Endocrine Abstracts

Introduction: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of Cushing’s syndrome and is more often diagnosed as bilateral adrenal incidentalomas with subclinical cortisol production. It is mainly a heterogeneous disease, but familial cases have been reported. Treatment of PBMAH with overt Cushing’s syndrome is usually bilateral adrenalectomy with unilateral adrenalectomy occasionally used to normalize urinary free cortisol (UFC) in patients with less severe Cushing’s syndrome.

Case summary: 51-year-old male, known to have migraine, hypertension, dyslipidaemia and generalized anxiety disorder for which he takes topiramate 100 mgs bd, Lisinopril od, Indapamide 2.5 mgs od, and Atorvastatin 20 mgs od. He was investigated for chest pain with CT scan which shown incidental multiple bilateral intermediate adrenal lesions (Bilateral nodular adrenal hyperplasia, right > left). Further assessment in Endocrine clinic revealed central obesity, plethoric face and emotional liability, otherwise unremarkable history and examination. Investigations showed 24-hour urinary cortisol was 117 nmol (Normal value <165nmol/24hours) and his urine was negative for catecholamines. Overnight Dexamethasone suppression test was unsuppressed at 370 nmol/lstarting at 570 nmol/land his ACTH was suppressed at 0.4 pmol/l(2.0 - 11.0 pmol/l). His cortisol failed to supress with high dose Dexamethasone suppression test (day 1 cortisol 500 nmol/l, day 3 cortisol 561 nmol/l, day 5 cortisol 508 nmol/l). MRI scan of his pituitary showed a normal enhancing pituitary with no evidence of any pituitary tumour. Adrenal Venous sampling did not revealed any lateralization. Bilateral laparoscopic adrenalectomy was performed, and post-operative Hydrocortisone and fludrocortisone were started. Histology has shown Primary Bilateral Macronodular Adrenal hyperplasia (PBMAH). Furthermore, Genetic testing consist with a ‘genetic diagnosis of ARMC5-realted ACTH-independent macronodular adrenal hyperplasia type2’ with recommendation to refer the offspring to clinical genetics as would be 50% change of inheritance.

Conclusion: A significant proportion of what is thought to be sporadic cases of bilateral macronodular adrenal hyperplasia are due to ARMC5 genetic mutations and family history is not a reliable indicator. Patients with large multinodular adrenal gland and cortisol excess may be more likely to harbour ARMC5 germline mutation and there should be a low threshold for genetic testing.