Abstract
Background: Posaconazole can cause pseudohyperaldosteronism via inhibition of 11-beta hydroxylase and 11-beta-hydroxysteroid dehydrogenase type 2 (1). The accumulation of 11-deoxycorticosterone and increased cortisol-to-cortisone ratio in the kidney causes apparent mineralocorticoid excess. The effect of posaconazole on the glucocorticoid axis is less established.
Clinical Case: A 56-year-old Hispanic man with a history of chronic septic arthritis of the left ankle from Coccidioides presented with 3 months of malaise, nausea, weight loss of 30 pounds, and recurrent hypokalemia. He was recently switched from long-term fluconazole therapy to posaconazole around the time his symptoms began. His initial labs at our hospital were notable for low potassium (2.9 mmol/L, nl 3.5–5.5 mmol/L) and a random cortisol of 5.8 mcg/dL (nl ≥2.0 mcg/dL). A Cosyntropin stimulation test revealed elevated ACTH (168 pg/mL, nl 7.2–63.3 pg/mL) with minimal rise of cortisol from 4.6 to 7.2 mcg/dL at 1 hour after Cosyntropin administration (nl ≥18 mcg/dL at 1-hour post-Cosyntropin). His plasma renin activity was below detection (<0.6 ng/ml/h, nl 0.6–3.0 ng/mL/h), consistent with renin suppression from apparent mineralocorticoid excess. Hydrocortisone for glucocorticoid deficiency was started. A posaconazole determination indicated elevation (5240 ng/mL, usual therapeutic range ≥1000 ng/mL). His posaconazole was stopped, and he was switched back to fluconazole. Three months later, his symptoms were improved with regain of lost weight. Repeat Cosyntropin stimulation test showed ongoing primary glucocorticoid deficiency (ACTH 123 pg/mL, cortisol 4.1 mcg/dL at 1-hour post-Cosyntropin) but normal levels of plasma renin activity (1.2 ng/mL/h), aldosterone (8.6 ng/dL, nl ≤21 ng/dL), and potassium. Quantiferon TB and 21-hydroxylase antibody tests were negative. Hydrocortisone has been continued with plans to repeat Cosyntropin testing in 3 months to reassess.
Conclusion: Pseudohyperaldosteronism with glucocorticoid deficiency requiring hydrocortisone treatment has thus far not been reported with posaconazole. Our case shows that posaconazole may lead to true primary glucocorticoid deficiency that can persist after discontinuation of posaconazole and reversal of pseudohyperaldosteronism.
Reference: (1) Sanchez-Niño MD, Ortiz A. Unravelling drug-induced hypertension: Molecular mechanisms of aldosterone-independent mineralocorticoid receptor activation by posaconazole. Clin Kidney J 2018;11(5):688–90.
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