Delayed diagnosis of ectopic ACTH-secreting tumors following transsphenoidal surgery for presumed MRI-negative Cushing's disease: implications for long-term surveillance.

Authors

Risa Waki, Atsushi Ishida, Go Matsuoka, Koji Takano, Noriaki Fukuhara, Akira Takeshita, Yutaka Oki, Shozo Yamada

Published in

Pituitary. Volume 29. Issue 4. Jul 28, 2026. Epub Jul 28, 2026.

Abstract

To determine the long-term diagnostic outcomes of rigorously defined magnetic resonance imaging (MRI)-negative ACTH-dependent Cushing's syndrome.
We retrospectively reviewed 530 patients who underwent transsphenoidal surgery (TSS) for Cushing's disease (CD) between 1992 and 2026. Among them, 59 patients had no identifiable pituitary adenoma on the highest-quality preoperative MRI. After excluding two patients with insufficient follow-up, 57 patients (10.8%) were included in the analysis.
During long-term follow-up, 5 of 57 patients (2 men and 3 women; median age, 58 years; range, 34-61 years) were ultimately diagnosed with ectopic ACTH-secreting tumors. Preoperative endocrinological evaluation suggested cyclic CD in one patient and CD in four patients. Bilateral inferior petrosal sinus sampling (BIPSS) indicated a pituitary source in four patients and an ectopic source in one; however, no definitive ectopic lesion was identified by radiological or functional imaging in any case. TSS was performed after informed consent, but no tumor was identified intraoperatively or on pathological examination. During follow-up, ectopic tumors were detected approximately 2 years after surgery in three patients (pulmonary, adrenal, and pancreatic neuroendocrine tumors), whereas a pulmonary neuroendocrine tumor and a thymic neuroendocrine tumor were identified 9 and 18 years later, respectively, in the remaining two patients. All tumors were surgically resected, confirmed to be ectopic ACTH-secreting tumors, and resulted in complete remission.
Differentiating between pituitary adenoma and ectopic tumors remains challenging in MRI-negative cases. In patients who fail to achieve remission after TSS, careful long-term follow-up, with continued consideration of ectopic ACTH secretion, is essential.

PMID:
42517988
Bibliographic data and abstract were imported from PubMed on 28 Jul 2026.

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