Hereditary endocrine tumours

Genetic testing is clinically relevant for the following indications, including but not limited to:

• Two or more -associated endocrine tumours (parathyroid, pituitary or gastroenteropancreatic neuroendocrine tumours), or one such tumour in an individual with a relevant family history
• Medullary thyroid carcinoma at any age, or suggestive of or
• Early-onset, recurrent or familial primary hyperparathyroidism, parathyroid carcinoma, atypical parathyroid tumours, or ossifying fibroma of the jaw
• Pituitary gigantism, a growth-hormone-secreting pituitary adenoma of childhood or young adulthood, or a pituitary macroadenoma diagnosed before age 30 years
• Retinal or central nervous system haemangioblastoma, multiple renal cysts, pancreatic neuroendocrine tumour, or clear-cell renal cell carcinoma diagnosed before age 40 years
• Macrocephaly with multinodular goitre, differentiated thyroid carcinoma (particularly follicular thyroid carcinoma), mucocutaneous lesions, or other features suggestive of
• At-risk relatives of a known variant carrier, for predictive testing

Genetic testing is used when a hereditary endocrine tumour syndrome is suspected from the tumour pattern or the family history. The tumour patterns overlap, so the clinical picture alone rarely identifies the responsible gene. The identification of the genetic cause determines which organs enter surveillance, at which age surveillance starts and if prophylactic surgery should be considered.

A pathogenic or likely pathogenic variant establishes the specific molecular diagnosis, identifying the causative gene and the associated tumour-predisposition syndrome. A variant of uncertain significance (VUS) is an unclear finding: current evidence is insufficient to classify it as likely benign or likely pathogenic, and reanalysis can be offered after a few years as evidence accumulates. In other cases, no pathogenic variant is detected in the analysed genes. The presence of a pathogenic variant cannot, however, be entirely excluded: the causative change may lie in a gene not yet linked to the condition, or in a regulatory region that current methods cannot reliably capture.

Each variant is classified according to ACMG/AMP criteria.

When a germline pathogenic variant is identified, organ-specific surveillance can begin and risk-reducing options can be considered for the confirmed syndrome. Penetrance differs widely across these conditions, so the counselling that accompanies a positive result differs with the gene. The finding also concerns relatives, who can be offered predictive testing, so that carriers enter surveillance and non-carriers are spared it.

is an essential part of the testing process and is available both before and after testing. Our genetic counsellors conduct comprehensive family history assessments, explain the chosen testing methodology, its benefits, risks, and limitations, and provide guidance on result interpretation, management strategies, and recurrence risk. Counselling supports physicians in delivering informed care and helps patients and families make well-informed medical decisions. Availability of genetic counselling services may vary by country, so please to check for more information on access in your region.

Testing uses next-generation sequencing (NGS) based multi-gene panels.

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