Endocrine Abstracts

Introduction: In up to 50 percent of Cushing’s disease patients, corticotroph adenomas are not clearly identified on MRI and long-term medical treatment to lower cortisol may be needed. Osilodrostat, which inhibits 11 beta hydroxylase, is effective in normalising urinary free cortisol (UFC). We are the UK’s first centre to use osilodrostat for Cushing’s disease in MRI negative patients.

Method: Five patients (one male) with Cushing’s disease (excluded ectopic ACTH secretion by IPSS) started osilodrostat when there was no demonstrable adenoma on pituitary MRI.

Results: An initial daily dose of osilodrostat at 2-4 mg was started, followed by dose increments every 2-4 weeks aimed at normalising UFC levels. By week 2, the median daily dose was 4 mg, increasing to 8 mg by week 12. There were significant reductions in UFC concentrations, with a median decrease of 57.29% (range: -67.4% to +12.9%) after 2 weeks and 86.2% (range: -98.9% to -50.6%) after 12 weeks. Four out of five patients achieved normal UFC concentrations by week 12. Median ACTH concentration rose from 51.8 ng/l to 116 ng/l at week 12 (normal range: 10-30 ng/l). Mild to moderate increases in testosterone levels in female patients were noted without causing clinically apparent hyperandrogenism (median 1.5 nmol/l at baseline to 7.3 nmol/l at week 12). Blood pressure improved, leading to reduced antihypertensive medications in three of four patients. One patient with type 2 diabetes mellitus experienced a significant reduction in HbA1c from 80mmol/mol to 50 mmol/mol by week 20. No side effects were reported.

Conclusion: Osilodrostat rapidly normalises UFC levels and is well-tolerated. ACTH levels increased during treatment, possibly due to reduced negative feedback after achieving eucortisolaemia. Further studies are needed to assess long-term efficacy.