Treatment of thyroid disorders Jamaluddin Shaikh, Ph.D. School of Pharmacy, University of Nizwa Lecture 18 April 29, 2013

Thyroid Hormones Following hormones are synthesized from thyroid gland: Triiodothyronine (T3) Thyroxine (T4)

Role of Thyroid Hormones Changes the size and shape of the thyroid gland Changes in secretion of hormones from the gland

Types of Thyroid Disorders Following disorders are associated with thyroid gland hormone: Hyperthyroidism Hypothyroidism Hyperthyroidism N O R M A L Hypothyroidism

Goal of Antithyroid Therapy To decrease synthesis and / or release of additional hormone. This can be accomplished by (1) removing part or all of the thyroid gland (2) by inhibiting synthesis of the hormones (3) by blocking release of the hormones from the follicle or

Removing Thyroid Gland This can be accomplished either surgically or by destruction of the gland by beta particles emitted by radioactive iodine (131I) Younger patients are treated with the isotope without prior pretreatment with methimazole, whereas the opposite is the case in elderly patients Most patients become hypothyroid as a result of this drug and require treatment with levothyroxine.

Advantage of Radiotherapy No tissue other than thyroid is exposed to sufficient ionizing radiation. Hypoparathyroidism is a risk of surgery, whereas in case of radiotherapy, this is not so. No discomfort which is associated with surgery No hospitalization Hypoparathyroidism is is an endocrine disorder in which the parathyroid glands in the neck do not produce enough parathyroid hormone Disadvantage of Radiotherapy High incidence of delayed hypothyroidism 7

Inhibition of Hormone Synthesis Thioamides, propylthiouracil (PTU) and methimazole are concentrated in the thyroid, where they inhibit both the oxidative processes required for iodination of tyrosyl groups and the coupling of iodotyrosines to form T3 and T4. PTU can also block the conversion of T4 to T3 The thioamides are well absorbed from the GI tract, but they have short half-lives Several doses of PTU are required per day, whereas a single dose of methimazole suffices due to the duration of its antithyroid effect Rare adverse effects include agranulocytosis, rash, and edema Agranulocytosis: an acute condition involving a severe and dangerous leukopenia (lowered white blood cell) 8

Blockade of Hormone Release A pharmacologic dose of iodide inhibits the iodination of tyrosines, but this effect lasts only a few days Iodide inhibits the release of thyroid hormones from thyroglobulin Iodide is not useful for long-term therapy, because the thyroid ceases to respond to the drug after a few weeks Administered orally Adverse effects are relatively minor and include sore mouth and throat, swelling of the tongue or larynx, rashes 9

Hypothyroidism: Treatments Hypothyroidism usually results from autoimmune destruction of the thyroid gland or the peroxidase and is diagnosed by elevated TSH Hypothyroidism: Treatments Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone It is treated with levothyroxine (T4) Drug is given once daily because of its long half-life. Steady state is achieved in 6 to 8 weeks Toxicity is directly related to T4 levels and manifests itself as nervousness, heart palpitations and tachycardia, intolerance to heat, and unexplained weight loss

Hyperthyroidism: Treatments Excessive amounts of thyroid hormones in the circulation are associated with a number of disease states, including Graves' disease, toxic adenoma, and goiter In these situations, TSH levels are reduced Hyperthyroidism: Treatments Graves' disease is an autoimmune disease where the thyroid is overactive An adenoma is a benign tumor (-oma) of glandular origin; goiter (Latin gutteria, struma), is a swelling in the thyroid gland The goal of therapy is to decrease synthesis and/or release of additional hormone Types of therapy: Removing part or all of the thyroid gland Inhibiting synthesis of the hormones Blocking release of the hormones from the follicle

Inhibiting Synthesis of the Hormones The thioamides, propylthiouracil (PTU) and methimazole, are belong this group The thioamides are well absorbed from the gastrointestinal tract, but they have short half-lives Several doses of PTU are required per day, whereas a single dose of methimazole is sufficient Relatively rare adverse effects include agranulocytosis, rash, and edema Agranulocytosis, is an acute condition involving a severe and dangerous leukopenia (lowered white blood cell)