Hyperthyroidism

Hyperthyroidism is shown to increase tolerance of the myocardium to ischemia and reperfusion injury. The mechanisms of this phenomenon are diverse. Hyperthyroidism 

Primary hyperthyroidism Graves disease Thyroid adenoma/carcinoma Secondary hyperthyroidism 

Hyperthyroidism induced by excessive hypothalamic or pituitary stimulation 

Genetic deficiency of enzymes that synthesize thyroid hormones 

Hypothyroidism induced by peripheral insensitivity to thyroid hormones, inadequate hormone transport, other causes 

Thyroid disorders can be divided into two primary categories conditions that increase thyroid function (hyperthyroidism) and conditions that decrease thyroid function (hypothyroidism).8 There are several different types of hyperthyroidism and hypothyroidism, depending on the apparent etiology, symptoms, and age of onset of each type. The types of hyperthyroidism and hypothyroidism are listed in Table 31-1. Although we cannot review the causes and effects of all the various forms of thyroid dysfunction at this time, this topic is dealt with elsewhere exten-sively.6,8,56 74 

For the treatment of thyroid hyperactivity, there is a range of options  

Apart from surgery, blocking of the biosynthesis of the thyroid hormones is of particular interest. There are several hundred thionamides known, which exert their activity by inhibiting thyroperoxidase, an enzyme required for iodination and coupling of the tyrosine residues. However, only a few of these drugs are approved and in clinical use. Their synthesis employs conventional heterocyclic chemistry. 

A disadvantage for 6-isopropyl-2-thioxo-lf/-pyrimidin-4-one is its short plasma half-life. The corresponding glucuronide is excreted very rapidly via the urine. To overcome the bitter taste of l-methylimidazole-2-thiol, the corresponding ethylcarbamate has been developed as a suitable prodrug. 

Prior to the synthetic preparation of thyroxine, hypothyroidism was treated with extracts of dried thyroid glands from animals. Standardisation was however not easy, and the use of these nutritional supplements caused occasionally serious side-effects. Industrial manufacturing of the pure hormone began around 60 years ago. Its synthetic challenges consist in the formation of the diphenyl ether linkage and the iodination of the aromatic rings. [89] 

The advantage of this synthesis is that it provides both hormones in pure form. The modular construction of the diphenyl ether allows also introducing any substituent at the 3 - and 5 -positions, which is extraordinarily useM for exploring structure-activity relationships. 

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Iodine. Of the 10—20 mg of iodine in the adult body, 70—80 wt % is in the thyroid gland (see Thyroid and antithyroid preparations). The essentiahty of iodine, present in all tissues, depends solely on utilisation by the thyroid gland to produce thyroxine [51-48-9] and related compounds. Well-known consequences of faulty thyroid function are hypothyroidism, hyperthyroidism, and goiter. Dietary iodine is obtained from eating seafoods and kelp and from using iodized salt. 

Catecholamine receptors are well estabUshed to be altered by a variety of homologous and heterologous influences (104). Thus, in hyperthyroidism, there is an increased level of sympathetic activity associated with increased expression of a- and P-adrenoceptors. 

The selective uptake of iodide ion by the thyroid gland is the basis of radioiodine treatment in hyperthyroidism, mainly with although various other radioactive isotopes ate also used (40,41). With a half-life of eight days, the decay of this isotope produces high energy P-particles which cause selective destmction within a 2 mm sphere of their origin. The y-rays also emitted are not absorbed by the thyroid tissue and are employed for external scanning. 

Lithium. In the lithium carbonate treatment of certain psychotic states, a low incidence (3.6%) of hypothyroidism and goiter production have been observed as side effects (6,36) (see Psychopharmacologicalagents). It has been proposed that the mechanism of this action is the inhibition of adenyl cyclase. Lithium salts have not found general acceptance in the treatment of hyperthyroidism (see Lithiumand lithium compounds). 

Hyperthyroidism may be treated in several ways. One of these is interference with the synthesis of the thyroid hormones, possibly by removal of iodine. Thiourea and cyclic thioureas have this effect and of such cyclic compounds, thiouracil (1030 R = H), its 6-alkyl derivatives (1030 R = Me or Pr) and thiobarbital (1031) are effective thyroid drugs. Today only propylthiouracil (1030 R = Pr) is widely used, probably because it has fewer side effects than the others (71MI21302). The thiouracils are made by the Principal Synthesis from a /3-oxo ester (1032 R = H, Me, Pr, etc.) and thiourea (45JA2197) their fine structures are experimentally based (64AF1004). 

Hyperthyroidism, that is, the overproduction of thyroid hormones, is usually treated by surgical removal of the thyroid gland. Before such a procedure is undertaken, the hyperthyroidism is usually first brought under control by treatment with so-called antithyroid agents. 

Non-selective P-adrenergic receptor antagonists (e.g. propranolol) can suppress tachycardia and tremor in patients with hyperthyroidism or tremor caused by... 

Initial daily doses of 10-40 and 100-600 mg are recommended in clinical practice for MMI and PTU, respectively [1, 2]. Several studies have shown that treatment of hyperthyroidism with single daily doses of 10-40 mg of MMI is effective in the induction of euthyroidism in 80-90% of patients within 6 weeks [2]. The aim of the further antithyroid therapy is to maintain euthyroidism with the lowest necessary diug dose. Intrathyroidal diug accumulation is one cause for the efficiency of a single daily dose regimen. Moreover, a once daily dose yields better patients compliance. Single daily doses of PTU have been shown to be less effective in achieving euthyroidism than administration of three divided doses a day. If a once daily... 

Antitrypanosomal Drugs. Table 1 Different treatment strategies depending on the cause of hyperthyroidism... 

Hyperthyroidism (thyrotoxicosis), defined as excessive thyroid activity, causes a state of thyroid hormone excess (thyrotoxicosis) characterized by an increased metabolic rate, increase in body temperature, sweating, tachycardia, tremor, nervousness, increased appetite and loss of weight. Common causes of hyperthyroidism are toxic multinodular goiter, toxic adenoma or diffuse toxic goitre ( Graves disease). Antithyroid diugs (methimazol, carbimazole, propylthiouracil) block thyroid hormone production and are hence suitable for the treatment of hyperthyroidism. 

The drug is contraindicated in die presence of an allergy to die drug, pregnancy (Category C), lactation, and phenylketonuria (oral form only). Linezolid is used cautiously in patients with bone marrow depression, hepatic dysfunction, renal impairment, hypertension, and hyperthyroidism. 

The skeletal muscle relaxants are contraindicated in patients with known hypersensitivity. Baclofen is contraindicated in skeletal muscle spasms caused by rheumatic disorders. Carisoprodol is contraindicated in patients with a known hypersensitivity to meprobamate. Cyclobenzaprine is contraindicated in patients with a recent myocardial infarction, cardiac conduction disorders, and hyperthyroidism, hi addition, cyclobenzaprine is contraindicated within 14 days of the administration of a monoamine oxidase inhibitor. Oral dantrolene is contraindicated in patients with active hepatic disease and muscle spasm caused by rheumatic disorders and during lactation. See Chapter 30 for information on diazepam. 

These drugp are contraindicated in patients with known hypersensitivity to die drugs, asthma, peptic ulcer disease, coronary artery disease, and hyperthyroidism. Bethanecol is contraindicated in those with mechanical obstruction of die gastrointestinal or genitourinary tracts. Fhtients with secondary glaucoma, iritis, corneal abrasion, or any acute inflammatory disease of the eye should not use die ophtiialmic cholinergic preparations. 

The MAOI antidepressant drag s are contraindicated in patients widi known hypersensitivity to die drug s, liver and kidney disease, cerebrovascular disease, hypertension, or congestive heart failure and in die elderly. These drag s are given cautiously to patients witii impaired liver function, history of seizures, parkinsonian symptoms, diabetes, or hyperthyroidism. 

The decongestants are used cautiously in patients with hyperthyroidism, diabetes mellitus, prostatic hypertrophy, ischemic heart disease, and glaucoma Safe use of the... 

The xanHiine derivatives are contraindicated in Hiose wiHi known hypersensitivity, peptic ulcers, seizure disorders (unless well controlled with appropriate anticonvulsant medication), serious uncontrolled arrhytinnias, and hyperthyroidism. 

About 4.5 million Americans have heart failure (HF). It is the most frequent cause of hospitalization for individuals older than 65 years. Some patients, with treatment, may lead nearly normal lives, whereas more than 50% of individuals with severe HF die each year. HF is a complex clinical syndrome that can result from any number of cardiac or metabolic disorders such as ischemic heart disease, hypertension, or hyperthyroidism. Any condition that impairs the ability of the ventricle to pump blood can lead to HF In HF, die heart... 

The symptoms of hypothyroidism and hyperthyroidism are given in Table 51-1. A severe form of hyperthyroidism, called thyrotoxicosis or tiiyroid storm, is characterized by high fever, extreme tachycardia, and altered mental status. Thyroid hormones are used to treat hypothyroidism and antithyroid... 

During initial therapy, the most common adverse reactions seen are signs of overdose and hyperthyroidism (see Table 51-1). Adverse reactions other than symptoms of hyperthyroidism are rare. 

Lugol s Solution, To prepare Thyro-Block, hyperthyroid... 

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