Endocrine Abstracts

Congenital adrenal hyperplasia (CAH) is a group of inherited disorders, characterised by impaired cortisol synthesis. 21-hydroxylase deficiency (21OHD) accounts for >95% of CAH cases. Lack of negative feedback on the hypothalamic–pituitary–adrenal (HPA) axis results in increased adrenal androgen production due to elevated steroid precursors, such as 17-hydroxyprogesterone, that are shifted towards androgen synthesis. Long term sequelae of poor CAH control include development of testicular adrenal rest tumours (TART) and adrenocortical tumours, with high ACTH concentrations likely contributing to their development. Up to one third of adults with 21OHD may harbour an adrenal tumour. Although there is no evidence that adrenocortical carcinoma (ACC) is more prevalent in 21OHD, urine steroid profiling (USP) has been shown to be a powerful tool to discriminate ACC from benign adrenocortical adenoma (ACA). Here we present the case of an 8 year old boy with salt wasting 21OHD, originally presenting in the neonatal period. There had been long standing challenges with management of his condition and he had known bilateral TART. On ultrasound and subsequent MRI he was also found to have a non-specific left adrenal nodule. To investigate this further, USP was performed which showed high levels of 17-hydroxyprogesterone and 21-deoxycortisol metabolites, consistent with poorly controlled 21OHD, but unexpectedly showed highly elevated 11-oxo-pregnanediol, a corticosterone metabolite. This metabolite is not a feature of the 21OHD metabolome, but has previously been seen in association with ACC. AFP, plasma metanephrines and total hCG were normal. To determine whether the 11-oxo-pregnanediol production was under HPA axis control, a long low dose dexamethasone test in conjunction with USP was performed. The 11-oxo-pregnanetriol suppressed in response to the dexamethasone, establishing that it was under HPA axis control and so ruling out autonomous production/ACC. Following excision of the tumour, histological features were compatible with an ACA. Subsequent USP showed barely detectable 11-oxo-pregnanediol, confirming the suspicion this was an adrenal tumour product. This case highlights that USP can be used alongside a long dexamethasone suppression test in 21OHD patients with adrenal tumours, to assess potential tumour metabolites, and post-resection can be used to assess recurrence or completeness of resection.