Rapid Resolution of Megestrol Acetate Associated Adrenal Insufficiency

Abstract

Introduction Megestrol acetate (MA) is a synthetic progestin commonly used for appetite stimulation. Several case reports have associated use of MA with adrenal insufficiency (AI) through suppression of the hypothalamic-pituitary-adrenal axis. To our knowledge, our case is the first to establish a timeline of onset and resolution of AI associated with MA.

Case We present a 52-year-old female with a past medical history significant for hypothyroidism, systemic lupus erythematosus, Raynaud’s, chronic diarrhea, anemia, and reflex sympathetic dystrophy. She was admitted for small bowel obstruction requiring exploratory laparotomy with lysis of a single adhesion. She developed hypoglycemia blood glucose ranging from 55-60 mg/dL on hospital day 24, after starting nocturnal nasogastric tube feedings. She had poor appetite, weight loss, and intermittent nausea. She did not have a history of exogenous steroids. Physical exam was unremarkable aside from cachectic-appearing body habitus with a BMI of 17. Vital signs were stable. Her TSH, renal function, and liver studies were normal. Serum cortisol was checked on hospital day 27 and was very low, 1.1 mCg/dL (normal range, 5-25 mCg/dL). Endocrine was consulted for evaluation of hypoglycemia and adrenal insufficiency (AI). She had an adequate cortisol response to a 250 mcg cosyntropin stimulation. However, baseline ACTH was inappropriately normal, given her very low serum cortisol, suggesting secondary AI. Upon detailed chart review, we noted that she was started on megestrol acetate (MA) 20 mg PO daily on hospital day 20 for appetite stimulation. We suspected megestrol acetate to be the cause of her secondary AI and hypoglycemia. Within three days after discontinuation of MA, the patient’s hypoglycemia resolved and serum cortisol returned to normal.

Discussion Megestrol acetate is a synthetic progestin frequently used as appetite stimulant. MA is known to have glucocorticoid properties with affinity for glucocorticoid receptors. There are several case reports associating MA with AI which is a potentially life-threatening condition. The mechanism is thought to be suppression of the HPA axis. AI has been noted with doses of 400-600 mg however exact dose and timeline has never been described. Our case is unique where she developed AI after a relatively very low dose of 20 mg daily for only one week. Within three days following identification of the possibility of MA as the inducing agent and subsequent discontinuation, the patient’s AI resolved. This rapid recovery is remarkable and gives important insight about possible impact of dose and duration in resolution of AI associated with MA. MA is frequently used as an appetite stimulant and it is very important to be aware of potentially life threatening side effects of AI. A timeline for development of MA induced AI and resolution has not been shown in previous case reports; ours is the first case to outline the dose and timeline for recovery, although further research is needed to confirm these findings.