CHAPTER 55 DRUGS FOR THYROID DISORDERS

Thyroid hormones have profound effects on metabolism, cardiac function, growth and
development.
- stimulate the metabolic rate of most cells, increase the force and rate of
cardiac contraction
- promote maturation
- severe deficiency can produce dwarfism and permanent mental impairment
Thyroid drugs are the most misused drugs in the diet industry.

I. THYROID PHYSIOLOGY

A. CHEMISTRY & NOMENCLATURE

- thyroid gland produces two active hormones: triiodothyronine (T3)
thyroxine (T4, tetraiodothyronine)
- T3 is more potent than T4
- the body secretes more T4 than T3 and converts it to T3 as needed

B. THYROID HORMONE ACTIONS

- thyroid hormones are protein bound
- synthetic drugs are better than natural drugs to mimic the natural thyroid
hormone actions

1. Stimulation of Energy Use – elevates the basal metabolic rate, resulting

in increased oxygen
consumption and increased heat production
2. Stimulation of the Heart – increases both the rate and force of
contraction, resulting in increased
cardiac output and increased oxygen demand
3. Promotion of Growth and Development – essential for normal
development of the brain and other
components of the nervous system, and have a significant impact on
maturation of skeletal
muscle

II. THYROID PATHOPHYSIOLOGY

A. HYPOTHYROIDISM – mild deficiency of thyroid hormone; malfunction of the thyroid

gland
- myxedema - severe deficiency in adults
- cretinism – hypothyroidism in infancy

1. Hypothyroidism in Adults
a. Clinical Presentation - produces pale, puffy and expressionless facial
characteristics, cold and
dry skin, hair is brittle and loss occurs, heart rate and
temperature are lowered, patient
 may have complaints of lethargy, fatigue, and intolerance to
cold
- mentality is impaired
- thyroid enlargement (goiter) may occur if reduced levels of T3
and T4 promote
excessive release of TSH (thyroid stimulating hormone)
b. Causes - usually due to malfunction of the thyroid itself
- in iodine sufficient countries, the principal cause is chronic
autoimmune thyroiditis
(Hasimoto’s disease)
- other causes are insufficient iodine in the diet, surgical
removal of the thyroid and
destruction of the thyroid by radioactive iodine
- may also result from insufficient secretion of TSH and TRH
(thyrotropin releasing
hormone)
c. Therapeutic Strategy - requires replacement therapy with thyroid
hormones and treatment must
continue for life
- standard replacement regimen consists of levothyroxine (T4)
alone
- when adequate, doses eliminate all signs and symptoms of
deficiency

2. Hypothyroidism During Pregnancy

- maternal hypothyroidism can result in permanent neuropsychologic
deficits in the child
- congenital hypothyroidism can cause mental retardation and other
developmental problems
- in the absence of fetal hypothyroidism, maternal hypothyroidism
can decrease IQ and other
aspects of neuropsychologic function
- limited largely to the first trimester, a time during which the fetus
is unable to produce thyroid
hormones on its own
- maternal hypothyroidism must be diagnosed and treated very early
- symptoms of hypothyroidism are often nonspecific (irritability,
tiredness, poor concentration,
etc.) – or there may be no symptoms at all
- recommended routine screening as soon as pregnancy is confirmed
- thyroid hormone levels should be monitored and dosage increased
as needed

3. Hypothyroidism in Infants
a. Clinical Presentations - causes mental retardation and derangement
of growth
- the child develops a large and protruding tongue, potbelly,
and dwarfish stature
 - development of the nervous system, bones, teeth, and
muscles is impaired
- cretinism usually results from a failure in thyroid
development
- other causes include autoimmune disease, severe
iodine deficiency, TSH
deficiency, and exposure to radioactive iodine in
utero
- requires replacement therapy with thyroid hormones
- if treatment is initiated within a few days of birth,
physical and mental
development will be normal
- if treatment is delayed for several months, some
permanent retardation will be
evident
- treatment must continue for life

B. HYPERTHYROIDISM
- elevated levels of thyroid hormones
- thyrotoxic crisis – extremely high levels of thyroid hormone

1. Graves’ Disease (Barbara Bush has this disease)

- most common cause of excessive thyroid hormone secretion
- occurs most frequently in women 20 to 40 yrs. old (incidence in
females is 6 times greater
than males)
- results from elevated levels of thyroid hormone
- heartbeat is rapid and strong, and dysrhythmias and angina
may develop
- central nervous system is stimulated, resulting in rapid
thought flow and rapid speech,
nervousness and insomnia
- skeletal muscles may weaken and atrophy
- metabolic rate is raised, resulting in increased heat
production, increased body
temperature, intolerance to heat and skin that is warm
and moist
- appetite is increased; however, despite increased food
consumption, weight loss
occurs is caloric intake fails to match the increased
metabolic rate
- patients often present with exophthalmos (protrusion of the
eyeballs)
Cause: - thyroid stimulating immuglobulins (TSIs) which are
antibodies produced by an
autoimmune process
- increase thyroid activity by stimulating receptors for
TSH on the thyroid gland
(mimic the effects of TSH on thyroid function)
 - not responsible for exophthalmos

Treatment (directed at decreasing production of thyroid hormones):

a) surgical removal of thyroid tissue
b) destruction of thyroid tissue with radioactive iodine
(preferred treatment for adults)
c) suppression of thyroid hormone synthesis with antithyroid
drugs (preferred treatment
for younger patients)

- Propranolol (suppresses tachycardia) and nonradioactive

(inhibits synthesis and
release of thyroid hormones) iodine may be used as
adjunctive therapy

2. Toxic Nodular Goiter (Plummer’s Disease)

- result of thyroid adenoma
- results from elevated levels of thyroid hormone
- heartbeat is rapid and strong, and dysrhythmias and angina
may develop
- central nervous system is stimulated, resulting in rapid
thought flow and rapid speech,
nervousness and insomnia
- skeletal muscles may weaken and atrophy
- metabolic rate is raised, resulting in increased heat
production, increased body
temperature, intolerance to heat and skin that is warm
and moist
- appetite is increased; however, despite increased food
consumption, weight loss
occurs is caloric intake fails to match the increased
metabolic rate
- persistent condition that rarely undergoes spontaneous remission

Treatment (directed at decreasing production of thyroid hormones):

a) surgical removal of thyroid tissue, which provides long-term
control (preferred)
b) destruction of thyroid tissue with radioactive iodine, which
provides long-term control
(preferred)
c) suppression of thyroid hormone synthesis with antithyroid
drugs (symptoms return
rapidly when drugs are withdrawn)

3. Thyrotoxic Crisis (Thyroid Storm)

- occurs when levels of thyroid hormone become extremely high
- characterized by hyperthermia, severe tachycardia, and profound
weakness
- unconsciousness, coma, and heart failure may ensue
 - can be caused by excessive production of endogenous thyroid
hormones or by overdose with
thyroid hormones during replacement therapy
- can be life threatening and requires immediate treatment
- high doses of potassium iodide or strong iodine solution are
given to suppress thyroid
hormone release
- propylthiouracil is given to suppress thyroid hormone
synthesis and conversion of T4
to T3 in the periphery
- propranolol is given to reduce heart rate
- additional measures include sedation, cooling, and giving
clucocorticoids and IV fluids

III. THYROID FUNCTION TESTS

A. SERUM (BLOOD) T4 TEST

- measures total (bound plus free) thyroxine
- useful for initial screening of thyroid function: levels of T4 will be
low in hypothyroid patients
levels of T4 will be high in hyperthyroid
patients
- can also be used to monitor thyroid hormone replacement therapy: T4
levels should rise

B. SERUM (BLOOD) T3 TEST

- measures total (bound plus free) triiodothyronine
- useful for diagnosing hyperthyroidism because in this disorder levels of T3
often rise sooner and to a
greater extent than levels of T4
- can also be employed to monitor thyroid hormone replacement therapy:
T3 levels should increase

C. SERUM (BLOOD) TSH

- most sensitive method for diagnosing hypothyroidism because very small
reductions in serum T3 and
T4 cause a dramatic rise in serum TSH
- even when the degree of hypothyroidism is minimal, it will be
reflected by an abnormally high
TSH level
- can also be used to distinguish primary hypothyroidism (high TSH levels)
from secondary
hypothyroidism (hypothyroidism resulting from anterior pituitary
dysfunction; low TSH levels)

IV. THYROID HORMONE PREPARATIONS FOR HYPOTHYROIDISM

A. LEVOTHYROXINE (T4) – (trade names: Levothroid, Levoxyl, Synthroid)
- synthetic preparation of thyroxine (T4)
- the drug of choice for most patients who require thyroid hormone
replacement
- highly protein bound with half-life of about 7 days
- indicated for all forms of hypothyroidism, regardless of cause
- levothyroxine and other thyroid hormones should not be taken to treat
obesity

Adverse Effects: in appropriate doses, rarely causes adverse effects

- excessive doses, thyrotoxicosis may result (symptoms:
tachycardia, angina, tremor,
nervouseness, insomnia, hyperthermia, heat intolerance, and
sweating)

Drug Interactions:
Absorption Reduction: Cholestyramine (Questran)
Calcium supplements (Tums, Os-Cal)
Sucralfate (Carafate)
Aluminum containing antacids (Maalox, Mylanta)
Iron supplements (ferrous sulfate)
- to ensure adequate absorption, patients should separate
administration of
levothyroxine and these drugs by 3 – 4 hours

Metabolism Increase: Phenytoin (Dilantin)

Rifampin (antibiotic)
sertraline (Zoloft) Phenobarbital
- patients taking these drugs may need to increase
levothyroxine dosage

- levothyroxine accelerates the degradation of vitamin K

dependent clotting factors
Warfarin effects are enhanced, therefore, dosage
should be reduced

- thyroid hormones increase cardiac responsiveness to

catecholamines (epinephrine,
dopamine, dobutamine), increasing the risk of
catecholamine-induced
dysrhythmias

Others: can increase requirements for insulin and digitalis,

therefore, dosages may need to be
increased

V. DRUGS FOR HYPERTHYROIDISM

A. PROPYTHIOURACIL (PTU)
- inhibits thyroid hormone synthesis
- rapidly absorbed following oral administration
- short half-life of about 75 minutes, therefore must be administered
several times a day
- can cross the placenta and can enter the breast milk
- can be used alone as the sole form of therapy for Graves’ disease
- used as an adjunct to radiation therapy
- administered to control hyperthyroidism until the effects of
radiation become manifest
- given to suppress thyroid hormone synthesis in preparation for
thyroid gland surgery
- given to patients experiencing thyrotoxic crisis

Adverse Effects: relatively rare

agranulocytosis is the most serious toxicity
- reaction is rare and usually develops during the 1st 2
months of therapy
- sore throat and fever may be the earliest indications
- patients should be instructed to report these
immediately
hypothyroidism – occurs in high doses
pregnancy and lactation – PTU crosses the placenta and has
caused neonatal
hypothyroidism and goiter
- PTU enters the breast milk
others – rash, nausea, arthralgia, headache, dizziness and
paresthesias

B. RADIOACTIVE IODINE (131I) – (TRADE NAME: IODOTOPE)

- radioactive isotope of stable iodine that emits a combination of beta
particles and gamma rays
- half-life of 8 days
- can be used to destroy thyroid tissue in patients with hyperthyroidism
(Graves’ Disease)
- objective is to produce clinical remission without causing complete
destruction of the thyroid
gland
- patients over the age of 30 may be candidates for this therapy
- children are inappropriate candidates
- pregnant and lactating mothers are inappropriate candidates