Presentation: Patient with medullary thyroid carcinoma

A 25-year-old woman presents with a painless neck mass and a 12-week history of diarrhoea. Ultrasound imaging identifies a 2cm thyroid nodule and surrounding cervical adenopathy, and a staging CT scan reveals a 5cm heterogeneous left-sided adrenal mass. Biochemical testing reveals an elevated fasting serum calcitonin and elevated plasma normetadrenaline and metadrenaline, confirming a diagnosis of medullary thyroid carcinoma and a phaeochromocytoma.

Constitutional (germline) genomic testing should be considered for all patients with:

• confirmed medullary thyroid carcinoma at any age;
• more than two multiple endocrine neoplasia type 2 (MEN2)-related endocrine anomalies (at any age); or
• more than one MEN2-related endocrine anomaly and a first-degree relative with more than one MEN2-related endocrine anomaly.

Note that MEN2-related endocrine anomalies include:

• medullary thyroid carcinoma;
• pheochromocytoma;
• paraganglioma;
• parathyroid adenoma;
• hyperplasia; and
• Hirschsprung disease.

• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria, which provides information about individual tests and their associated eligibility criteria. You can also access a spreadsheet of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• For patients who have a confirmed diagnosis of medullary thyroid carcinoma, or meet test directory eligibility criteria for MEN2 testing, and do not have a personal or family history of a genetic variant in the RET gene, select the following:
  • R218 Multiple endocrine neoplasia type 2 (this involves RET single gene testing).
• Similar or overlapping tests include the below.
  • R217 Endocrine neoplasia: This should be considered for patients who meet test directory eligibility criteria for endocrine neoplasia. It currently comprises the following genes: AIP, CDC73, CDKN1B, MEN1, PRKAR1A, RET and VHL. It involves small gene panel sequencing.
  • R225 Von Hippel Lindau syndrome: This should be considered for patients who meet test eligibility criteria for Von Hippel-Lindau (VHL). It involves VHL single gene testing.
  • R213 PTEN hamartoma tumor syndrome: This should be considered for patients with macrocephaly (over the 99th centile) and epithelial non-medullary thyroid cancer. It involves PTEN single gene testing.
  • R156 Carney complex: This should be considered for patients with two or more tumours or non-tumour syndromic features. It involves PRKAR1A single gene testing. For more information about testing, see Presentation: Patient with Carney complex.
• None of the tests outlined above include whole genome sequencing, so you should use your local Genomic Laboratory Hub test order and consent (record of discussion) forms.
• The majority of tests are DNA based, and an EDTA sample (typically a purple-topped tube) is required. The sample is best stored at four degrees Celsius until it can be posted to the genomic laboratory.
• Information about patient eligibility and test indications were correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• NHS England: National Genomic Test Directory

For patients

• Association for Multiple Endocrine Neoplasia (AMEND)