Predicting hypogonadotropic hypogonadism persistence in male macroprolactinoma

Abstract

To study the baseline characteristics predicting hypogonadotropic hypogonadism (HH) persistence in men with macroprolactinoma that achieved prolactin normalization. Design:Retrospective cohort study. Methods:Male patients diagnosed with macroprolactinoma and HH that received cabergoline treatment with subsequent prolactin normalization were included: men that achieved eugonadism, and men that remained hypogonadal. Patient's demographic, clinical and biochemical parameters, sellar imaging and visual elds tests were obtained.Univariate and multivariate models were used to identify predictors of HH persistence. Results:Fifty-eight male patients (age, 49.2±12.6 years) with a median baseline prolactin of 1154 ng/mL (IQR, 478-2763 ng/mL) and adenoma (maximal) diameter of 25.9±14.8 mm were followed for a median of 5.6 years (IQR, 3.0-10.7). Twelve men (21%) suffered from HH persistence at the end of follow-up and 46 men achieved eugonadism. Forty-two out of 46 men (91%) accomplished eugonadism within the rst year following prolactin normalization.In a multivariate logistic regression model, hypopituitarism (OR=10.1; 95% CI 1.10 -101.94), visual eld defect (OR=9.9; 95% CI 1.07 -92.33), and low baseline testosterone levels (OR=0.5; 95% CI 0.29 -0.93) were independent predictors of HH persistence. Conclusion:In our cohort of men with macroprolactinoma that reached prolactin normalization with cabergoline treatment, 21% had HH persistence. Pituitary hormone de ciency, visual eld defects, and low baseline testosterone levels were independently associated with HH persistence. 91% of men achieved eugonadism within the rst year following prolactin normalization. These ndings may support informed clinical decision-making regarding the initiation of testosterone replacement in men with macroprolactinomas.

Diagnosis and management of prolactin-secreting pituitary adenomas: a Pituitary Society international Consensus Statement

“…Increased prolactin secretion during stress, pregnancy and lactation inhibits hypothalamic kisspeptin neuron function, and consequently reduces gonadotrophin-releasing hormone (GnRH) production 26 . Prolactinoma clinical presentation in part reflects prolactin-induced suppression of the hypothalamic-pituitarygonadal axis that usually reverts after normalization of prolactin serum levels 27 , although hypogonadism can persist, especially in men with macroprolactinoma 28,29 .…”

The Role of Aromatase Inhibitors in Male Prolactinoma

“…In our recent study of 58 men with macro-prolactinoma, 79% of male patients who were followed for 5.6 years achieved eugonadism, while 21% had persistence of hypogonadism. Our data show that low baseline testosterone levels, visual field defects, and pituitary hormone deficiency are predictors of the persistence of hypogonadism within the first year following prolactin normalization, a finding that may aid in identifying patients who are suitable for testosterone replacement therapy [ 33 ].…”

Prolactin-secreting pituitary adenomas: male-specific differences in pathogenesis, clinical presentation and treatment

“…However, in some men (11-73% depending on the study), HH persists even after hyperprolactinemia normalization (31, 131, 133-136, 140, 141). The proposed independent predictors of HH persistence in men PRLomas include higher baseline PRL levels (135,136,141,142), larger tumor size (16,135,136,141,142), lower baseline testosterone levels (135,(140)(141)(142), hypopituitarism (140,142), and visual field defect (140). It is postulated that persistent HH in males with PRLomas is mainly an effect of chronic hypothalamus functional modification caused by the inhibitory effect of PRL (136, 143), and, to a lesser extent, derives from direct structural damage of the pituitary (24).…”

“…As mentioned previously, despite PRL normalization, HH may persist in up to 73% of men (31, 131, 133-136, 140, 141). Higher baseline PRL concentrations (135,136,141,142), larger tumor size (16,135,136,141,142), lower baseline testosterone levels (135,(140)(141)(142), pituitary hormone deficiency (140,142), and visual field defect (140) are considered as independent factors of its persistence. After observation in many studies, prolonging the follow-up period increases the percentage of men obtaining eugonadism (136,140,142).…”

“…Higher baseline PRL concentrations (135,136,141,142), larger tumor size (16,135,136,141,142), lower baseline testosterone levels (135,(140)(141)(142), pituitary hormone deficiency (140,142), and visual field defect (140) are considered as independent factors of its persistence. After observation in many studies, prolonging the follow-up period increases the percentage of men obtaining eugonadism (136,140,142). Therefore, before initiation of TRT, it is important to consider the possible presence of risk factors of persistent HH and the time since normoprolactinemia was achieved, usually starting after 3-6 months since then (12).…”