Page 710 - Basic _ Clinical Pharmacology ( PDFDrive )

696 SECTION VII Endocrine Drugs

and incorporated into storage follicles. Its therapeutic effect The etiology and pathogenesis of hypothyroidism are outlined
depends on emission of β rays with an effective half-life of 5 days in Table 38–5. Hypothyroidism can occur with or without thy-
and a penetration range of 400–2000 μm. Within a few weeks roid enlargement (goiter). The laboratory diagnosis of hypothy-
after administration, destruction of the thyroid parenchyma is roidism in the adult is easily made by the combination of low free
evidenced by epithelial swelling and necrosis, follicular disrup- thyroxine and elevated serum TSH levels (Table 38–2).
tion, edema, and leukocyte infiltration. Advantages of radioio- The most common cause of hypothyroidism in the United
dine include easy administration, effectiveness, low expense, and States at this time is probably Hashimoto’s thyroiditis, an immu-
absence of pain. Fears of radiation-induced genetic damage, leuke- nologic disorder in genetically predisposed individuals. In this
mia, and neoplasia have not been realized after more than 50 years condition, there is evidence of humoral immunity in the presence
of clinical experience with radioiodine therapy for hyperthyroid- of antithyroid antibodies and lymphocyte sensitization to thyroid
ism. Radioactive iodine should not be administered to pregnant antigens. Genetic mutations as discussed previously and certain
women or nursing mothers, since it crosses the placenta to destroy medications also can cause hypothyroidism (Table 38–5).
the fetal thyroid gland and it is excreted in breast milk.
MANAGEMENT OF HYPOTHYROIDISM
ADRENOCEPTOR-BLOCKING AGENTS
Except for hypothyroidism caused by drugs, which can be
Beta blockers without intrinsic sympathomimetic activity (eg, treated in some cases by simply removing the depressant agent,
metoprolol, propranolol, atenolol) are effective therapeutic the general strategy of replacement therapy is appropriate. The
adjuncts in the management of thyrotoxicosis since many of these most satisfactory preparation is levothyroxine, administered as
symptoms mimic those associated with sympathetic stimulation. either a branded or generic preparation. Multiple trials have
Propranolol has been the β blocker most widely studied and documented that combination levothyroxine plus liothyronine
used in the therapy of thyrotoxicosis. Beta blockers cause clinical is not superior to levothyroxine alone although some patients
improvement of hyperthyroid symptoms but do not typically remain unwell on thyroxine alone. Genetic variations in deio-
alter thyroid hormone levels. Propranolol at doses greater than dinases or hormone transporters may account for some of this
160 mg/d may also reduce T levels approximately 20% by lack of efficacy.
3
inhibiting the peripheral conversion of T to T . There is some variability in the absorption of thyroxine;
3
4
dosage will also vary depending on age and weight. Infants and
■ CLINICAL PHARMACOLOGY OF children require more T per kilogram of body weight than
4
adults. The average dosage for an infant 1–6 months of age is
THYROID & ANTITHYROID DRUGS 10–15 mcg/kg per day, whereas the average dosage for an adult
is about 1.7 mcg/kg per day (0.8 mcg/lb per day ) or 125 mcg/d.
HYPOTHYROIDISM Older adults (>65 years of age) may require less thyroxine
(1.6 mcg/kg per day or 0.7 mcg/lb per day ) for replacement as
Hypothyroidism is a syndrome resulting from deficiency of thy- body mass declines. In patients requiring suppression therapy
roid hormones and is manifested largely by a reversible slowing post-thyroidectomy for thyroid cancer, the average daily dosage of
down of all body functions (Table 38–4). In infants and children, T is 2.2 mcg/kg or 1 mcg/lb. Higher thyroxine requirements have
4
there is striking retardation of growth and development that also been reported in patients with celiac disease and Helicobacter
results in dwarfism and irreversible mental retardation. pylori gastritis; thyroxine doses may be lower following treatment.

TABLE 38–5 Etiology and pathogenesis of hypothyroidism.

Cause Pathogenesis Goiter Degree of Hypothyroidism
Hashimoto’s thyroiditis Autoimmune destruction of thyroid Present early, absent later Mild to severe
Drug-induced 1 Blocked hormone formation 2 Present Mild to moderate
Dyshormonogenesis Impaired synthesis of T 4 due to enzyme Present Mild to severe
deficiency
Radiation, 131 I, X-ray, Destruction or removal of gland Absent Severe
thyroidectomy
Congenital (cretinism) Athyreosis or ectopic thyroid, iodine defi- Absent or present Severe
ciency; TSH receptor-blocking antibodies
Secondary (TSH deficit) Pituitary or hypothalamic disease Absent Mild
1
Iodides, lithium, fluoride, thioamides, aminosalicylic acid, phenylbutazone, amiodarone, perchlorate, ethionamide, thiocyanate, cytokines (interferons, interleukins), bexarotene,
tyrosine kinase inhibitors, etc. See Table 38–3.
2
See Table 38–3 for specific pathogenesis.