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Chapter 58

Drugs for Thyroid Disorders

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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

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Thyroid Hormones Profound effect on:

Metabolism Cardiac function Growth

• Promotes maturation in infancy and childhood Development

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Thyroid Hormone Actions Stimulation of energy use Stimulation of the heart Promotion of growth and development

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Thyroid Produces two active hormones whose

synthesis is stimulated by low plasma levels of iodine Triiodothyronine (T3)

• Synthetic T3 is liothyronine Thyroxine (T4, tetraiodothyronine)

• Synthetic T4 is levothyroxine

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Thyroid Function Tests Serum thyroid-stimulating hormone (TSH)

Screening and diagnosis of hypothyroidism Elevated TSH is indication of hypothyroidism

Serum T4 test Can measure total T4 or free T4

Serum T3 test Can measure total T3 or free T3

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Hypothyroidism Severe deficiency of thyroid hormone

Myxedema (adults) Cretinism (infancy)

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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

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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)

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Hypothyroidism Treatment Therapeutic strategy Lifelong replacement therapy

Levothyroxine (T4) Liothyronine (T3)

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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

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Two Forms of Hyperthyroidism Graves’ disease

Most common form Affects women 20–40 years old Causes exophthalmos

Toxic nodular goiter (Plummer’s disease)

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Hyperthyroidism Cause

Thyroid-stimulating immunoglobulins (TSIs) Treatment

Surgical removal of thyroid tissue Destruction of thyroid tissue Suppression of thyroid hormone synthesis

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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

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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

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Thyroid Hormone Preparations Levothyroxine (Synthroid)

Synthetic preparation of thyroxine (T4) and drug of choice for hypothyroidism

Conversion to T3 Half-life: 7 days Used for all forms of hypothyroidism

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Thyroid Hormone Preparations Levothyroxine (Synthroid) (cont’d)

Should be taken in the morning at least 30 to 60 minutes before breakfast

Adverse effects• Tachycardia• Angina• Tremors• Can intensify effects of warfarin

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Thyroid Hormone Preparations Levothyroxine (Synthroid) (cont’d)

Drug interactions• Drugs that reduce levothyroxine absorption• Drugs that accelerate levothyroxine metabolism• Warfarin• Catecholamines

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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

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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)

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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

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Propylthiouracil (PTU) Adverse effects

Agranulocytosis (most serious) Hypothyroidism Pregnancy and lactation Can cause severe liver damage

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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 T4 to T3 in the periphery, whereas methimazole does not.

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Radioactive Iodine-131 (131I) 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 131I therapy

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Radioactive Iodine-131 (131I) Effect on thyroid Advantages and disadvantages of (131I)

therapy Who should be treated and who should not Use in thyroid cancer Diagnostic use Preparations

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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

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Beta Blockers Can suppress tachycardia and other

symptoms of Graves’ disease Benefits derive from beta-adrenergic

blockade, not from reducing levels of T3 or T4

Beneficial in thyrotoxic crisis