ATC Class:H03AA05

VA Class:HS851

AHFS Class:

• Thyroid Agents 68:36.04

Generic Name(s):

• Thyroid

• Thyroid Strong

Thyroid is the cleaned, dried, and powdered thyroid gland, previously deprived of connective tissue and fat, that is obtained from domesticated animals that are used for food by humans.

Thyroid is used for replacement or substitution of diminished or absent thyroid function resulting from primary causes including functional deficiency, primary atrophy, partial or complete absence of the gland, or the effects of surgery, radiation, or antithyroid agents. Thyroid may also be used for replacement or supplemental therapy in patients with secondary (pituitary) or tertiary (hypothalamic) hypothyroidism. Therapy must be maintained continuously to control the symptoms of hypothyroidism. Because of the potential problems associated with the variable hormonal content of thyroid preparations and the recognition that triiodothyronine is derived principally from thyroxine in peripheral tissues, the continued use of thyroid has been questioned, and levothyroxine sodium is now generally the preferred thyroid agent for replacement therapy. Although levothyroxine sodium is also considered the drug of choice for the treatment of congenital hypothyroidism (cretinism), thyroid has been used in the treatment of this condition. For a discussion on the use of thyroid agents in the treatment of congenital hypothyroidism, see Cautions: Pediatric Precautions, in the Thyroid Agents General Statement 68:36.04.

Thyroid may be used to suppress the secretion of thyrotropin (TSH) in the management of simple (nontoxic) goiter and in chronic lymphocytic thyroiditis. Thyroid therapy may cause a reduction in goiter size.

Thyroid may be used with antithyroid agents in the treatment of thyrotoxicosis to prevent goitrogenesis and hypothyroidism. While administration of thyroid agents may occasionally be useful to prevent antithyroid agent-induced hypothyroidism in the management of thyrotoxicosis during pregnancy, combination therapy is generally considered unnecessary since it may increase the requirement for antithyroid agents and therefore the risk of fetal hypothyroidism, which is not amenable to exogenous thyroid agent therapy.

Administration

Thyroid is administered orally, usually as a single daily dose before breakfast.

Dosage

Dosage of thyroid must be carefully adjusted according to individual requirements and response. The age and general physical condition of the patient and the severity and duration of hypothyroid symptoms determine the initial dosage and the rate at which dosage may be increased to the eventual maintenance dosage. Dosage should be initiated at a lower level in geriatric patients; in patients with long-standing disease, other endocrinopathies, or functional or ECG evidence of cardiovascular disease; and in patients with severe hypothyroidism. Adjustment of thyroid replacement therapy should be determined mainly by the patient's clinical response and confirmed by appropriate laboratory tests. Because some commercially available thyroid preparations may be standardized according to their iodine content rather than the concentrations of levothyroxine and triiodothyronine and the ratio of these hormones, patients stabilized on a particular manufacturer's thyroid preparation should generally not be switched to another manufacturer's preparation unless under the direction and supervision of a physician. Because of differences in the levothyroxine:liothyronine ratio in thyroid preparations, replacement doses of thyroid that result in normalization of serum thyroxine concentrations may result in excessive serum triiodothyronine concentrations.

For the management of mild hypothyroidism in adults, the usual initial dosage of thyroid is 60 mg daily; dosage may be increased by increments of 60 mg daily at intervals of 30 days until the desired response is obtained. For the management of severe hypothyroidism in adults, the usual initial dosage is 15 mg daily; dosage may be increased to 30 mg daily after 2 weeks, and 2 weeks later increased to 60 mg daily. It is recommended that the patient's response be carefully assessed, including the use of appropriate laboratory tests, following administration of this dosage for 1 month, and again after an additional month of therapy at this dosage. If necessary, dosage may then be increased to 120 mg daily for 2 months, and the assessment repeated. If the clinical response is inadequate or if the values of the laboratory tests are low, dosage may be increased to 180 mg daily. Subsequent increases in dosage may be made in increments of 30 or 60 mg daily. The usual adult maintenance dosage of thyroid is 60-180 mg daily; however, dosage may vary in individual patients.

In infants and children, it is essential to achieve rapid and complete thyroid replacement because of the critical importance of thyroid hormone in sustaining growth and maturation. Slightly excessive dosages of thyroid agents were previously recommended for replacement therapy in congenital hypothyroidism, since it was thought that slight underdosage was harmful while slightly excessive dosage was not. However, it is currently recommended that excessive dosage be avoided since minimal brain damage has occurred in children with thyrotoxicosis during infancy and excessive dosage may accelerate bone age and cause craniosynostosis. For additional information on the use of thyroid agents in the treatment of congenital hypothyroidism, see Cautions: Pediatric Precautions, in the Thyroid Agents General Statement 68:36.04. In general, despite the smaller body size, the dosage (on a weight basis) required to sustain a full rate of growth, development, and general thriving is higher in children than in adults. Although levothyroxine sodium is considered the drug of choice for the treatment of congenital hypothyroidism (cretinism), thyroid has been used. For the treatment of congenital hypothyroidism or severe hypothyroidism in children, the dosage regimen of thyroid is the same as for adults with severe hypothyroidism (i.e., initiate therapy with 15 mg daily); however, in infants and childen, increases in dosage should be made at 2-week intervals. The eventual maintenance dosage of thyroid may be higher in growing children than in adults.

Thyroid shares the toxic potentials of other thyroid agents, and the usual precautions of thyroid agent therapy should be observed. (See Toxicity and Cautions in the Thyroid Agents General Statement 68:36.04.) Adverse reactions to thyroid result from overdosage and are manifested principally as signs and symptoms of hyperthyroidism.

Pharmacology

The principal pharmacologic effect of exogenous thyroid hormones is to increase the metabolic rate of body tissues. Thyroid hormones are also involved in the regulation of cell growth and differentiation. Although the precise mechanism of action by which thyroid hormones affect metabolism and cellular growth and differentiation is not clearly established, it is known that these physiologic effects are mediated at the cellular level, principally via triiodothyronine; a major portion of triiodothyronine is derived from thyroxine by deiodination in peripheral tissues. Thyroxine is the major component of normal secretions of the thyroid gland and is therefore the principal determinant of normal thyroid function.

Chemistry and Stability

Chemistry

Thyroid is the cleaned, dried, and powdered thyroid gland, previously deprived of connective tissue and fat, that is obtained from domesticated animals that are used for food by humans. Hog thyroid glands are usually used in the manufacture of thyroid. Thyroid is free from iodine in inorganic or any form of combination other than that peculiar to the thyroid gland.

During 1985, the USP standards for thyroid were revised; however, these revisions and possible resultant changes in labeling have not been fully implemented by manufacturers of these preparations. USP previously defined thyroid as containing 0.17-0.23% of iodine in thyroid combination and being free from iodine in inorganic or any form of combination other than that peculiar to the thyroid gland such as monoiodotyrosine, diiodotyrosine, and iodinated amino acids; if the iodine concentration was greater than 0.17-0.23% (e.g., thyroid strong; no longer commercially available in the US), the thyroid contained 85-115% of the iodine concentration labeled by the manufacturer. Although some manufacturers perform bioassays of their thyroid preparations (e.g., Armour^® Thyroid) to assure batch-to-batch reproducibility of metabolic potency of the preparation, USP previously required that thyroid be standardized only by its iodine content and therefore the concentrations of levothyroxine and liothyronine and the ratio of these hormones in commercially available preparations may vary considerably. Even preparations that are standardized for metabolic potency via a bioassay may differ from other bioassayed preparations in the ratio of levothyroxine:liothyronine concentration. In one study of commercially available thyroid preparations, the mean levothyroxine and liothyronine concentrations in each 60 mg of thyroid ranged from 8.8 to 59 mcg and 7.9 to 18 mcg, respectively. Current USP standards specify the measurable amounts of levothyroxine and liothyronine as 38 and 9 mcg, respectively, in each 65 mg of thyroid; however, because of difficulty in measuring the actual hormonal content of thyroid USP, these measurable amounts may be less than the clinical equivalent. Each 60-65 mg of thyroid is approximately clinically equivalent to 100 mcg or less of levothyroxine sodium or to 25 mcg of liothyronine sodium. In guiding dosage adjustment, the clinical equivalent and not the measurable amount should be used.

Thyroid occurs as a yellowish to buff-colored, amorphous powder having a slight, characteristic meat-like odor and a saline taste. Thyroid is insoluble in water and in alcohol.

Stability

The biologic activity of thyroid deteriorates on exposure to moisture and light. Thyroid tablets should be stored in tight containers at a temperature less than 40°C, preferably between 15-30°C.

Additional Information

For further information on chemistry, pharmacology, pharmacokinetics, uses, toxicity, cautions, acute toxicity, drug interactions, laboratory test interferences, and dosage and administration of thyroid, see the Thyroid Agents General Statement 68:36.04.