Endocrine Abstracts

Background

Ectopic ACTH syndrome (EAS) is a rare cause of endogenous hypercortisolism.

Objective

To analyze clinical, biochemical features and treatment outcomes of patients with EAS.

Materials and methods

Retrospective, observational study on 129 patients (79 women, 50 men) with EAS diagnosed between 1990 and 2020. Plasma levels of ACTH (reference range: morning 7.2–63.3 pg/ml), late-night serum cortisol (64–327 nmol/l), late-night salivary cortisol (LNSC) (0.5–9.6 nmol/l) were measured by ECLIA Cobas 601; 24-h urinary free cortisol (24 hUFC) (100–379 nmol/l) – on Vitros ECi. Various imaging studies were performed in all patients to find the source of ACTH.

Results

The median age at diagnosis was 40 years [28;54]. 80 patients (62%) had bronchopulmonary neuroendocrine tumor (NET), 7 – thymic carcinoid, 7 – pancreatic NET, 5 – pheochromocytoma, 1– cecum NET, 1– appendix carcinoid tumor, 1 – medullary thyroid cancer and 27 (21%) patients had an occult source of ACTH. Mean time to diagnosis for patients with EAS was 32.5 months, 11 patients (8.5%) had cyclic course of the disease. Median basal plasma ACTH level at the time of the diagnosis was 141.1 pg/ml [101.9;202], median 24 hUFC was 2821.0 nmol/l [1691;6534.6], median late-night serum cortisol at 23:00 h and LNSC were 1228 nmol/l [959.1;1431.3] and 71.8 nmol/l [40.5;121], respectively. The most common complications in the active stage of the disease were type 2 diabetes mellitus (55%), cardiovascular disease (55%), arterial hypertension (84.5%), osteoporosis with low-energy fractures (60.5%). The median follow-up period of the patients was 27 months [10.5;61.0] with a maximum follow-up of 372 months. Currently, primary tumor was removed in 82 (63.6%) patients. Regional and distant metastases were revealed in 22 patients (17%). At the time of the last observation 58 patients (45%) were exhibited a full recovery, 12 (9%) – had relapse of the disease and received treatment with octreotide (20–50 mg/4 weeks) or ketoconazole (400 mg/day) to control severe hypercortisolism and 26 patients (20%) died from multiple organ failure (n = 21), pulmonary embolism (n = 4) or COVID-19 (n = 1). Bilateral adrenalectomy was performed in 23 patients (18%), in 16 of them there was an occult source of ACTH-producing tumor and in 7 patients – in order to control hypercortisolism at incurable stage of the disease.

Conclusion

In our study EAS was most commonly associated with intrathoracic tumors such as bronchopulmonary and thymic carcinoid. Surgical treatment of patients with the established source of the disease leads to remission of hypercortisolism in most cases.