Precipitated Adrenal Insufficiency by Osilodrostat and Fluconazole in Ectopic Adrenocorticotrophic Hormone Syndrome...

Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a challenging condition, particularly when the primary tumor cannot be localized. This case report described a patient with EAS and a concomitant pituitary tumor who developed adrenal crisis while receiving osilodrostat for EAS and fluconazole for cryptococcal infection before bilateral adrenalectomy.

A 27-year-old man presented with progressive fatigue, proximal muscle weakness, resistant hypertension, and weight gain. Laboratory tests showed significant hypercortisolemia. Magnetic resonance imaging showed a 5 mm pituitary tumor, but inferior petrosal sinus sampling confirmed ectopic ACTH source. Given the severity of hypercortisolism, osilodrostat was initiated. Subsequently, a positron emission tomography scan revealed a hypermetabolic right lung nodule. Biopsy confirmed the nodule to be a cryptococcus infection for which fluconazole was started. Due to failure to locate the primary tumor, bilateral adrenalectomy was planned. Two weeks after starting fluconazole, the patient developed adrenal insufficiency prompting hospital admission. Osilodrostat was held and stress dose steroid was initiated. He underwent bilateral adrenalectomy and had significant improvement in his clinical status.

This case presented a patient with EAS and a concomitant pituitary tumor. Osilodrostat was used before bilateral adrenalectomy. After discovery of a rare opportunistic fungal infection, antifungal treatment was initiated which appeared to have synergistic action with osilodrostat in suppressing cortisol production.

Presence of a pituitary tumor in ACTH-dependent hypercortisolemia does not always signify Cushing disease. Concomitant use of adrenal steroidogenesis inhibitors may precipitate adrenal crisis.