A Diagnostic Dilemma in Ectopic ACTH Syndrome: When Biochemistry and Imaging Conflict
https://doi.org/10.15605/jafes.041.S1
- Author:
Ioanna Ting Yung Sim
1
;
Florence Hui Sieng Tan
2
;
Sing Yee Sim
1
;
Pei Lin Chan
2
;
Ee Wen Loh
2
Author Information
1. Endocrine Unit, Sarawak General Hospital;Universiti Malaysia Sarawak (UNIMAS)
2. Endocrine Unit, Sarawak General Hospital
- Publication Type:Journal Article
- MeSH:
ACTH Syndrome, Ectopic
- From:
Journal of the ASEAN Federation of Endocrine Societies
2026;41(S1):83-84
- CountryPhilippines
- Language:English
-
Abstract:
Introduction:Ectopic ACTH secretion (EAS) is a rare cause of Cushing’s
syndrome, accounting for 5–15% of cases. Pulmonary
neuroendocrine tumors are the most frequent cause.
However, primary tumor localization remains a significant
diagnostic challenge, delaying effective treatment.
Case:A 59-year-old female with diabetes mellitus presented
with refractory hypertension and hypokalemia. Initial
laboratory findings revealed a baseline cortisol of 1,164
nmol/L and morning adrenocorticotropic hormone
(ACTH) of 19.5 pmol/L (normal <10.2 pmol/L), with an
overnight dexamethasone suppression test cortisol of
624 nmol/L. Pituitary magnetic resonance imaging (MRI)
and computed tomography (CT) scans of the thorax,
abdomen, and pelvis were initially unremarkable. A PET
scan identified mild hypermetabolism in the left adrenal
gland and gastrointestinal tract, though colonoscopy
revealed only chronic colitis. An intravenous desmopressin
stimulation test demonstrated a 181% rise in ACTH and a
35% rise in cortisol, pointing toward pituitary Cushing’s.
However, repeat pituitary MRI remained normal.
A high-dose dexamethasone suppression test showed
approximately 34% cortisol suppression (cortisol 1,128
nmol/L to 745 nmol/L), suggesting ectopic Cushing’s
syndrome. Bilateral inferior petrosal sinus sampling
demonstrated a peak central-to-peripheral ACTH ratio of
1.8 on the right and 1.6 on the left, pointing toward ectopic
Cushing’s.
Localization with DOTATATE PET-CT identified a 7 × 9 ×
8 mm nodule in the right middle lobe. A wedge resection
was performed. Histopathology confirmed a typical
carcinoid tumor with clear resection margins. Immunohistochemistry revealed tumor cells positive for CK AE1/ AE3, synaptophysin, chromogranin, and INSM-1, with
weak positivity for ACTH. The latest 8 am cortisol was 117
nmol/L and ACTH 1.74 pmol/L, confirming biochemical
cure. Hypokalemia resolved, with improvement in her
metabolic profile.
Conclusion:This case highlights the diagnostic complexities of EAS,
particularly when initial imaging is inconclusive and
biochemical tests yield conflicting results. Timely, precise
localization of the causative tumor is crucial for successful
surgical intervention and to prevent severe complications
of hypercortisolism, thereby improving patient outcomes.
- Full text:2026080414123617942EP_A116.pdf
