Endocrine Abstracts

Case history: A 70 years old man with longstanding resistant hypertension on five antihypertensive agents, type two diabetes and raised BMI at 35.6 was referred to the endocrinology clinic for exclusion of possible Cushing’s disease. Clinically he had truncal obesity with plethoric face but no telangiectasia, easy bruising, purple striae or myopathy.

Investigations: Endocrine examinations revealed normal 24 h urine free cortisol levels on two separate occasions (82 and 152 nmol/l, reference range <270 nmol/l). Overnight dexamethasone suppression test did not suppress the cortisol level (132 nmol/l). Cortisol also failed to suppress after low dose and high dose dexamethasone suppression tests (111 and 253 nmol/l respectively). In-patient midnight cortisol level was 39 nmol/l while 0900 h cortisol was 169 nmol/l showing intact circadian rhythm.

Results and treatment: In conclusion he had normal 24 h urine free cortisol and midnight cortisol but cortisol levels failed to suppress after ODST, LDDST or HDDST. Clinical history identified he was on long-term treatment with phenytoin and phenobarbitone for epilepsy. We believe these two agents are responsible for the failure of dexamethasone suppression in view of their previously well reported enzyme induction effect.

Conclusions and points for discussion: While current antiepileptic agents include lamotrigine, levetiracetam, topiramate, some patients are still well controlled on older agents as phenobarbitone and phenytoin. A good clinical history including drug history is still a necessity before enrolling on complicated dynamic function tests which are not without patient inconvenience and financial burden to a department. Agents that induce CYP3A4 include phenytoin, phenobarbitone, carbamazepine, rifampicin, and alcohol. These are well recognised to produce falsely positive dexamethasone suppression tests by accelerating its clearance. In consequence we only rely on 24 h urine free cortisol levels and midnight cortisol as screening tests for such cases and we need to bear in mind their limitations too.