UNRAVELING THE ENIGMA

TRIMETHOPRIM-SULFAMETHOXAZOLEINDUCED SIADH

Abstract

Introduction/Background Syndrome of inappropriate antidiuretic hormone secretion (SIADH) presents a complex clinical scenario characterized by the aberrant secretion of antidiuretic hormone (ADH), leading to hyponatremia, water retention and potential neurological manifestations. Trimethoprimsulfamethoxazole (TMP-SMX, Bactrim) is a potential cause of medication-induced SIADH. Case A 21-year-old female came in with left gluteal abscess and newly diagnosed diabetes mellitus complicated by diabetic ketoacidosis (DKA). Following treatment for DKA and abscess incision and drainage, which grew Staphylococcus argenteus, she received intravenous cloxacillin for 7 days. Antibiotics were then shifted to oral TMP-SMX as she was deemed fit for discharge. After 3 days on TMP-SMX, she developed severe hyponatremia with a sodium level of 114 mmol/L, despite having baseline sodium levels ranging between 135-143 mmol/L. Despite hydration with 4 L of NaCl per day, her serum sodium levels continued to decline, reaching a nadir of 108 mmol/L. She was then referred to the medical team for further management. Urine sodium and osmolarity were elevated at 95 mEq/L and 316 mOsm/L, respectively, with a low serum osmolality at 262 mOsm/L. Morning cortisol level and thyroid function tests were within normal level and she was euvolemic. A diagnosis of medication TMP-SMX-induced SIADH was made. She was started on fluid restriction of less than 1 L per day. Serum sodium levels gradually improved to 130 mmol/L, with stable electrolytes, and renal function and she was discharged well. Conclusion TMP-SMX is a potential cause of medication-induced SIADH. Additionally, trimethoprim (TMP) shares structural similarities with amiloride and functions on the identical epithelial sodium channels (eNAC) in the distal nephron, leading to natriuresis and hyponatremia. Prompt identification of the cause of hyponatremia (diuresis vs SIADH) is crucial in averting severe complications linked with hyponatremia.