Escalating beyond standard dosing: High-dose osilodrostat in metastatic ACC associated Cushing syndrome — ASN Events
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Escalating beyond standard dosing: High-dose osilodrostat in metastatic ACC associated Cushing syndrome (#462)

Richard Yang 1 , Alia Tun Ismail 1 , Krupali Bulsari 1
  1. Endocrinology, Campbelltown and Camden Hospitals, Sydney, NSW, Australia

Background:

Metastatic adrenocortical carcinoma (ACC) can cause severe hypercortisolism that is difficult to control. Osilodrostat has been shown to be an effective steroidogenesis inhibitor for Cushing’s disease.

Case:

54-year-old women with metastatic ACC underwent left adrenalectomy plus nephrectomy and hepatic metastatectomy for a 11cm left adrenal tumour and liver metastases. Due to low cortisol levels in post-operative period, she was commenced on dexamethasone for steroid replacement along with chemotherapy, radiotherapy and mitotane therapy. She was unable to tolerated mitotane beyond 500mg twice daily due to gastrointestinal side effects. Unfortunately, disease progression was noted 6-7 months after surgery on FDG-PET with recurrence of disease at the left adrenal bed plus new liver and pulmonary metastases. 24-hour urine free cortisol (UFC) level began to rise, and she developed worsening symptoms of hypercortisolaemia with hyperglycaemia, hypertension, and recurrent bruising. Osilodrostat was initiated at 5mg twice daily however, 24-hour UFC continued to rise, from 925 nmol/24hour to peak 1628 nmol/24hour, despite uptitrating dose to 30mg twice daily. Symptoms worsened with new onset dyspnoea from malignant pleural effusion. To improve symptom management and reduce risk of venous thromboembolism, osilodrostat was increased to 50mg twice daily, leading to decline in 24-hour UFC to 323 nmol/24hour after 3 months and significant improvement in symptom burden.

Discussion:

Metastatic ACC associated hypercortisolaemia can cause significant morbidity. The use of osilodrostat for the management hypercortisolaemia in metastatic ACC is off label with small number of case reports showing efficacy. In our case, standard osilodrostat up to 30 mg twice daily was inadequate in controlling hypercortisolism. We demonstrated efficacy in using high dose osilodrostat for biochemical control of hypercortisolaemia with improved clinical symptoms. The use of high dose osilodrostat, up to 50mg twice daily, can be effective in achieving biochemical control of severe hypercortisolism in metastatic ACC.