Cyclic Cushing’s – a diagnostic challenge
Zac-Varghese, S., Mendoza, N., Mehta, A., Roncaroli, F
History and examination
A 49 year old gentleman presented with clinical features of Cushing’s syndrome. He had a two year history of 15 kg weight gain, type 2 diabetes mellitus and had recently fractured his left fibula. He had previously been investigated and was found to have an elevated random cortisol of 1,922 nmol/L. In addition, he had failed an overnight dexamethasone suppression test with a cortisol following suppression of 330 nmol/L with an ACTH of 70 ng/L. He had reports of an MRI pituitary scan which did not suggest an obvious pituitary lesion and a CT abdomen was also reported as normal. Physical examination revealed central obesity and abdominal striae.
Two 24 hour urine collections for urinary free cortisol were obtained. The first was elevated at 281 nmol/L (normal values <270) and the second normal, 217 nmol/L. We also carried out a dexamethasone suppression test. On day 1, the cortisol suppressed to 41 nmol/ L and on day 2 the cortisol level increased to 185 nmol/ L. Results were reported in real-time, and despite the apparent normal cortisol response after the first day, the test was allowed to continue. The variance in cortisol levels on days 1 and 2 was unexpected. The test was repeated and on the second occasion the cortisol increased on day 1 and suppressed on day 2. Anterior pituitary investigation did not reveal any other abnormality. We next undertook an IPSS, the results of which excluded an ectopic source of ACTH secretion and demonstrated lateralisation of the tumour to the right
Explorative TSPS was arranged to investigate a pituitary ACTH secreting tumour. Our experienced pituitary surgeon has dealt with several cases of microadenoma where no lesion is visible on MRI scanning. However, the patient was not cured after a limited right hemihypophysectomy, so he went on to have a more extensive procedure. On the second occasion a right sided tumour was identified and removed; histological analysis confirmed an ACTH chromophobe adenoma.
Our patient had clinical features of Cushing’s and biochemical features of cyclic Cushing’s. Cyclic Cushing’s is demonstrated by episodic hypercortisolaemia and is most commonly caused by Cushing’s disease although has been reported to be associated with Ectopic ACTH secretion. The mechanism of periodicity is unknown but may include infarction, necrosis, tumour calcification or patient stress.