ergoline and Acromegaly

Uncontrolled acromegaly results in approximately 2-fold excess mortality. Pituitary surgery is first-line therapy, and medical treatment is indicated for persistent disease. While cabergoline and pegvisomant are used in select patients, somatostatin receptor ligands (SRLs) remain the cornerstone of medical treatment. Management of patients poorly responsive to SRLs is therefore, challenging. The purpose of this review is to highlight the options for combination medical therapy in the treatment of acromegaly, with an emphasis on efficacy and safety.. All original articles/abstracts detailing combination medical therapy in acromegaly were identified from a PubMed search.. Studies reviewed included retrospective and open-label prospective studies. While the combination of SRL and cabergoline was generally well tolerated, a lower baseline insulin-like growth factor-1 (IGF-1) level was the best predictor of efficacy; this combination may be most effective in patients with mildly elevated IGF-1. SRL-pegvisomant combination normalized IGF-1 in the majority of patients; continued efficacy despite individual drug dosing reduction was also reported. The risk of significant liver enzyme elevation was, however, higher than that reported with SRL monotherapy; close monitoring is recommended. Data on pegvisomant-cabergoline combination is limited, but this may be an option in the setting of SRL intolerance. Reports on temozolomide used in combination with other medical therapies in patients with aggressive GH-secreting tumors are also summarized.. While more prospective, randomized controlled trials on long-term efficacy and safety are needed, combination medical therapy remains a treatment strategy that should be considered for acromegaly patients poorly responsive to SRLs.

Topics: Acromegaly; Cabergoline; Combined Modality Therapy; Ergolines; Humans; Receptors, Somatostatin; Receptors, Somatotropin

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

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

Treatment of acromegaly aims to correct (or prevent) tumor compression of surrounding tissues by excising the disease-causing lesion and reduce growth hormone (GH) and IGF-1 levels to normal values. When surgery (the usual first-line treatment) fails to correct GH/IGF-1 hypersecretion, medical treatment with dopamine agonists (DAs; particularly cabergoline) or somatostatin analogs (SAs) can be used. The GH receptor antagonist pegvisomant is helpful in patients who are totally or partially resistant to SAs and can be given in association with both SAs and/or DAs. Thanks to this multistep therapeutic strategy, adequate hormonal disease control is achieved in most patients, giving them normal life expectancy. Comorbidities associated with acromegaly generally improve after treatment, but persistent sequelae may nonetheless impair quality of life.

Topics: Acromegaly; Cabergoline; Dopamine Agonists; Ergolines; Growth Hormone; Human Growth Hormone; Humans; Somatostatin

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

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

This review focuses on combination drug treatment for acromegaly patients, including novel concepts and experimental therapies, with an emphasis on the author's personal experience.. A review of published clinical studies demonstrates that combination therapy; somatostatin receptor ligands and dopamine agonists, somatostatin receptor ligands and pegvisomant, or cabergoline and pegvisomant could provide significant additive biochemical control of acromegaly in patients inadequately controlled with conventional somatostatin receptor ligand therapy.. Advances in combination medical therapy have opened up new perspectives for acromegaly patients who are poorly, or nonresponsive to, presently available single drug therapies.

Topics: Acromegaly; Cabergoline; Dopamine Agonists; Drug Therapy, Combination; Ergolines; Human Growth Hormone; Humans; Ligands; Receptors, Somatostatin

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

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

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

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

Cabergoline is widely considered to be poorly effective in acromegaly.. The aim of this study was to obtain a more accurate picture of the efficacy of cabergoline in acromegaly, both alone and in combination with somatostatin analogs.. We systematically reviewed all trials of cabergoline therapy for acromegaly published up to 2009 in four databases (PubMed, Pascal, Embase, and Google Scholar). We identified 15 studies (11 prospective) with a total of 237 patients; none were randomized or placebo-controlled. A meta-analysis was conducted on individual data (n = 227).. Cabergoline was used alone in nine studies. Fifty-one (34%) of the 149 patients achieved normal IGF-I levels. In multivariate analysis, the decline in IGF-I was related to the baseline IGF-I concentration (β = 1.16; P <0.001), treatment duration (β = 0.28; P < 0.001), and baseline prolactin concentration (β = -0.18; P = 0.01), and with a trend toward a relation with the cabergoline dose (β = 0.38; P =0.07). In five studies, cabergoline was added to ongoing somatostatin analog treatment that had failed to normalize IGF-I. Forty patients (52%) achieved normal IGF-I levels. The change in IGF-I was significantly related to the baseline IGF-I level (β = 0.74; P < 0.001) but not to the dose of cabergoline, the duration of treatment, or the baseline prolactin concentration.. This meta-analysis suggests that cabergoline single-agent therapy normalizes IGF-I levels in one third of patients with acromegaly. When a somatostatin analog fails to control acromegaly, cabergoline adjunction normalizes IGF-I in about 50% of cases. This effect may occur even in patients with normoprolactinemia.

Topics: Acromegaly; Adult; Antineoplastic Agents; Cabergoline; Data Interpretation, Statistical; Ergolines; Female; Growth Hormone-Secreting Pituitary Adenoma; Hormone Antagonists; Human Growth Hormone; Humans; Hyperprolactinemia; Insulin-Like Growth Factor I; Male; Middle Aged; Somatostatin; Treatment Outcome

The treatment of patients with persistently active acromegaly has been facilitated over the past decade by the advent of highly specific and selective pharmacological agents. Somatostatin analogs, derived from the native inhibitory hormone somatostatin, are available in extended-duration preparations and are effective in reducing serum levels of growth hormone (GH) and insulin-like growth factor-I (IGF-I) as well as in improving the adverse clinical effects of acromegaly. Cabergoline, an agonist with a specificity for the dopamine D-2 receptor, has been shown to suppress IGF-I levels and induce tumor shrinkage in 35 and 50% of patients, respectively. The GH receptor antagonists compete with naturally occurring GH for binding with the GH receptor. As such, pegvisomant normalizes circulating IGF-I levels in 80 to 90% of patients with acromegaly. This last line of therapy should be considered for use in patients in whom surgery and medical therapy with somatostatin and/or dopamine agonists are either ineffective or poorly tolerated.

Topics: Acromegaly; Algorithms; Cabergoline; Dopamine Agonists; Ergolines; Health Care Costs; Human Growth Hormone; Humans; Octreotide; Peptides, Cyclic; Receptors, Somatotropin; Somatostatin; Treatment Outcome

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

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

The treatment of acromegaly and hyperprolactinaemia has been improved by the availability of effective and well-tolerated slow-release somatostatin analogues and dopamine agonists with long-lasting activity, such as cabergoline. The use of these drugs has extended the possibility of treatment to patients who would have responded poorly to the previously available compounds, such as octreotide or bromocriptine, and to those who were intolerant to pharmacotherapy. Moreover, the improvement in the management of acromegaly has enabled the reversal, at least partly, of cardiomyopathy and sleep apnoea, two important risk factors for morbidity and mortality in these patients.

Topics: Acromegaly; Cabergoline; Dopamine Agonists; Ergolines; Hormone Antagonists; Human Growth Hormone; Humans; Hyperprolactinemia; Somatostatin

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

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

The present study aimed to evaluate the efficacy of add-on therapy of cabergoline versus raloxifene to long-acting somatostatin analogues (SAs) in patients with inadequately controlled acromegaly.. This was a prospective, randomized open label clinical trial. Forty-four patients (22 per group) completed the study; where participants received either cabergoline (3 mg/week) or raloxifene (60 mg twice daily) add-on therapy for 12 weeks in a parallel manner. The primary outcome was the rate of reduction in serum insulin-like growth factor 1 (IGF-1) from baseline. Secondary outcomes comprised normalization of serum IGF-1 for age and sex.. Serum IGF-1 was significantly decreased in both the cabergoline (40.3 ± 25.6%, P<.001) and raloxifene (31.5 ± 24.6%, P<.001) groups, with no significant difference between arms ( P>.05). Normalization in serum IGF-1 values occurred in 40.9% of patients who were on cabergoline compared to 45.5% of those receiving raloxifene ( P = .76). The subsequent logistic regression analysis highlighted baseline IGF-1 as a significant predictor of IGF-1 normalization (odds ratio, 0.995; 95% confidence interval, 0.990-0.999; P = .02). Using the receiver operating characteristic (ROC) curve analysis for the entire group, the baseline IGF-1 value of 1.47 the upper limit of normal (ULN) was the best cut-off point to identify patients with normal IGF-1 at the end of the study (sensitivity: 52.6%, specificity: 84.0%, Yoden's index: 0.366). Full biochemical control of acromegaly was achieved in 22.7% of patients in the cabergoline group compared to 13.6% of those in the raloxifene group ( P = .43).. Cabergoline and raloxifene add-on therapy could effectively decrease serum IGF-1 level in patients with inadequately controlled acromegaly. The efficacy profiles of both drugs are comparable.. DA = dopamine agonist; FBG = fasting blood glucose; GH = growth hormone; IGF1 = insulin-like growth factor-1; IQR = interquartile range; OR = odds ratio; ROC = receiver operating characteristic; SA = somatostatin analogue; SERM = selective estrogen modulator receptor; ULN = upper limit of normal.

Topics: Acromegaly; Adult; Blood Pressure; Cabergoline; Ergolines; Female; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Logistic Models; Male; Middle Aged; Prospective Studies; Raloxifene Hydrochloride; Selective Estrogen Receptor Modulators; Somatostatin

With adequate dose titration, pegvisomant normalizes IGF-I in up to 97% of patients with acromegaly. Pegvisomant is indicated for treatment-resistant disease but is expensive, particularly at a high dose. It has been used successfully in combination with somatostatin analogs. However, there are no therapeutic reports of pegvisomant in combination with dopamine agonists. Cabergoline is orally active, well-tolerated, and relatively inexpensive, and as monotherapy for acromegaly it is reported to normalize IGF-I in up to 30% of patients.. The aim of the study was to investigate the efficacy of cabergoline monotherapy and pegvisomant in combination with cabergoline to control serum IGF-I in patients with active acromegaly. Twenty-four patients were recruited into a United Kingdom, multicenter, open-label, prospective clinical trial.. We measured the change in serum IGF-I.. After 18 wk of dose titration to a maximum dose of 0.5 mg once daily, cabergoline monotherapy did not significantly reduce IGF-I (454 ± 219 baseline vs. 389 ± 192 ng/ml cabergoline), although two patients did normalize IGF-I. The addition of 10 mg pegvisomant daily for 12 wk significantly reduced IGF-I (389 ± 192 ng/ml cabergoline vs. 229 ± 101 ng/ml combination), and 68% achieved a normal IGF-I. Twelve weeks after cabergoline withdrawal, while continuing to receive pegvisomant 10 mg, only 26% of patients maintained an IGF-I within the reference range (229 ± 101 ng/ml combination vs. 305 ± 177 ng/ml pegvisomant). There were no significant changes in liver transaminases or glucose metabolism throughout the study.. These data suggest that combination treatment with cabergoline and pegvisomant is more effective at reducing IGF-I levels than either cabergoline or pegvisomant monotherapy.

Topics: Acromegaly; Adult; Aged; Aged, 80 and over; Cabergoline; Dopamine Agonists; Drug Monitoring; Drug Resistance; Drug Therapy, Combination; Ergolines; Female; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Patient Dropouts; Receptors, Somatotropin; United Kingdom

Nearly 40% of acromegalic patients fail to control GH/IGF-I levels with somatostatin analogues (SA). Dopaminergic agonists (DA) are even less effective, but combination therapy with SA and DA normalizes IGF-I levels in 33-56% of patients not controlled by octreotide alone in short-term studies. This study was designed to evaluate short- and long-term efficacy of cabergoline in controlling IGF-I levels in acromegalic patients receiving octreotide.. Open-label, single arm, prospective trial. Nineteen patients (14 females, 29-78 years of age) with high IGF-I on octreotide-LAR (30 mg/month IM) for > or =6 months were enrolled. Study I: Cabergoline (PO) was started at 1.0, increased to 2.0 and 3.5 mg/week, and withdrawn at 6-week intervals. IGF-I, GH, and PRL were measured at baseline and at 6-week intervals. Study II: Responder patients (IGF-I < or =1 ULN) resumed cabergoline at individual lowest effective doses and were evaluated at 6-month intervals for > or =12 months. Study III: Responders were withdrawn from octreotide and hormonally evaluated at 3-month intervals.. Serum IGF-I (IRMA), GH (ICMA) and PRL (ICMA) levels were determined by commercially available kits.. Addition of cabergoline to octreotide-LAR normalized IGF-I levels in 7 of 19 patients (37%) during both short- and long-term follow-up (12-27 months, mean: 18 months). Octreotide withdrawal increased IGF-I levels in only 2 of 6 responder patients. Normalization of IGF-I levels by cabergoline was strongly associated with IGF-I < or =2.2 ULNR and/or GH < or =4.0 ng/ml under octreotide treatment.. Addition of cabergoline to octreotide was effective in both short- and long-term control of IGF-I in acromegaly, especially in patients with mild/moderately elevated GH/IGF-I levels during octreotide.

Topics: Acromegaly; Adult; Aged; Cabergoline; Dopamine Agonists; Drug Therapy, Combination; Ergolines; Female; Humans; Insulin-Like Growth Factor I; Middle Aged; Octreotide; Somatostatin

To evaluate the long-term efficacy and safety of pegvisomant as a treatment for acromegaly.. Retrospective analysis of clinical and trial data from all patients treated with pegvisomant since 1997 at two centres with common protocols.. Fifty-seven patients (age range 27-78 years) have been treated with pegvisomant since 1997 for up to 91 months (median 18 months). Before commencing pegvisomant, patients had an IGF-I above the upper limit of normal (ULN) of the age-related reference range (median 1.8 x ULN, range 1.2-4.1). Ninety-five per cent normalized IGF-I using a median dose of 15 mg daily (range 10 mg alternate day to 60 mg daily) with no influence of gender on dose requirement. Five patients had combination therapy with either somatostatin analogues (SSA) or cabergoline. Two patients initially controlled on 10 mg and 20 mg required dose increases (to 20 mg + 40 mg) over 24 months to reduce IGF-I. Twenty-seven patients stopped pegvisomant. Reasons included side-effects [abnormal liver function tests (LFTs)] and patient choice. Two patients developed elevated liver transaminases, which normalized on stopping pegvisomant. Patients had 6-12-monthly pituitary magnetic resonance imaging (MRI) scans. One patient had significant tumour size increase.. This long-term experience in 57 patients indicates pegvisomant to be effective, safe and well-tolerated. Raised transaminases occurred within the first month of therapy in two patients, and tumour growth was seen in one patient (tumour was growing prior to pegvisomant). In two patients increasing doses of pegvisomant were required to keep IGF-I within the target range.

Topics: Acromegaly; Adult; Aged; Cabergoline; Drug-Related Side Effects and Adverse Reactions; Ergolines; Female; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Retrospective Studies; Somatostatin; Treatment Outcome

Previous data indicate a beneficial effect of cabergoline (CAB) association to somatostatin analogs (SA) in acromegalics resistant to SA monotherapy.. To assess the efficacy of CAB association on acromegalics with high IGF-I on stable long-acting release octreotide (OCT-LAR) (30 mg/28 days).. 34 patients (17 male, 25-85 years, 33 macroadenomas) were enrolled in this prospective study. OCT-LAR was administered as primary (n = 4) and as secondary (n = 30) treatment: after surgery (n = 16), after surgery + radiotherapy (RT) (n = 11), and after RT only (n = 3). Duration of OCT-LAR therapy prior to CAB was 24 +/- 12 months. The immunohistochemical features of the tumors disclosed GH/PRL co-secretion in 11/21 patients. 13 patients had high PRL levels prior to CAB. The initial CAB dose was 1.5 mg/week. No IGF-I normalization led to a dose increase to 3.5 mg/week. The OCT-LAR dose was kept stable during treatment. IGF-I, GH and PRL levels were compared before and after CAB association. OCT-LAR was withdrawn in patients who achieved IGF-I normalization, in order to assess the influence of CAB.. Comparing OCT-LAR to OCT-LAR/CAB treatment, there was a significant decrease in mean GH, IGF-I, %ULNR-IGF-I and PRL levels. During OCT-LAR/CAB treatment, IGF-I normalized in 19 patients (56%). IGF-I normalization was correlated to lowest IGF-I levels on OCT-LAR monotherapy, but not to baseline PRL levels or GH/PRL co-expression. OCT-LAR withdrawn in all who had achieved IGF-I normalization on combined therapy resulted in IGF-I elevation to abnormal levels in all patients. Gastrointestinal symptoms were reported by 12 patients.. OCT-LAR and CAB association has been shown to be an effective alternative therapy for those acromegalics who still have active acromegaly despite monotherapy with SA, mainly for those with lower pretreatment IGF-I concentrations. According to previous studies, the beneficial effects of CAB occur even when pretreatment PRL is normal and/or there is no tumor GH/PRL co-expression.

Topics: Acromegaly; Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Cabergoline; Delayed-Action Preparations; Drug Therapy, Combination; Ergolines; Female; Growth Hormone; Humans; Immunohistochemistry; Male; Middle Aged; Octreotide; Prospective Studies; Time Factors; Treatment Outcome

Somatostatin analogues (SA) are currently the mainstay in the medical treatment of acromegaly. However, even high doses of depot SA for prolonged periods do not achieve GH-IGF-I normalization in some patients. Even though some data were reported about the addition of cabergoline, a long-acting dopamine agonist (DA), to SA in resistant patients, definite data are still lacking.. Prospective open trial.. In 19 acromegalic patients with active disease (34-82 years old, seven males, 12 females) resistant to chronic (9-12 months) depot SA (octreotide-LAR, 30 mg/28 days in 13 patients, lanreotide, 60 mg/28 days intramuscularly in six patients) cabergoline was added (combined treatment). In these patients, SA treatment had partially relieved GH and IGF-I hypersecretion but no patient had achieved 'safe' GH and normal IGF-I-values. Eight patients had PRL levels greater than 15 micro g/l (range 16-60 micro g/l; 1 micro g = 21.2 mIU). Immunohistochemistry (IHC) was positive for PRL in four out of eight operated patients.. The addition of cabergoline, using the minimal effective and the maximal tolerated dose (range 1-3.5 mg/week), decreased GH from 6.6 +/- 0.9 to 4.6 +/- 0.6 micro g/l (P = 0.018), and IGF-I from 552 +/- 44 to 428 +/- 54 micro g/l (P = 0.019) after 6 months (median, range 3-18 Months). Combined treatment decreased GH to < 2.5 micro g/l in four patients (21%) and normalized IGF-I for age in eight patients (42%). It obtained a decline of both GH and IGF-I (-49 +/- 7%, and -47 +/- 5%, respectively) in nine patients (47%), and a partial improvement in six (32%) patients (GH decreased by 43 +/- 8% in four, and IGF-I by 35-38% in two patients). No change was observed in two patients, and worsening in two other patients. Results were not dependent on PRL status (serum levels or IHC). Combined treatment was well tolerated.. The addition of cabergoline to depot SA-resistant acromegalic patients is effective, not dependent on PRL values and normalizes IGF-I levels in 42% of patients. The association of long-acting DA and SA deserves a more relevant role in the therapeutical algorithm of acromegaly.

Topics: Acromegaly; Adult; Aged; Aged, 80 and over; Cabergoline; Delayed-Action Preparations; Dopamine Agonists; Drug Therapy, Combination; Ergolines; Female; Gastrointestinal Agents; Human Growth Hormone; Humans; Immunohistochemistry; Insulin-Like Growth Factor I; Male; Maximum Tolerated Dose; Middle Aged; Octreotide; Peptides, Cyclic; Prolactin; Prospective Studies; Somatostatin

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

Cabergoline, the new long-acting dopaminergic ergoline derivative, was given orally in single doses of 0.3 and 0.6 mg to eight dopamine-responsive acromegalic patients. Serum GH and PRL levels were determined before treatment, 3, 4, and 6 h and 1, 3, 5, 7 and 14 days after treatment. A control test with a single oral dose of 2.5 mg of bromocriptine was also performed. Cabergoline induced a marked fall in serum PRL level, starting within 3 h and continuing for 7 days after administering 0.3 mg, and for 14 days after 0.6 mg. The mean maximal decrease was 49% after 0.3 mg and 63% after 0.6 mg and occurred after 24 h in both cases. The latter was of similar magnitude to that induced by bromocriptine (67% at 4 h). Serum GH levels did not change after 0.3 mg of cabergoline, but decreased significantly from 3 h to 3 days after 0.6 mg of the compound with a mean maximal decrease of 42% after 24 h, and from 3 to 6 h after giving bromocriptine (mean maximal decrease 63% at 4 h). Once a week repeated administration of 0.3-0.6 mg of cabergoline was carried out in six patients, five of whom had completed the acute study; a normalization of serum GH and insulin-like growth factor I (IGF-I) levels occurred in three patients, one of whom had very high pretreatment values. In three poorly or nonresponsive patients, a better response, as assessed by both GH and IGF-I levels, was induced by increasing the dose up to 0.6 mg twice or 0.4 mg three times a week; in one case this was associated with marked tumour shrinkage. Sustained normalization of PRL levels was achieved in all cases. These data indicate that a single dose of 0.6 mg of cabergoline inhibits GH as well as PRL secretion in dopamine-responsive acromegalic patients and suggests that doses of 0.3-0.6 mg once to three times a week may prove suitable for treatment of this condition.

Topics: Acromegaly; Adult; Animals; Cabergoline; Chick Embryo; Dopamine; Dopamine Agents; Ergolines; Female; Growth Hormone; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Prolactin

The effect of a new dopamine agonist, CU 32-085 (8 alpha-amino-ergoline), on pituitary function in acromegaly was evaluated by a controlled, single blind study of 12 acromegalics. The study included a single dose placebo/drug (0.5 mg CU 32-085) trial and a long-term crossover trial with 3 month periods (placebo/CU 32-085 8 mg daily). The patients were evaluated clinically and biochemically (oral glucose tolerance (OGTT), TRH- and LHRH-tests) before and after each 3 month period. Nine patients completed this long-term trial; one died from myocardial infarction during the placebo period, and two dropped out because of side effects. The release of GH, judged from more than 9 h suppression of serum GH following the single dose, and from the response to OGTT after the long-term treatment, was significantly inhibited by CU 32-085. Serum GH reached normal values in 4 of 9 patients. Serum PRL was also markedly suppressed, to subnormal values after the 3 months in all but one hyperprolactinemic patient. Serum TSH, cortisol, FSH and LH were generally unaffected. Glucose tolerance was not significantly altered, although an improvement was found in six of nine patients. A semiquantitative evaluation of subjective symptoms showed a significant improvement following the long-term treatment, while objective signs of acromegaly were unaffected. The blood pressure was slightly lowered, both after a single dose and after 3 months' treatment. Seven patients experienced nausea and dizziness, two of them with vomiting, after a single dose of the drug. Four of these had similar symptoms initially during the long-term treatment, which forced two to interrupt the trial. We conclude that CU 32-085 caused a marked suppression of the release of GH and PRL and an improvement of the major symptoms of acromegaly, a therapeutic effect that is comparable to the previous experience with bromocriptine.

Topics: Acromegaly; Adult; Aged; Blood Pressure; Clinical Trials as Topic; Ergolines; Female; Growth Hormone; Hormones; Humans; Hydrocortisone; Male; Middle Aged; Prolactin

The effects of the ergoline derivative, lergotrile mesylate, on the serum levels of PRL, GH, TSH, LH, FSH, cortisol, and blood sugar were studied in six normal males. The effects of lergotrile mesylate on the serum levels of GH and PRL were also studied in eight patients with acromegaly and in two with idiopathic hyperprolactinemia. In the normal subjects, 2 mg oral lergotrile lowered basal PRL levels after 90 min and markedly impaired the PRL response to TRH (200 micrograms iv); the mean peak value +/- SE was 8.3 +/- 1.1 micrograms/liter, compared to the control value of 66.6 /+- 11.3 micrograms/liter. Lergotrile raised serum GH levels in five of the six subjects to peaks of 8-49 micrograms/liter, compared to 2-8 micrograms/liter after placebo. In three subjects, the GH response to lergotrile was attenuated by the prior administration of the dopamine antagonist, metoclopramide (10 mg orally). Lergotrile had no effect on FSH and LH levels under basal conditions or after the gonadotrophin-releasing hormone (GnRH; 100 micrograms iv). Circulating TSH levels were unaltered basally but impaired after TRH. Blood sugar levels were unaltered; serum cortisol was elevated in five of six subjects; there was a brief depression of diastolic blood pressure, but no change in pulse rate. The side effects after lergotrile were variable, with drowsiness as a consistent feature. These actions are similar to those of bromocriptine (an ergot derivative treatment of hyperprolactinemia and acromegaly, to suppress PRL and GH secretion, and in parkinsonism. Therefore, it may be expected that lergotrile could fulfill these clinical uses; however, in the studies comparing the effects of single oral doses of lergotrile (2 mg) and bromocriptine (2.5 mg) on GH and PRL secretion in patients with acromegaly and hyperprolactinemia, lergotrile in the dose used has been found to have an earlier onset and shorter duration of action.

Topics: Acromegaly; Adult; Double-Blind Method; Ergolines; Follicle Stimulating Hormone; Growth Hormone; Humans; Hydrocortisone; Kinetics; Luteinizing Hormone; Male; Middle Aged; Pituitary Hormones, Anterior; Prolactin; Reference Values; Thyrotropin; Thyrotropin-Releasing Hormone

Topics: Acromegaly; Bromocriptine; Clinical Trials as Topic; Drug Evaluation; Ergolines; Humans

Topics: Acromegaly; Adult; Aged; Bromocriptine; Clinical Trials as Topic; Ergolines; Female; Humans; Male; Middle Aged; Time Factors

Topics: Acromegaly; Bromocriptine; Clinical Trials as Topic; Ergolines; Female; Galactorrhea; Humans; Lactation; Parkinson Disease; Pregnancy

Bromocriptine (CB-154, Sandoz) has been given to 21 acromegalic patients (11 female, 10 male) for a period of 6-10 months. The mean serum growth-hormone (G.H.) levels ranged from 10 mug/1 to 512 mug/1 before therapy. Bromocriptine suppressed G.H. values to 5 mug/1 or less in 4 patients and to less than 10 mug/1 in a further 8 patients, but in 2 patients G.H. levels did not show any significant reduction. Bromocriptine did not block stress-induced G.H. secretion. It did not distrub pituitary function other than secretion of prolactin and had negligible side-effects. Its effect on tumour size is uncertain and it is therefore unsuitable for patients with suprasellar extension of the tumour. Otherwise it seems reasonable to offer a trial of bromocriptine to all patients with acromegaly where therapy is deemed necessary. In those who show a full response of G.H. levels with a dose of 20-40 mg of bromocriptine per day, external radiation to the pituitary can be used to prevent tumour expansion and bromocriptine withdrawn at intervals to assess the effect of the radiation. In patients with a partial response to bromocriptine, the decision to offer alternative therapy depends on the extent of the response and on the age and medical condition of the patient. In patients who fail to respond to bromocriptine, particularly those younger patients with active disease, more definitive local treatment (e.g., trans-sphenoidal removal of the tumour or yttrium-90 implantation) would be indicated. Bromocriptine may also be used with benefit in the large number of patients who have shown a partial response to other forms of therapy.

Topics: 11-Hydroxycorticosteroids; Acromegaly; Administration, Oral; Adult; Aged; Blood Glucose; Bromocriptine; Clinical Trials as Topic; Drug Evaluation; Ergolines; Female; Follicle Stimulating Hormone; Growth Hormone; Humans; Luteinizing Hormone; Male; Middle Aged; Pituitary Function Tests; Thyrotropin; Thyrotropin-Releasing Hormone; Time Factors

The aim of this study was to evaluate the efficacy of cabergoline in normalizing plasma IGF-I levels in acromegaly patients with elevated IGF-I levels after surgery and/or SRL therapy. Acromegaly patients (n: 143) were evaluated retrospectively. Patients with elevated IGF-I levels after surgery and/or SRLs therapy and a fixed dose of SRLs treatment for the last six months with no history of radiotherapy in the last three years were included in the study (n: 12). Previous treatment regimens, baseline PRL and IGF-I levels (ULNR), sella MRI, and immunohistochemical findings were evaluated. Cabergoline was used as an add on (n: 11) or single medical treatment (n: 1). The median duration of treatment with SRL alone was 12 months (range 6-48 months). The mean IGF-I value before cabergoline therapy was 1.45±0.4 ULNR. The mean cabergoline dose and duration of treatment were 1.55±0.75 mg/week and 9±6.3 months, respectively. IGF-I normalization was only achieved in patients with serum IGF-I concentration<1.5×ULNR before the onset of cabergoline treatment (n: 9). In some of the patients with IGF-I normalization, baseline prolactin levels were normal (n: 3). Immunopositivity for prolactin in adenoma tissue was found in three patients with IGF-I normalization. Cabergoline therapy is effective in the normalization of IGF-I levels even in normoprolactinemic acromegaly patients when IGF-I levels are mildly or moderately elevated during SRL therapy.

Topics: Acromegaly; Cabergoline; Ergolines; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Prolactin; Retrospective Studies

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

The approach to acromegalic patients with persistent acromegaly after surgery and inadequate response to first-generation somatostatin receptor ligands (SRLs) should be strictly tailored. Current options include new pituitary surgery and/or radiosurgery, or alternative medical treatment with SRLs high dose regimens, pegvisomant (PEG) as monotherapy, or combined therapy with the addition of PEG or cabergoline to SRLs. A new pharmacological approach includes pasireotide, a second-generation SRL approved for patients who do not adequately respond to surgery and/or for whom surgery is not an option. No reports on efficacy and safety of combined therapy with pasireotide and pegvisomant (PEG) in acromegaly are available.. Here we report the case of a 41-year-old acromegalic man with a mixed GH/PRL pituitary adenoma post-surgical resistant to first-generation SRLs both alone and in combination with cabergoline and PEG who achieved biochemical and tumor control with the combined triple treatment with pasireotide, PEG and cabergoline without adverse events and with a good compliance to treatment.. Twelve months of therapy with pasireotide, PEG and cabergoline proved to be safe and effective in this particular patient and the clinical improvement of disease resulted in an improved compliance to treatment.

Topics: Acromegaly; Adult; Antineoplastic Agents; Cabergoline; Drug Therapy, Combination; Ergolines; Hormones; Human Growth Hormone; Humans; Male; Prognosis; Salvage Therapy; Somatostatin

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

Acromegaly is characterized by growth hormone (GH) and insulinlike growth factor-1 (IGF-1) hypersecretion, and GH and IGF-1 play important roles in regulating body composition and glucose homeostasis.. The purpose of our study was to investigate body composition including ectopic lipids, measures of glucose homeostasis, and gonadal steroids in patients with active acromegaly compared with age-, body mass index (BMI)-, and sex-matched controls and to determine changes in these parameters after biochemical control of acromegaly.. Cross-sectional study of 20 patients with active acromegaly and 20 healthy matched controls. Prospective study of 16 patients before and after biochemical control of acromegaly.. Body composition including ectopic lipids by magnetic resonance imaging/proton magnetic resonance spectroscopy; measures of glucose homeostasis by an oral glucose tolerance test; gonadal steroids.. Patients with active acromegaly had lower mean intrahepatic lipid (IHL) and higher mean fasting insulin and insulin area under the curve (AUC) values than controls. Men with acromegaly had lower mean total testosterone, sex hormone-binding globulin, and estradiol values than male controls. After therapy, homeostasis model assessment of insulin resistance, fasting insulin level, and insulin AUC decreased despite an increase in IHL and abdominal and thigh adipose tissues and a decrease in muscle mass.. Patients with acromegaly were characterized by insulin resistance and hyperinsulinemia but lower IHL compared with age-, BMI-, and sex-matched healthy controls. Biochemical control of acromegaly improved insulin resistance but led to a less favorable anthropometric phenotype with increased IHL and abdominal adiposity and decreased muscle mass.

Topics: Acromegaly; Adipose Tissue; Adult; Aged; Blood Glucose; Body Composition; Cabergoline; Case-Control Studies; Cross-Sectional Studies; Ergolines; Female; Gonadal Steroid Hormones; Human Growth Hormone; Humans; Insulin Resistance; Insulin-Like Growth Factor I; Lipid Metabolism Disorders; Lipodystrophy; Male; Middle Aged; Peptides, Cyclic; Prednisone; Somatostatin

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

Remission of acromegaly has been reported after somatostatin analogs withdrawal, but not after withdrawal of combination therapy with cabergoline, and only in case reports of patients controlled by cabergoline alone.. To establish the remission rates (normal IGF-1 for age/sex: IGF-1 ≤ 1.00 xULN) after withdrawal of combined treatment with octreotide LAR and cabergoline and of cabergoline alone, we prospectively studied 16 patients with acromegaly controlled by those treatments in the preceding 2 years as part of a larger study on remission of acromegaly after withdrawal of different medical treatments.. Among 97 patients with controlled acromegaly included in the entire study, only 16 patients had been on combination therapy (n = 12) or cabergoline alone (n = 4). At 8 weeks after treatment withdrawal, three patients (19%) were in remission (short-term remission). At 60 weeks (long-term remission), IGF-1 levels were still in the normal range in two patients (12.5%) and remained normal up to 108 weeks after treatment withdrawal (last visit). One patient had been treated with cabergoline alone and another one with combination of octreotide and cabergoline before treatment withdrawal.. Remission of acromegaly after treatment withdrawal seems to be uncommon in patients controlled by cabergoline, either as monotherapy or in combination with octreotide. In the future, larger studies and/or meta-analysis will be necessary to accurately establish the remission rates of acromegaly after withdrawal of cabergoline with or without somatostatin analogs.

Topics: Acromegaly; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cabergoline; Ergolines; Female; Follow-Up Studies; Humans; Male; Middle Aged; Octreotide; Prognosis; Prospective Studies; Remission Induction; Withholding Treatment

To establish a baseline pattern of care across academic and community settings, it is important to examine the contemporary treatment of acromegaly. We characterized medical treatment patterns for acromegaly in the US to develop a basis for tracking concordance with guidelines.. Acromegaly patients were identified in two commercial claims databases for this retrospective analysis. Study subjects had ≥2 medical claims with acromegaly (ICD-9-CM code 253.0) and ≥1 claim for pharmacotherapy (bromocriptine, cabergoline, octreotide SA, octreotide LAR, lanreotide, or pegvisomant) in the study timeframe (1 January 2002-31 December 2013). Patients were considered newly treated if they were continuously enrolled for ≥6 months before first observed treatment and had no claim for pharmacologic treatment during that time. Outcomes included various pharmacotherapies, including combination treatments, and differences between lines of therapy.. A total of 3150 patients had ≥1 pharmacotherapy (mean age: 46.5 years; 50.1% were female); 1471 were newly treated. Somatostatin receptor ligands (SRLs) were the most common drug class used first line (57.2%); cabergoline (27.8%) was the most common treatment, followed by octreotide LAR (22.3%) and lanreotide (19.7%). SRLs were also the most commonly used second-line (42.8%) and third-line pharmacotherapies (43.9%), with combination therapy (23.2%) and octreotide LAR (19.8%) as the most commonly used treatments, respectively.. This study, representing the largest claims-based analysis of acromegaly to date, used two databases across a 12 year period to examine complex treatment patterns in a difficult-to-study disease. Although wide variation in acromegaly treatment patterns exists in US clinical practice, in first-line, second-line, and third-line therapy, SRL was the most commonly used drug class. Drug combinations also varied considerably across lines of therapy. The switching between different monotherapies and varied use of drugs in combination may suggest an unmet need for alternative treatment options. Our claims-based technique of examining treatment patterns may be used for other rare diseases, although high censoring rates may be a challenge.

Topics: Acromegaly; Adult; Cabergoline; Databases, Factual; Ergolines; Female; Human Growth Hormone; Humans; Male; Middle Aged; Octreotide; Peptides, Cyclic; Retrospective Studies; Somatostatin

To describe real-world use of lanreotide combination therapy for acromegaly.. ACROCOMB is a retrospective observational Spanish study of patients with active acromegaly treated with lanreotide combination therapy between 2006 and 2011. 108 patients treated at 44 Spanish Endocrinology Departments were analyzed separately: 61 patients received lanreotide/cabergoline (cabergoline cohort) and 47 lanreotide/pegvisomant (pegvisomant cohort).. Patient median age was 50.8 years in the cabergoline cohort and 42.7 years in the pegvisomant cohort. Prior medical treatments were somatostatin analogue (SSA) monotherapy (40 [66%] patients) or dopamine agonists (7 [11%] patients) in the cabergoline cohort and SSA (29 [62%] patients) or pegvisomant monotherapy (16 [34%] patients) in the pegvisomant cohort. Across both cohorts 12 patients were previously untreated, and prior therapy was unknown/missing in 4 patients. Median duration of combined treatment was 1.6 years (0.1-6) and 2.1 years (0.4-6.3) in the cabergoline and pegvisomant cohorts, respectively. At baseline, median insulin growth factor (IGF)-I values were 149% upper limit of normal (ULN) (15-505%) in the cabergoline cohort and 156% ULN (15-534%) in the pegvisomant cohort, and decreased to 104% ULN (13-557%) p<0.001 and 86% ULN (23-345%) p<0.0001, respectively, at end of study (EOS). Normal age-adjusted values of IGF-I were obtained in 48% of lanreotide/cabergoline-treated patients and 70% of lanreotide/pegvisomant-treated patients at EOS. There were no significant changes in hepatic, cardiac or glycaemic parameters in either cohort.. In clinical practice lanreotide treatment combinations are useful options for patients with acromegaly when monotherapy is insufficient; particularly, the combination of lanreotide and pegvisomant in patients not controlled with either SSA or pegvisomant alone has high efficacy and is well-tolerated.

Topics: Acromegaly; Cabergoline; Dopamine Agonists; Drug Therapy, Combination; Ergolines; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Peptides, Cyclic; Retrospective Studies; Somatostatin

We described biochemical outcome in regards to different treatment modalities in patients with acromegaly in Bulgaria.. It was a retrospective analysis using data from the Bulgarian Acromegaly Database. Patients with eligible data on at least one treatment modality were included in the study. Disease control was assessed by both GH and IGF-1 values or by GH/IGF-1 alone in cases with one marker. Last follow-up was median 7.0 (range 0.5-51) years after diagnosis.. We identified 534 patients with interpretable data, 65.4% of whom were females. Overall surgical cure rate was 28.8%. Adjuvant bromocriptine and cabergoline treatment was analyzed in 133 and 70 patients with disease control achieved in 18.8% and 31.4% respectively. Patients without prior radiotherapy had 16.3% and 18.2% control rates respectively. Predictors of response to dopamine agonist (DA) therapy were disease activity, radiotherapy and medication dose. Adjuvant somatostatin analog (SSA) treatment led to biochemical control in 38.6% of 70 patients. Combination of SSA and cabergoline led to remission in 25% of 20 patients. Growth hormone receptor antagonist (GHRA) alone or in combination resulted in remission in 61.5% of 13 patients. Approximately one third of the patients were cured median 10 years after irradiation. Overall disease control was observed in 51.4% of our patients increasing to 70.3% in the last 5 years of the study period.. DAs are efficient in less than 20% of non-irradiated patients. They are a good cost-effective alternative for carefully selected patients.

Topics: Acromegaly; Adolescent; Adult; Aged; Bromocriptine; Bulgaria; Cabergoline; Child; Databases, Factual; Dopamine Agonists; Ergolines; Female; Follow-Up Studies; Humans; Male; Middle Aged; Radiotherapy; Remission Induction; Retrospective Studies; Somatostatin

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

The effect of pegvisomant on IGF1 levels in patients with acromegaly is well documented, but little is known of its long-term impact on comorbidity.. The aim of this retrospective study was to evaluate the effects of long-term pegvisomant therapy on cardiorespiratory and metabolic comorbidity in patients with acromegaly.. We analyzed the long-term (up to 10 years) effect of pegvisomant therapy given alone (n=19, 45%) or in addition to somatostatin analogues and/or cabergoline (n=23, 55%) on echocardiographic, polysomnographic and metabolic parameters in respectively 42, 12 and 26 patients with acromegaly followed in Bicêtre hospital.. At the first cardiac evaluation, 20±16 months after pegvisomant introduction, IGF1 levels normalized in 29 (69%) of the 42 patients. The left ventricular ejection fraction (LVEF) improved significantly in patients whose basal LVEF was ≤60% and decreased in those whose LVEF was >70%. The left ventricular mass index (LVMi) decreased from 123±25 to 101±21 g/m(2) (P<0.05) in the 17 patients with a basal LVMi higher than the median (91 g/m(2)), while it remained stable in the other patients. Pegvisomant reduced the apnoea-hypopnea index and cured obstructive sleep apnea (OSA) in four of the eight patients concerned. Long-term follow-up of 22 patients showed continuing improvements in cardiac parameters. The BMI and LDL cholesterol level increased minimally during pegvisomant therapy, and other lipid parameters were not modified.. Long-term pegvisomant therapy not only normalizes IGF1 in a large proportion of patients but also improves cardiac and respiratory comorbidity.

Topics: Acromegaly; Adolescent; Adult; Antineoplastic Agents; Apnea; Cabergoline; Comorbidity; Ergolines; Female; Follow-Up Studies; Heart Diseases; Human Growth Hormone; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Retrospective Studies; Somatostatin; 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

The interaction between pregnancy and acromegaly has been studied only retrospectively. We used prospective data to assess those interactions.. Prospective, interventional, multicentric study.. TEN PREGNANCIES IN EIGHT ACROMEGALIC PATIENTS WERE INCLUDED ACCORDING TO THE FOLLOWING CRITERIA: previous diagnosis of acromegaly; and active acromegaly before pregnancy. Sellar magnetic resonance image (MRI), GH, and IGF1 measurements were carried out before pregnancy. The exclusion criterion was radiotherapy.. Withdrawal of pharmacological treatment (octreotide and/or cabergoline and/or pegvisomant) following pregnancy diagnosis.. Clinical/biochemical evaluations throughout pregnancy/puerperium and sellar MRI after delivery; and GH and IGF1 measurements before pregnancy. GH was measured by an interference-free IFMA assay during pregnancy and IGF1 by measured by Immulite 2000 assay in patients and 64 control pregnancies.. No tumor growth was observed. Nine deliveries were at term and one at 35 weeks (preeclampsia). All newborns were healthy. Mean IGF1 levels before and during pregnancy were similar, but increased significantly during puerperium. As IGF1 in controls increased after midgestation, the prevalence of controlled IGF1 rose significantly from 2/10 (<20 weeks) to 9/10 (>30 weeks). Diabetes mellitus and hypertension/preeclampsia developed in one patient in each group; both complications were nonsignificantly (P=0.06) associated with IGF1 >1.3 ULN before pregnancy.. Acromegaly control usually improved and tumor growth was not stimulated during pregnancy in spite of withdrawal of drug treatment. Drug treatment can be discontinued in most patients. Uncontrolled disease before pregnancy may pose a higher risk for diabetes and hypertension.

Topics: Acromegaly; Adult; Cabergoline; Ergolines; Female; Human Growth Hormone; Humans; Infant, Newborn; Insulin-Like Growth Factor I; Magnetic Resonance Imaging; Octreotide; Pregnancy; Pregnancy Complications, Neoplastic; Prospective Studies; Sella Turcica

Many options are available for the treatment of acromegaly, including surgery, radiotherapy, and medical treatment. Cabergoline (CAB), a dopamine agonist with high affinity for dopamine receptor type 2, has been used both in monotherapy and in conjunction with somatostatin analogs (SSAs). Although it is administered orally and has a relatively lower-cost in comparison with SSAs, few studies have demonstrated its usefulness, there is a lack of randomized-controlled trials and other drugs (SSAs and pegvisomant) with more data in the literature are available; these issues are the main drawbacks of adopting CAB for the treatment of acromegaly.

Topics: Acromegaly; Cabergoline; Dopamine Agonists; Drug Therapy, Combination; Ergolines; Humans; Octreotide

Cabergoline is an ergot-derived dopamine D2 receptor agonist which may be effective for the medical management of acromegaly. Its efficacy in reducing growth hormone and IGF-I levels, as well as its antiproliferative and pro-apoptotic effects on pituitary tumor cells, has been observed in several studies. Cabergoline may be used alone or as an add-on therapy to patients who are partially resistant to somatostatin analogs (SSA), or who do not achieve complete control with maximum doses of pegvisomant (PEG). Additionally, the convenience of its oral administration, allowing better compliance, and its lower economic cost, in comparison with SSA and PEG, favor cabergoline as an attractive option for acromegalic patients, who frequently require long-life medical treatment to achieve disease control. The few adverse events observed with prolonged DA therapy, mainly regarding cardiac valve disease, are not frequent at the doses generally used in acromegaly.

Topics: Acromegaly; Cabergoline; Dopamine Agonists; Drug Therapy, Combination; Ergolines; Humans; Octreotide; Treatment Outcome

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

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

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

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

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

Combination with cabergoline may offer additional benefits to acromegalic patients on pegvisomant monotherapy. We evaluated the safety and efficacy profile of this combination and investigated the determinants of response. An observational, retrospective, cross-sectional study. Fourteen acromegalic patients (9 females), who were partially resistant to somatostatin analogs and on pegvisomant monotherapy. Cabergoline was added because of the presence of persistent mildly increased IGF-I. The mean follow-up time was 18.3 ± 10.4 months. The efficacy and safety profile was assessed. The influence of clinical and biochemical characteristics on treatment efficacy was studied. IGF-I levels returned to normal in 4 patients (28%) at the end of the study. In addition, some decline in IGF-I levels was observed in a further 5 patients. The % IGF-I decreased from 158 ± 64% to 124 ± 44% (p = 0.001). The average change in IGF-I was -18 ± 27% (range -67 to +24%). Lower baseline IGF-I (p = 0.007), female gender (p = 0.013), lower body weight (p = 0.031), and higher prolactin (PRL) levels (p = 0.007) were associated with a better response to combination therapy. There were no significant severe adverse events. Significant tumour shrinkage was observed in 1 patient. Combination therapy with pegvisomant and cabergoline could provide better control of IGF-I in some patients with acromegaly. Baseline IGF-I levels, female gender, body weight, and PRL levels affect the response to this combination therapy.

Topics: Acromegaly; Adult; Cabergoline; Drug Therapy, Combination; Ergolines; Female; Human Growth Hormone; Humans; Male; Middle Aged; Retrospective Studies

Acromegaly is a rare, chronic, and debilitating disease that results from excessive growth hormone production. Clinically, this disease is associated with enlargement of soft tissue, excessive skeletal growth, and increased risk of cardiovascular disease. Acromegaly is often diagnosed late, when a wide range of comorbidities may already be present. First-line therapy for acromegaly is typically surgery; but a number of highly-specific pharmacological agents have recently enabled a more aggressive medical management of acromegaly. Since surgical cure of acromegaly is low for macroadenomas, medical control of active acromegaly is an important component of treatment. There are no published US data currently available regarding real-world rates of comorbidities and treatment patterns among patients with acromegaly. This retrospective study examined the comorbidities and treatment patterns of 949 health plan enrollees, who had acromegaly diagnosis and/or procedure codes in an administrative claims database from July 1, 2002 through June 30, 2010. Acromegaly was associated with high rates of hypertension and diabetes along with a number of other comorbidities. The incidence of comorbidities was highest among patients with acromegaly-related treatment, which may have resulted, in part, from inadequate disease management and/or poor disease control. Unexpectedly, 55% of patients identified with acromegaly received no treatment for acromegaly (i.e., surgery, radiotherapy, and medication) and only 28% received a medication treatment during the observation period. However, some patients may have received a curative surgery prior to the observation period, which may have reduced the use of other acromegaly-related treatments during the study period. Of those treated with medications, the most common first medications were octreotide, cabergoline, and bromocriptine. Given the high incidence of serious comorbidities associated with active acromegaly, earlier diagnosis and treatment, along with appropriate follow-up care, may potentially avoid the life-long consequences of uncontrolled disease.

Topics: Acromegaly; Adult; Bromocriptine; Cabergoline; Databases, Factual; Ergolines; Female; Human Growth Hormone; Humans; Male; Middle Aged; Octreotide; Peptides, Cyclic; Retrospective Studies; Somatostatin; United States

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

The effects of cabergoline on cardiac valves have been extensively studied in Parkinson's disease and hyperprolactinemia but not in acromegaly, a condition at risk of cardiac valve abnormalities.. We examined the prevalence and incidence of heart valve disease and regurgitation in a series of patients with acromegaly treated with cabergoline, by comparison with matched patients who had never received this drug.. We conducted a cross-sectional and longitudinal study in a single referral center.. Forty-two patients who had received cabergoline at a median cumulative dose of 203 mg for a median of 35 months were compared to 46 patients with acromegaly who had never received cabergoline and who were matched for age, sex, and disease duration. A subgroup of patients receiving cabergoline (n = 26) was evaluated longitudinally before and during cabergoline treatment and compared to a group not receiving cabergoline and followed during the same period (n = 26). Two-dimensional and Doppler echocardiographic findings were reviewed by two cardiologists blinded to treatment.. Demographic and clinical features were not significantly different between the groups. Compared to acromegalic controls, patients receiving cabergoline did not have a higher prevalence or incidence of valve abnormalities. A slightly higher prevalence of aortic valve regurgitation and remodeling was found in the controls relative to the cabergoline-treated patients (P < 0.02 and P < 0.03, respectively), but this was related to the presence of aortic dilatation.. Cabergoline therapy is not associated with an increased risk of cardiac valve regurgitation or remodeling in acromegalic patients at the doses used in this study.

Topics: Acromegaly; Adolescent; Adult; Aged; Aortic Valve Insufficiency; Cabergoline; Cross-Sectional Studies; Dopamine Agonists; Echocardiography; Echocardiography, Doppler; Ergolines; Female; Heart Valve Diseases; Heart Valves; Humans; Hypertrophy, Left Ventricular; Longitudinal Studies; Male; Middle Aged; Mitral Valve Insufficiency; Retrospective Studies; Tricuspid Valve Insufficiency; 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

Cabergoline, a dopamine agonist used to treat hyperprolactinemia, is associated with an increased risk of fibrotic adverse reactions, e.g. cardiac valvular fibrosis, pleuropulmonary, and retroperitoneal fibrosis.. This study evaluated the prevalence and risk of fibrotic adverse reactions during cabergoline therapy in hyperprolactinemic and acromegalic patients.. A cross-sectional study was conducted in a University Hospital.. A total of 119 patients with hyperprolactinemia and acromegaly who were on cabergoline therapy participated in the study.. All patients were requested to undergo a cardiac assessment, pulmonary function test, chest X-ray, and blood tests as recommended by the European Medicine Agency. Matched controls were recruited to compare the prevalence of valvular regurgitation. Cardiac valvular fibrosis was evaluated by assessing valvular regurgitation and the mitral valve tenting area (MVTa). The risk of pleuropulmonary fibrosis was assessed by a pulmonary function test, a chest X-ray, and if indicated, by additional imaging studies.. The prevalence of clinically relevant valvular regurgitation was not significantly different between cases (11.3%) and controls (6.1%; P=0.16). The mean MVTa was 1.27+/-0.17 and 1.24+/-0.21 cm(2) respectively (P=0.54). Both valvular regurgitation and the MVTa were not related to the cumulative dose of cabergoline. A significantly decreased pulmonary function required additional imaging in seven patients. In one patient, possible early interstitial fibrotic changes were seen. Lung function impairment was not related to the cumulative cabergoline dose.. Cabergoline, typically dosed for the long-term treatment of hyperprolactinemia or acromegaly, appears not to be associated with an increased risk of fibrotic adverse events.

Topics: Acromegaly; Blood Sedimentation; C-Reactive Protein; Cabergoline; Creatinine; Cross-Sectional Studies; Dopamine Agonists; Echocardiography; Electrocardiography; Ergolines; Female; Fibrosis; Glomerular Filtration Rate; Heart Valve Diseases; Heart Valves; Humans; Hyperprolactinemia; Lung; Lung Diseases; Male; Middle Aged; Respiratory Function Tests; Retroperitoneal Fibrosis; Statistics, Nonparametric

Treatment with pegvisomant, an antagonist of growth hormone (GH) receptors, increases GH levels in a dose dependent manner. Cabergoline can suppress GH secretion in approximately 40% of acromegalic patients. However, the acute effects of cabergoline have not been studied in patients treated with pegvisomant. We performed this cross-sectional study to evaluate endogenous GH after an additional single cabergoline administration.. 9 acromegalic patients on pegvisomant therapy were included. A 6h GH profile after pegvisomant alone (P) and a 9h profile in combination with oral cabergoline 0.5mg (PC) were performed. After 3 or 6h, all patients received a standardized light mixed meal. Endogenous serum GH and pegvisomant levels were measured by special in-house assays. The GH assay showed no interference with pegvisomant.. Endogenous GH levels at baseline did not differ significantly between the profiles (P: 16.5 μg/l (range 3.2-36.6 μg/l), PC: 8.0 μg/l (1.6-48 μg/l), p>0.05). In both profiles, GH fluctuated before meal. GH decreased more pronounced in PC but this decrease was not statistically significant. After meal, a significant decline in endogenous GH levels from 16.4 μg/l (0.4-27.1 μg/l, 100%) to 8.1 μg/l (0.2-24.7 μg/l, 66%) appeared in P at 300 min (p<0.01). Also in PC a decline from 7.8 μg/l (1.1-29.6 μg/l, 100%) to 5.2 μg/l (0.4-23.9 μg/l, 75%) at 300 min was observed but it was not significant.. Endogenous GH is not significantly decreased after a single oral cabergoline application during pegvisomant treatment in acromegaly.

Topics: Acromegaly; Adult; Aged; Blood Glucose; Cabergoline; Cross-Sectional Studies; Ergolines; Female; Human Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor I; Male; Middle Aged; Receptors, Somatotropin

Cabergoline, an ergot-derived dopamine receptor agonist, is used widely in the treatment of Parkinson's disease (PD) and hyperprolactinemia, but may cause heart valve fibrosis, retraction, and clinically significant regurgitation in PD patients. While cabergoline has been used at much lower doses in patients with hyperprolactinemia, controversy persists as to whether it may cause heart valve disease in this situation. Cabergoline is also used in acromegaly at doses similar to those used in hyperprolactinemia. The case is reported of a female patient with acromegaly who had been taking low-dose (0.5 mg/day) cabergoline for one year, and presented with signs and symptoms of right-sided heart failure. Echocardiography revealed a thickened and retracted tricuspid valve associated with severe tricuspid regurgitation and enlargement of the right-heart chambers. The morphology of the tricuspid valve was typical for cabergoline-related valvulopathy. Cabergoline may not be totally safe even at lower doses, and close echocardiographic monitoring is recommended in patients receiving cabergoline treatment, regardless of the dose level employed.

Topics: Acromegaly; Cabergoline; Diuretics; Echocardiography, Doppler, Color; Ergolines; Female; Furosemide; Heart Failure; Hormone Antagonists; Humans; Middle Aged; Severity of Illness Index; Treatment Outcome; Tricuspid Valve Insufficiency

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

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 agonists are effective in some patients with acromegaly and in this condition treatment is considered to be chronic. We describe two acromegalic patients who responded adequately to the long-acting dopamine agonist cabergoline, but surprisingly maintained normal GH and IGF-I levels once therapy was discontinued after 42 and 76 months because of possibly related side effects. A 32-year-old woman with mild acromegaly (IGF-I: 423 microg/l, GH after OGTT: 2.5 microg/l, adenoma 4 mm) was treated with cabergoline as primary therapy and reached safe GH levels (2 microg/l or less) and normal IGF-I levels with 3.5 mg cabergoline weekly. After 42 months of therapy the patient experienced a progressive decrease of libido, which she attributed to the intake of cabergoline. After stopping medication, serum levels of GH and IGF-I remained normal during the following 2.5 years. A 53-year-old man with moderate acromegaly (serum IGF-I: 547 microg/l, GH after OGTT: 5.9 microg/l, adenoma 7 mm) preferred cabergoline as primary therapy. Serum GH levels below 2 microg/l and normal levels of IGF-I were obtained with 3.5 mg cabergoline weekly. When the patient experienced severe stomach pains after 76 months of treatment, cabergoline was held responsible and discontinued. Serum GH and IGF-I did not increase again and stayed at the same level during a follow-up of 5.5 years. These two cases demonstrate that acromegalic patients with a good response to cabergoline may occasionally remain in remission after stopping therapy. This phenomenon has previously only been described in patients with a prolactinoma.

Topics: Abdominal Pain; Acromegaly; Adult; Biomarkers; Cabergoline; Dopamine Agonists; Drug Administration Schedule; Ergolines; Female; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Libido; Male; Middle Aged; Secondary Prevention; Time Factors; Treatment Outcome

Insulin-like growth factor type I (IGF-I) is an important promoter in the tumorigenesis of several extracranial and intracranial neoplasms. In astrocytic-cell tumors, the role of autocrine and paracrine IGF-I expression in enhancing tumoral progression is well established. However, the influence of systemic IGF-I levels on the clinical behavior of astrocytic neoplasms remains an open subject of research. We report the case of a 28-year-old man who presented simultaneously with acromegaly and an anaplastic astrocytoma, which had rapidly progressed from a low-grade astrocytoma. The coexistence of systemic IGF-I hypersecretion with a quick progression in the histopathological grade of the astrocytoma raises the compelling question of whether the clinical behavior of the astrocytic tumor was influenced by the acromegalic status. The role of IGF-I signaling in the pathogenesis of astrocytic-cell tumors and the experience with therapeutic strategies addressing this pathway in astrocytomas are also discussed.

Topics: Acromegaly; Adult; Astrocytoma; Brain Neoplasms; Cabergoline; Cranial Irradiation; Craniotomy; Disease Progression; Ergolines; Humans; Insulin-Like Growth Factor I; Magnetic Resonance Imaging; Male; Neoplasm Staging; Peptides, Cyclic; Somatostatin; Treatment Outcome; Up-Regulation

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

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

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

The excess mortality and morbidity associated with acromegaly are secondary to prolonged elevation of GH and IGF-I. Vigorous control of these biochemical parameters results in improved morbidity and mortality. Somatostatin analogues (SAs) allow adequate control of GH and IGF-I in approximately 65% of subjects, leaving a significant cohort uncontrolled. Dopamine agonists (DAs), a cheap alternative to SAs, allow control of GH and IGF-I in less than 20% of patients with acromegaly.. To assess the effectiveness of adding DA therapy to SA in the biochemical control of acromegaly.. One hundred and twenty cases from the Sheffield Acromegaly Register were reviewed; 24 (20%) did not require medical treatment following pituitary surgery alone; 16 (13%) had safe GH levels following surgery and radiotherapy; and 58 (48%) required medical treatment despite having had surgery, radiotherapy or both. The remaining 22 (18%) received only medical treatment.. In nine subjects a DA (three bromocriptine, six cabergoline) was added to an SA to control active disease. GH day curves and IGF-I levels were compared before and after the addition of a DA to existing SA treatment. All were on stable maximum-dose treatment with an SA, with inadequate biochemical control prior to addition of DA therapy. Mean duration of treatment on a DA before biochemical assessments were made was 10.3 months. Six subjects had previously been treated with either transsphenoidal surgery, radiotherapy or both. In three subjects SA was the primary therapy.. All subjects exhibited a fall in median GH and IGF-I levels. Introduction of a DA resulted in a 36.1% reduction in median GH levels (8.3 vs 5.3 mIU/l; P = 0.008) on a GH day curve and a 35.2% reduction in IGF-I levels (387.2 vs 251.0 microg/l; P = 0.018). Only four subjects had elevated prolactin levels prior to the addition of a DA (>368 mIU/l).. Addition of DAs to SAs is of benefit in the biochemical control of acromegaly and should be considered in those inadequately controlled. Furthermore, the beneficial effects of DAs occur even when pre-treatment prolactin levels are within the normal range.

Topics: Acromegaly; Adult; Aged; Aged, 80 and over; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Female; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Prolactin; Retrospective Studies; Somatostatin

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

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

Topics: Acromegaly; Adult; Aged; Antineoplastic Agents; Cabergoline; Dopamine Agonists; Drug Therapy, Combination; Ergolines; Female; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Octreotide

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

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

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

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

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

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

The aim of this study was to evaluate the efficacy of a 6-month treatment with lanreotide (LAN) (60-90 mg/month) alone and combined with cabergoline (CAB) (1.5-3 mg/week) in 10 acromegalic patients previously demonstrated to be poor responders to octreotide (OCT) (0.6 mg/day) alone and combined with quinagolide (CV) (0.6 mg/day). All patients had previously undergone unsuccessful surgery and none of them received radiotherapy. Immunohistochemistry showed intense positive GH staining in all adenomas, positive PRL staining in 5 adenomas and faint ACTH or FSH/LH positive staining in other 2 adenomas. Moderately elevated serum PRL levels (35 and 47 ng/ml) were recorded in two patients. Fasting plasma IGF-I and serum GH levels were assayed at baseline and 30, 60, 90 and 120 days after each treatment. Gallbladder ultrasonography and sellar MRI were performed before and after 6 months of OCT and LAN treatments. After OCT treatment circulating GH and IGF-I levels remained elevated in all patients, while after 3 months of combined OCT + CV treatment, serum GH levels were suppressed (below 2.5 ng/ml) in only 1 patient. Significant increase of the percent GH (83.9 +/- 4.3 vs. 70.3 +/- 5.6%, p < 0.01) and IGF-I suppression (54 +/- 4.4 vs. 45.3 +/- 5.7, p < 0.01) and decrease of the nadir of GH (8.5 +/- 1.2 vs. 14.6 +/- 1.9 ng/ml, p < 0.01) and IGF-I (400.9 +/- 32.8 vs. 462.1 +/- 45.1 ng/ml) were obtained with the combined treatment when compared to OCT treatment alone. After a 15-30 days wash-out, circulating GH and IGF-I levels significantly increased up to pretreatment level in all patients. After 6 months of treatment with LAN, suppression of serum GH was achieved in 1 patient, but no difference in GH (66.3 +/- 6.3%) and IGF-I (43.9 +/- 4.6%) suppression was recorded in comparison to OCT treatment. After 3 months of treatment with LAN combined with CAB, suppression of serum GH and normalization of plasma IGF-I levels was achieved in 4 and 5 patients, respectively. Percent suppression of GH (88.1 +/- 2.1%) and IGF-I (57.5 +/- 2.8%) was significantly greater with the combined treatment than with LAN treatment alone. In the 7 patients with evident residual mass no change was documented by magnetic resonance imaging (MRI). None of the patients withdrew LAN + CAB treatment for poor tolerance, one patient had mild hypotension. Sludge was shown after 6 months of LAN treatment in one patient without notable change after 3 months of LAN + CAB treatment. In conclusion, the

Topics: Acromegaly; Adult; Aminoquinolines; Cabergoline; Dopamine Agonists; Drug Synergism; Drug Therapy, Combination; Ergolines; Female; Hormones; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Octreotide; Peptides, Cyclic; Somatostatin; Time Factors

Medical treatment of acromegaly with dopamine agonists possesses 2 main advantages: the oral administration and the low costs. In this study, we reported on the results of chronic treatments with quinagolide (CV 205-502), cabergoline (CAB) and long-acting depot preparation of bromocriptine (BRC-LAR) in 34 acromegalics. Patients were divided into three groups on the basis of different treatment: CV 205-502 given to 16 patients at the dose of 0.3-0.6 mg/day for 6 months; CAB given to 11 patients at the dose of 1.0-2.0 mg weekly for 6 months; and BRC-LAR injected into 7 patients at the dose of 100 mg/month for 6-12 months. Basal and oral glucose tolerance test-stimulated serum GH levels, basal and TRH-stimulated PRL levels, plasma insulin-like growth factor I (IGF-I) levels, computed tomography scan, and/or magnetic resonance imaging were assessed before and quarterly during treatments. The chronic administration of CV 205-502, CAB, and BRC-LAR caused a significant decrease of circulating GH, IGF-I, and PRL levels (P < 0.005). Normalization of circulating GH and IGF-I levels was obtained in 7 of 16 (43.8%) patients treated with CV 205-502. Serum GH response to oral glucose tolerance test (oGTT) significantly improved (P < 0.005), and PRL levels were significantly suppressed during treatments. No correlation was found between basal and TRH-stimulated PRL levels and GH suppression during different therapies. Immunohistochemical staining revealed 19 GH-positive and 10 GH + PRL-positive adenomas. A significant association was found between GH/PRL staining and responsiveness to chronic treatments (chi 2 = 7.985, P < 0.005). Three patients had significant adenoma shrinkage. Slight nausea and hypotension which spontaneously disappeared within therapy progression, were referred by 5/16 patients during CV 205-502 and 2/7 during BRC-LAR. The results of this study indicate that CAB and BRC-LAR cannot be considered as useful medical approaches for acromegalics, whereas CV 205-502 normalized circulating GH and IGF-I levels in 47.8% of patients.

Topics: Acromegaly; Adult; Aminoquinolines; Bromocriptine; Cabergoline; Delayed-Action Preparations; Dopamine Agonists; Ergolines; Female; Human Growth Hormone; Humans; Male; Middle Aged; Prolactin

Studies of the dopamine agonist cabergoline in the treatment of hyperprolactinaemia have shown it to be a potent, long-acting and well-tolerated. The older dopamine agonist, bromocriptine, has traditionally had a place in the medical management of acromegaly, but poor patient tolerance of the high doses required, the need for multiple daily administration and incomplete biochemical responses have limited its role. We therefore sought to investigate the effect of cabergoline on growth hormone (GH) secretion in acromegaly and to define the most appropriate dose for suppression of GH DESIGN AND MEASUREMENTS: Patients with active acromegaly (defined as most recent random GH > 5 mU/l) were identified from the departmental clinical information system. After informed consent was obtained, basal GH levels were estimated during a 5 point day curve at least 2 months after withdrawal of any existing medical therapy for acromegaly. The cabergoline dose was escalated on a monthly basis for 4 months with a repeat 5 point GH day curve at the highest dose, and 0900 and 0930 GH estimations at the intermediate dose increment stages. Serum IGF-1 and prolactin were estimated on each occasion. Biochemical remission was defined as serum GH < 5 mU/l.. Eleven acromegalics were investigated. Previous treatment included surgery (7), radiotherapy (5) and bromocriptine (5). Three patients had not received any previous treatment. All had random GH persistently > 5 mU/l prior to the study.. Ten patients completed the study. Of these, 7 showed a fall in the GH to < or = 33% and IGF-1 to < or = 67% of the basal value but only 2 achieved biochemical remission. All subjects showed maximum GH response at a dose of 0.5 mg daily of cabergoline. Four patients were unable to tolerate the maximum dose of 1 mg daily (nausea in one and nonspecific symptoms in three). The patient excluded from the analysis discontinued cabergoline and underwent surgery after 1 month because of worsening visual field defects.. Cabergoline may be a useful adjunct to the currently available treatment for acromegaly, but rarely achieves the goal of mean GH < 5 mU/l. The maximum suppression of GH is achieved within the dose range 1 mg twice weekly to 0.5 mg daily.

Topics: Acromegaly; Adult; Aged; Cabergoline; Depression, Chemical; Dopamine Agonists; Dose-Response Relationship, Drug; Drug Administration Schedule; Ergolines; Female; Growth Hormone; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Prolactin

The acute GH lowering effects of a single dose of either octreotide (OCT) or cabergoline (CAB), given alone and in combination, were studied in a series of 21 patients with acromegaly.. Plasma GH was measured for 8 hours after a single subcutaneous injection of OCT (100 micrograms) and for 48 hours after a single oral dose of CAB (0.5 mg) in all patients. Fourteen patients, who did not suppress GH levels below 5 micrograms/L after either OCT or CAB given alone, also received a combination of both drugs (OCT 100 micrograms s.c. + CAB 0.5 mg p.o. 24 h before OCT).. GH levels were acutely suppressed by more than 50% in 15/21 cases after OCT alone and in 5/21 after CAB alone, respectively (P < 0.01). In the 14 patients who received the combined test, the magnitude of GH suppression was significantly higher than after OCT alone 4, 6 and 8 hours after OCT administration (P < 0.02). In patients with mixed GH/PRL-secreting tumors, the additive effect of OCT and CAB was observed at each time point.. These results suggest that combined therapy with OCT and CAB may be more effective in suppressing GH secretion than either compound given alone, especially in patients with GH/PRL-secreting adenomas.

Topics: Acromegaly; Administration, Oral; Adult; Aged; Cabergoline; Data Interpretation, Statistical; Dopamine Agonists; Drug Therapy, Combination; Ergolines; Female; Growth Hormone; Hormones; Humans; Injections, Subcutaneous; Male; Middle Aged; Octreotide

The increasing use in clinical practice of octreotide (a somatostatin analogue which inhibits the secretion of GH and other peptide hormones) led us to study the effects of this treatment on GH, insulin-like growth factors (IGF)-I and II and IGF-binding protein (IGFBP)-3, as well as on circulating IGFBP complexes in acromegalic patients.. The circulating concentrations of GH, IGF-I, IGF-II and IGFBP-3 were measured in acromegalic patients before and after 3, 6, 9, and 12 months of treatment with octreotide (group I: n = 5), and compared with those found in a group of patients (group II) treated with bromocriptine (n = 3), cabergoline (n = 7) radiotherapy (n = 3) or surgical therapy (n = 2). In pools of serum obtained from patients treated with octreotide, dopaminergic drugs, surgery and radiation, before and after therapy, immunoreactive IGF-I and IGFBP-3 were also evaluated after Superdex 200 gel filtration in neutral conditions.. Before treatment, the concentration of IGF-I and IGFBP-3 were above the normal range in all patients, while IGF-II levels were slightly reduced. After treatment with octreotide, IGF-I (P = 0.004), IGF-II (P = 0.02) and IGFBP-3 (P < 0.001) were significantly reduced as compared to basal levels. In subjects of group II, only IGF-I concentration was significantly reduced by the treatment (P = 0.02), and a negative correlation between IGF-I and IGF-II concentrations was found (r = -0.58, P < 0.0001). After gel filtration immunoreactive IGF-I and IGFBP-3 were found in the 150-kDa mol.wt. region in serum obtained from untreated patients and from treated patients of group II, while in the serum of octreotide-treated patients the IGF-I and IGFBP-3 peaks were shifted to the 60-kDa mol.wt. region, thus suggesting that the acid-labile subunit of the 150-kDa complex was drastically reduced. Since the GH concentrations in groups I and II were similar (M +/- SEM; 13.8 +/- 7.4 and 21.2 +/- 10.6 mU/l respectively), the marked reduction in acid-labile subunit in the octreotide treated patients can be explained by a direct inhibitory effect of somatostatin on the subunit.. Octreotide exerts an inhibitory effect not only on IGF-I but also on IGF-II. The reduced formation of the 150-kDa complex probably causes an increased metabolic clearance rate of IGF peptides which can account for the reduced concentration of both IGFs after treatment with octreotide.

Topics: Acromegaly; Adult; Bromocriptine; Cabergoline; Carrier Proteins; Ergolines; Growth Hormone; Humans; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Middle Aged; Octreotide

Lysenyl-forte, a derivative of polysynthetic ergot alkaloids, producing a dopaminergic and antiserotoninergic action was employed to treat acromegaly and prolactin hypersecretion in 11 and 71 patients, respectively. Clinical effect was established basing on a complex of clinical, x-ray, neuro-ophthalmologic and hormonal evidence. Acromegaly treatment proved efficient: 7 patients (63%) showed partial relief of clinical signs, reduced STH blood level. Out of 48 patients with prolactinemia a response was registered in 34 (71%): a more than 50% decrease in prolactin concentration, normal levels of the hormone in 35% of the patients. A menstrual cycle recovered, galactorrhea diminished, 2 women got pregnant. A positive effect was noticed in management of 13 sterile men with prolactin hypersecretion, in 6 patients with idiopathic prolactin hypersecretion, in 4 women with primary hypothyrosis and galactorrhea. Compared to parlodel, lysenyl was not superior in the frequency of side effects, though was inferior in clinical effectiveness. The drug is recommended for wide-scale use.

Topics: Acromegaly; Adolescent; Adult; Aged; Aged, 80 and over; Bromocriptine; Drug Evaluation; Ergolines; Female; Humans; Hyperprolactinemia; Lisuride; Male; Middle Aged; Syndrome

17 hyperprolactinemic and 2 acromegalic patients, aged 19-73, and 47 and 59 years, respectively, were treated with Lisuride (dopergin). 12 of the hyperprolactinemic patients were treated with Lisuride because they could not tolerate the side effects of bromocriptine (Group A), and the other 5 because large doses of bromocriptine failed to reduce their plasma prolactin to normal (Group B). The 2 acromegalic men, were treated with Lisuride because of persistently high levels of growth hormone after hypophysectomy and irradiation of the sella turcica, and because of intolerance to bromocriptine. Lisuride reduced prolactin to normal in 11 of the 12 in Group A (from 217 +/- 175 to 27 +/- 10 micrograms/l, p less than 0.01) and reduced it in the last patient from 3900 to 270 micrograms/l. The prolactin-lowering effect of Lisuride was unsatisfactory in Group B since like bromocriptine, it failed to reduce prolactin levels. One of the acromegalics improved both clinically and biochemically and growth hormone levels were reduced from 56 to 18 ng/ml, while the other did not respond to Lisuride. Its main side effects were somnolence, nausea, and increased appetite (4 patients). These effects lasted only a few weeks. One patient stopped Lisuride because of severe constipation, which had been caused by bromocriptine as well. Lisuride is an effective drug in hyperprolactinemia, especially in those with severe side effects after other dopaminergic drugs. It is effective in some cases of acromegaly, but has little to offer to those resistant to bromocriptine.

Topics: Acromegaly; Adult; Aged; Ergolines; Growth Hormone; Humans; Hyperprolactinemia; Lisuride; Male; Middle Aged; Prolactin

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

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

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

Topics: Acromegaly; Adolescent; Adult; Aged; Ergolines; Female; Humans; Hyperprolactinemia; Lisuride; Male; Middle Aged; Pregnancy

Topics: Acromegaly; Ergolines; Female; Hormones; Humans; Lipids; Lipoproteins, HDL; Lisuride; Male; Middle Aged

Terguride, a derivative of lisuride, has been shown to possess a mixed dopaminergic-antidopaminergic activity in experimental models. We have studied the effects on PRL and GH levels of 0.2 mg po of terguride in 8 normal subjects, in 15 patients with pathological hyperprolactinemia (PHP) and in 17 patients with active acromegaly. In PHP, PRL levels were significantly reduced up to 300 min after terguride with a nadir (45 +/- 4.0% SE) significantly lower (p less than 0.05) than the one observed in the 8 normal subjects (72 +/- 3.5%). There was no significant difference in plasma PRL levels after 0.2 mg terguride or lisuride in 7 out of 15 patients tested with both drugs. Terguride did not significantly modify GH levels in PHP and in normals but when considering basal and peak (occurring between 60 and 150 min) GH values, a significant difference was found (p less than 0.01). Mean peak of GH did not differ significantly between PHP (5.0 +/- 1.1 ng/ml) and normals (6.8 +/- 1.7 ng/ml). Plasma GH levels of 17 acromegalics were not modified by 0.2 mg of terguride but were significantly reduced by 2.5 mg of bromocriptine. Terguride and bromocriptine reduced PRL levels in acromegalics (p less than 0.01) without any significant difference between the two drug. 0.2 mg terguride bid given for 15 days to 7 healthy volunteers significantly reduced both basal and sulpiride (25 mg im)-stimulated PRL levels. Side effects were observed only in 4 out of 47 subjects tested with terguride and in 8 out of 34 tested with bromocriptine.

Topics: Acromegaly; Adolescent; Adult; Bromocriptine; Ergolines; Female; Growth Hormone; Humans; Lisuride; Male; Middle Aged; Prolactin; Time Factors

Topics: Acromegaly; Adult; Aged; Ergolines; Female; Growth Hormone; Humans; Hyperprolactinemia; Lisuride; Male; Middle Aged; Prolactin

Urinary excretion of free adrenaline, noradrenaline and dopamine was examined in 12 patients with active acromegaly before and during long-term therapy (6-22 months) with ergoline derivatives bromocriptine (20-30 mg daily) and lisuride (1-2 mg daily). A significant fall in noradrenaline values (4.5 +/- 0.95 (SEM) nmol/h on v.s. 15.3 +/- 3.8 nmol/h before the treatment, P less than 0.01) was found in the treated patients. Adrenaline excretion rose in most patients but the difference was not significant (1.43 +/- 0.33 nmol/h on v.s. 1.02 +/- 0.36 nmol/h before the treatment, P greater than 0.05). No significant change was seen in the dopamine excretion (71.3 +/- 9.58 nmol/h on v.s. 75.0 +/- 7.0 nmol/h before the treatment, P greater than 0.05). Our studies confirm the blood pressure lowering effect of bromocriptine and lisuride even when used on a long-term basis. This effect seems to be associated with reduced sympathetic activity.

Topics: Acromegaly; Adult; Aged; Blood Pressure; Bromocriptine; Dopamine; Epinephrine; Ergolines; Female; Humans; Lisuride; Male; Middle Aged; Norepinephrine; Somatostatin

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

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

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 effect of pergolide mesylate, a new potent longacting dopamine agonist, was investigated in eight patients with active acromegaly, none of whom had received pituitary irradiation. Patients were assessed at different dose levels for clinical response and biochemical response by measuring mean fasting growth hormone (GH), mean ambulant GH and glucose-induced GH response. Six patients had definite clinical improvement. No major side effects were noted. All patients showed a statistically significant reduction in GH, although in two reduction was not below 75% of pretreatment levels. On 500 micrograms pergolide daily the overall response for the group of eight patients was a reduction of fasting serum GH, mean ambulant GH and of GH response to glucose to 55% of pretreatment values. When the daily dose was increased to 1000 micrograms there was a further significant reduction in GH in some patients; on this dose the response for the group was a decrease in fasting serum GH and mean ambulant GH to 40% of pretreatment values. In three patients GH concentrations of 5 mU/l or less were achieved. In two patients the daily dose was increased to 1500 micrograms but no extra benefit was obtained. We conclude that pergolide given once daily has a beneficial effect in acromegaly, with significant reduction in serum GH; it promises to be a useful therapeutic agent.

Topics: Acromegaly; Adult; Ergolines; Female; Glucose; Growth Hormone; Humans; Male; Middle Aged; Pergolide; Prolactin

39 patients with hyperprolactinaemia (32 adenomas of the pituitary gland, 7 idiopathic hyperprolactinaemias) were treated with the ergot derivative Lisurid. In 3 patients side-effects appeared which did not allow an increase to the therapy-effective dose. In all other patients with a dose of 0.075 to 6 mg Lisurid a day a normalisation of the prolactinaemia was achieved. A pregnancy appeared in 15 of 16 women who wished a child. In 4 men with normal gonadotropic reserve libido, potency and plasma testosterone normalised after the treatment with Lisurid. In addition of Lisurid also other ergot derivatives with prolactin-inhibiting effect, such as dironyl, deprenone and propyldeprenone were tested. Here dironyl has an advantage showing less side-effects and no changes of blood pressure. The ergot derivatives may be used also in the treatment of acromegaly. In 7 of 21 patients with acromegaly who were treated a longer time we succeeded in reducing the level of the growth hormone below 50%, in 2 patients the condition completely normalised. On the other hand, a normalisation of the somatomedin level appeared only in 11 of 21 patients. Patients with central Cushing's disease only exceptionally react to the treatment with ergot derivatives.

Topics: Acromegaly; Adult; Aged; Cushing Syndrome; Ergolines; Ergotamines; Female; Humans; Lisuride; Male; Middle Aged; Pregnancy; Prolactin

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

Topics: Acromegaly; Adult; Ergolines; Female; Growth Hormone; Humans; Lisuride; Male; Middle Aged; Thyrotropin-Releasing Hormone

Topics: Acromegaly; Adult; Bromocriptine; Ergolines; Female; Growth Hormone; Humans; Lisuride; Male; Middle Aged; Receptors, Dopamine; Thyrotropin; Thyrotropin-Releasing Hormone; Triiodothyronine

Topics: Acromegaly; Adult; Alkaline Phosphatase; Blood Glucose; Bone and Bones; Bromocriptine; Ergolines; Female; Glucose Tolerance Test; Growth Hormone; Humans; Hydroxyproline; Insulin; Isoenzymes; Lisuride; Male; Somatomedins

Topics: Acromegaly; Ergolines; Glucose; Growth Hormone; Humans; Insulin; Levodopa; Pituitary Gland, Anterior; Somatostatin; Thyrotropin-Releasing Hormone

It has been reported that the plasma growth hormone (GH) and prolactin (PRL) levels in acromegalic patients were suppressed after intensive administration of dopaminergic drugs, but we found that the plasma GH levels in some acromegalic patients were not suppressed. Plasma GH and PRL levels after a single oral administration of CB-154 (2.5mg) and L-DOPA (1g) were measured in 18 active acromegalic patients with and without galactorrhea. 1. The mean plasma GH levels after the administration were clearly suppressed in 8 patients with galactorrhea, while they were not suppressed in 10 patients without galactorrhea. These drugs were more effective in suppressing plasma GH levels in acromegalic patients with galactorrhea and hyperprolactinemia. 2. We calculated the responsiveness of the plasma GH level as follows: GH responsiveness (%) = (mean plasma GH level after the administration of CB-154 or L-DOPA)/ (basal GH level) x 100. The basal plasma PRL levels were inversely correlated with GH responsiveness (CB-154: r=-0.690, p less than 0.01. L-DOPA: r=-0.541, p less than 0.05). It was found that the effect of dopaminergic drugs on plasma GH levels was closely correlated with basal PRL levels in acromegalic patients. This implies that the chronic administration of CB-154 may be effective in acromegalic patients with galactorrhea and hyperprolactinemia.

Topics: Acromegaly; Adult; Ergolines; Female; Galactorrhea; Growth Hormone; Humans; Levodopa; Male; Middle Aged; Pregnancy; Prolactin

In 12 acromegalics a single oral dose of 0.2 mg lisuride, an ergoline derivative, significantly reduced plasma PRL but not GH concentrations. Three-tenths milligram of the drug significantly reduced plasma levels of the two hormones. Four-tenths milligram of lisuride did not augment this inhibitory effect. Plasma PRL levels were suppressed in all patients, whereas GH levels were reduced by more than 50% of the base-line values in only seven patients who also responded to the administration of 2.5 mg bromocriptine (CB154). In the patients unresponsive to lisuride, CB154 also failed to change GH levels. The suppressive effect of lisuride started at 60 min (at 150 min for CB154) and plasma GH and PRL levels were still markedly suppressed at 300 min. Plasma GH and PRL concentrations were consistently reduced in two acromegalic patients during 2 weeks of chronic treatment with 0.3 mg lisuride four times a day. In six normal subjects, TRH-induced PRL release was significantly inhibited by pretreatment with 0.3 mg of the drug. The similarity in the effects of lisuride and CB154 suggests that the observed effects of lisuride on GH and PRL are attributable to the known dopaminergic activity of the drug. This conclusion is supported by the data showing that pimozide effectively counteracted the inhibitory action of lisuride on GH and PRL release. We suggest that lisuride may be of value in the medical treatment of acromegaly and hyperprolactinemic states.

Topics: Acromegaly; Adult; Bromocriptine; Dose-Response Relationship, Drug; Ergolines; Female; Growth Hormone; Humans; Lisuride; Male; Middle Aged; Pimozide; Placebos; Prolactin; Thyrotropin-Releasing Hormone

Topics: Acetonitriles; Acromegaly; Adult; Blood Glucose; Drug Evaluation; Ergolines; Female; Growth Hormone; Humans; Middle Aged; Pituitary Gland, Anterior; Prolactin

Topics: Acetonitriles; Acromegaly; Adult; Blood Pressure; Carpal Tunnel Syndrome; Ergolines; Female; Growth Hormone; Humans; Male; Middle Aged; Prolactin; Thyrotropin

In twenty-two patients with active acromegaly who were untreated or unsuccessfully operated or irradiated (mean growth hormone (GH) values greater than 4 ng/ml) the following investigations were performed: routine laboratory tests, tomography of pituitary fossa, oral glucose tolerance tests, TRH and other pituitary function tests and GH profiles over 5-10 h before and during bromocriptine treatment with daily doses between 7.5 and 50 mg. In seventeen patients GH was suppressed to less than 50% by bromocriptine, in thirteen of them it was normalized on at least one occasion. A TRH induced GH release was observed in all but two responders to bromocriptine before therapy. This effect of TRH was not blunted during treatment with bromocriptine and also in the two patients with negative tests before therapy a significant GH increase was observed. In no non-responder to bromocriptine was a significant increase of GH after TRH observed. One patient showed a secondary resistance to bromocriptine during a period of treatment with griseofulvin. In the remaining sixteen patients the GH suppression has been consistent for between 3 and 22 months. A single dose of pimozide abolished the bromocriptine effect on GH totally in one patient; in others a slight or no significant effect was observed. Tissue swelling and sweating decreased in all bromocriptine responders and glucose tolerance improved in five patients. In four diabetic patients a partial or full remission of diabetes occurred. Apart from postural hypotension after the first administration in two patients no other severe side effects have been observed. Sella size and the other pituitary functions did not change during the time of the study. It seems that a high percentage of acromegalics may be successfully treated with bromocriptine.

Topics: Acromegaly; Adult; Aged; Bromocriptine; Diabetes Mellitus; Ergolines; Female; Growth Hormone; Humans; Male; Middle Aged; Pimozide; Thyrotropin-Releasing Hormone

Thirty acromegalic subjects underwent chronic CB154 therapy (10-20 mg daily) for periods ranging from 3 months up to 2 years. In 18 out of 21 patients, who exhibited consistent HGH reduction following acute administration of the drug, there was also during chronic treatment, a suppression of the plasma HGH levels exceeding 50% of base line values, e.g. from mean daily values between 14-197 ng/ml (mean +/- SEM = 57.8 +/- 12.4 ng/ml pre-treatment) to 2-19 ng/ml (mean 8.3 +/- 1.2 ng/ml post-treatment). In 12 of the subjects who responsed to chronic CB154 treatment, the mean daily values of HGH were below 10 ng/ml. The suppression of plasma HGH was maintained unaltered throughout the whole course of therapy. In the 9 subjects, in whom no consistent HGH decrease was evidenced with acute CB154 administration, there was accordingly a minor or no suppression of HGH values during the chronic treatment. In 13 subjects, irrespective of the degree of their GH responses, the plasma prolactin levels were constantly inhibited by CB154; instead the drug failed to modify significantly the TRH or insulin-induced GH release. These changes in the hormonal parameters were paralleled by marked clinical amelioration and improvement of some of the metabolic alterations frequently encountered in acromegaly, e.g. reduced carbohydrate tolerance, increased insulin resistance, diminished fall of plasma phosphorus after insulin, decreased urinary excretion of phosphate, hyper-hydroxyprolinuria and hyper-calciuria. Collectively, these data demonstrate that CB154 thrapy is effective in reducing HGH hyper-secretion in many acromegalic patients during long-term treatment.

Topics: Acromegaly; Adult; Blood Glucose; Bromocriptine; Calcium; Drug Evaluation; Ergolines; Female; Glycosuria; Growth Hormone; Humans; Hydroxyproline; Insulin; Insulin Secretion; Male; Middle Aged; Phosphates; Phosphorus; Prolactin; Thyrotropin-Releasing Hormone; Time Factors

Topics: Acromegaly; Adult; Aged; Bromocriptine; Ergolines; Growth Hormone; Humans; Hypothyroidism; Middle Aged; Prolactin; Thyrotropin-Releasing Hormone

In an attempt to evaluate the dynamics of growth hormone (GH) and prolactin secretion in acromegalic patients, the response of serum GH as well as prolactin to 2-bromo-alpha-ergocriptine (CB154) alone or to CB154 combined with thyrotropin-releasing hormone (TRH) was studied in 8 subjects with this disease. Oral administration of CB154 unequivocally decreased serum prolactin levels in all of the 8 patients, while GH-inhibitory action of the drug was observed only in 6 subjects who responded to TRH with secretion of GH. The response of serum GH to TRH was not qualitatively and quantitatively altered by the treatment of patients with CB154 in a daily dose of 5 mg for two weeks. This treatment, on the other hand, remarkably suppressed basal levels of prolactin and completely blocked TRH-induced prolactin release in all of the subjects. The results suggest that there exists a dissociation between GH and prolactin responses to CB154 in acromegalic patients, and that CB154 and TRH may not share a common site of action on GH release in this pathologic state.

Topics: Acromegaly; Adult; Bromocriptine; Ergolines; Female; Growth Hormone; Humans; Kinetics; Male; Middle Aged; Prolactin; Radioimmunoassay; Thyrotropin-Releasing Hormone

Plasma growth hormone (GH) concentrations were measured over 24 h in seven acromegalic patients before and during treatment with 2-bromo-alpha-ergocriptine (CB-154). Before treatment basal plasma GH levels were consistently elevated but no significant change was observed between the mean plasma GH levels during sleep and during waking in five of the seven patients examined. The daily administration of CB-154 (5 to 10 mg, orally) for 14 days resulted in a significant fall in the 24 h mean plasma GH levels in six of the seven patients. In all of the six patients who responded to CB-154 treatment, the mean plasma GH concentrations during sleep were significantly greater than during waking. Daytime sleep was associated with a significant rise in plasma GH in both of the two patients examined. It is concluded that CB-154 treatment resulted in a significant decrease in plasma GH levels with sleep-related increase in some acromegalics although the mechanism responsible for this sleep-related GH rise remains to be further investigated.

Topics: Acromegaly; Adult; Bromocriptine; Circadian Rhythm; Electroencephalography; Ergolines; Female; Growth Hormone; Humans; Male; Middle Aged; Sleep; Wakefulness

Topics: Acromegaly; Adult; Aged; Bromocriptine; Ergolines; Female; Growth Hormone; Humans; Male; Middle Aged; Pimozide; Receptors, Dopamine; Stimulation, Chemical

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

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

Seventy-three patients with active acromegaly were treated for three to 25 months with bromocriptine 10-60 mg/day. Seventy-one patients showed symptomatic and objective clinical improvement. This included reduction in excessive sweating, hand and foot size, and the number of headaches; improved facial appearance; and increased energy and libido. Abnormal visual fields became normal in two patients, one of whom had concomitant radiotherapy. Mean circulating growth hormone levels, obtained by averaging serial samples through the day, fell by more than 7 microng/l or became undetectable in 58 patients (79%) but did not reach normal values: only 15 patients had mean levels on treatment of 5 microng/l or less. Twenty-three patients were diabetic before treatment, and glucose tolerance became normal in 15 and improved in a further five. Provided the drug was started slowly side effects were minor when compared with the considerable clinical benefit obtained.

Topics: Acromegaly; Adolescent; Adult; Aged; Bromocriptine; Ergolines; Female; Growth Hormone; Humans; Male; Middle Aged; Time Factors

Topics: Acromegaly; Bromocriptine; Ergolines; Female; Galactorrhea; Humans; Lactation Disorders; Parkinson Disease; Pregnancy

Topics: Acromegaly; Adult; Bromocriptine; Ergolines; Female; Humans; Male; Middle Aged

Topics: Acromegaly; Bromocriptine; Ergolines; Evaluation Studies as Topic; Humans

Topics: Acromegaly; Bromocriptine; Cold Temperature; Ergolines; Fingers; Humans; Vasoconstrictor Agents

Topics: Acromegaly; Adult; Blood Pressure; Bromocriptine; Drug Therapy, Combination; Ergolines; Humans; Hydralazine; Hypertension; Male; Propranolol

Topics: Acromegaly; Adult; Aged; Bromocriptine; Ergolines; Female; Humans; Male; Middle Aged; Peptic Ulcer; Peptic Ulcer Hemorrhage

Topics: Acromegaly; Bromocriptine; Ergolines; Humans; Peptic Ulcer; Peptic Ulcer Hemorrhage

Topics: Acromegaly; Aged; Bromocriptine; Ergolines; Humans; Hypotension; Male

Fourteen patients with acromegaly were treated with bromocryptine (CB 154, Sandoz), 4 X 2.5 mg, for periods of up to eleven months. One patient did not tolerate the drug, ten of the remaining thirteen experienced considerable clinical improvement. There was a dose-dependent suppression of plasma growth hormone levels, but growth hormone response to TRH injection and to glucose administration was still present during therapy although reduced. TSH response to TRH was not significantly altered. The suppressive power of bromocryptine on growth hormone appears to be related to the mechanism by which TRH stimulates growth hormone secretion in acromegaly, but long-term administration of this drug may be successful in spite of an absent response to TRH in some cases. Bromocryptine appears to be a safe and effective drug for the treatment of acromegaly.

Topics: Acromegaly; Adrenocorticotropic Hormone; Adult; Aged; Bromocriptine; Diet; Ergolines; Female; Follicle Stimulating Hormone; Glucose; Glucose Tolerance Test; Growth Hormone; Humans; Luteinizing Hormone; Male; Middle Aged; Thyrotropin; Thyrotropin-Releasing Hormone; Time Factors; Vasopressins

Topics: Acromegaly; Adult; Blood Glucose; Bromocriptine; Ergolines; Ergot Alkaloids; Female; Glucose Tolerance Test; Growth Hormone; Humans; Male; Middle Aged

Topics: Acromegaly; Bromocriptine; Ergolines; Female; Humans; Hypogonadism; Lactation; Lactation Disorders; Male; Parkinson Disease; Pregnancy

Plasma levels of growth hormone (GH) and prolactin (PRL) were measured in twelve acromegalic patients after acute administration of an ergoline derivative (methergoline) which has been proposed as a specific serotoninergic blocking agent. The administration of methergoline (4 mg p.o.) was followed by a significant decrease in plasma GH and PRL concentrations. The administration to the same subjects of CB 154 (2.5 mg p.o.), a known stimulator of dopaminergic receptors, led to results almost superimposable to those obtained with methergoline although the suppressive effect of CB 154 on GH and PRL levels was more sustained. Also on the ground of results obtained in these patients with the use of cyproheptadine, phentolamine, or pimozide, we have concluded that methergoline inhibition of GH and PRL release is, in acromegalic patients, most probably due to a dopaminergic mechanism of action.

Topics: Acromegaly; Adult; Aged; Bromocriptine; Cyproheptadine; Ergolines; Female; Growth Hormone; Humans; Male; Metergoline; Middle Aged; Phentolamine; Pituitary Gland; Prolactin; Serotonin Antagonists

Topics: Acromegaly; Bromocriptine; Ergolines; Female; Glucose Tolerance Test; Growth Hormone; Humans; Hydroxyproline; Male

Topics: Acromegaly; Ergolines; Humans; Hypophysectomy

Topics: Acromegaly; Adolescent; Adult; Bromocriptine; Ergolines; Female; Growth Hormone; Humans; Male; Middle Aged

In six acromegalite patients oral administration of 4 mg of metergoline, an antiserotonin agent, produced a fall in plasma growth hormone (GH) and prolactin (PRL) concentrations. In the same patients this inhibitory effect was observed after administration of dopaminergic drugs, L-Dopa and 2-Br-alpha-ergocryptine. Both GH and PRL levels remained suppressed during a 6 day course of treatmnt with metergoline. These results are consistent with the hypothesis that the inhibitory effect of netergoline on GH and PRL release is determined by inactivation of serotonin receptors in the hypothalamus or at the pituitary.

Topics: Acromegaly; Adult; Animals; Bromocriptine; Ergolines; Growth Hormone; Humans; Levodopa; Male; Metergoline; Middle Aged; Prolactin; Serotonin; Serotonin Antagonists

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

Topics: Acromegaly; Bromocriptine; Depression, Chemical; Ergolines; Female; Humans; Lactation; Parkinson Disease; Pregnancy; Prolactin

Topics: Acromegaly; Administration, Oral; Bromine; Ergolines; Growth Hormone; Humans

Growth hormone (GH) responses to L-dopa, 2-Br-alpha-ergocryptine (CB-154), thyrotropine-releasing hormone (TRH), luteinizing hormone-releasing hormone (LH-RH), glucagon and glucose were investigated in six patients with active acromegaly. The following results were obtained. 1) Subcutaneous injection of 1 mg glucagon caused a clear-cut decrease in plasma GH levels in 5 out of 6 active acromegalic patients at 30 minutes after the injection. In 2 out of 6 patients a rebound of plasma GH was observed. 2) In three out of six patients with active acromegaly, oral administration of 0.5 g L-dopa caused a significant suppression of plasma GH levels. 3) CB-154 (2.5mg) administered orally elicited a marked decrease in plasma GH levels in the same three patients who showed a significant suppressive GH reponse to L-dopa, and the inhibitory effect of CB-154 on GH secretion lasted for 6 hours. These patients who had a GH response to L-dopa or CB-154 were named "responders". 4) Intravenous administration of TRH resulted in a significant increase in plasma GH in 4 patients 3 of whom were responders and the other a non-responder. 5) Pretreatment with CB-154 did not modify the TRH-induced GH increase in all patients who had a positive response to TRH. 6) A significant increase in plasma GH was elicited by the intravenous injection of 100 mug LH-RH in 3 out of 6 patients with acromegaly. 7) When oral administration of CB-154 had been given 2 hours before LH-RH, the GH response to LH-RH was blunted in two of three patients who had a LH-RH-induced increase in plasma GH levels.

Topics: Acromegaly; Adult; Aged; Ergolines; Female; Glucagon; Gonadotropin-Releasing Hormone; Growth Hormone; Humans; Levodopa; Male; Middle Aged; Thyrotropin-Releasing Hormone

Four men and 4 women with active acromegaly were treated with bromocryptine for 4 to 5 weeks. Serum growth hormone levels response to a glucose load were measured before and in the last weed of treatment. In only 1 patient was the grwotoh hormone response rendered normal by the drug. This patient, but none of the others, also showed an improvement in glucose tolerance and a reductin of the raised serum insulin levels during the glucose load. In three of the 8 patients vomiting was troublesome side effect of treatment.

Topics: Acromegaly; Adult; Aged; Blood Glucose; Bromocriptine; Ergolines; Fasting; Female; Growth Hormone; Humans; Male; Middle Aged; Time Factors

Oral administration of 1.0 or 2.5 mg bromocriptine (CB 154: 2-brom-alpha-ergocryptine) in nine of twelve patients with active acromegaly resulted in a reduction of growth hormone level by 80-90% over 8-10 hours. During treatment for 2-9 months with daily doses of 4.0 to 10.0 mg bromocriptine, there was a sustained reduction of growth hormone levels in these patients. At the same time soft-tissue swellings and tendency towards sweating decreased. In two patients with diabetes mellitus the blood sugar profile improved and in one of them the insulin dose could be markedly reduced. The rise in growth hormone levels after TRH administration also occurred during bromocriptine treatment. In those patients in whom growth hormone levels failed to react to either acute or chronic administration of bromocriptine no rise followed TRH administration. It is possible that in these patients there is a hypophyseal adenoma without hypothalamic control. On gradually increasing dosage bromocriptine was tolerated without side effects.

Topics: Acromegaly; Administration, Oral; Blood Glucose; Bromocriptine; Diabetes Complications; Diabetes Mellitus; Ergolines; Female; Growth Hormone; Humans; Male; Sweating; Time Factors

Topics: Acromegaly; Amantadine; Bromocriptine; Ergolines; Growth Hormone; Humans; Hypothalamo-Hypophyseal System; Levodopa; Phentolamine; Pituitary Gland; Propranolol

Topics: Acromegaly; Bromocriptine; Ergolines; Humans

The effect of 5 dopaminergic drugs, 2-Br-alpha-ergocryptine (CB 154), L-dopa, 1-(2-pyrimidyl)-4-piperonylpiperazine (Piribedil), amantadine and 1,3-dimethyl-5-amino-adamantan (d 145), on human growth hormone levels (hGH) was studied in 38 acromegalic subjects. Acute administration of CB 154 (2.5 mg p.o.) in 34 patients was followed by a significant and sustained fall in plasma hGH levels; in 19 cases (55.6%) the observed fall was clearly below the +/- 2SD of the mean GH changes present in the same subjects after placebo. In patients previously shown to be responsive to CB 154, Significant GH falls were also present following the single administration of L-dopa (500 mg p.o.) (9 patients) and Piribedil (100 mg p.o.) (5 patients), although CB 154 exhibited a more frequent, striking (reduction of up to 1-2 ng/ml) and long-lasting (4 h more) effect. In contrast, amantadine (200 mg p.o.) or D 145 (20 or 50 mg p.o.) did not induce significant changes in hGH levels (7 patients). These results broaden and corroborate previous findings on the hGH-lowering effect of dopaminergic stimulation in acromegaly. The possible reason(s) for the difference in hGH response with different dopaminergic compounds is discussed.

Topics: Acromegaly; Adult; Aged; Amantadine; Bromocriptine; Ergolines; Female; Growth Hormone; Humans; Levodopa; Male; Memantine; Middle Aged; Piperazines; Piribedil

Topics: Acromegaly; Bromocriptine; Ergolines; Female; Humans; Lactation; Male; Pregnancy; Prolactin

An acromegalic patient with galactorrhea was treated with an ergot alkaloid, 2-Br-alpha-ergocryptine (CB-154). Serum prolactin decreased rapidly to normal level by CB-154 and the complete cessation of galactorrhea was noted. The inhibitory effect of CB-154 On growth hormone (GH) release was also noted, but slight. The mechanism of inhibitory action of CB-154 on both prolactin and GH secretion was discussed in connection with the experimental model of pituitary tumors, in which both hormones were produced by a single type of tumor cells. The discontinuation of CB-154 treatment was associated with the return of both prolactin and GH levels to the initial high values with resumption of galactorrhea.

Topics: Acromegaly; Ergolines; Female; Galactorrhea; Growth Hormone; Humans; Lactation Disorders; Levodopa; Pregnancy; Prolactin

Topics: Acromegaly; Adult; Ergolines; Female; Growth Hormone; Humans; Male; Somatostatin