Co-secretion of ACTH and CRH by a rare ectopic small bowel neuroendocrine tumour causing Cushings Syndrome — ASN Events
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Co-secretion of ACTH and CRH by a rare ectopic small bowel neuroendocrine tumour causing Cushings Syndrome (#123)

Sonia Saxena 1
  1. John Hunter Hospital, New Lambton, NSW, Australia

Presentation:
A 66year old male reported a 6-month history of fullness of his face, central adiposity,skin tears and proximal myopathy. On reviewing old photographs it was evident the cushingoid features may have started almost 5years prior.

Investigations:
24-hour Urine free cortisol (UFC) measurements were elevated to 5 times the upper limit of normal. Cushing’s syndrome was confirmed with a low-dose dexamethasone suppression test and elevated midnight salivary cortisol levels. The ACTH was elevated to 20pmol/L (normal range <11) suggesting ACTH-dependant Cushing’s syndrome.
A high-dose dexamethasone suppression test (HDDST) showed >90% reduction in  UFC suggesting a pituitary source for Cushing’s syndrome however the pituitary-MRI did not identify an adenoma. Inferior petrosal sinus sampling (IPSS) contrary to the HDDST, did not result in a gradient and thus suggested an ectopic source. No ectopic lesions were identified on CT scanning, Octreotide scan or 18-FDG PET scan.


A peripheral-CRH study showed a 4-fold rise in ACTH and 70% rise in peak cortisol response again suggestive of pituitary source. Due to this result a second IPSS was performed and did reveal a 3:1 central to peripheral ACTH gradient also suggesting a pituitary source.
Management:
Given the number of tests supporting a probable pituitary source the patient underwent transphenoidal pituitary surgery. Histology showed staining positive for ACTH. The post-pituitarysurgery cortisol levels remained elevated and therefore a full hypophysectomy was performed resulting in a reduction in both UFC and 9am cortisol levels. Thyroid hormone and testosterone replacement was required.
Progress:
Unfortunately within 2months ACTH-dependant Cushing’s syndrome was confirmed to have persisted despite pituitary surgery. At this time Gallium 68-Ocreotate PET scanning became available and revealed a solitary lesion in the lower abdomen. On surgical exploration in the region of the terminal ileum an intraluminal tumour was found. On histology this was confirmed to be a low-grade carcinoid tumour with positive staining for ACTH with mesenteric metastasis

Outcome:
There was a dramatic fall in cortisol levels to undetectable levels and for the first time reduction in ACTH levels to the normal range. Clinically the cushingoid signs and symptoms resolved over the following year


The Ectopic Small bowel lesion was found to be Co-secreting CRH and ACTH

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