Treatment Of Macroprolactinomas Research Articles

Medically induced CSF rhinorrhea following treatment of macroprolactinoma: case series and literature review.

Although several reports have addressed cerebrospinal fluid (CSF) rhinorrhea following dopamine agonist (DA) therapy of macroprolactinomas, further study is warranted for this relatively uncommon entity. Toward this aim, our retrospective series and review of literature further clarifies recommendations in treatment of this rare problem. We retrospectively reviewed all macroprolactinoma cases in our hospital for a 15-year period. Our systematic search of PubMed identified original articles and reviews of all macroprolactinoma cases with an associated medication-induced CSF leak. Five patients with drug-induced CSF leak were identified; four of these patients received cabergoline therapy an average of 6 weeks before the onset of rhinorrhea and then underwent surgical repair of the CSF leak. Of 35 published studies included, we identified 60 patients with medication-induced CSF leak. Medical therapy included bromocriptine in 34 patients, cabergoline in 21 patients, and use of both DAs in two patients. Three cases did include complete diagnostic and treatment data. Median time from initiation of the DA treatment to occurrence of rhinorrhea was 6weeks. For CSF rhinorrhea, 49 patients underwent surgical repair (38 by the transnasal approach) and seven patients were treated nonoperatively. Baseline skull base erosion in macroprolactinomas in combination with subsequent tumor shrinkage induced by DA therapy may result in spontaneous CSF rhinorrhea. Therefore, such patients should be advised about and monitored for this potential setback. Once CSF leak is diagnosed, prompt treatment must be carried out to avoid infectious complications. Transnasal surgery appears the most effective therapeutic approach.

Cabergoline Tapering Is Almost Always Successful in Patients With Macroprolactinomas.

Context:Cabergoline (CAB) is very effective in the treatment of macroprolactinomas, but there are few data on the CAB dose necessary to achieve and maintain normal prolactin (PRL) levels.Design and Patients:We retrospectively studied 260 patients. CAB was introduced at a mean dose of 0.83 ± 0.52 mg/wk. When the PRL level had normalized, the patient's physician chose to either maintain the CAB dose (fixed-dose group) or to taper it (de-escalation group) until the minimal effective dose required to maintain a normal PRL level was established.Results:PRL normalized in 157 patients (60.8%) during CAB treatment. CAB de-escalation was attempted in 84 (53.5%) of these 157 patients and was successful in 77 (91.7%) cases. The mean CAB dose was reduced from 1.52 ± 1.17 mg/wk to 0.56 ± 0.44 mg/wk at the last visit (P < 1 × 10−4). De-escalation was also possible in some “CAB-resistant” patients, namely those requiring ≥2 mg/wk to normalize PRL. CAB de-escalation had no negative long-term effect on tumor size. At the last visit, maximal diameter was 8.8 ± 8.8 mm in the de-escalation group and 13.4 ± 8.5 mm in the fixed-dose group (P < 0.01).Conclusion:In patients with macroprolactinomas, the CAB dosage required to maintain a normal PRL level long term is lower than the initial dosage necessary to normalize the PRL level. After PRL normalization, CAB tapering was almost always successful, even when very high initial doses were necessary. CAB tapering does not undermine tumor control and may attenuate the potential adverse effects of CAB, which appear to be dependent on the cumulative dose.

Serial 3 T magnetic resonance imaging during cabergoline treatment of macroprolactinomas

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

Additional Effects of Radiotherapy to Dopamine Agonists in the Treatment of Macroprolactinomas

INTRODUCTION: The aim of our study was to evaluate the cure rate of macroprolactinomas treated for a long term (> 4 years) or a short term (<4 years) with dopamine agonists (DA) alone or combined with radiotherapy (RT). Sometimes pituitary surgery was performed. MATERIAL AND METHODS: We performed a retrospective study in 111 patients with macroprolactinomas, hospitalized in the Institute of Endocrinology, Bucharest, between 1978-2005. There were two groups, according to the length of DA therapy: group A =41 patients, treated more than 4 years and group B =70 patients, treated less than 4 years. Overall, 25 patients underwent additional radiotherapy, 13 in group A and 12 in group B. 28 patients were submitted to pituitary surgery, 9 in group A and 19 in group B. RESULTS: The cure rate (i.e. normalization of prolactin=PRL level and absence or minimal residual tumor mass, stable minimum 2 years after DA withdrawal) was 5/41 (12.1%) in group A and none in group B. 48 out of 111 patients achieved significant improvement (serum prolactin level less than 20 ng/ml and tumor shrinkage more than 50%) during DA therapy, but not after DA withdrawal: 17/41patients (41.5%) in group A and in 31/70 patients (44.3%) in group B, p=NS. Radiotherapy produced an additional improvement: in serum PRL levels only in group A, in 4/13 patients- 2/8 patients responsive to DA therapy and 2/5 patients resistant to DA therapy. In group B, the 3 patients resistant to DA submitted to radiotherapy were evaluated before the interval necessary for maximal effect of radiotherapy, but in 4/9 patients responsive to DA, we noticed further reduction in tumor volume, 2/4 progressing from mild to significant tumor shrinkage and ¼ progressing from no shrinkage to mild shrinkage. After radiotherapy, the medium prolactin level was 5.1 ng/ml in 10 patients from both groups on low bromocriptine (BRC) dose (7.5 mg/day), significantly less than in patients without radiotherapy, i.e. than in 19 patients from group A

Meningitis four years after treatment of macroprolactinoma

After treatment of macroprolactinoma, patients are advised to look out for cerebrospinal fluid (CSF) rhinorrhoea. But meningitis can develop without this warning sign.

Treatment of Macroprolactinoma With Cabergoline

Treatment of Macroprolactinoma With Cabergoline

Treatment of Macroprolactinoma With Cabergoline: A Study of 85 Patients

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

Treatment of macroprolactinoma with cabergoline: a study of 85 patients.

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

Treatment of prolactin-secreting macroadenomas with the once-weekly dopamine agonist cabergoline.

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

Treatment of macroprolactinomas with the long-acting and repeatable form of bromocriptine: a report on 29 cases.

Twenty-nine patients with macroprolactinomas were treated by monthly intramuscular injections of the long-acting and repeatable form of bromocriptine (Parlodel-LAR) in doses ranging from 50-150 mg. They were divided into two groups: group I consisted of 22 patients who received Parlodel LAR before transsphenoidal adenomectomy; group II was composed of 7 patients with earlier neurosurgery and of 2 patients from group I not cured by transsphenoidal adenomectomy. Duration of therapy varied from 1-12 months, and a total of 104 injections was given. At nadir day, serum PRL levels were situated between less than 1% and 43% of pretreatment values. At day 28 after the first injection, serum PRL levels varied between less than 1% to 139% of initial values. No difference could be detected between the two groups regarding the percent of PRL inhibition. Long-term treatment with Parlodel-LAR resulted in a sustained inhibition of PRL secretion, except for 1 case. Resumption of menstrual cycles occurred in 4 out of 15 women and correction of hypogonadism in 4 out of 14 men. Amelioration of disturbed visual fields was recorded in 3 out of 8 patients. Diminution of the adenoma volume was radiologically documented in 14 out of 22 cases. Only few and mild side effects were recorded. One patient with partial adrenal deficiency suffered from a syncope, but this was prevented by hydrocortisone supplementation during the subsequent Parlodel-LAR administration. In conclusion, Parlodel-LAR proved effective in the treatment of macroprolactinomas, achieving rapid inhibition of PRL secretion, and in some patients amelioration of hypopituitarism, reduction in tumor size, and improvement in visual fields, and caused no serious side effects. It is a valuable preparation to surgery and can also be used in long-term medical therapy.

Treatment of macroprolactinomas with the long-acting and repeatable form of bromocriptine: a report on 29 cases

Treatment of macroprolactinomas with the long-acting and repeatable form of bromocriptine: a report on 29 cases

Endocrine Function, Psychiatric and Clinical Consequences in Patients With Macroprolactinomas After Long-term Treatment With the New Non-ergot Dopamine Agonist CV205–502

Although bromocriptine is the mainstay of treatment of macroprolactinomas, its therapeutic usefulness may be limited by poor tolerance, lack of consistent reduction in serum prolactin levels and tumour size, and the necessity for multiple dosing. Consequently new dopamine agonists have been developed, including the long acting non-ergot agonist CV205-502 which has been shown to date to be consistently effective in reducing serum PRL levels and causing tumour shrinkage. Twelve patients were treated for periods of up to 24 months with CV205-502 in doses ranging from 0.075 mg to 1.65 mg once daily. Clinical and psychiatric assessments, biochemical parameters, tumour size determination, and anterior pituitary function tests were performed regularly. Tumour shrinkage was noted in all patients, and varied from 11 per cent reduction to complete disappearance of tumour. Prolactin levels became normal in seven patients and were reduced by more than 90 per cent in the remaining five. Normal menstruation resumed in six of the eight women, one of whom conceived after one year of therapy; libido returned in all patients. Psychiatric complications occurred in three patients necessitating withdrawal of therapy in one. Significant weight loss was noted in 11 of 12 patients. Triglyceride concentrations fell from 1.5 +/- 0.1 to 1.0 +/- 0.1 mmol/l at 12 months (p = 0.006), and cholesterol fell from 6.3 +/- 0.4 to 5.3 +/- 0.3 mmol/l (p = 0.04). The mean TSH response 20 min following TRH injection fell from 14.3 +/- 2.9 to 8.7 +/- 1.3 mU/l at 2 months (p = 0.027). There was a significant increase in the peak growth hormone response to the insulin stress test from basal median (25th-75th centiles) values of 15 (4.4-25.5) mU/l to 24.5 (9-37) mU/l at 2 months (p less than 0.01) and 31 (19.3-63.5) at 12 months (p less than 0.005). CV205-502 is highly effective in the medical management of patients with macroprolactinomas, reducing prolactin levels and tumour size and restoring normal anterior pituitary function. It is, however, associated with the important side effects of weight loss and psychiatric complications which should be drawn to the attention of clinicians.

Bromocriptine-unresponsive prolactin macroadenoma in a prepubertal female

Macroprolactinomas occur rarely in prepubertal children. A prepubertal 11 10/12-year-old female with a macroprolactinoma presented with a diagnosis of anorexia nervosa. Findings included severe headaches, anorexia, weight loss, and growth failure. The initial serum prolactin level was 2,916 ng/ml. This value fell after beginning treatment witli bromocriptine, but later rose despite a doubling of the dose. Transsphenoidal surgical resection was performed and postoperative radiation given. The use of bromocriptine, surgical resection, and radiation therapy in the treatment of macroprolactinomas are discussed.