Guidelines for Diagnosis and Therapy of MEN Type 1 and Type 2
Author: Maria Luisa Brandi, Robert F. Gagel, Alberto Angeli, John P. Bilezikian, Paolo Beck-peccoz, Cesare Bordi, Bernard Conte-devolx, Alberto Falchetti, Riccardo Gionata Gheri, Alfonso Libroia, Cornelius J. M. Lips, Gaetano Lombardi, Massimo Mannelli, Furio Pacini, Bruce A. J. Ponder, Frank Raue, Britt Skogseid, Guido Tamburrano, Rajesh V. Thakker, Norman W. Thompson, Paola Tomassetti, Francesco Tonelli, Samuel A. Wells, Jr., And Stephen J. Marx
References: The Journal of Clinical Endocrinology & Metabolism 86(12):5658–5671
This is a consensus statement from an international group, mostly of clinical endocrinologists. MEN1 and MEN2 are hereditary cancer syndromes. The commonest tumors secrete PTH or gastrin in MEN1, and calcitonin or catecholamines in MEN2. Management strategies improved after the discoveries of their genes. MEN1 has no clear syndromic variants. Tumor monitoring in MEN1 carriers includes biochemical tests yearly and imaging tests less often. Neck surgery includes subtotal or total parathyroidectomy, parathyroid cryopreservation, and thymectomy. Proton pump inhibitors or somatostatin analogs are the main management for oversecretion of entero-pancreatic hormones, except insulin. The roles for surgery of most entero-pancreatic tumors present several controversies: exclusion of most operations on gastrinomas and indications for surgery on other tumors. Each MEN1 family probably has an inactivating MEN1 germline mutation. Testing for a germline MEN1 mutation gives useful information, but rarely mandates an intervention. The most distinctive MEN2 variants are MEN2A, MEN2B, and familial medullary thyroid cancer (MTC). They vary in aggressiveness of MTC and spectrum of disturbed organs. Mortality in MEN2 is greater from MTC than from pheochromocytoma. Thyroidectomy, during childhood if possible, is the goal in all MEN2 carriers to prevent or cure MTC. Each MEN2 index case probably has an activating germline RET mutation. RET testing has replaced calcitonin testing to diagnose the MEN2 carrier state. The specific RET codon mutation correlates with the MEN2 syndromic variant, the age of onset of MTC, and the aggressiveness of MTC; consequently, that mutationshouldguidemajormanagementdecisions, suchaswhether and when to perform thyroidectomy. (J Clin Endocrinol Metab 86: 5658–5671, 2001).
Clinical Practice Guidelines for Multiple Endocrine Neoplasia Type 1 (MEN1)
Author: Rajesh V. Thakker, Paul J. Newey, Gerard V. Walls, John Bilezikian, Henning Dralle, Peter R. Ebeling, Shlomo Melmed, Akihiro Sakurai, Francesco Tonelli, and Maria Luisa Brandi
References: J Clin Endocrinol Metab, September 2012, 97(9):2990–3011
Objective: The aim was to provide guidelines for evaluation, treatment, and genetic testing for multiple endocrine neoplasia type 1 (MEN1).
Participants: The group, which comprised 10 experts, including physicians, surgeons, and geneticists from international centers, received no corporate funding or remuneration.
Process: Guidelines were developed by reviews of peer-reviewed publications; a draft was prepared, reviewed, and rigorously revised at several stages; and agreed-upon revisions were incorporated.
Conclusions: MEN1 is an autosomal dominant disorder that is due to mutations in the tumor suppressor gene MEN1, which encodes a 610-amino acid protein, menin. Thus, the finding of MEN1 in a patient has important implications for family members because first-degree relatives have a 50% risk of developing the disease and can often be identified by MEN1 mutational analysis. MEN1 is characterized by the occurrence of parathyroid, pancreatic islet, and anterior pituitary tumors. Some patients may also develop carcinoid tumors, adrenocortical tumors, meningiomas, facial angiofibromas, collagenomas, and lipomas. Patients with MEN1 have a decreased life expectancy, and the outcomes of current treatments, which are generally similar to those for the respective tumors occurring in non-MEN1 patients, are not as successful because of multiple tumors, which may be larger, more aggressive, and resistant to treatment, and the concurrence of metastases. The prognosis for MEN1 patients might be improved by presymptomatic tumor detection and undertaking treatment specific for MEN1 tumors. Thus, it is recommended thatMEN1patients and their families should be cared for by multidisciplinary teams comprising relevant specialists with experience in the diagnosis and treatment of patients with endocrine tumors.
Multiple endocrine neoplasia type 1 (MEN1):
recommendations and guidelines for best practice
Author: Maria Luisa Brandi, Carolina R C Pieterman, Katherine A English, Kate E Lines, Omair A Shariq, Francesca Marini, Thomas Cuny, Mark A Lewis, Constantine A Stratakis, Nancy D Perrier, Steven G Waguespack, Frederic Castinetti, Gerlof D Valk, Rajesh V Thakker; Delphi Expert Panel
References: J Clin Endocrinol Metab, September 2012, 97(9):2990–3011
Multiple endocrine neoplasia type 1 (MEN1) is characterised by combined occurrence of parathyroid tumours, duodenopancreatic neuroendocrine tumours, and anterior pituitary adenomas. Some patients might also develop thymic and bronchopulmonary neuroendocrine tumours, and adrenal tumours. MEN1 is an autosomal dominant disorder caused by mutations in the tumour-suppressor gene MEN1, which encodes a scaffold protein, menin. Without treatment, patients with MEN1 have high morbidity and premature mortality, which can be mitigated by early tumour detection and intervention. Identification of individuals at high risk for MEN1 can be facilitated by genetic testing of patients and their first-degree relatives, and undertaking periodic clinical, biochemical, and radiological screening in patients and MEN1 mutation carriers. However, no consensus exists regarding the optimal assessment and management of MEN1. To provide such recommendations, a multidisciplinary group was convened to undertake systematic reviews and a meta-analysis of the literature, and to use a Delphi approach for the development of consensus statements. 55 clinical recommendations were developed to guide clinicians, patients, and stakeholders about approaches for MEN1 in adults and children.