Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 58 Drugs for Thyroid Disorders

2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Thyroid Physiology  Chemistry and nomenclature  Synthesis and fate of thyroid hormones  Thyroid hormone actions  Regulation of thyroid function by the hypothalamus and anterior pituitary  Effect of iodine deficiency on thyroid function

3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Thyroid Hormones  Profound effect on:  Metabolism  Cardiac function  Growth Promotes maturation in infancy and childhood Promotes maturation in infancy and childhood  Development

4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Thyroid Hormone Actions   Stimulation of energy use   Stimulation of the heart   Promotion of growth and development

5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Thyroid  Produces two active hormones whose synthesis is stimulated by low plasma levels of iodine  Triiodothyronine (T 3 ) Synthetic T 3 is liothyronine Synthetic T 3 is liothyronine  Thyroxine (T 4, tetraiodothyronine) Synthetic T 4 is levothyroxine Synthetic T 4 is levothyroxine

6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Thyroid Function Tests  Serum thyroid-stimulating hormone (TSH)  Screening and diagnosis of hypothyroidism  Elevated TSH is indication 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

7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Hypothyroidism  Severe deficiency of thyroid hormone  Myxedema (adults)  Cretinism (infancy)

8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Hypothyroidism  Clinical presentation (adults)  Pale, puffy, and expressionless face  Cold and dry skin  Brittle hair or loss of hair  Heart rate and temperature are lowered  Lethargy and fatigue  Intolerance to cold  Impaired mentality

9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Hypothyroidism  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  Adults: insufficient secretion of TSH and thyrotropin-releasing hormone (TRH)

10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Hypothyroidism Treatment  Therapeutic strategy  Lifelong replacement therapy  Levothyroxine (T 4 )  Liothyronine (T 3 )

11Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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

12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Two Forms of Hyperthyroidism   Graves’ disease   Most common form   Affects women 20–40 years old   Causes exophthalmos   Toxic nodular goiter (Plummer’s disease)

13Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Hyperthyroidism  Cause  Thyroid-stimulating immunoglobulins (TSIs)  Treatment  Surgical removal of thyroid tissue  Destruction of thyroid tissue  Suppression of thyroid hormone synthesis

14Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Thyrotoxic Crisis (Thyroid Storm)  Cause  Patients with thyrotoxicosis who undergo significant stress (surgery, illness, etc.)  Not triggered by a rise in thyroid hormones  Cannot be identified by laboratory testing

15Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Thyrotoxic Crisis (Thyroid Storm)  Signs  Hyperthermia (105°F or higher), severe tachycardia, restlessness, agitation, tremor, unconsciousness, coma, hypotension, heart failure  Treatment  Potassium iodide, propylthiouracil (PTU), and beta blocker  Sedation, cooling, glucocorticoids, IV fluids

16Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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

17Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Thyroid Hormone Preparations  Levothyroxine (Synthroid) (cont’d)  Should be taken in the morning at least 30 to 60 minutes before breakfast  Adverse effects Tachycardia Tachycardia Angina Angina Tremors Tremors Can intensify effects of warfarin Can intensify effects of warfarin

18Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Thyroid Hormone Preparations  Levothyroxine (Synthroid) (cont’d)  Drug interactions Drugs that reduce levothyroxine absorption Drugs that reduce levothyroxine absorption Drugs that accelerate levothyroxine metabolism Drugs that accelerate levothyroxine metabolism Warfarin Warfarin Catecholamines Catecholamines

19Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Methimazole  First-line drug for hyperthyroidism  Prototype of the thionamides  Does not cause the liver damage associated with PTU  Does not destroy existing stores of thyroid hormone  May take 3–12 weeks for euthyroid state  More dangerous than PTU during lactation and during the first trimester of pregnancy

20Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Methimazole Four applications in hyperthyroidism  Sole form of therapy for Graves’ disease  Adjunct to radiation therapy until the effects of radiation become manifest  Suppress thyroid hormone synthesis in preparation for thyroid gland surgery (subtotal thyroidectomy)  Patients experiencing thyrotoxic crisis (although PTU is preferred)

21Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Propylthiouracil (PTU)  Inhibits thyroid hormone synthesis  Second-line drug for Graves’ disease  Short half-life (about 90 minutes)  Full benefits may take 6–12 months  Therapeutic uses  Graves’ disease  Adjunct to radiation therapy  Preparation for thyroid gland surgery  Thyrotoxic crisis

22Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Propylthiouracil (PTU)  Adverse effects  Agranulocytosis (most serious)  Hypothyroidism  Pregnancy and lactation  Can cause severe liver damage

23Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. PTU vs. Methimazole  PTU can cause severe liver injury, whereas methimazole does not  PTU has a shorter half-life than methimazole (90 minutes vs. 6 to 13 hours), hence it requires two or three daily doses rather than one.  PTU crosses the placenta less readily than does methimazole and achieves lower concentrations in breast milk.  PTU blocks conversion of T 4 to T 3 in the periphery, whereas methimazole does not.

24Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Radioactive Iodine-131 ( 131 I)  Radioactive isotope of stable iodine  Emits gamma and beta rays  Half-life: 8 days  2–3 months for full effect  Used in Graves’ disease  Effect on the thyroid  Advantages and disadvantages of 131 I therapy

25Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Radioactive Iodine-131 ( 131 I)  Effect on thyroid  Advantages and disadvantages of ( 131 I) therapy  Who should be treated and who should not  Use in thyroid cancer  Diagnostic use  Preparations

26Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Nonradioactive Iodine  Strong iodine solution (Lugol’s solution)  Used to suppress thyroid function in preparation for thyroidectomy  Adverse effects Brassy taste Brassy taste Burning sensation in the mouth and throat Burning sensation in the mouth and throat Soreness of the teeth and gums Soreness of the teeth and gums Frontal headache Frontal headache Coryza Coryza Salivation Salivation Various skin eruptions Various skin eruptions

27Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Beta Blockers  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