An extremely rare association of TSH-secreting pituitary adenoma, metastatic neuroendocrine tumor and Cushing’s syndrome in a patient with MEN-1 gene mutation

Giuseppe Giuffrida, Erika Messina, Petronilla Daniela Romeo, Adriana Albani, Valeria Barresi, Sergio Baldari, Giuseppe Navarra, Francesco Ferraù, Salvatore Cannavò


Multiple endocrine neoplasia (MEN)-1 syndrome is a rare disorder, due to the loss of function of the tumor suppressor menin. It consists of the association of two or more endocrine tumors, often presenting in a familial setting, being inherited in an autosomal dominant fashion. The most frequent manifestations of MEN-1 syndrome are primary hyperparathyroidism, followed by pituitary adenomas (mainly prolactinomas) and gastrointestinal neuroendocrine tumors, but several other associated conditions have been reported. Herein we describe the case of a male patient, affected by sporadic MEN-1, diagnosed with primary hyperparathyroidism, TSH-secreting pituitary adenoma and bilateral adrenal hyperplasia causing Cushing’s syndrome, due to a de novo MEN-1 gene mutation. The patient has been successfully treated with first generation somatostatin analog Octreotide LAR (30 mg every 28 days) -with stabilization of the known neuroendocrine lesions and shrinkage of the pituitary adenoma- and with bilateral adrenalectomy. The patient is still regularly followed-up at our Endocrine Unit, and his clinical conditions are stable.


MEN-1; TSH-secreting pituitary adenomas; adrenal hyperplasia; Cushing’s syndrome; hyperparathyroidism

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1. Matkar, S., Thiel, A., Hua, X. (2013) Menin: a scaffold protein that controls gene expression and cell signaling. Trends Biochem Sci, 38(8):394-402.

2. Thakker, R.V., Newey, P.J., Walls, G.V., Bilezikian, J., Dralle, H., Ebeling, P.R. et al, Endocrine Society. (2012) Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab, 97(9):2990-3011.

3. Giusti, F., Marini, F., Brandi, M.L. (2005, updated 2017) Multiple Endocrine Neoplasia Type 1.

In: Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Stephens, K., Amemiya, A., editors, GeneReviews® [Internet], Seattle (WA): University of Washington, Seattle; 1993-2018.

4. Carroll, R.W. (2013) Multiple endocrine neoplasia type 1 (MEN1). Asia-Pacific J Clin Oncol, 9: 297–309.

5. Giusti, F., Cianferotti, L., Boaretto, F., Cetani, F., Cioppi, F., Colao, A. et al. (2017) Multiple endocrine neoplasia syndrome type 1: institution, management, and data analysis of a nationwide multicenter patient database. Endocrine, 58(2):349-359.

6. Marini, F., Giusti, F., Fossi, C., Cioppi, F., Cianferotti, L., Masi, L. et al. (2018) Multiple endocrine neoplasia type 1: analysis of germline MEN1 mutations in the Italian multicenter MEN1 patient database. Endocrine (in press), doi: 10.1007/s12020-018-1566-8.

7. Beck-Peccoz, P., Brucker-Davis, F., Persani, L., Smallridge, R.C. & Weintraub, B.D. (1996) Thyrotropin-secreting pituitary tumors. Endocrine Reviews, 17:610–638.

8. Valdes Socin, H., Chanson, P. Delemer, B., Tabarin, A., Rohmer, V., Mockel, J. et al. (2003) The changing spectrum of TSH-secreting pituitary adenomas: diagnosis and management in 43 patients. Eur J Endocrinol, 148:433-442.

9. Taylor, T.J, Donlon, S.S., Bale, A.E., Smallridge, R.C., Francis, T.B., Christensen R.S. et al. (2000) Treatment of a Thyrotropinoma with Octreotide-LAR in a Patient with Multiple Endocrine Neoplasia-1. Thyroid, 10(11):1001-1007.



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