Multiple Endocrine Neoplasias - MEN

  • Diagnosis
  • Algorithms
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics
  • Videos

Multiple Endocrine Neoplasia 1 (MEN1)

  • Periodic screening for MEN1-associated endocrine tumors beginning in early childhood and continuing for life (NCCN, 2016)
    • Consider annual testing for the following
      • Parathyroid tumor
      • Pancreatic neuroendocrine tumor
      • Bronchial carcinoid/thymic carcinoid previously
        • Chest imaging at 1-3 years
      • Pituitary
        • Previous pituitary – MRI at 3-5 years
        • No previous pituitary
          • IGF-1
        • Prolactin
  • Risk for malignant progression of MEN1-associated tumors depends on tumor type
    • Malignancy uncommon before early adulthood

Multiple Endocrine Neoplasia 2 (MEN2)

Multiple endocrine neoplasia (MEN) syndromes are characterized by tumors involving multiple endocrine glands. Subtypes MEN1 and MEN2 are distinguished by clinical features and molecular testing. MEN2 includes the additional subtypes MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC).

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Multiple Endocrine Neoplasia Type 1 (MEN1) Sequencing and Deletion/Duplication 2005360
Method: Polymerase Chain Reaction/Sequencing/Multiplex Ligation-dependent Probe Amplification

Limitations 

Not evaluated – regulatory region mutations, deep intronic mutations, breakpoints of large deletions/duplications, and mutations in genes other than MEN1

Diagnostic errors can occur due to rare sequence variations

Multiple Endocrine Neoplasia Type 2 (MEN2), RET Gene Mutations by Sequencing 0051390
Method: Polymerase Chain Reaction/Sequencing

Limitations 

Not evaluated – regulatory region mutations, deep intronic mutations, large deletions/duplications, and RET exons other than 5, 8, 10, 11, 13-16 

Diagnostic errors can occur due to rare sequence variations

Endocrine Hereditary Cancer Panel, Sequencing and Deletion/Duplication, 13 Genes 2010193
Method: Massively Parallel Sequencing/Exonic Oligonucleotide-based CGH Microarray

Limitations 

Diagnostic errors can occur due to rare sequence variations

Not determined or evaluated – Mutations in genes not included on the panel; deep intronic and regulatory region mutations; structural and numerical chromosomal abnormalities; breakpoints for large deletions/duplications

Deletions/duplications may not be detected in exon 1 in RET gene; exon 8 in PTEN gene; exons 4, 6, and 7 in STK11 gene

Lack of a detectable gene mutation does not exclude a diagnosis of hereditary endocrine cancer; not all predisposing genes are analyzed

Familial Mutation, Targeted Sequencing 2001961
Method: Polymerase Chain Reaction/Sequencing

Follow-up 

For assistance in ordering this test, contact a genetic counselor

Guidelines

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, Marx SJ. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 2001; 86(12): 5658-71. PubMed

NCCN Clinical Practice Guidelines in Oncology, Neuroendocrine Tumors. National Comprehensive Cancer Network. Fort Washington, PA [Accessed: Mar 2016]

Protocol for the Examination of Specimens from Patients with Carcinomas of the Thyroid Gland. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: Jan 2016. College of American Pathologists (CAP). Northfield, IL [Accessed: Nov 2015]

Protocol for the Examination of Specimens from Patients with Neuroendocrine Tumors (Carcinoid Tumors) of the Appendix. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: Jan 2016. College of American Pathologists (CAP) . Northfield, IL [Accessed: Sep 2015]

Protocol for the Examination of Specimens from Patients with Neuroendocrine Tumors (Carcinoid Tumors) of the Colon and Rectum. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: Oct 2013. College of American Pathologists (CAP). Northfield, IL [Accessed: Sep 2015]

Protocol for the Examination of Specimens from Patients with Neuroendocrine Tumors (Carcinoid Tumors) of the Small Intestine and Ampulla. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: Oct 2013. College of American Pathologists (CAP). Northfield, IL [Accessed: Sep 2015]

Protocol for the Examination of Specimens from Patients with Neuroendocrine Tumors (Carcinoid Tumors) of the Stomach. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: Oct 2013. College of American Pathologists (CAP). Northfield, IL [Accessed: Nov 2015]

Protocol for the Examination of Specimens from Patients with Tumors of the Brain/Spinal Cord. No AJCC/UICC TNM Staging System. Protocol web posting date: Dec 2014. College of American Pathologists (CAP). Northfield, IL [Revised Dec 2014; Accessed: Jun 2015]

Protocol for the Examination of Specimens from Patients with Tumors of the Endocrine Pancreas. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: Jan 2016. College of American Pathologists (CAP). Northfield, IL [Accessed: Nov 2015]

Thakker RV, Newey PJ, Walls GV, Bilezikian J, Dralle H, Ebeling PR, Melmed S, Sakurai A, Tonelli F, Brandi ML, Endocrine Society. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012; 97(9): 2990-3011. PubMed

General References

Almeida MQ, Stratakis CA. Solid tumors associated with multiple endocrine neoplasias. Cancer Genet Cytogenet. 2010; 203(1): 30-6. PubMed

DeLellis RA. Parathyroid tumors and related disorders. Mod Pathol. 2011; 24 Suppl 2: S78-93. PubMed

Duerr E, Chung DC. Molecular genetics of neuroendocrine tumors. Best Pract Res Clin Endocrinol Metab. 2007; 21(1): 1-14. PubMed

Giusti F, Marini F, Brandi M. Multiple Endocrine Neoplasia Type 1. In: Pagon RA, Adam MP, Ardinger HH, et al, editors. GeneReviews, University of Washington, 1993-2015. Seattle, WA [Last updated Feb 2015; Accessed: Nov 2015]

Marquard J, Eng C. Multiple Endocrine Neoplasia Type 2. In: Pagon RA, Adam MP, Ardinger HH, et al, editors. GeneReviews, University of Washington, 1993-2015. Seattle, WA [Last updated Jun 2015; Accessed: Nov 2015]

Marsh DJ, Gimm O. Multiple endocrine neoplasia: types 1 and 2. Adv Otorhinolaryngol. 2011; 70: 84-90. PubMed

Nosé V. Familial thyroid cancer: a review. Mod Pathol. 2011; 24 Suppl 2: S19-33. PubMed

Raue F, Frank-Raue K. Update multiple endocrine neoplasia type 2. Fam Cancer. 2010; 9(3): 449-57. PubMed

Thakker RV. Multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4). Mol Cell Endocrinol. 2014; 386(1-2): 2-15. PubMed

Walls GV. Multiple endocrine neoplasia (MEN) syndromes. Semin Pediatr Surg. 2014; 23(2): 96-101. PubMed

Zhang Y, Nosé V. Endocrine tumors as part of inherited tumor syndromes. Adv Anat Pathol. 2011; 18(3): 206-18. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Agarwal AM, Bentz JS, Hungerford R, Abraham D. Parathyroid fine-needle aspiration cytology in the evaluation of parathyroid adenoma: cytologic findings from 53 patients. Diagn Cytopathol. 2009; 37(6): 407-10. PubMed

ARUP Scientific Resource for Research and Education. Multiple endocrine neoplasia and MEN1 missense variants. ARUP Laboratories, University of Utah. Salt Lake City, UT [Accessed: Nov 2012]

Margraf RL, Calderon FR, Mao R, Wittwer CT. RET mutation scanning update: exon 15. Clin Chem. 2009; 55(11): 2059-61. PubMed

Margraf RL, Crockett DK, Krautscheid PM, Seamons R, Calderon FR, Wittwer CT, Mao R. Multiple endocrine neoplasia type 2 RET protooncogene database: repository of MEN2-associated RET sequence variation and reference for genotype/phenotype correlations. Hum Mutat. 2009; 30(4): 548-56. PubMed

Margraf RL, Durtschi JD, Stephens JE, Perez M, Voelkerding KV. Determination of RET Sequence Variation in an MEN2 Unaffected Cohort Using Multiple-Sample Pooling and Next-Generation Sequencing. J Thyroid Res. 2012; 2012: 318232. PubMed

Margraf RL, Mao R, Highsmith E, Holtegaard LM, Wittwer CT. RET proto-oncogene genotyping using unlabeled probes, the masking technique, and amplicon high-resolution melting analysis. J Mol Diagn. 2007; 9(2): 184-96. PubMed

Margraf RL, Mao R, Wittwer CT. Rapid diagnosis of MEN2B using unlabeled probe melting analysis and the LightCycler 480 instrument. J Mol Diagn. 2008; 10(2): 123-8. PubMed

Marquard J, Eng C. Multiple Endocrine Neoplasia Type 2. In: Pagon RA, Adam MP, Ardinger HH, et al, editors. GeneReviews, University of Washington, 1993-2015. Seattle, WA [Last updated Jun 2015; Accessed: Nov 2015]

Medical Reviewers

Last Update: August 2016