Thyroid hormone dysfunction

There is no discrete target tissue for thyroid hormones virtually every cell in the body is affected by thyroid hormones in some way. These hormones are intimately involved in the maintenance of normal function in virtually every cell type, including cellular responsiveness to other hormones, to the availability of metabolic substrates, to growth factors, and so on. Thyroid dysfunction can produce dramatic changes in the metabolism of proteins, carbohydrates, and lipids at the cellular level that can have repercussions for the operation of the cardiovascular, gastrointestinal, musculoskeletal, reproductive, and nervous systems. Some of the clinical manifestations of thyroid dysfunction are presented next in the discussions of hypothyroid and hyperthyroid states. 

Lithium Plus Thyroid Supplementation. Treatment-resistant and rapid-cycling bipolar patients may have an increased frequency of thyroid dysfunction. Further, some patients suffer from subclinical hypothyroidism and improve with the addition of thyroid supplementation. In this context, several case reports involving this population found that high doses of the thyroid hormone levothyroxine sodium (T ) were clinically beneficial (122,123 and 124). Kusalic (1.25) found that 6 of 10 rapid cyclers had hypothyroidism, based on their thyrotropin-releasing hormone stimulation tests. Further, the average number of mood episodes per year decreased by more than 75% (i.e., from 9.7 to 2.2) after thyroxine was added to the treatment regimen. 

The function of the target molecule may be critical or mncritical. Thus, if the target molecule is an enzyme, this could be involved in a crucial metabolic pathway, such as mitochondrial oxidative phosphorylation. In this case, an adverse interaction with the ultimate toxicant is likely to lead to cell dysfunction and possibly death (e.g., as with cyanide or salicylate). Chemicals such as methimazole and resorcinol, which are activated to free radical intermediates by thyroperoxidase, cause destruction of the enzyme. This then disturbs thyroid hormone synthesis and thyroid function with pathological consequences such as thyroid tumors. 

Fever, liver dysfunction, and eosinophilia occurred during liothyronine or levothyroxine treatment of a hypothyroid patient and disappeared after withdrawal of therapy (47). In vitro lymphocyte testing confirmed sensitization for thyroid hormones. 

The clinical manifestations of hyperthyroidism and hypothyroidism are listed in Table 31-2. From a pharmacotherapeutic standpoint, hyperthyroidism is treated with drugs that attenuate the synthesis and effects of thyroid hormones. Hypothyroidism is usually treated by thyroid hormone administration (replacement therapy). The general aspects and more common forms of hyperthyroidism and hypothyroidism are discussed here, along with the drugs used to resolve these primary forms of thyroid dysfunction. 

Hypothyrodism and hyperthyroidism can both be due to a number of causes, one of which is metabolic dysfunction. Hypothyroidism is caused by undersecretion, of thyroid hormones. In one form of childhood hypothyroidism, children born with abnormally small thyroids produce insufficient levels of the thyroid hormones T3 and T4, which are important for metabolically directed bone development. If detected in the first 6 months of life, this disorder can be treated with synthetic thyroid hormones such that its effects can be avoided. The most severe early onset hypothyroidisms are characterized by Cretinism, a type of dwarfism, and mental retardation. Adult hypothyroidism is called myxedema. Myxedema symptoms include slowed speech, yellowed skin, and generally slowed body functions. Myxedema can also be treated with synthetic T4, but if left untreated, can lead to coma. 

Hypothyroidism and hyperthyroidism are the two primary pathological conditions that involve the thyroid glands. Laboratory testing of thyroid hormones is used to diagnose and document the presence of thyroid disease, a condition that often presents with vague and subtle symptoms. Accurate measurement of thyroid hormone concentrations is key to the proper diagnosis of thyroid gland dysfunction. 

Laboratory tests most commonly used to evaluate patients for thyroid gland dysfunction are listed in Table 52-1. Familiarity with normal physiology and with pathophysiology is important if these tests are to be properly used and selected. However, it is important to note that normal serum thyroid hormone concentrations do not exclude thyroid disease, and abnormal thyroid tests do not always indicate thyroid disease. Diffuse or nodular thyroid enlargement, for example, maybe seen in euthyroid patients. ... 

Rigorous evaluation of free thyroid hormone methods is required before new assays are placed into clinical service. Performance data on analytical accuracy should be obtained not only on serum from patients with thyroid dysfunction but also in serum from patients with binding protein abnor-mahties. Effects of drugs that compete for hormone binding sites on serum proteins should also be evaluated. Moreover, adequate assessment requires an examination of the effects of progressive sample dilution. In theory, the free concentration of T4 and T3 should not decrease with dilution until about 20% of the bound ligand is dissociated. In the case of... 

A beneficial effect of thyroid hormone on left ventricular remodeling is also reported. In an experimental model of acute myocardial infarction in rats, a decline in serum T3 was observed associated with left ventricular dysfunction and changes in T3 responsive genes. Treatment with high doses of T3 for three weeks resulted in improved cardiac function with normalization of most of the changes in gene expression.89 Similarly, administration of DITPA (a thyroid analogue) after myocardial infarction in rabbits was associated with improved cardiac function.90... 

Objective weakness is common, with proximal muscles being affected more than distal muscles. Slow relaxation of deep tendon reflexes is common. The most common signs of decreased levels of thyroid hormone include coarse skin and hair, cold or dry skin, periorbital puffiness, and bradycardia. Speech is often slow as well as hoarse. Reversible neurologic syndromes such as carpal tunnel syndrome, polyneuropathy, and cerebellar dysfunction may also occur. 

If the feedback hypothesis of thyroid hormone regulation is correct, TSH levels in the blood of hypothyroid people should be increased. Several reports (Table 1) confirm this, including reports based on studies using radioimmunoassay techniques. TSH levels decline when patients are treated by thyroid hormone replacement (02). This does not apply when the hypothyroidism is secondary to pituitary dysfunction. 

Thyroid dysfunction is common in the elderly. Diagnosis may be overlooked since many of the clinical manifestations of thyroid disease may be misinterpreted as just the normal ageing process (Fig. 2). Unusual presentations arc common e.g. elderly patients with hyperthyroidism are more likely than younger patients to present with the cardiac-related effects of increased thyroid hormone. 

Congenital hypothyroid disorders occur with a frequency of one in every 4000 live births (pp. 144—145). If diagnosed at an early age. replacement thyroid hormone can be given and normal development can occur. Delays in treatment result in cretinism (see p. 144). Elevated T.SH, measured in blood spots, is diagnostic of disorders of the thyroid itself, i.e. primary neonatal hypothyroidism. The TSH screening test does not pick up pituitary dysfunction in the newborn. 

Other possibilities for identification (ID) of patients with thyroid disorders are searching in different records or databases, such as records of diagnoses of discharge from hospitals, prescriptions of thyroid medicaments (antithyroid drugs and levothyroxine), and records of treatments for thyroid disorders including thyroid surgery and radioiodine treatments. Finally, diagnosis of overt thyroid dysfunction is based on a biochemical thyroid function test, and laboratory databases with results of analyses of thyrotrophin (TSH) and thyroid hormones in a population cohort, and records of serum TSH in newborns may be used to identify new patients (Kempers et al., 2006). 

Notes iodine or iodine moduiators may have potentiai uses as moduiators of the endocrine axis, thus treating diseases such as syndrome X, infertiiity, and growth retardation, increased production of thyroid hormone in the presence of high iodine ieveis ieads to increased catechoiamine production, which in turn may produce age-reiated sympathetic bias, a process that appears to drive many of the systemic dysfunctions associated with aging. 

The nature of the toxic effects of bromide on the thyroid gland and mechanisms of its interference with the biosynthesis of thyroid hormones however, has not been explained so far. Most probably, interaction of bromide with iodide uptake by the thyroid gland is the underlying mechanism leading to thyroid dysfunction and, consequently, to the observed alterations in the pituitary—thyroid axis (see below). 

Behavioral disorders, including hyperactivity and impaited concentration, are known to be associated with hyperthyroidism and hypothyroidism, respectively. This evidence validated the hypothesis that ADHD might be similarly related to thyroid disease. Nonetheless, the vast majority of the studies carried out to address this issue failed to demonstrate a definite association between ADHD and thyroid function abnormalities, and therefore the effective role of thyroid hormones in the pathogenesis of the disorder became a candidate for reassessment. It must be pointed out however, that most of these studies evaluated thyroid function in schoolchildren or adults, without taking into account any previous thyroid dysfunction suffered either by them or their mothers during gestation. 

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