Skip to main content
Public beta This website is in public beta – please give your feedback.

Example clinical scenario

A 36-year-old woman presents with amenorrhea and is found to have an elevated serum prolactin level of 1600mU/l. Investigation identifies an 8mm pituitary microadenoma consistent with a microprolactinoma. She is also found to have biochemical evidence of primary hyperparathyroidism. Her father has a history of primary hyperparathyroidism and is on treatment for recurrent peptic ulcers.

When to consider genomic testing

  • Indications for genomic testing for multiple endocrine neoplasia type 1 (MEN1) include:
    • parathyroid multiglandular disease (hyperplasia or adenomas) at 35 years of age or younger;
    • any pituitary adenoma or insulinoma at 20 years of age or younger;
    • pituitary macroadenoma at under 30 years of age;
    • two or more MEN1-related endocrine anomalies at any age,
    • one or more MEN1-related endocrine anomaly and one or more MEN1-related non-endocrine tumour at any age; and
    • one or more MEN1-related endocrine anomaly and a first-degree relative with one or more MEN1-related endocrine anomaly.

Please bear the following points in mind.

  • MEN1-related endocrine anomalies include:
    • parathyroid hyperplasia or multiglandular adenomas;
    • pituitary tumours;
    • endocrine tumours of the gastro-entero-pancreatic tract;
    • carcinoid tumours; and
    • adrenocortical tumours.
  • MEN1-related non-endocrine tumours include:
    • facial angiofibromas;
    • collagenoma; and
    • meningioma.
  • Due to constitutional (germline) pathogenic variants in the CDKN1B gene, multiple endocrine neoplasia type 4 (MEN4) has a similar phenotype to MEN1 but occurs less frequently.
  • If a patient does not meet the above criteria for genomic testing, but there is strong clinical suspicion of MEN1 (or MEN4), testing may be appropriate after discussion in a specialist multidisciplinary team meeting.

What do you need to do?

  • 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 containing details of all available tests.
  • To find out which genes are included on the different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
  • Genomic testing for MEN1 is included in several panels, and selecting the most appropriate panel will depend on the clinical context.
  • For patients who present with a combination of relevant MEN1-associated endocrine tumours, meet the test directory eligibility criteria for MEN1 and do not have a personal or family history of a genetic variant, you should select the endocrine neoplasia panel:
    • R217 Endocrine neoplasia. This currently comprises the genes AIP, CDC73, CDKN1B, MEN1, PRKAR1A, RET and VHL. It involves small gene panel sequencing for these genes, as well as exon-level copy number variant (CNV) analysis by multiplex ligation-dependent probe amplification (MLPA) or equivalent (R217.2) for AIP, CDC73 CDKN1B and MEN1. Typically, both R217.1 and R217.2 are performed simultaneously, but discussion with the local testing laboratory may be appropriate in some situations (for example, if you wish to request CNV or MLPA analysis for patients in whom prior testing has been limited to gene sequence analysis).
    • This panel is also used to investigate other endocrine neoplasia disorders (for example, familial isolated pituitary adenoma and multiple endocrine neoplasia type 2 (MEN2)).
  • Overlapping clinical indications for MEN1 genomic testing are listed below.
    • R151: Familial hyperparathyroidism or FHH test panel. Patients with early onset and/or multi-gland parathyroid disease in the absence of other features of MEN1 should be assessed with this panel. It currently comprises the genes AP2S1, CASR, CDC73, CDKN1B, GNA11, MEN1 and RET. For more information, see Presentation: Patient with possible familial hyperparathyroidism.
    • R223 Inherited phaeochromocytoma and paraganglioma (PPGL) excluding NF1. Patients presenting with PPGL, which is extremely rare in MEN1, should undergo testing via the R223 panel, which currently comprises the genes DLST1, FH, MAX, MDH2, MEN1, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, SLC25A11, TMEM127 and VHL.
    • R226 Inherited parathyroid cancer. Patients with parathyroid carcinoma, which is extremely rare in MEN1, should undergo testing via the R226 panel. This includes CDC73 single gene testing. For more information, see Presentation: Patient with parathyroid carcinoma.
    • R359 Childhood solid tumours. This panel is only used for solid invasive tumours in children (less than 18 years of age) in whom no other testing indication is appropriate. The R359 panel contains 83 ‘green’ genes, including MEN1.
  • For patients in whom a genetic diagnosis of MEN1 has been established in another family member, single gene testing for the specific variant in MEN1 can be considered.
    • If the patient has clinical features of endocrine disease, R240 Diagnostic testing for known mutation(s) could be selected – provided the pathogenic variant report about the close family member is available and testing was performed in an accredited laboratory.
    • If the patient reports a family history of endocrine neoplasia but has no clinical features of disease themselves, referral to clinical genetics for consideration of predictive genomic testing should be undertaken, provided the pathogenic variant report about the close family member is available and testing was performed in an accredited laboratory.
    • Because these tests do not include whole genome sequencing, you should use your local Genomic Laboratory Hub test order and record of discussion forms.
  • These tests are DNA based, and an EDTA sample (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 was 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.

Resources

For clinicians

References:

↑ Back to top
  • Last reviewed: 29/06/2023
  • Next review due: 29/06/2024
  • Authors: Dr Paul Newey
  • Reviewers: Dr Danielle Bogue, Dr Louise Izatt, Professor Márta Korbonits, Dr Tobi Soge