Abstract Disclosure: M.H. Islam: None. D.R. Jimenez Corado: None. S. Siddiqui: None. M.F. Aquino Camey: None. S. Yeasmin: None. Background: Myxedema coma is a rare and life-threatening complication of hypothyroidism.Although it is rare in the era of better diagnostics and treatment modalities, its life-threatening nature mandates its timely recognition and better understanding. Case:81-year-old female with a history of hypothyroidism (unclear medication compliance) and alcohol use disorder was admitted due to alcohol withdrawal and treated with benzodiazepines. A few days prior to the presentation, she was found to have worsening confusion, unsteady gait, and multiple falls. On presentation, she was hemodynamically stable, tremulous, anxious, and oriented to person only. Blood work was remarkable for mild transaminitis. CT scan of the head revealed sequelae of microvascular disease. The day after admission, she was noted to be lethargic, and benzodiazepines were held. Later, she became hypothermic, hypotensive, bradycardic, and hyponatremic. Further investigation was pursued, revealing a TSH of 55 (normal 0.27 to 4.2 mlU/L), free T4 of <0.10 ng/dL (normal 0.8-1.7 ng/dL), free T3 of <1.0 pg/mL (normal 2.2-4 pg/mL), and cortisol of 10.7 ug/dL. Due to concerns of myxedema coma, she was started on stress dose steroids and IV levothyroxine. She was transferred to the ICU as her mental status continued to deteriorate; she underwent endotracheal intubation and received additional doses of IV levothyroxine and liothyronine. After a few days, her clinical condition and her cortisol, free T4, and free T3 levels improved; she was extubated and later discharged with an adjusted levothyroxine dose. Conclusion: It is of absolute importance to keep myxedema coma as a differential diagnosis when evaluating encephalopathic elderly patients, especially those with a history of thyroid disorders.There is a paucity of evidence to suggest a clear benefit of combining levothyroxine-liothyronine over levothyroxine alone. Treating initially with intravenous levothyroxine over oral is beneficial, as GI absorption and bioavailability are likely variable and unpredictable. In this case, oral liothyronine was used with IV levothyroxine to speed up clinical and biochemical recovery.Adrenal insufficiency often coexists with hypothyroidism, with considerable overlap in clinical features like hypotension, hypoglycemia, and hyponatremia. Administration of levothyroxine before steroids can lead to a rapid increase in metabolic rate and subsequent depletion of the existing reserves. Considering this, it can be said with fair confidence that patients need prior or concomitant stress doses of corticosteroids on an emergent basis. Later, biochemical testing can be done to evaluate the functioning of the hypothalamic-pituitary-adrenal axis and then adjust steroid doses accordingly. Presentation: 6/1/2024