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MEN 2b (Multiple Endocrine Neoplasia 2b) Sippels Syndrome

last modified on: Mon, 12/11/2023 - 15:26

return to: Medullary Thyroid Carcinoma

see also: Neural Crest Cell Tumors (PNT = peripheral neuroblastic tumors)

MEN IIB: Sippels syndrome

  1. Background
    1. MEN IIB is caused by mutations in the RET proto-oncogene, generally in the TK1 domain. 
    2. Classic clinical symptoms include Medullary thyroid cancer in infancy or childhood, pheochromocytoma, marfanoid habitus (Tall, thin, increased joint laxity), mucosal neuromas (tongue, eyelids, GI tract).
    3. Early recognition is key to preventing metastatic medullary thyroid cancer.
  2. Workup
    1. Baseline serum calcitonin, calcium, CEA
    2. Screening for pheochromocytoma
    3. Thyroid, central and lateral neck ultrasound
    4. CT chest or PET imaging for large tumors (>1cm), evidence of nodal disease or serum calcitonin >400pg/ml
    5. Genetic testing, genetic counseling
  3. Management: Multidisiplinary team approach with Otolaryngology, Endocrinology, Gastroenterology, Oncology, Genetics, Social Work
    1. Thyroid: 
      1. Total thyroidectomy with level VI (central neck) lymph node dissection before age 1 is recommended for all known MENII patients (see Thyroidectomy and Thyroid Lobectomy)
      2. If tumor is >0.5cm at presentation, consider extensive neck dissection (levels II-V)
      3. For large tumors, positive surgical margin, ETE (extra-thyroidal extension), may benefit from external beam radiation
      4. Tyrosine kinase inhibitors: vandetanib or cabozantinib
    2. Parathyroids: 
      1. Hyperparathyroid is common and can manifest with elevated serum calcium, bone pain, kidney stones, nausea, and depression
      2. Management is removal of adenoma or 3.5 parathyroid glands (see Parathyroidectomy)
    3. Monitoring: 
      1. Patients should be followed regularly after thyroidectomy to monitor for recurrence
      2. 2-3 month post-op calcitonin and CEA levels. If >150pg/ml, image neck, chest and abdomen for persistent/recurrent disease
      3. Annual calcitonin, CEA and calcium levels
      4. Regular blood pressure checks

Multiple mucosal neuromas are a dominant feature of MEN 2b

Multiple endocrine neoplasia IIb

MEN2b intraoral mucosal neuromas

References

Pujol RM, Matias-Guiu X, Miralles J, Colomer A, de Moragas JM (August 1997). "Multiple idiopathic mucosal neuromas: a minor form of multiple endocrine neoplasia type 2B or a new entity?". J. Am. Acad. Dermatol. 37 (2 Pt 2): 349–52.

Ferreira CV, Siqueira DR, Ceolin L, Maia AL. May 2012.  Advanced medullary thyroid cancer: pathophysiology and management Cancer Manag Res. 2013 May 8;5:57-66. doi: 10.2147/CMAR.S33105. Print 2013.

Shankar RK, Rutter MJ, Chernausek SD, Samuels PJ, Mo JQ, Rutter MM. Medullary thyroid cancer in a 9-week-old infant with familial MEN 2B: Implications for timing of prophylactic thyroidectomy. Int J Pediatr Endocrinol. 2012 Sep 19;2012(1):25. doi: 10.1186/1687-9856-2012-25.

NCCN National comprehensive Cancer Network Guidelines, Thyroid Carcinoma version 2.2013

Mathiesen JS, Effraimidis G, Rossing M, Rasmussen ÅK, Hoejberg L, Bastholt L, Godballe C, Oturai P, Feldt-Rasmussen U. Multiple endocrine neoplasia type 2: A review. Semin Cancer Biol. 2022 Feb;79:163-179. doi: 10.1016/j.semcancer.2021.03.035. Epub 2021 Apr 1. PMID: 33812987.