The long search for an occult ectopic ACTH-producing tumour
E Mills, A Naqvi, C Uduku, F Wernig & JF Todd, Imperial Centre for Endocrinology, Endocrine Unit, Hammersmith Hospital, Imperial College Healthcare NHS Trust
Ectopic adrenocorticotropic hormone (ACTH) production accounts for 10-20% of all endogeneous Cushing’s syndrome. The commonest tumour types are those with neuroendocrine features, such as carcinoid tumours; bronchial carcinoid accounts for 10%. Such cases are challenging and may require repeat investigations over many years. The ideal treatment is curative surgery of the underlying tumour. In difficult cases, such as non-operable or non-localised tumours, bilateral adrenalectomy with glucocorticoid and mineralocorticoid replacement is an option.
We report a 58-year-old woman with an aggressive ectopic Cushing’s syndrome that required bilateral adrenalectomy undertaken in 1989 at age 32-years. At 16 years post adrenalectomy, two right lung nodules became apparent on subsequent surveillance imaging. One nodule was identified in the upper part of the right lower lobe and another central nodule close to the bronchus. Over a 10-year period, these two foci on CT and Octreotide imaging demonstrated only marginal interval growth. The lung multidisciplinary team therefore advised against surgical intervention in 2006. However, in 2015, these two foci increased in size with growth noted in proximity to the main vessels and bronchi. She was therefore referred for surgery and underwent a right lung wedge resection. Histology was consistent with bronchial typical carcinoids measuring 24mm and 13mm with clear resection margins and stained positive for ACTH. Post-operative imaging (CT chest, abdomen and pelvis, and gallium DOTATATE) demonstrated surgical lung changes, but no evidence of new or recurrent DOTATATE avid disease. Since surgery, her tan significantly decreased. ACTH fell from a preoperative level of 1465ng/L to 12ng/L postoperatively with reduction in pigmentation, suggesting cure from ectopic ACTH-secretion.
Ectopic ACTH-secreting tumours present challenges and require careful clinical, biochemical, radiological and pathological investigations. As this case demonstrates, ectopic ACTH-producing tumours can be extremely difficult to localise and often require multiple modalities of imaging. At present, there is no accepted frequency for imaging in occult ACTH-producing tumours. Our patient had an occult and indolent tumour that took almost two decades to present but has now had curative surgery. These tumours are best managed in a multidisciplinary setting involving the endocrinologists, endocrine surgeon, radiologist and pathologist.