What is Multiple Endocrine Neoplasia Type 1 (Wermer Syndrome)?
Multiple endocrine neoplasia type 1 (MEN1), also known as Wermer syndrome, is a rare disease affecting the body’s hormone-producing (endocrine) systems. This syndrome causes an excessive formation of tumors (neoplasia) in the parathyroid glands, the front part of the pituitary gland, and the hormone-making tissues of organs in the digestive system like the stomach, intestines, and pancreas.
The most common sign of this disease is hyperparathyroidism, a condition where the parathyroid glands produce too much hormone, which occurs in around 90% of cases. Tumors in the pancreas appear in about 60% of cases, while tumors in the pituitary gland occur in 40% of cases. Also, patients could develop other less common hormone-related or non-hormone-related tumors such as carcinoids in the thymus, bronchus, or stomach, adrenal gland tumors, skin tumors, brain tumors, leiomyomas (smooth muscle tumors), lipomas (fat tissue tumors), collagenomas (skin tumors), and angiofibromas (blood vessel tumors).
An MEN1 gene test can confirm the disease in people experiencing symptoms, and it can also detect the disease in people who have no symptoms several years before a tumor associated with MEN1 can be detected. However, this test is not always accurate as about 20% of people with a family history of MEN1 do not have the MEN1 gene mutation. Moreover, the mutations in the MEN1 gene can lead to different symptoms even among those related by blood. Some studies have shown that certain types of mutations are associated with more aggressive tumors.
What Causes Multiple Endocrine Neoplasia Type 1 (Wermer Syndrome)?
MEN1 Syndrome is caused by changes, or mutations, to a gene found on chromosome 11 called the MEN1 or menin gene. This syndrome is usually passed down from parent to child in what’s known as an autosomal dominant pattern. This means that even if a child gets only one changed gene from one parent, they can get the syndrome. About 90% of the time, this gene is inherited from a parent who has the syndrome. In 10% of cases, the syndrome happens because of a new mutation that wasn’t inherited.
This is why it’s crucial to use specific criteria for diagnosing the syndrome, because sometimes it isn’t passed down from a parent.
A study by Marini and his team looked at the MEN1 gene mutations in 410 people and found 99 different mutations. These mutations ranged from simple shifts in the gene frame, to missing sections of the gene, or other changes in the gene structure. The study found that some types of tumors in the gastrointestinal tract were more common in people with a specific kind of mutation called nonsense mutations. On the other hand, tumors in the chest were more common in people with mutations at the splice site – the point where the gene gets “cut” and pieced back together.
A different gene called CDKN1B has also been connected to specific types of tumors such as those in the pituitary gland, the parathyroid glands and the pancreas. It’s possible that changes in this gene could cause MEN1 Syndrome in people who do not have a mutation in the MEN1 gene.
Risk Factors and Frequency for Multiple Endocrine Neoplasia Type 1 (Wermer Syndrome)
MEN1 Syndrome is a condition that’s diagnosed if a person has at least two specific types of tumors (in the parathyroid glands, anterior pituitary gland, or certain parts of the digestive system) or at least one MEN1-related tumor and a close relative with confirmed MEN1. Alternately, a diagnosis is made if a person has a specific mutation in their MEN1 gene.
This syndrome is rare, affecting roughly 0.25% of people, or anywhere between 0.02 to 0.2 per thousand people. It impacts males and females equally. Out of 734 patients with MEN1, slightly more were female (57.8%). Interestingly, pancreatic tumors were more common in men, while pituitary tumors were slightly more common in women. Thymic tumors, however, were only found in men.
Over 94% of patients show signs of the syndrome by the time they reach their 50s. However, it can affect all age groups, even children as young as five. In fact, some children may initially present Cushing disease, which can be an early indication of MEN1.
- This condition can be diagnosed by the presence of two specific types of tumors or by having one MEN1-related tumor and a close relative with confirmed MEN1.
- Alternatively, having a certain mutation in the MEN1 gene can also confirm a diagnosis.
- About 0.02 to 0.2 per thousand people are affected by this syndrome, with men and women being affected equally.
- Pancreatic tumors were found to be more common in men, pituitary tumors more in women, and thymic tumors were found only in men.
- Most patients start showing symptoms by their 50s, but the syndrome can affect anyone at any age, even as young as five.
Signs and Symptoms of Multiple Endocrine Neoplasia Type 1 (Wermer Syndrome)
When a person first visits their doctor due to concerns about MEN1 Syndrome, it’s essential to provide a comprehensive history. This disease can impact multiple organ systems, so it’s critical to get as much detail as possible. Also, a detailed family history can be incredibly helpful. MEN1 often impacts several family members, and although it might show up in different ways due to its varied expression, knowing that MEN1 is present in someone’s family can help make an early diagnosis.
Thorough physical examinations are also essential, both during the initial visit and any follow-ups. Doctors need to look for changes in vision, or any lumps in the neck or stomach area. In many cases, MEN1 is discovered after unexpected results in laboratory or imaging tests. The symptoms can vary because it depends on which organs are affected. Additionally, because the tumors associated with MEN1 may be small, many patients may have a normal physical examination.
Testing for Multiple Endocrine Neoplasia Type 1 (Wermer Syndrome)
Multiple Endocrine Neoplasia Type 1 (MEN1) is a health condition that affects several areas of your body – the hormones releasing glands or ‘endocrine’ system. Doing an in-depth analysis using labs tests and body scans helps in spotting issues. This condition can impact three parts of your body – your parathyroid glands, the front part of your pituitary gland, and certain nerve endings in your body.
Parathyroid Glands
In the case of your parathyroid glands, doctors start by checking the levels of calcium and parathyroid hormone (PTH) in your blood. Sometimes, the PTH level might be only slightly high or nearing the upper limit of what’s normal. This might prevent MED1 getting noticed. Using ultrasound or Technetium Sestamibi scans (a type of nuclear medicine scan that can depict parathyroid diseases) might not always be useful, because MED1 often involves more than one gland, which could be missed in these scans.
Neuroendocrine Tissue Systems
Nerve endings in your body release a number of substances that regulate bodily functions. In the case of MEN1, doctors will check for the levels of several hormones and substances in your bloodstream. These include gastrin, glucagon, insulin, proinsulin, C-peptide, chromogranin A, pancreatic polypeptide, and vasoactive intestinal peptide (VIP). High levels of one or more of these substances can indicate a problem.
To get a better idea of what’s going on, your doctor might order a transabdominal ultrasound, computed tomography (CT), magnetic resonance angiography (MRI), octreotide scan (Octreoscan), or 68Ga-DOTATOC PET. These scans help doctors get a clear picture of the affected areas and check if any tumors have spread. Of all these scans, endoscopic ultrasound (EUS) is considered the most accurate in detecting tumors in the pancreas or the first part of the small intestine.
Anterior Pituitary Gland
The pituitary gland is a small, pea-sized gland that controls many of your body’s hormones. With MEN1, it is crucial to measure pituitary hormones levels, including prolactin (PRL), growth hormone (GH), insulin-like growth factor 1 (IGF-1), and others. These tumors most commonly release prolactin, followed by the growth hormone. Elevated IGF-1 levels and failing to suppress GH during a glucose tolerance test (where you drink a sugary solution and your blood sugar levels are monitored) indicates a GH-releasing tumor. MRI scans provide the most effective way to diagnose any presence of tumors in the pituitary gland. This imaging can also be used to evaluate the effectiveness of the treatment for pituitary tumors.
Treatment Options for Multiple Endocrine Neoplasia Type 1 (Wermer Syndrome)
Primary hyperparathyroidism (an overactivity of the parathyroid glands) is the most common symptom of multiple endocrine neoplasia type 1 (MEN1) – a hereditary condition where several glands in the body’s endocrine system become overactive. It affects roughly 90% of those with MEN1 and usually starts in their teens.
This disease causes multiple gland growths, leading to an excess of calcium in the blood or other related complications. Despite fewer apparent symptoms, those with MEN1-related hyperparathyroidism may suffer from more severe bone disease.
Parathyroid cancer is rare for those with MEN1. Roughly 59% of the reported cases have been found in men, typically around the age of 50.
Treatment of this disorder in MEN1 patients is still up for debate. There are two main methods considered – subtotal parathyroidectomy and total parathyroidectomy, both involve removing either part or all of the overactive glands. Total parathyroidectomy has less chance of persistent hyperparathyroidism, however, it comes with a higher risk of hypoparathyroidism (an underactivity of the parathyroid glands).
In some cases of MEN1, non-functioning gastro-entero-pancreatic tumors may occur. These don’t cause typical symptoms but may still produce small amounts of pancreatic hormones (pancreatic polypeptide and gastrin), making them difficult to diagnose early. This type of tumor represents the most frequent cause of death for MEN1 patients.
Managing these non-functioning tumors is challenging due to differing opinions on when a patient should go through surgery. The decision usually depends on the size of the tumor; however, aggressive surgical treatment can lead to significant complications like diabetes or issues with fat digestion.
Functioning gastro-entero-pancreatic tumors affect roughly 30% to 75% of MEN1 patients. These tumors can produce hormones that may cause conditions like Zollinger-Ellison syndrome, a condition that results in the production of too much gastric acid and leads to ulcers.
Insulinomas or tumors that produce excessive amounts of insulin, can occur in 10% to 30% of MEN1 patients. These can lead to symptoms of low blood sugar such as seizures or a loss of consciousness. Surgical treatment is necessary to remove these types of tumors.
Aside from pancreatic tumors, anterior pituitary tumors are quite common in MEN1 patients, affecting around 20% to 60% of patients. These tumors are more common in women and are usually larger. In some cases, they may not respond well to medications, requiring surgical intervention.
Carcinoid tumors affect the digestive tract, bronchi, pancreas, and thymus and occur in roughly 3% of MEN1 patients. Surgical removal is typically the best treatment.
Asymptomatic adrenal tumors are found in around 20% to 73% of MEN1 patients. If the tumor is larger than 1 cm, the likelihood of adrenal cancer increases.
Breast cancer is prevalent amongst female MEN1 patients and tends to occur at an earlier age compared to the general population. Therefore, breast cancer screening is essential for these patients.
What else can Multiple Endocrine Neoplasia Type 1 (Wermer Syndrome) be?
When looking to diagnose MEN1 (multiple endocrine neoplasia type 1), doctors also consider other conditions with similar symptoms. These include:
- Von Hippel-Lindau Syndrome
- Neurofibromatosis Type 1
- Tuberous Sclerosis Complex
- Multiple Endocrine Neoplasia Type 4
What to expect with Multiple Endocrine Neoplasia Type 1 (Wermer Syndrome)
The future health outcomes for patients with MEN1, a rare genetic disorder, can vary greatly. Tumors associated with MEN1 are more aggressive and difficult to treat. Consequently, life expectancy tends to be shorter in patients with non-functioning pancreatic NET (Net Tumors), a type of tumor that develops in the pancreas. This is due to complications arising from the tumor’s growth.
Moreover, these types of neuroendocrine tumors can spread quickly to other parts of the body which can lead to premature death. Studies have shown that patients with MEN1 have a higher risk of dying prematurely and on average have a shorter life expectancy.
Patients with MEN1 can also experience substantial health problems stemming from surgical complications. Therefore, it’s crucial to diagnose and treat this condition early.
Possible Complications When Diagnosed with Multiple Endocrine Neoplasia Type 1 (Wermer Syndrome)
In MEN1, problems can arise either due to the disease itself or the treatments like surgery.
With respect to the disease, pituitary tumors could lead to either pituitary insufficiency, where the pituitary gland underperforms, or visual field defects affecting your vision. Parathyroid tumors, on the other hand, can cause metabolic bone disease, making your bones more prone to fractures, and kidney stones.
Tumors in the tissue lining the stomach, intestine, and pancreas may lead to over-production of several gastrointestinal hormones including gastrin, insulin, glucagon, or vasoactive intestinal peptide, which can damage the digestive system. In addition, there might be full-body complications when these tumors spread to other parts of the body.
Common Complications:
- Pituitary insufficiency
- Visual field defects
- Metabolic bone disease
- Kidney stones
- Damage to the digestive system due to overproduction of hormones
- Full-body complications due to the spread of tumors
Preventing Multiple Endocrine Neoplasia Type 1 (Wermer Syndrome)
It is extremely important for patients to understand their health conditions. Once a doctor identifies a condition known as MEN1, the family of the patient should meet with a specialized professional called a genetic counselor. This counselor can help them understand the disease and how it could affect the patient and their family. The genetic counselor can also recommend that other family members undergo genetic testing. This comprehensive understanding of the disease can help the patient make well-informed decisions about their health.
