Predictors of Chronic LH-Testosterone Axis Suppression in Male Macroprolactinomas With Normoprolactinemia on Cabergoline

• Published in: The journal of clinical endocrinology and metabolism 2020-12, Vol.105 (12), p.1-e4557
• Main Authors: Sehemby, Manjeetkaur, Lila, Anurag Ranjan, Sarathi, Vijaya, Shah, Ravikumar, Sankhe, Shilpa, Jaiswal, Sanjeet Kumar, Ramteke-Jadhav, Swati, Patil, Virendra, Shah, Nalini, Bandgar, Tushar
• Format: Article
• Language: English
• Subjects: Adult; Cabergoline; Cabergoline - therapeutic use; Cross-Sectional Studies; Dopamine; Down-Regulation - drug effects; Drug therapy; Follicle-stimulating hormone; Health aspects; Hormone therapy; Humans; Hypogonadism; Hypogonadism - blood; Hypogonadism - drug therapy; Hypogonadism - etiology; Hypothalamic-pituitary-gonadal axis; Hypothalamus; Inhibin; Luteinizing hormone; Luteinizing Hormone - blood; Luteinizing Hormone - metabolism; Male; Men; Middle Aged; Patient outcomes; Pituitary (anterior); Pituitary gland; Pituitary Neoplasms - complications; Pituitary Neoplasms - diagnosis; Pituitary Neoplasms - drug therapy; Pituitary Neoplasms - metabolism; Pituitary-gonadal axis; Prognosis; Prolactin; Prolactin - blood; Prolactinoma; Prolactinoma - complications; Prolactinoma - diagnosis; Prolactinoma - drug therapy; Prolactinoma - metabolism; Prospective Studies; Remission Induction; Retrospective Studies; Risk factors; Signal Transduction - drug effects; Statistics; Testosterone; Testosterone - blood; Testosterone - metabolism; Treatment Outcome; Tumors; Young Adult
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgaa650

Abstract Context Data are limited regarding prevalence, predictors, and mechanisms of persistent hypogonadotropic hypogonadism (HH) in males with a macroprolactinoma who achieve normoprolactinemia on dopamine-agonist therapy. None of the previous studies provide cutoffs to predict the achievement of eugonadism. Objective The objective of this work is to evaluate the prevalence of persistent HH and its determinants in men with a macroprolactinoma who achieve normoprolactinemia on cabergoline monotherapy. Design and Setting This retrospective study with prospective cross-sectional evaluation took place at a tertiary health care center. Patients Study participants included men with a macroprolactinoma and baseline HH who achieved normoprolactinemia on cabergoline monotherapy. Main Outcome Measures Outcome measures of this study included the prevalence of persistent HH and its predictors. Results Thirty participants (age, 38.3 ± 10.1 years) with baseline tumor size of 4.08 ± 1.48 cm and median (interquartile range) prolactin of 2871 ng/mL (range, 1665-8425 ng/mL) were included. Eight of 30 participants achieved eugonadism after a median follow-up of 3 years. Patients with persistent HH had suppression of the luteinizing hormone (LH)-testosterone axis with sparing of other anterior pituitary hormonal axes, including follicle-stimulating hormone-inhibin B. Baseline prolactin (1674 vs 4120 ng/mL; P = .008) and maximal tumor diameter (2.55 ± 0.36 vs 4.64 ± 1.32 cm; P = .003) were lower in patients who achieved eugonadism. Baseline maximal tumor diameter less than or equal to 3.2 cm (sensitivity: 75%, specificity: 63.6%) and serum prolactin less than or equal to 2098 ng/mL (sensitivity: 87.5%, specificity: 77.3%) best predicted reversal of HH. Conclusion Recovery of the LH-testosterone axis occurred in 26.7% of men with a macroprolactinoma who achieved normoprolactinemia on cabergoline monotherapy. Higher baseline tumor size and serum prolactin predict persistent HH. Our data favor chronic functional modification of the hypothalamic-pituitary-gonadal axis over gonadotroph damage as the cause of persistent HH.