Multiple Endocrine Neoplasia: Causes, Symptoms & Treatment

Multiple endocrine neoplasia (MEN) is the collective term for various cancers – based on genetic defects – of endocrine glands, i.e. hormone-producing glands such as the pancreas, parathyroid gland and pituitary gland. Sustained therapy is usually only possible by complete removal of the corresponding gland.

What is multiple endocrine neoplasia?

Graphic illustration and infogram of a typical cancer cell. Multiple endocrine neoplasms can be divided into type 1 (MEN 1, Wermer syndrome), type 2A (MEN 2A, Sipple syndrome), and type 2B, (MEN 2B, William syndrome and Gorlin syndrome), depending on physiologic features and other specifics. MEN 1 mainly affects the parathyroid gland, building salivary gland, and pituitary gland. Typically, the neoplasms in affected endocrine glands do not respond to regulatory control hormones, so there is usually excess hormone production in the glands. Thyroid, parathyroid and adrenal medulla can develop neoplasms of type MEN 2A and 2B. In type 2B, neoplasms may develop in other organs in parallel. Strictly speaking, there are the other subgroups of type 3A, 3B, and 3C, which mainly affect the parathyroid glands, the sympathetic nervous system, and the digestive tract.

Causes

Multiple endocrine neoplasms type 1 are “allowed” – not caused – by a mutated tumor suppressor gene on chromosome 11. The gene that normally gives the command to fight such growths loses its effectiveness because of the mutation, allowing endocrine-active tumors and other neoplasms to form on the affected endocrine glands without being suppressed by endogenous means. Type 2 MEN are caused by a mutation of another gene that causes loss of function of protooncogenes. When cells divide in the affected organs, the growth process can no longer be controlled, so that the development of neoplasms is not controlled and slowed down by the body’s own means. Both gene mutations can be detected in a genetic analysis, and both gene mutations are inherited in an autosomal dominant manner, meaning that the parent affected by one of the gene defects passes the gene defect on to all children, who carry a 50% risk of developing the disease.

Symptoms, complaints, and signs

The symptoms of multiple endocrine neoplasia depend on the form of the disease. For example, in MEN type 1 (Wermer syndrome), the parathyroid glands, pancreas, and pituitary gland are most commonly affected. In the parathyroid glands, there is hyperplasia associated with so-called hyperparathyroidism. Patients have too much parathyroid hormone in their blood. This leads primarily to bone loss. Neoplasms of the pancreas with excessive production and release of hormones have a negative effect on the metabolism in particular. One consequence of this neoplasia is Zollinger-Ellison syndrome, which is characterized by gastric and small intestinal ulcers. In the pituitary gland, prolactinomas in particular occur in multiple endocrine neoplasia. These are tumors that produce the hormone prolactin. As a result, ovulation and menstruation fail to occur in women. Some patients also develop galactorrhea, i.e. they produce breast milk in the mammary glands even outside pregnancy and breastfeeding. In men, on the other hand, the main symptoms are potency disorders and loss of libido. Galactorrhea rarely occurs here. Multiple endocrine neoplasia may also affect the thyroid gland and adrenal medulla. Nervousness, increases in blood pressure, or diarrhea are then among the complaints.

Diagnosis and course

In principle, a predisposition to the onset of multiple neoplasia types 1 and 2 can be determined in a genetic analysis, which is particularly useful if there are already known cases of MEN in the family and ethical reasons do not oppose a genetic analysis. Early indicators of the presence of MEN 1 are elevated levels of certain hormones produced by the endocrine glands. The elevated levels may be an indicator of already formed endocrine-active neoplasms that do not respond to control hormones. If tumors have already formed simultaneously in at least 2 of the 3 affected organs, the suspicion of MEN 1 is strengthened. The course of the disease in MEN 1 and 2 is very severe without treatment.Usually, in the case of endocrine-active neoplasms, there are significant overconcentrations of the specific hormones of the affected glands and, on the other hand, malignant carcinomas can be life-threatening.

Complications

As a result of this disease, affected individuals usually suffer from various cancers. Thereby, the further course depends very much on the respective pronounced disease, so that a general prediction of the course of the disease is usually not possible. In most cases, those affected suffer from pain in the abdomen and stomach and, associated with this, not infrequently also from a lack of appetite. This also leads to malnutrition and, as a rule, weight loss. Patients may suffer from vomiting or nausea and complain of pain in the muscles. As a rule, this disease leads to a significantly reduced quality of life and also to various limitations in the daily life of the affected person. As a rule, without treatment, premature death of the patient occurs. Self-healing does not occur in this case. Patients depend on surgical interventions to remove the tumors. No further complications occur in this process. However, the further course of the disease strongly depends on the extent of the tumors. Possibly, the life expectancy of the patient is also reduced by the disease in the process.

When should one go to the doctor?

If characteristic symptoms such as hormonal disturbances or a disturbed bone structure are noticed, a physician should be consulted. Multiple endocrine neoplasia is a serious condition that must be diagnosed and treated as early as possible. Otherwise, serious physical problems may develop, permanently affecting the patient’s quality of life and well-being. Therefore, medical advice should be sought at the first sign of a disease. Anyone who notices disorders of the nervous system, organ pain or psychological complaints such as depression and mood swings is best advised to inform their family doctor. He or she can diagnose any tumors and initiate further treatment measures. In addition to the general practitioner, an internist or neurologist can also be consulted if multiple endocrine neoplasia is suspected. Depending on the localization of the tumors, gastroenterologists and nephrologists should also be consulted. The actual treatment takes place as an inpatient in a specialized clinic for internal diseases. Close monitoring by a specialist is necessary during treatment, as there is a risk of serious complications due to the usually already advanced symptoms.

Treatment and therapy

Treatment of multiple endocrine neoplasia depends largely on the organ affected and the stage of the carcinoma. For example, if a child’s genetic analysis reveals mutated genes that most likely predict MEN 2 disease, prompt surgical removal of the thyroid gland (thyroidectomy) is strongly advised, including removal of all lymph nodes in the neck to remove any metastases in the lymphatic area near the thyroid gland from the outset. Depending on the severity of the analyzed gene mutations, this total operation should be performed in children between the ages of 6 and 12. In some cases, the so-called pentagastrin test can be performed at regular time intervals, which indicates the development of endocrine active carcinoma of the thyroid or parathyroid gland. If, for example, all 4 parathyroid glands are affected, the tissue must be removed almost completely except for a small remnant in order to preserve the natural production of the hormone of the parathyroid gland (parathormone), which plays a very important role in calcium balance. In specialized clinics, some of the removed parathyroid tissue is frozen to be reimplanted into the patient if needed, in case the parathyroid tissue left in the body does not “kick in” and produce parathyroid hormone.

Outlook and prognosis

The prognosis of multiple endocrine neoplasia is unfavorable. Patients who receive such a diagnosis suffer from a genetic defect. Current legislation prohibits researchers and scientists from being able to alter human genetics. Therefore, the measures of a treatment are limited to the alleviation of the existing and individually pronounced symptoms.Although there are many therapeutic approaches that alleviate numerous symptoms, the prospect of recovery is not given at the current state. Long-term therapy and regular check-ups are necessary so that an optimal response can be made as quickly as possible if irregularities occur. Without adequate and comprehensive medical care, the risk of shortening the expected lifespan is significantly increased. Patients suffer from various cancers that contribute to a significant deterioration in the overall quality of life. The possibilities for shaping everyday life are reduced, so that the focus of the treatment initiated includes optimizing well-being in addition to improving physical possibilities. In many patients, removal of the affected glands is performed. This reduces the probability of recurrence of cancer. At the same time, however, this procedure results in numerous side effects and consequences for the patient. Therefore, dealing with the disease is a particular challenge for the affected person.

Prevention

There is no direct prevention against the occurrence of the various forms of MEN. If genetic analysis based on familial genesis confirms suspicion of one of the MEN forms, ongoing screening is recommended starting at age 10. Laboratory tests monitor certain hormone levels to determine if endocrine active neoplasms have already formed. In addition, the use of diagnostic imaging techniques such as ultrasound, CT, MRI and fMRI is necessary as determined by the medical specialists. It may even be life-saving to prophylactically remove a threatened endocrine organ.

Follow-up

Patients with multiple endocrine neoplasia are more likely than other people to suffer from carcinomas of organs related to the body’s hormone balance. Not only do those affected develop tumors more often, but on average they develop cancer at a younger age. Therefore, the follow-up of persons with multiple endocrine neoplasia refers primarily to the postoperative condition. If possible, diagnosed carcinomas should be surgically removed or treated by other types of therapy. After the surgical procedure, patients must remain under medical observation for a specified period of time. This reduces the likelihood of postoperative complications while allowing for rapid intervention. However, some forms of cancer in multiple endocrine neoplasia have the ability to recur. Therefore, the focus of follow-up is on control examinations that regularly check the patient’s health status and investigate recurrence or the development of new types of carcinoma. In this way, rapid medical intervention is possible in the event that sufferers become ill again. In general, patients with multiple endocrine neoplasia support their health condition by living as healthy a lifestyle as possible, especially with regard to predisposition to certain carcinomas. However, because it is a genetic disease, there is little that can be done to influence the risk for cancer.

Here’s what you can do yourself

The symptoms caused by multiple endocrine neoplasia can be countered in everyday life with targeted measures. Typically, multiple organs are affected by the disease. Therefore, it is important to identify any genetic defects and also to examine family members. It is imperative that those with the disease have the screening examinations. To avoid problems with elevated acid levels, dietary changes are advisable. In addition, the MEN disease affects the blood sugar level and leads to strong fluctuations here. Those affected must therefore keep a close eye on any changes in the gastrointestinal tract. This can reduce problems such as constipation and diarrhea. Changes in the skin can also occur. Increased awareness is required here in order to take action in good time if necessary. Depending on the severity of the multiple endocrine neoplasia, doctors often recommend that the thyroid gland be surgically removed as a preventive measure. Here it is important to follow the doctor’s recommendations and learn about the following drug therapy. After the removal of the thyroid gland, the intake of thyroid hormones cannot be avoided.So it requires a lot of attention and heightened awareness to properly manage medications and monitor one’s body.