Endocrine Abstracts

In 2009 a 39 year old gentleman presented to the Endocrine clinic with symptoms, signs and biochemistry consistent with severe glucocorticoid excess (urinary free cortisol level was significantly raised at >1380mol/24 hours, normal up to 124; early morning cortisol levels varying between 760nmol/land 1225nmol/lwith failure of suppression on a low dose dexamethasone suppression test). An ACTH level taken at this time was 43ng/l. He underwent an MRI pituitary gland which showed a normal gland with no evidence of an adenoma. He also underwent inferior petrosal sinus sampling; this showed consistent ACTH level several minutes following CRH stimulation; confirming ectopic ACTH secretion. Cross-sectional and nuclear medicine imaging showed no evidence of an ectopic source of ACTH. He was started on a combination of metyrapone, ketoconazole and hydrocortisone, via a block and replace regimen, to manage his symptoms as discussions and decisions were made about definitive intervention. Although initially hesitant, hypercortisolaemic complications (including vertebral crush fractures, reduced mobility and difficult glycaemic control) were important in the patient agreeing to a bilateral adrenalectomy. This was performed with good outcome at the end of 2009. He was started on hydrocortisone and fludrocortisone replacement and made significant improvement in his physical symptoms. He returned to work and remains well, active on maintenance SSRI therapy for mood. Between 2010 and 2022 he had intermittent imaging, recognising the issue of radiation exposure, but no source of ACTH production was identified. In December 2022, 13 years after the original diagnosis, a Dotatate scan identified a 9mm left lower lobe lung nodule demonstrating somatostatin receptor activity. He has subsequently been referred to the thoracic surgeons for removal. Ectopic ACTH secretion accounts for around 10% of cases of ACTH-dependent Cushing’s disease. The clinical features are similar to that of a pituitary source of Cushing’s, but frequently more severe. Having confirmed ACTH-mediated cortisol excess, the gold standard investigation to differentiate a pituitary from an ectopic source is inferior petrosal sinus sampling before and after injection of CRH.¹ Ideally the definitive management plan would be to remove the source of ectopic ACTH however as seen in this case the identification of this ectopic source can be difficult and given debilitating symptoms of Cushing’s this may be time sensitive. Bilateral adrenalectomy is an excellent treatment in this situation but efforts should continue to locate the primary source of ACTH excess.