Endocrine Abstracts

Introduction: Cushing’s disease (CD) is the most common cause of hypercortisolism. Therefore, the majority of studies focused on the efficacy and safety of novel steroidogenesis inhibitors included CD patients only. This is exactly the case with osilodrostat – new potent inhibitor of 11β-hydroxylase. However, approximately 10% of hypercortisolism result from cortisol-secreting adrenal adenoma. Data on potential differences in the treatment with osilodrostat between CD and Cushing’s syndrome of adrenal origin (ACS) are lacking.

Aim: Hereby, we presents two patients with ACS, in whom, the response and doses of osilodrostat were different from CS patients regardless whether the CS patients were treated in our centre or described in the literature.

Cases: Case 1

A 55-year-old women with cortisol secreting left adrenal adenoma, with UFC 2× upper normal limit (UNL). Decompensated diabetes mellitus and hypertension were contraindications for surgery. Osilodrostat was started with a dose of 2 mg/day and gradually increased to 8 mg/day with – surprisingly – simultaneous increase in UFC to 10 × UNL, severe deterioration of hypertension and life-threatening hypokalaemia of 2.1 mmol/l, despite active potassium supplementation. Due to the extremely high hypercortisolism, the dose was increased by 5 mg every two days up to 45 mg, with gradual decrease of cortisol level and UFC normalisation with the dose of 45 mg/day.

Case 2

A 45-year-old women with ACS and UFC 5 × UNL, was treated with osilodrostat, starting from 2 mg/day and increasing by 2 mg/day every day, and then, from the dose of 10 mg/day, increasing by 5 mg every other day, with no cortisol reduction up to the dose of 20 mg/day. The dose was escalated up to 45 mg/day, and after a week of treatment UFC normalisation was reached. No side effects was observed, no potassium supplementation was required.

Conclusions: 1. Doses of osilodrostat required for ACS are usually much higher than those in CD.

2. Dose acceleration can be faster and the risk of overdosing and later necessity of dose reduction is low

3. Low initial doses can be ineffective or can even cause exacerbation of hypercortisolism

4. Typical dose which allowed to safe adrenalectomy with UFC slightly below upper normal limit was 45 mg/day

5. Side effects of osilodrostat can be rapid with severe hypokalaemia even despite active potassium supplementation or can be totally absent with potassium level above 4.0 mmol/l without any supplementation. Therefore, cloSemonitoring of potential side effects is mandatory.