Thyroid hormone Hypothyroidism

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. 

The thyroid gland facilitates normal growth and maturation by maintaining the level of metabolism in the tissues that is optimal for their normal function. The two major thyroid hormones are T3 (triiodothyronine, the most active form), and T4 (thyroxine). Although the thyroid gland is not essential for life, inadequate secretion of thyroid hormone (hypothyroidism) results in bradycardia, poor resistance to cold, and mental and physical slowing (in children this can cause mental retardation and dwarfism). If, however, an excess of thyroid hormones is... 

Some symptoms of depression can be caused by nutrient or electrolyte imbalances such as in calcium, potassium, sodium, vitamin B,2, or folate, as well as by an excess of thyroid hormone (hyperthyroidism) or not enough thyroid hormone (hypothyroidism). If you think you are depressed, the first step would be to consult with your doctor, who may run a blood panel to test for these kinds of abnormalities. 

Iodine Iodized salt, fish, dairy products Component of thyroid hormones Hypothyroidism, goiter... 

Thyroid-stimulating hormone can be used clinically to test thyroid function but has not found practical apphcation in the treatment of human thyroid insufficiency. Direct replacement therapy with thyroid hormone is easy and effective, owing to a simple molecular stmcture. TSH has been used in the veterinary treatment of hypothyroidism, and preparations of TSH ate produced by Cooper Animal Health, Inc. and Armour Pharmaceuticals. 

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). 

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... 

Thyroid hormones are used as replacement therapy when the patient is hypothyroid. By supplementing the decreased endogenous thyroid production and secretion with exogenous thyroid hormones, an attempt is made to create a euthyroid (normal thyroid) state Levotliyroxine (Synthroid) is the drug of choice for hypothyroidism because it is relatively inexpensive, requires once-a-day dosages, and lias a more uniform potency than do other thyroid hormone replacement drugs. 

These drugp are contraindicated in patients with known hypersensitivity to the drug or to any constituents of the drug, after a recent myocardial infarction (heart attack), or in patients with thyrotoxicosis. When hypothyroidism is a cause or contributing factor to a myocardial infarction or heart disease, the physician may prescribe small doses of thyroid hormone... 

Once a euthyroid state is achieved, tlie primary health care provider may add a thyroid hormone to tlie therapeutic regimen to prevent or treat hypothyroidism, which may develop slowly during long-term antithyroid drug therapy or after administration of 131I. 

Figure 42-11. Model of iodide metabolism in the thyroid follicle. A follicular cell is shown facing the follicular lumen (top) and the extracellular space (at bottom). Iodide enters the thyroid primarily through a transporter (bottom left). Thyroid hormone synthesis occurs in the follicular space through a series of reactions, many of which are peroxidase-mediated. Thyroid hormones, stored in the colloid in the follicular space, are released from thyroglobulin by hydrolysis inside the thyroid cell. (Tgb, thyroglobulin MIT, monoiodotyrosine DIT, diiodotyro-sine Tj, triiodothyronine T4, tetraiodothyronine.) Asterisks indicate steps or processes that are inherited enzyme deficiencies which cause congenital goiter and often result in hypothyroidism.

Lithium is concentrated in the thyroid gland and can impair thyroid hormone synthesis. Although goiter is uncommon, as many as 30% of patients develop at least transiently elevated thyroid-stimulating hormone values. Lithium-induced hypothyroidism is not usually an indication to discontinue the drug. Patients can be supplemented with levothyroxine if continuation of lithium is desired.30... 

O In most patients with thyroid hormone disorders, the measurement of a serum thyroid-stimulating hormone (TSH) level is adequate for the diagnosis of hypothyroidism and hyperthyroidism. The target TSH for most patients being treated for thyroid disorders should be the mean normal value of 1.4 milliunits/L or 1.4 microunits/mL (target range 0.5-2.5 milliunits/L or 0.5-2.5 microunits/mL). 

Despite the availability of a wide array of thyroid hormone products, it is clear that synthetic levothyroxine (LT4) is the treatment of choice for almost all patients with hypothyroidism. LT4 mimics the normal physiology of the thyroid gland, which secretes mostly T4 as a prohormone. As needed, based on metabolic demands, peripheral tissues convert thyroxine (T4)... 

Lithium is associated with hypothyroidism in up to 34% of patients, and hypothyroidism may occur after years of therapy. Lithium appears to inhibit thyroid hormone synthesis and secretion. Patients with underlying autoimmune thyroiditis are more likely to develop lithium-induced hypothyroidism. Patients may require LT4 replacement even if lithium is discontinued. 

Hypothyroidism State caused by inadequate production of thyroid hormone. 

Raff You end up with pretty normal cell numbers in hypothyroid animals, although it takes longer to get there. Thyroid hormone seems to play a coordinating role in development. 

Thyroid hormones are still available, with a prescription, for patients with an underactive thyroid (hypothyroidism). These drugs are never given for weight loss. 

The answers are 450-a, 451-b, 452-b. (Katzung, p 652. Hardman, pp 1397—1406.) Agents that can interfere directly or indirectly with the synthesis of thyroid hormone are called thyroid inhibitors. Perchlorate, an ionic inhibitor, interferes with the ability of the thyroid to concentrate F by acting as a competitive inhibitor. It is used in patients with iodide-induced hypothyroidism, such as can occur with the antiarrhythmic agent amio-darone. 

The answer is e. (Hardman, p 1395J Thyroid hormone is used for HRT in hypothyroidism T4 is the hormone of choice because of its consistent potency and prolonged duration of action. 

Developmentally, thyroid hormones interact with sex hormones such that hypothyroidism prolongs the critical period for testosterone-induced defeminization (see below) [3] in contrast, the hyperthyroid state prematurely terminates the sensitivity to testosterone [3]. Undoubtedly, an important link in these and other effects is synapse formation. Hypothyroidism increases synaptic density, at least transiently [3]. Interesting parallels with synapse formation are reported for learning behavior in rats neonatal hypothyroidism impairs learning ability, whereas hyperthyroidism accelerates learning initially, followed by a decline later in life [3]. 

The adult brain is endowed with nuclear as well as cytosolic and membrane T3 receptors that have been visualized by autoradiography and studied biochemically [30-33]. Both neurons and neuropil are labeled by [ 1251]T3, and the labeling is selective across brain regions. Functionally, one of the most prominent features of neural action of thyroid hormone in adulthood is subsensitivity to norepinephrine as a result of a hypothyroid state [27], These changes may be reflections of loss of dendritic spines in at least some neurons of the adultbrain. Clinically, thyroid hormone deficiency increases the probability of depressive illness, whereas thyroid excess increases the probability of mania (Ch. 52) in susceptible individuals [27],... 

Thyroid disorders encompass a variety of disease states affecting thyroid hormone production or secretion that result in alterations in metabolic stability. Hyperthyroidism and hypothyroidism are the clinical and biochemical syndromes resulting from increased and decreased thyroid hormone production, respectively. 

Amiodarone may induce thyrotoxicosis (2% to 3% of patients) or hypothyroidism. It interferes with type I 5 -deiodinase, leading to reduced conversion of T4 to T3, and iodide release from the drug may contribute to iodine excess. Amiodarone also causes a destructive thyroiditis with loss of thyroglobulin and thyroid hormones. 

In subacute thyroiditis, thyroid function tests typically run a triphasic course in this self-limited disease. Initially, serum T4 levels are elevated due to release of preformed thyroid hormone from disrupted follicles. The 24-hour RAIU during this time is less than 2% because of thyroid inflammation and TSH suppression by the elevated T4 level. As the disease progresses, intrathyroidal hormone stores are depleted, and the patient may become mildly hypothyroid with an appropriately elevated TSH level. During the recovery phase, thyroid hormone stores are replenished and serum TSH elevation gradually returns to normal. 

The treatment goals for hypothyroidism are to normalize thyroid hormone concentrations in tissue, provide symptomatic relief, prevent neurologic deficits in newborns and children, and reverse the biochemical abnormalities of hypothyroidism. 

During treatment of hyperthyroidism, Lp(a), as well as LDL cholesterol and apolipoprotein B, increases, indicating an effect of thyroid hormone on receptor activity and on protein synthesis. The opposite effect is observed in treatment of hypothyroidism (B27, E9, K16). 

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