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Multiple endocrine neoplasia type 1
MEN1 is an inherited condition that causes tumours, most commonly in the parathyroid glands, pituitary gland, and pancreas. These tumours are often benign, but some can be cancerous, and they may lead to an overproduction of hormones, affecting various body functions.
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Overview
Multiple Endocrine Neoplasia Type 1 (MEN1) is a rare inherited disorder that significantly increases the risk of developing tumours in several endocrine glands. Endocrine glands are responsible for producing and releasing hormones that regulate various bodily functions. Individuals with MEN1 most frequently develop tumours affecting the parathyroid glands, pituitary gland, and specific cells within the pancreas [PMID:33671239]. While many of these tumours are benign (non-cancerous), some can be malignant (cancerous) or cause significant health problems due to excessive hormone production.
The condition affects approximately 1 in 30,000 people and typically presents in young to middle adulthood, though symptoms can begin earlier or later in life. As it is an inherited condition, MEN1 can run in families, and understanding its genetic basis informs diagnosis and management approaches.
Symptoms & clinical features
The symptoms of MEN1 are varied and depend on which glands are affected and whether the tumours are producing excess hormones. Parathyroid gland tumours are the most common feature, occurring in the vast majority of individuals with MEN1. These typically lead to hyperparathyroidism, where too much parathyroid hormone is produced, causing high calcium levels in the blood (hypercalcaemia). Symptoms of hypercalcaemia can include kidney stones, bone pain, fatigue, and stomach problems.
Pancreatic neuroendocrine tumours (pNETs) are also common and can produce various hormones, leading to symptoms such as recurrent stomach ulcers (gastrinomas), low blood sugar (insulinomas), or severe diarrhoea (VIPomas). Pituitary gland tumours are also a feature of MEN1 and can cause headaches, visual disturbances, or symptoms related to excess hormone production, such as galactorrhoea (milk production) or acromegaly (abnormal growth) [PMID:33671239]. Less commonly, tumours may also occur in the adrenal glands, thymus, or lungs.
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Affected organs
MEN1 primarily affects endocrine glands, which are responsible for hormone production. The most commonly affected organs include:
* **Parathyroid glands:** Four small glands located in the neck, behind the thyroid, that regulate calcium levels. Tumours here lead to hyperparathyroidism. * **Pancreas:** Specifically, the endocrine cells (islet cells) within the pancreas that produce hormones like insulin and glucagon. Tumours can lead to conditions such as Zollinger-Ellison syndrome or hypoglycaemia. * **Pituitary gland:** A gland at the base of the brain that controls many other endocrine glands. Tumours can affect hormone regulation, vision, and cause headaches.
Other endocrine tissues that may be affected include the adrenal glands (located above the kidneys), the thymus gland (in the chest), and certain neuroendocrine cells in the lungs or stomach lining.
Risks & severity
The severity of MEN1 can vary significantly among affected individuals, even within the same family. The risk of developing tumours in the parathyroid glands, pancreas, and pituitary gland is very high, with parathyroid tumours being a very common manifestation [PMID:33671239]. While most tumours are benign, some pancreatic and thymic tumours can be malignant (cancerous) and may spread to other parts of the body, potentially impacting life expectancy.
Symptoms typically begin in early adulthood, though clinical signs can appear earlier or later. Regular surveillance is crucial for individuals with MEN1 to detect and manage tumours early, which can help mitigate severe complications and improve long-term outcomes. The clinical course can be complex, requiring coordinated care from multiple medical specialists.
Genetic causes
Multiple Endocrine Neoplasia Type 1 is caused by pathogenic variants in MEN1. This gene encodes menin, a protein that acts as a tumour suppressor. In its normal role, menin helps regulate how cells grow and divide, preventing uncontrolled proliferation that could otherwise lead to tumour formation [PMID:33671239].
When a pathogenic variant occurs in MEN1, the menin protein may be absent, non-functional, or function incorrectly. This disruption compromises the cell's ability to control its growth, leading to an increased likelihood of tumour development in endocrine glands. Most people with this condition inherit one copy of an altered MEN1 gene from a parent, and a second, acquired change in the remaining functional copy in a cell can then initiate tumour growth.
- MEN1 menin 1The MEN1 gene provides instructions for producing menin, a protein crucial for regulating cell proliferation and acting as a tumour suppressor, with pathogenic variants linked to multiple endocrine neoplasia type 1.
Inheritance pattern
Multiple Endocrine Neoplasia Type 1 has an autosomal dominant pattern of inheritance. This means that only one altered copy of MEN1 in each cell is sufficient to cause the condition. An individual with MEN1 has a 50% chance of passing on the altered gene to each of their children, regardless of the child's sex.
MEN1 can also occur in individuals with no family history of the condition due to a new (de novo) pathogenic variant in MEN1. However, once such a variant occurs, it can then be passed down through generations in an autosomal dominant manner. Genetic counselling is important for affected individuals and their families to understand the inheritance patterns and risks.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
The diagnosis of MEN1 is typically established based on a combination of clinical features, biochemical testing, and genetic testing. Clinical diagnosis may be suspected if an individual develops two or more of the main MEN1-related tumours (parathyroid, pituitary, or pancreatic neuroendocrine tumours) or if a first-degree relative has MEN1 and the individual develops at least one such tumour. Biochemical tests measure hormone levels (e.g., parathyroid hormone, calcium, gastrin, prolactin) to detect overproduction by affected glands.
Confirmation of MEN1 usually involves genetic testing for pathogenic variants in MEN1. This can be accessed through the NHS Genomic Medicine Service (GMS) pathways, often following a referral from a specialist clinician or clinical geneticist. Genetic counsellors play a vital role in discussing the implications of testing, the results, and family planning.
Management & lifestyle
Management of MEN1 focuses on surveillance for tumour development, early detection, and appropriate treatment to minimise complications. There is no cure for MEN1, so care is aimed at managing the manifestations of the condition. Regular biochemical screening (e.g., calcium, parathyroid hormone, glucose, gastrin) and imaging studies (e.g., MRI or CT scans) are typically recommended to monitor for new or growing tumours [PMID:28773992].
Treatment options depend on the type, size, and activity of the tumours. This may include surgery to remove tumours, medication to control hormone levels, or other targeted therapies. Individuals with MEN1 receive care through multidisciplinary teams, including endocrinologists, surgeons, oncologists, and clinical geneticists, within the NHS. Lifestyle modifications, such as maintaining good hydration, may be advised to help manage certain symptoms, like kidney stones.
UK care pathway
In the UK, individuals suspected of having or diagnosed with MEN1 are typically managed through the NHS Genomic Medicine Service. A referral to a clinical genetics service is often the starting point, where a genetic counsellor can provide detailed information, discuss genetic testing options, and offer support. Genetic testing for MEN1 pathogenic variants falls under specific NHS Genomic Test Directory R-codes.
Once a diagnosis is confirmed, individuals usually enter a long-term surveillance programme tailored to their specific needs. This involves regular monitoring by a team of specialists to detect and manage any new tumour developments proactively. Genetic counsellors also play a crucial role in providing support, education, and discussing the implications for family members.
Frequently asked questions
What is the difference between MEN1 and MEN2?
MEN1 and MEN2 are both genetic conditions causing endocrine tumours, but they are caused by different genes and affect different glands. MEN1, caused by MEN1, primarily affects the parathyroid, pancreas, and pituitary. MEN2, caused by RET, typically affects the thyroid (medullary thyroid cancer), adrenal glands (phaeochromocytoma), and sometimes the parathyroid.
If I have MEN1, will all my children inherit it?
No, if you have MEN1, there is a 50% chance that each of your children will inherit the altered MEN1 gene. This is because it is an autosomal dominant condition, meaning only one copy of the altered gene is needed to have the condition. Genetic counselling can provide more personalised information.
Are the tumours caused by MEN1 always cancerous?
No, many of the tumours associated with MEN1 are benign (non-cancerous), particularly those in the parathyroid glands and pituitary gland. However, some tumours, especially certain pancreatic neuroendocrine tumours and thymic tumours, can be malignant (cancerous) and may require more aggressive treatment. Regular monitoring helps detect these early.
How often do I need check-ups if I have MEN1?
Individuals with MEN1 typically require regular, lifelong surveillance. The frequency and type of check-ups, including blood tests and imaging scans, are determined by your medical team based on your specific tumour profile, age, and symptoms. This ongoing monitoring aims to detect new tumours or changes in existing ones as early as possible [PMID:28773992].
Can MEN1 skip a generation?
No, because MEN1 is an autosomal dominant condition, it does not skip generations in the traditional sense. If an individual has the altered gene, they will typically show signs of the condition, though the severity can vary. If the altered gene is present, there is always a 50% chance of passing it to each child.
References
- Brandi ML, Pieterman CRC, English KA. Multiple endocrine neoplasia type 1 (MEN1): recommendations and guidelines for best practice. The lancet. Diabetes & endocrinology. 2025. PMID: 40523372
- Greenberg LA. Multiple Endocrine Neoplasia Type 1, Type 2A, and Type 2B. Primary care. 2024. PMID: 39067973
- Del Rivero J, Gangi A, Annes JP. American Association of Clinical Endocrinology Consensus Statement on Management of Multiple Endocrine Neoplasia Type 1. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2025. PMID: 40232217
- Norton JA, Foster DS, Ito T. Gastrinomas: Medical or Surgical Treatment. Endocrinology and metabolism clinics of North America. 2018. PMID: 30098717
- Herder WW. Familial gigantism. Clinics (Sao Paulo, Brazil). 2012. PMID: 22584702
- Singh G, Mulji NJ, Jialal I. Multiple Endocrine Neoplasia Type 1. 2023. PMID: 30725665
- Ito T, Jensen RT. Imaging in multiple endocrine neoplasia type 1: recent studies show enhanced sensitivities but increased controversies. International journal of endocrine oncology. 2016. PMID: 26834963
- Pannett AA, Thakker RV. Multiple endocrine neoplasia type 1. Endocrine-related cancer. 1999. PMID: 10730900