Abstract
Background
Neuroendocrine tumors can cause ectopic Cushing syndrome, and most patients have metastatic
disease at diagnosis. We identified risk factors for outcome, evaluated ectopic Cushing
syndrome management, and explored the role of bilateral adrenalectomy in this population.
Methods
This was a retrospective study including patients with diagnosis of ectopic Cushing
Syndrome secondary to neuroendocrine tumors with adrenocorticotropic hormone secretion
treated at our quaternary referral center over a 40-year period (1980–2020).
Results
Seventy-six patients were included. Mean age at diagnosis was 46.3 ± 15.8 years. Most
patients (N = 61, 80%) had metastases at ectopic Cushing syndrome diagnosis. Average follow-up
was 2.9 ± 3.7 years (range, 4 months–17.2 years). Patients with neuroendocrine tumors
before ectopic Cushing syndrome had more frequent metastatic disease and resistant
ectopic Cushing syndrome. Patients with de novo hyperglycemia, poor neuroendocrine
tumor differentiation, and metastatic disease had worse survival. Of those with nonmetastatic
disease, 8 (53%) had ectopic Cushing syndrome resolution after neuroendocrine tumor
resection, 3 (20%) were medically controlled, and 4 (27%) underwent bilateral adrenalectomy.
In patients with metastatic neuroendocrine tumors, hypercortisolism was initially
medically managed in 92%, 3% underwent immediate bilateral adrenalectomy, 2% had control
after primary neuroendocrine tumor debulking, and 2% were lost to follow-up. Medical
treatment resulted in hormonal control in 7 (13%) patients. Of the 49 patients with
metastatic disease and medically resistant ectopic Cushing syndrome, 23 ultimately
had bilateral adrenalectomy with ectopic Cushing syndrome cure in all.
Conclusion
Patients with neuroendocrine tumors before ectopic Cushing syndrome development were
more likely metastatic and had worse survival. De novo hyperglycemia and poor neuroendocrine
tumor differentiation were predictive of worse prognosis. Medical control of hypercortisolism
is difficult to achieve in patients with neuroendocrine tumors–ectopic Cushing syndrome.
Well-selected patients may benefit from bilateral adrenalectomy early in the treatment
algorithm, and multidisciplinary management is essential in this complex disease.
Graphical abstract
Graphical Abstract
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Article info
Publication history
Published online: April 15, 2022
Accepted:
March 14,
2022
Footnotes
This research was presented as an oral presentation at the ACS Clinical Congress 2020.
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
