Endocrine Abstracts

Introduction: Endogenous Cushing’s disease is a serious and rare endocrine disorder. Medical therapy is mostly used as second-line treatment after failed surgery or recurrence and comprises several pituitary-directed drugs, glucocorticoid receptor blocker and adrenal steroidogenesis inhibitors such as osilodrostat. We here describe a case of a Tunisian patient with uncured cushing’s disease who developed iatrogenic adrenal insufficiency in the setting of Osilodrostat treatment.

Case Presentation: A 46-year-old female presented to our department with invalidant asthenia and abdominal pain. She has an uncured cushing’s disease, following transsphenoidal surgery, complicated with diabetes and hypertension. There was no visible residue on the post operative pituitary MRI. Adrenal CT-scan showed: Nodule of the external arm of the left adrenal gland of 30x17 mm with spontaneous density 7UH, Nodule of the external arm of the right adrenal gland of 15×9 mm with spontaneous density 7UH. She was proposed for bilateral adrenalectomy which was not performed; hence she was given osilodrostat with an initiation dose of 2 mg *2/day. The patient wrongly took a dose of 7 mg *2/day for 13 days then consulted us with an acute adrenal insufficiency: asthenia, vomiting and abdominal pain. Physical examination showed melanoderma with low blood pressure at 80/60 mm Hg. Basal cortisol was low at 17 ng/ml. Natremia and kaliemia were in the normal ranges. Osilodrostat was stopped and hydrocortisone was commenced (200 mg/day). The dose of hydrocortisone was rapidly decreased to 20 mg/day, and osilodrostat was reinitiated (5 mg in the morning, 5 mg in the evening) on Day 7.

Discussion: The effective cortisol inhibition achieved by osilodrostat therapy in Cushing’s disease has been demonstrated by several studies. Detailed education of patients treated with osilodrostat should be systematically performed. Titration should be very progressive, or the dose increase could be more rapid in patients for whom a ‘block and replace’ approach may appear necessary. Given the risk of adrenal insufficiency in this setting of a highly effective drug, our case suggest that ‘block and replace’ approach should be systematically considered in patients treated with osilodrostat.