Understand the physiologic effects of thyroid hormone.

  Describe the etiology, pathophysiology, and clinical manifestations of hyperthyroidism.

  Describe the etiology, pathophysiology, and clinical manifestations of hypothyroidism.

  Identify the prototype and describe the action, use, adverse effects, contraindications, and nursing implications of the drugs administered for the treatment of hyperthyroidism.

  Identify the prototype and describe the action, use, adverse effects, contraindications, and nursing implications of the drugs administered for the treatment of hypothyroidism.

  Implement the nursing process in the care of the patient receiving medications for the treatment of hyperthyroidism or hypothyroidism.

KEY TERMS

Cretinism: congenital hypothyroidism that occurs when a child is born with a poorly functioning or absent thyroid gland

Euthyroid: normal thyroid gland functioning

Goiter: visible enlargement of the thyroid gland

Graves’ disease: antibody-mediated autoimmune disease resulting in hyperthyroidism; most common cause of hyperthyroidism

Hyperthyroidism: excessive secretion of thyroid hormone; usually involves an enlarged thyroid gland that has an increased number of cells and an increased rate of secretion

Hypothyroidism: diminished secretion of thyroid hormone; occurs when disease or destruction of thyroid gland tissue causes inadequate production of thyroid hormones

Myxedema: adult hypothyroidism that occurs more often in women than men

Thyroid storm: rare but severe complication characterized by extreme symptoms of hyperthyroidism; most likely to occur in patients with hyperthyroidism that has been inadequately treated, especially when stressful situations occur; also known as thyrotoxic crisis

Thyroiditis: common cause of primary hypothyroidism; an autoimmune disorder characterized by inflammation of the thyroid gland

Thyroxine: known as T₄; one of three hormones produced by the thyroid gland

Introduction

This chapter introduces the pharmacological care of the patient experiencing increased or decreased function of the thyroid gland. The two types of thyroid disorders requiring drug therapy are hyperthyroidism and hypothyroidism.

Overview of the Thyroid Gland

Physiology

Normal serum levels of thyroid hormones and a euthyroid physiologic state (normal thyroid function) require a functioning thyroid gland and feedback mechanism. The thyroid gland produces three hormones: thyroxine, triiodothyronine, and calcitonin. Thyroxine (also called T4) contains four atoms of iodine and triiodothyronine (also called T₃) contains three atoms of iodine. T₃ is more potent than T₄ and has a more rapid onset but a shorter duration of action. Despite these minor differences, the two hormones produce the same physiologic effects and have the same actions and uses. Chapter 42 discusses calcitonin functions in calcium metabolism.

Production of T₃ and T₄ depends on the presence of iodine and tyrosine in the thyroid gland. In a series of chemical reactions, iodine atoms become attached to tyrosine, an amino acid derived from dietary protein, to form the thyroid hormones T₃ and T₄. After they are formed, the hormones are stored within the chemically inactive thyroglobulin molecule. Tyrosine forms the basic structure of thyroglobulin.

Thyroid hormones are released into the circulation when the thyroid gland is stimulated by thyroid-stimulating hormone (thyrotropin; TSH) from the anterior pituitary gland (Fig. 40.1). The hormones become largely bound to plasma proteins, with only the small unbound ones remaining biologically active. The bound thyroid hormones are released to tissue cells very slowly. In tissue cells, the hormones combine with intracellular proteins so they are again stored. They are released slowly within the cell and used over a period of days or weeks. When they are used by the cells, the thyroid hormones release iodine atoms. Most of the iodine is reabsorbed and used to produce new thyroid hormones; the remainder is excreted in the urine.

Thyroid hormones control the rate of cellular metabolism and thus influence the functioning of virtually every cell in the body. The heart, skeletal muscle, liver, and kidneys are especially responsive to the stimulating effects of thyroid hormones. The brain, spleen, and gonads are less responsive. Thyroid hormones are required for normal growth and development and are considered especially critical for brain and skeletal development and maturation. These hormones are thought to act mainly by controlling intracellular protein synthesis.

Thyroid hormones also influence linear growth; brain function, including intelligence and memory; neural development; dentition; and bone development. These hormones are thought to act mainly by controlling intracellular protein synthesis. Some specific physiologic effects include:

Etiology and Pathophysiology

Hyperthyroidism

Hyperthyroidism is characterized by excessive secretion of thyroid hormone and usually involves an enlarged thyroid gland that has an increased number of cells and an increased rate of secretion. It may be associated with Graves’ disease, nodular goiter, thyroiditis, overtreatment with thyroid drugs, functioning thyroid carcinoma, and pituitary adenoma that secretes excessive amounts of TSH.

The hyperplastic thyroid gland may secrete 5 to 15 times the normal amount of thyroid hormone. As a result, body metabolism is greatly increased. Specific physiologic effects vary (see Clinical Manifestations), depending on the amount of circulating thyroid hormone, and they usually increase in incidence and severity with time if hyperthyroidism is not treated.

Subclinical hyperthyroidism is defined as a reduced TSH (less than 0.1 microunit/L) and normal T₃ and T₄ levels. The most common cause is excess thyroid hormone therapy. Subclinical hyperthyroidism is a risk factor for osteoporosis in postmenopausal women who do not take estrogen replacement therapy, because it leads to reduced bone mineral density. It also greatly increases the risk of atrial fibrillation in patients older than 60 years of age.

Hypothyroidism

Hypothyroidism is characterized by diminished secretion of thyroid hormone. Primary hypothyroidism occurs when disease or destruction of thyroid gland tissue causes inadequate production of thyroid hormones. Common causes of primary hypothyroidism include chronic (Hashimoto’s) thyroiditis, an autoimmune disorder characterized by inflammation of the thyroid gland, and treatment of hyperthyroidism with antithyroid drugs, radiation therapy, or surgery. Other causes include previous radiation to the thyroid area of the neck and treatment with amiodarone, lithium, or iodine preparations. Secondary hypothyroidism occurs when there is decreased TSH from the anterior pituitary gland or decreased thyrotropin-releasing hormone (TRH) secreted from the hypothalamus.

Clinical Manifestations

Table 40.1 lists specific effects of hyperthyroidism and hypothyroidism.

Hyperthyroidism

Thyroid storm or thyrotoxic crisis is a rare but severe complication characterized by extreme symptoms of hyperthyroidism, such as severe tachycardia, fever, dehydration, heart failure, and coma. It is most likely to occur in patients with hyperthyroidism that has been inadequately treated, especially when stressful situations occur (e.g., trauma, infection, surgery, emotional upset).

It should be noted that iodine is present in foods (especially seafood and kelp) and in radiographic contrast dyes. Reports of iodine-induced hyperthyroidism have been reported after ingestion of dietary sources of iodine.

Hypothyroidism

Congenital hypothyroidism, or cretinism, occurs when a child is born with a poorly functioning or absent thyroid gland. Cretinism is uncommon in the United States but may occur with a lack of iodine in the mother’s diet. Symptoms are rarely present at birth but develop gradually during infancy and early childhood, and they include poor growth and development, lethargy and inactivity, feeding problems, slow pulse, subnormal temperature, and constipation. If cretinism is untreated until the child is several months old, permanent mental retardation is likely to result.

Adult hypothyroidism, or myxedema, may be subclinical or clinical and occurs much more often in women than in men. Subclinical hypothyroidism, the most common thyroid disorder, involves a mildly elevated serum TSH and normal serum thyroxine levels. It is usually asymptomatic. If the thyroid gland cannot secrete enough hormones despite excessive release of TSH, hypothyroidism occurs, and a goiter (visible enlargement of the thyroid gland) may occur from the overstimulation. Clinical hypothyroidism produces variable signs and symptoms, depending on the amount of circulating thyroid hormone. Initially, manifestations (see Table 40.1) are mild and vague. They usually increase in incidence and severity over time as the thyroid gland gradually atrophies and functioning glandular tissue is replaced by nonfunctioning fibrous connective tissue.

Myxedema coma is severe, life-threatening hypothyroidism characterized by coma, hypothermia, cardiovascular collapse, hypoventilation, and severe metabolic disorders such as hyponatremia, hypoglycemia, and lactic acidosis. Predisposing factors include exposure to cold, infection, trauma, respiratory disease, and administration of central nervous system (CNS) depressants (e.g., anesthetics, analgesics, sedatives).

A person with severe hypothyroidism cannot metabolize and excrete the drugs. It is necessary to assess the patient for signs of adverse drug effects.

NCLEX Success

Drug Therapy

The goal of treatment is to restore the euthyroid state and normal metabolism. In hyperthyroidism, the goals are to reduce thyroid hormone production to relieve symptoms, return serum TSH and thyroid hormone levels to normal, and avoid complete destruction of the thyroid gland. Antithyroid drugs act by decreasing the production or release of thyroid hormones. The thioamide drugs inhibit synthesis thyroid hormones. Iodine preparations inhibit the release of thyroid hormones and cause them to be stored within the thyroid gland. Radioactive iodine emits rays that destroy the thyroid gland tissue.

In hypothyroidism, the goal (of thyroid-replacement therapy) is to administer a dosage in sufficient amounts to compensate for the thyroid deficit—to resolve symptoms and restore serum TSH and thyroid hormone to normal.

Table 40.2 summarizes the drugs administered for thyroid disease.

Antithyroid Drugs

PROPYLTHIOURACIL AND RELATED DRUGS

Propylthiouracil (PTU) is the prototype of the thioamide antithyroid drugs. The U.S. Food and Drug Administration (FDA) approved it for the treatment of hyperthyroidism more than 60 years ago.

Pharmacokinetics

PTU is well absorbed with oral administration, and peak plasma levels occur within 30 minutes. The drug’s plasma half-life is 1 to 2 hours. However, its duration of action depends on the half-life within the thyroid gland rather than the plasma half-life. Because this time is relatively short, PTU must be given every 8 hours. It is metabolized in the liver and excreted in urine.

Action

PTU acts by inhibiting production of thyroid hormones and peripheral conversion of T₄ to the more active T₃. The drug does not interfere with release of thyroid hormones previously produced and stored. Thus, therapeutic effects do not occur for several days or weeks until the stored hormones have been used.

Use

Health care providers may use PTU alone to treat hyperthyroidism, as part of the preoperative preparation for thyroidectomy, before or after radioactive iodine therapy, and in the treatment of thyroid storm. Treatment of hyperthyroidism changes the rate of body metabolism, including the rate of metabolism of many drugs. In the hyperthyroid state, drug metabolism may be very rapid, and higher doses of most drugs may be necessary to achieve therapeutic results. When the patient becomes euthyroid, the rate of drug metabolism decreases. Consequently, it is necessary to evaluate and to reduce doses of all medications (probably); this avoids severe adverse effects. Table 40.3 contains standard route and dosage information for PTU and the other antithyroid drugs.

Use in Children

PTU (or methimazole) is useful. Potential risks for adverse effects are similar to those in adults. Radioactive iodine may cause cancer and chromosome damage in children; therefore, it is essential that this agent be used only for hyperthyroidism that cannot be controlled by other antithyroid drugs or surgery.

Use in Older Adults

PTU (or methimazole) may be useful. However, radioactive iodine is often preferable because it is associated with fewer adverse effects than other antithyroid drugs or surgery. It is necessary that patients be monitored closely for hypothyroidism, which usually develops within 1 year after receiving treatment for hyperthyroidism.

Use in Patients With Hepatic Impairment

The FDA has issued a BLACK BOX WARNING ♦ for PTU stating that severe liver injury resulting in death or acute liver failure may occur within 6 months of treatment. All patients should receive instructions about the signs and symptoms of acute liver failure. Routine liver function testing to assess for liver failure is important.

Adverse Effects

Administration of PTU may have several adverse effects, including the following: