MULTIPLE ENDOCRINE ADENOMAS

Multiple Endocrine Adenomas – General Information

Multiple Endocrine Adenomas are also known as Multiple Endocrine Neoplasia (MEN) and are a cumulus of three syndromes presenting tumors of the endocrine glands, each with its own characteristics. Having any one these tumors does not mean that you are linked to MEN, but it usually recommended taking a series of tests to exclude this possibility, especially if there are obvious clinical signs. Multiple Endocrine Adenomas are inherited, as they are autosomal dominant pattern disorders.
There are three types of Multiple Endocrine Adenomas: MEN type 1, MEN type 2 and MEN type 3. The first type of MEN is named Wemer’s syndrome after the doctor who discovered it in 1954 – Dr. Paul Wermer- and described it:

• Wermer’s syndrome is a parathyroid hyperplasia/tumor which causes hyperparathyroidism (which is an over activity of the parathyroid glands which produce much more parathyroid hormone)
• Pancreatic islet cell tumors that cause hypoglycemia (also named insulinoma) and Zollinger Ellison syndrome (known as gastrionma, which is a tumor that secrets gastrin)
• Pituitary Adenoma which can cause an excess of pituitary hormone.

The other two types of Multiple Endocrine Adenoma are based on molecular genetics, and the mutation is in the RET (meaning “rearranged during transfection”) proto-oncogene and as the first type they are inherited in an autosomal dominant pattern. MEN type 2 is also known as Sipple syndrome after the doctor who discovered it, in 1961 – Dr. John H. Sipple. The MEN type 3 was discovered by Schimke in 1968.

Multiple Endocrine Adenomas - Symptoms

It is a well known the fact that everyone is born with the gene for MEN 1 and also that the over activity of the endocrine glands is starting after ten years of age, although different endocrine glands become overactive at different times in life. The same happens with the different zones of an endocrine gland that become active at different times. In general the development of Multiple Endocrine Adenomas is increasing with age. By the age of 30, the majority of people who inherit MEN 1 will have endocrine gland over activity. The bad part is that the symptoms do not develop until the person who has MEN 1 reaches the age of 30. This is why it very important for people that has a factor of risk to be tested, even though they are asymptomatic.
The clinical symptoms depend on the type of the gland that is affected of the Multiple Endocrine Adenomas:

• Parathyroid – hyperparathyroidism is present in over 90% of the patients. The most common manifestation in Hypercalcemia, but they can also develop: nephrolithiasis (which is a kidney stone) and nephrocalcinosis (which is the accumulation of the calcium in the form of phosphate or calcium oxalate in the kidney’s substance).
• Pituitary – the pituitary tumors occur in 50% of the people who have MEN type 1. These pituitary tumors secrete growth hormone and prolactin, which is why the patients have usually acromegaly. Local tumor expansion causes: visual disturbance, headaches and hypopituitarism.
• Pancreas – 30% of the tumors that develop in the pancreas are malignant.

Multiple Endocrine Adenomas – Treatment

Patients that have tumors of the pancreas, pituitary, parathyroids, especially those who have a family history of endocrinopathy, should have periodic investigations of the tumors by their doctor. These investigations consist in querying for symptoms as: peptic ulcer disease, hypoglycemia, hypopituitarism, nephrolithiasis, and diarrhea; for women there is needed a galatorrhea, acromegaly, measurement of serum Ca and prolactin and subcutaneous lipomas. There can also be done a radiologic test in case that the other tests indicate an endocrine abnormality. Here are some tests that can be done to see if there are any endocrine abnormalities:

• Adrenal biopsy
• MIBG scintiscan that can reveal tumors.
• MRI of abdomen that shows adrenal mass
• Elevated urine metanephrine
• Elevated urine catecholamine
• Ultrasound of the thyroid
• Elevated calcitonin
• Thyroid scan – that can show one or more nodules.
• Parathyroid biopsy that can reveal a tumor
• Increased serum calcium
• Decreased serum phosphorus
• Increased serum alkaline phosphatase
• Imaging of the kidneys and urethras to see if there are any calcifications or obstructions
• ECG that can possibly reveal abnormalities.
• Insulin tests
• Cortisol tests
• Serum adrenocorticotropic hormone
• Serum prolactin
• Serum luteinizing  hormone
• Serum follicle stimulating hormone
• Cranial CT scan – to see if there are any tumors
• MRI of the head

Patients who suffer from Multiple Endocrine Adenomas should consider the following. The first treatment of the parathyroid and pituitary lesions is surgery. The islet cell tumors are hard to manage as the lesions are usually small and difficult to find and if only a single tumor is not located it is necessary a total pancreatectomy. Streptozocin and many other cytotoxic drugs can ameliorate the symptoms by reducing the tumor’s weight. Diazoxide can help in the treatment of hypoglycemia.
If the cancer has spread patients who are suffering from Multiple Endocrine Adenomas should use:

• Chemotherapy
• Radiation
• Radiofrequency ablation

The advantages of radiofrequency ablation are:

• Effective treatment only for small cancers
• Minimally invasion with no skin incision
• The patient has no risk to take
• Usually there is little or no pain
• The patient has not a very long period to stay in hospital
• Can be repeated in case that new cancers develop.

Here is a list of drugs that can be used in the patients that have Multiple Endocrine Adenomas:

• Lansoprazole - is a proton pump inhibitor and it reduces the quantity of acid produced in the stomach.
• Omeprazole – that suppresses the acid produced in the stomach.

For parathyroids the recommended treatment is 3 and half parathyroidectomy and the cautious exploration of the thymic tissues. For pancreas it is recommended surgery: duodenopancreactomy in the heavy cases and it can be also used the antiacid treatment for the small and nonfunctional tumors. For adrenal glands tumors it is also recommended surgery for the lesions that are clearly identified. For thymic/bronchial carcinoids it is obligatory surgery as they are malignant and can affect the prognosis in MEN type 1.