Osilodrostat in patients with persistent or recurrent Cushing's Disease: a real-life single center experience  

A. Diamantopoulos*^a (Mr), P. Mourelatos^a (Mr), M. Koulenti^a (Mrs), E. Partsalaki^a (Mrs), M. Giannakou^a (Dr), DA. Vassiliadi^a (Dr), S. Tsagarakis^a (Dr)

^a Department of Endocrinology, Diabetes and Metabolism, National Expertise Center for Rare Endocrine Disorders and member of the Endo-ERN, “Evangelismos” General Hospital of Athens, Athens, GREECE

* aris_diamad@yahoo.gr

Introduction

Transphenoidal adenomectomy (TSA) remains the first-line treatment for Cushing's Disease (CD). However, the rates of both unsuccessful TSAs and recurrent CDs mandate the use of other treatments, such as medical therapy. Herein we report our real-life experience with the use of osilodrostat, a recently approved CYP11B1 inhibitor, in patients with CD, who were already on another medical therapy.

Material and Methods

Five patients with persistent/recurrent CD after TSA were included. All patients were on either single therapy with metyrapone (3 patients) or combination with pasireotide (1 patient) or ketoconazole (1 patient). Transition to osilodrostat was decided due to inadequate control of CD, significant metyrapone-induced hyperandrogenism or due to patient’s preference for fewer tablets per day. Cushing’s control was evaluated by the mean value of two 24h-Urinary Free Cortisol (mUFC) levels and a 5-point day rhythm of serum cortisol (CortMean).

Results

Median treatment duration was 45 weeks (range 23-68). Daily doses of osilodrostat were 4-10mg. In 2 patients uncontrolled on medical treatment, cortisol status (mUFC decrease: -52% and -90%, CortMean reduction: -14% and -68%) and comorbidities improved on osilodrostat. In 2 patients, who were controlled by medical treatment, remained also under control while on osilodrostat, but with fewer daily tablets. One patient, previously taking metyrapone and ketoconazole, showed no response to 10mg of osilodrostat daily and the dosage is being up-titrated. ACTH levels increased in most patients. One patient developed adrenal insufficiency on 8mg-dose and subsequently the dose was reduced to 4 mg daily. No side effects were observed while, on the contrary, testosterone levels were normalized in 3 patients (previously increased during metyrapone administration).

Conclusions

Osilodrostat treatment resulted in control of hypercortisolemia in patients unresponsive to previous medical therapies and sustained control but with a better dosing regimen and fewer side-effects in those who were already controlled. Based on our preliminary experience, it seems that osilodrostat is a promising effective and safe choice for the treatment of patients with CD with persistent or recurrent disease.

The author has declared no conflict of interest.