Endocrine Abstracts

Some patients with Cushing’s have only periodic hypercortisolism, known as cyclical Cushing’s, becoming eucortisolaemic or even transiently subnormal between periods of hypercortisolaemia. We report two cases and discuss the management.

A 23-year-old lady presented in March 2007 with Cushingoid features. Initial urinary free cortisol was raised at 594 nmol/l. A midnight cortisol of 568 nmol/l and post-48 h low dose dexamethasone cortisol of 351 nmol/l supported diagnosis of Cushing’s. CT scan of adrenals revealed slight bilateral hyperplasia. MR scan of the pituitary was normal. Inferior petrosal sinus sampling revealed no gradient of ACTH levels and no rise after CRH. She was commenced on metyrapone 250 mg tds and cortisol levels fell to <80 nmol/l. Metyrapone was therefore stopped, but the cortisol levels after stopping remained low, suggesting remission from Cushing’s syndrome with relative hypocortisolaemia. She remains off all medications and awaiting repeat assessments at regular intervals. Our second patient, a 58 year lady, initially presented in 2004, clinically Cushingoid. Serum cortisol was not suppressed by overnight dexamethasone (309 nmol/l). Twenty-four hour urinary cortisol was raised at 3112 nmol/24 h, and midnight cortisol was raised at 106 nmol/l. Subsequently her urine free cortisol measurements returned to normal with intermittent overactivity as shown:

Repeated MR pituitary scans during the years showed some asymmetry but no definite evidence of adenoma, and adrenal CT was normal. Petrosal sinus sampling, planned to be undertaken when hypercortisolemic, was not possible due to the unpredictability of the cycles. She has now been listed for bilateral adrenalectomy.

Cyclical Cushing’s is rare and classically three spikes and two troughs are required to establish the diagnosis. A review of 65 patients by Meinardi et al (EJE 157: 245, 2007) showed prevalence of site of origin as either a pituitary adenoma (54%), ectopic ACTH producing tumour (26%) or adrenal tumour (11%), the remaining unclassified. Awareness of the diagnosis and timing of investigations are important.