A 37-year old gentleman with MEN 1 was referred to our Centre for further assessment. MEN 1 had manifested as recurrent primary hyperparathyroidism and multiple pancreatic gastrinomas. He complained of reduced libido, with absent early morning erections for the preceding 18 months. Biochemistry confirmed hyperprolactinaemia (prolactin 1494, NR 0625 mU/l, testosterone 12 NR 1028 nmol/l, LH 2.6 NR 212 IU/l, FSH 3.7 NR 1.78 IU/l). During investigation of his gastrinomas, an abdominal CT scan had demonstrated nodular adrenal glands. On direct questioning, the patient complained of weight gain, but had no other symptoms of Cushings syndrome. Clinical features of Cushings syndrome were confined to a plethoric facies and central obesity.
Twenty four hour collections for urinary free cortisol were elevated (1529, 1364 and 1541 NR 270 nmol/24 h). Failed suppression of serum cortisol following a low dose dexamethasone suppression test (96 nmol/l at T=48), with a basal ACTH of 18.8 ng/l (NR<30 ng/l) confirmed ACTH-dependent Cushings syndrome. Inferior petrosal sinus sampling (IPSS) localised a left-sided pituitary source of ACTH. Notably, prolactin measured during IPSS to confirm petrosal sinus cannulation, was elevated four-fold on the left-side. MRI pituitary demonstrated two separate pituitary microadenomas, in the left anterior and posterior midline of the pituitary, raising the possibility of a co-existent prolactinoma and ACTH adenoma. Initial transphenoidal hypophysectomy resected a single adenoma that stained for prolactin and not for ACTH. Further transphenoidal surgery, resected a second lesion which had histological features of ACTH hyperplasia.
Corticotroph hyperplasia is a rare cause of Cushings syndrome, yet prolactinomas are the most common pituitary tumour described in MEN 1. Double pituitary adenomas have rarely been described in patients with and without MEN 1, but, to our knowledge, this is the first reported association between ACTH hyperplasia causing Cushings disease and prolactinoma.
06 - 07 Nov 2006
Society for Endocrinology