madman
Super Moderator
Predictors of chronic LH-testosterone axis suppression in male macroprolactinomas with normoprolactinemia on cabergoline
Abstract:
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 the 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 favor chronic functional modification of the hypothalamic-pituitary-gonadal axis over gonadotroph damage as the cause of persistent HH.
Introduction
Macroprolactinoma in males presents with tumor mass effects (visual field defect, headache) and/or symptoms of hypogonadism (decreased libido, erectile dysfunction, infertility) (1). This hypogonadism attributed to hypogonadotropic hypogonadism (HH) is seen in the majority of males (75%) at the time of diagnosis (2). Treatment goals in these patients are to restore eugonadism by normalizing prolactin and tumor mass reduction, both of which are achieved in most patients by using dopamine agonists (DA). Due to its highest efficacy (80-95%) among the available DA, cabergoline remains the preferred first-line agent (3).
Nevertheless, the problem of persistent HH is observed in ~40% of males with macroprolactinoma treated with DA monotherapy (4-8). Drug resistance is cited as a contributory factor, but some patients have persistent HH despite achieving normoprolactinemia. In these patients, the role of irreversible structural gonadotroph damage versus functional modification of the hypothalamic-pituitary-gonadal (HPG) axis with preserved gonadotroph function is constantly debated (9). As most of the published studies have mixed cohorts of patients treated with DA, surgery, and/or radiation therapy, the underlying mechanism for persistent HH and, consequently its predictors remain scarcely defined. Baseline tumor size and serum prolactin were identified as predictors of persistent HH in one study but again confounded by the inclusion of patients with baseline eugonadism and/or drug-resistance (6). Moreover, none of the studies have reported cut-offs for these predictors. Therefore, studying males with macroprolactinoma who are hypogonadal at baseline and achieve normoprolactinemia on DA monotherapy may help us to clarify the mechanisms underlying normoprolactinemic HH and to delineate predictors for persistent HH.
Hence, we have evaluated the prevalence of persistent HH, and its determinants in a cohort of males with a macroprolactinoma and HH at baseline who had achieved normoprolactinemia on cabergoline monotherapy.
Discussion: We report the prevalence and predictors of HPG axis recovery in a unique cohort of hypogonadal males with macroprolactinoma who achieved normoprolactinemia on cabergoline monotherapy. Importantly, our study reports the cut-offs for the baseline predictors, which may lead clinicians for timely initiation of testosterone/gonadotropin treatment. In addition, the data from our study support the hypothesis that persistent HH results from the functional alteration of the HPG axis rather than from irreversible structural gonadotroph damage.
Conclusion: Recovery of the HPG axis occurred only in around one-fourth of males with a macroprolactinoma who achieved normoprolactinemia on cabergoline monotherapy over a median follow-up of two years. Higher baseline maximal tumor diameter and serum prolactin level predict persistent HH, which may help to select patients for the early initiation of testosterone replacement. Selective suppression of the LH-testosterone axis with relative sparing of FSH.
Abstract:
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 the 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 favor chronic functional modification of the hypothalamic-pituitary-gonadal axis over gonadotroph damage as the cause of persistent HH.
Introduction
Macroprolactinoma in males presents with tumor mass effects (visual field defect, headache) and/or symptoms of hypogonadism (decreased libido, erectile dysfunction, infertility) (1). This hypogonadism attributed to hypogonadotropic hypogonadism (HH) is seen in the majority of males (75%) at the time of diagnosis (2). Treatment goals in these patients are to restore eugonadism by normalizing prolactin and tumor mass reduction, both of which are achieved in most patients by using dopamine agonists (DA). Due to its highest efficacy (80-95%) among the available DA, cabergoline remains the preferred first-line agent (3).
Nevertheless, the problem of persistent HH is observed in ~40% of males with macroprolactinoma treated with DA monotherapy (4-8). Drug resistance is cited as a contributory factor, but some patients have persistent HH despite achieving normoprolactinemia. In these patients, the role of irreversible structural gonadotroph damage versus functional modification of the hypothalamic-pituitary-gonadal (HPG) axis with preserved gonadotroph function is constantly debated (9). As most of the published studies have mixed cohorts of patients treated with DA, surgery, and/or radiation therapy, the underlying mechanism for persistent HH and, consequently its predictors remain scarcely defined. Baseline tumor size and serum prolactin were identified as predictors of persistent HH in one study but again confounded by the inclusion of patients with baseline eugonadism and/or drug-resistance (6). Moreover, none of the studies have reported cut-offs for these predictors. Therefore, studying males with macroprolactinoma who are hypogonadal at baseline and achieve normoprolactinemia on DA monotherapy may help us to clarify the mechanisms underlying normoprolactinemic HH and to delineate predictors for persistent HH.
Hence, we have evaluated the prevalence of persistent HH, and its determinants in a cohort of males with a macroprolactinoma and HH at baseline who had achieved normoprolactinemia on cabergoline monotherapy.
Discussion: We report the prevalence and predictors of HPG axis recovery in a unique cohort of hypogonadal males with macroprolactinoma who achieved normoprolactinemia on cabergoline monotherapy. Importantly, our study reports the cut-offs for the baseline predictors, which may lead clinicians for timely initiation of testosterone/gonadotropin treatment. In addition, the data from our study support the hypothesis that persistent HH results from the functional alteration of the HPG axis rather than from irreversible structural gonadotroph damage.
Conclusion: Recovery of the HPG axis occurred only in around one-fourth of males with a macroprolactinoma who achieved normoprolactinemia on cabergoline monotherapy over a median follow-up of two years. Higher baseline maximal tumor diameter and serum prolactin level predict persistent HH, which may help to select patients for the early initiation of testosterone replacement. Selective suppression of the LH-testosterone axis with relative sparing of FSH.
