Posaconazole-induced primary adrenal insufficiency concomitant with pseudoaldosteronism under normal blood pressure

Several reports focus on azole-induced primary adrenal insufficiency (PAI); however, none have specifically focused on the absence of hypotension and hyperkalemia among the clinical features of adrenal insufficiency (AI). Here, we report a case of posaconazole-induced PAI with normal blood pressure. A 74-year-old male patient was diagnosed with lymphoma in July 2019 and underwent chemotherapy. He gradually began to experience anorexia, fatigue, and a fever of 37°C-38°C from mid-March 2022. He was diagnosed with pneumonia on April 4, 2022, and antibiotics and posaconazole at 300 mg daily were initiated post-hospitalization. Symptoms of anorexia, nausea, fatigue, and fever demonstrated no improvement despite the regression of the consolidation on the chest computed tomography. The early morning cortisol level was 2.4 μg/dL despite a high adrenocorticotropic hormone (ACTH) level (101.7 pg/mL). Therefore, we diagnosed the patient with PAI according to the low cortisol level (maximum of 8.6 μg/dL at 60 min) in a rapid ACTH stimulation test. Despite having PAI, the patient exhibited normal blood pressure and hypokalemia. Posaconazole was considered to cause PAI; therefore, it was discontinued, and hydrocortisone replacement was initiated. His symptoms improved, and rapid ACTH stimulation test reassessment 1 month after posaconazole discontinuation revealed normal basal ACTH, cortisol, and ACTH response. However, the renin-angiotensin-aldosterone system did not fully improve, as opposed to the hypothalamic-pituitary-adrenal axis. Posaconazole inhibits 11β-hydroxylase and 11β-hydroxysteroid dehydrogenase type 2, causing pseudohyperaldosteronism, which persists. Notably, posaconazole causes PAI without hypotension and hyperkalemia, which are its major clinical characteristics.

Posaconazole causes PAI within 1 month of initial administration. Posaconazole-induced PAI may not present with hypotension or hyperkalemia. The hypothalamic-pituitary-adrenal axis improves, but the renin-angiotensin-aldosterone system may take longer to recover, as changes persist even 1 month after posaconazole discontinuation. Hypokalemia treatment should continue carefully until pseudohyperaldosteronism resolution.