Endocrine Abstracts

A case presents a 35 year old woman with a history of Cushing Disease (CD) diagnosed in 2014, who developed multiple complications of long lasting hypercortisolemia- obesity (BMI 55), poorly controlled diabetes mellitus (DM), heart failure, hypertension, hypercholesterolemia, mental disturbances and significant hepatic impairment. She underwent a non-radical pituitary adenoma removal in 2014 with subsequent radiotherapy in 2018. Choice of pharmacological treatment was challenged by patient’s great non-compliance and severe metabolic complications of CD. Due to significant elevation of liver function tests (LFT) she could not start either ketoconazole treatment or one of the clinical study drug. Pasireotid was contraindicated because of poorly controlled diabetes mellitus. Shortly she was treated with metyrapone, however due to side effects she refused therapy continuation. In December 2021 she consented to osilodrostat treatment. Pre-treatment laboratory evaluation showed sustained LFT elevation- alanine transaminase (ALT) 4×ULN, aspartate transaminase (AST) 1.7×ULN, gamma glutamyl transpeptidase (GGTP) 4×ULN, dyslipidemia (triglycerides 4 mmol/l, total cholesterol 7.4 mmol/l), non-controlled diabetes mellitus (glycohemoglobin- HBA1c%- 10.80 %), high free urine cortisol (1.7×ULN), elevated morning cortisol (32.2 mg/dl). In abdominal MRI liver steatosis with no other abnormalities was described. Since December 2021 patient started osilodrostat treatment with initial daily dose of 2 mg, followed by dose escalation in February 2022 to 4 mg daily. After 4 months of treatment we observed normalizing of serum morning cortisol (13.1 mg/dl), urine free cortisol (55.9 mg/day) and low late night salivary cortisol (0.091 mg/dl). ALT and AST started to lower down 1 year after treatment initiation, normalizing totally within 18 months since treatment. HBA1c% was going down gradually with significant drop after 12 months of treatment (7.2%) and normalisation after 24 months (6.2%). Prominent triglicerydes drop was observed 6 months since osilodrostat start and it normalised after 24 months. During treatment patient lost 3% of her baseline weight, thus the metabolic parameters improvement seems to be not related with weight changes. Liver evaluation on elastography 1 year since therapy start, showed liver steatosis and liver stifness value of 7.91 kPA. Osilodrostat is a steroidogenesis inhibitor which can be safely used in patients with Cushing Disease complicated with liver function impairment. Our case showed normalisation of LFTs during treatment with osilodrostat. Further multicenter studies are needed to investigate the link between hypercortisolemia, liver function and steroidogenesis inhibitors.