Wermer’s syndrome; Wermer syndrome; MEN1; MEN type 1
Multiple endocrine neoplasia type 1 is a rare inherited disease, which can result in tumours in the pituitary and parathyroid glands, and pancreas. It can be associated with adrenal nodules, carcinoid tumours and, very commonly, skin nodules.
Multiple endocrine neoplasia type 1 is caused by a defect in a gene called ‘the menin’ gene. This is found on Chromosome 11. Faults or 'spelling mistakes' have been found in over 90% of patients with multiple endocrine neoplasia type 1; however, in some patients and their families with the condition, a menin gene fault cannot be found. Some patients do not have a family history of multiple endocrine neoplasia type 1 and are the first person in their family in which the diagnosis is made.
The three endocrine tumours which constitute multiple endocrine neoplasia type 1 (MEN1) are:
Pituitary tumours – about 30–40% of patients with MEN1 develop pituitary tumours. The commonest are prolactinomas, occurring in about 20% of patients with MEN1. These tumours produces excess secretion of prolactin. In women, prolactinoma may cause breast milk production without pregnancy, lack of periods and may lead to infertility. In men, prolactinoma can cause impotence and infertility (see the article on prolactinoma for more information).
Other much rarer hormone-producing tumours include those making growth hormone, causing acromegaly; and those making adrenocorticotrophic hormone (ACTH), causing Cushing’s disease. Pituitary tumours may also not make any hormones being picked up during surveillance. Large pituitary tumours may cause problems with vision or headaches.
Insulinoma occur in about 10% of patients with MEN1. They are tumours of the B cells in the pancreas that overproduce insulin, causing a low blood sugar level (hypoglycaemia). This can cause confusion, sweating and can result in loss of consciousness.
Rarely, other functioning pancreatic NETs can occur in MEN1. These include:
VIPoma – the over-production of vasoactive intestinal peptide by a VIPoma can causes severe diarrhoea and a low potassium
Some of the pancreatic tumours in MEN1 are non-functioning (non-functioning pancreatic nets) and are found by surveillance imaging. Whilst most pancreatic NETs are benign, some, in particular gastrinomas, can spread to lymph nodes or the liver and are then described as a neuroendocrine cancer.
Other features described in patients with MEN1 include chest neuroendocrine tumours (2% of patients), adrenal gland nodules (up to 50% of patients), adrenal cancer (<1%), lipomas. Benign tumours of the skin, particularly over the face (collagenomas and angiofibromas) occur in almost all patients with MEN1.
Multiple endocrine neoplasia type 1 is a rare condition. It has been estimated that it affects between 1 out of 10,000 to 1 out of 30,000 people. The same number of men and women are affected. The age at which people with multiple endocrine neoplasia type 1 start to develop tumours differs, depending on the individual. Pituitary tumours have been described in patients from the age of 10 and primary hyperparathyroidism and pancreatic NETs have been described in patients in their teens.
Multiple endocrine neoplasia type 1 is an inherited condition due to an abnormality or ‘spelling mistake’ in the MENIN gene, which can be passed on from parent to child. It is inherited in an 'autosomal dominant' way, that is, there is a 50% (1 in 2) chance that a child will inherit the abnormal gene, and therefore, MEN 1. About 10% of patients with MEN1 do not have a family history and are the first people to develop a mutation (faulty gene) in their family.
Genetic testing – there is a genetic test for the faulty MENIN gene. This test is offered to people who have the manifestations of MEN1 (diagnostic testing), or to the relatives of people known to have MEN1 (predictive testing). This should be performed through a Clinical Genetics service so implications for the test can be discussed in advance of testing, and further counselling offered, if necessary, as a positive result has implications for a patient and their family, and can often come as a shock. Patients can then be referred on to an appropriate endocrinology centre as lifelong surveillance is needed for the tumours described.
The three different kinds of tumours are diagnosed and monitored in different ways.
Exact treatment depends on the type of tumours present. If no abnormalities are detected then there is no need for any specific treatment. The three different kinds of tumours are treated in different ways:
After parathyroid surgery, calcium level in the blood may drop (hypocalcaemia), which causes tingling in the hands and the face, as well as muscular spasms. This is treated with 1 alphacalcidol to restore normal calcium levels, possibly as a lifelong treatment.
Depending on how the pituitary is working, if pituitary surgery is performed, some patients will require long-term replacement with pituitary hormones such as growth hormone, hydrocortisone and thyroxine (see the article on hypopituitarism, for more information). Diabetes insipidus may occasionally occur, causing excessive thirst and the need to pass excessive urine, and, if the condition is permanent, it can be treated using a drug called desmopressin.
Effects after pancreatic surgery depends on how much of the pancreas in removed. After a total pancreatectomy, patients will have diabetes mellitus, requiring insulin injections, and will require supplements with pancreatic enzymes to help with digestion of food. The risk of these complications is much reduced for smaller operations, but patients should still be observed carefully for these complications, especially in the first few months after surgery. If patients have any concerns about any of these side-effects, they should contact their doctor.
Manifestations of MEN1 can vary greatly, even within families, although virtually all patients will develop primary hyperparathyroidism. Because tumours can manifest from the age of approximately 10 onwards, surveillance is recommended, which should be lifelong, through a specialist endocrinology clinic, with access to appropriate radiology and other specialities needed for the management of the tumours listed above.
Outlook is dependent upon which tumours a patient may develop, and what treatments are recommended. Some pancreatic NETs are malignant, which can be life-limiting.
It is important that genetic screening is offered through a specialist service together with genetic counselling so that anyone undergoing the test understands the implications for them and their families.
Last reviewed: Jan 2015