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Introduction: Megacolon is defined as abnormal dilatation of the colon, typically exceeding 6 cm in diameter. It often presents with severe constipation and abdominal distension. Common causes include Hirschsprung’s disease, inflammatory bowel disease, Clostridioides difficile colitis, and Ogilvie syndrome. We present a rare cause of megacolon: myxedema, a severe complication of untreated hypothyroidism. Description: A 54-year-old woman from a nursing home with a history of hypothyroidism, diverticulosis, bilateral DVTs, bipolar disorder, and ambulatory issues presented with nausea, vomiting, constipation, and bright red blood per rectum. She reported feeling cold over several days. She had not received levothyroxine for six months due to incomplete medication reconciliation. On arrival, she was hypotensive (BP 74/46 mmHg), tachycardic (HR 144 bpm), febrile (38.8°C), and had a diffusely tender abdomen with hyperactive bowel sounds. Labs revealed Hb 9.5 g/dL, glucose 60 mg/dL, lactic acid 2.5 mmol/L, calcium 7.3 mg/dL, albumin 2.3 g/dL, potassium 2.6 mmol/L, magnesium 1.4 mg/dL, and TSH >51.9 µIU/mL. EKG showed sinus tachycardia. CT thorax revealed large bilateral pleural effusions and ground-glass opacities. CT abdomen/pelvis showed cecal wall thickening and colonic distension with the transverse colon measuring 8.5 cm. She developed persistent bradycardia in the 40s. Thyroid panel showed free T4 0.6 ng/dL, free T3 1.5 pg/mL, and total T3 32 ng/dL. C. difficile testing was negative. She was treated with IV antibiotics, vasopressors, aggressive thyroid hormone replacement, NG decompression, LIS, and a rectal tube. Serial imaging showed improvement in colonic distension, and her stool output gradually increased as thyroid function improved. Discussion: Myxedema megacolon is a rare and potentially fatal complication of hypothyroidism. Proposed mechanisms include myxomatous infiltration of the submucosa and autonomic neuropathy. This case underscores the importance of recognizing myxedema as a rare cause of colonic pseudo-obstruction and initiating timely therapy. Note: Artificial intelligence was used for grammar refinement in this submission.