Endocrine Abstracts

Posaconazole is a member of triazole antifungal family. It is frequently used prophylaxis and treatment in invasive fungal infections. Among the azole group antifungals, ketoconazole is well known to affect steroidogenesis through cytochrome P450 enzymes, however, posaconazole-induced adrenal insufficiency has been reported in only two cases in the literature. Here, we present our case of adrenal insufficiency induced by posaconazole.

A 54-year-old male applied to Hacettepe University Hospital with fever and weakness. The patient with anemia, leukocytosis, and thrombocytopenia was followed up with the diagnosis of standard-risk acute myeloid leukemia (AML). His history was beginning with acute retinal artery thrombosis ten years ago. The patient with JAK2V617F mutation was diagnosed with overlap of myelodysplastic syndrome/myeloproliferative neoplasm and followed up with supportive blood product replacement if necessary. Calcitriol treatment was started, who had primary hypoparathyroidism during follow-up. After four years of hypoparathyroidism, thrombosis was detected in multiple veins simultaneously with pulmonary thromboembolism and primary hypothyroidism, then hydroxyurea and levothyroxine were started. He had received posaconazole for invasive fungal infection during AML treatment. He has persistently hypoglycemia, hypothermia, hypotension18th day on posaconazole treatment. Sodium and potassium level 149 mEq/l, 3.4 mEq/l respectively, that day. We suggest that he had adrenal insufficiency, with appropriate clinical and laboratory features. After taking the tests for arterial blood gas, ACTH, cortisol, and blood culture, treatment for adrenal insufficiency was started. Cortisol 2 mg/dl, ACTH 75 pg/ml, testosterone < 13 ng/dl and DHEA-SO₄ 21 mg/dl were observed in the blood sample taken at 6 PM. At the end of 12 hours, his clinical and laboratory response was dramatic. Sepsis is ruled out with this clinical and laboratory results, also no bacterial growth on the blood culture after five days. Posaconazole treatment was terminated, because it may cause adrenal insufficiency. In our patient, steroidogenesis appears to be affected as a whole under posaconazole treatment. He used steroid therapy for 45 days. His complaints did not recur during steroid dose reduction and after discontinuation of therapy. Together with the abdominal MRI and CT scans, which shows that adrenals were completely normal,and extensive iron accumulation on the liver, and we defined our patient as posaconazole-induced adrenal insufficiency on the background of hemochromatosis. We think that with the increase in prophylactic use of posaconazole, similar cases will increase. With the third case we present in the literature, clinicians should be careful in terms of adrenal insufficiency developed due to posaconazole use.