Objective: To present an Iranian patient with a nonclassic form of multiple endocrine neoplasia type 1 (MEN 1) who presented with ectopic Cushing syndrome (CS) secondary to a corticotropin (ACTH)-producing thymic neuroendocrine tumor (NET), recurrent renal stones, and a giant cell granuloma of the jaw due to primary hyperparathyroidism (PHPT) without involvement of the pituitary or pancreas.

Methods: Relevant imaging and hormonal evaluations were performed. The patient was operated on 2 occasions for a thymic NET and on 3 occasions for PHPT. DNA from a peripheral blood sample was extracted for sequencing of the MEN1 gene.

Results: Histopathologic evaluation of the thymic tumor removed during the first surgery showed an atypical carcinoid tumor with a Ki-67 labeling index of 5%. Evaluation after the second surgery revealed an invasive carcinoid tumor with a Ki-67 labeling index of 30%. Parathyroid pathology was suggestive of glandular hyperplasia. Menin gene sequencing revealed a novel frameshift mutation c.1642_1648dup in exon 10.

Conclusions: This case of MEN 1 is unusual because most thymic NETs in MEN 1 are nonfunctional, and secretion of ACTH or other ectopic hormones rarely occurs. In patients presenting with thymic NETs, the possibility of MEN 1 should be considered, especially in the presence of hyperparathyroidism. This case also demonstrates that the behavior of thymic NETs can change over time from slow-growing tumors to highly invasive neoplasia, and that ectopic ACTH can be produced by these tumors in the context of MEN 1.