Causes of Hyperthyroidism
Is It Graves' Disease or Toxic Multinodular Goiter or Thyroiditis?
May 7, 2006
Graves' disease (GD) is an autoimmune disorder that targets the Thyroid Stimulating Hormone receptor (TSHr) positioned on the surface of the Thyroid cell. The TSHr is the primary autoantigen targeted in this autoimmune disease. The subsequent binding of Thyroid Stimulating Immunoglobulins (TSI) or autoantibodies to the TSHr, leads to hyper-stimulation of the thyroid and over production of Thyroxine (T4) and Triiodothyronine (T3), hormones naturally produced by the Thyroid. Due to this hyper-stimulatory signal, the resulting symptoms are indicative of Graves' disease.
In the majority of cases of Hyperthyroidism, TSI autoantibodies are directly responsible (>85%); this makes the detection of TSI a fundamental aspect of a correct diagnosis, and monitoring their levels during treatment a diagnostic necessity. Another cause of Hyperthyroidism is Thyroid nodules which are abnormal growths in the Thyroid which over produce Thyroid hormones, causing the same type of symptoms as antibody driven hormone over production. Patients can have single or multiple nodule growth and these are usually benign. Thyroiditis or swelling of the Thyroid may also be caused by viral infections.
The gender profile for Graves' disease, similar to that of most autoimmune diseases, is that it is a predominately a female issue. Ranges vary from publication to publication, however the general consensus is that a ratio of 8:1 women to men are affected.
Current treatment strategies are Radio-Iodine Ablation (RIA), Anti-Thyroid Drugs and Surgical removal of the Thyroid.
It has been reported that almost 70% of the members of the American Thyroid Association prefer the ablative approach as a first option for treatment of Graves' patients. Physicians claim that the correct amount of I131 (Radioactive Iodine, RAI) can be administered to create a euthyroid or "normal" condition. Physicians try to adjust the dose of radioactive iodine to destroy only enough of the thyroid gland to bring its hormone production back to normal, without reducing thyroid function too much; others use a larger dose to completely destroy the thyroid. Most of the time, people who undergo this treatment must take thyroid hormone replacement therapy for the rest of their lives. (Merck Rx).
Nonetheless, a longterm study from 1965-2002 that included over 2000 patients, and was published in Clinical Endocrinology 2004, concluded that; RAI treatment of Hyperthyroid Graves' patients resulted in 82% developing Hypothyroidism between 1 and 25 years post treatment. In 17% of patients in the study multiple radio-active iodine treatments (from 2-6 additional treatments) were needed to achieve a "euthyroid" or hypothyroid state. The ablative therapy leaves the patient without any alternative treatment options and a lifetime of hormone replacement therapy.
Anti-Thyroid Drug (ATD) therapy involves the prescription of immunomodulatory drugs like Methimozole (MMI) or Propylthiouracil (PTU). These strategies allow the patient to maintain their own Thyroid, and 30-55% of patients will become euthyroid following ATD therapy, an option lost to those who no longer have their Thyroid. The standard school of thought has been 12-18 months of treatment and then the removal of the ATD therapy. However, in a paper published Clinical Endocrinology 2005 a study of patients that remained on ATD for an average of 4 years (some as many as 10 years) had a remission rate of 88%. Additionally, another study found in Thyroid 2000 vol. 10 demonstrated that GD patients that exhibited a "smooth" decline in their antibody levels, or population, after ATD therapy was said to be a predictor of remission. In 36 out of 44 patients, or 82%, exhibiting a "smooth" decline of TSI levels were antibody and symptom free 1 year after the removal of the ATD therapy.
Other Autoantibodies to the Thyroid also exist and their presence can be detected with diagnostic tests. Other thyroid antibodies include; Thyroid Peroxidase Antibodies (TPOAb), and Thyroglobulin Antibodies (TgAb). TPOAb assay is a test done to detect Autoantibodies directed against TPO, an enzyme in the Thyroid that is very important to the production of Thyroid Hormones. TPO is found in thyroid follicle cells where it catalyzes the iodination of T4 and T3 in the biosynthesis of thyroid hormones. These antibodies are present in a high number of patients (70-90%) with chronic Thyroiditis, an inflammation of the thyroid gland that causes the gland to become underactive. As the tissue is deteriorating due to the inflammation and is "dumping" enzyme and some tissue, the immune system responds by making antibodies. These antibodies are also present in lesser numbers of persons with other thyroid disease as well as other non-thyroid autoimmune disorders. Additionally, 3% of people have these antibodies and have no evidence of any disease. The chance of having TPOAbs increases in females as they advance in age. Therefore, although possibly indicative of general autoimmunity, this test is not specific to Graves' disease. The TgAb assay has a similar story. This again, brings us around to the detection of the one antibody TSI; that is specific to the disease and is correlated to the clinical presentation. There are bioassays that have been designed not to just detect, but in a semi-quantitative way, show the disease function in a living cell. The sensitivity is 93-96%. It's time to utilize this currently under-utilized assay and offer to patients and physicians alike, the best option for recovery and for the best quality of life that can currently be achieved.
