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Multiple Endocrine Neoplasia type II
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Multiple endocrine neoplasia type II is an endocrine disease involving several endocrine organs-either at once or staggered throughout a person's life. MEN II has two types: MEN IIA and MEN IIB. MEN IIA is less severe than MEN IIB but both involve pheochromocytomas or adrenal medullary tumors and thyroid cancer, which is more severe in MEN IIA. Parathyroid gland tumors are also involved with MEN type II. MEN II is a genetic disorder caused by specific gene mutations. It is an autosomal dominant disorder, meaning that fifty percent of one's children will inherit the disease if one parent has the disorder. Some people have developmental disorders.
About half of all patients develop a pheochromocytoma or a tumor that produces epinephrine or norepinephrine in the adrenal gland. They can cause a serious high blood pressure crisis or a cardiac arrhythmia leading to death. Almost all patients with MEN 2A develop medullary cancer of the thyroid in the teens or twenties. It is usually on both sides of the thyroid making it necessary to remove the thyroid gland entirely.
The incidence of multiple endocrine neoplasia type II is about one per 50,000 individuals. The prognosis of the disease depends on the stage of the disease at the time of diagnosis and is why the patient should have a prophylactic removal of the thyroid gland as soon as they know they have the condition. This prevents advanced thyroid cancer. Genetic screening for MEN II is possible and can be done while the individual is young. The elevated parathyroid condition occurs in 20-30 percent of the cases of MEN IIA. The symptoms are usually vague and can present with high calcium in the blood.
The disease in its entirety develops in half the cases by age 50 years and 70 percent of individuals develop the case by age 70 years. The finding of medullary thyroid cancer has been found as early as infancy. Symptoms include hypertension or high blood pressure, diarrhea, sweating, itchy skin lesions, and a neck mass. If you have high calcium, you tend to get excessive urination, constipation, thirstiness, depression, kidney stones, memory difficulties and elevated blood sugar from glucose intolerance. The symptoms can be mild or very severe, depending on the calcium level and the individual.
The physical exam of MEN II shows a neck mass or masses that do not hurt, elevated pulse and elevated blood pressure. There is a high arched palate, a sunken chest, flat feet and scoliosis. There can be neuromas of the eyelids and thick lips. There is itching of primarily the upper back.
The causes of MEN II are mutations in the RET proto-oncogene on chromosome 10. It is not known exactly what the gene does but in makes a crucial protein during embryonic development. It appears to affect the endocrine glands, particularly the parathyroid, adrenal and thyroid glands.
The diagnosis of MEN II involves the genetic screening for the RET mutations in suspected patients. Family members should be screened as well. Calcitonin levels can identify parathyroid disease and the levels of epinephrine or norepinephrine can be detected as elevated in adrenal disease. A pentagastrin stimulation test checks for medullary thyroid cancer. It measures calcitonin levels over a period of time after receiving pentagastrin. Disease of the parathyroid gland is assessed by checking the calcium levels and parathyroid hormone levels.
A CT scan can be done or an MRI screen can be done to assess the thickness and nodularity of the adrenal gland. A special test known as an MIBG scan can find pheochromocytomas in the adrenal gland. CT scanning or MRI scanning of the neck can show the presence of thyroid nodules. If one is found, a needle aspirate can be taken so that the tissue can be biopsied. If the medullary thyroid cancer has spread, an OctreoScan can be done. It uses radioactive iodine to find areas of uptake elsewhere in the body.
There is a staging process for medullary thyroid cancer. Stage I involves a tumor less than 2 cm with no lymph node involvement. Stage II involves a tumor 2-4 cm in diameter with limitations only to the thyroid gland. Stage III involves regional lymph node involvement. Stage IVA involves tumor that spreads outside of the thyroid with metastases to cervical lymph nodes or mediastinal lymph nodes. Stage IVB involves tumor invasion into the pre-vertebral fascia and stage IVC involves the presence of distant metastases.
MEN IIA is often treated with surgery to remove the affected areas. Doctors use prostaglandin inhibitors to manage the diarrhea associated with thyroid cancer. Alpha blockers are used to treat pheochromocytomas before surgery is used to definitively take care of the problem. Lasix is used to treat the high calcium due to hyperactivity of the parathyroid gland. Calcitonin is used to treat the condition as well, especially if the Lasix fails to control the high calcium condition. The parathyroid gland is eventually removed. The pheochromocytoma is removed first because, if other surgeries are done first, the person doesn't tolerate surgery very well.