Endocrine Abstracts

Introduction: Pituitary – dependent Cushing’s disease accounts for approximately 80% of endogenous Cushing’s syndrome but a target lesion is only detectable on MRI in 60% of cases. 11C-methionine PET CT improves detection of indeterminate pituitary lesions. Osilodrostat is a novel steroidogenesis inhibitor which reduces cortisol levels with resultant rise in ACTH and may further enhance the sensitivity of 11C-methionine PET CT in difficult cases.

Case Presentation: A 42 year-old woman presented with central weight gain, hypertension and proximal myopathy. Initial investigations were consistent with ACTH-dependent Cushing’s disease including raised morning cortisol (599 nmol/l) and failure to suppress following 1mg dexamethasone (219 nmol/l), with raised 24 hr urinary free cortisol (1907 nmol/l), midnight salivary free cortisol (26.2 nmol/l) and elevated ACTH (55.3 ng/l). Inferior petrosal sinus sampling (IPSS) showed central:peripheral ratio > 2.0 thus excluding ectopic ACTH. MRI pituitary did not demonstrate a clear surgical target and medical management was commenced with metyrapone, which was switched to osilodrostat due to inability to optimise cortisol levels and poor tolerability. Serum and free cortisol levels normalised by week five of osilodrostat (12mg/day). ACTH increased on osilodrostat and after 11 weeks of treatment, 11C-Methionine PET CT was performed (ACTH 135 ng/l, cortisol 145 nmol/l). A methionine-avid lesion was identified in the posterior-lateral pituitary and trans-sphenoidal resection was performed. This achieved biochemical cure with serum and free cortisol levels in the normal range and return of diurnal variation on cortisol day curves post-operatively.

Discussion: This case illustrates the diagnostic and management challenges in pituitary - dependent Cushing’s disease without a clear lesion on initial imaging. Adjunctive use of 11C-methionine PET CT can enhance imaging sensitivity for indeterminate lesions and additional ACTH stimulation through downregulation of the steroidogenesis pathway by osilodrostat may further improve detection.