Endocrine related neoplasia syndromes in pregnancy

Key points

• Endocrine neoplasia syndromes are rare but are estimated to affect 100 pregnancies per year in the UK.
• There are currently no guidelines for the management or surveillance of women with MEN1, MEN2/3 or VHL in pregnancy.
• Data on pregnancy outcomes and risks for women with endocrine neoplasia syndromes are limited and largely based on anecdotal case reports or small retrospective series focused on specific tumour types or a specific endocrine condition.
• There is a need to better understand the impact of MEN1, MEN 2/3 and VHL on pregnancy outcomes to enable clinicians to more accurately counsel women of reproductive age with these syndromes.

Surveillance period

1st October 2026 – 30th September 2028

Background

Multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2/3 (MEN2/3) and Von Hippel Lindau (VHL) are hereditary endocrine tumour syndromes that are most frequently identified through genetic testing of at-risk family members. These genetic syndromes are rare but cumulatively are estimated to affect 100 pregnancies per year in the UK. Small studies and anecdotal case reports suggest increased maternal and neonatal complications in pregnancies affected by these genetic syndromes, but at present there are no guidelines for the management or surveillance of pregnancy for women with MEN1, MEN2/3 and VHL. This study will enable us to determine the incidence of MEN1, MEN2/3 and VHL in pregnancy and describe the management of both maternal and neonatal outcomes.

Objective

To use the UK Obstetric Surveillance System (UKOSS) to describe the incidence and management of endocrine related neoplasia syndromes in pregnancy in the UK, and the maternal and neonatal outcomes.

Research questions

• What is the incidence of MEN1, MEN2/3 and VHL in pregnancy in the UK?
• What are the risk factors associated with MEN1, MEN2/3 or VHL and adverse pregnancy outcomes?
• How are pregnant women with MEN1, MEN2/3 or VHL managed in the UK?
• What are the outcomes of MEN1, MEN2/3 or VHL in pregnancy for mothers and their babies?
• Are there differences in pregnancy outcomes associated with the surveillance strategy and duration of the surveillance prior to pregnancy in women with MEN1, MEN2/3 or VHL?

Case definition

All pregnant women identified as having a genetic diagnosis of MEN1*, MEN 2/3** (former name MEN2B) or VHL***.

*Multiple endocrine neoplasia type 1 (caused by an inherited pathogenic variant in the MEN1)

**Multiple endocrine neoplasia type 2 or 3 (caused by inherited pathogenic variants in the RET gene)

***Von Hippel Lindau syndrome (caused by inherited pathogenic variants in the VHL gene)

Funding

This study is funded by Addenbrookes Charitable Trust.

Ruth Casey is supported by the Cambridge NIHR Biomedical Research Centre (NIHR203312).

Ethics committee approval

This study has been approved by the London Brent REC (Ref. Number: 10/H0717/20).

Lead Investigator

Dr Ruth Casey, Cambridge University Hospitals NHS Foundation Trust.

References

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