Predictors of chronic LH-testosterone axis suppression in male macroprolactinomas with normoprolactinemia on cabergoline.

CONTEXT Data regarding prevalence, predictors, and mechanisms of persistent hypogonadotropic hypogonadism (HH) in males with a macroprolactinoma who achieve normoprolactinemia on dopamine-agonist therapy is limited. None of the previous studies provide cut-offs to predict the achievement of eugonadism. OBJECTIVE To evaluate the prevalence of persistent HH and its determinants in males with a macroprolactinoma who achieve normoprolactinemia on cabergoline monotherapy. DESIGN Retrospective study with prospective cross-sectional evaluation. SETTING Tertiary health care center. PATIENTS Males with a macroprolactinoma and baseline HH who achieve normoprolactinemia on cabergoline monotherapy. INTERVENTION None. MAIN OUTCOME MEASURES Prevalence of persistent HH and its predictors. RESULTS Thirty subjects (age: 38.3±10.1 years) with baseline tumor size of 4.08±1.48 cm and median (IQR) prolactin of 2871 (1665-8425) ng/ml were included. Eight of 30 participants achieved eugonadism after a median follow-up of three years. Patients with persistent HH had suppression of LH-testosterone axis with sparing of other anterior pituitary hormonal axes including FSH-Inhibin B. Baseline prolactin (1674 vs. 4120 ng/ml; p=0.008) and maximal tumor diameter (2.55±0.36 vs. 4.64±1.32 cm; p=0.003) were lower in patients who achieved eugonadism. Baseline maximal tumor diameter ≤ 3.2 cm (sensitivity: 75%, specificity: 63.6%) and serum prolactin ≤ 2098 ng/ml (sensitivity: 87.5%, specificity: 77.3%) best predicted reversal of HH. CONCLUSION Recovery of LH-testosterone axis occurred in 26.7% of males with a macroprolactinoma who achieved normoprolactinemia on cabergoline monotherapy. Higher baseline tumor size and serum prolactin predict persistent HH. Our data favors chronic functional modification of hypothalamic-pituitary-gonadal axis over gonadotroph damage as the cause of persistent HH.