What testing can be done for a patient with a family history of thyroid cancer who is adopted?

Testing for Adopted Patients with Family History of Thyroid Cancer

For an adopted patient with a family history of thyroid cancer, refer them for genetic counseling and RET proto-oncogene testing if the family history suggests medullary thyroid cancer (MTC), and consider thyroid ultrasound screening if the family history indicates non-medullary thyroid cancer (NMTC) with three or more affected family members. 1, 2

Initial Assessment and History Gathering

The critical first step is determining what type of thyroid cancer affected the biological family members, as this fundamentally changes your testing approach 1:

• Type of thyroid cancer (medullary vs. non-medullary/papillary/follicular) 1
• Number of affected first-degree relatives (parents, siblings) 1
• Age at diagnosis of affected relatives 1
• Ethnicity (particularly relevant for certain hereditary syndromes) 1
• Any known genetic testing results in biological relatives 1

For Medullary Thyroid Cancer (MTC) Family History

If the family history suggests MTC, immediate referral for genetic counseling and RET genetic testing is mandatory 1, 2:

• RET proto-oncogene testing should be performed, as germline RET mutations cause Multiple Endocrine Neoplasia type 2 (MEN2A, MEN2B) and familial MTC 2
• The de novo mutation rate is 9% in MEN2A and up to 50% in MEN2B, making testing essential even without detailed family history 2
• RET mutations are found in at least 95% of MEN2A kindreds and 88% of familial MTC cases 2

Additional biochemical screening for MTC includes 1:

• Serum calcitonin levels (though controversy exists about routine screening in the U.S.) 1
• Carcinoembryonic antigen (CEA) levels 1
• Screening for pheochromocytoma (plasma metanephrines) before any intervention, as 50% of MEN2 patients develop pheochromocytomas 2
• Screening for hyperparathyroidism (calcium, PTH) as 20-30% of MEN2A patients develop this 2

Risk-Stratified Management Based on RET Mutation

If a RET mutation is identified, the specific codon determines timing of prophylactic thyroidectomy 2:

• Highest Risk (Grade 1) mutations (codons 883,918,922): thyroidectomy within first year of life 2
• High Risk (Grade 2) mutations (codons 609,611,620,630,634,804,891): thyroidectomy before age 5-6 years 2
• Moderate Risk (Grade 3) mutations (codons 768,790,791): annual calcitonin testing and ultrasound with deferred surgery if normal 1, 2

For Non-Medullary Thyroid Cancer (NMTC) Family History

The approach differs significantly based on the number of affected family members 1, 3:

Three or More Affected Family Members

Implement annual thyroid ultrasound screening 3:

• Screening detected thyroid cancer in 22.7% of at-risk individuals from families with three or more affected members 3
• Cancers detected by screening were smaller (0.7 cm vs. 1.5 cm), had fewer lymph node metastases (17.6% vs. 51.1%), and required less aggressive treatment 3
• Fine-needle aspiration (FNA) should be performed for nodules >0.5 cm 3

Two Affected Family Members

Consider thyroid ultrasound screening, though yield is lower 3:

• Only 4.6% of at-risk individuals from families with two affected members developed cancer during screening 3
• The decision should weigh individual risk factors and patient preference 3

Associated Syndrome Screening

Evaluate for familial cancer syndromes that include thyroid cancer 1, 4:

• Cowden syndrome (PTEN mutation): Look for 2+ additional Cowden criteria (macrocephaly, mucocutaneous lesions, breast cancer, endometrial cancer) 1
• Familial adenomatous polyposis (APC mutation): Screen for cribriform-morular variant papillary thyroid cancer and gastrointestinal polyps 1
• Carney complex (PRKAR1A mutation): Look for additional Carney criteria (cardiac myxomas, skin pigmentation, endocrine tumors) 1

Genetic Counseling Referral Criteria

Refer for cancer predisposition assessment if 1:

• Any medullary thyroid cancer in the family history 1
• Non-medullary thyroid cancer plus one additional Carney complex criterion 1
• Non-medullary thyroid cancer plus two additional Cowden syndrome criteria 1
• Papillary thyroid cancer (cribriform-morular variant) 1

Important Clinical Caveats

Familial non-medullary thyroid cancer characteristics 5, 6:

• Papillary thyroid carcinoma constitutes 91% of familial cases 5
• Familial papillary thyroid cancer shows more multifocality (49%), bilateral growth, and concomitant nodular goiter compared to sporadic cases 6
• Family history is an independent risk factor for recurrence, particularly in papillary thyroid microcarcinoma 6

Avoid overtreatment 3, 5:

• Active screening may lead to detection of indolent disease that would never become clinically significant 3
• Implement screening with caution, particularly in elderly individuals 3
• Treatment should be based on disease stage and risk factors, not solely on family history 5

Genetic testing limitations 7:

• Unlike MTC, specific susceptibility genes for familial papillary and follicular thyroid cancer remain poorly defined 7
• These likely follow autosomal dominant inheritance with reduced penetrance 4, 7
• Only 5-6% of non-medullary thyroid cancers are familial 4, 7