1. 1 Dr: Wael H.Mansy, MD Assistant Professor College of Pharmacy King Saud University

2. 2  There are two main hormones produced by the thyroid gland: 1.Thyroxin (T4) and 2.Triiodothyronine (T3).  Both hormones are derived from the amino acid Tyrosine and contain Iodine that is extracted from the blood.  The release of thyroid hormones from the thyroid is regulated by TRH secreted from the anterior pituitary gland. Function of the thyroid gland

3. 3 T4 versus T3 T3 ~5X as active as T4 T4 secreted solely form thyroid gland <20% T3 secreted from the thyroid gland Majority of T3 from breakdown of T4 (de-iodination) in peripheral tissue Mostly liver and kidneys

5. 5 The main actions of T3 and T4 1.Increased basal metabolic rate 2.Maintenance of normal metabolic function. 3.Normal physical, mental and sexual development. 4.Development of the nervous system in the fetus

6. 6 Definitions Goiter – Enlargement of the thyroid gland Hypothyroidism – Inadequate thyroid hormone production Thyroiditis – Inflammation of the thyroid gland Thyrotoxicosis a term that is used to describe the “toxic” effects of excess thyroid hormones on the body. – State resulting from excess production/exposure to thyroid hormone Hyperthyroidism – Thyrotoxicosis caused by a hyperfunctioning thyroid gland – Excludes thyroiditis or excessive exogenous thyroid hormone Thyroid Diseases

7. 7 Common causes of Hypothyroidism Thyroiditis: Hashimoto’s thyroiditis in which antibodies are produced against the tissue of the thyroid. Although the exact etiology of this autoimmune disorder is unknown, it can lead to progressive destruction of the thyroid gland and loss of thyroid function. Thyroid Surgery or Irradiation Iodine deficiency (Goiter) –Most common cause of hypothyroidism worldwide Hypothyroidism

8. 8 Hashimoto’s Thyroiditis Most common cause of hypothyroidism Women 30-50 years of age HLA-DR5 + Autoimmune thyroiditis – Antimicrosomal antibodies Against peroxidase – Antithyroglobulin antibodies Against thyroglobulin – Autoantibodies against TSH receptor Net effect is prevent TSH stimulation of gland

9. 9 Nontoxic goiter: 1. Hypertrophy of the thyroid gland that is not accompanied by excess secretion of thyroid hormones. 2. May occur as a result of dietary iodine deficiency, during pregnancy and at puberty. 3. Symptoms are those of hypothyroidism. Toxic goiter : 1. Hypertrophy of the thyroid that is accompanied by excess thyroid production. 2.May be associated with Graves’ disease. 3.Symptoms are those of hyperthyroidism. Goiter

10. 10 GOITER

11. 11  Hypothyroidism that occurs during fetal development  May occur as a result of a congenital defect in thyroid development  Severe mental retardation due to poor development of the brain  Poor overall development and growth retardation Hypothyroidism Cretinism

12. 12  Hypothyroidism in the adult  May result from autoimmune destruction of the thyroid or thyroid injury or removal  Presents with signs of hypometabolism including:  Cold intolerance  Weight gain  Fatigue  Bradycardia  Cool, dry skin  Anorexia  Constipation  Edema of the face (swelling around the eyes), hands and ankles; drooping eyelids. Hypothyroidism Myxedema

13. 13 Possible long-term complications of untreated hypothyroidism: cardiac hypertrophy, heart failure, and myxedema coma, which presents with hypothermia, seizures and respiratory depression. Treatment Thyroid hormone replacement therapy. A variety of synthetic and natural T3/T4 preparations are available for use orally. Hypothyroidism

14. 14 Increased synthesis and release of T3 and T4, Hyperthyroidism is also referred to as Thyrotoxicosis. Hyperthyroidism may be 1.A primary condition that results from an overactive thyroid gland. 2. Secondary to excessive stimulation of the thyroid by TSH from the pituitary. 3.Grave’s disease: the most common causes of hyperthyroidism 4.Plummer’s disease: toxic goiter not associated with Grave’s disease. 5.a tumor of the thyroid. In rare cases carcinomas arising outside of the thyroid may produce thyroid hormone or TSH. Hyperthyroidism

15. 15 *Patients with Graves’ disease produce (Thyroid Stimulating Immunoglobulin) antibodies that bind TSH receptors on the thyroid and mimic the actions of TSH leading to excess production of thyroid hormones. Hyperthyroidism Graves’ disease *Classic Triad (15-20%): Diffuse goiter, Hyperthyroidism, and Ophthalmopathy (exophthalmos)

16. 16 The manifestations of hyperthyroidism are essentially the same regardless of the cause of the hyperthyroidism: 1. Increased basal metabolic rate 2. Increased heat production, patient always feels “hot” 3. Tachycardia 4. Increased catecholamine sensitivity; patients are at risk for cardiac arrhythmias 5. Increased appetite 6. Weight loss 7. Enhanced bowel activity 8. Behavioral changes : nervousness and hyperactivity Hyperthyroidism Manifestations

17. Laboratory tests to evaluate thyroid function Serum total thyroxine (total) Unbound or serum free thyroxine Serum total triiodothyronine Serum TSH Serum thyroglobulin Antibodies

18. Thyroid Antibodies Antithyroglobulin and Antiperoxidase – Markers for Hashimoto’s but not specific Thyroid stimulating immunoglobulin—TSI – Against the TSH receptor – The cause of Graves’ disease – Predict neonatal hyperthyroidism

19. Thyroid Scan

20. 20  β-Blocking drugs to blunt the effects of excess adrenergic stimulation.  Antithyroid drugs (propylthiouracil, carbimazole, methimazole) that block production of thyroid hormone.  Surgical ablation of a portion of the thyroid may be used. Following surgery, patients may likewise become hypothyroid and require thyroid hormone replacement therapy. Hyperthyroidism Treatment

21. 21  Radioiodine: Given orally and taken up by hormone-producing cells of the thyroid as if it were normal iodine. The cytotoxic actions of the β and γ radiation destroy the hormone-producing cells of the thyroid. After treatment the patient usually becomes hypothyroid and must be managed with thyroid hormone replacement therapy. Radioactive iodine should not be used in patients of childbearing age due to the possible effects on offspring. Hyperthyroidism Treatment

22. Hyperthyroid emergencies Thyroid Storm Rare complication of hyperthyroidism where manifestations of thyrotoxicosis become life threatening. Also may be termed Thyrotoxic Crisis.

23. Precipitating factors: Infection Trauma/Surgery Parturition DKA MI CVA PE Withdrawal of thyroid meds 20-25% cases no precipitant found

24. Fever >38.5 Sinus tachycardia out of proportion to fever. SVT or dysrhythmias with or without CHF GI symptoms (nausea, vomiting, diarrhea, rarely jaundice) Volume depletion. CNS dysfunction (agitation, confusion, delirium, stupor, coma, seizure)

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