Sippel's Syndrome
Monday, May 8, 2017

Return to: Medullary Thyroid Carcinoma

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

Overview

  1. Background
    • MEN IIB is caused by mutations in the RET proto-oncogene, generally in the TK1 domain.
    • 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) - multiple mucosal neuromas are a dominant feature of MEN 2B
    • Early recognition is key to preventing metastatic medullary thyroid cancer.
  2. Workup
    • Baseline serum calcitonin, calcium, CEA
    • Screening for pheochromocytoma
    • Thyroid, central and lateral neck ultrasound
    • CT chest or PET imaging for large tumors (>1cm), evidence of nodal disease or serum calcitonin >400pg/ml
    • Genetic testing, genetic counseling
  3. Management: Multidisciplinary team approach with Otolaryngology, Endocrinology, Gastroenterology, Oncology, Genetics, Social Work
    • Thyroid:
      • 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)
      • If tumor is >0.5cm at presentation, consider extensive neck dissection (levels II-V)
      • For large tumors, positive surgical margin, ETE (extra-thyroidal extension), may benefit from external beam radiation
      • Tyrosine kinase inhibitors: vandetanib or cabozantinib
    • Parathyroids:
      • Hyperparathyroid is common and can manifest with elevated serum calcium, bone pain, kidney stones, nausea, and depression
      • Management is removal of adenoma or 3.5 parathyroid glands (see Parathyroidectomy)
    • Monitoring:
      • Patients should be followed regularly after thyroidectomy to monitor for recurrence
      • 2-3 month post-op calcitonin and CEA levels. If >150pg/ml, image neck, chest and abdomen for persistent/recurrent disease
      • Annual calcitonin, CEA and calcium levels
      • Regular blood pressure checks

Images

MEN2b intraoral mucosal neuromas

 

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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.