S5945 Myxedema Coma, an Initial Presenting Symptom of Hypothyroidism, Secondary to End-Stage Liver Disease

Introduction: Myxedema coma is a rare but life-threatening disease. The term coma might be misleading, as patients rarely do present with coma. The typical symptoms start with lethargy progressing to stupor and, finally, to coma associated with acute respiratory failure and hypothermia. Eighty percent of patients affected are women >60 years old. To add, it is extremely rare for myxedema coma to be the initial presentation of undiagnosed hypothyroidism. Case Description/Methods: A 73-year-old woman with a complex medical history of hypertension, type 2 Diabetes Mellitus, alcohol induced end-stage liver disease (ESLD), with recurrent ascites (treated by multiple paracentesis). She presented to the hospital with shortness of breath and lethargy. Abdominal exam showed severe distention. Laboratory findings revealed new-onset hypothyroidism, with a markedly elevated TSH of 16 uIU/mL (normal 0.27-4.2 uIU/mL), T3: 57 ng/dL, T4 of 0.6 ng/dL, Model for End-Stage Liver Disease-Sodium score of 15 and normal ammonia level. Her myxedema score was 25, indicating probable myxedema coma. Thyroid peroxidase antibodies were negative. Additionally, her thyroxine-binding globulin (TBG) was low at 5 ug/mL (Ref Range: 13-39 ug/mL). She was treated with hydrocortisone and levothyroxine, leading to normalization of TSH, T3 and T4 levels. Decreased TBG caused by ESLD likely contributed to the hypothyroid state. Discussion: ESLD significantly impacts thyroid hormone levels, primarily causing non-thyroidal illness syndrome (NTIS) and, less often, secondary hypothyroidism. Mechanisms include reduced conversion of T4 to T3, impaired liver synthesis of thyroid hormone binding proteins (TBG, TTR, albumin), and increased binding inhibitors (free fatty acids and bilirubin). Chronic inflammation and elevated cytokines can also suppress thyroid hormone production and disrupt the hypothalamic-pituitary-thyroid axis. Furthermore, malnutrition in ESLD can lead to a deficiency in essential nutrients like iodine, crucial for thyroid hormone synthesis. In rare, severe cases, prolonged ESLD can even impair hypothalamic and pituitary function, potentially resulting in secondary hypothyroidism. NTIS, marked by low T3 with normal or low T4 and TSH, is the most frequent in ESLD and often indicates the severity of liver dysfunction, with low T3 levels being a negative prognostic sign. Less commonly, as in our patient, reduction in TBG levels causes lower levels of T3 and T4, with elevation in TSH.