MON-479 - Central Adrenal Insufficiency Following 3,4-Methylenedioxymethamphetamine (MDMA) Induced Serotonin Syndrome

Introduction: Ecstasy, or 3,4-methylenedioxymethamphetamine (MDMA), functions as a direct agonist and reuptake inhibitor of serotonin, with downstream effects on cortisol. Acute MDMA use markedly elevates cortisol through stimulation of the hypothalamic-pituitary-adrenal (HPA) axis; single doses can increase serum cortisol by up to 800% when combined with physical exertion. While cortisol responses to serotonergic challenge in chronic MDMA users typically normalize after 12 months of abstinence, the long-term effects following single use or overdose are unknown. There is also limited evidence regarding MDMA toxicity contributing to central adrenal insufficiency. We present a case of central adrenal insufficiency precipitated after MDMA intoxication with subsequent serotonin syndrome.

Case: A previously healthy 30-year-old female was found minimally responsive at home. The day prior, she ran a 5K race and attended a concert where she ingested MDMA. The patient presented to the hospital febrile and in shock with metabolic acidosis, rhabdomyolysis causing AKI, and encephalopathy requiring intubation—concerning for serotonin syndrome. Her hospital course was notable for persistent hypotension, fever, and variable heart rate, thought to reflect post-serotonin-syndrome dysautonomia. Her MRI revealed mild bilateral globus pallidus ischemia and a slightly small pituitary without other acute abnormalities; CT imaging showed normal adrenal glands. Further work-up was pursued one week after multiple failed extubation attempts despite improvement in dysautonomia. Her AM cortisol was 1.4 µg/dL, ACTH < 1.5 pg/mL, and cosyntropin stimulation tests showed no response (8.2ug/dL at 30 and 60 minutes). Additional labs showed C-peptide 3.5 ng/mL, TSH 18.08 ulU/mL with free T4 1.19 ng/dL, FSH 4.9 mlU/mL, LH 3.8 mlU/mL, and prolactin 15.9 ng/mL. Weight-based hydrocortisone was started and transitioned to a prednisone taper before discharge. At 3-month endocrinology follow-up, the patient reported significant improvement, TSH levels normalized, and steroids were tapered for repeat testing. ACTH remained undetectable and AM cortisol was 0.8 µg/dL, warranting long-term replacement. At 6 month follow-up, she continues daily 5 mg prednisone.

Conclusion: This case describes central adrenal insufficiency following MDMA intoxication complicated by serotonin syndrome in an individual without chronic MDMA use. Although adrenal testing during critical illness is often confounded, this case demonstrates a reasonable diagnostic and follow-up approach. Understanding that MDMA is known to modulate serotonin, we wonder if neurotoxicity from serotonin syndrome may have precipitated central adrenal insufficiency in this individual. This case raises questions about the long-term impacts of one-time MDMA use.

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