Endocrine Abstracts

Introduction: We report the complexities in the management of two patients with functioning adrenocortical tumours (ACTs), presenting with features of androgen and cortisol excess, secondary to TP53 variants.

Case report: Patient 1 presented with androgen excess (P1, TVs 2mls, penis 10 cm) aged 18 months. He was a known carrier of a maternally inherited TP53 variant. Adrenal androgens were elevated, with a DHEAS level of 86 umol/l (0.0-1.9 umol/l). A urine steroid profile (USP) indicated an ACT. The diagnosis was confirmed by MRI, following a normal abdominal ultrasound. Patient 2 presented aged 19 months with virilisation (P1, TVs 3-4mls, penis 6 cm) and signs of cortisol excess (Cushingoid facies, hypertension and growth failure). He had a family history of cancer predisposition. He similarly had elevated adrenal androgens, with a DHEAS level of > 30 umol/l and a USP indicative of an ACT. His 24-hour urine free cortisol results were elevated, with a suppressed 9am ACTH and absent cortisol circadian rhythm. Patient 2 required amlodipine for pre-operative blood pressure stabilisation. Early open surgical resection was performed for both. Histology reported an ACT with no evidence of malignancy for Patient 1 and an ACT of uncertain malignant potential for Patient 2. DHEAS levels rapidly decreased to 0.1 umol/l for both patients. Patient 1 discontinued glucocorticoids after six months following contralateral adrenal gland recovery. Patient 2 remains on glucocorticoids and mineralocorticoids. Both continue under close clinical, biochemical and radiological surveillance. Behavioural management is a significant challenge. A TP53 variant of uncertain significance has since been identified in Patient 2.

Discussion: ACTs are rare in children, but may occur in genetically susceptible individuals. Genetic investigation and counselling must be offered to families with a positive TP53 mutation and irradiation should be avoided if possible. Abdominal ultrasound is the first line radiological investigation however a normal scan does not exclude ACT. For functioning ACTs, DHEAS is a useful post-operative tumour marker for residual disease detection. Recovery time of the contralateral adrenal axis varies. Long-term follow-up to include developmental assessment and behavioural management is essential, given the impact of adrenal disorders on the developing brain.