Ectopic Cushing syndrome associated with thymic carcinoid tumor as the first presentation of MEN1 syndrome-report of a family with MEN1 gene mutation

Abstract

Multiple endocrine neoplasia type 1(MEN1) is an autosomal dominant syndrome. Although thymic carcinoid tumor is recognized as a part of MEN1 syndrome but functioning thymic carcinoid tumor as the first presentation of the MEN1 seems to be very rare. In this report, we present a 29-year-old male who developed ectopic Cushing syndrome secondary to thymic carcinoid tumor and was diagnosed as MEN1 syndrome 2 years later. Further evaluation revealed the presence of carcinoid tumor and other MEN 1 manifestations in several other member of family. Genetic evaluation showed presence of a previously reported mutation in exon 10(R527X) of MEN1 gene in these patients. This presentation showed that thymic neuroendocrine tumor could be the first manifestation of the MEN1 syndrome and it might be diagnosed as a dominant manifestation of this syndrome in a family. We suggest biochemical or genetic screening for MEN-1 syndrome for patients with thymic carcinoid.

Multiple hormone secretion may indicate worse prognosis in patients with ectopic Cushing’s syndrome

“…Almost all patients had very high hormone levels. ACTH was 1-2 × ULN in 16 Twenty-one patients (41%) (10 pancreatic NENs and 11 thoracic NENs) had concomitant hypersecretion of other hormones than ACTH from their tumor (Table 3). Five of those had simultaneous hypersecretion of two or more hormones in addition to ACTH.…”

“…There are published case reports of ECS in connection with other types of malignancies as well, for example, pheochromocytoma [3,4], medullary thyroid cancer [5][6][7], paraganglioma [8,9], prostate cancer [10,11], and even more rare ectopic sources of ACTH secretion [12][13][14][15]. Patients with genetically inherited syndromes, which are associated with a risk of development of NENs, can also develop ECS [16][17][18][19]. In 12.5-19% of patients with ECS, the source of ACTH secretion is never found [20,21].…”

Cushing’s Syndrome Due to a Functional Thymic Neuroendocrine Tumor in Multiple Endocrine Neoplasia Type 1 Syndrome

“…About 25% of thymic NET is associated with MEN 1 syndrome, while only 3-8% of patients with MEN 1 syndrome develop thymic NET. As a result, the presence of thymic NET at initial presentation like in this patient is rare [ 3 , 4 ]. A functioning thymic NET in MEN 1 syndrome occurring as ectopic ACTH-dependent Cushing’s syndrome is even rarer and may be diagnosed during the disease course or at initial presentation [ 3 ].…”

“…Inheritance of a mutation in the MEN 1 gene, a tumor suppressor gene mapped to chromosome 11q13 is responsible for MEN 1 syndrome and commonly predisposes individuals to tumors of the parathyroid glands, pituitary and pancreatic islet cells [2]. The clinical spectrum has now been expanded and tumors may develop in several endocrine and non-endocrine organs including foregut neuroendocrine tumors (NET) such as bronchial and thymic NET, duodenal gastrinoma, adrenal adenoma, meningioma, collagenomas, and thyroid tumors [2,3]. Thymic NET-associated tumor with MEN 1 syndrome is extremely rare, has an aggressive course, is usually nonfunctional and has a poor prognosis [3][4][5].…”

“…The clinical spectrum has now been expanded and tumors may develop in several endocrine and non-endocrine organs including foregut neuroendocrine tumors (NET) such as bronchial and thymic NET, duodenal gastrinoma, adrenal adenoma, meningioma, collagenomas, and thyroid tumors [2,3]. Thymic NET-associated tumor with MEN 1 syndrome is extremely rare, has an aggressive course, is usually nonfunctional and has a poor prognosis [3][4][5]. In rare cases, they may be functional and secrete adrenocorticotropic hormone (ACTH) leading to Cushing's syndrome [4,5].…”