MEN syndromes are familial disorders characterized by neoplastic changes that affect multiple endocrine organs.[
There are two main types of MEN syndromes:
For more information about MEN syndromes, see Genetics of Endocrine and Neuroendocrine Neoplasias.
The main clinical features and genetic alterations of the multiple endocrine neoplasia (MEN) syndromes are shown in Table 1.
| MEN type 1 (Wermer syndrome)[
|11q13 (MEN1 gene)
|11q13 (MEN1 gene)
|11q13 (MEN1 gene)
|Other associated tumors (less common):
|Carcinoid—bronchial and thymic
|11q13 (MEN1 gene)
|MEN type 2A (Sipple syndrome)
|Medullary thyroid carcinoma
|10q11.2 (RET gene)
|MEN type 2B
|Medullary thyroid carcinoma
|10q11.2 (RET gene)
MEN Type 1 (MEN1) Syndrome (Wermer Syndrome)
MEN1 syndrome is an autosomal dominant disorder characterized by the presence of tumors in the parathyroid, pancreatic islet cells, and anterior pituitary. Diagnosis of this syndrome should be considered when two endocrine tumors listed in Table 1 are present.
Clinical practice guidelines recommend that screening for patients with MEN1 syndrome begins by the age of 5 years and continues throughout life. The tests for screening are age specific and may include yearly serum calcium, parathyroid hormone, gastrin, glucagon, secretin, proinsulin, chromogranin A, prolactin, and IGF-1. Radiological screening should include magnetic resonance imaging of the brain and computed tomography of the abdomen every 1 to 3 years.[
One study documented the initial presentation of MEN1 syndrome occurring before age 21 years in 160 patients.[
MEN1 germline mutations are found in 70% to 90% of patients; however, this gene is frequently inactivated in sporadic tumors.[
MEN Type 2A (MEN2A) and MEN Type 2B (MEN2B) Syndromes
A germline activating mutation in the RET oncogene (a receptor tyrosine kinase) is responsible for the uncontrolled growth of cells in medullary thyroid carcinoma associated with MEN2A and MEN2B syndromes.[
MEN2A is characterized by the presence of two or more endocrine tumors (see Table 1) in an individual or in close relatives.[
The most-recent literature suggests that this entity should not be identified as a form of hereditary medullary thyroid carcinoma that is separate from MEN2A and MEN2B. Familial medullary thyroid carcinoma should be recognized as a variant of MEN2A, to include families with only medullary thyroid cancer who meet the original criteria for familial disease. The original criteria includes families of at least two generations with at least two, but less than ten, patients with RET germline mutations; small families in which two or fewer members in a single generation have germline RET mutations; and single individuals with a RET germline mutation.[
MEN2B is characterized by medullary thyroid carcinomas, parathyroid hyperplasias, adenomas, pheochromocytomas, mucosal neuromas, and ganglioneuromas.[
A pentagastrin stimulation test can be used to detect medullary thyroid carcinoma in these patients. However, the patient management is driven primarily by the results of genetic analysis for RET mutations.[
A review of 38 patients with genetically confirmed MEN2B at the National Institutes of Health identified eight patients who developed pheochromocytoma in the course of follow-up.[
A retrospective analysis identified 167 children with RET mutations who underwent prophylactic thyroidectomy. This group included 109 patients without a concomitant central node dissection and 58 patients with a concomitant central node dissection. Children were classified into risk groups by their specific type of RET mutation.[
For more information, see Table 1 in Childhood Thyroid Cancer Treatment.
In a small percentage of cases, Hirschsprung disease has been associated with the development of neuroendocrine tumors such as medullary thyroid carcinoma. RET germline inactivating mutations have been detected in up to 50% of patients with familial Hirschsprung disease and less often in the sporadic form.[
Guidelines for genetic testing of patients suspected of having MEN2 syndrome and the correlations between the type of mutation and the risk levels of aggressiveness of medullary thyroid cancer have been published.[
|Medullary Thyroid Carcinoma
| a Sources: de Krijger,[
|20% to 30%
Cancer in children and adolescents is rare, although the overall incidence has been slowly increasing since 1975.[
For information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.
The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer.[
Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[
Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[
The designation of a rare tumor is not uniform among pediatric and adult groups. In adults, rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people. They account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[
Most cancers in subgroup XI are either melanomas or thyroid cancers, with other cancer types accounting for only 2% of the cancers in children aged 0 to 14 years and 9.3% of the cancers in adolescents aged 15 to 19 years.
These rare cancers are extremely challenging to study because of the low number of patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the lack of clinical trials for adolescents with rare cancers.
Treatment options for childhood MEN syndromes, according to type, are as follows:
MEN Type 1 (MEN1) Syndrome
The treatment of patients with MEN1 syndrome is based on the type of tumor. The outcomes of patients with MEN1 syndrome are generally good provided adequate treatment can be obtained for parathyroid, pancreatic, and pituitary tumors.
The standard approach to patients who present with hyperparathyroidism and MEN1 syndrome is genetic testing and treatment with a cervical resection of at least three parathyroid glands and transcervical thymectomy.[
For more information, see the Interventions section in Genetics of Endocrine and Neuroendocrine Neoplasias.
MEN Type 2 (MEN2) Syndromes
The management of medullary thyroid cancer in children from families having MEN2 syndromes relies on presymptomatic detection of the RET proto-oncogene mutation responsible for the disease.
For children with MEN2A, thyroidectomy is commonly performed by approximately age 5 years or older if that is when a RET mutation is identified.[
A retrospective analysis identified 262 patients with MEN2A syndrome.[
Young children who are relatives of patients with MEN2A undergo genetic testing before the age of 5 years. Carriers undergo total thyroidectomy as described above, with autotransplantation of one parathyroid gland by a certain age.[
Patients with MEN2B syndrome have worse outcomes primarily because medullary thyroid carcinoma is more aggressive. Because of the increased severity of medullary thyroid carcinoma in children with MEN2B and in those with RET mutations in codons 883, 918, and 922, it is recommended that these children undergo prophylactic thyroidectomy in infancy.[
Targeted therapy has been used for patients with the RET gene mutation and medullary thyroid cancer. Types of targeted therapy include the following:
Vandetanib (a kinase inhibitor)
A randomized phase III trial included adult patients with unresectable locally advanced or metastatic hereditary or sporadic medullary thyroid carcinoma who were treated with either vandetanib (a selective inhibitor of RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor) or placebo. The study found that vandetanib administration was associated with significant improvements in progression-free survival (PFS), response rate, disease control rates, and biochemical response.[
Children with locally advanced or metastatic medullary thyroid carcinoma were treated with vandetanib in a phase I/II trial.[
Selpercatinib (a RET inhibitor)
A phase I/II trial of selpercatinib therapy included patients with RET-mutant cancers. The study enrolled 55 patients with medullary thyroid cancer (age range, 17–84 years) who were previously treated with vandetanib and/or cabozantinib and 88 patients with medullary thyroid cancer (age range, 15–82 years) who were not previously treated with vandetanib or cabozantinib.[
Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website.
The following are examples of national and/or institutional clinical trials that are currently being conducted:
Patients with tumors that have molecular variants addressed by open treatment arms in the trial may be enrolled in treatment on Pediatric MATCH. Additional information can be obtained on the NCI website and ClinicalTrials.gov website.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
This summary was reformatted.
Special Considerations for the Treatment of Children With Cancer
Revised text to state that between 1975 and 2020, childhood cancer mortality decreased by more than 50% (cited National Cancer Institute as reference 4 and Surveillance Research Program, National Cancer Institute as reference 5).
Revised text to state that rare pediatric cancers account for about 5% of the cancers diagnosed in children aged 0 to 14 years and about 27% of the cancers diagnosed in adolescents aged 15 to 19 years. Also revised text to state that most cancers in subgroup XI are either melanomas or thyroid cancers, with other cancer types accounting for only 2% of the cancers in children aged 0 to 14 years and 9.3% of cancers in adolescents aged 15 to 19 years.
This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of pediatric multiple endocrine neoplasia (MEN) syndromes. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
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PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Multiple Endocrine Neoplasia (MEN) Syndromes Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/multiple-endocrine-neoplasia/hp-child-men-syndromes-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 31909948]
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Last Revised: 2023-01-06
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