Endocrine Abstracts

JOINT2542

Background: Optimal long-term outcomes in Cushing’s disease (CD) rely on precise localisation and complete resection of the ACTH-secreting adenoma while preserving normal pituitary function. However, adenomas can sometimes evade detection on conventional MRI. 11C-methionine PET/CT (11C-MET PET/CT) has emerged as an alternative imaging modality that may improve visualisation of these elusive tumours. We hypothesised that preoperative cortisol-lowering therapy would lead to increased ACTH levels, heightened tumour metabolic activity, and enhanced 11C-MET PET signal intensity. Osilodrostat, a potent 11-β-hydroxylase inhibitor, has demonstrated superior efficacy and tolerability compared to traditional steroidogenesis inhibitors such as metyrapone and ketoconazole.

Case: A 28-year-old man with a history of juvenile arthritis, total hip replacement, and postoperative pulmonary embolism presented with uncontrolled hypertension, centripetal obesity, purple striae, and significant weight gain, consistent with Cushing’s syndrome (CS). Laboratory investigations confirmed ACTH-dependent hypercortisolism, with markedly elevated post-1 mg dexamethasone cortisol of 807 nmol/l (<50 nmol/l), ACTH of 56.7 ng/l (10–30 ng/l), and 24-hour urinary free cortisol (UFC) of 774 nmol/24h (0–164 nmol/24h). Salivary cortisol and cortisone levels were 13.5 nmol/l (<2.6 nmol/l) and 42.7 nmol/l (<18 nmol/l), respectively. Inferior petrosal sinus sampling (IPSS) ruled out an ectopic source of ACTH secretion, however, MRI failed to identify a discrete pituitary adenoma. Functional imaging with 11C-MET PET/CT demonstrated equivocal tracer uptake near the left cavernous sinus, but did not provide definitive adenoma localisation. Given persistent hypercortisolism, the patient was initially treated with metyrapone but intolerance, leading to a switch to osilodrostat (2 mg twice daily, titrated to achieve eucortisolaemia). With cortisol normalisation, ACTH levels tripled, suggesting increased tumour metabolic activity. After three months of sustained eucortisolaemia, repeat 11C-MET PET/CT revealed a markedly increased focal tracer avidity near the left cavernous sinus, providing a precise target for transsphenoidal surgery.

Conclusion: This case highlights a novel preoperative strategy for enhancing adenoma detection in CD. Cortisol-lowering therapy may improve the sensitivity of functional imaging, enabling more accurate tumour localisation and optimising surgical outcomes. If validated in larger cohorts, this approach could significantly enhance surgical cure rates while preserving normal pituitary function.