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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Hasani-Ranjbar S, Amoli MM, Ebrahim-Habibi A et al (2011) A new frameshift MEN1 gene mutation associated with familial malignant insulinomas. Fam Cancer 10(2):343–348. doi:10.1007/s10689-010-9412-z
Brandi ML, Gagel RF, Angeli A et al (2001) Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 86:5658–5671
Ferolla P, Falchetti P, Filosso P et al (2005) Thymic neuroendocrine carcinoma (carcinoid) in multiple neoplasia type 1 syndrome: the Italian series. J Clin Endocrinol Metabol 90:2603–2609
Burgess JR, Shepherd JJ, Parameswaran V et al (1996) Spectrum of pituitary disease in multiple endocrine neoplasia type 1 (MEN 1): clinical, biochemical, and radiological features of pituitary disease in a large MEN 1 kindred. J Clin Endocrinol Metab 81(7):2642–2646
Swarts DRA, Ramaekers FCS, Speel EJM (2012) Molecular and cellular biology of neuroendocrine lung tumors: evidence for separate biological entities. Biochim Biophys Acta 1826:255–271
Wick MR, Scott RE, Li CY, Carney JA (1980) Carcinoid tumor of thymus: a clinic pathologic report of seven cases with a review of the literature. Mayo Clin Proc 55:246–254
Roy A, Kucukural A, Zhang Y (2010) I-TASSER: a unified platform for automated protein structure and function prediction. Nat Protoc 5:725–738
Chandrasekharappa SC, Guru SC, Manickam P et al (1997) Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science 18(276):404–407
Hai N, Aoki N, Matsuda A et al (1999) Germline MEN1 mutations in sixteen Japanese families with multiple endocrine neoplasia type 1 (MEN1). Eur J Endocrinol 141:475–480
Murai MJ, Chruszcz M, Reddy G et al (2011) Crystal structure of menin reveals binding site for mixed lineage leukemia (MLL) protein. J Biol Chem 286(36):31742–31748. doi:10.1074/jbc.M111.258186
Burgess JR, Shepherd JJ, Parameswaran V et al (1996) Spectrum of pituitary disease in multiple endocrine neoplasia type 1 (MEN1): clinical, biochemical and radiological features of pituitary in a large MEN 1 kindred. J Clin Endocrinol Metab 81:2642–2646
Rosaie J, Higa E, Davie J (1972) Meditational endocrine neoplasm in patients with multiple endocrine adenomatosis: a previously unrecognized association. Cancer 29:1075–1083
Gibril F, Chen YJ, Schrump DS et al (2003) Prospective study of thymic carcinoid in patients with multiple endocrine neoplasia type 1. J Clin Endocrinol Metab 88:1066–1081
Takagi J, Otake K, Morishita M et al (2006) Multiple endocrine neoplasia type 1 and Cushing syndrome due to an aggressive ACTH producing thymic carcinoid. Intern Med 45:1427–1431
Yano M, Fukai I, kobayashi Y et al (2006) ACTH secreting carcinoid associated with multiple endocrine neoplasia type 1. Ann Thorac Surg 81:366–368
Ghazi AA, Dezfooli AA, Mohamadi F et al (2011) Cushing syndrome secondary to a thymic carcinoid tumor due to multiple endocrine neoplasia type 1. Endocr Pract 17:e92–e96
Teh BT, Zedenius J, Kytola S et al (1998) Thymic carcinoid in multiple endocrine neoplasia type 1. Ann Surg 228:99–105
Larraza-Hernandez O, Albores-Saavedra J, Benavides J et al (1982) Multiple endocrine neoplasia. Pituitary adenoma, multicenteric papillary throid carcinoma, bilateral carotid body paraganglioma, parathyroid hyperplasia, gastric leiomyoma, and systemic amyloidosis. Am J Clin Pathol 78:527–532
Brandi ML, Gagel RF, Angeli A et al (2011) Guidelines for diagnosis and therapy of MEN type 1 and 2. J Clin Endocinol Metab 86:5658–5671
Lemos MC, Thakker RV (2008) Multiple endocrine neoplasia type 1 (MEN1): analysis of 1336 mutations reported in the first decade following identification of the gene. Hum Mutat 29:22–32
Papaconstantinou M, Maslikowski BM, Pepper AN et al (2009) The protein behind the MEN1 syndrome. Adv Exp Med Biol 668:27–36
Guru SC, Goldsmith PK, Burns AL et al (1998) Menin, the product of the MEN1 gene, is a nuclear protein. Proc Natl Acad Sci USA 95(4):1630–1634
Acknowledgments
We appreciate Mrs. Parvin Amiri for her cooperation in this study. This study is funded by Endocrinology and Metabolism Research Institute (EMRI).
Conflict of interest
There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Hasani-Ranjbar, S., Rahmanian, M., Ebrahim-Habibi, A. et al. Ectopic Cushing syndrome associated with thymic carcinoid tumor as the first presentation of MEN1 syndrome-report of a family with MEN1 gene mutation. Familial Cancer 13, 267–272 (2014). https://doi.org/10.1007/s10689-013-9692-1
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10689-013-9692-1