Contemporary Challenges in the Management of Thyroid Cancer
May 2011
Volume 2, Issue 1

Familial Syndromes Associated with Thyroid Cancer in the Era of Personalized Medicine

Thyroid. 2010;20(7):707-13

Introduction:  Well-differentiated thyroid cancer makes up 95% of all thyroid malignancies.  Of those patients 5% will have familial disease. Medullary thyroid cancer (MTC) makes up only 1% of all patients with thyroid cancer, but 25% of these patients will have a familial or hereditary form.

The majority of cases of familial thyroid cancer are nonmedullary (NMFTC).  They are present in familial cancer syndromes such as:

  • Familial adenomatous polyposis
  • Cowden syndrome
  • Carney complex
  • Pendred syndrome
  • Werner syndrome

This review is on current management of  patients with familial syndrome-associated thyroid cancer. It advises screening and management practices based on their risks for developing thyroid cancer.

Summary:  In studying familial thyroid cancer, the most progress has been made in patients with MTC and the genetic details for this group, related to the RET proto oncogene, are well characterized.  However, the mutations in patients with isolated NMFTC have not been as well defined.  Likely, they are autosomal dominant with reduced penetrance.  It is likely that patients with these familial syndromes have a susceptibility gene that increases their risk of thyroid cancer.

Most of the familial cancer syndrome patients related to NMFTC will have papillary thyroid cancer. This suggests that there is a specific gene for papillary thyroid cancer that may also be present in these patients, although it has not been identified yet.

Patients who have one of the above familial syndromes have an increased risk for thyroid cancer. In most, if not all cases, these individuals should have thyroid ultrasound screening for the presence of suspicious nodules.

Conclusion:  In treating a patient with a familial syndrome associated with thyroid cancer, clinicians should categorize the patient based on syndrome risks for developing thyroid cancer.  It is also necessary for the clinician to be knowledgeable in recognizing various familial syndromes. Thus, when encountering a patient who may come to attention first because of thyroid cancer, appropriate referral to a genetic specialist can be made.


This excellent review article was presented at the national meeting of the American Thyroid Association in 2010. It helps to raise awareness of thyroid cancers that may have a hereditary basis. It describes the clinical picture seen with six different syndromes that are known to be associated with thyroid cancer. For the specialist who treats patients with thyroid disease, this article is a comprehensive resource. It provides guidelines about what to do when thyroid cancer is the abnormality that is diagnosed first. An astute clinician can recognize the possibility of an underlying hereditary condition and promote the further direction of medical care, beyond the thyroid problem. It also identifies the appropriate screening practices for patients who already carry a genetic syndrome diagnosis and may not have been evaluated yet for co-existing thyroid disease. Thyroid ultrasound is warranted as a basic and initial component of screening for thyroid cancer. Genetic counselors and physicians who specialize in genomic medicine are crucial to the care of these patients. They often are the center for personalized medicine that coordinates life-long care tailored to the needs of the individual patient and their families.

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