Posaconazole-Induced Primary Adrenal Insufficiency

Presentation Number: SUN 411
Date of Presentation: April 2nd, 2017

Lauren Karp Brooks*1, Silpa Poola-Kella1, Ann Miller2 and Rana Malek3
1University of Maryland, 2University of Maryland Medical Center, 3University of Maryland Medical Center, Baltimore, MD

Abstract

Posaconazole-Induced Primary Adrenal Insufficiency

 

Lauren K. Brooks, Silpa Poola-Kella, Ann Miller, and Rana Malek

Division of Endocrinology and Nutrition, University of Maryland School of Medicine

 

Introduction:

Posaconazole is an azole used in treatment and prophylaxis of a broad spectrum of fungal infections. Antifungals such as ketoconazole have been shown to cause primary adrenal insufficiency (AI) as a result of direct inhibition on the steroidogenesis pathway.(1) There is only one reported case of primary AI induced by posaconazole in a patient with mucormycosis.(2) We report two cases of posaconazole-related primary AI.

 

Clinical cases:

 

Case 1

A 42-year-old man with end stage renal disease (ESRD) was diagnosed with osteomyelitis due to Cerinosterus cyanescens. He was placed on posaconazole 400mg po twice daily. While hospitalized, he was evaluated for hypoglycemia refractory to a dextrose 10% drip. Hypoglycemia panel revealed insulin level of 1.0 uIU/mL, C-peptide of 2.4 ng/mL, pro-insulin of 3.0 pmol/L, negative sulfonylurea screen, and cortisol of 6 mcg/dL. Diazoxide was temporarily initiated to treat hypoglycemia. He failed a cosyntropin stimulation (CS) with time 0, 30-minute, and 60-minute cortisol levels of 9.5 mcg/dL, 9.5 mcg/dL, and 10.1 mcg/dL respectively. ACTH level was 244.1 pg/mL. He was started on hydrocortisone dosed for body surface area (BSA), and hypoglycemia resolved. Fludrocortisone was deferred due to ESRD and concern for volume overload.

 

Case 2

A 62-year-old man with history of chronic myelomonocytic leukemia was admitted for hematemesis and failure to thrive. He reported progressive fatigue and intermittent nausea and vomiting. He noted prior prolonged steroid courses, but no use within the last year. He had recently discontinued prophylactic posaconazole 300mg daily due to concern that nausea and vomiting were an adverse effect. He was assessed for AI with an AM cortisol of 1.9 mcg/dL followed by failed CS test with cortisol level of 3.7 mcg/dL and 4.1 mcg/dL at 30- and 60-minutes respectively. ACTH level was 154.6 pg/mL. 21-Hydroxylase antibodies were undetectable rendering autoimmune etiology unlikely. It is hypothesized that posaconazole led to primary AI in this case. The patient’s symptoms improved with initiation of hydrocortisone dosed for BSA and fludrocortisone 0.1mg daily.

 

Conclusion

In these cases, we demonstrate prolonged use of posaconazole is associated with primary AI. As there is increasing use of posaconazole to treat and prophylax against invasive fungal infections, knowledge of the potential risk of AI is important and must be included in the differential when these patients present with hypotension, hypoglycemia, and failure to thrive.

 

Nothing to Disclose: LKB, SP, AM, RM