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