What is multiple endocrine neoplasia type I?
Multiple endocrine neoplasia type I MEN I is a rare disease that affects certain endocrine glands. Most commonly affected are parathyroid glands, the pituitary gland and the endocrine pancreas. MEN I is a genetic disease that affects both sexes without preferences. MEN I is inherited as an autosomal dominant trait and the chance of inheriting the disease is 50%. In MEN I, the specific endocrine glands mentioned above, become overactive and secrete inappropriate amounts of different combinations of hormones, leading to various and individually different symptoms. Which glands that are involved varies from person to person, but to get the diagnosis at least two glands have to be overactive. There is no cure for the disease, but the lesions associated with MEN I can be diagnosed at an early stage and controlled or treated before they become serious problems. MEN I usually presents with symptoms at an age of 40-50 years, however, the disease can be diagnosed biochemically earlier, at an age of 20-30, before symptoms have occurred.
What kind of symptoms may MEN I cause? How is the diagnosis made, and how is the disease treated?
The most common lesion in MEN I is that of the parapthyroids, nearly 90% of the persons with MEN I gets primary hyperparathyroidism. The parathyroid hormone (PTH) normally is released by the four parathyroid glands, located close to the thyroid gland at the front of the neck. PTH regulates the levels of calcium in the body. In MEN I one or several parathyroid glands are overactive, leading to excess of calcium in the blood. High blood calcium can cause excess calcium to spill into the urine resulting in kidney stones formation, tiredness, muscle weakness or pain, constipation, indigestion, or thinning of bones. Surgery is the treatment of choice for MEN I parathyroid affection.
The pituitary gland secretes hormones that are responsible for regulation of several other hormonal processes in the body. About 25% of MEN I patients developed benign pituitary tumours. The most common overproduced pituitary hormone is prolactine, which normally is involved in fertility and breast milk control. Symptoms could be excessive production of breast milk or it can interfere with fertility. The tumour mass itself can disturb the optical nerve passing above the gland resulting in impaired vision. Surgery or radiation is seldom needed. Medical treatment with bromcryptine is highly effective and normalizes the hormonal levels as well as shrinks the tumour. The normal function of the pancreas gland is to produce and release enzymes into the intestines for facilitation of digestion, as well as defined functions such as insulin production and regulation. The endocrine cells of the pancreas normally release the hormones to the blood stream in appropriate amounts as timely response to food intake and neural signals. About 75% of MEN I affected persons developed multiple tumours of the endocrine pancreas. These are called endocrine pancreatic tumours (EPT) and produce excessive amounts of several different hormones in different combinations. If for example insulin is secreted in excess the patient may experience symptoms of low blood sugar such as hunger, sweating, anxiety, and attention deficit. Another hormone quite commonly involved in MEN I pancreatic tumours is gastrin. Too much gastrin increases the acidity of the stomach which could result in ulcers and diarrhoea, this is called the Zollinger-Ellison syndrome. Some of the MEN I pancreatic tumours are malignant, unfortunately reliable methods to identify the patients at risk of harbouring more clinically aggressive lesions are lacking. The diagnosis of EPT involves measuring the levels of hormones in the blood as well as radiological investigations. The aim of the treatment of MEN I pancreatic tumours is to prevent spread to the lymph nodes and liver. Surgery is the treatment of choice. During surgery intraoperative ultrasonography is used in order to find small tumours that otherwise easily could have been overlooked by the surgeon. It is important to limit the surgical procedure in order to secure a maintained function of the pancreas postoperatively. By this approach the disease will most certainly relapse within some years but it will take another 10 years before new small tumours will endanger the health of the patient and before reoperation will have to be performed.
Why screen for MEN I?
Physicians all over the world agree upon the value of early diagnosis and treatment of MEN I. Genetic screening is possible and involves blood sampling and analysis to detect a mutation in a specific gene called MEN I. The normal unmutated gene is responsible growth regulation in certain in endocrine cells (those of the parathyroid glands, the pituitary gland and of the endocrine pancreas). One of the major benefits of genetic screening is the possibility to identify MEN I family member that do not have a risk of developing the disease. The trait does not skip generations which means that if a MEN I patient gets a child that is unaffected and has not inherited the mutation, the disease will not be seen later in the grandchildren. Upon identification of cases with the mutation biochemical and radiological examinations should be performed regularly also in young asymptomatic patients.
Literature worth reading if you want to know more
Chandrasekharappa, S. C., Guru, S. C., Manickam, P., Olufemi, S. E., Collins, F. S., Emmert-Buck, M. R., Debelenko, L. V., Zhuang, Z., Lubensky, I. A., Liotta, L. A., Crabtree, J. S., Wang, Y., Roe, B. A., Weisemann, J., Boguski, M. S., Agarwal, S. K., Kester, M. B., Kim, Y. S., Heppner, C., Dong, Q., Spiegel, A. M., Burns, A. L., & Marx, S. J. (1997). Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science, 276(5311), 404-407.
Dean, P. G., van Heerden, J. A., Farley, D. R., Thompson, G. B., Grant, C. S., Harmsen, W. S., & Ilstrup, D. M. (2000). Are patients with multiple endocrine neoplasia type I prone to premature death? World J Surg, 24(11), 1437-1441..
Doherty, G. M., & Skogseid, B. (Eds.). (2001). Surgical Endocrinology. Philadelphia: Lippincott Williams & Wilkins. Skogseid, B., Eriksson, B., Lundqvist, G., Lorelius, L. E., Rastad, J., Wide, L., Akerstrom, G., & Oberg, K. (1991). Multiple endocrine neoplasia type 1: a 10-year prospective screening study in four kindreds. J Clin Endocrinol Metab, 73(2), 281-287..
Skogseid, B., Oberg, K., Eriksson, B., Juhlin, C., Granberg, D., Akerstrom, G., & Rastad, J. (1996). Surgery for asymptomatic pancreatic lesion in multiple endocrine neoplasia type I. World J Surg, 20(7), 872-876; discussion 877.