Type 4 Renal Tubular Acidosis (RTA) Induced by Spironolactone Use in Secondary Adrenal Insufficiency

Type 4 RTA is caused by either decreased aldosterone production or resistance. Primary adrenal insufficiency results in decreased aldosterone whereas spironolactone can cause aldosterone resistance(1). We present a case of spironolactone-induced type 4 RTA in a patient with suspected primary adrenal insufficiency. A 70-year-old female with liver cirrhosis on spironolactone and chronic bronchitis on inhaled steroids (ICS) presented for altered mental status. Laboratories showed hyponatremia 131 mmol/L (135–145 mmol/L) and hyperammonemia 113 µmol/L (11–51 µmol/L). She was successfully treated with oral lactulose for hepatic encephalopathy. However, on day 3, she developed worsening hyponatremia (126 mmol/L) and hyperkalemia 5.8 mmol/L (3.5–5.4 mmol/L). Spironolactone was discontinued, and hyperkalemia improved after medical treatment. Nonetheless, hyperkalemia recurred with worsening hyponatremia (125 mmol/L), hypoglycemia (57 mg/dL), and mild non-anion gap metabolic acidosis without other signs or symptoms of adrenal insufficiency. On day 5, her morning cortisol was 1.5 µg/dL (5–20 µg/dL), with ACTH 11 pg/mL (6–70 pg/mL). Her hyperkalemia persisted (6.3–6.8 mmol/L), and she was started on oral patiromer. Due to suspected adrenal insufficiency, she received dexamethasone 10 mg daily, and endocrinology was consulted. On day 7, an ACTH stimulation test (250 µg IV) showed a baseline ACTH <3 pg/mL, baseline cortisol 0.7 µg/dL (3–15 µg/dL), cortisol 30 minutes 9.9 µg/dL, and 60 minutes 12.2 µg/dL, consistent with incomplete response attributed to the supraphysiologic dexamethasone versus chronic ICS. On day 8, endocrinology discontinued dexamethasone and enoxaparin, and started hydrocortisone 10 mg orally in AM and 5 mg in PM. Aldosterone (measured at day 6) was 7.2 ng/dL (<= 31.0 ng/dL), renin activity 3.1 ng/mL/hr (0.5–4.0 ng/mL/hr), and aldosterone/renin ratio 2.3 (<= 25) consistent with hyporeninemic hypoaldosteronism since aldosterone and renin were inappropriately normal for the hyperkalemia. Repeat cosyntropin test on day 11 showed low ACTH (3 pg/mL), low baseline cortisol 1.1 µg/dL, cortisol 30 minutes 7.9 µg/dL, and 60 minutes 11.2 µg/dL, consistent with secondary adrenal insufficiency, ascribed to chronic ICS. Potassium level normalized seven days after spironolactone discontinuation, related to its approximate duration of action(1). The patient was discharged with hydrocortisone 10 mg daily, and spironolactone was permanently discontinued. Spironolactone use can result in type 4 RTA due to aldosterone resistance and mimic mineralocorticoid deficits characteristic of primary adrenal insufficiency. 1. O’Connell JE, Colledge NR. Type IV renal tubular acidosis and spironolactone therapy in the elderly. Postgrad Med J. 1993;69(817):887–889.