Cushing's syndrome hypertension and virilisation from a malignant adrenal cortical tumour in a 5 months old baby with Li Fraumeni syndrome (#114)
OB presented to a paediatrician at 5 months of age with a 2 month history of virilisation, linear growth failure and slowing head growth. His weight gain was maintained but he had delayed gross motor milestones. He was noted to have had recent pubic hair and penile growth, significant acne on face and trunk with body odour. His blood pressure was elevated. The provisional diagnosis was Cushing’s syndrome due to adrenal tumour with mixed androgen and glucocorticoid secretion was made and subsequent investigation confirmed the clinical findings and identified a 3cm left adrenal mass on ultrasound. He was referred to Sydney Children Hospital for staging and surgical management.
He was born by LUSCS at 41 weeks weighing 4.9kg pregnancy complicated by maternal pregnancy induced hypertension and was treated for neonatal hypoglycaemia with formula feeding. His father had been diagnosed with Non Hodgkin’s lymphoma at 2-3 years earlier and mother had PCOS, duplex kidney with scarring and hypertension from 22 years of age.
The initial blood tests showed normal renal function and hypokalaemia of 3.3 mmol/L. Endocrine evaluation showed an elevated midnight cortisol with low ACTH. The testosterone and DHEAS were elevated with normal renin and aldosterone. The CT abdomen confirmed the complex left adrenal mass with no metastases seen in lungs or on bone scan.
He underwent laparoscopic left adrenalectomy to removal of a 20.8 gram tumour, indeterminate, stage 1 (virilisation alone) adrenal cortical carcinoma. He required stress dose of hydrocortisone and antihypertensive peri-operatively. The tumour had favourable prognostic features and no chemotherapy was required. Postoperative surveillance included regular MRI imaging and biochemistry
At 9 months the Cushingoid features and virilisation had resolved, cortisol levels were normal, testosterone and DHEAS levels and quarterly MRI scans remain normal. Short synacthen test demonstrates HPA axis recovery. Literature review revealed that a 5 year survival rate of 91% with stage 1-2 disease. Higher grade tumours show a poorer response to chemotherapy.
Genotyping identified a de novo TP53 germline mutation in OB (with both parents being normal) confirming suspicion of Li Fraumeni Syndrome, a rare autosomal dominant cancer syndrome. Li Fraumeni syndrome is associated with increased susceptibility to various cancers in particular, breast, brain (esp. choroid plexus), bony and soft tissue sarcomas, adrenal cortical carcinoma and acute leukaemias.