1. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Chapter 58 Drugs for Thyroid Disorders

2. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Thyroid Hormones  Profound effect on:  Metabolism  Cardiac function  Growth Promotes maturation in infancy and childhood  Development 2

3. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Thyroid Hormone Actions  Stimulate energy use  Stimulate the heart  Promote growth and development 3

4. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Thyroid  Produces two active hormones whose synthesis is stimulated by low plasma levels of iodine  Triiodothyronine (T 3 ) Synthetic T 3 : Liothyronine  Thyroxine (T 4, tetraiodothyronine) Synthetic T 4 : Levothyroxine 4

5. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Thyroid Function Tests  Serum thyroid-stimulating hormone (TSH)  Screening and diagnosis of hypothyroidism  Elevated TSH is an indicator of hypothyroidism  Serum T 4 test  Can measure total T 4 or free T 4  Serum T 3 test  Can measure total T 3 or free T 3 5

6. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Hypothyroidism  Severe deficiency of thyroid hormone  Myxedema (adults) Replacement therapy with thyroid hormones; in almost all cases, treatment must continue lifelong Hypothyroidism during pregnancy To help ensure healthy fetal development, maternal hypothyroidism must be diagnosed and treated very early  Cretinism (infancy) Replacement therapy with thyroid hormones 6

7. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Hypothyroidism in Adults  Clinical presentation  Pale, puffy face  Cold, dry skin  Brittle hair or loss of hair  Lowered heart rate and temperature  Lethargy and fatigue  Intolerance to cold  Impaired mentality 7

8. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Hypothyroidism in Adults  Causes  Usually due to malfunction of the thyroid  Hashimoto’s disease: Chronic autoimmune thyroiditis  Insufficient iodine in the diet  Surgical removal of thyroid and destruction of thyroid with radioactive iodine  Insufficient secretion of TSH and thyrotropin- releasing hormone (TRH) 8

9. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Hypothyroidism Treatment in Adults  Therapeutic strategy  Lifelong replacement therapy  Levothyroxine (T 4 )  Liothyronine (T 3 ) 9

10. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Hypothyroidism: Life Span Issues  During pregnancy  In first trimester can result in permanent neuropsychologic deficits in the child  In infants  May be permanent or transient  Can cause mental retardation and derangement of growth 10

11. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Two Forms of Hyperthyroidism  Graves’ disease  Most common form  Affects women age 20 to 40 years  Causes exophthalmos  Toxic nodular goiter (Plummer’s disease) 11

12. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Hyperthyroidism  Cause  Thyroid-stimulating immunoglobulins (TSIs)  Treatment  Surgical removal of thyroid tissue  Destruction of thyroid tissue  Suppression of thyroid hormone synthesis  Beta blockers (for example, propranolol)  Nonradioactive iodine 12

13. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Thyrotoxic Crisis (Thyroid Storm)  Cause  Patients with thyrotoxicosis who undergo significant stress (for example, surgery, illness)  Not triggered by a rise in thyroid hormones  Cannot be identified by laboratory testing 13

14. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Thyrotoxic Crisis (Thyroid Storm)  Signs  Hyperthermia (105º F or higher), severe tachycardia, restlessness, agitation, tremor, unconsciousness, coma, hypotension, heart failure  Treatment  Methimazole  Beta blocker  Sedation, cooling, glucocorticoids, IV fluids 14

15. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Thyroid Hormone Preparations  Levothyroxine [Synthroid]  Synthetic preparation of thyroxine (T 4 ) and drug of choice for hypothyroidism  Conversion to T 3  Half-life: 7 days  Used for all forms of hypothyroidism  Levothyroxine [Synthroid] (Cont.)  Should be taken in the morning at least 30 to 60 minutes before breakfast  Adverse effects Tachycardia, Angina, Tremors Can intensify effects of warfarin 15

16. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Thyroid Hormone Preparations  Other thyroid preparations  Liotrix [Thyrolar]  Thyroid (Armour Thyroid, others) 16

17. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Hyperthyroidism: Methimazole  First-line drug for hyperthyroidism  Prototype of the thionamides  Does not cause the liver damage associated with propylthiouracil (PTU)  Does not destroy existing stores of thyroid hormone  May take 3 to 12 weeks for euthyroid state  More dangerous than PTU during lactation and during the first trimester of pregnancy  Agranulocytosis 17

18. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Methimazole  Four applications in hyperthyroidism:  Sole form of therapy for Graves’ disease  Adjunct to radiation therapy until the effects of radiation become manifest  Suppresses thyroid hormone synthesis in preparation for thyroid gland surgery (subtotal thyroidectomy)  Thyrotoxic crisis 18

19. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Propylthiouracil (PTU)  Inhibits thyroid hormone synthesis  Second-line drug for Graves’ disease  Short half-life (about 90 minutes)  Full benefits may take 6 to 12 months  Therapeutic uses  Graves’ disease  Adjunct to radiation therapy  Preparation for thyroid gland surgery  Thyrotoxic crisis 19

20. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Propylthiouracil (PTU)  Adverse effects  Agranulocytosis (most serious)  Hypothyroidism  Pregnancy and lactation  Can cause severe liver damage 20

21. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. PTU vs. Methimazole  PTU can cause severe liver injury, whereas methimazole does not  PTU has a shorter half-life than methimazole (90 minutes compared to 6 to 13 hours), so it requires two or three daily doses rather than one  PTU crosses the placenta less readily than does methimazole, and concentrations in breast milk are lower  PTU blocks conversion of T 4 to T 3 in the periphery, whereas methimazole does not 21

22. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Radioactive Iodine-131 ( 131 I)  Radioactive isotope of stable iodine  Emits gamma and beta rays  Half-life: 8 days  2 to 3 months for full effect  Used in Graves’ disease  Effect on the thyroid  Advantages and disadvantages of 131 I therapy 22

23. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Radioactive Iodine-131 ( 131 I)  Effect on the thyroid  Advantages and disadvantages of ( 131 I) therapy  Who should be treated and who should not  Use in thyroid cancer  Diagnostic use  Preparations 23

24. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Nonradioactive Iodine  Strong iodine solution (Lugol’s solution)  Used to suppress thyroid function in preparation for thyroidectomy  Adverse effects Brassy taste Burning sensation in the mouth and throat Soreness of the teeth and gums Frontal headache Coryza Salivation Various skin eruptions 24

25. Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Beta Blockers  Propranolol: Can suppress tachycardia and other symptoms of Graves’ disease  Benefits derive from beta-adrenergic blockade, not from reducing levels of T 3 or T 4  Beneficial in thyrotoxic crisis 25