Thyrotoxicosis

THYROTOXICOSIS -Thyrotoxicosis is defined as the state of thyroid hormone excess and is not synonymous with hyperthyroidism, which is the result of excessive thyroid function. -However, the major etiologies of thyrotoxicosis are hyperthyroidism caused by Graves' disease, toxic multinodular goiter, and toxic adenomas Causes of thyrotoxicosis A.Primary hyperthyroidism 1) Graves' disease 2) Toxic multinodular goiter 3) Toxic adenoma 4) Functioning thyroid carcinoma metastases 5) Activating mutation of the TSH receptor 6) Activating mutation of Gsα (McCune-Albright syndrome) 7) Struma ovarii 8) Drugs: iodine excess (Jod-Basedow phenomenon) B. Secondary hyperthyroidism 1) TSH-secreting pituitary adenoma 2) Thyroid hormone resistance syndrome: occasional patients may have features of thyrotoxicosis 3) HCG-secreting tumors 4) Gestational thyrotoxicosis C. Thyrotoxicosis without hyperthyroidism 1) Sub acute thyroiditis 2) Silent thyroiditis 3) Other causes of thyroid destruction: amiodarone, radiation, infarction of adenoma 4) Ingestion of excess thyroid hormone (thyrotoxicosis factitia) GRAVES DISEASE Introduction -Is an autoimmune disease characterized by hyperthyroidism due to circulating autoantibodies. -Thyroid-stimulating immunoglobulins (TSIs) bind to and activate thyrotropin receptors, causing the thyroid gland to grow and the thyroid follicles to increase synthesis of thyroid hormone. -Graves disease, along with Hashimoto thyroiditis, is classified as an autoimmune thyroid disorder. -In some patients, Graves disease represents part of a more extensive autoimmune process called autoimmune polyglandular syndrome, which is also associated with  Pernicious anemia  Vitiligo  DM type 1  Autoimmune Adrenal insufficiency  SLE

Race -Susceptibility is influenced by genes in the human leukocyte antigen (HLA) region on chromosome 6 and in CTLA4 on band 2q33 Sex -F;M ratio 7-8:1. -The female-to-male ratio for pretibial myxedema is 3.5:1. -Only 7% of patients with localized myxedema have thyroid acropachy. -Unlike the other manifestations of Graves’s disease, the female-to-male ratio for thyroid acropachy is 1:1. Age -Typically, Graves’s disease is a disease of young women,

Pathophysiology -B and T lymphocyte–mediated autoimmunity are known to be directed at 4 well-known thyroid antigens:  Thyrotropin receptor.(TSH receptor) -primary autoantigen of Graves disease responsible for the manifestation of hyperthyroidism  Thyroglobulin  Thyroid peroxidase  Sodium-iodide symporter -Direct proof of an autoimmune disorder is the development of hyperthyroidism in healthy subjects by transferring thyrotropin receptor antibodies from serum of patients with Graves disease -Also the passive transfer of thyrotropin receptor antibodies to the fetus in pregnant women. -The thyroid gland is under continuous stimulation by circulating autoantibodies against the thyrotropin receptor, and pituitary thyrotropin secretion is suppressed because of the increased production of thyroid hormones. -The stimulating activity of thyrotropin receptor antibodies is found mostly in the immunoglobulin G1 subclass. These thyroid-stimulating antibodies cause release of thyroid hormone and thyroglobulin that is mediated by adenosine 3,'5'-cyclic phosphate and they also stimulate iodine uptake, protein synthesis, and thyroid gland growth. -The anti–sodium-iodide symporter, antithyroglobulin, and antithyroid peroxidase antibodies appear to have little role in the etiology of hyperthyroidism -.However, they are markers of autoimmune disease against the thyroid. -Intrathyroidal lymphocytic infiltration is the initial histologic abnormality in persons with autoimmune thyroid disease and can be correlated with the titer of thyroid antibodies. Prevalence -Among the causes of spontaneous thyrotoxicosis, Graves disease is the most common. -Graves disease represents 60-90% of all causes of thyrotoxicosis in different regions of the world 80 cases per 100,000 women per year. Mortality/Morbidity -If left untreated, life-threatening thyrotoxic crisis (ie, thyroid storm) can occur. - Long-standing severe thyrotoxicosis leads to severe weight loss with catabolism of bone and muscle. -Cardiac complications and psychocognitive complications can cause significant morbidity. - Graves disease is also associated with ophthalmopathy and acropachy. -Long-term excess of thyroid hormone can lead to osteoporosis in men and women. - Maternal Graves disease can lead to neonatal hyperthyroidism by transplacental transfer of thyroidstimulating antibodies. Usually, the TSI titer falls during pregnancy. -Severe acropachy can be disabling and can lead to total loss of hand function. -Progression of ophthalmopathy can lead to compromised vision and blindness. Visual loss due to corneal lesions or optic nerve compression can be seen in severe Graves ophthalmopathy. Lipid metabolism - Decreased total cholesterol levels, decreased triglyceride levels Physical Common physical findings associated with thyrotoxicosis include  Widening of the palpebral fissures  Tachycardia  Hand tremor (fine and usually bilateral)  Proximal muscle weakness  Brisk deep tendon reflexes  Fidgetiness  Warm velvety skin.  Upon careful examination, the thyroid gland