Bronchial and Thymic Carcinoids Emerge as Leading Causes of Ectopic Cushing's Syndrome, Suggests Study

While small-cell lung carcinoma was historically considered the primary culprit for this rare condition, the recent emergence of neuroendocrine tumors as the leading cause has created a clinical gap in characterizing their varied presentations, prompting Dr. Rama Walia and colleagues at the Post Graduate Institute of Medical Education and Research, Chandigarh, India, to evaluate the clinical profile of a localized cohort. By mapping these shifting etiological trends, the authors aimed to provide actionable insights for physicians differentiating ectopic hypercortisolism from pituitary-dependent disease.

Therefore, over 35 years, researchers at a North Indian center evaluated 21 patients with ectopic Cushing's syndrome using both retrospective and prospective data. The study primarily focused on localizing the causative tumors, tracking metabolic complications, and assessing patient outcomes after surgery.

Key Clinical Findings of the Study Includes:

• Clinical Presentation Profiling: Investigators observed that alongside cuticular atrophy in all subjects, proximal muscle weakness and hyperpigmentation were the predominant symptoms affecting over three-quarters of the cohort, while hypertension was recorded in 90.5% of the patients.

• Biochemical Anomalies: Researchers highlighted that all participants exhibited a disrupted cortisol circadian rhythm, with a particularly intriguing finding being that 22.2% displayed an unexpected paradoxical increase in morning cortisol following a high-dose dexamethasone suppression test (HDDST).

• Advanced Tumor Localization: Scientists noted that computed tomography successfully identified the underlying neoplastic source in most cases, whereas functional nuclear imaging utilizing Gallium-68 DOTATATE positron emission tomography-computed tomography (PET-CT) demonstrated an unparalleled 100% sensitivity in all seven patients subjected to it.

• Therapeutic Survival: Clinicians reported that while primary tumor resection or total bilateral adrenalectomy was definitively required, individuals harboring indolent gut or bronchial carcinoids ultimately demonstrated the most favorable long-term prognoses.

The results suggest that bronchial and thymic carcinoids have equally become the most prevalent etiologies of the syndrome, each accounting for 33.3% of the localized cases. Furthermore, these findings emphasize that relying solely on traditional suppression tests may be misleading due to paradoxical cortisol responses, necessitating a multimodal diagnostic approach.

Thus, the study concludes that clinicians may find it beneficial to maintain a high index of suspicion for diverse occult neuroendocrine sources during the evaluation of hypercortisolism, utilizing a combination of vigilant clinical monitoring and advanced nuclear imaging modalities to guide appropriate and timely surgical interventions.

Although the current findings are inherently constrained by the small sample size and the limited utilization of inferior petrosal sinus sampling, future molecular investigations into the mechanisms behind the paradoxical cortisol response could gently expand our understanding of this complex condition without undermining these valuable clinical observations.

Reference

Arjunan, D., Jain, N., Shah, R., Ahuja, C. K., Mavuduru, R. S., Bora, G. S., Pal, R., Bhadada, S. K., Bhansali, A., Basher, R. K., Saikia, U. N., & Walia, R. (2025). Salient observations from clinical profile and long-term outcome of a cohort of patients with ectopic Cushing’s syndrome. Indian Journal of Endocrinology and Metabolism, 29, 434-439.