Thyroid preparations

Thyrotropin is indicated in diagnosis of thyroid cancer remnant with after surgery (see Table 20) in the differential diagnosis of primary and secondary hypothyroidism in protein-bound iodine or uptake determinations for differential diagnosis of subclinical hypothyroidism or low thyroid reserve as therapy for thyroid carcinoma (local or 

FIGURE 97 The production of thyroid hormones is regulated in two ways (1) by thyrotropin, and (2) by a variety of nutritional, hormonal, and illness-related factors. 

Thyrotropin is synthesized by thyrotrophs located in the anterior pituitary gland and consists of two peptide subunits, the alpha subunit (see also Lnteinizing Hormone, Follicle-Stimulating Hormone, and Chorionic Gonadotropin), and the beta subunit, which determines the biologic activities of thyrotrophs. T3 and T4 inhibit both the synthesis and release of thyrotropin. 

The concentration of TSH increases rapidly following the administration of TRH. In hyperthyroidism, the high levels of T3 and T4 inhibit the action of TSH and cause a lack of response to TRH. 

FIGURE 98 The secretion of thyrotropin is regulated by the circulating levels of T4 and by thyrotropin-releasing hormone (TRH). 

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The main role of the human thyroid gland is production of thyroid hormones (iodinated amino acids), essential for adequate growth, development, and energy metaboHsm (1 6). Thyroid underfunction is an occurrence that can be treated successfully with thyroid preparations. In addition, the thyroid secretes calcitonin (also known as thyrocalcitonin), a polypeptide that lowers excessively high calcium blood levels. Thyroid hyperfunction, another important clinical entity, can be corrected by treatment with a variety of substances known as antithyroid dmgs. 

Myxedema and goiter are the main conditions for which thyroid preparations are indicated. The treatment of cretinism is difficult because it is recognized only at or after birth. Even if this disease could be diagnosed m utero, thyroid hormones do not readily cross the placental barrier. In addition, the fetus, as does a premature infant, rapidly deactivates the thyroid hormones. The halogen-free analogue DlMlT [26384-44-7] (3), which is resistant to fetal deiodinases, may prove useful for fetal hypothyroidism (cretinism). 

When administered with cholestyramine or colestipol there is a decreased absorption of the oral thyroid preparations. These drugs should not be administered within 4 of 6 hours of the thyroid hormones. When administered with the oral anticoagulants there is an increased risk of bleeding. It may be advantageous to decrease the dosage of the anticoagulant when a thyroid preparation is prescribed. There is a decreased effectiveness of the digitalis preparation if taken with a thyroid preparation. 

The preferred thyroid preparation for maintenance replacement therapy is which of the following drugs ... 

Levothyroxine (L-thyroxine, T4) is the drug of choice for thyroid hormone replacement and suppressive therapy because it is chemically stable, relatively inexpensive, free of antigenicity, and has uniform potency however, any of the commercially available thyroid preparations can be used. Once a particular product is selected, therapeutic interchange is discouraged. 

BrtVHaWBa Thyroid Preparations Used in the Treatment of Hypothyroidism ... 

Exchange therapy - Nhen switching a patient to liothyronine from thyroid levothyroxine or thyroglobulin, discontinue the other medication, initiate liothyronine at a low dosage, and increase gradually according to the patient s response. Liothyronine has a rapid onset of action and that residual effects of the other thyroid preparation may persist for the first several weeks of therapy. 

Monitoring Treatment of patients with thyroid hormones requires the periodic assessment of thyroid status by means of appropriate laboratory tests. The TSH suppression test can be used to test the effectiveness of any thyroid preparation. 

Other reported side effects include vomiting, salivation, lacrimation, shivering, skin rash, and an interaction with thyroid preparations that may lead to hypertension and tachycardia. Ketamine also may raise intracranial pressure and elevate pulmonary vascular resistance, especially in children with trauma or congenital heart disease. Increases in intraocular pressure also may occur, and vigilance is required if ketamine is used in ocular surgery. 

The idea. In 1961, Judah Folkman, a young surgeon, noted that cancer cells injected into isolated in vitro thyroid preparations grew to small tumors and then stopped growing. However, the same cancer cells grew into massive tumors when implanted into mice. Folkman realized that the in vivo tumors had something the in vitro system did not have—a rich vascular bed and blood supply. 

Formulation effects, such as bioavailability differences, can cause ADRs when patients are switched to generic products. For example, significant adverse effects have occurred with anticonvulsants and thyroid preparations. ... 

Any of the commercially available thyroid preparations accomplish this goal (Table 73-8) however, levothyroxine (1-thyroxine) is considered to be drug of choice. The thyroid preparations are either natural (i.e., desiccated thyroid and thyroglobulin) or synthetic (levothyroxine, fiothyronine, and fiotrix) in origin. The availability of sensitive and specific assays for total and free hormone levels as well as TSH... 

Sodium salicylate tablets Solutions, pharmaceutical Spirits, pharmaceutical Suppositories Syrups, pharmaceutical Tablets, pharmaceutical Thyroid preparations... 

In 1962 Klainer et al. (K4) reported that TSH increased the amount of cyclic AMP in incubated sheep thyroid particulate fractions by 25-35%. Gilman and Rail (Gl) reported that TSH increased the level of cyclic AMP in incubated bovine thyroid slices. Cyclic AMP itself is not a good stimulator of CO2 production from glucose in some thyroid preparations. This may be due to inactivation of cyclic AMP by phosphodiesterase (P6). However, an analog of cyclic AMP, dibutyryl cyclic AMP, will enhance the conversion glucose-l- C to CO2 (PI). Hie dibu-... 

Liothyronine, a thyroid preparation, has a short half-life and hence is used diagnostically in the T3-suppression test. 

In the treatment of hypothyroidism, levothyroxine (Levo-throid and Synthroid Sodium 2 to 25 J.g/kg) is given for replacement therapy in patients with hypothyroidism. Following are other thyroid preparations ... 

Thrombolytic agents a need for improvement Thyroid preparations Trace minerals essential for health Traveler s diarrhea prevention of Tuberculosis treatment of Upper respiratory tract infection treatment of Urinary tract infections treatment of Uveitis management of Vaginal candidiasis treatment of Vasodilators effects on cardiac output (CO)... 

Richheimer, S.L. Jensen, C.B. Determination of liothyronine and levothyroxine in thyroid preparations by liquid chromatography. J.Pharm.ScL, 19S6, 75, 215—217... 

No. Thus, exogenous thyroid preparations may be administered in case of overdose. 

The synthetic preparations used are the sodium salts of the natural isomers of the thyroid hormones. Levothyroxine sodium (L-T, synthroid, levoxyl, levothroid, unithroid, others) is available in tablets in a variety of doses and as a lyophilized powder for injection. L-T has a narrow therapeutic index, and the FDA has mandated demonstration of bioequivalence for brand and generic preparations by the various producers. Liothyronine sodium (L-Tft is available in tablets (cytomel) and in an injectable form (triostat). A mixture of L-T and L-T is marketed as liotrix (thyroiar). Desiccated thyroid preparations, derived from whole animal thyroids and containing both T and T have highly variable biologic activity and are much less desirable. 

General protein iodination however, such intracellular protein iodination does not take place without the addition of huge amounts of H2O2 to the thyroid preparation. Moreover, the concentrations of methima-zole necessary to relieve the XI effect are 10 times higher than those inhibiting protein iodination (Pereira et al., 1990). 

Desiccated thyroid preparations (Thyroid USP) are essentially acetone powders of bovine or porcine thyroid glands compressed into oral tablets. A diluent usually is present, because the preparations (especially those of porcine origin) commonly exceed the 0.17 to 0.23% iodine content required by the U.S. Pharmacopeia (USP). Because the iodine of desiccated thyroid is in the form of iodinated tyrosyl and thyronyl residues of the precipitated thyrogiobuiin, the preparation owes its efficacy to the hormones that eventually are liberated by intestinal proteases. In desiccated preparations, T3 and T4 may be present in a ratio of approximately the same as found in humans. Desiccated preparations are iess expensive than synthetic hormones but have been shown to produce variabie T4/T3 biood ieveis because of inconsistencies both between and within animai sources of the thyroid giand. Most comments regarding desiccated thyroid also apply to partially purified thyrogiobuiin, because the two preparations differ in their total and their relative amounts of T4 and T3. 

Because of its firmer binding to carrier proteins, synthetic crystalline L-T4 sodium salt (levothyroxine sodium, Synthtoid, Euthyrox) has a slower onset of action than crystalline T3 or a desiccated thyroid preparation. Its administration leads to a greater increase in serum T4 but a lesser increase in serum T3 than compared with Thyroid USP (62). The availability of 11 different tablet strengths, ranging from 25 to 300 pg, allows individual dosing. 

Insulin or oral hypoglycemics—Initiating thyroid replacement therapy causes increases in insulin or oral hypoglycemic requirements. The effects seen are poorly understood and depend on a variety of factors, such as endocrine status of the patient and type of thyroid preparations. 

Allergic reactions to thyroid hormones per se have not been reported, although Romanski and Walczynski (1966) suggested that these hormones may influence the susceptibility of children to urticarial lesions. In a group of 103 children treated with thyroid preparations, 43 developed urticaria, but none had bronchial symptoms. The authors noted that this incidence of urticaria was much higher than might be expected in a nontreated population of children and that the complete absence of bronchial symptoms was remarkable. They postulated that excess thyroid hormones might create a favorable environment for the development of urticaria. Further studies would be required to substantiate this hypothesis. 

A calorigenic action of thyroid hormones can also be demonstrated in tissues excised from animals with experimentally induced hyperthyroidism. In 1924, Rohrer demonstrated increased oxygen consumption in liver, kidney, and muscle isolated from mice which had been made hyperthyroid with desiccated thyroid. Most subsequent experiments have been performed with tissue sUces excised from other species, especially the rat. Differences in the metabolic responses of various tissues to thyroid stimulation have been ob.served, depending upon the species studied and the thyroid preparations used these differences will be discussed in the subsequent section. In contrast to the response of isolated tissues to thyroid hor-... 

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