A 32 year old man with a history of epilepsy since childhood presented in 1992 with a grand mal seizure and clinical features of tuberous sclerosis (TSC). One year later he was referred with classical Cushingoid features. His serum Na was 140 mmol/l, K 3.4 mmol/l, 9 AM cortisol 1018 nmol/l with lack of diurnal variation and ACTH 42-50 ng/l. Urinary cortisol: 797 nmol/24 h. After overnight, low and high dose dexamethasone suppression, cortisol was 1018, 1154, and 62 nmol/l respectively. Adrenal CT revealed bilateral adrenal enlargement and brain MRI revealed calcified periventricular lesions and a rounded area of low signal within the pituitary. His condition deteriorated and he underwent emergency bilateral adrenalectomy. Histology was consistent with adrenocortical hyperplasia. 11 years later he was readmitted with Addisonian crisis secondary to poor compliance with hydrocortisone replacement, and seizures. He was treated with IV fluids and hydrocortisone but complained of headaches, difficulty in walking, and deterioration in his mental state. Repeat MRI showed a deep thalamic cystic lesion causing hydrocephalus, consistent with a giant cell xanthoastrocytoma. At neurosurgery he underwent frontal craniotomy, biopsy of the tumour, and fenestration of the cyst. 6 months later he remains well on hydrocortisone replacement and antiepileptic medication. His ACTH remains raised at 134 ng/l, and MRI revealed a pituitary microadenoma. He is awaiting further treatment with either radiotherapy or transphenoidal hypophysectomy. TSC is caused by mutations in one of two tumour suppressor genes, TCS1 and TCS2 on chromosome 9 and 16 respectively. Although the TSC gene products (hamartin and tuberin) are expressed in most tissues, including the anterior pituitary, the most common TSC-associated hamartomas are limited to relatively few organs: brain, heart, kidney, and skin. To our knowledge, this is the first report of a case of florid Cushing's associated with tuberous sclerosis.
03 - 05 Nov 2003
Society for Endocrinology