Ermelinda Guerra

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 Parkinsons 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.

Hypertension in acromegaly and in the normal population: prevalence and determinants

Background  The GH/IGF‐I axis has a relevant role to play in the cardiovascular system but its implication in the pathogenesis of hypertension in the normal population and in acromegaly is not yet clear.

Predictors of remission of hyperprolactinaemia after long‐term withdrawal of cabergoline therapy

Background  Remission rates of 76, 69·5 and 64·3% have been reported in patients with nontumoural hyperprolactinaemia (NTH), microprolactinoma and macroprolactinoma, respectively, 2–5 years after cabergoline (CAB) withdrawal.

PRL Secreting Adenomas in Male Patients

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

Drug Insight: cabergoline and bromocriptine in the treatment of hyperprolactinemia in men and women

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

Results of a Single-Center Observational 10-Year Survey Study on Recurrence of Hyperprolactinemia after Pregnancy and Lactation

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

Quality of life in women with microprolactinoma treated with dopamine agonists

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

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.

Circulating IGF-I levels are associated with increased biventricular contractility in top-level rowers

Background  The intensive physical activity is often associated with cardiac changes.

Predittori della remissione dell’iperprolattinemia dopo sospensione della terapia con cabergolina a lungo termine

RiassuntoBACKGROUND. È stato riportato che la frequenza di remissione, 2–5 anni dopo la sospensione di cabergolina (CAB) è del 76, 69,5 e 64,3% rispettivamente nei pazienti con iperprolattinemia non tumorale (INT), microprolattinoma (µ) e macroprolattinoma (M). OBIETTIVO. Osservare la frequenza stimata di recidiva 24–96 mesi dopo la sospensione di CAB e identificare i fattori predittivi di remissione della malattia. DISEGNO. Osservazionale, analitico, prospettico. PAZIENTI. In una casistica di 381 pazienti de novo con iperprolattinemia senza precedente trattamento, sono stati studiati 221 pazienti (58%) (173 donne, 48 uomini; 27 con INT, 115 con µ e 79 con M). METODI. Utilizzando le curve ROC (receiver operating characteristic), è stata analizzata l’accuratezza diagnostica dei valori nadir di PRL (t=7,6, p<0,0001) e del nadir del massimo diametro tumorale (t=3,9, p<0,001) come indici predittivi di recidiva. RISULTATI. Si è osservata recidiva di iperprolattinemia nel 25,9, 33,9 e 53,1% dei pazienti con INT, µ e M, rispettivamente. Il cut-off ottimale predittivo della recidiva di iperprolattinemia dopo la sospensione di CAB si è dimostrato 5,4 ng/ml come livello nadir di PRL [sensibilità (95% IC) 76% (67–84%), specificità 65% (51–77%)] e 3,1 mm come nadir del massimo diametro tumorale in trattamento [sensibilità 52% (41–63%), specificità 86% (79–91%)]. I pazienti che raggiungevano durante il trattamento sia PRL <5,4 ng/ml che diametro tumorale massimo <3,1 mm (n=111) mostravano recidiva di iperprolattinemia 24–96 mesi dopo la sospensione della CAB significativamente minore (20%, analisi di Kaplan-Meier) rispetto a quelli che non soddisfacevano questi criteri (n=38, 90%, p<0,0001). La frequenza stimata di recidiva di iperprolattinemia dopo la sospensione del farmaco è risultata rispettivamente del 50 e 56% nei pazienti che raggiungevano PRL nadir <5,4 ng/ml (n=26) o diametro tumorale massimo <3,1 mm (n=46) durante trattamento con CAB. CONCLUSIONE. La persistenza di remissione di iperprolattinemia senza nessuna evidenza di ricrescita tumorale 24–96 mesi dopo la sospensione di CAB si manifesta nella maggioranza dei pazienti con INT e µ e in circa la metà di quelli con M. Il nadir dei livelli di PRL <5,4 ng/ml e del diametro tumorale massimo alla sospensione di CAB <3,1 mm predicono la remissione di iperprolattinemia nell’80% dei pazienti.