Clinical characteristics of adrenocorticotropic hormone ⁃ dependent Cushing's syndrome complicated with multiple endocrine neoplasia

Abstract

Objective To summarize the clinical features of adrenocorticotropic hormone (ACTH)⁃dependent Cushing's syndrome (CS) with multiple endocrine neoplasia (MEN). Methods Based on the pituitary tumor database of Peking Union Medical College Hospital of China Pituitary Disease Register Network (CPDRN), 18 patients with ACTH ⁃ dependent CS complicated with MEN from January 1984 to September 2020 were collected. The clinical manifestations, involved other endocrine glands, laboratorial and imageological examinations were analyzed. Results Among 18 patients, 13 cases were Cushing's disease and 5 cases were ectopic ACTH syndrome (EAS); 15 cases were MEN1 type, 2 cases were MEN2 type and one case was MEN4 type. The clinical manifestations were subclinical CS in 6 cases and overt CS in 12 cases. All cases had osteopenia or osteoporosis. Urolithiasis accounted for 11/18 cases. Regarding the involved endocrine glands, pituitary ACTH adenoma accounted for 13/18 cases, prolactinoma accounted for 4/18 cases, hyperparathyroidism accounted for 15/18 cases, pancreatic neuroendocrine tumors accounted for 13/18 cases and adrenal adenomas and hyperplasia accounted for 10/18 cases. Laboratorial examinations showed the average morning serum cortisol was (652.90 ± 254.90) nmol/L, the morning ACTH was (13.38 ± 8.73) pmol/L and the 24 h urinary free cortisol was 446.35 (233.08, 531.10) µg. Serum prolactin was elevated in 2 cases, parathyroid hormone was elevated in 13 cases and serum calcium was elevated in 11 cases. In imageological examinations, there were pituitary microadenoma in 12 cases, pituitary macroadenoma in 3 cases, adrenal adenoma in 8 cases, thickened adrenal in 4 cases, adrenal pheochromocytoma in 2 cases, and paraganglioma in one case. Genetic test showed 3 cases had MEN1 gene mutation including c.1183C ＞ T, c.1579C ＞ T and c.1174G ＞ T. Conclusions ACTH⁃dependent CS with MEN is a rare disease with complex manifestations. The most common symptom is osteopenia/osteoporosis. The most common cause of CS is pituitary microadenoma. MEN1 is the most common MEN type, and primary hyperparathyroidism is the most common type of affected endocrine glands, followed by pancreatic neuroendocrine tumors.

doi：10.3969/j.issn.1672⁃6731.2021.03.008