Cushing's Syndrome Secondary to a Thymic Carcinoid Tumor Due to Multiple Endocrine Neoplasia Type 1
1Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2Departments of Thoracic Surgery and Pathology, Masih Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3Department of Radiology, Taleghani General Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4Consultant Histopathologists, Barts and the London NHS Trust, London, United Kingdom
5Consultants Molecular Geneticist, Royal Devon & Exeter NHS Foundation Trust, Exeter, London, United Kingdom
6William Harvey Research Institute, Barts, London School of Medicine, London, United Kingdom
Objective: To present an Iranian patient who had a non-classic form of MEN1 and presented with ectopic Cushing's syndrome (CS) secondary to an 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.
Result: Histopathologic evaluation of thymic tumor showed atypical carcinoid tumor at first surgery with a Ki-67 of 5% and an invasive carcinoid tumor, with a Ki-67 of 30% at second surgery. Parathyroid pathology was in favor of glandular hyperplasia. Menin gene sequencing revealed a novel frame shift mutation "c1642-1648" in exon 10.
Conclusion: This case of MEN1 is unusual because most thymic NETs in MEN1 have been claimed to be non-functional, and secretion of ACTH or other ectopic hormones to rarely occur. In patients presenting with thymic NETs, the possibility of a MEN1 should be considered, especially in the presence of hyperparathyroidism. The case also shows that the behavior of thymic NETs can change with the passage of time from a slow-growing tumor to a highly invasive neoplasia, and that ectopic ACTH can be produced by these tumors in the context of MEN1.