phenotype characterized by inappropriately normal stature, TRH responsiveness, prolactin cosecretion, small or absent pituitary tumors, a consistent but inadequate response to treatment with cabergoline, and an intermediate response to LAO.

Topics: Adenoma; Antineoplastic Agents; Body Height; Cabergoline; DNA Mutational Analysis; Ergolines; Fibrous Dysplasia, Polyostotic; GTP-Binding Protein alpha Subunits, Gs; Human Growth Hormone; Insulin-Like Growth Factor I; Magnetic Resonance Imaging; Octreotide; Pituitary Neoplasms

The differential diagnosis of tumors at the base of the skull comprises meningiomas, neurinomas, gliomas, metastatic carcinomas, chordomas, epidermoids, and pituitary adenomas. About half of the pituitary adenomas are prolactinomas which are unique in a sense that medical therapy causes rapid tumor shrinkage and symptomatic improvement. We report on two patients in which the diagnosis of an invasive macroprolactinoma was masked by apparently low prolactin levels caused by a high-dose hook effect in the chemiluminometric assay. The first case a 49 year old male with impairment of hearing on the left side was presented in the Department of Otorhinolaryngology. A massive invasively growing tumor was demonstrated on a cranial MRI. Endocrine tests revealed normal pituitary function and normoprolactinemia. The patient underwent debulking surgery, occipitocervical fusion because of destruction of the first cervical vertebra and subsequent irradiation. The histopathological diagnosis was invasive prolactinoma. A repeat prolactin (PRL) sample, which was assayed using serial dilutions, revealed a real PRL level of 89,700 ng/ml. Dopamine agonist therapy was initiated under which PRL levels declined in parallel with tumor size. The second case a 40 year old male was presented with acute visual loss. Cranial MRI showed a large tumor at the base of the skull. Based on a transnasal biopsy, the preliminary diagnosis was a poorly differentiated carcinoma for which emergency irradiation was performed. Endocrine tests demonstrated partial hypopituitarism and moderate hyperprolactinemia. Hydrocortisone was substituted and dopamine agonist therapy was started because of moderate hyperprolactinemia. The final histopathological diagnosis was invasive prolactinoma. A repeat PRL sample assayed in serial dilution demonstrated an apparent rise in PRL with a maximum value of 6,460 ng/ml. Under dopamine agonist therapy, PRL declined to normal values, tumor size decreased and cranial nerve palsies disappeared. The apparently falsely low prolactin levels in the initial work-up of both patients were caused by a high-dose hook effect in the PRL assay. Serial dilutions of serum PRL samples is, therefore, mandatory in the diagnostic work-up of patients with large invasive tumors at the base of the skull. This avoids unnecessary aggressive and dangerous treatment like surgery or radiotherapy in cases where pharmacological treatment may be the choice.

Topics: Adult; Cabergoline; Dopamine Agonists; Ergolines; False Negative Reactions; Headache; Humans; Immunohistochemistry; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Invasiveness; Pituitary Function Tests; Pituitary Neoplasms; Prolactin; Prolactinoma; Skull Base Neoplasms; Vision Disorders

Prolactinomas invading the skull base are rare, and could easily be confused with skull base tumors of nonpituitary origin.. We report a series of 4 cases of giant prolactinomas invading the skull base and presenting with atypical symptoms. Case 1 presented with a short history of headache and nasal obstruction. Case 2 presented with progressive hypoacusia, dizziness, and ophthalmoplegia. In Case 3, the patient developed rapid progressive visual failure and psychiatric symptoms. Case 4 presented with a 1-year history of headache and retrorbital pain. The diagnosis of prolactinoma was made on the basis of tumor immunohistochemistry and/or high plasma prolactin levels (range from 650-6,500 ng/mL). Medical treatment with the dopamine agonist cabergoline was given; it was effective in normalizing prolactin levels and inducing tumor shrinkage.. Prolactin levels should be measured in all large skull base tumors involving the pituitary region before any surgery or inappropriate radiotherapy is performed.

Topics: Adult; Cabergoline; Diagnosis, Differential; Dopamine Agonists; Ergolines; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Invasiveness; Pituitary Neoplasms; Prolactin; Prolactinoma; Skull Base Neoplasms

Multiple pituitary hormone hypersecretions have already been described, but the co-occurrence of PRL and ACTH excess is very rare. To our knowledge, medical treatment with cabergoline only, avoiding pituitary surgery and radiotherapy in this type of tumor has never been reported before. This case report deals with a 31-yr-old man affected with a macroprolactinoma associated with a florid clinical image of Cushing's disease. Normalization of the prolactin levels and the disappearance of clinical and biochemical features of Cushing's disease were obtained after administration of medical treatment only.

Topics: Adrenocorticotropic Hormone; Adult; Antineoplastic Agents; Cabergoline; Cushing Syndrome; Dexamethasone; Ergolines; Glucocorticoids; Humans; Hydrocortisone; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Prolactin; Prolactinoma; Thyrotropin-Releasing Hormone; Treatment Outcome

We report a pregnant woman with a large macroprolactinoma successfully treated with cabergoline after a suboptimal response to bromocriptine. A 7 week pregnant woman with a history of a prolactinoma presented to the endocrine clinic with the complaints of headaches and nausea. She had a prolactin level of 65 microg/L 1 1/2 weeks following her last menstrual period. Bromocriptine was discontinued at 6 weeks gestation when pregnancy was confirmed. A PRL concentration was 1899 microg/L (non-pregnant normal range 1.39-24.20 microg/L, the mean peak levels during pregnancy reported from the literature are 200-210 microg/L) at 7 weeks gestation, and a repeat was 2197 microg/L. An MRI showed a 3 x 2.2 x 2.5 cm seller mass abutting the optic chiasm and displacing the optic nerves superiorly; the visual field testing was normal. Bromocriptine was reinitiated and the patient responded initially with decreasing headaches and declining PRL concentrations to 1488 microg/L at 15 weeks gestation. However, PRL increased to 1836 microg/L at 16 weeks and remained elevated despite bromocriptine 2.5 mg three times a day; in addition, she complained of severe nausea, vomiting, and persistent headaches. Cabergoline was added at 18 weeks gestation. PRL decreased dramatically from 1710 to 859 microg/L in 1 week, and to 488 microg/L within 4 weeks. A repeat MRI showed more than 30% reduction in tumor size. Bromocriptine was discontinued at 24 weeks gestation; she was maintained on cabergoline 0.5 mg twice a week without complaints. PRL levels ranged from 190 to 278 microg/L during the last 10 weeks of pregnancy. She had a C-section electively at 37 weeks gestation and delivered a healthy baby. Management options in this patient and during pregnancy are discussed.

Topics: Adult; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Magnetic Resonance Imaging; Pituitary Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Prolactinoma

The secretory capacity, in vivo, of clinically non-functioning pituitary adenomas may possibly predict tumour volume reduction during intensive medical therapy. Ten patients (mean (range) 53 years (26-73)) with clinically non-functioning macroadenomas, > or = 10 mm were studied. The secretory capacity of the adenomas was examined using basal, NaCl and TRH-stimulated LH, FSH and alpha-subunit levels. The effect on tumour volume of 6 months' therapy with the combination of a somatostatin analogue, octreotide 200 microg x 3/day and a dopamine-D2-agonist, cabergoline 0.5 mg x 1/day was studied. The basal LH, FSH and alpha-subunit levels were determined before and during 6 months' therapy with octreotide and cabergoline, and MR scans were used to evaluate tumour volume before and during this period of therapy. Octopus-perimetry was used to examine the visual fields. A reduction in tumour volume (mean +/- SEM (range); 30% +/- 4% (18-46%)) during 6 months of combination therapy with octreotide and cabergoline was recorded only in patients with in vivo secretory potential. Tumour volume was not reduced in four patients: in three of these patients it remained unchanged while in one patient it was observed to have increased (by 14%). Of the six patients with pretherapy secretory capacity, one displayed a very high basal level of alpha-subunit (74 microg/l) despite unmeasurable levels of LH and TSH, and an FSH-level of 1 IU/l. The other five patients presented paradoxical LH, FSH and/or alpha-subunit responses to TRH. A reduction in basal levels of LH, FSH and/or alpha-subunit was observed in all six patients, and the maximum reduction of at least one of the hormonal levels was 66% +/- 7% (50-98%). The basal levels of LH, FSH and alpha-subunit in the 10 patients were (mean +/- SEM (range)), 3.0 IU/l +/- 1.0 (0.0-7.4), 12.7 IU/l +/- 5.0 (0.0-39.0) and 9.0 IU/l +/- 7.0 (0.2-74.0). During six months of therapy with octreotide and cabergoline, the basal levels of LH, FSH and alpha-subunit were reduced by > or = 50% in seven patients - including the six patients with in vivo secretion prior to therapy. No new visual field defects were detected during therapy and no deterioration of existing visual field defects was recorded. The medical therapy was well tolerated. The in vivo basal and TRH-stimulated secretory capacity of LH, FSH and alpha-subunit predicted tumour reduction following intensive medical therapy in all of our patients with non-functioning pituitary adenomas

Topics: Adenoma; Adult; Aged; Antineoplastic Agents, Hormonal; Cabergoline; Dopamine Agonists; Drug Therapy, Combination; Ergolines; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Male; Middle Aged; Octreotide; Pituitary Neoplasms; Prognosis; Thyrotropin

Topics: Adult; Antineoplastic Agents; Cabergoline; Ergolines; Hernia; Humans; Magnetic Resonance Imaging; Male; Optic Chiasm; Optic Nerve Diseases; Pituitary Neoplasms; Prolactinoma

The authors present a case report that proposes the use of cabergoline treatment in silent ACTH adenoma, an unusual member of the heterogeneous group of the so-called clinically non-functioning pituitary adenomas.. Following the clinical and radiological improvement of a recurrent silent ACTH adenoma in a 77-year-old patient treated with cabergoline (0.5 mg every 2 days for 2 years), in vitro studies of the original tumor were performed.. The original tumor from the patient was studied by in situ hybridization and dopamine D2 receptor autoradiography. It was compared with four macroprolactinomas and two macroadenomas from patients with Cushing's disease.. The D2 receptor mRNA signal of the reported case was intense and of the same order of magnitude as that observed in control prolactinomas. Dopamine D2 receptor autoradiography was twice that of control corticotroph adenomas and was close to that observed in prolactinomas.. This is the first description of an in vivo shrinkage of an ACTH silent adenoma under cabergoline. We demonstrate in vitro, the presence of D2 receptors in the primitive tumor in concentrations similar to those found in control prolactinomas. These results suggest that therapeutic trials with cabergoline might be undertaken in recurring cases of ACTH silent tumors and more generally, non-functioning pituitary adenomas.

Topics: Adenoma; Adrenocorticotropic Hormone; Aged; Antineoplastic Agents; Autoradiography; Cabergoline; Ergolines; Humans; In Situ Hybridization; Male; Neoplasm Recurrence, Local; Pituitary Neoplasms; Prolactinoma; Receptors, Dopamine D2; RNA, Messenger

Pituitary adenomas in childhood and adolescence constitute 2-6% of all operated pituitary adenomas. We report the clinical features, treatment and follow-up of 10 pediatric patients affected by pituitary adenomas. All patients underwent clinical evaluation, endocrine tests, magnetic resonance imaging and visual field assessment. Follow-up ranged from 8 to 132 months (median 52.6). All patients were older than 10 years of age; 60% were males. In 50% the initial complaints were headache and/or visual impairment, all except one had clear evidence of endocrine dysfunction. Ninety percent were macroadenomas. According to hormone measurements and immunostaining 50% were prolactinomas, 20% were pure GH-secreting and 30% were non-functioning adenomas. Prolactinomas in two females were successfully treated with cabergoline. The other patients underwent surgery: three prolactinomas are still being treated with dopamine agonists and a GH-secreting adenoma is being treated with octreotide LAR and cabergoline. Two patients were also treated with conventional radiotherapy. Treatments were completely successful in 50% of patients: these have normal hormone secretion, full pubertal development, no significant tumor mass and normal visual field. Hypersecretion of prolactin persists in two cases; partial or complete hypopituitarism is present in four, relevant tumor remnant in another four and impairment of visual field is present in two cases. In conclusion, pediatric adenomas occur mostly in pubertal age, are prevalently macroadenomas and clinically functioning. Medical therapy should be preferred for secreting adenomas, but in some cases, notably prolactinomas in males, surgery and eventual radiotherapy may be needed.

Topics: Acromegaly; Adenoma; Adolescent; Amenorrhea; Bromocriptine; Cabergoline; Child; Ergolines; Female; Headache; Human Growth Hormone; Humans; Male; Neoplasm Recurrence, Local; Octreotide; Pituitary Neoplasms; Prolactinoma; Puberty, Delayed; Radiotherapy; Treatment Outcome; Vision Disorders; Visual Fields

induces the macroprolactinoma shrinkage. Endoscopic transsphenoidal surgery offers a safe, minimally invasive and efficient management of this complication, which allows to regularly perform the following steps of the therapeutical strategy against the prolactinoma.

Topics: Adult; Cabergoline; Cerebrospinal Fluid Rhinorrhea; Endoscopy; Ergolines; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma; Tomography, X-Ray Computed

GH and PRL cosecretion frequently occurs in acromegaly and the sensitivity of both hormones to somatostatin analogs (SA) and dopamine agonists (DA) alone or in combination, is still debated. This study was designed to evaluate the in vivo and in vitro sensitivity to SA and/or DA and correlate the response in terms of hormone suppression to the results of in vivo somatostatin and dopamine receptor scintigraphy and to the immunohistochemical findings.. Scintigraphy using 111In-DTPA-D-Phe(1)-OCT (111In-OCT) and 123I-methoxybenzamide (123I-IBZM) was performed in four patients with acromegaly and high circulating GH, PRL and IGF-I levels. The results were correlated with the response to long-term treatment with octreotide (OCT), quinagolide (QN) and/or cabergoline (CAB), to the in vitro hormone suppression by OCT and DA in primary cultures from the pituitary tumors and to the immunohistochemical findings.. The first patient showed high tumour uptake of 111In-OCT and 123I-IBZM, the second high uptake of only 111In-OCT, while the third one showed faint tumour uptake of only 123I-IBZM, and the fourth a faint uptake of 111In-OCT. In the first and in the fourth patients OCT or CAB administered alone failed to normalize hormone levels while the combined treatment induced circulating GH, IGF-I and PRL normalization. In the second patient OCT administered alone normalized hormone levels while QN reduced PRL levels only. In the third patient both OCT and QN, alone or in combination, failed to normalize hormone levels. However, in this patient GH and PRL suppression was significantly greater after QN than OCT treatment. After medical therapy, all the patients were operated on. Immunohistochemistry showed diffuse GH and focal PRL staining in the first patient, while diffuse GH and PRL staining in the remaining three. In vitro, OCT significantly suppressed GH secretion in the four primary pituitary tumor cultures, while PRL secretion was significantly suppressed only in the second and the fourth cases. Dopamine agonists (DA) significantly suppressed PRL release in all the cultures, while GH secretion was significantly suppressed in three out of four.. These four acromegalics, presenting similar clinical findings and comparable peripheral hormone levels, showed different responsiveness to SA and DA. Moreover, during the in vitro study on primary tumor cell cultures, OCT and DA displayed an inhibiting activity on GH and PRL secretion positively correlated with the response observed in vivo. This evidence together with the in vivo receptor imaging study suggest the existence of somatostatin and/or dopamine D2 receptor heterogeneity in this class of pituitary tumors. The new potent DA might be primarily considered in the medical treatment of hyperprolactinemic acromegalics, while SA alone or in combination with DA in case of ineffective hormone suppression.

Topics: Acromegaly; Adrenocorticotropic Hormone; Adult; Aminoquinolines; Analysis of Variance; Antineoplastic Agents, Hormonal; Cabergoline; Dopamine Agonists; Ergolines; Female; Follicle Stimulating Hormone; Growth Hormone; Humans; Immunohistochemistry; Indium Radioisotopes; Insulin-Like Growth Factor I; Iodine Radioisotopes; Luteinizing Hormone; Male; Octreotide; Pituitary Neoplasms; Prolactin; Prolactinoma; Receptors, Dopamine; Receptors, Somatostatin; Thyrotropin; Tumor Cells, Cultured

Topics: Antineoplastic Agents, Hormonal; Cabergoline; Dopamine Agonists; Ergolines; Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactinoma; Treatment Outcome

To evaluate the effect of hyperprolactinaemia and its treatment with dopamine-agonists on bone mass and turnover in adolescent patients compared to adults.. Forty patients with hyperprolactinaemia (20 with disease onset during adolescence and 20 during adulthood) and 40 healthy control subjects.. Open transverse (in patients and controls) and open longitudinal (in the patients).. Bone mineral density (BMD) at lumbar spine and femoral neck, serum osteocalcin (OC) and urinary cross-linked N-telopeptides of type-1 collagen (Ntx) levels were evaluated in patients and controls. In the 40 patients, bone mass and turnover were re-evaluated after 12 and 24 months of treatment with bromocriptine (BRC, dose 2.5-10 mg daily), quinagolide (CV, dose 0.075-0.3 mg daily) or cabergoline (CAB, dose 0.5-1.5 mg weekly).. Transverse study: BMD values were significantly lower in hyperprolactinaemic patients than in controls, both at lumbar spine (0.81 +/- 0.01 vs. 1.010 +/- 0.01 g/cm2; P < 0.001) and femoral neck (0.71 +/- 0.01 vs. 0.873 +/- 0.03 g/cm2; P < 0.001). Thirty-two patients (80%) had osteoporosis and/or osteopenia at one or both skeletal sites. A significant inverse correlation was found between T score values measured at lumbar spine and femoral neck and the estimated disease duration. BMD was significantly lower in young than adult patients both at lumbar spine (T score, -2.4 +/- 0.1 vs. -1.4 +/- 0.3, P < 0.01) and at femoral neck (T score, -2.1 +/- 0.05 vs. -1.5 +/- 0.2, P < 0.05). Similarly, serum OC levels were significantly lower (2.0 +/- 0.11 vs. 9.1 +/- 2.4 micrograms/l, P < 0. 01) while Ntx levels were significantly higher in patients than in controls (129.2 +/- 1.7 vs. 80.7 +/- 2.9 nmol Bone collagen equivalent (BCE)/mmol creatinine; P < 0.001). A significant inverse correlation was found between prolactin (PRL) levels and OC levels, lumbar and femoral T score values, as well as between disease duration and OC levels, lumbar and femoral T score values. A significant direct correlation was also found between Ntx levels and PRL levels and disease duration. Longitudinal study: Normalization of serum PRL levels was obtained in all patients after 6-12 months of treatment. A significant increase of serum OC levels together with a significant decrease of Ntx levels was observed after 12 and 24 months of treatment (P < 0.01). Urinary and serum calcium, phosphorus, creatinine, and serum alkaline phosphatase and parathyroid hormone levels did not change during the study period in all patients. After 12 months of therapy OC and Ntx concentrations were restored to normal. A slight but not significant increase of BMD values was recorded after 12 and 24 months of treatment. After 12 months of treatment the percent increment of BMD values in the whole group of patients was 1.13 +/- 0.6% at lumbar spine and 1.2 +/- 0.4% at femoral neck level, whereas after 24 months, it was 2.8 +/- 0.7% at lumbar spine and 3.5 +/- 0.7% at femoral neck level. After 12 months of treatment, the percent increment of BMD values was 0.7 +/- 0.2% and 1.6 +/- 1.1% at lumbar spine and 0.9 +/- 0.5% and 1.6 +/- 0.5% at femoral neck level in the young and adult patients, respectively, whereas after 24 months, it was 2.1 +/- 0.8% and 3.4 +/- 1.3% at lumbar spine and 2.6 +/- 0.8% and 4.4 +/- 1.0% at. Adolescents with prolactinoma have osteopenia or osteoporosis, a finding that strengthens the need for a prompt diagnosis. Since normalization of PRL concentrations by dopamine agonist therapy is unable to restore the bone mass, other therapeutic approaches should be considered in order to prevent further long-term problems.

Topics: Adolescent; Adult; Aminoquinolines; Analysis of Variance; Biomarkers; Bone Density; Bone Remodeling; Bromocriptine; Cabergoline; Case-Control Studies; Collagen; Collagen Type I; Dopamine Agonists; Ergolines; Female; Femur Neck; Humans; Longitudinal Studies; Lumbar Vertebrae; Male; Middle Aged; Osteocalcin; Osteoporosis; Peptides; Pituitary Neoplasms; Prolactinoma; Regression Analysis

Three patients with hyperprolactinemia due to pituitary adenomas (two patients) or empty sella (one patient) and osteopenia are described. Their ages at presentation ranged from 8 to 17 years. Each patient was treated with cabergoline. Serum prolactin levels became normal in all patients within one month. Bone density and pubertal stage improved after 12 months of treatment.

Topics: Adolescent; Antineoplastic Agents; Bone Density; Bone Diseases, Metabolic; Cabergoline; Child; Empty Sella Syndrome; Ergolines; Female; Humans; Hyperprolactinemia; Male; Pituitary Neoplasms; Prolactinoma; Puberty, Delayed

Gigantism is caused by GH hypersecretion occurring before epiphyseal long bone closure and usually is associated with pituitary adenoma. A 15-yr-old female patient presented with accelerated growth due to a large pituitary tumor that was surgically resected to relieve pressure effects. Second surgery to remove residual tumor tissue was followed by administration of octreotide LAR, a long-acting depot somatostatin analog, together with long-acting cabergoline. Height was over the 95th percentile, with evidence of a recent growth spurt. Serum GH levels were more than 60 ng/mL (normal, <10 ng/mL) with no suppression to 75 g oral glucose, and serum PRL (>8,000 ng/mL; normal, <23 ng/mL) and insulin-like growth factor I levels (845 ng/mL; age-matched normal, 242-660 ng/mL) were elevated. Histology, immunostaining, and electron microscopy demonstrated a pituitary acidophil stem cell adenoma. Tumor tissue expressed both somatostatin receptor type 2 and dopamine receptor type 2. The Gs alpha subunit, GHRH receptor, and MEN1 genes were intact, and tumor tissue abundantly expressed pituitary tumor transforming gene (PTTG). Serum GH and PRL levels were controlled after two surgeries, and with continued cabergoline and octreotide LAR GH, PRL, and insulin-like growth factor I levels were normalized. In conclusion, administration of long-acting somatostatin analog every 4 weeks in combination with a long-acting dopamine agonist biweekly controlled biochemical parameters and accelerated growth in a patient with gigantism caused by a rare pituitary acidophil stem cell adenoma.

Topics: Adenoma, Acidophil; Adolescent; Antineoplastic Agents, Hormonal; Cabergoline; Delayed-Action Preparations; Dopamine Agonists; Ergolines; Female; Gigantism; Hormones; Humans; Magnetic Resonance Imaging; Octreotide; Pituitary Neoplasms; Receptors, Dopamine D2; Receptors, Somatostatin; Reverse Transcriptase Polymerase Chain Reaction; Stem Cells

Topics: Antineoplastic Agents; Cabergoline; Child; Ergolines; Exophthalmos; Humans; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Prolactinoma

Topics: Aminoquinolines; Cabergoline; Cross-Over Studies; Dopamine Agonists; Ergolines; Female; Humans; Magnetic Resonance Imaging; Pituitary Neoplasms; Prolactinoma; Research Design; Treatment Outcome

Cabergoline therapy normalizes prolactin levels and reduces the size of macroprolactinomas. However there are no data indicating whether cabergoline can normalize growth hormone secretion in patients who were growth hormone deficient at the time of diagnosis of a macroprolactinoma.. We studied nine patients with biochemical and radiological evidence of a macroprolactinoma who were also growth hormone deficient (peak growth hormone response to insulin-induced hypoglycaemia < 10 mU/l). Patients were assessed before and after cabergoline therapy to assess their growth hormone secretory status, IGF-I levels, cortisol response and change in tumour size.. Treatment with cabergoline was associated with a significant reduction in prolactin concentration (74341 +/- 31939 mU/l vs. 265.9 +/- 86.3, P = 0.009). The mean change in peak growth hormone response to insulin-induced hypoglycaemia was significantly greater following cabergoline therapy compared with pretreatment levels (33.5 +/- 11.8 mU/l vs. 4. 34 +/- 1.21 mU/l, P = 0.022). However IGF-I levels were not different after treatment when compared with baseline although a nonsignificant trend towards improvement was noted (24.2 +/- 3.97 nmol/l vs. 18.4 +/- 4.94 nmol/l, P = 0.058). The mean peak cortisol concentration was 407.7 +/- 64.1 nmol/l before treatment with a nonsignificant rise to 477.4 +/- 84.8 nmol/l, P = 0.813 after treatment. These changes were associated with a significant reduction in mean maximal tumour diameter (21.2 +/- 2.9 mm vs. 29.1 +/- 2.8 mm, P = 0.009). There was no significant difference in either prolactin concentration or tumour size pre- or post-treatment between those who recovered growth hormone secretion and those that did not. Six of the nine (67%) patients recovered a normal growth hormone response (> 10 mU/l) after cabergoline therapy. Those that remained growth hormone deficient after treatment were all panhypopituitary at baseline while those that recovered showed only partial anterior hypopituitarism.. These data indicate that growth hormone secretion may recover following successful reduction of prolactin levels after cabergoline therapy for a mean of 22 months (range 6-28 months) in most but not all subjects with a macroprolactinoma. It is therefore advisable that individuals with a macroprolactinoma in whom growth hormone replacement therapy is being considered undergo repeat assessment of growth hormone secretion following medical treatment.

Topics: Adolescent; Adult; Cabergoline; Dopamine Agonists; Ergolines; Female; Human Growth Hormone; Humans; Hydrocortisone; Hypopituitarism; Insulin-Like Growth Factor I; Male; Pituitary Neoplasms; Prolactin; Prolactinoma; Recovery of Function; Treatment Outcome

We report a case of hepatolithiasis (intrahepatic stone) complicated by gram-negative sepsis in a 37 year old male with acromegaly being treated with octreotide. As a child, he had suffered a traumatic injury to his liver requiring the surgical repair of a laceration. This is the first reported case of hepatolithiasis during octreotide therapy. Gallstones and bile sludge are common side effects of octreotide therapy but rarely become symptomatic or require treatment. Hepatolithiasis is uncommon in western countries but is quite prevalent in East Asia and is often associated with a predisposing condition that causes intrahepatic bile stasis (eg. bile duct stricture). In addition to its known effect on gallbladder stasis, octreotide alters bile acid composition and may thus hasten intrahepatic sludge and stone formation. Extra caution should be taken in using octreotide or its long-acting analog in patients otherwise predisposed to intrahepatic bile stasis.

Topics: Abdominal Pain; Acromegaly; Adenoma; Adult; Anti-Bacterial Agents; Bile Ducts, Intrahepatic; Bilirubin; Cabergoline; Chemical and Drug Induced Liver Injury; Cholangiopancreatography, Endoscopic Retrograde; Cholelithiasis; Cholesterol; Ergolines; Gram-Negative Bacterial Infections; Hepatectomy; Humans; Insulin-Like Growth Factor I; Liver; Liver Diseases; Male; Octreotide; Pituitary Neoplasms; Postoperative Complications; Sepsis; Surgical Wound Infection

Cabergoline decreases both serum PRL levels and size of prolactinomas, including some tumors resistant to other dopamine-agonists. It is common observation that the shrinkage of the adenoma is preceded by suppression of PRL levels. A minority of patients, who do not show a significant decrease of PRL after a short trial with dopamine-agonists, undergoes neurosurgery or radiotherapy. We report on the case of a 14-year-old girl with a huge prolactinoma who showed, during cabergoline treatment (0.5 mg twice a week), a significant shrinkage of the pituitary mass but no decrease of the very high PRL values. She was referred to us after partial removal of the suprasellar extension of the pituitary tumor. The post-surgical evaluation showed very high PRL levels (9352 microg/l; 20941 microg/l before surgery), which did not decrease during the 2-year treatment with cabergoline (nadir value: 8735 microg/l). However, one month after the beginning of therapy, MRI showed a significant shrinkage of the tumor (tumor volume 5.7 ml, compared with 45.1 ml prior to surgery and 24.4 ml after surgery). Subsequently MRIs demonstrated a progressive reduction of the size with a complete disappearance of the suprasellar and parasellar tissue (tumor volume 1.8, 0.9 and 0.2 ml, at 3, 6 and 12 months, respectively). The MRI performed at the 24th month showed a secondary empty sella, with residual tumor tissue in the right sphenoidal sinus. Increasing cabergoline, up to 3 mg a week, failed to induce any decrease of PRL levels. In conclusion, in such macroprolactinomas the shrinkage of tumor is not strictly correlated with (or it is partially dissociated from) the inhibition of PRL hypersecretion. The choice of other therapeutic options in cabergoline-resistant macroprolactinomas needs careful neuroradiological evaluation after a short trial of pharmacological treatment.

Topics: Adenoma; Adolescent; Antineoplastic Agents; Cabergoline; Drug Resistance, Neoplasm; Ergolines; Female; Humans; Magnetic Resonance Imaging; Pituitary Neoplasms; Prolactin; Time Factors

Cabergoline is a new long-acting dopamine agonist that is very effective and well tolerated in patients with pathological hyperprolactinemia. The aim of this study was to examine, in a very large number of hyperprolactinemic patients, the ability to normalize PRL levels with cabergoline, to determine the effective dose and tolerance, and to assess the effect on clinical symptoms, tumor shrinkage, and visual field abnormalities. We also evaluated the effects of cabergoline in a large subgroup of patients with bromocriptine intolerance or -resistance. We retrospectively reviewed the files of 455 patients (102 males and 353 females) with pathological hyperprolactinemia treated with cabergoline in 9 Belgian centers. Among these patients, 41% had a microadenoma; 42%, a macroadenoma; 16%, idiopathic hyperprolactinemia; and 1%, an empty sella. The median pretreatment serum PRL level was 124 microg/L (range, 16-26,250 microg/L). A subgroup of 292 patients had previously been treated with bromocriptine, of which 140 showed bromocriptine intolerance and 58 showed bromocriptine resistance. Treatment with cabergoline normalized serum PRL levels in 86% of all patients: in 92% of 244 patients with idiopathic hyperprolactinemia or a microprolactinoma and in 77% of 181 macroadenomas. Pretreatment visual field abnormalities normalized in 70% of patients, and tumor shrinkage was seen in 67% of cases. Side effects were noted in 13% of patients, but only 3.9% discontinued therapy because of side effects. The median dose of cabergoline at the start of therapy was 1.0 mg/week but could be reduced to 0.5 mg/week once control was achieved. Patients with a macroprolactinoma needed a higher median cabergoline dose, compared with those with idiopathic hyperprolactinemia or a microprolactinoma: 1.0 mg/week vs. 0.5 mg/week, although a large overlap existed between these groups. Twenty-seven women treated with cabergoline became pregnant, and 25 delivered a healthy child. One patient had an intended abortion and another a miscarriage. In the patients with bromocriptine intolerance, normalization of PRL was reached in 84% of cases, whereas in the bromocriptine-resistant patients, PRL could be normalized in 70%. We confirmed, in a large-scale retrospective study, the high efficacy and tolerability of cabergoline in the treatment of pathological hyperprolactinemia, leaving few patients with unacceptable side effects or inadequate clinical response. Patients with idiopathic hyperprolactin

Topics: Adenoma; Adult; Antineoplastic Agents; Bromocriptine; Cabergoline; Dopamine Agonists; Drug Resistance; Drug Tolerance; Ergolines; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Pituitary Neoplasms; Pregnancy; Retrospective Studies; Sex Characteristics

Topics: Antineoplastic Agents; Cabergoline; Ergolines; Humans; Pituitary Neoplasms; Prolactinoma

Topics: Antineoplastic Agents; Cabergoline; Ergolines; Humans; Pituitary Neoplasms; Prolactinoma

We report the case of a giant prolactinoma in a 7-year-old boy, which was complicated by unilateral exophthalmos. The initial levels of prolactin (PRL) were about 80,000 microU/ml. Treatment with cabergoline (CAB) resulted in rapid normalization of serum PRL (6 weeks after initiation of treatment) and reduction of tumor size. In particular, magnetic resonance imaging (MRI), which was done 2.5 months after the patient was put on CAB, revealed tremendous improvement with a decrease in the size of the tumor which now showed no extrasellar extension. Subsequent MRI studies demonstrated further improvement. Exophthalmos, anisocoria and visual fields improved. In summary, this patient represents the first report of the therapeutic use of CAB as the primary mode of treatment in a 7-year-old boy with infiltrative giant prolactinoma complicated by unilateral exophthalmos. It is a noninvasive treatment that can preserve and restore vision, as well as pituitary function, and is preferable to surgery or radiation in the treatment of prolactin-secreting macroadenoma in childhood and adolescence.

Topics: Antineoplastic Agents; Cabergoline; Child; Ergolines; Exophthalmos; Humans; Male; Pituitary Neoplasms; Prolactin; Prolactinoma

In this case report we demonstrated that treatment with the long-acting D2 receptor agonist cabergoline for 1 year induced normalization of plasma ACTH levels and disappearance of the pituitary tumor in a patient with Nelson's syndrome. A young man underwent bilateral adrenalectomy and subsequent pituitary irradiation for Cushing's disease after unsuccessful neurosurgical treatment. Thereafter, he was given cortisone acetate replacement at the dose of 62.5 mg a day. Fifteen months after pituitary irradiation, he developed Nelson's syndrome, having skin hyperpigmentation, high plasma ACTH levels (376 ng/l) and a pituitary microadenoma (5 mm) documented at magnetic resonance imaging (MRI) of the pituitary region. After 6 months of cabergoline treatment, given at the dose of 1 mg a week, plasma ACTH levels were significantly decreased (from 376 to 113 ng/l) but they were not normalized. Cabergoline dose was then increased up to 2 mg a week. Six months later plasma ACTH levels were normalized (22 ng/l) and MRI demonstrated the disappearance of the pituitary adenoma. In order to investigate on the direct effect played by cabergoline treatment on the remission of Nelson's syndrome, the treatment was withdrawn. Plasma ACTH levels significantly increased (119 ng/l) after 3 months of treatment withdrawal. At the last follow-up, during cabergoline treatment at the dose of 2 mg/week plasma ACTH levels were normalized (40.4 ng/l). This case demonstrated that cabergoline treatment is able to induce the remission of Nelson's syndrome and may be a valid therapeutic alternative in this syndrome.

Topics: Adenoma; Adrenalectomy; Adrenocorticotropic Hormone; Adult; Antineoplastic Agents; Cabergoline; Cushing Syndrome; Dopamine Agonists; Ergolines; Humans; Magnetic Resonance Imaging; Male; Nelson Syndrome; Pituitary Neoplasms; Remission Induction

We report the case of a man with an invasive macroprolactinoma who developed resistance to bromocriptine to which he had previously responded satisfactorily for 5 years. Subsequently, hyperprolactinemia was controlled equally well with 600 microg quinagolide daily and later with 4.5 mg cabergoline weekly. This observation suggests that a loss of dopamine receptors at the tumoral cell surface might be the mechanism underlying acquired resistance to bromocriptine. In addition, no tumor growth was observed over a 10-year follow-up, which virtually excludes a malignant transformation of the prolactinoma. This case emphasizes the need for close supervision of patients with macroprolactinoma, even after the serum prolactin concentration has been normalized by bromocriptine. It furthermore illustrates the usefulness of quinagolide and cabergoline when resistance to bromocriptine develops after a prolonged period of adequate response to this drug.

Topics: Aminoquinolines; Bromocriptine; Cabergoline; Dopamine Agonists; Drug Resistance, Neoplasm; Ergolines; Humans; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma

Cabergoline (CAB), a new, potent, and long-lasting PRL-lowering agent, was shown to be effective in tumoral hyperprolactinemia. The aim of this study was to investigate the effectiveness of CAB in patients with prolactinoma proven to be resistant to bromocriptine (BRC) and quinagolide (CV 205-502). Twenty-seven patients (19 macro- and 8 microprolactinomas) were treated with CAB at a weekly dose of 0.5-3 mg for 3-22 months. All patients were previously shown to be resistant to BRC, and 20 of them were resistant to CV 205-502 as well. Basal serum PRL levels before CAB treatment ranged from 108-3500 micrograms/L in macroprolactinomas and from 64-205 micrograms/L in microprolactinomas. Gonadal failure was present in all patients, whereas symptoms of tumor expansion, such as visual field defects and headache, were present in 10 of 27 patients. Eight macroprolactinomas had previously undergone surgery and/or radiotherapy. CAB treatment normalized serum PRL levels in 15 of 19 macroprolactinomas and in all 8 microprolactinomas. In 3 of the remaining 4 patients it caused a notable decrease in prolactinemia (89%, 80.5%, and 68.7% of the baseline). Only 1 patient was withdrawn from CAB therapy after 3 months at the weekly dose of 2 mg due to the absence of any significant clinical, hormonal, or radiological improvement. Gonadal function was restored in 18 of 27 patients, galactorrhea disappeared in 5 of 6 women, and headache improved in 7 of 8 patients. A significant tumor shrinkage was detected by computed tomography and/or magnetic resonance imaging in 9 macroprolactinomas and 4 microprolactinomas. CAB was well tolerated by all patients, except 6 who referred slight and short-lasting nausea, postural hypotension, abdominal pain, dizziness, and sleepiness at the beginning of treatment. In particular, CAB was well tolerated by 19 patients previously shown to be poorly tolerant to BRC and CV 205-502. In conclusion, CAB may represent, at the moment, the only successful therapy for prolactinoma-bearing patients resistant to BRC and CV 205-502, as it normalized PRL levels in 22 of 27 patients, reduced tumor size in 13 of 27 patients, and improved clinical symptoms in 25 of 27 patients in the present study.

Topics: Adolescent; Adult; Cabergoline; Dopamine Agonists; Drug Administration Schedule; Drug Resistance; Ergolines; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma

Cabergoline is now established as an effective and well-tolerated treatment for prolactinoma. However, there are relatively few published data on the treatment of macro-, as opposed to micro-, prolactinoma. We have therefore reviewed the efficiency and safety of cabergoline in the treatment of patients with prolactin-secreting macroadenomas treated on a compassionate basis.. Eighty-five patients with prolactin-secreting macroadenomas were treated with cabergoline 0.25 to 10.5 mg per week (median 1 mg) given to one to seven doses. Treatment durations ranged between 3 months and 8 years. Sixty-five patients (32 intolerant, 16 resistant) had been treated previously with other dopamine agonists. Pretreatment prolactin levels ranged between 80 and 8300 micrograms/I and tumour maximum diameters were between 11 and 42 mm.. Serum prolactin, visual fields if initially abnormal, occurrence of menses or return of libido and potency, blood chemistry and adverse events were assessed at 1 month and then at 3-month intervals during treatment. Pituitary computed tomography or magnetic resonance imaging was usually repeated at 3 months and 1 year, then yearly, in most patients (n = 62).. Normalization of prolactin levels was achieved in 52 patients (61.2%) and a prolactin decrease of at least 75% of pretreatment values occurred in 24 others (28.2%). Of the 20 de novo patients, 17 had prolactin normalized and the remainder had at least 75% reduction. Disappearance of tumour image was found in eight of 62 evaluable patients (12.9%) and reduction of the largest diameter by at least 25% in another 33 (53.2%), with an overall success rate of 66.1%; among the 17 evaluable de novo patients the success rate was 82.3%. Fifteen of 21 patients who failed to show tumour shrinkage had previously demonstrated resistance/intolerance to other prolactin-lowering treatments. Of the 12 patients with visual field defects at baseline, six normalized and two showed an improvement. Menses resumed during cabergoline treatment in 79.5% of premenopausal women. Restoration of potency was reported by seven of eight evaluable men. Adverse events were recorded in 24.7% of cases, four of whom (4.7%) discontinued treatment.. Although the present data were not obtained in a formal study we conclude that cabergoline is an effective and well-tolerated treatment for macroprolactinoma patients.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Infertility, Male; Male; Menstruation Disturbances; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma

Topics: Aminoquinolines; Antineoplastic Agents; Cabergoline; Dopamine Agonists; Drug Resistance, Neoplasm; Ergolines; Humans; Pituitary Neoplasms; Prolactinoma

Topics: Aminoquinolines; Antineoplastic Agents; Cabergoline; Dopamine Agonists; Drug Resistance, Neoplasm; Ergolines; Humans; Pituitary Neoplasms; Prolactinoma

A 49-yr-old woman presented with an extensive prolactinoma (serum PRL > 10,000 mU/L, normal range < 450 mU/L). Over a 5-yr period following transsphenoidal surgery and pituitary irradiation, she became increasingly resistant to high doses of bromocriptine and underwent transfrontal surgery followed by stereotactic radiotherapy. In spite of these treatments, serum prolactin estimations rose progressively to > 100,000 mU/L. Magnetic resonance imaging scanning demonstrated a massive cystic tumor invading the temporal lobes, extending into the cervical and thoracic spine, with metastases to cervical lymph nodes. High-dose cabergoline administration resulted in a 30% decrease in serum PRL. Octreotide was administered as a continuous sc infusion with a profound analgesic effect on facial pain but with no effect on tumor progression. She was treated with a course of chemotherapy consisting of carboplatin and etoposide without any noticeable effect. The patient died 6 months following chemotherapy. Immunocytochemical analysis demonstrated positive nuclear staining for WAF-1, Rb protein, c-myc, and p53 both in the original and metastatic tumors. The metastases but not the primary tumor stained for c-jun. Metastatic prolactinoma remains a therapeutic challenge. It is associated with a variable proto-oncogene expression, which may be coincidental or causal. Cabergoline had no advantage over bromocriptine. Octreotide relieved facial pain but did not alter tumor progression. An effective therapy for metastatic prolactinoma remains to be identified.

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Cabergoline; Carboplatin; Ergolines; Etoposide; Female; Gene Expression; Humans; Immunohistochemistry; Indium Radioisotopes; Magnetic Resonance Imaging; Middle Aged; Octreotide; Pituitary Neoplasms; Prolactinoma; Proto-Oncogene Mas; Proto-Oncogenes; Somatostatin; Treatment Failure

A patient with a pituitary adenoma secreting follicle-stimulating hormone with co-existent primary hyperaldosteronism is described. After his second transsphenoidal surgery, the patient developed a Staphylococcus aureus pituitary abscess. Symptoms improved after abscess drainage. Subsequent cabergoline therapy arrested the deterioration of symptoms. and decreased serum follicle-stimulating hormone concentrations. Cabergoline may be a useful treatment for aggressively growing non-prolactin-secreting pituitary adenomas.

Topics: Adenoma; Antineoplastic Agents; Cabergoline; Dopamine Agonists; Ergolines; Follicle Stimulating Hormone; Humans; Male; Middle Aged; Pituitary Neoplasms

Cabergoline (CAB), a new long-acting ergoline derivative, was shown to be very effective in reducing PRL levels in normal volunteers and in hyperprolactinemic patients. We evaluated the hormonal changes after discontinuation of long-term therapy with CAB as well as the safety of drug exposure during pregnancy both for mothers and babies. We therefore studied 48 patients (47 females and one male) with pathological hyperprolactinaemia (mean +/- SE, 117.2 +/- 15.2: median 73.2 micrograms/l), treated for 1-82 months (mean +/- SE, 28.3 +/- 3; median 18). After long-term treatment, CAB was withdrawn in 11 patients and PRL levels were persistently normal for almost 15 days and significantly lower (p < 0.05) than basal at 30, 45, 60, 90, 120 days. Three patients had normal PRL levels still at 45 days after treatment discontinuation. Nine patients became pregnant after 1-37 months (mean 12.4) of therapy. In two patients the pregnancy was interrupted spontaneously in one case and voluntarily in the other. In all but one patients after delivery or three-month breast feeding, PRL levels trended towards reduction. In two cases (one with microadenoma and one with idiopathic hyperprolactinaemia) PRL remained in the normal levels for 1-3 years after delivery. In conclusion CAB is able to inhibit plasma PRL levels for long time (up to 120 days) after withdrawal in patients with pathological hyperprolactinaemia treated with long-term therapy.

Topics: Adenoma; Adolescent; Adult; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Hyperprolactinemia; Kinetics; Male; Middle Aged; Pituitary Neoplasms; Pregnancy; Pregnancy Complications; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Prolactin

Dopamine agonist administration is the primary therapy for macroprolactinomas, but bromocriptine is the only agent approved in the United States. Its use is limited by a high incidence of side effects, a short duration of action, and a lack of effectiveness in some patients. Cabergoline is a long-acting dopamine agonist specific for the D2 receptor that is more effective and better tolerated than bromocriptine in women with microadenomas or idiopathic hyperprolactinemia. However, experience with cabergoline in the treatment of patients with macroadenomas is limited. We report the first study of chronic administration of cabergoline conducted exclusively in patients with macroprolactinomas. Fifteen patients (8 women, 7 men) ages 18-76 yr were studied in an open-label 48-week dose escalation trial of cabergoline administered once per week. Eleven patients had received prior therapy with other dopamine agonists. Mean prolactin (PRL) levels decreased by 93.6%, and normal levels were attained in 73% of patients at doses of 0.5-3.0 mg per week. Three of five patients who had failed to normalize PRL on prior dopamine agonists achieved normal levels. Gonadal function was restored in all hypogonadal men and in 75% of premenopausal women with amenorrhea. Tumor size decreased in 11 of the 15 patients. Side effects were minimal. Of the 5 patients who had experienced side effects in prior dopamine agonists, 4 had none on cabergoline, and the fifth had milder symptoms. During two further years of follow up, the improvement in PRL levels, gonadal function, and tumor size has persisted during cabergoline administration, and three patients have experienced a further decline in PRL and/or tumor size. This study demonstrates the effectiveness and minimal side effects of once-weekly cabergoline for treatment of macroprolactinomas.

Topics: Adenoma; Adolescent; Adult; Aged; Cabergoline; Dopamine Agonists; Ergolines; Female; Follow-Up Studies; Gonads; Humans; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Visual Fields

Cabergoline (CG) is a dopamine agonist that inhibits the secretion of prolactin (PRL) and growth hormone. In the present study, we evaluated the in vivo effect of CG on PRL secretion and the pituitary tumor induced by estrogen. Estrogen was administered by subcutaneous injection to 4-week-old Fischer 344 rats weekly for 10 weeks to induce tumors. On the last day of estrogen administration, doses of either CG or bromocriptine (BC), 0.6 mg/kg, were administered as a single oral route or chronically, given every third day. Sera and pituitary tumors were sampled on each treatment schedule. Serum levels of PRL were measured and the pituitary glands were weighed. Immunohistological evaluation was performed by optical and electron microscopy. A single dose of CG significantly inhibited the serum levels of PRL for 6 days. Following a single dose of BC, the PRL level was significantly inhibited only at 6 hours' postadministration. The continued oral administration of CG significantly reduced both the serum PRL level and the weight of the pituitary during 15 to 60 days of treatment as compared with BC. Morphologic studies revealed that CG reduced the size of the cells and of the granules, and increased the number of granules per unit area of the cytoplasm. These findings suggest that CG inhibits the maturation of PRL secretory granules and the secretion of PRL more than its synthesis. Thus, CG induced a prolonged lowering of PRL and had a good antitumor effect on rat pituitary tumors induced by estrogen.

Topics: Animals; Antineoplastic Agents; Bromocriptine; Cabergoline; Cytoplasmic Granules; Dopamine Agonists; Endoplasmic Reticulum; Ergolines; Estradiol; Female; Microscopy, Electron; Organ Size; Pituitary Neoplasms; Prolactin; Rats; Rats, Inbred F344

Cabergoline (CG) is a dopamine agonist that inhibits secretion of prolactin (PRL) and growth hormone. The purpose of this study was to investigate the PRL-lowering effect and antitumor effect of CG on estradiol-induced rat pituitary tumors in vitro and to elucidate these mechanisms. We compared the effects of CG with those of bromocriptine (BC) in terms of the inhibition of hormone secretion as well as antitumor effects on rat pituitary tumors. Primary cultures of dissociated pituitary tumor cells were used in these studies. A significant inhibition of prolactin (PRL) secretion was observed for both drugs within 12 h after treatment, and the inhibitory effects of CG and BC were antagonized by sulpiride or haloperidol. Inhibitory effect on PRL secretion after 12-h BC or CG pretreatment was more pronounced with CG than BC treatment at all time points. PRL secretion in group pretreated with CG was significantly suppressed at 72 h when compared to that of vehicle. Inhibition of de novo PRL synthesis was better demonstrated in the CG group. These findings suggest that CG has a higher affinity for the D2 receptor of pituitary cells as compared to BC and may preferentially inhibit PRL secretion rather than PRL production. An antitumor effect of CG has been confirmed at a lower dosage than that of BC.

Topics: Animals; Antineoplastic Agents; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Estradiol; Female; Pituitary Neoplasms; Prolactin; Rats; Rats, Inbred F344; Tumor Cells, Cultured

The dopamine D2 receptor antagonist remoxipride (30 microM) stimulated prolactin release from the prolactin-producing rat pituitary tumour cell strains GH3 and GH4C1 as well as from transfected GH4C1 cells expressing the short isoform of the rat D2 receptor (GH4ZR7). The effect of remoxipride on prolactin release is probably not due to an interaction with D2 receptors since GH4C1 cells, in contrast to GH3 and GH4ZR7 cells, are completely devoid of D2 receptors; in contrast, we have previously shown that the D2 antagonist haloperidol causes prolactin release from D2 receptor-expressing cells, only. Exposure of GH3 cells to the inhibitor of intracellular Ca2+ mobilization, 8-(diethylamino)-octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8) prevented the prolactin-releasing effect of remoxipride whereas pretreatment with the membrane Ca2+ channel antagonist nimodipine did not influence the response. The D2 receptor antagonist raclopride counteracted the reduction of VIP-stimulated prolactin release induced by the D2 agonist quinpirole but caused no prolactin release per se.

Topics: Animals; Calcium Channel Blockers; Clone Cells; Dopamine Agonists; Dopamine Antagonists; Ergolines; Gallic Acid; Nimodipine; Pituitary Neoplasms; Prolactin; Quinpirole; Raclopride; Rats; Remoxipride; Salicylamides; Tumor Cells, Cultured

The D2 dopamine agonist, bromocriptine, has been used as treatment for human PRL-secreting pituitary adenomas. The result of bromocriptine treatment is often a substantial reduction of tumor mass, suggesting that the dopamine agonist is acting as an antiproliferative agent. This action can be observed with a clonal pituitary tumor cell line. The agonist activation of the D2 dopamine receptor inhibits the growth of GH4ZR7 cells, a GH4C1 cell line stably transfected with the cDNA encoding the short form of the D2 dopamine receptor. This effect of dopamine was not sensitive to overnight treatment with 100 ng/ml pertussis toxin. Treatment of GH4ZR7 cells with the phorbol ester 4 beta-phorbol 12,13-didecanoate resulted in the loss of dopaminergic inhibition of growth, whereas treatment with 4 alpha-phorbol 12,13-didecanoate had no effect. Inhibitors of protein kinase-C (PKC), such as staurosporine and H7, also blocked the effect of dopamine. Down-regulation of cellular PKC by phorbol ester treatment resulted in a complete loss of dopaminergic inhibition of growth. Long term treatment of GH4ZR7 cells with TRH results in a specific down-regulation of the epsilon form of PKC and abolished the ability of dopamine to inhibit growth. These results suggest that PKC epsilon is involved in mediating the antiproliferative effects of dopamine. This mediation of growth appears to be through a novel signaling pathway for the D2 dopamine receptor.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Alprenolol; Animals; Apomorphine; Benzazepines; Butaclamol; Carcinogens; Cell Division; Cell Line; DNA; Dopamine; Ergolines; Humans; Isoenzymes; Kinetics; Norepinephrine; Pertussis Toxin; Phorbol Esters; Pituitary Neoplasms; Protein Kinase C; Quinpirole; Receptors, Dopamine D2; Salicylamides; Spiperone; Thymidine; Transfection; Tumor Cells, Cultured; Virulence Factors, Bordetella

Dopaminergic drugs have been reported to be effective in the treatment of FSH-secreting adenomas. We describe the case of a young woman suffering from amenorrhea with radiologic signs of pituitary macroadenoma. The enlargement of both ovaries with hemorrhagic and serous cysts suggest that FSH was active biologically. The short-term (13 weeks) chronic treatment with 0.5 mg cabergoline one time per week, a dopaminergic drug with long-lasting effect, was effective in reducing FSH and PRL hypersecretion and restoring the function of the pituitary ovarian axis, as confirmed by the occurrence of pregnancy.

Topics: Adenoma; Adult; Amenorrhea; Cabergoline; Dopamine Agonists; Ergolines; Female; Follicle Stimulating Hormone; Humans; Infertility, Female; Pituitary Neoplasms; Pregnancy; Prolactin

The serotonin2A and serotonin2C receptors are unique among receptors coupled to guanine nucleotide binding proteins in that chronic treatment in vivo with agonists as well as antagonists decreases receptor density. In an attempt to uncover molecular events involved in down-regulation of the serotonin2A receptor, the ability of agonists and antagonists to alter receptor density was examined in three heterologous expression systems, i.e., transfected NIH 3T3, transfected Madin-Darby canine kidney, and transfected AtT-20 cells. All three transfected cell lines exhibited pharmacological properties consistent with that predicted for cells expressing the serotonin2A receptor. However, the three cell lines displayed different receptor regulation properties in response to drugs acting at the serotonin2A receptor. In transfected NIH 3T3 cells, neither agonist nor antagonist treatment altered receptor density. Treatment with agonist as well as antagonist led to up-regulation of the serotonin2A receptor in transfected Madin-Darby canine kidney cells. In transfected AtT-20 cells, treatment with agonist led to receptor down-regulation, whereas antagonist treatment increased receptor density. Thus, the cellular background in which the serotonin2A receptor is expressed appears to determine the regulation properties of the receptor.

Topics: 3T3 Cells; Animals; Antiparkinson Agents; Binding, Competitive; Cell Line; Dogs; DOM 2,5-Dimethoxy-4-Methylamphetamine; Ergolines; Gene Expression Regulation; Ketanserin; Kidney; Kinetics; Mice; Pituitary Neoplasms; Receptor, Serotonin, 5-HT2A; Receptors, Serotonin; Recombinant Proteins; Transfection; Tumor Cells, Cultured

Recent evidence suggests that an important mechanism underlying the inhibition of PRL secretion by dopamine in the anterior pituitary is a direct inhibition of current through voltage-gated calcium channels. An alternative mechanism involves the activation of G protein-coupled potassium channels by D2 receptor activation, subsequent hyperpolarization of the lactotroph membrane, and an indirect inhibition of calcium influx as spontaneous electrical activity is reduced. Using patch voltage clamp methods, we have reexamined the effect of D2 receptor activation on calcium currents (ICa) in pituitary cells from normal cycling female rats and in GH4Cl pituitary tumor cells expressing cloned D2 receptors. Furthermore, we have examined secretory responses using a single cell immunoblot method. Dopamine (0.1-10 microM) failed to significantly inhibit ICa in either GH4Cl cells or normal female lactotrophs. Similarly, the D2 agonist quinpirole (20-100 microM) did not reduce ICa in lactotrophs. No responses to D2 agonists were seen when barium was substituted for calcium or when experiments were performed using the nystatin-permeabilized patch technique to avoid loss of intracellular macromolecules. Quinpirole also failed to inhibit ICa in lactotrophs isolated from lactating female rats. We have thus far been unable to observe a significant inhibition of ICa by activation of D2 receptors. PRL secretion assessed by immunoblotting methods was dramatically inhibited by quinpirole at normal (5 mM) extracellular K+. However, in elevated (50 mM) K+ that depolarizes the cells and activates calcium channels, quinpirole produced only a very modest inhibition of secretion. We conclude that direct inhibition of ICa by D2 receptor activation is not a major mechanism underlying the dopaminergic inhibition of PRL, secretion in normal female lactotrophs.

Topics: Animals; Barium; Calcium Channels; Dopamine; Electric Conductivity; Ergolines; Female; Lactation; Pituitary Gland, Anterior; Pituitary Neoplasms; Prolactin; Quinpirole; Rats; Receptors, Dopamine D2; Signal Transduction; Transfection; Tumor Cells, Cultured

In contrast to lactotrophs, tumoral pituitary cells like GH3 and GH4C1 lack expression of dopamine D2short and D2long receptors. In GH4C1 cells, we observed that the expression of only the short isoform of D2 receptor can be induced after transfection with a plasmid which confers resistance to neomycin (pRSVNeo). High levels of fully functional D2short receptor were obtained in GH4C1 following transfection (528fmol/mg protein). Sequence, pharmacology and coupling of the induced-D2 receptor do not show any difference with the cloned rat D2 short receptor.

Topics: Animals; Apomorphine; Base Sequence; Colforsin; Cyclic AMP; Dopamine; Dose-Response Relationship, Drug; Ergolines; Gene Expression; Kanamycin Kinase; Kinetics; Molecular Sequence Data; Oligodeoxyribonucleotides; Phosphotransferases; Pituitary Neoplasms; Polymerase Chain Reaction; Potassium Chloride; Prolactin; Quinpirole; Rats; Receptors, Dopamine D2; Recombinant Fusion Proteins; Spiperone; Sulpiride; Transfection; Tumor Cells, Cultured; Vasoactive Intestinal Peptide

The efficacy and safety of the new long-acting dopamine agonist cabergoline were evaluated in 127 hyperprolactinemic patients (124F and 3M; 71 with microprolactinoma, 14 with macroprolactinoma, 5 with operated macroprolactinoma and 37 with idiopathic disorder) who were treated with the drug for from 3 to 52 months (median, 14 months). Cabergoline was administered orally at dose levels ranging between 0.2 and 3.5 mg per week, given once weekly in 92 patients, twice weekly in 22, thrice weekly in 9 and daily in 4. Serum prolactin and progesterone levels, hematology, blood chemistry and electrocardiograms were frequently evaluated throughout treatment. CT or MR imaging of the pituitary was repeated during treatment in patients with macroprolactinoma and in 38 with microprolactinoma. After drug discontinuation, serum prolactin and gonadal function were evaluated monthly for three months in 65 patients and for up to two years in 12. Serum prolactin levels were normalized in 114 patients (90%). Of 56 women with amenorrhea, 52 resumed menses (with presumptive evidence of ovulation in 49); 17 women became pregnant; and sexual potency was restored in the 3 men. Evidence of tumor shrinkage was obtained in 13 of the 14 patients with macroprolactinoma and in 28 of 38 with microprolactinoma; complete disappearance of the tumor image was achieved in 2 macro and 14 microprolactinomas. A total of 48 adverse events was reported by 29 patients (23%), almost all typical of the pharmacological class and mild to moderate; no patient withdrew from treatment due to adverse events. Safety parameters did not change. Following cabergoline discontinuation, prolactin levels increased slowly, being still markedly lower than pretreatment values after three months; 10 patients out of 32 had persistently normal prolactin levels during one year of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Bromocriptine; Cabergoline; Drug Resistance; Ergolines; Female; Humans; Hyperprolactinemia; Male; Menstruation Disturbances; Middle Aged; Ovulation; Pituitary Neoplasms; Prolactinoma

GH3 cells are a clonal strain from a rat pituitary tumor that synthesizes and secretes both PRL and GH. The peculiarity of these cells is that they do not express receptors for dopamine; thus the hormone release is insensitive to the inhibitory effect of dopamine and D2 receptor agonists. Exposure of GH3 cells to epidermal growth factor for 4 consecutive days markedly altered the cell morphology, from a spherical appearance to an elongated flattened shape, and increased the cell size. These morphological changes were accompanied by the functional expression of D2 dopamine receptors as shown by the presence of a specific, saturable, and stereoselective high affinity binding for [3H]spiroperidol in epidermal growth factor-treated cells and by the fact that the selective D2 agonist quinpirole recovered the property to inhibit PRL secretion in the cell cultures exposed to the neurotrophic factor. The effect of EGF on the functional expression of D2 receptors was dose dependent (EC50 = 8 pM) and reversible. These data suggest that EGF elicits major effects on the expression of specific genes leading to the differentiation of GH3 cells into lactotroph-like cells endowed with dopamine D2 receptors.

Topics: Animals; Binding, Competitive; Cell Line; Cells, Cultured; Dopamine Agents; Epidermal Growth Factor; Ergolines; Kinetics; Pituitary Gland, Anterior; Pituitary Neoplasms; Potassium; Prolactin; Quinpirole; Rats; Receptors, Dopamine; Receptors, Dopamine D2; Spiperone

Hypophyseal portal dopamine is a major negative regulator of pituitary prolactin (PRL) production. Dopamine has been reported to repress PRL gene transcription in pituitary cells. To facilitate further study of the effect of dopamine on PRL gene activation, we introduced PRL promoter and D2 receptor (D2R) constructs into GH3 cells. Since two D2R isoforms (termed D2S and D2L) have been cloned previously, we first determined which isoform(s) is present in the lactotroph by measuring the level of each mRNA species in rat prolactinoma. mRNA for each D2R isoform was found to be present, with the D2L mRNA in great (c. 6-fold) excess. Because the lactotroph contains both isoforms, the effect of each on the PRL promoter was investigated. The cDNA for each receptor isoform was synthesized by polymerase chain reaction, and cloned into an RSV-based expression vector. GH3 cells were then transiently co-transfected with either of the resulting RSV-D2R constructs plus a PRL-chloramphenicol acetyltransferase (CAT) construct containing the first 1957 base-pairs of PRL gene 5'-flanking DNA. The cells were then incubated 48 h plus or minus the dopamine agonist ergocryptine (ECR). In the presence of either RSV-D2R isoform, ECR yielded a 4-5-fold decrease in CAT activity, an effect not seen in the absence of the RSV-D2R. The promoter specificity of this effect was demonstrated by the inability of ECR to regulate expression of a control RSV-CAT construct. The PRL promoter repression mediated by each receptor isoform had appropriate pharmacology: the specific D2R agonist, quinpirole, yielded results similar to ECR, and the ECR repression was reversed by the dopamine antagonist spiperone.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cell Line; Ergolines; Female; Hysterectomy; Ovariectomy; Pituitary Neoplasms; Plasmids; Prolactin; Prolactinoma; Promoter Regions, Genetic; Rats; Rats, Inbred F344; Receptors, Dopamine; Receptors, Dopamine D1; RNA, Messenger; Signal Transduction; Spiperone; Transcription, Genetic

Osteocalcin (OC) concentration, a specific index of bone formation, was measured in 29 female patients with microprolactinoma (serum prolactin, PRL: 105 +/- 10.9 ng/ml; mean +/- SE). Mean OC levels were significantly lower than in controls (1.7 +/- 0.2 vs 5.1 +/- 0.3 ng/ml; p less than 0.001), being below the normal range in 28 out of 29 patients. All patients were treated with dopaminergic agents (dihydroergocriptine, bromocriptine or cabergoline). After treatment mean serum PRL levels were significantly reduced (12 +/- 3.1 ng/ml; p less than 0.001), a full normalization being obtained in 26 patients. There were no significant differences in both basal and after treatment PRL levels among patients treated with different drugs, although a greater PRL decrease was induced by cabergoline. Serum OC levels significantly increased after 12 month therapy (4.7 +/- 0.6 ng/ml, p less than 0.001), a normal concentration being reached in 14 of 29 cases. During treatment there were no significant differences in serum estradiol and PRL concentrations between patients who normalized or not their OC levels, while the reduction in PRL levels with respect to baseline was more pronounced in the former group. The absolute increase in OC levels positively correlated with serum PRL decrements (p less than 0.01). It is noteworthy that serum OC normalized in 1/10 patients during dihydroergocriptine, 3/8 during bromocriptine and 10/11 during cabergoline. Four patients, previously treated with dihydroergocriptine and bromocriptine without normalizing OC and PRL levels, underwent a second course of therapy with cabergoline and then normalized OC concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Antineoplastic Agents; Bone Density; Cabergoline; Dihydroergotoxine; Dopamine Agents; Ergolines; Estradiol; Female; Humans; Hyperprolactinemia; Osteocalcin; Pituitary Neoplasms; Prolactin; Prolactinoma

We performed 113 new treatments in 98 patients (pts) (69 females and 27 males), 41 with macroprolactinoma, 26 with microprolactinoma, 5 with empty sella and 26 with idiopathic hyperprolactinemia. Parlodel LA was administered in 31/113, Parlodel LAR in 51/113, Parlodel SRO in 24/113 and Cabergoline in 8/113. In each pt the clinical effect, PRL plasma level CT-scan and visual field examination were monitored. PRL plasma levels normalized in 84/98 pts. In 13/41 macroadenoma pts a complete disappearance of the adenomatous mass was observed at CT-scan after 0.5-3 years' oral bromocriptine or Parlodel LAR therapy. The clinical features normalized in most of the pts. In conclusion, the new long acting dopamine agonists may represent the future of the management of hyperprolactinemic states because of their effectiveness, tolerability and good compliance.

Topics: Adenoma; Bromocriptine; Cabergoline; Delayed-Action Preparations; Empty Sella Syndrome; Ergolines; Female; Humans; Hyperprolactinemia; Male; Pituitary Neoplasms

Different weekly doses (400 to 3,000 micrograms) of the new, long-acting dopamine agonist Cabergoline (Farmitalia Carlo Erba, Milan, Italy) were given to 11 hyperprolactinemic women with pituitary tumor. Pituitary computerized tomography (CT) scans were performed before the start of treatment and after 3 (n = 5), 6 (n = 3), and 9 (n = 3) months of Cabergoline administration. Plasma prolactin (PRL) was determined in blood samples collected before and at weekly intervals during Cabergoline administration. Cabergoline induced marked inhibition of PRL secretion in conjunction with a CT demonstration of reduction in the pituitary tumor size in all patients. The potent, long-lasting PRL inhibitory effect of Cabergoline and the absence of side effects typical of dopaminergic compounds suggest that the use of this drug is advantageous over others in the medical treatment of hyperprolactinemia.

Topics: Adolescent; Adult; Antineoplastic Agents; Cabergoline; Dopamine Agents; Ergolines; Female; Humans; Pituitary Neoplasms; Prolactin; Prolactinoma; Time Factors; Tomography, X-Ray Computed

Cabergoline (CAB) is a new oral dopaminergic compound showing a very long-lasting PRL-lowering activity and reported to be well tolerated. The efficacy and tolerability of chronic treatment with CAB in 30 female hyperprolactinemic patients, aged 18-52 yr (6 microadenomas, 3 macroadenomas, and 21 functional hyperprolactinemias), were studied. In a group of 10 patients who received CAB (0.8 mg once weekly or 0.4 mg twice weekly) for 8 weeks PRL levels normalized while on treatment and remained normal (8 patients) or greatly reduced (1 patient) for 1-2 months after discontinuation of the drug. Twenty-six patients underwent chronic treatment (6-12 months) with an initial dose of 0.5 mg once weekly, subsequently increased to 1-2 mg in 10 patients and decreased in the other 2. Due to severe side-effects CAB was discontinued in 3 patients, in 1, 8, and 12 weeks. A significant reduction of PRL levels was already observed after the first week of treatment (mean +/- SEM basal values, 90.1 +/- 13.3 vs. 29.5 +/- 6.3 micrograms/L; P less than 0.001). Twenty-two patients had normal PRL levels in 1-36 weeks (mean, 6 weeks) with 0.5-2 mg CAB. Twenty-two patients resumed regular menses; 2 patients became pregnant after 3-11 months of treatment. Thirteen patients complained of side-effects (nausea, hypotension, headache, gastric pain, dizziness, and weakness) that disappeared with time in 10 of them. The comparison with a previous bromocriptine treatment regimen in 20 patients had shown that the number of patients requiring discontinuation of the latter drug was significantly higher (7 vs. 3 patients; P less than 0.001). However, 2 patients who needed to discontinue CAB were able to tolerate bromocriptine therapy. A computed tomographic scan performed after 12 months of therapy in 7 patients showed a significant reduction (50%) of the adenoma in 5. In conclusion, our results show that CAB is a well tolerated new dopamine agonist with long-lasting activity that represents an advance in chronic medical treatment of hyperprolactinemic conditions.

Topics: Adenoma; Adult; Amenorrhea; Bromocriptine; Cabergoline; Dopamine Agents; Ergolines; Female; Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactin

Cabergoline 1-[(6-allylergolin-8 beta-yl)carbonyl]-1-[3-(dimethylamino) propyl]-3-ethylurea is a recently developed ergot derivative with a long-lasting dopamine agonist action. We now studied the ability of cabergoline to counteract the development of a prolactin-secreting tumor (prolactinoma) induced in female rats by long-term administration of high doses of estrogens. The effect of cabergoline was compared to that of bromocriptine. Cabergoline (0.6 mg/kg p.o.) had a marked and sustained prolactin-lowering effect in freely moving female rats, its effect still being present 3 days after a single dose. Bromocriptine, at a dose 5-fold higher (3 mg/kg s.c.), induced a strong and short-lasting prolactin inhibitory effect which, however, had completely disappeared 24 h post-injection. Intermittent administration of cabergoline (0.6 mg/kg p.o. every 3 days), starting from the first day of estrogen treatment, completely counteracted the development of the prolactinoma, as judged by the weight of the pituitary and the stimulating effect of estrogens on plasma prolactin and mitotic rate and DNA synthesis of pituitary cells. These effects of cabergoline were shared by a 5-fold higher dose of bromocriptine (3 mg/kg s.c.) given daily. The potent anti-tumorigenic effect of cabergoline, coupled to a sustained prolactin-lowering effect, the most prolonged ever seen with an ergot derivative, makes cabergoline a most suitable drug for the treatment of human macroprolactinomas.

Topics: Adenoma; Animals; Antineoplastic Agents; Body Weight; Bromocriptine; Cabergoline; DNA, Neoplasm; Ergolines; Estrogens; Female; Mitosis; Pituitary Neoplasms; Prolactin; Rats

Twelve hyperprolactinemic women were administered the alpha aminoergoline derivative, CU 32-085 (Sandoz, Inc., East Hanover, NJ), in order to determine its effect on prolactin (PRL) secretion. The mean pretreatment serum PRL level was 145.0 +/- 11.5 ng/ml. Significant declines of serum PRL occurred with total daily doses of CU 32-085 of 0.1 to 0.5 mg (P less than 0.001). The magnitude of response to therapy was dose-related. In six patients, PRL levels were reduced to less than 25 ng/ml; this effect lasted at least 24 hours after intake of a single dose. In the other six patients, the response was less dramatic. No subjects developed adverse cardiovascular side effects. The results of this study demonstrate that CU 32-085 exhibits a clinically significant dopaminomimetic action on PRL secretion in hyperprolactinemic women.

Topics: Adenoma; Adult; Ergolines; Female; Humans; Hyperprolactinemia; Kinetics; Menstruation Disturbances; Pituitary Neoplasms; Prolactin

Two novel dopaminergic drugs, designated CV 205-502 and CQP 201-403 have recently been developed by Sandoz Pharmaceuticals Ltd (Basle, Switzerland). The effects of these drugs on PRL and GH secretion by normal rat and tumorous human pituitary cells in vitro have been investigated. Low doses of both CV 205-502 and CQP 201-403 immediately and profoundly suppressed PRL secretion, which failed to recover up to 7 h after removal of the drugs. Similarly, CQP 201-403 significantly suppressed basal GH secretion by human pituitary somatotropic tumours in culture, and both drugs significantly reduced the stimulatory effect of GHRH. These effects are more potent and longer acting than the previously described in vitro effects of bromocriptine. It is concluded that CV 205-502 and CQP 201-403 hold potential for the treatment of patients with hyperprolactinaemia and, possibly, also in patients with acromegaly.

Topics: Aminoquinolines; Animals; Ergolines; Growth Hormone; Humans; Pituitary Gland, Anterior; Pituitary Neoplasms; Prolactin; Rats; Receptors, Dopamine; Tumor Cells, Cultured

Two patients with macroprolactinomas were treated with the partial dopamine agonist, terguride. The prolactin (Prl) levels were lowered very effectively and in both cases the clinical symptoms improved markedly during the first days of treatment. Computerized tomography (CT) and magnetic resonance imaging (MRI) follow-up studies showed distinct tumour shrinkages which were first documented by MRI within 2 weeks of treatment. Tumour residues were, however, still demonstrable by MRI after more than one year respectively 3 months of therapy. In principal, results from both imaging techniques were comparable with the exception of the one year follow-up study of patient 1. In CT no residual tumour mass was visible whereas MRI showed only little reduction when compared to the 30th week scan. Throughout the treatment terguride was well tolerated without any side effects up to a maximal daily dosage of 3 mg given orally. Presumably the partial agonistic features of terguride contributed to the good tolerance of the treatment as compared to that of full dopamine agonists like bromocriptine of lisuride. Thus, these preliminary results indicate that terguride may be a beneficial alternative in the treatment of prolactinomas and other hyperprolactinaemic states.

Topics: Adenoma; Adult; Ergolines; Female; Follow-Up Studies; Humans; Lisuride; Pituitary Neoplasms; Prolactin; Receptors, Dopamine; Thyrotropin-Releasing Hormone; Tomography, X-Ray Computed

The pharmacokinetics of oral terguride 1 mg was evaluated in a single-dose study in 8 patients with a prolactinoma and one with acromegaly. A radioreceptor assay was used to measure the plasma levels of terguride. The peak plasma concentration (2.3 +/- 0.7 ng/ml, mean +/- SEM) was attained within 1 h of drug administration. Moment analysis gave a mean residence time of 4.3 +/- 0.6 h. Plasma prolactin was also determined by radioimmunoassay. The plasma prolactin was reduced to 30 +/- 3% of its pretreatment value after 4 h.

Topics: Acromegaly; Adult; Ergolines; Female; Half-Life; Humans; Kinetics; Lisuride; Male; Middle Aged; Pituitary Neoplasms; Prolactin

A 19-year-old woman presented with headaches, temporal lobe epilepsy and primary amenorrhoea. There was a family history of multiple endocrine adenomatosis. Investigation revealed normal visual fields and acuity, hyperprolactinaemia (48 000 mU/l) and a very large pituitary tumour with extrasellar spread. Treatment with bromocriptine reduced the tumour size and the prolactin level to 2440 mU/l. Six months after the start of therapy, resistance to bromocriptine developed and the prolactin concentration progressively rose to pretreatment levels, despite increasing the dose of bromocriptine to 40 mg/d. At this stage treatment with a second dopamine agonist, pergolide, was effective in reducing the prolactin concentration to normal within four months. Serial CT scans at 1, 6 and 12 months on dopamine agonist therapy showed a progressive decrease in tumour size, which seemed to be maintained even during the period of rising prolactin concentrations due to bromocriptine resistance. This case illustrates that during dopamine agonist therapy a discrepancy may exist in the clinical response as judged by reduction in tumour size and decrease in the circulating prolactin level. Furthermore, in patients with prolactinomas, pergolide may induce a response when resistance to bromocriptine develops.

Topics: Adult; Bromocriptine; Drug Resistance; Ergolines; Female; Humans; Pergolide; Pituitary Neoplasms; Prolactin; Tomography, X-Ray Computed

The long term effectiveness and tolerance of terguride, a new ergot derivative, as initial therapy were evaluated in 20 patients with pathological hyperprolactinemia (PHP; group A) and 7 patients with acromegaly. We also studied 10 patients with PHP whose treatment was changed from bromocriptine or lisuride to terguride (group B). Terguride, given for at least 6 months in divided doses ranging from 0.25-1.50 mg/day to group A patients, resulted in normal (11 patients) or markedly reduced plasma PRL levels. Gonadal function was restored in all but 2 patients in this group, and the tumors shrank in 3 of 5 patients with a macroprolactinoma and in 1 of 3 patients with a microprolactinoma. In group B patients, positive effects of the previous treatment on PRL levels, gonadal function, and tumor growth were maintained by terguride. Terguride suppressed plasma GH levels below 50% of baseline in 4 of the 7 acromegalic patients. Two of the 27 patients initially treated with terguride complained of mild nausea and postural hypotension only after the first dose (0.25 mg) of the drug. No patient in group B had any side-effects during terguride, with the exception of 1 patient who was also intolerant to bromocriptine. We conclude that terguride is an effective well tolerated dopaminergic agent in PHP.

Topics: Acromegaly; Adenoma; Adolescent; Adult; Ergolines; Female; Humans; Hyperprolactinemia; Lisuride; Male; Menstruation; Middle Aged; Pituitary Neoplasms

19 macroprolactinomas and 1 microprolactinoma were analysed by light microscopical, immunohistological and ultrastructural as well as morphometrical methods. 8 adenomas were removed from patients who were treated preoperatively with bromocriptine and/or Lisurid for different periods. 18 of 20 adenomas were positive for PRL on the immunohistological level. One case was negative. This patient showed a good response to the pharmacological treatment. The ultrastructure of this case revealed many secretory granules. A morphometric analysis of the ultrastructure could be performed in 19 cases; 1 case had to be excluded because of large necrotic areas. The following qualitative significant alterations after the treatment could be established: Reduction of the volume density of the rough endoplasmatic reticulum; Reduction of the size of the granula diameter; Increase of the volume density of the more irregular and indented nuclei. Other alterations were as follows: Reduction of the nuclear size; Increase of the number of secretory granules and of the volume density of lysosomes. These changes were to be observed in most of those tumors which responded to the dopamine agonist treatment. The non-responding adenomas and one which was removed 6 days after having discontinued a successful preoperative medical therapy were similar to the untreated adenomas. The results display the influence of dopamine agonist on the hormone synthesis, release and degradation in PRL secreting adenoma cells.

Topics: Adenoma; Adolescent; Adult; Bromocriptine; Cell Nucleolus; Cell Nucleus; Dopamine; Endoplasmic Reticulum; Ergolines; Ergot Alkaloids; Exocytosis; Female; Humans; Lisuride; Male; Mitochondria; Organoids; Pituitary Neoplasms; Prolactin

The ergoline derivative, Metergoline, in a dosage of 4 to 24 mg/day, was administered for one to eight months to 42 patients with hyperprolactinemic amenorrhea. Mean serum prolactin (PRL) concentrations before treatment were 91.2 ng/mL in the patients with functional hyperprolactinemia (N = 29) and 256.9 ng/mL in the patients with pituitary tumor (N = 13). Within four weeks, Metergoline treatment reduced these PRL concentrations to 39.5 ng/mL and 82.9 ng/mL, respectively. In this study Metergoline treatment resulted in restoration of menstruation in a total of 37 patients; 28 patients ovulated, and eight became pregnant. It is considerably more effective in functional hyperprolactinemia than in hyperprolactinemia caused by adenoma.

Topics: Adenoma; Adult; Amenorrhea; Ergolines; Female; Humans; Hyperprolactinemia; Metergoline; Metoclopramide; Nausea; Ovulation; Pituitary Neoplasms; Progesterone; Prolactin; Tomography, X-Ray Computed

We have studied the in vitro TSH secretion and the adenylate cyclase (AC) activity of a human pituitary adenoma surgically removed from a hyperthyroid patient showing high serum TSH levels. The tumor appeared almost homogeneously constituted by cells positive for an anti-TSH-beta antiserum and showing the ultrastructural characteristics of the adenomatous thyrotrophs. Adenoma fragments released in vitro a large amount of TSH (148.4 microU/mg prot/30 min), alpha-subunit (35.5 ng/mg prot/30 min) and TSH-beta (10.1 ng/mg prot/30 min). The effects of somatostatin (GHRIH) and dopamine (DA) on the hormone release have been tested in vitro. Both agents markedly inhibited the release of intact TSH and TSH-beta whereas the release of alpha-subunit was less affected. The two agents were effective at concentrations higher than 10(-8)M. The ability of GHRIH and DA in modulating the AC activity was investigated in membrane fraction preparations. GHRIH inhibited AC at concentrations higher than 10(-7)M. The maximal inhibition was 32% at 10(-5)M. Conversely, DA slightly stimulated AC activity. This effects was not mimicked by the dopaminergic ergot CH 29-717, which was completely ineffective on the enzyme. These results suggest that: 1) in this TSH-secreting pituitary adenoma a normal secretory response to the inhibiting agents (GHRIH and DA) is present; 2) different mechanisms of transduction of the GHRIH and DA signals (cAMP dependent and cAMP independent) could be operating in this tumor.

Topics: Adenoma; Adenylyl Cyclases; Dopamine; Dose-Response Relationship, Drug; Ergolines; Female; Humans; Hyperthyroidism; In Vitro Techniques; Middle Aged; Pituitary Neoplasms; Radioimmunoassay; Somatostatin; Thyrotropin

In some cases of Cushing's syndrome both bromocriptine and lisuride inhibit the secretion of ACTH but it is still unknown if they act at pituitary or at higher levels. In order to evaluate this aspect, we set up an in vitro perfusion system with anterior pituitary cells from rats and from human ACTH-secreting tumors. In both preparations lysine-vasopressin (LVP) and epinephrine (EPI) stimulated ACTH secretion; prazosin (alpha-1 blocker) inhibited the EPI but not the LVP-mediated stimulation. Similarly, the infusion of lisuride blocked ACTH response to EPI but not to LVP. These data may suggest that "dopaminergic" drugs could act by an adrenergic blockade and not necessarily by a dopaminergic inhibition.

Topics: Adenoma; Adrenergic alpha-Antagonists; Adrenocorticotropic Hormone; Animals; Dopamine; Epinephrine; Ergolines; Female; Humans; In Vitro Techniques; Lisuride; Lypressin; Pituitary Gland, Anterior; Pituitary Neoplasms; Prazosin; Rats; Rats, Inbred Strains

Pituitary adenomas may produce local endocrine and neurological effects, as well as systemic metabolic complications due to hormonal hypersecretion. Medical therapy with pharmacological agents has been developed and is based on the neurotransmitter regulation of normal pituitary hormonal secretion. 189 patients with secretory pituitary adenomas underwent medical therapy for the hypersecretory state. 156 of these were prolactin-secreting adenomas, 16 of which were in males. The response of bromocriptine was almost universal with lowering of serum prolactin and reversal of the clinical symptoms, as well as tumor shrinkage of most large adenomas with suprasellar extension. 23 patients with acromegaly were treated with bromocriptine, with 11 noting clinical improvement, and decreased tumor size in two. Five patients with Cushing's disease were treated with cyproheptadine, with only one showing a biochemical and clinical improvement. Two patients with Nelson's syndrome each had progressive tumor growth stabilized with cyproheptadine and bromocriptine in one, and sodium valproate in the other. There appears to be a role for medical therapy in the majority of prolactin-secreting pituitary tumors, some growth hormone secreting pituitary tumors, and selected adrenocorticotropin secreting-pituitary tumors.

Topics: Adenoma; Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Bromocriptine; Cyproheptadine; Ergolines; Female; Humans; Male; Middle Aged; Pergolide; Pituitary Gland; Pituitary Neoplasms; Prolactin; Valproic Acid

Work in recent years has revealed that prolactin can no longer be considered exclusively as a lactation hormone, and must be seen in a much wider physiological perspective. Biochemical and pharmacological studies in animals have made a special contribution, and prolactin is becoming increasingly important in toxicological investigations. The general custom of using rats for such studies has its own inherent problems, involving both the analytical methodology and the special requirements that must be observed in the housing and handling of these experimental animals. The aim of workshop conference was to review these special problems, together with our present knowledge of the mechanisms of prolactin secretion, and to present examples of pharmacological and toxicological studies on prolactin. Döhler (Hannover) spoke on the effect of experimental and pre-experimental conditions on the results of prolactin determination in rats. He described in detail the influence of sex, age and animal strain, and of biological rhythms. Alongside these physiological factors, however, a very great influence is exerted by the conditions of housing, and any external interference leads to often dramatic alterations in prolactin secretion. Wuttke (Göttingen) discussed the mechanisms of prolactin secretion in the rat. Here, dopamine holds a key position. This is also pharmacologically important, because prolactin secretion is stimulated by all dopamine antagonists and inhibited by all dopamine agonists. Vasointestinal polypeptide (VIP) and thyroliberin (TRH) stimulate prolactin secretion directly. The contribution by Nagy (Budapest) dealt with prolactin secretion in lactating rats and its modification by various transmitters.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aging; Anesthesia; Animals; Circadian Rhythm; Environment; Ergolines; Ergot Alkaloids; Female; Lactation; Male; Pituitary Neoplasms; Pregnancy; Prolactin; Rats; Rats, Inbred Strains; Seasons; Sex Factors; Species Specificity

Topics: Adenoma; Bromocriptine; Ergolines; Female; Humans; Lisuride; Metergoline; Pergolide; Pituitary Neoplasms; Pregnancy; Prolactin; Radiotherapy Dosage; Radiotherapy, High-Energy; Time Factors

A patient with a primary adenohypophyseal neoplasm who had a long course marked by multiple surgical resections, radiation therapy, and high-dose dopamine agonist therapy developed local invasion as well as cranial and extracranial osseous metastatic lesions. The serum prolactin levels were greatly elevated, and immunohistochemical studies demonstrated prolactin in the cytoplasm of primary and metastatic tumor cells. Ultrastructural features of lactotrophic differentiation, including misplaced granule exocytosis, were observed. This is the third reported case of prolactin cell carcinoma that metastasized despite high-dose dopamine agonist therapy. Analysis of the patient's serum prolactin showed no abnormality in the chromatographic profile of biologic activity.

Topics: Biological Assay; Brain Neoplasms; Bromocriptine; Combined Modality Therapy; Ergolines; Female; Histocytochemistry; Hormones; Humans; Microscopy, Electron; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis; Pergolide; Pituitary Neoplasms; Prolactin

To evaluate the long-term effects of dopamine agonists in the treatment of macroprolactinoma, we studied prolactin levels and tumor size for 30 to 88 months (57 +/- 14, mean +/- S.D.) in 38 patients treated with bromocriptine or lisuride. Elevated prolactin levels became normal in 30 patients, and the tumor shrank in 29. After two years of treatment, we attempted to reduce the maintenance dose (5 to 20 mg of bromocriptine per day or 0.4 to 0.8 mg of lisuride per day); in 21 patients no changes in prolactin levels or tumor size were observed over 6 to 52 months with 0.625 to 10 mg of bromocriptine per day or 0.05 mg of lisuride per day. However, it was possible to withdraw the drug in only one patient. We conclude that dopamine agonists are usually effective treatments for macroprolactinoma and that after a response has been obtained, it can be maintained in many patients with a greatly reduced dose.

Topics: Adenoma; Adult; Aged; Bromocriptine; Ergolines; Female; Humans; Lisuride; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Radiography; Receptors, Dopamine

The clinical activity of the new ergoline, mesulergine, was compared to pergolide in the treatment of hyperprolactinaemia. Mesulergine was given to 22 women and five men with hyperprolactinaemia. Serum prolactin was substantially lowered in 10 women; two subsequently conceived and completed normal pregnancies. Twelve women stopped treatment due to side-effects, usually nausea and vomiting, or inadequate responses. The side-effects were generally similar to those on bromocriptine; in one patient they were better and in four worse than on bromocriptine. The male patients were more tolerant of mesulergine, and substantial falls in serum prolactin were seen with evidence of tumour shrinkage. Twenty-seven women with hyperprolactinaemia received pergolide; serum prolactin was lowered or normalized in 16. Side-effects necessitating cessation of treatment were similar to those seen with bromocriptine. Nevertheless, four women tolerated pergolide better than bromocriptine and two women adequately treated with mesulergine had previously been intolerant of pergolide. We conclude that both pergolide and mesulergine may be useful and effective drugs in the treatment of hyperprolactinaemia as alternatives to bromocriptine.

Topics: Adenoma; Adult; Ergolines; Female; Humans; Male; Middle Aged; Pergolide; Pituitary Neoplasms; Pregnancy; Prolactin

Fifteen patients (12 male) with large pituitary tumours and serum prolactin levels below 1000 mU/l were given dopamine agonist therapy (bromocriptine, mesulergine or pergolide) for a mean of 9 months (range 3-36 months). Serum prolactin became undetectable in all. Despite this, significant suprasellar extensions and any associated neurological defect remained in 14 patients, who therefore were referred for surgery. In one patient there was evidence of spontaneous pituitary infarction unrelated to dopamine agonist therapy. At operation 12 patients had apparently functionless pituitary adenomas which failed to immunostain for prolactin, one had an epidermoid cyst and one a Rathke's pouch cyst. We conclude that patients with large pituitary tumours and only a mildly elevated serum prolactin are unlikely to have prolactinomas, and that such tumours are not likely to show significant tumour shrinkage with medical treatment with dopamine agonists.

Topics: Adenoma, Chromophobe; Adult; Bromocriptine; Dopamine; Ergolines; Female; Humans; Male; Middle Aged; Pergolide; Pituitary Neoplasms; Prolactin; Prospective Studies

Topics: Adenoma; Bromocriptine; Ergolines; Female; Humans; Male; Metergoline; Pituitary Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Prolactin

The clinical, radiological, and biochemical effects of dopamine agonist withdrawal after long-term treatment were investigated in seven women and eight men who had been treated for prolactinomas for 1.5 to 7 (mean 3.7) years. Before treatment, serum prolactin concentrations were 1473 to 115 000 mU/l, all patients had abnormal radiological findings, and six had suprasellar extensions of pituitary tumours. Treatment with either bromocriptine or pergolide relieved symptoms and suppressed prolactin secretion in most patients. The size of the residual tumour was defined by doing fourth generation computerised tomographic scans immediately before termination of therapy, and evidence of tumour re-expansion was sought on scans repeated 5-39 weeks later. After discontinuation of treatment, symptoms recurred in 13 of 15 patients and hyper-prolactinaemia redeveloped in 14. Other pituitary function tests remained unchanged or improved. In 13 of 15 patients tumour or gland size did not change after withdrawal of treatment. One man had a marginal increase in tumour size, while in another the pituitary tumour shrank. Thus, although cessation of long-term dopamine agonist therapy leads to recurrence of symptoms and hyperprolactinaemia, rapid tumour regrowth is uncommon and of small extent, and other pituitary function is not altered in the short term.

Topics: Adult; Aged; Bromocriptine; Dopamine; Ergolines; Female; Humans; Male; Middle Aged; Pergolide; Pituitary Function Tests; Pituitary Neoplasms; Pregnancy; Prolactin; Sella Turcica; Tomography, X-Ray Computed

The outcome of treatment of 36 women with prolactinomas using megavoltage radiotherapy combined with interim dopamine agonists (bromocriptine, lysuride, pergolide) was reviewed; 16 of the women showed radiological evidence of a macroadenoma. The most common presenting symptom was secondary amenorrhoea; 26 of the patients had galactorrhoea. In 29 patients who wished to conceive the ovulation rate (as indicated by circulating progesterone concentrations) was 97% and the successful fertility rate 86%. No patient had enlargement of the tumour during pregnancy and there were no complications of radiotherapy. No further tumour enlargement was detected in serial skull radiographs, and an improvement in size of the fossa was noted in 45% of those assessed. When medical treatment was withdrawn a mean of 4.2 years (range 1-11) after radiotherapy in the 27 patients who had completed their families the serum prolactin concentration had fallen appreciably in 26 of them and later became normal in eight. The incidence of growth hormone deficiency rose from 24% of the whole group before radiotherapy to 79% afterwards. Only one patient required thyroxine, and one was receiving gonadotrophin. No patient became deficient in adrenocorticotrophic hormone. A regimen of megavoltage radiotherapy and interim bromocriptine allows women with prolactinomas safely to undergo pregnancy and results in the long term prospect of tumour shrinkage and control of hyperprolactinaemia.

Topics: Adenoma; Adolescent; Adult; Combined Modality Therapy; Ergolines; Female; Fertility; Humans; Middle Aged; Pituitary Hormones, Anterior; Pituitary Neoplasms; Prolactin; Radiotherapy, High-Energy

Of 600 patients treated with the dopamine agonist drugs bromocriptine and lisuride for functioning pituitary tumours, eight developed drug related psychoses. Symptoms included auditory hallucinations, delusional ideas, and appreciable changes in mood. These reactions occurred with lower doses of the drugs than previously reported and remitted when treatment was stopped. The possibility of psychiatric side effects with dopamine agonist treatment should be recognised in view of the strain that may be placed on patients and their families.

Topics: Acromegaly; Adenoma; Adult; Bromocriptine; Ergolines; Female; Humans; Lisuride; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Psychoses, Substance-Induced

The tolerance and prolactin (PRL) release-inhibiting action of the 8 alpha-aminoergoline, mesurlergine, were investigated. In a blind crossover study in six subjects with hyperprolactinemia, 0.5 mg mesulergine induced fewer side effects than did 2.5 mg bromocriptine, while the PRL release-inhibiting effect of the two was of the same order. Six different subjects with suspected PRL-secreting pituitary adenomas who (repeatedly) had to discontinue bromocriptine because of nausea, vomiting, or symptoms of orthostatic hypotension were treated for 20 mo with mesulergine (1 to 2 mg/day). Mesulergine did not induce side effects and its actions resembled those of bromocriptine. Mesulergine induced cessation of galactorrhea and resumption of normal menstrual cycles in five subjects, while in one subject an insufficient luteal phase persisted. No abnormalities in routine blood parameter estimations were observed. In two of three subjects there was shrinkage of a pituitary tumor after 12 to 15 mo on mesulergine. Mesulergine did not directly inhibit PRL release by cultured normal rat pituitary cells and human prolactinoma cells and it antagonized the action of dopamine in a dose-dependent manner. This suggests that the dopaminergic action is carried out by a metabolite of mesulergine, while the parent drug probably prevents the well-known side effects of dopamine-agonistic drugs by its dopamine receptor blocking activity. Because of its acceptability, mesulergine might be important in the treatment of hyperprolactinemia and perhaps also of acromegaly and Parkinson's disease.

Topics: Adenoma; Administration, Oral; Adult; Animals; Blood Pressure; Bromocriptine; Cells, Cultured; Dopamine Antagonists; Drug Evaluation; Ergolines; Female; Humans; Hypotension; Male; Menstruation; Middle Aged; Nausea; Pituitary Neoplasms; Prolactin; Radioimmunoassay; Random Allocation; Rats

Topics: Acromegaly; Ergolines; Female; Growth Hormone; Humans; Middle Aged; Pergolide; Pituitary Neoplasms; Prolactin

Serum prolactin (PRL) was estimated for up to 2 months after discontinuation of therapy with either bromocriptine (n = 33; 15 with idiopathic disease, 12 with pituitary microadenoma, and six with macroadenoma) or metergoline (n = 23; 11 with idiopathic disease, and 12 with microadenoma) that had been administered for 8-30 months. Only five patients treated with bromocriptine and two treated with metergoline had PRL levels that remained normal or below 50% of pretreatment values. Among the patients followed-up for up to 12 months, four showed a fall in PRL at 3-4 months, but this was followed by a rise in one patient. Five patients showing persistently lower or normal PRL after drug withdrawal were retested with thyrotrophin-releasing hormone; the two responsive women also had a normal response before treatment. Of 10 patients followed for 9 months, three had persistently normal PRL levels. Amenorrhoea and anovulation recurred, with some delay, in all the patients showing PRL rebound except one. Medical treatment of hyperprolactinaemia only rarely results in permanent benefit.

Topics: Adenoma; Amenorrhea; Bromocriptine; Ergolines; Female; Humans; Metergoline; Ovulation; Pituitary Neoplasms; Progesterone; Prolactin; Prospective Studies; Recurrence

We studied the effects of long term treatment with bromocriptine (Br) or lisuride (L) on GH secretion and tumor size in 19 acromegalic patients with large pituitary adenomas. In 22 additional patients with smaller adenomas, only plasma GH levels were monitored during treatment. All patients underwent an acute test with 2.5 mg Br or 0.3 mg L and, on the basis of GH changes, were classified as responders, i.e. reduction in circulating GH concentrations by at least 50% below baseline, or as nonresponders. The chronic treatment was 5-20 mg/day Br in 26 patients or 0.3-2.0 mg/day L in 15 patients. Treatment was given for 4-26 months (mean +/- SE, 13.3 +/- 2.8 months). Plasma GH levels (baseline, 46.3 +/- 8.3 ng/ml) were significantly lower in the group as a whole (22.7 +/- 3.6 ng/ml; P less than 0.01) after the first month of treatment with dopamine agonist agents. GH levels decreased significantly in those acromegalic patients who responded to the acute test (P less than 0.001), but were unchanged in the nonresponders. In addition, there was a significant correlation between the maximal percent GH decrease in the acute test and the response during chronic treatment (r = 0.73; P less than 0.01). Computed tomography failed to show any tumor size changes in any of the GH nonresponders who had a macroadenoma . However, in two patients in the acute responder group with macroadenomas, chronic dopamine agonist therapy resulted in reduction of the extrasellar portion of the tumor (-30% and -40% of tumor area, respectively). These data show that although dopaminergic drugs lower GH levels and reverse signs and symptoms of active disease in those acromegalic patients who are responsive to an acute challenge, tumor size reduction occurred in a minority of such patients.

Topics: Acromegaly; Adenoma; Adult; Aged; Bromocriptine; Ergolines; Female; Growth Hormone; Humans; Lisuride; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Tomography, X-Ray Computed

Twenty five patients with hyperprolactinaemia were treated with pergolide mesylate, a new dopamine receptor agonist. Twenty three received treatment for six to 20 months, and in all serum prolactin concentrations were considerably reduced. In most patients prolactin concentrations were maintained in the normal range by a low, once daily dose of pergolide and reversal of associated reproductive disorders was observed. Tumour volume as assessed by computed tomography decreased considerably during treatment in three out of four patients with a pituitary tumour. The drug was well tolerated. Side effects were similar to those of bromocriptine, but four out of eight patients who had been forced to stop taking bromocriptine because of untoward effects were subsequently able to tolerate treatment with pergolide. Pergolide mesylate promises to be a useful addition to the currently available long acting dopamine agonists in the management of hyperprolactinaemia.

Topics: Adult; Ergolines; Female; Humans; Hypogonadism; Male; Menstruation Disturbances; Middle Aged; Pergolide; Pituitary Neoplasms; Prolactin; Time Factors

Eighteen hyperprolactinaemic patients were orally treated for up to 16 months with pergolide mesylate, a new potent long-lasting dopaminergic ergot derivative. In all cases, Prl normalization (less than 25 ng/ml) was achieved at a once-a-day dose of 50-300 micrograms. All women recovered and/or exhibited normal menstrual function. Among the 6 women wishing to become pregnant, 4 of them conceived within 4 months; there were other causes for infertility than hyperprolactinaemia in the 2 other couples. A macroprolactinoma man experienced important improvement in well-being as well as objective regression of his visual fields defect. This suggests a shrinkage effect of pergolide on the tumoural process. Another man regained normal potency and normal testosterone within 2 weeks. While 10 patients were completely free of any side effect, 7 experienced transiently mild gastro-intestinal side effects or postural hypotension. Only one patient discontinued her treatment because of dizziness. The present study demonstrates the high potency, the good tolerance and the excellent efficacy of pergolide in the treatment of hyperprolactinaemia.

Topics: Adolescent; Adult; Amenorrhea; Dose-Response Relationship, Drug; Ergolines; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Male; Middle Aged; Oligomenorrhea; Pergolide; Pituitary Neoplasms; Prolactin; Time Factors

59 patients affected by amenorrhea or anovulation, 37 of whom also with galactorrhea, and with hyperprolactinemia of unknown origin (idiopathic hyperprolactinemia, 24 patients) or due to a pituitary microadenoma (tumoral hyperprolactinemia, 35 patients) were treated with metergoline (4-12 mg/day) or with bromocriptine (2.5 to 10 mg/day) for 90 days. The effectiveness of the two treatments was assessed on clinical grounds and by evaluating at monthly intervals serum progesterone levels, during the presumed luteal phase, and serum prolactin levels. The success rate with the two drugs was superimposable in terms of disappearance of galactorrhea and return of menses, normalization of prolactin levels and induction of ovulation. Also the number of pregnancies obtained (7 with metergoline, 9 with bromocriptine) was similar. With both drugs, the majority of patients responded to the treatment within the first month.

Topics: Adenoma; Adult; Amenorrhea; Anovulation; Bromocriptine; Ergolines; Female; Galactorrhea; Humans; Metergoline; Middle Aged; Pituitary Neoplasms; Pregnancy; Prolactin

Topics: Adenoma; Ergolines; Female; Humans; Lisuride; Male; Pituitary Neoplasms; Prolactin

Forty patients with hyperprolactinaemia were treated with metergoline (8 to 12 mg/day) for periods up to 5 years. Analysis of the results of clinical and biological tolerability showed that treatment was generally well tolerated and although 28 patients complained of drug-related side-effects of various kinds, principally nausea, these were usually mild, present at the beginning of treatment and disappeared spontaneously in spite of continued metergoline administration over a prolonged period. No patient stopped treatment because of side-effects. Laboratory parameters also stayed within normal levels and there was no evidence of any alterations in the ECG. It is concluded, therefore, that metergoline is a well-tolerated as well as an effective ergolinic compound for use in those patients in whom prolonged treatment with a prolactin-lowering drug is considered necessary.

Topics: Adenoma; Adult; Drug Tolerance; Ergolines; Female; Humans; Metergoline; Pituitary Neoplasms; Prolactin; Retroperitoneal Fibrosis; Time Factors

We gave pergolide mesylate, a new long-acting ergot derivative with dopaminergic properties, to 47 patients with hypersecretion of prolactin or growth hormone. Single doses produced long-lasting reductions of serum prolactin levels; after 24 hours, the values remained depressed at a mean of 28.8 per cent of the base-line value. Among 41 patients (22 women and 19 men) with hyperprolactinemia who took pergolide for three months or more, prolactin levels fell to normal in 37 and remained slightly elevated in 2. In the two patients in whom the levels fell to only 38 to 52 per cent of base line, treatment was regarded as a failure. The level of growth hormone fell to a mean of 52.8 per cent of base line in patients with acromegaly who were taking 100 micrograms of pergolide per day. Among patients for whom adequate CT scans were available, definite tumor shrinkage occurred in 10 of 13 with macroadenomas and definite or probable shrinkage in 5 of 9 with microadenomas. Menses returned in 76 per cent of treated women and testosterone levels rose in 10 of 14 men. We conclude that pergolide reduces hypersecretion and shrinks most prolactin-secreting macroadenomas. In some patients long-term pergolide therapy may be superior to surgery and x-ray treatment.

Topics: Acromegaly; Adenoma; Ergolines; Female; Fertility; Growth Hormone; Humans; Male; Menstruation; Pergolide; Pituitary Neoplasms; Prolactin; Testosterone; Tomography, X-Ray Computed

The effect of pergolide mesylate was studied in two previously untreated men with large prolactinomas and exceptionally high prolactin concentrations. The study was designed to determine whether pergolide would be effective in alleviating symptoms, correcting hormonal abnormalities and shrinking the tumour. Starting with 50 micrograms daily the dose of pergolide was slowly increased over 10 weeks to 1 mg once daily, when repeat assessment was performed. Both patients reported complete relief of symptoms, with no side effects. Serum prolactin concentration was suppressed to normal in both subjects, and evidence to suggest tumour shrinkage was observed. Pergolide appears to be effective treatment for men with large prolactinomas.

Topics: Antineoplastic Agents; Ergolines; Humans; Male; Middle Aged; Pergolide; Pituitary Neoplasms; Prolactin

The effects of bromocriptine or metergoline treatment were evaluated in 80 hyperprolactinaemic patients (62 women and 18 men). The patients were subdivided into 4 groups: group A) 16 women with idiopathic hyperprolactinaemia; group B) 19 women with untreated Prl-secreting microadenomas; group C) 27 women with unsuccessfully operated prolactinomas; group D) 18 men with unsuccessfully treated macroprolactinomas. Sixty-eight patients were given bromocriptine (2.5-20 mg/day) for 3-58 months and 33 patients were given metergoline (4-16 mg/day) for 3-19 months. Bromocriptine and metergoline were equally effective in the treatment of functional hyperprolactinaemia and of untreated microadenomas, while bromocriptine showed a more potent Prl-lowering effect than metergoline in patients with higher Prl levels and large prolactinomas; both drugs restored the gonadal function to a similar extent, though metergoline was effective in some cases, even in the absence of full Prl suppression. Bromocriptine seems to exert an antitumoral effect, as documented by CT scan in some patients with macroadenomas, but the precise role of both drugs with respect to dose, length of treatment and effectiveness after withdrawal needs to be evaluated further.

Topics: Adenoma; Adolescent; Adult; Bromocriptine; Ergolines; Estradiol; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menopause; Metergoline; Middle Aged; Pituitary Neoplasms; Pregnancy; Progesterone; Prolactin; Testosterone

The effect of dopamine (DA) on GH release was studied in monolayer cultures obtained from 21 GH-secreting pituitary adenomas. DA at a concentration of 10(-6) M inhibited GH release in 13 adenomas (group 1: inhibition from 27--74%), had no effect in 3 (group II), and elicited a marked stimulation in 5 (group III: stimulation from 62--170%). The adenomas of acromegalic patients which were preoperatively responsive to DNA infusion (4 micrograms/kg . min) al fell into group I, whereas adenomas from patients not responsive to DA in vivo fell into groups II and III. The dose dependency of the effect of DA on GH secretion was studied in groups I and III. In group I adenomas the maximal inhibition was from 32--76% between 10(-7) and 2 x 10(-5) M DA. At high concentrations DA elicited a stimulatory effect. In group III adenomas the maximal stimulation was from 95--310% between 10(-7) and 10(-5) M DA. The dopaminergic ergot derivative CH 29--717 was as potent as DA in inhibiting GH release but, in contrast to DA, was nearly ineffective in stimulating the secretion of the hormone. We hypothesize that the different in vitro responsiveness of GH-secreting pituitary adenomas to DA could be due to the presence of multiple forms of DA receptors.

Topics: Adenoma; Cells, Cultured; Dopamine; Dose-Response Relationship, Drug; Ergolines; Female; Growth Hormone; Humans; Male; Pituitary Neoplasms; Prolactin

One hundred ninety-one hyperprolactinemic patients (78 women and 13 men; 54 with pituitary macroadenoma, 53 with microadenoma, and 84 with idiopathic disease) were treated for 2 to 48 months with one or two of the following prolactin (PRL)-lowering drugs: bromocriptine, metergoline, and lisuride. All of the three drugs used were highly effective in lowering PRL levels and restoring gonadal function both in females and in males in the majority of patients with either idiopathic or tumorous disease. In poorly responsive patients, increasing the drug doses resulted in further PRL lowering for all the three drugs. Mild side effects were frequently encountered with initiation of drug treatment but spontaneously subsided in most cases; severe side effects, necessitating stopping of the treatment, occurred in only 12 instances, but changing of the drug allowed PRL-lowering treatment to be continued in 11 of them.

Topics: Adenoma; Adolescent; Adult; Amenorrhea; Bromocriptine; Erectile Dysfunction; Ergolines; Female; Galactorrhea; Humans; Lisuride; Male; Metergoline; Middle Aged; Ovarian Function Tests; Pituitary Neoplasms; Pregnancy; Prolactin; Visual Fields

Topics: Adenoma; Adult; Amenorrhea; Bromocriptine; Ergolines; Female; Galactorrhea; Humans; Hyperprolactinemia; Lisuride; Pituitary Neoplasms; Pregnancy; Prolactin

8 or 12 mg/day methergolin was administered for an average of 8 months to 80 patients with hyperprolactinaemia of tumoural (20 cases), idiopathic (39 cases), and iatrogenic (21 cases) origin. The success of the treatment was apparent in the return of ovulation and the establishment of pregnancy in 80% of patients with microadenoma, and 85% of those with a normal sella turcica.

Topics: Adenoma; Adolescent; Adult; Dose-Response Relationship, Drug; Ergolines; Female; Galactorrhea; Humans; Metergoline; Ovulation; Pituitary Neoplasms; Pregnancy; Prolactin; Sella Turcica

We have administered to 29 patients with macroprolactinoma the dopamine agonists bromocriptine and lisuride for 1-50 months (mean +/- SE, 12.7 +/- 1.8) in order to assess the effects of these drugs on tumor size. Fourteen patients were treated with bromocriptine (dose range, 7.5-20 mg/day), 12 patients were treated with lisuride (0.6-2 mg/day), and 3 patients were given both drugs. Computed tomography performed before and during treatment showed the occurrence of tumor shrinkage in 18 patients (62%), but in no case was a complete disappearance of the tumor observed. In 5 of these patients, it was even possible to document tumor shrinkage within the first month of treatment with low doses of the dopamine agonists, whereas in other patients, tumors shrank only after prolonged treatment with higher doses. Visual field and acuity improved or normalized in 8 of the 13 patients with visual defects; in some cases, the improvement was reported as early as 2 days after the treatment was started. Plasma PRL levels fell in all patients who showed a reduction in tumor size; in 2 other patients, PRL levels were only poorly suppressed, and tumor size remained unchanged. In the remaining patients, PRL levels were lowered without convincing evidence of tumor shrinkage. In considering the high percentage of patients showing tumor shrinkage under medical treatment, we propose a course with dopamine agonists as the first step in the management of patients with macroprolactinomas regardless of the presence of visual impairments.

Topics: Adolescent; Adult; Bromocriptine; Ergolines; Female; Humans; Lisuride; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Tomography, X-Ray Computed

Twenty-five patients, aged 23-39, with amenorrhea of 18 to 168 months' duration, galactorrhea, hyperprolactinemia (prolactin levels of 45 to 370 ng/ml), and radiologic evidence of a pituitary microadenoma, were treated with bromocriptine or lergotrile, 7.5 mg daily for 2 to 16 weeks until conception occurred. All conceived and were delivered of infants. Follow-up during pregnancy included frequent office visits and monthly visual field examinations from the sixth month until delivery. All the pregnancies resulted in single infants and uneventful and no neurological or visual symptoms developed. All infants born were normal. Twelve patients breast-fed while the others did not by choice. Menstrual function resumed in two patients after delivery and one of them subsequently conceived spontaneously. We believe that the presence of a pituitary microadenoma without neurological or visual symptoms should not be a contraindication to ovulation induction and pregnancy. Most of such pregnancies are uneventful. If symptoms arise during pregnancy, they can be treated medically or, in extreme emergencies, surgically.

Topics: Adenoma; Adult; Amenorrhea; Bromocriptine; Ergolines; Female; Galactorrhea; Humans; Infant, Newborn; Pituitary Neoplasms; Pregnancy; Pregnancy Complications; Prolactin

Topics: Adenoma; Ergolines; Female; Infertility, Female; Lisuride; Pituitary Neoplasms; Prolactin

A 38-year-old amenorrhoeic woman suffering from a prolactin (PRL) secreting adenoma, which had suprasellar extension as shown by caroe agonist (lisuride). PRL levels were lowered and after 1 year of treatment CAT showed a marked reduction of the tumour size. After 2 years of treatment menstruation returned and CAT demonstrated a further reduction of the adenomatous tissue. This study supports the suggestion that dopamine agonists possess an anti-proliferative effect on tumoural lactotrophic cells of humans.

Topics: Adenoma; Adult; Ergolines; Female; Humans; Lisuride; Pituitary Neoplasms; Prolactin; Sella Turcica; Time Factors; Tomography, X-Ray Computed

Normally menstruating volunteers as well as patients with hyperprolactinaemic menstrual disorders were treated with lisuride hydrogen maleate (200 micrograms b.i.d.), an ergoline derivative with dopaminergic properties. Within 3 h after an oral dose of 200 micrograms lisuride, PRL levels decreased significantly in all subjects to a plateau which lasted up to 3 h. Thereafter a gradual increase of serum PRL was noted. In the normally menstruating volunteers lisuride treatment did not result in any significant change of gonadotrophin or of sex steroid secretion, while both, basal as well as metoclopramide (MTCL) stimulated PRL release were significantly diminished. The inhibition of PRL secretion in patients with short luteal phases resulted in an increase of luteal progesterone output. In both treated groups ovulation occurred 1 to 5 days earlier in cycles on lisuride than in control cycles. LF-RH/MTCL tests performed in the patient bearing a pituitary prolactinoma before and after lisuride treatment revealed a continuous increase of pituitary LH pools, while PRL secretion decreased under lisuride therapy. Subsequently ovulation and menstruation occurred. The data presented demonstrate that lisuride is a potent inhibitor of PRL secretion and has proven its clinical usefulness for treatment of hyperprolactinaemic menstrual disorders. Application of lisuride resulted in an increase of luteal progesterone secretion in previously demonstrated corpus luteum insufficiency as well as in restoration of normal cyclical feedback mechanisms in tumorous hyperprolactinaemic anovulation. The MTCL-PRL stimulation test is suitable to monitor PRL suppression during lisuride treatment, while LH-RH testing reveals the effectiveness of lisuride by demonstrating an increase of pituitary gonadotrophin pools.

Topics: Adenoma; Administration, Oral; Adult; Ergolines; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hydroxyprogesterones; Lisuride; Luteinizing Hormone; Menstruation; Menstruation Disturbances; Metoclopramide; Pituitary Neoplasms; Progesterone; Prolactin

Topics: Adenoma; Adult; Amenorrhea; Bromocriptine; Dopamine; Ergolines; Female; Humans; Metergoline; Pituitary Gland; Pituitary Neoplasms; Prolactin; Sulpiride

The natural history of prolactin-secreting adenomas is not known. For this reason, optimal therapy for women harboring these adenomas who desire to conceive is also unknown. Argument can be found to favor surgical excision, radiation therapy, prolactin-suppressing chemotherapy, and clinical observation. In a large series of women with prolactin-secreting pituitary adenomas, 21 have conceived and delivered healthy infants, all of whom had ergocryptine-induced prolactin suppression as the sole form of therapy. Endocrinologic, neurologic, biochemical, and radiologic assessment failed to demonstrate any obvious growth of the pituitary adenoma, except for slight enlargement of the sella turcica in one patient who delivered twins. The failure to demonstrate any worsening of the clinical state may reflect the fact that no large tumors were included in this series, only small but definite microadenomas found on sellar tomography. All of the various modalities of therapy must be considered with each patient, but this series suggests that ergocryptine treatment with careful clinical follow-up is relatively safe in patients with small pituitary tumors.

Topics: Abortion, Spontaneous; Adenoma; Adult; Ergolines; Female; Humans; Pituitary Neoplasms; Pregnancy; Prolactin

Studies of prolactin secretion in humans have confirmed the concept, derived originally from animal investigations, that prolactin is predominantly controlled by tonic inhibition from the hypothalamus. The locus of action of dopamine and dopaminergic agents such as the ergot alkaloids inhibiting prolactin secretion appears to be primarily at the pituitary level, though a hypothalamic action to increase secretion of prolactin inhibitory factor may also contribute. Prolactin hypersecretion, through any of several possible mechanisms, is frequently but not always found in patients with galactorrhea. Recent studies have shown that hyperprolactinemia is considerably more common than was previously appreciated among patients without galactorrhea. It is present in at least two-thirds of all patients with pituitary tumors and in a significant minority of patients with secondary amenorrhea. Its clinical measurement in these conditions is therefore of considerable diagnostic importance. Whatever the pathophysiology of its production, hyperprolactinemia of all forms is responsive to treatment with the newer ergot alkaloids. The potential use of these agents for therapeutic purposes, particularly in the treatment of infertility, appears to be wider than was originally anticipated.

Topics: Acetonitriles; Amenorrhea; Bromocriptine; Dopamine; Ergolines; Ergot Alkaloids; Female; Galactorrhea; Humans; Levodopa; Pituitary Neoplasms; Pregnancy; Prolactin; Prolactin Release-Inhibiting Factors

A patient with amenorrhea due to a prolactin-secreting pituitary microadenoma was treated with the antiserotoninergic drug metergoline for 8 months. The first menstruation occurred after 1 month of therapy, and it was followed by regular menses by the 3rd month. Presumptive evidence of ovulation was obtained in at least some instances by serum progesterone and gonadotropin determination. Serum prolactin was only slightly lowered by treatment. The patient had menses and possibly ovulation in the 2 months following drug withdrawal. Metergoline might restore ovarian function in hyperprolactinemic amenorrhea either by prolactin suppression or perhaps by direct stimulation of gonadotropin release.

Topics: Adenoma; Adult; Amenorrhea; Ergolines; Female; Humans; Menstruation; Metergoline; Ovary; Pituitary Neoplasms; Prolactin

The development of homologous prolactin assays, multiple pituitary stimulation, tomography, and computerised axial tomography permit more detailed investigation of patients with secondary amenorrhoea than was formerly possible. 39% of 90 patients with secondary amenorrhoea had hyperprolactinaemia. 10 patients (11% of total) had pituitary tumours. 8 of these women had galactorrhoea (27% of those with galactorrhoea). For patients with hyperprolactinaemia but no tumour, bromocriptine is the treatment of first choice rather than clomiphene or human gonadotrophins. The best treatment for patients with detectable tumour is controversial, particularly when the tumour is confined to the sella turcica. Whether or not these tumors are true neoplasms remains to be determined. Clinically, a history of secondary anemorrhoea with or without galactorrhoea following withdrawal of oral contraceptives remains the commonest presenting syndrome.

Topics: Amenorrhea; Bromocriptine; Contraceptives, Oral; Diagnosis, Differential; Ergolines; Female; Galactorrhea; Humans; Lactation Disorders; Pituitary Function Tests; Pituitary Neoplasms; Pneumoencephalography; Pregnancy; Prolactin; Tomography; Tomography, X-Ray Computed

Topics: Adenoma; Bromocriptine; Culture Techniques; Ergolines; Growth Hormone; Humans; Pituitary Neoplasms; Prolactin

A patient is described with a galactorrhea-amenorrhea syndrome and an enlargement of the sella turcica. Pregnancy occurred after induction of ovulation with bromocriptine (and 2.5 years after pituitary irradiation). Periodic assessment of the visual fields showed an increase in size of the blind spots after 10 weeks and a moderate bitemporal hemianopsia after 22 weeks, which improved spontaneously after 30 weeks of pregnancy. One month after delivery the visual field of the left eye was almost normalized, while that of the right eye showed a definite improvement. Prior radiotherapy need not prevent visual complications from enlargement of pituitary adenomas during pregnancy.

Topics: Adult; Amenorrhea; Bromocriptine; Ergolines; Estradiol; Female; Follicle Stimulating Hormone; Galactorrhea; Hemianopsia; Humans; Lactation Disorders; Luteinizing Hormone; Pituitary Neoplasms; Pregnancy; Pregnancy Complications; Prolactin; Syndrome; Visual Fields

Of 28 patients presenting with amenorrhea-galactorrhea, pituitary tumors were confirmed in eight. Six patients had occult hypothyroidism and the rest had an endocrine profile suggestive of pituitary tumor or of an idiopathic etiology. Treatment with bromocryptine resulted in suppression of the inappropriate lactation and restoration of regular menstrual function. In five cases, however, the galactorrhea was only diminished and in four of these cases, normal ovarian function did not return. Of the 19 patients that were seeking fertility and continued the medication for at least 20 days, nine pregnancies resulted. A similar response to bromocryptine was observed regardless of the underlying cause of the amenorrhea-galactorrhea.. 28 women with amenorrhea-galactorrhea were investigated endocrinologically and treated with bromocryptine 2.5 mg twice daily, ranging from 18 to 150 days. These women were classified into 6 with hypothyroidism, having prolactin (PRL) over 30 ng/ml, thyroid stimulating hormone (TSH) over 8 mcU/ml, luteinizing hormone (LH)6-20 mlU/ml and greater than follicle stimulating hormone (FSH); 8 with radiologically diagnosed pituitary tumors, LH, FSH, and increased PRL; 9 with similar endocrine profiles and suspected pituitary tumors; and 3 with high PRL considered idiopathic. 5 of the hypothyroid group were followed, and achieved ovulation, reduced TSH, PRL, and lactation, and 3 became pregnant. Of the 8 with tumors, 5 menstruated, 4 ovulated, 3 conceived, 3 had reduced lactation, 2 had reduced PRL, and 1 failed to respond clinically; 9 with suspected tumors took bromocryptine for at least 20 days, resulting in 4 pregnancies and 3 with regular menses. The 3 idiopathic cases showed lower PRL and regular ovarian function, 1 pregnancy, yet 1 developed pseudocyesis and recurrent galactorrhea. 2 women had to stop bromocryptine because of vomiting. This drug is longer-acting than L-dopa and safer than estrogen-progestagen combinations in cases of pituitary tumors. Bromocryptine reduces galactorrhea and associated hypothyroidism temporarily.

Topics: Adult; Amenorrhea; Bromocriptine; Ergolines; Female; Follicle Stimulating Hormone; Galactorrhea; Humans; Hypothyroidism; Lactation Disorders; Luteinizing Hormone; Pituitary Neoplasms; Pregnancy; Prolactin; Thyrotropin

Bromocriptine at a dose of 7.5-30 mg/day was given to 12 acromegalics for 6 mo. Mean serum growth hormone (GH) levels during a glucose tolerance test (GTT) were significantly lowered by the drug. In four patients the serum GH response during a GTT was suppressed to normal (i.e. less than or equal to 5 mlU/liter). If bromocriptine had not brought the serum GH response to a GTT to normal at a dose of 20 mg/day, this effect was not achieved by raising the dose to 30 mg/day. Bromocriptine was effective for the duration of treatment. On discontinuing therapy there was an increase in serum GH levels. No obvious clinical changes in the acromegalic features were noted. One patient with impaired glucose tolerance and one with established diabetes had normal glucose tolerance while on bromocriptine and another two patients with impaired glucose tolerance showed no obvious changes while on the drug. Side effects were minor. X-rays of the pituitary fossa before starting and at the end of treatment showed no significant change. We conclude that although bromocriptine is the most promising form of medical treatment for acromegaly to date, it is fully effective only in a minority of patients.

Topics: Acromegaly; Adult; Bromocriptine; Dose-Response Relationship, Drug; Drug Evaluation; Ergolines; Female; Glucose Tolerance Test; Growth Hormone; Humans; Male; Middle Aged; Pituitary Neoplasms

A patient with hyperprolactinemia, amenorrhea, and an enlarged sella turcica, but without galactorrhea, was treated with Bromocriptin to effect restoration of ovarian function. The subsequent pregnancy was without problems from an obstetric point of view, but visual field abnormalities developed progressively, leading to termination of the pregnancy in the 39th week. However, within 1 week after delivery, the field defects disappeared and the visual acuity returned to normal.

Topics: Adult; Amenorrhea; Bromocriptine; Cesarean Section; Ergolines; Female; Follicle Stimulating Hormone; Humans; Infertility, Female; Luteinizing Hormone; Pituitary Neoplasms; Pregnancy; Pregnancy Complications; Prolactin; Sella Turcica; Thyrotropin; Tomography, X-Ray; Vision Disorders; Visual Acuity; Visual Fields

Topics: Amenorrhea; Bromocriptine; Ergolines; Female; Humans; Pituitary Neoplasms; Prolactin

Thirteen patients with pituitary tumors had a total of seventeen pregnancies. Nine of these patients were treated prior to conception (four by radiation therapy, four by hypophysectomy, and one with lergotrile); four patients received no treatment. The untreated group had a total of six pregnancies, two of which were complicated by visual symptoms which regressed spontaneously after delivery. One of the hypophysectomized patients developed diabetes insipidus at 34 weeks' gestation which resolved spontaneously after delivery. Of the four irradiated patients, one had a child with Down's syndrome and another had a child with multiple congenital anomalies who died. The clinical course and various modes of treatment of these patients are discussed and the pertinent literature is reviewed.

Topics: Ergolines; Female; Humans; Labor, Obstetric; Lactation; Menstruation; Ovulation; Pituitary Neoplasms; Pregnancy; Pregnancy Complications

Fifteen patients with galactorrhea-amenorrhea syndromes were studied before, during, and after treatment with bromergocryptine. Galactorrhea and amenorrhea were noted after pregnancy (6 patients), after oral contraceptive therapy (5 patients), and in association with pituitary adenoma (4 patients). Before treatment prolactin values were elevated ranging from 27 to 125 ng/ml, while luteinizing hormone and progesterone levels failed to show ovulatory peaks or luteal phase progression. Eleven patients had luteinizing hormone-releasing hormone tests before therapy. Response was normal in 8, subnormal in 2 pituitary adenoma, and supranormal in 1 patient with premature ovarian failure. Treatment with bromergocryptine was associated with a lowering of serum prolactin, cessation of lactation in all, and return of ovulatory menses in 14 of 15 patients. All relapsed when therapy was discontinued. Four patients became pregnant while on therapy. Long-term bromergocryptine therapy is effective for all forms of galactorrhea-amenorrhea syndromes studied.

Topics: Adenoma; Amenorrhea; Bromocriptine; Chiari-Frommel Syndrome; Ergolines; Female; Galactorrhea; Humans; Lactation Disorders; Pituitary Function Tests; Pituitary Neoplasms; Pregnancy; Recurrence; Syndrome

Topics: Bromocriptine; Ergolines; Female; Galactorrhea; Humans; Hypogonadism; Male; Pituitary Neoplasms; Pregnancy; Prolactin

Topics: Acromegaly; Aged; Bromocriptine; Ergolines; Female; Humans; Infertility, Female; Parkinson Disease; Pituitary Neoplasms; Receptors, Dopamine

A woman developed amenorrhoea and galactorrhoea after partial removal of a pituitary tumor during pregnancy. Hyperprolactinaemia was supressed by therapy with bromocryptine (CB 154, Sandoz) resulting in cessation of galactorrhoea in two months, spontaneous menstruation after eight months, and pregnancy after twelve months.

Topics: Adenoma, Chromophobe; Adult; Amenorrhea; Bromocriptine; Ergolines; Female; Galactorrhea; Humans; Lactation Disorders; Pituitary Neoplasms; Pregnancy; Syndrome

Topics: Adenoma; Adult; Bromocriptine; Ergolines; Female; Humans; Infertility, Female; Pituitary Neoplasms

One group of male Syrian hamsters received diethylstilbestrol (DES) over a period of 9 months. All developed widespread and severe renal tumors. Another group of male Syrian hamsters was given DES plus 2-bromo-alpha-ergocryptine methanesulfonate (CB154) over the same period. These hamsters either did not develop renal tumors or had renal tumors that were minimal in severity. DES treatment induced hyperplastic and neoplastic changes in the intermediate lobe of the pituitary glands of treated animals, increased the number of prolactin-secreting cells, and decreased the number of somatotrophin-secreting cells. Adding CB154 significantly inhibited those changes in the pituitary gland. Histopathologic and ultrastructural examinations indicated that the renal tumors were carcinomas originating from proximal convoluted tubules.

Topics: Animals; Body Weight; Bromocriptine; Cell Count; Cricetinae; Diethylstilbestrol; Ergolines; Growth Hormone; Hyperplasia; Kidney Neoplasms; Kidney Tubules, Proximal; Male; Mesylates; Organ Size; Pituitary Gland; Pituitary Neoplasms; Prolactin; Testis

Thirteen pregnancies occurred in 12 women who were treated with bromocriptine for infertility. Pretreatment prolactin levels were recorded in 11 patients and were normal in three. Five patients had suspected pituitary tumours, and they received irradiation to prevent swelling of the pituitary and the consequent visual field defects caused by the pressure of the swollen gland on the optic nerve. Ten of the 13 pregnancies have come to term, and all the babies were normal. When a patient with a pituitary tumour developed a visual field defect in the 38th week of pregnancy labour was induced and the defect disappeared after delivery. No multiple pregnancies occurred and there were no major complications.

Topics: Adult; Bromocriptine; Ergolines; Female; Humans; Infertility, Female; Pituitary Irradiation; Pituitary Neoplasms; Pregnancy; Pregnancy Complications; Prolactin; Vision Disorders; Visual Fields

Daily injections of ergocornine or ergonovine, for 3 weeks, into rats carrying a prolactin- and growth hormone-secreting pituitary tumor (MtW15) induced significant regression or inhibition of tumor growth, whereas ergocryptine had no significant effect. Ergocornine caused a decrease in cells and a disappearance or pycnosis of nuclei in the tumor tissue, and a reduced concentration of prolactin in blood.

Topics: Animals; Ergolines; Female; Injections, Intraperitoneal; Neoplasm Transplantation; Neoplasms, Experimental; Pituitary Neoplasms; Prolactin; Radioimmunoassay; Rats; Rats, Inbred Strains; Uterine Cervical Neoplasms