Endocrine Abstracts

A 57-year-old woman was referred in 2012 following an incidental finding of a pituitary macroadenoma. It measured 17×9 mm and was confined to the sella. There was no clinical or biochemical evidence of pituitary dysfunction. In 2017, she was found to have proximal myopathy, plethoric facies and purple abdominal striae. She was also on medication for hypertension and type 2 diabetes. There was no history of sleep apnoea, fractures or use of exogenous steroids. An MRI showed tumour shrinkage and screening tests revealed ACTH dependent Cushing's syndrome: cortisol following overnight dexamethasone = 307 nmol/l (NR <50 nmol/l), 24-h UFC = 390 (NR 50 – 270 nmol/24 h), cortisol 48 h post low dose dexamethasone = 227, and baseline ACTH = 59 ng/l. She was subsequently referred to the Imperial Pituitary Multidisciplinary Service in 2019, and underwent inferior petrosal sinus sampling (IPSS) which excluded ectopic ACTH: basal central-to-peripheral ACTH ratio of >2:1 and a CRH stimulated ratio of >3:1. This confirmed Cushing's disease and she was commenced on metyrapone, and rivaroxaban (for DVT prophylaxis). A trans-sphenoidal pituitary hypophysectomy was performed on 6th of June 2019 and histology confirmed a corticotroph adenoma. Unfortunately, her day 5+9 post-operative cortisol levels (taken 24 h after the last dose of glucocorticoid) remained elevated and a pituitary MRI showed residual tissue. This prompted re-explorative surgery. Despite this second procedure, her hypercortisolaemia persisted, and a day curve showed cortisol burden with loss of diurnal variation: cortisol 199 nmol/l (at 09:00), 324 nmol/l (at 12:00), 218 nmol/l (at 15:00) and 363 nmol/l (at 18:00). Interestingly, no pituitary lesion was detected on imaging or histology; and following discussion at the Pituitary MDT, bilateral adrenalectomy was proposed. Whilst awaiting adrenalectomy she reported significant weight reduction (around 15 kg) and a vast improvement in diabetic control. Her cortisol day curve (3 months following pituitary surgery) showed a lower cortisol burden: cortisol 187 nmol/l (at 09:00), 87 nmol/l (at 12:00), 51 nmol/l (at 15:00) and 144 nmol/l (at 18:00). In view of these results, her adrenalectomy has been cancelled, and the plan is for surveillance.

Discussion: 1. Is she in remission? If she relapses, what treatment strategies are appropriate?

2. What surveillance should be offered?

3. Given the 1500 h cortisol of 51 nM, should she be started on steroid replacement?