Increased prevalence of tricuspid regurgitation in patients with prolactinomas chronically treated with cabergoline.

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

Age changes the diagnostic accuracy of mean profile and nadir growth hormone levels after oral glucose in postoperative patients with acromegaly.

BACKGROUND: This analytical, retrospective study was designed to select cut-off thresholds of mean GH levels during a diurnal profile and nadir GH levels after oral glucose tolerance test (OGTT) according to age to diagnose surgical remission of acromegaly. METHODS: One hundred forty-one patients (76 women, aged 44 +/- 15 years and 65 men, aged 43 +/- 13 years) were included in this study. For the purpose of this study, remission was based on insulin-like growth factor-I (IGF-I) levels in the normal range for age. Diagnostic accuracy was analysed by receiving-operator characteristics (ROC) curves in the entire series, and in young (20-40 years), middle-aged (41-60 years) and older patients (> 60 years), separately. RESULTS: Sixty patients (42.6%) had normal IGF-I levels after surgery. In the entire series, in young and in middle-aged patients, the ROC analysis showed that optimum cut-off for mean GH levels was 2.3 microg/l (diagnostic accuracy range, 94-97%) whereas that for nadir GH after OGTT were, respectively, 0.85, 0.9 and 0.8 microg/l (diagnostic accuracy range, 90-95%). In the older patients, the optimum cut-off selected for mean GH levels was 1.4 microg/l and that for nadir GH after OGTT was 0.5 microg/l (diagnostic accuracy, 100% for both). The comparative analysis of the ROC curves did not show any significant difference between mean GH and nadir GH after OGTT (P = 0.21). CONCLUSIONS: The criteria currently accepted for diagnosing post-surgical remission of acromegaly have high diagnostic accuracy only in the patients aged below 60 years. In older patients, lower cut-offs (i.e. = 1.4 microg/l for fasting GH and = 0.5 microg/l for nadir GH after OGTT) predict normal IGF-I levels. Mean GH levels during a diurnal profile have similar diagnostic accuracy of nadir GH levels after OGTT. This suggests that OGTT is not necessary to establish surgical cure.

The treatment with cabergoline for 24 month normalizes the quality of seminal fluid in hyperprolactinaemic males.

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

Somatostatin analogs in treatment of non-growth hormone-secreting pituitary adenomas.

Besides well-known effects in GH-secreting adenomas, somatostatin analogs such as octreotide and lanreotide have been used in TSH-secreting adenomas and in the so-called clinically nonfunctioning adenomas. The rationale for their use is based on the evidence that both these tumor types express large amounts of somatostatin receptor subtypes 2 and 5, which are preferentially bound by octreotide and lanreotide. However, whether in TSH-secreting adenomas the results are excellent in the nonfunctioning type, the results are controversial. Some preliminary results showing a very rapid recovery of the visual field have not been confirmed subsequently. No evident effect of tumor shrinkage has been reported. At present, the use of somatostatin analogs in clinically nonfunctioning adenomas is questioned.

Hyperprolactinemia in men: clinical and biochemical features and response to treatment.

Hyperprolactinemia induces hypogonadism by inhibiting gonadotropin-releasing hormone pulsatile secretion and, consequently, follicle-stimulating hormone, luteinizing hormone, and testosterone pulsatility. This leads to spermatogenic arrest, impaired motility, and sperm quality and results in morphologic alterations of the testes similar to those observed in prepubertal testes. Men with hyperprolactinemia present more frequently with a macroadenoma than a microadenoma. Symptoms directly related to hypogonadism are prevalent. In men hypogonadism leads to impaired libido, erectile dysfunction, diminished ejaculate volume, and oligospermia. It is present in 16% of patients with erectile dysfunction and in approx 11% of men with oligospermia. Treatment with bromocriptine or cabergoline (CAB) is effective in men with prolactinomas, with a response that is in general comparable to treatment in women. Seminal fluid abnormalities rapidly improve with CAB treatment, while other dopaminergic compounds require longer periods of treatment. Moreover, to improve gonadal function in men, the integrity of the hypothalamic-pituitary-gonadal axis is necessary. New promising data indicate that a substantial proportion of patients with either micro- or macroprolactinoma do not present hyperprolactinemia after long-term withdrawal from CAB. Whether this corresponds to a definitive cure is still unknown, but treatment withdrawal should be attempted in patients achieving normalization of prolactin levels and disappearance of tumor mass to investigate this issue.