, Volume 22, Issue 2, pp 113–123 | Cite as

Pituitary adenomas in patients with multiple endocrine neoplasia type 1: a single-center experience in China

  • Yanyan Wu
  • Lu Gao
  • Xiaopeng Guo
  • Zihao Wang
  • Wei Lian
  • Kan Deng
  • Lin Lu
  • Bing XingEmail author
  • Huijuan ZhuEmail author



To explore the clinical characteristics of pituitary adenomas in patients with MEN1 and to summarize treatment strategies for MEN1 in a Chinese population.


We retrospectively analyzed 54 MEN1 patients with pituitary adenomas diagnosed at Peking Union Medical College Hospital from March 2003 to January 2017. Clinical data, laboratory testing results, treatments of involved glands and treatment responses were collected and analyzed.


The mean age at pituitary adenoma diagnosis was 53.9 ± 17.8. The patients initially consulted the Endocrinology, General Surgery and Neurosurgery departments, in descending frequency. The nonfunctioning adenoma, prolactinoma, GH-secreting adenoma, cosecreting adenoma, and ACTH-secreting adenoma subtypes accounted for 48.1%, 27.8%, 9.3%, 9.3% and 5.6% of the cases, respectively. The remission rate for prolactinomas was 46.2% (6/13) treated with bromocriptine. And the remission rates were 87.5% (7/8) and 100% (3/3) for GH-secreting adenomas and ACTH-secreting adenomas respectively achieved by transsphenoidal surgery. Nineteen (35.2%) patients with asymptomatic nonfunctioning pituitary adenomas showed no progression after a 35-month follow-up with close observation. Regarding treatment priority, patients with thymic carcinoid tumors received first-line surgery, 54% of the patients with enteropancreatic tumors had these tumors treated first, and 26% of all patients had their pituitary adenomas treated first. In acromegalic patients, pituitary lesions tended to be treated first (75%, p = 0.002). PHPT and adrenocortical adenomas can be managed with elective surgery.


The treatment of MEN1 requires cooperation between multidisciplinary teams. Individualized treatment according to the severity of glandular involvement is needed. GH-secreting and ACTH-secreting pituitary adenomas require active treatment, while nonfunctioning pituitary adenomas can be observed closely.


Multiple endocrine neoplasia type 1 Pituitary adenoma Treatment Chinese population 



This study did not receive any specific grant from any funding agency in the public, commercial or non-for-profit sector.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

Ethical approval

This study was performed in accordance with the ethical standards of the Institutional Ethics Committee of Peking Union Medical College Hospital at the Chinese Academy of Medical Sciences & Peking Union Medical College and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Written or verbal informed consent was obtained from all individual participants included in the study.


  1. 1.
    Brandi ML, Gagel RF, Angeli A, Bilezikian JP, Beck-Peccoz P, Bordi C, Conte-Devolx B, Falchetti A, Gheri RG, Libroia A, Lips CJ, Lombardi G, Mannelli M, Pacini F, Ponder BA, Raue F, Skogseid B, Tamburrano G, Thakker RV, Thompson NW, Tomassetti P, Tonelli F, Wells SA Jr, Marx SJ (2001) Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 86:5658–5671CrossRefGoogle Scholar
  2. 2.
    Agarwal SK (2017) The future: genetics advances in MEN1 therapeutic approaches and management strategies. Endocr Relat Cancer 24:T119–Tt134CrossRefGoogle Scholar
  3. 3.
    Larsson C, Shepherd J, Nakamura Y, Blomberg C, Weber G, Werelius B, Hayward N, Teh B, Tokino T, Seizinger B (1992) Predictive testing for multiple endocrine neoplasia type 1 using DNA polymorphisms. J Clin Invest 89:1344–1349CrossRefGoogle Scholar
  4. 4.
    Thakker RV, Newey PJ, Walls GV, Bilezikian J, Dralle H, Ebeling PR, Melmed S, Sakurai A, Tonelli F, Brandi ML (2012) Endocrine Society: Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab 97:2990–3011CrossRefGoogle Scholar
  5. 5.
    Asgharian B, Chen YJ, Patronas NJ, Peghini PL, Reynolds JC, Vortmeyer A, Zhuang Z, Venzon DJ, Gibril F, Jensen RT (2004) Meningiomas may be a component tumor of multiple endocrine neoplasia type 1. Clin Cancer Res 10:869–880CrossRefGoogle Scholar
  6. 6.
    Thakker RV, Newey PJ, Walls GV, Bilezikian J, Dralle H, Ebeling PR, Melmed S, Sakurai A, Tonelli F, Brandi ML (2012) Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab 97:2990–3011CrossRefGoogle Scholar
  7. 7.
    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 29:22–32CrossRefGoogle Scholar
  8. 8.
    Brandi ML, Marx SJ, Aurbach GD, Fitzpatrick LA (1987) Familial multiple endocrine neoplasia type I: a new look at pathophysiology. Endocr Rev 8:391–405CrossRefGoogle Scholar
  9. 9.
    Lourenco DM Jr, Toledo RA, Mackowiak II, Coutinho FL, Cavalcanti MG, Correia-Deur JE, Montenegro F, Siqueira SA, Margarido LC, Machado MC, Toledo SP (2008) Multiple endocrine neoplasia type 1 in Brazil: MEN1 founding mutation, clinical features, and bone mineral density profile. Eur J Endocrinol 159:259–274CrossRefGoogle Scholar
  10. 10.
    van Leeuwaarde RS, van Nesselrooij BP, Hermus AR, Dekkers OM, de Herder WW, van der Horst-Schrivers AN, Drent ML, Bisschop PH, Havekes B, Vriens MR, de Laat JM, Pieterman CR, Valk GD (2016) Impact of delay in diagnosis in outcomes in MEN1: results From the Dutch MEN1 Study Group. J Clin Endocrinol Metab 101:1159–1165CrossRefGoogle Scholar
  11. 11.
    Burgess JR, Shepherd JJ, Parameswaran V, Hoffman L, Greenaway TM (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 81:2642–2646Google Scholar
  12. 12.
    Giusti F, Cianferotti L, Boaretto F, Cetani F, Cioppi F, Colao A, Davì MV, Faggiano A, Fanciulli G, Ferolla P, Ferone D, Fossi C, Giudici F, Gronchi G, Loli P, Mantero F, Marcocci C, Marini F, Masi L, Opocher G, Beck-Peccoz P, Persani L, Scillitani A, Sciortino G, Spada A, Tomassetti P, Tonelli F, Brandi ML (2017) Multiple endocrine neoplasia syndrome type 1: institution, management, and data analysis of a nationwide multicenter patient database. Endocrine 58:349–359CrossRefGoogle Scholar
  13. 13.
    de Laat JM, Dekkers OM, Pieterman CR, Kluijfhout WP, Hermus AR, Pereira AM, van der Horst-Schrivers AN, Drent ML, Bisschop PH, Havekes B, de Herder WW, Valk GD (2015) Long-term natural course of pituitary tumors in patients With MEN1: results from the DutchMEN1 Study Group (DMSG). J Clin Endocrinol Metab 100:3288–3296CrossRefGoogle Scholar
  14. 14.
    Verges B, Boureille F, Goudet P, Murat A, Beckers A, Sassolas G, Cougard P, Chambe B, Montvernay C, Calender A (2002) Pituitary disease in MEN type 1 (MEN1): data from the France-Belgium MEN1 multicenter study. J Clin Endocrinol Metab 87:457–465CrossRefGoogle Scholar
  15. 15.
    Nunes VS, Souza GL, Perone D, Conde SJ, Nogueira CR (2014) Frequency of multiple endocrine neoplasia type 1 in a group of patients with pituitary adenoma: genetic study and familial screening. Pituitary 17:30–37CrossRefGoogle Scholar
  16. 16.
    Sakurai A, Suzuki S, Kosugi S, Okamoto T, Uchino S, Miya A, Imai T, Kaji H, Komoto I, Miura D, Yamada M, Uruno T, Horiuchi K, Miyauchi A, Imamura M, MEN Consortium of Japan, Fukushima T, Hanazaki K, Hirakawa S, Igarashi T, Iwatani T, Kammori M, Katabami T, Katai M, Kikumori T, Kiribayashi K, Koizumi S, Midorikawa S, Miyabe R, Munekage T, Ozawa A, Shimizu K, Sugitani I, Takeyama H, Yamazaki M (2012) Multiple endocrine neoplasia type 1 in Japan: establishment and analysis of a multicentre database. Clin Endocrinol (Oxf) 76:533–539CrossRefGoogle Scholar
  17. 17.
    Goroshi M, Bandgar T, Lila AR, Jadhav SS, Khare S, Shrikhande SV, Uchino S, Dalvi AN, Shah NS (2016) Multiple endocrine neoplasia type 1 syndrome: single centre experience from western India. Fam Cancer 15:617–624CrossRefGoogle Scholar
  18. 18.
    Wilson JD (1993) Peking Union Medical College Hospital, a palace of endocrine treasures. J Clin Endocrinol Metab 76:815–816Google Scholar
  19. 19.
    Casanueva FF, Molitch ME, Schlechte JA, Abs R, Bonert V, Bronstein MD, Brue T, Cappabianca P, Colao A, Fahlbusch R, Fideleff H, Hadani M, Kelly P, Kleinberg D, Laws E, Marek J, Scanlon M, Sobrinho LG, Wass JA, Giustina A (2006) Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol (Oxf) 65:265–273CrossRefGoogle Scholar
  20. 20.
    Katznelson L, Laws ER Jr, Melmed S, Molitch ME, Murad MH, Utz A, Wass JA (2014) Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 99:3933–3951CrossRefGoogle Scholar
  21. 21.
    Melmed S, Casanueva FF, Klibanski A, Bronstein MD, Chanson P, Lamberts SW, Strasburger CJ, Wass JA, Giustina A (2013) A consensus on the diagnosis and treatment of acromegaly complications. Pituitary 16:294–302CrossRefGoogle Scholar
  22. 22.
    Nieman LK, Biller BM, Findling JW, Murad MH, Newell-Price J, Savage MO, Tabarin A (2015) Treatment of Cushing’s syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 100:2807–2831CrossRefGoogle Scholar
  23. 23.
    Findling JW, Raff H (2017) DIAGNOSIS OF ENDOCRINE DISEASE: Differentiation of pathologic/neoplastic hypercortisolism (Cushing’s syndrome) from physiologic/non-neoplastic hypercortisolism (formerly known as pseudo-Cushing’s syndrome). Eur J Endocrinol 176:R205–Rr216CrossRefGoogle Scholar
  24. 24.
    Wilhelm SM, Wang TS, Ruan DT, Lee JA, Asa SL, Duh QY, Doherty GM, Herrera MF, Pasieka JL, Perrier ND, Silverberg SJ, Solorzano CC, Sturgeon C, Tublin ME, Udelsman R, Carty SE (2016) The American Association of Endocrine Surgeons guidelines for definitive management of primary hyperparathyroidism. JAMA Surg 151:959–968CrossRefGoogle Scholar
  25. 25.
    Oberg K, Jelic S, ESMO Guidelines Working Group (2008) Neuroendocrine bronchial and thymic tumors: ESMO clinical recommendation for diagnosis, treatment and follow-up. Ann Oncol 19(Suppl 2):ii102–i103Google Scholar
  26. 26.
    Oberg K, Knigge U, Kwekkeboom D, Perren A, ESMO Guidelines Working Group (2012) Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 23(Suppl 7):vii124–130Google Scholar
  27. 27.
    Fassnacht M, Arlt W, Bancos I, Dralle H, Newell-Price J, Sahdev A, Tabarin A, Terzolo M, Tsagarakis S, Dekkers OM (2016) Management of adrenal incidentalomas: European society of endocrinology clinical practice guideline in collaboration with the European network for the study of adrenal tumors. Eur J Endocrinol 175:G1–Gg34CrossRefGoogle Scholar
  28. 28.
    Sakurai A, Suzuki S, Kosugi S, Okamoto T, Uchino S, Miya A, Imai T, Kaji H, Komoto I, Miura D, Yamada M, Uruno T, Horiuchi K, Miyauchi A, Imamura M (2012) Multiple endocrine neoplasia type 1 in Japan: establishment and analysis of a multicentre database. Clin Endocrinol 76:533–539CrossRefGoogle Scholar
  29. 29.
    Zhang H, Han W, Jin M, Lai Y, Wang X, Wang J, Yao Y, Wu D, Qian J, Yang H (2018) Establishment and verification of a scoring model for the differential diagnosis of pancreatic cancer and chronic pancreatitis. Pancreas 47:459–465CrossRefGoogle Scholar
  30. 30.
    Fan JH, Zhang YQ, Shi SS, Chen YJ, Yuan XH, Jiang LM, Wang SM, Ma L, He YT, Feng CY, Sun XB, Liu Q, Deloso K, Chi Y, Qiao YL (2017) A nation-wide retrospective epidemiological study of gastroenteropancreatic neuroendocrine neoplasms in china. Oncotarget 8 71699–71708Google Scholar
  31. 31.
    Han G, Wang O, Nie M, Zhu Y, Meng X, Hu Y, Liu H, Xing X (2013) Clinical phenotypes of Chinese primary hyperparathyroidism patients are associated with the calcium-sensing receptor gene R990G polymorphism. Eur J Endocrinol 169:629–638CrossRefGoogle Scholar
  32. 32.
    Yan ST, Tian H, Li CL, Zong WY, Shao YH, Zhong WW, Gong YP (2007) A preliminary survey of primary hyperparathyroidism in middle-aged and elderly Beijing Chinese. Zhonghua Nei Ke Za Zhi 46:651–653Google Scholar
  33. 33.
    Ferolla P, Falchetti A, Filosso P, Tomassetti P, Tamburrano G, Avenia N, Daddi G, Puma F, Ribacchi R, Santeusanio F, Angeletti G, Brandi ML (2005) Thymic neuroendocrine carcinoma (carcinoid) in multiple endocrine neoplasia type 1 syndrome: the Italian series. J Clin Endocrinol Metab 90:2603–2609CrossRefGoogle Scholar
  34. 34.
    Ye L, Wang W, Ospina NS, Jiang L, Christakis I, Lu J, Zhou Y, Zhu W, Cao Y, Wang S, Perrier ND, Young WF Jr, Ning G, Wang W (2017) Clinical features and prognosis of thymic neuroendocrine tumours associated with multiple endocrine neoplasia type 1: a single-centre study, systematic review and meta-analysis. Clin Endocrinol (Oxf) 87:706–716CrossRefGoogle Scholar
  35. 35.
    Brown E, Watkin D, Evans J, Yip V, Cuthbertson DJ (2018) Multidisciplinary management of refractory insulinomas. Clin Endocrinol 88:615–624CrossRefGoogle Scholar
  36. 36.
    Faggiano A, Ferolla P, Grimaldi F, Campana D, Manzoni M, Davi MV, Bianchi A, Valcavi R, Papini E, Giuffrida D, Ferone D, Fanciulli G, Arnaldi G, Franchi GM, Francia G, Fasola G, Crino L, Pontecorvi A, Tomassetti P, Colao A (2012) Natural history of gastro-entero-pancreatic and thoracic neuroendocrine tumors. Data from a large prospective and retrospective Italian epidemiological study: the NET management study. J Endocrinol Invest 35:817–823Google Scholar
  37. 37.
    Trouillas J, Labat-Moleur F, Sturm N, Kujas M, Heymann MF, Figarella-Branger D, Patey M, Mazucca M, Decullier E, Verges B, Chabre O, Calender A (2008) Pituitary tumors and hyperplasia in multiple endocrine neoplasia type 1 syndrome (MEN1): a case–control study in a series of 77 patients versus 2509 non-MEN1 patients. Am J Surg Pathol 32:534–543CrossRefGoogle Scholar
  38. 38.
    Scheithauer BW, Laws ER Jr, Kovacs K, Horvath E, Randall RV, Carney JA (1987) Pituitary adenomas of the multiple endocrine neoplasia type I syndrome. Semin Diagn Pathol 4:205–211Google Scholar
  39. 39.
    Molitch ME, Elton RL, Blackwell RE, Caldwell B, Chang RJ, Jaffe R, Joplin G, Robbins RJ, Tyson J, Thorner MO (1985) Bromocriptine as primary therapy for prolactin-secreting macroadenomas: results of a prospective multicenter study*. J Clin Endocrinol Metab 60:698–705CrossRefGoogle Scholar
  40. 40.
    Hammer GD, Tyrrell JB, Lamborn KR, Applebury CB, Hannegan ET, Bell S, Rahl R, Lu A, Wilson CB (2004) Transsphenoidal microsurgery for Cushing’s disease: initial outcome and long-term results. J Clin Endocrinol Metab 89:6348–6357CrossRefGoogle Scholar
  41. 41.
    Fernandez Mateos C, Garcia-Uria M, Morante TL, Garcia-Uria J (2017) Acromegaly: surgical results in 548 patients. Pituitary 20:522–528CrossRefGoogle Scholar
  42. 42.
    Jeffcoate WJ, Pound N, Sturrock ND, Lambourne J (1996) Long-term follow-up of patients with hyperprolactinaemia. Clin Endocrinol (Oxf) 45:299–303CrossRefGoogle Scholar
  43. 43.
    Huang W, Molitch ME (2018) Management of nonfunctioning pituitary adenomas (NFAs): observation. Pituitary 21 162–167CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Neurosurgery, Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
  2. 2.China Pituitary Disease Registry CenterChinese Pituitary Adenoma Specialist CouncilBeijingChina
  3. 3.Key Laboratory of Endocrinology of National Health and Family Planning CommissionBeijingChina
  4. 4.Department of EndocrinologyPeking Union Medical College HospitalBeijingChina

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