Distinguishing Cushing's disease from the ectopic ACTH syndrome: Needles in a haystack or hiding in plain sight?

Abstract

In the context of ACTH-dependent Cushing's syndrome, ectopic ACTH secretion from a neuroendocrine tumour is not uncommon, and needs to be carefully differentiated from pituitary-dependent Cushing's syndrome, Cushing's disease, in order to optimise therapy. Some cases may be quite obvious, while in others the diagnosis may be difficult to confirm and the source of ACTH problematic, as many clinical and biochemical tests may overlap with Cushing's disease. Imaging is essential, but needs to be interpreted in the light of both anatomical as well as functional imaging modalities. In this review we summarise some of the main diagnostic problems, and emphasise the multimodal and interdisciplinary nature of the diagnostic pathways.

Keywords: ACTH; Cushing's; carcinoid; diagnosis; ectopic; neuroendocrine tumour.

FIGURE 1

Establishing the cause of ACTH‐dependent Cushing's syndrome and management (adapted from ²² ). Abbreviations: ACTH, adrenocorticotropic hormone; LDDST, low dose dexamethasone suppression test; CRH, corticotropin releasing hormone; MRI, magnetic resonance imaging; BIPSS, bilateral inferior petrosal sinus sampling; CT, computed tomography; SCLC, small cell lung cancer

FIGURE 2

⁶⁸Ga‐DOTATATE PET/CT showing intensely avid hepatic metastases and abdominal and left supraclavicular nodal metastases in a 55 year old woman with a well‐differentiated, grade 2 (Ki‐67 8%), pancreatic neuroendocrine tumour (primary tumour previously resected) and ectopic ACTH syndrome (images courtesy of Dr Shaunak Navalkissoor, Department of Nuclear Medicine, Royal Free Hospital)