ACTH-dependent severe hypercortisolaemia treated with osilodrostat and etomidate combination therapy - a case report. 

L. Dzialach*^a (Dr), J. Sobolewska^a (Dr), W. Respondek^b (Dr), A. Wojciechowska-Luzniak^a (Dr), P. Witek^a (Prof)

^a Medical University of Warsaw, Department of Internal Medicine, Endocrinology and Diabetes, Warsaw, POLAND ; ^b Department of Internal Medicine, Endocrinology and Diabetes, Mazovian Brodno Hospital, Warsaw, POLAND

* l.dzialach@wp.pl

Introduction

Severe hypercortisolaemia (SH) is a life-threatening condition defined as a notably elevated random serum cortisol level (>36μg/dL) or 24-hour urinary free cortisol level higher than fourfold the upper limit and/or intense hypokalaemia (<3.0mmol/L). In cases of life-threatening hypercortisolemia, achieving control can be difficult with standard therapy. Treatment efficiency with higher doses may be limited by drugs side effects, which prompts consideration of the combinative therapy. We report a 32-year-old female with ACTH-dependent SH brought into control in non-ICU conditions through combined therapy of two steroidogenesis inhibitors: etomidate and osilodrostat, and then maintaining a stable cortisol level with osilodrostat monotherapy.

Observations

The patient was admitted to the Endocrinology Clinic due to the general condition’s deterioration, polydipsia, polyuria, disturbance of consciousness, and profound hypokalemia. A significant degree of ACTH-dependent hypercortisolemia has been identified (UFC: 7155mg/24h, serum cortisol: 106 mg/dL, ACTH: 167 pg/mL). Initially, treatment with osilodrostat in increasing doses was conducted with a temporary improvement. Then, due to the persistent hypokalemia despite supplementation, oedema, and slow decrease in cortisol concentration, accompanied by deterioration of well-being, treatment with etomidate began simultaneously with osilodrostat in a gradually increased dosage. The doses of etomidate and osilodrostat were adjusted and titrated according to cortisol, potassium, glucose, and blood pressure measurements. The patient tolerated therapy well, without side effects, and obtained from +1 to 0 points on the RASS scale. After the correct levels of cortisol and potassium were obtained, the therapy with etomidate was ended and the treatment with osilodrostat dose according to the hormonal assessments was continued.

Discussion

To conclude, we report a case of ACTH-dependent SH successfully treated with a well-tolerated combination of osilodrostat and etomidate. This approach reduced the risk of medications sides effects or adrenal insufficiency occurrence in non-ICU conditions. A higher beginning dose of osilodrostat, more rapid dose titration, or earlier involved etomidate should be taken into consideration to increase the regimen efficacy, although, it may require the "block and replace" strategy. Further observations are needed to confirm the efficacy and safety of such approach and the optimal drug dosing schedule.

The author has declared no conflict of interest.