A 14 year old girl, with a family history of MEN1, presented with secondary amenorrhoea and weight gain. Biochemical investigation revealed raised 24-hour urinary free cortisol excretions (1455, 1190, 614 nmol/24 hours; normal <290) and failure of cortisol suppression following 48 hours of low dose (0.5 mg qds) dexamethasone (199 nmol/l to 202 nmol/l). High dose dexamethasone administration (2 mg qds) for 48 hours resulted in further suppression of serum cortisol to 49 nmol/l. ACTH was easily measurable (37.5 pmol/l) but MRI of the pituitary failed to show clear evidence of an adenoma. Bilateral inferior petrosal sinus sampling (IPSS) failed to support a pituitary source for her hypercortisolism, though there was a modest rise in peripheral ACTH levels post-CRH. CT scanning of the thorax and abdomen was normal but endoscopic ultrasound showed a well circumscribed 5 mm lesion in the head of the pancreas. To determine whether this was a source of ectopic ACTH production, ACTH samples were obtained peripherally and at various drainage points from the coeliac axis via the trans-hepatic route. There was no convincing step-up in the ACTH gradient. Subsequent repeat pituitary MRI with dynamic post-contrast image acquisition showed an area of relative delayed enhancement on the left side of the gland consistent with a microadenoma. She underwent transsphenoidal adenomectomy with a postoperative cortisol confirming remission of the disease. Cushings syndrome is a rare presentation in MEN1 and this case illustrates the difficulties in determining the underlying source of cortisol excess in some of these patients. Furthermore, the data indicate that patients with a central:peripheral ratio suggestive of a non-pituitary source of ACTH in MEN1 may still have Cushings disease. Transsphenoidal pituitary exploration is indicated in cases of negative IPSS where search for an ectopic source is unrewarding, particularly if peripheral ACTH levels rise with CRH administration.
01 - 05 Apr 2006
European Society of Endocrinology