ergoline and Adenoma

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

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

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

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

Prolactinoma is the most frequent pituitary tumor histotype. Men generally have macroadenomas whereas women generally have microadenomas. The major objectives of treating prolactinomas are to suppress excessive hormone secretion and its clinical consequences, to remove the tumor mass while preserving the residual pituitary function, and possibly to prevent disease recurrence or progression. Primary therapy of prolactinomas is based on use of dopamine-receptor agonists. Bromocriptine induces normalization of prolactin levels in 80-90% of patients with microprolactinomas and approximately 70% of those with macroprolactinomas. Tumor-mass shrinkage and improvement of visual-field defects are found in the majority of treated macroprolactinomas, but bromocriptine often causes side effects. Cabergoline is very effective and well tolerated in more than 90% of patients with either microprolactinomas or macroprolactinomas. Cabergoline treatment also induces tumor shrinkage in the majority of patients with macroprolactinomas. Tumor shrinkage is more evident if patients have not previously been treated with other dopamine agonists. Fewer results are available for men than for women, but there is no evidence that men are less responsive to dopamine agonists than are women.

Topics: Adenoma; Antineoplastic Agents; Bromocriptine; Cabergoline; Ergolines; Female; Humans; Hyperprolactinemia; Male; Prolactin; Prolactinoma; Sex Characteristics

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

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

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

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 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

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

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 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

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

Although somatostatin analogues (SSAs) are recommended as the first-line medical therapy for acromegaly, dopamine agonists (DAs) are also a therapeutic option for treatment. We aimed to assess and compare the efficacies of DAs and SSAs in treating acromegaly in clinical practice. We included 89 patients with acromegaly who took DAs (bromocriptine [BCT], n = 63; cabergoline [CAB], n = 11) or SSAs (n = 15) as a primary medical therapy for more than 3 months in the Seoul National University Hospital. The CAB (45.5%) and SSA (33.3%) groups achieved random GH levels of <2.5 ng/mL and the normal IGF-1 levels were significantly higher than in the BCT group (11.1%) (p = 0.009). We further included all the patients with acromegaly (n = 132) who had taken CAB, BCT, and SSAs as first- or second-line medical therapy. The CAB group showed similar efficacy as the SSA group in terms of the GH and insulin-like growth factor-1 (IGF-1) levels (57.6% for random GH level <2.5 ng/mL, 42.4% for normal IGF-1 levels, 36.4% for both). Logistic regression analysis revealed that medications, age, GH level, or IGF-1 level before medication, hyperprolactinemia, and prior gamma-knife surgery or radiation therapy, did not affect the therapeutic response. High pretreatment GH levels predicted poor treatment outcomes (odds ratio [95% confidence interval] = 0.95 [0.90-0.99]). CAB was effective in treating acromegaly at a relatively lower cost in patients with low pretreatment GH levels.

Topics: Acromegaly; Adenoma; Adult; Antineoplastic Agents; Bromocriptine; Cabergoline; Cohort Studies; Dopamine Agonists; Drug Resistance, Neoplasm; Ergolines; Female; Follow-Up Studies; Growth Hormone-Secreting Pituitary Adenoma; Hospitals, University; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Neoplasm Grading; Republic of Korea; Retrospective Studies; Somatostatin; Tumor Burden

Hyperprolactinemia is common in acromegaly and in these patients, insulin-like growth factor (IGF)-1 level may decrease with dopamine agonist. We report a series of patients with prolactinoma and a paradoxical increase of IGF-1 levels during cabergoline treatment.. Clinical characteristics and response to treatment of patients with prolactinomas, in whom normal or slightly elevated baseline IGF-1 levels increased with cabergoline.. The cohort consisted of ten prolactinoma patients (nine males, mean age 48 ± 14 years). Mean adenoma size was 23.8 ± 16.2 mm, with cavernous sinus invasion in eight. In five patients baseline IGF-1 levels were normal and in four levels were 1.2-1.5-fold the upper limit of the normal (ULN). One patient had IGF-1 measured shortly after initiating cabergoline and it was 1.4 × ULN. During cabergoline treatment (dose range 0.5-2 mg/week) PRL normalization was achieved in all and tumor shrinkage occurred in seven patients. The mean IGF-1 increase on cabergoline was 1.7 ± 0.4 × ULN. Cabergoline dose reduction or interruption was attempted in five patients and resulted in decreased IGF-1 levels in all, including normalization in two patients. Three patients were eventually diagnosed with acromegaly, one was referred for pituitary surgery followed by complete remission, another patient was switched to somatostatin analogue, and the third was treated by combination of somatostatin analogues with pegvisomant, with reduction of IGF-1 in all these patients.. IGF-1 levels may increase to clinically significant levels during cabergoline treatment for PRL-adenoma. We suggest IGF-1 monitoring in all patients treated with dopamine agonists and not only in those presenting symptoms of acromegaly.

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

Insulinlike growth factor I (IGF-I) measurement is essential for the diagnosis and management of growth hormone (GH) disorders. However, patient classification may vary substantially according to the assay technique.. We compared individual patient data and classifications obtained with six different IGF-I assay kits in a group of patients with various GH disorders.. In this cross-sectional study, we measured IGF-I with six immunoassays in 102 patients with active or treated acromegaly or GH deficiency. IGF-I normative data previously established for the same six assay kits were used to classify the patients (high, low, or normal IGF-I levels), using both raw data and standard deviation scores (SDSs). Pairwise concordance between assays was assessed with Bland-Altman plots and with the percentage of observed agreement and the weighted κ coefficient for categorized IGF-I SDS.. We observed marked variability both across each individual's IGF-I raw data and across IGF-I SDS values obtained with each of the six immunoassays. Pairwise concordance between assay values, as assessed with the weighted κ coefficient, ranged from 0.50 (moderate) to 0.81 (excellent).. Even when using normative data obtained in the same large population of healthy subjects and when using calculated IGF-I SDSs, agreement among IGF-I assay methods is only moderate to good. Differences in assay performance must be taken into account when evaluating and monitoring patients with GH disorders. This argues for the use of the same IGF-I assay for a given patient throughout follow-up.

Topics: Acromegaly; Adenoma; Adult; Aged; Cabergoline; Cross-Sectional Studies; Dopamine Agonists; Drug Therapy, Combination; Dwarfism, Pituitary; Ergolines; Female; Growth Hormone-Secreting Pituitary Adenoma; Human Growth Hormone; Humans; Immunoassay; Insulin-Like Growth Factor I; Male; Middle Aged; Neurosurgical Procedures; Somatostatin; Young Adult

Cushing disease (CD) results from excessive exposure to glucocorticoids caused by an adrenocorticotropic hormone-secreting pituitary tumor. Inadequately treated CD is associated with significant morbidity and elevated mortality. Multicenter data on CD patients treated in routine clinical practice are needed to assess treatment outcomes in this rare disorder. The study purpose was to describe the burden of illness and treatment outcomes for CD patients.. Eight pituitary centers in four U.S. regions participated in this multicenter retrospective chart review study. Subjects were CD patients diagnosed at ≥18 years of age within the past 20 years. Descriptive statistical analyses were conducted to examine presenting signs, symptoms, comorbidities, and treatment outcomes.. Of 230 patients, 79% were female (median age at diagnosis, 39 years; range, 18 to 78 years). Length of follow-up was 0 to 27.5 years (median, 1.9 years). Pituitary adenomas were 0 to 51 mm. The most common presenting comorbidities included hypertension (67.3%), polycystic ovary syndrome (43.5%), and hyperlipidemia (41.5%). Biochemical control was achieved with initial pituitary surgery in 41.4% patients (91 of 220), not achieved in 50.0% of patients (110 of 220), and undetermined in 8.6% of patients (19 of 220). At the end of follow-up, control had been achieved with a variety of treatment methods in 49.1% of patients (110 of 224), not achieved in 29.9% of patients (67 of 224), and undetermined in 21.0% of patients (47 of 224).. Despite multiple treatments, at the end of follow-up, biochemical control was still not achieved in up to 30% of patients. These multicenter data demonstrate that in routine clinical practice, initial and long-term control is not achieved in a substantial number of patients with CD.. BLA = bilateral adrenalectomy CD = Cushing disease CS = Cushing syndrome eCRF = electronic case report form MRI = magnetic resonance imaging PCOS = polycystic ovary syndrome.

Topics: 14-alpha Demethylase Inhibitors; ACTH-Secreting Pituitary Adenoma; Adenoma; Adolescent; Adrenalectomy; Adult; Aged; Antineoplastic Agents; Cabergoline; Comorbidity; Enzyme Inhibitors; Ergolines; Female; Follow-Up Studies; Hirsutism; Hormone Antagonists; Hormones; Humans; Hyperlipidemias; Hypertension; Hypoglycemic Agents; Ketoconazole; Male; Metyrapone; Middle Aged; Mifepristone; Muscle Weakness; Muscular Atrophy; Neurosurgical Procedures; Obesity, Abdominal; Pituitary ACTH Hypersecretion; Pituitary Irradiation; Polycystic Ovary Syndrome; Retrospective Studies; Rosiglitazone; Somatostatin; Striae Distensae; Thiazolidinediones; Treatment Outcome; Tumor Burden; Young Adult

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

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

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

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

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

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

Patients with acromegaly usually harbor macroadenomas measuring between 10 and 30 mm in maximal diameter. Giant (adenoma size ≥40 mm) GH-secreting pituitary tumors are rarely encountered and the aim of this study is to analyze different methods for managing them.. We have identified 34 patients (15 men and 19 females) with giant adenomas among 762 subjects (4.5%) with acromegaly in our records, and characterized their clinical characteristics and response to treatment.. Mean age at diagnosis was 34.9±12.5 years (range, 16-67 years). Mean adenoma size was 49.4±9.4 mm (range, 40-80 mm); 30 adenomas showed cavernous sinus invasion and 32 had suprasellar extension. Twenty-nine (85%) patients had visual field defects. Mean baseline IGF1 was 3.4±1.8×ULN. All patients except one underwent pituitary surgery (one to three procedures), but none achieved hormonal remission following first surgery. Among the 28 subjects with visual disturbances, 14 recovered post-operatively and 13 improved. Treatment with somatostatin analogs was given to all patients after surgical failure. Six achieved remission, nine others were partially controlled (IGF1<1.5×ULN; 3/9 when combined with cabergoline), and 17 did not respond (two were lost). Nine patients were treated with pegvisomant, alone (n=4) or in combination with somatostatin analogs (n=5); five are in remission and two are partially controlled. Pasireotide-LAR achieved hormonal remission in one of the six patients. Currently, after a mean follow-up period of 8.9 years, 17 patients are in biochemical remission, eight are partially controlled, and seven are uncontrolled (two were lost to follow-up).. Giant GH-secreting adenomas are invasive, uncontrolled by surgery, and respond poorly to medical treatment. Aggressive multimodal therapy is critical for their management, enhancing control rate and biochemical remission.

Topics: Acromegaly; Adenoma; Adolescent; Adult; Aged; Antineoplastic Agents; Cabergoline; Combined Modality Therapy; Drug Therapy, Combination; Ergolines; Female; Growth Hormone-Secreting Pituitary Adenoma; Human Growth Hormone; Humans; Male; Middle Aged; Remission Induction; Somatostatin; Treatment Outcome; Young Adult

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

Pegvisomant is an effective treatment for acromegaly.. To investigate escape (loss of biochemical control in patients previously controlled) and lipodystrophy in acromegalic patients treated with pegvisomant and to evaluate possible associations with clinical features.. Multicentre retrospective study involving 19 Spanish centres.. Ninety-seven patients were included (59% women, mean age at diagnosis 42 ± 13 years, 80% macroadenomas); mean follow-up on pegvisomant was 5 ± 2·5 years, and 89 (92%) achieved normal IGF-1. Escape was reported in 30/89 (34%) of responders, after a mean treatment duration of 25 ± 21 months. The mean initial dose of pegvisomant was 11 ± 5 mg/day, and mean dose at escape was 14 ± 7 mg/day. Most patients (26/30, 87%) achieved control with dose increase (57%), additional medical treatment (3%) or both (27%). Mean new dose that controlled IGF-1 after escape was 20 ± 7 mg/day. Treatments associated were somatostatin analogues (SSA in 47%), cabergoline (CAB in 47%) and both (6%). Lipodystrophy was observed in 15 patients (13 females), mild in six, moderate in six, severe in three and persistent in four. Among patients with lipodystrophy, three escaped and three were nonresponders to pegvisomant. Four patients discontinued the drug, and four had dose reductions because of lipodystrophy. It tended to be more frequent in females (P = 0·06) and in patients treated with triple association SSA+CAB+PEG (P = 0·018). No relationship between escape and clinical variables was found, except prior CAB (P = 0·04) and metformin treatment (0·02) and grade of lipodystrophy (P = 0·02).. A significant proportion of patients treated with pegvisomant escaped (34%); however, the majority (87%) was easily controlled with either dose increase, further medical treatment or both. Lipodystrophy developed in 15%, mostly females, and influenced the response to treatment.

Topics: Adenoma; Adult; Antineoplastic Agents; Cabergoline; Drug Therapy, Combination; Ergolines; Female; Growth Hormone-Secreting Pituitary Adenoma; Human Growth Hormone; Humans; Injections, Subcutaneous; Insulin-Like Growth Factor I; Lipodystrophy; Male; Middle Aged; Octreotide; Receptors, Somatotropin; Retrospective Studies; Spain; Treatment Failure; Treatment Outcome

Acromegaly, if untreated, leads to numerous complications and premature death of patients. In recent years, significant changes in the treatment of acromegaly were achieved. The surgical approach was innovated, what allows completely selective removal of most microadenomas without any damage of the pituitary and safe debulking of the tumor mass in macroadenomas. Radiosurgery took the first place among irradiation methods, in our conditions it is the irradiation by the Leksell gamma knife. It allows selective irradiation of an adenoma without damaging the surrounding tissue. However, its effect on the secretory activity of the adenoma remains to be long lasting. Before this effect is attained, it is necessary to suppress the secretory activity pharmacologically. The infrequently effective, but economically advantageous and comfortable for patients is cabergoline, which is administered in tablet form. If cabergolin is not efficient, depot injections of somatostatin analogues - octreotide LAR and lanreotide autogel or their combination with cabergoline are used. The most efficient but financially costly is pegvisomant, blocking the receptors for growth hormone. In our conditions it is reserved for patients unresponsive to other treatments. With sufficient dosage it is possible to normalize hormonal activity of acromegly in 95 % of patients. New forms of the drugs as octreotide implants, oral octreotide octreolin or a new blocker of growth hormone receptors ATL-1103 are in the development.

Topics: Acromegaly; Adenoma; Antineoplastic Agents; Cabergoline; Ergolines; Growth Hormone-Secreting Pituitary Adenoma; Human Growth Hormone; Humans; Octreotide; Peptides, Cyclic; Radiosurgery; Receptors, Somatotropin; Somatostatin

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

Although somatostatin analogues are effective medical therapy for acromegaly, the serum insulin-like growth factor-I (IGF-I) levels remain uncontrolled in 35% of patients. Combined therapy with octreotide LAR and cabergoline has been reported to normalize IGF-I levels in 42-56% of Caucasian patients with acromegaly. However, it remains to be clarified whether combination therapy is effective in Japanese patients and on tumor shrinkage. We conducted a retrospective study on combined therapy in patients with octreotide-resistant acromegaly. Ten patients with acromegaly who showed octreotide-resistance were enrolled in this study. Cabergoline was added in doses of 0.25-2.0mg/week. Serum GH and IGF-I levels and tumor volume were assessed before and after treatment, and factors correlated with effect of the combined therapy were analyzed. Although serum GH levels did not decrease, serum IGF-I levels significantly decreased by 20% after 6 months of combined therapy compared with baseline (p < 0.05). As a result, serum IGF-I levels normalized in 30% of the patients. Tumor volume after combined therapy also significantly decreased (p < 0.01). There were no correlations between the decrease of serum IGF-I levels during combined therapy and the response of GH in a bromocriptine test, random GH, IGF-I, and PRL levels, the tumor volume, and the expression of PRL and dopamine D2 receptor in the tumor. In conclusion, we demonstrated that the addition of cabergoline to octreotide LAR is a beneficial option in Japanese patients with octreotide-resistant acromegaly, irrespective of serum PRL levels and the response of GH levels in a bromocriptine test.

Topics: Acromegaly; Adenoma; Adolescent; Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cabergoline; Delayed-Action Preparations; Drug Resistance; Ergolines; Female; Growth Hormone-Secreting Pituitary Adenoma; Humans; Insulin-Like Growth Factor I; Japan; Male; Middle Aged; Octreotide; Pituitary Gland; Retrospective Studies; Somatostatin; Tumor Burden; Young Adult

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

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

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

Men with hypogonadism tend to have low hemoglobin (HGB) levels. We have investigated a cohort of 36 consecutive male patients with macroprolactinomas to evaluate HGB during presentation and following treatment with cabergoline to suppress prolactin (PRL). Patients' mean age at diagnosis was 48 years, the mean adenoma size measured 31 mm. The median PRL at baseline was 1,969 ng/ml; the mean testosterone level was low, 1.5 ng/ml. PRL had been successfully normalized in all but six men by using cabergoline. Mean baseline HGB at diagnosis was 13.1 gr%. Sixteen patients had HGB ≤ 13 gr%, including 4 men with HGB ≤ 11.5 gr%. In the subgroup of 15 men with very low testosterone (≤ 1 ng/ml), baseline HGB was 12.6 gr% compared with 13.5 gr% in patients with higher testosterone (P < 0.005). In 30 men in whom follow-up CBC data were available, mean baseline HGB increased from 13.2 to 13.9 gr% following PRL suppression by cabergoline. Baseline HGB levels inversely correlated with tumor size, reaching levels of 13.7 gr% in 10 men with macroprolactinomas of 10-20 mm in size, 13.0 gr% in 18 subjects with macroadenomas of 21-40 mm, and 12.4 gr% in 7 patients with giant prolactinomas (>40 mm). In 22 men with normal follow-up testosterone, current HGB levels measured 14.5 gr%, but only 12.8 gr% in 9 men with current low testosterone (P < 0.0005). In men with macroprolactinomas, anemia is common. It is associated with hypogonadism and tumor size, and improves following treatment that normalizes PRL and increases testosterone.

Topics: Adenoma; Adult; Aged; Antineoplastic Agents; Cabergoline; Ergolines; Hemoglobins; Humans; Hypogonadism; Male; Middle Aged; Prolactin; Prolactinoma; Retrospective Studies; Testosterone

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

The aim of this prospective open trial was to evaluate the efficacy in normalizing IGF-I levels of the addition of cabergoline to the treatment of acromegalic patients partially responsive to Octreotide-LAR (OCT-LAR), a long acting somatotastin analog (SSA). Fifty-two patients who did not achieve hormonal control after longterm therapy (at least, 12 months) with OCT-LAR (30 mg every 28 days intramuscularly) were given cabergoline in addition to the SSA treatment. Normalization of IGF-I levels was achieved in 40.4% of patients by 6 months after the addition of cabergoline (1.0-3.0 mg/week; mean, 2.19 ± 0.64), and these patients were considered responsive. Compared to non-responsive subjects, responsive patients had significantly lower mean %ULNR-IGF-I and GH levels. However, the rate of hyperprolactinemia and positive immunohistochemical staining for PRL was similar in both groups, before the addition of cabergoline. Responsive patients were followed for at least 12 months on combination treatment and persisted with normal IGF-I levels. Patients with baseline %ULNR IGF-I up to 220% and/or GH up to 5 ng/ml were those who benefited the most from combination treatment. No patients with %ULNR-IGF-I>250% reached normalization of IGF-I levels. Our findings demonstrated that the addition of cabergoline, even at relatively low doses, is effective in both short- and long-term control of IGF-I levels in acromegalic patients partially responsive to octreotide LAR, particularly in those with mild/moderately elevated GH/IGF-levels, irrespective of prolactin status.

Topics: Acromegaly; Adenoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cabergoline; Delayed-Action Preparations; Drug Resistance, Neoplasm; Ergolines; Female; Growth Hormone-Secreting Pituitary Adenoma; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Octreotide; Time Factors; Young Adult

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

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

Double pituitary adenomas are difficult to recognize pre-operatively as only a single mass may be appreciated on imaging. We present herein a giant prolactin-secreting pituitary adenoma in a middle-aged man that had responded partially to dopamine agonist therapy. The excised specimen demonstrated a double adenoma. The prolactin-producing one displayed the expected morphological changes resulting from medical therapy, while the other, a gonadotroph adenoma, did not. The failure of tumor shrinkage can be attributed to the presence of a double adenoma, a previously unreported cause of failure of medical therapy in prolactinoma.

Topics: Adenoma; Adult; Antineoplastic Agents; Breast Neoplasms, Male; Cabergoline; Combined Modality Therapy; Ergolines; Gonadotrophs; Humans; Male; Microscopy, Electron, Transmission; Neoplasms, Multiple Primary; Neoplasms, Second Primary; Neurofibromatosis 1; Neurosurgical Procedures; Prolactinoma

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

The effects of growth hormone are mediated in part by stimulating the production of insulin-like growth factor-1. Insulin-like growth factor-1 has significant effects on cell proliferation and differentiation, it is a potent mitogen, and it is a powerful inhibitor of programmed cell death (apoptosis). Insulin-like growth factor-1 also has a well-established role in the transformation of normal cells to malignant cells. Case reports on a possible association between elevated growth hormone and cancer risk in a variety of patient groups have been published. Here, we describe clinical and laboratory findings for a patient with acromegaly who first developed thyroid cancer, and then, in the follow up period, probably due to poorly controlled insulin-like growth factor-1 levels, developed a large cell non-Hodgkin's lymphoma. A search revealed that a case with these peculiarities had not previously been reported.

Topics: Acromegaly; Adenoma; Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Cabergoline; Cyclophosphamide; Ergolines; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Lymphoma, Non-Hodgkin; Male; Neoplasms, Multiple Primary; Octreotide; Prednisone; Thyroid Neoplasms; Thyroidectomy; Thyroxine; Vincristine

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

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

Cabergoline is a dopamine agonist that may be used as primary or adjunctive therapy for acromegaly. Although one study suggested biochemical control may be achieved in a substantial proportion of patients, it is still commonly perceived to be a relatively ineffective treatment.. A prospective audit was performed of 15 consecutive acromegalic patients (eight males, seven females, median age 55, range 31-92 at presentation) treated with cabergoline to determine the effective dose and tolerability. All had normal anterior pituitary function; two patients had hyperprolactinaemia. Magnetic resonance imaging revealed nine adenomata, two partially empty sellae and four structurally normal pituitary glands. Nine patients had undergone transsphenoidal surgery 1-12 months, and one patient had received pituitary radiotherapy 18 years, prior to commencement of cabergoline. All patients had biochemical GH excess; median serum IGF1 471 ng/ml, range 239-746 ng/ml. The calculated mean of a series of GH measurements ranged from 2.7-45.8 mIU/l, median 9.7 mIU/l.. On a median weekly dose of cabergoline of 1.75 mg (range 0.5-7 mg) normalisation of both IGF1 and GH occurred in 4 out of the 15 patients (27%). Out of the 15 patients (33%), 5 achieved a serum IGF1 within the reference range with notable reductions seen in a further five patients. Nine patients (60%) achieved a mean serum GH level of less than 5 mIU/l. Duration of treatment was 2-52 months and was well tolerated in 14 patients.. Cabergoline can be an effective and well tolerated primary or adjunctive therapy for acromegaly and useful clinical responses are noted even with modest doses.

Topics: Acromegaly; Adenoma; Adult; Aged; Aged, 80 and over; Cabergoline; Dopamine Agonists; Ergolines; Female; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Magnetic Resonance Imaging; Male; Medical Audit; Middle Aged; Pituitary Gland; Prospective Studies; 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

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

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

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

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

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

Topics: Acromegaly; Adenoma; Cabergoline; Dopamine Agonists; Ergolines; Humans; Somatostatin

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

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

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

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

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 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

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

Topics: Adenoma; Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cabergoline; Ergolines; Female; Humans; Peptides, Cyclic; Somatostatin; Thyrotropin; Time Factors

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

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

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

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 agonists are known to increase the incidence of Leydig cell hyperplasia/adenomas when administered to rats over periods of 1-2 years. We have examined the early changes in factors affecting Leydig cell growth/hyperplasia after chronic oral administration of one of these dopamine agonists, Mesulergine (CU32-085) [N-(1-6-dimethylergolin-8 alpha-yl)-N,N-dimethylsulphamide hydrochloride), to Sprague-Dawley (SD) rats. Eight-week-old rats were given the dopamine agonist (2 mg/kg body weight/day) in food for 5 or 57 weeks. The dopamine agonist treatment had no significant effect on food intake, body weight, and testis and seminal vesicle size, but significantly decreased testicular interstitial fluid volume at 5 weeks (by 51%). Leydig cells isolated from rats treated with the dopamine agonist for 5 weeks exhibited an increase in the rate of protein synthesis compared with the controls (by 28%). This treatment, however, had no significant effect on the number of Leydig cells or macrophages as assessed by histological examination of testicular sections. Treatment with the dopamine agonist for 57 weeks caused a 36 and 28% increase in the number of Leydig cells and macrophages, respectively. Nodules of Leydig cells, indicating the first signs of tumor development, were present in testes from the 57- but not the 5-week-treated animals or the controls of both groups, although an increase in the number of Leydig cells occurred with aging. Thick-walled arterioles were found in the intertubular spaces of the testis sections from rats treated for 57 weeks. These findings suggest that chronic treatment of male SD rats with the dopamine agonist causes hypertrophy of Leydig cells within 5 weeks (as assessed by [3H]methionine incorporation), followed by hyperplasia within 2 years, prior to the development of Leydig cell adenomas, which occur within 1-2 years after the initiation of treatment.

Topics: Adenoma; Animals; Antiparkinson Agents; Body Weight; Dopamine Agonists; Dose-Response Relationship, Drug; Ergolines; Extracellular Space; Hyperplasia; Leydig Cell Tumor; Leydig Cells; Male; Organ Size; Rats; Rats, Sprague-Dawley; Testicular Neoplasms

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

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

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

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 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 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

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

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

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

Two series of experiments were performed to determine whether nicergoline possesses an alpha-adrenergic blocking action on the lower urinary tract musculature in dogs and humans. One series consisted of in vivo studies of urethral pressure profile recordings in 19 female dogs, and their responses to adrenergic stimulation with noradrenaline or methoxamine, alone and following administration of nicergoline. The other series consisted of in vitro isometric studies of 61 strips of human prostate, and the establishment of dose response curves to nor-adrenaline alone and in the presence of various concentrations of nicergoline. In both sets of experiments clear evidence of an alpha-adrenergic blocking effect was obtained. From the in vitro experiments, the Kb of nicergoline was calculated as less than or equal to 9 X 10(-9) M.

Topics: Adenoma; Adrenergic alpha-Antagonists; Animals; Dogs; Dose-Response Relationship, Drug; Ergolines; Female; Humans; Male; Methoxamine; Muscle Contraction; Muscle, Smooth; Nicergoline; Norepinephrine; Propranolol; Prostate; Prostatic Neoplasms; Urethra

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

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

The mechanism by which metoclopramide stimulates aldosterone secretion is still unclear, since it cannot be explained by known regulatory systems. On the other hand we have recently shown that serotonin is also a potent aldosterone-stimulatory substance in man and its action can be blunted by the antiserotoninergic drug, metergoline. To test if metoclopramide could act through a serotoninergic pathway we have studied the effect of metergoline on the aldosterone response to metoclopramide in 8 normal subjects. The effect of metoclopramide (10 mg i.v.) on plasma aldosterone, PRA, cortisol, prolactin and K was studied before and after acute metergoline administration. Metergoline pretreatment significantly reduced the aldosterone response to metoclopramide, together with a slight reduction of prolactin, whereas no changes were seen on PRA, cortisol and K. In vitro, metoclopramide induced a significant aldosterone output from human adrenal adenoma cells, which was partially reduced by metergoline and not by bromocriptine. Despite a lack of specificity of metergoline these data may suggest the hypothesis of a serotoninergic component in the aldosterone-stimulating properties of metoclopramide.

Topics: Adenoma; Adrenal Gland Neoplasms; Adult; Aldosterone; Ergolines; Female; Humans; Hydrocortisone; Kinetics; Metergoline; Metoclopramide; Middle Aged; Potassium; Renin

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 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

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

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

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

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