SUN-031 Megestrol Acetate for Bodybuilding Resulting in Abrupt Hypothalamic-Pituitary Dysfunction

Abstract

Introduction: Megestrol acetate (MA) is a synthetic progestin often used for appetite stimulation and weight gain in patients with cachexia related to AIDS, cancer or terminal illness. MA is frequently implicated in development of both glucocorticoid excess and adrenal insufficiency (AI) in a somewhat unpredictable manner. Less commonly reported adverse effects of MA include dysfunction of the hypothalamic pituitary axis. Few cases in literature exist regarding the use of MA in young, healthy patients and the potential clinical severity of pituitary dysfunction in this population. Case: A 24-year-old male was previously healthy but frustrated by an inability to gain muscle mass. Evaluation one-year prior was unrevealing and included a total testosterone of 1100ng/dL (264-916ng/dL). In the interim, he was prescribed MA 625/5mg for 2 months with rapid development of abdominal adiposity, depressed mood, low libido and erectile dysfunction. Repeat evaluation revealed a precipitous drop in total testosterone to 66 ng/dL at which point he self-discontinued MA. He then began to experience palpitations, sweats, poor concentration, and undesirable weight loss along with worsening symptoms of sexual and erectile dysfunction.Three months after MA discontinuation, he appeared well with physical examination and vital signs within normal limits. Surprisingly, repeat studies revealed total testosterone <3, free testosterone <0.2 (9.3 -26.5 pg/mL), LH 1.3 (1.7-8.6 mIU/mL), FSH 2.2 (1.5-12.3 mIU/mL), Prolactin 33.4 (4.0-15.2 ng/mL) as well as 8AM cortisol 2.2 ug/dL and ACTH 22.7 pg/mL. A basic metabolic panel, thyroid function studies and pituitary MRI were unremarkable. The patient was empirically placed on prednisone 5mg daily pending ACTH stimulation testing for HPA axis reassessment. Topical testosterone replacement therapy was initiated due to intolerance of hypogonadal symptoms. Discussion: MA, by virtue of affinity for glucocorticoid receptors, has the potential to cause hyperglycemia and Cushing’s syndrome. Secondary AI often results from withdrawal of MA however central AI can also occur with active administration by unclear mechanisms. Hypogonadism and hyperprolactinemia are additional under-reported adverse effects of MA with symptoms often masked by AI or elements of chronic illness. In study of men age 60-85 year on MA, a mean percentage change of ACTH -89.5%, LH -49%, TSH -14.7% and Prolactin +150% were seen from baseline after 12 weeks of therapy as was decreased cortisol. Limited data exists in young patients such as ours given limited indications for the agent’s use. Importantly, MA should be prescribed with understanding that weight gain is predominantly adipose rather than muscle mass and that its safety is limited by potential HP axis dysfunction, namely adrenal and gonadal deficiencies.