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Chapter 58
Drugs for Thyroid Disorders
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Thyroid Physiology
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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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Thyroid Hormones
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Profound effect on:
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Metabolism
Cardiac function
Growth
• Promotes maturation in infancy and childhood
Development
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Thyroid Hormone Actions
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Stimulation of energy use
Stimulation of the heart
Promotion of growth and development
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Thyroid
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Produces two active hormones whose
synthesis is stimulated by low plasma levels
of iodine
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Triiodothyronine (T3)
• Synthetic T3 is liothyronine
Thyroxine (T4, tetraiodothyronine)
• Synthetic T4 is levothyroxine
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Thyroid Function Tests
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Serum thyroid-stimulating hormone (TSH)
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Serum T4 test
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Screening and diagnosis of hypothyroidism
Elevated TSH is indication of hypothyroidism
Can measure total T4 or free T4
Serum T3 test
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Can measure total T3 or free T3
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Hypothyroidism
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Severe deficiency of thyroid hormone
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Myxedema (adults)
Cretinism (infancy)
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Hypothyroidism
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Clinical presentation (adults)
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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
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Causes
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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)
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Hypothyroidism Treatment
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Therapeutic strategy
Lifelong replacement therapy
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Levothyroxine (T4)
Liothyronine (T3)
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Hypothyroidism: Life Span Issues
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During pregnancy
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In first trimester can result in permanent
neuropsychologic deficits in the child
In infants
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May be permanent or transient
Can cause mental retardation and derangement of
growth
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Two Forms of Hyperthyroidism
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Graves’ disease
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Most common form
Affects women 20–40 years old
Causes exophthalmos
Toxic nodular goiter (Plummer’s disease)
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Hyperthyroidism
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Cause
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Thyroid-stimulating immunoglobulins (TSIs)
Treatment
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Surgical removal of thyroid tissue
Destruction of thyroid tissue
Suppression of thyroid hormone synthesis
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Thyrotoxic Crisis (Thyroid Storm)
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Cause
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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)
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Signs
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Hyperthermia (105°F or higher), severe
tachycardia, restlessness, agitation, tremor,
unconsciousness, coma, hypotension, heart
failure
Treatment
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Potassium iodide, propylthiouracil (PTU), and beta
blocker
Sedation, cooling, glucocorticoids, IV fluids
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Thyroid Hormone Preparations
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Levothyroxine (Synthroid)
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Synthetic preparation of thyroxine (T4) and drug of
choice for hypothyroidism
Conversion to T3
Half-life: 7 days
Used for all forms of hypothyroidism
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Thyroid Hormone Preparations
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Levothyroxine (Synthroid) (cont’d)
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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
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Levothyroxine (Synthroid) (cont’d)
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Drug interactions
• Drugs that reduce levothyroxine absorption
• Drugs that accelerate levothyroxine metabolism
• Warfarin
• Catecholamines
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Methimazole
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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)
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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)
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Adverse effects
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Agranulocytosis (most serious)
Hypothyroidism
Pregnancy and lactation
Can cause severe liver damage
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PTU vs. Methimazole
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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)
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Radioactive isotope of stable iodine
Emits gamma and beta rays
Half-life: 8 days
2–3 months for full effect
Used in Graves’ disease
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Effect on the thyroid
Advantages and disadvantages of 131I therapy
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Radioactive Iodine-131 (131I)
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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
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Strong iodine solution (Lugol’s solution)
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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
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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
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