The Natural Thyroid Diet

Thyroid Factor

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Thyroid Factor Summary


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Functional Anatomy Of The Thyroid Gland

The human thyroid gland consists of two lobes attached to either side of the trachea by connective tissue. The two lobes are connected by a band of thyroid tissue or isthmus, which lies just below the cricoid cartilage. A normal thyroid gland in a healthy adult weighs about 20 g. Each lobe of the thyroid receives its arterial blood supply from a superior and an inferior thyroid artery, which arise from the external carotid and subclavian artery, respectively. Blood leaves the lobes of the thyroid by a series of thyroid veins that drain into the external jugular and innominate veins. This circulation provides a rich blood supply to the thyroid gland, giving it a higher rate of blood flow per gram than even that of the kidneys. The thyroid gland receives adrenergic innervation from the cervical ganglia and cholinergic innervation from the vagus nerves. This innervation regulates vasomotor function to increase the delivery of TSH, iodide, and metabolic substrates to the thyroid gland....

Thyroid Hormones Are Formed From the Hydrolysis of Thyroglobulin

When the thyroid gland is stimulated to secrete thyroid hormones, vigorous pinocytosis occurs at the apical membranes of follicular cells. Pseudopods from the apical membrane reach into the lumen of the follicle, engulfing bits of the colloid (see Fig. 33.3). Endocytotic vesicles or colloid droplets formed by this pinocytotic activity migrate toward the basal region of the follicular cell. Lysosomes, which are mainly located in the basal region of resting fol-

Thyroid Hormones Are Metabolized by Peripheral Tissues

Thyroid hormones are both activated and inactivated by deiodination reactions in the peripheral tissues. The enzymes that catalyze the various deiodination reactions are regulated, resulting in different thyroid hormone concentrations in various tissues in different physiological and pathophysiological conditions. Conversion of T4 to T3. As noted earlier, T4 is the major secretory product of the thyroid gland and is the predominant thyroid hormone in the blood. However, about 40 of the T4 secreted by the thyroid gland is converted to T3 by enzymatic removal of the iodine atom at position 5' of the thyronine ring structure (Fig. 33.5). This reaction is catalyzed by a 5'-deiodinase (type 1) located in the liver, kidneys, and thyroid gland. The T3 formed by this deiodination and that secreted by the thyroid react with thyroid hormone receptors in target cells,- therefore, T3 is the physiologically active form of the thyroid hormones. A second 5'-deiodinase (type 2) is

TSH Regulates Thyroid Hormone Synthesis and Secretion

When the concentrations of free T4 and T3 fall in the blood, the anterior pituitary gland is stimulated to secrete thyroid-stimulating hormone (TSH), raising the concentration of TSH in the blood. This action results in increased interactions between TSH and its receptors on thyroid follicular cells. TSH and Thyroid Hormone Formation and Secretion. TSH stimulates most of the processes involved in thyroid hormone synthesis and secretion by follicular cells. The rise in cAMP produced by TSH is believed to cause many of these effects. TSH stimulates the uptake of iodide by follicular cells, usually after a short interval during which io-

Dietary Iodide Is Essential for the Synthesis of Thyroid Hormones

Verely deficient in iodide, as in some parts of the world, T4 and T3 synthesis is limited by the amount of iodide available to the thyroid gland. As a result, the concentrations of T4 and T3 in the blood fall, causing a chronic stimulation of TSH secretion, which, in turn, produces a goiter. Enlargement of the thyroid gland increases its capacity to accumulate iodide from the blood and to synthesize T4 and T3. However, the degree to which the enlarged gland can produce thyroid hormones to compensate for their deficiency in the blood depends on the severity of the deficiency of iodide in the diet. To prevent iodide deficiency and the consequent goiter formation in the human population, iodide is added to the table salt (iodized salt) sold in most developed countries.

Thyroid Hormones Are Essential for Normal Body Growth

The thyroid hormones are important factors regulating the growth of the entire body. For example, an individual who is deficient in thyroid hormones, who does not receive thyroid hormone therapy during childhood, will not grow to a normal adult height. Thyroid Hormones and the Gene for GH. A major way thyroid hormones promote normal body growth is by stimulating the expression of the gene for growth hormone (GH) in the somatotrophs of the anterior pituitary gland. In a thyroid hormone-deficient individual, GH synthesis by the somatotrophs is greatly reduced and consequently GH secretion is impaired therefore, a thyroid hormone-deficient individual will also be GH-deficient. If this condition occurs in a child, it will cause growth retardation, largely a result of the lack of the growth-promoting action of GH (see Chapter 32). Other Effects of Thyroid Hormones on Growth. The thyroid hormones have additional effects on growth. In tissues such as skeletal muscle, the heart, and the...

Thyroid Hormones Stimulate Intermediary Metabolism

In addition to their ability to regulate the rate of basal energy metabolism, thyroid hormones influence the rate at which most of the pathways of intermediary metabolism operate in their target cells. When thyroid hormones are deficient, pathways of carbohydrate, lipid, and protein metabolism are slowed, and their responsiveness to other regulatory factors, such as other hormones, is decreased. However, these same metabolic pathways run at an abnormally high rate when thyroid hormones are present in excess. Thyroid hormones, therefore, can be viewed as amplifiers of cellular metabolic activity. The amplifying effect of thyroid hormones on intermediary metabolism is mediated through the activation of genes encoding enzymes involved in these metabolic pathways. Thyroid-stimulating

Thyroid Hormones Regulate Their Own Secretion

An important action of the thyroid hormones is the ability to regulate their own secretion. As discussed in Chapter 32, T3 exerts an inhibitory effect on TSH secretion by thy-rotrophs in the anterior pituitary gland by decreasing thy-rotroph sensitivity to thyrotropin-releasing hormone (TRH). Consequently, when the circulating concentration of free thyroid hormones is high, thyrotrophs are relatively insensitive to TRH, and the rate of TSH secretion decreases. The resulting fall of TSH levels in the blood reduces the rate of thyroid hormone release from the follicular cells in the thyroid. When the free thyroid hormone level falls in the blood, however, the negative-feedback effect of T3 on thyrotrophs is reduced, and the rate of TSH secretion increases. The rise in TSH in the blood stimulates the thyroid gland to secrete thyroid hormones at a greater rate. This action of T3 on thyrotrophs is thought to be due to changes in gene expression in these cells. The physiological actions of...

Parathyroid Hormone and Calcitonin

Calcitonin Osteoporosis

Whenever the plasma concentration of Ca2+ begins to fall, the parathyroid glands are stimulated to secrete increased amounts of parathyroid hormone (PTH), which acts to raise the blood Ca2+ back to normal levels. As might be predicted from this action of PTH, people who have their parathyroid glands removed (as may occur accidentally during surgical removal of the thyroid) will experience hypocalcemia. This can cause severe muscle tetany, for reasons previously discussed, and serves as a dramatic reminder of the importance of PTH. As mentioned in chapter 11, the thyroid gland secretes a hormone called calcitonin. Though its physiological significance in humans is questionable, its pharmacological action (as a drug) can be useful it inhibits the resorption of bone. People with stress fractures of vertebrae due to osteoporosis (discussed in the next Clinical box), may be helped by injections or nasal sprays of calcitonin.

Thyroid Hormone Synthesis


Thyroid hormone synthesis and secretion. (See text for details.) DIT, diiodotyrosine MIT, monoiodotyrosine. Thyroid hormone synthesis and secretion. (See text for details.) DIT, diiodotyrosine MIT, monoiodotyrosine. Binding of T4 and T3 to Plasma Proteins. Most of the T4 and T3 molecules that enter the bloodstream become bound to plasma proteins. About 70 of the T4 and 80 of the T3 are noncovalently bound to thyroxine-binding globulin (TBG), a 54-kDa glycoprotein that is synthesized and secreted by the liver. Each molecule of TBG has a single binding site for a thyroid hormone molecule. The remaining T4 and T3 in the blood are bound to transthyretin or to albumin. Less than 1 of the T4 and T3 in blood is in the free form, and it is in equilibrium with the large protein-bound fraction. It is this small amount of free thyroid hormone that interacts with target cells. cleared from the blood. This reservoir provides the body with a buffer against drastic changes in circulating thyroid...

Diseases of the Thyroid

Cretinism Disease

Thyroid-stimulating hormone (TSH) from the anterior pituitary stimulates the thyroid to secrete thyroxine however, it also exerts a trophic (growth-stimulating) effect on the thyroid. This trophic effect is evident in people who develop an iodine-deficiency (endemic) goiter, or abnormal growth of Thyroid follicle Thyroid uptake of iodide Thyroid Thyroid Figure 11.23 The production and storage of thyroid hormones. Iodide is actively transported into the follicular cells. In the colloid, it is converted into iodine and attached to tyrosine amino acids within the thyroglobulin protein. MIT (monoiodotyrosine) and DIT (diiodotyrosine) are used to produce T3 and T4 within the colloid. Upon stimulation by TSH, the thyroid hormones, bound to thyroglobulin, are taken into the follicular cells by pinocytosis. Hydrolysis reactions within the follicular cells release the free T4 and T3, which are secreted. Figure 11.24 Endemic goiter is caused by insufficient iodine in the diet. A lack of iodine...

Thyroxine and Triiodothyronine Are Synthesized and Secreted by the Thyroid Follicle

The Thyroid Spherical Follicles

The lobes of the thyroid gland consist of aggregates of many spherical follicles, lined by a single layer of epithelial cells (Fig. 33.1). The apical membranes of the follicular A cross-sectional view through a portion of the human thyroid gland. A cross-sectional view through a portion of the human thyroid gland. The lumen of the follicle contains a thick, gel-like substance called colloid (see Fig. 33.1). The colloid is a solution composed primarily of thyroglobulin, a large protein that is a storage form of the thyroid hormones. The high viscosity of the colloid is due to the high concentration (10 to 25 ) of thyroglobulin. The thyroid follicle produces and secretes two thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Their molecular structures are shown in Figure 33.2. Thy-roxine and triiodothyronine are iodinated derivatives of the amino acid tyrosine. They are formed by the coupling of the phenyl rings of two iodinated tyrosine molecules in an ether linkage. The...

Parathyroid hormone elevates blood calcium

The parathyroid glands are four tiny structures embedded in the posterior surface of the thyroid gland. Their single hormone product, parathyroid hormone (also called PTH or parathormone), is the critical hormone in the regulation of blood calcium levels. Levels of calcium in the blood are sensed by receptors in the plasma membrane of the parathyroid cells. When these receptors are activated, they inhibit the synthesis and release of PTH. A fall in blood calcium levels removes this inhibition and triggers the synthesis and release of PTH.

Mechanism of Thyroid Hormone Action

Mechanisms Hormones Action

As previously discussed, the major hormone secreted by the thyroid gland is thyroxine, or tetraiodothyronine (T4). Like steroid hormones, thyroxine travels in the blood attached to carrier proteins (primarily to thyroxine-binding globulin, or TBG). The thyroid also secretes a small amount of triiodothyronine, or T3. The carrier proteins have a higher affinity for T4 than for T3, however, and, as a result, the amount of unbound (or free ) T3 in the plasma is about ten times greater than the amount of free T4. Approximately 99.96 of the thyroxine in the blood is attached to carrier proteins in the plasma the rest is free. Only the free thyroxine and T3 can enter target cells the protein-bound thyroxine serves as a reservoir of this hormone in the blood (this is why it takes a couple of weeks after surgical removal of the thyroid for the symptoms of hypothyroidism to develop). Once the free thyroxine passes into the target cell cytoplasm, it is en-zymatically converted into T3. As...

TSH Regulates the Function of the Thyroid Gland

Trh Ca2 Dag

The thyroid gland is composed of aggregates of follicles, which are formed from a single layer of cells. The follicular cells produce and secrete thyroxine (T4) and triiodothyronine (T3), thyroid hormones that are iodinated derivatives of the amino acid tyrosine. The thyroid hormones act on many cells by changing the expression of certain genes, changing the capacity of their target cells to produce particular proteins. These changes are thought to bring about the important actions of the thyroid hormones on the differentiation of the CNS, on body growth, and on the pathways of energy and intermediary metabolism. Thyroid-stimulating hormone (TSH) is the physiological regulator of T4 and T3 synthesis and secretion by the thyroid gland. It also promotes nucleic acid and protein synthesis in the cells of the thyroid follicles, maintaining their size and functional integrity. The actions of TSH on thyroid hormone synthesis and secretion, and the physiological effects of the thyroid...

Thyroid Hormones Are Essential for Development of the Central Nervous System

Thyroid hormones first appear in the fetal blood during the second trimester of pregnancy, and levels continue to rise during the remaining months of fetal life. Thyroid hormone receptors increase about 10-fold in the fetal brain at about the time the concentrations of T4 and T3 begin to rise in the blood. These events are critical for normal brain development because thyroid hormones are essential for timing the decline in nerve cell division and the initiation of differentiation and maturation of these cells. If thyroid hormones are deficient during these prenatal and postnatal periods of differentiation and maturation of the brain, mental retardation occurs. The cause is thought to be inadequate development of the neuronal circuitry of the CNS. Thyroid hormone therapy must be given to a thyroid hormone-deficient child during the first few months of postnatal life to prevent mental retardation. Starting thyroid hormone therapy after behavioral deficits have occurred cannot reverse...

Thyroid Stimulating Hormone Secreting Tumors

These are rare tumors, representing approx 2 of all pituitary adenomas (28). Typically, the presentation is with features of hyperthyroidism, often a mass lesion is present, and these tumors may cosecrete GH or prolactin (29). Most TSH-secreting adenomas produce an excess of the a-subunit, and an elevated molar ratio of a-subunit to intact TSH is present in the serum. Treatment of TSH-secreting tumors is directed at both correction of hyperthyroidism and therapy for the tumor. Antithyroid drugs are usually indicated before surgery. The initial management should be surgical, but data regarding the usefulness of operation are scanty. Success, defined as normalization of thyroid function, has been reported to be approx 40 (30) therefore, postsurgical follow-up is essential. If TSH a-subunit levels remain elevated, radiation therapy should be considered. Dopamine agonist drugs and somatostatin analogs have also been used, with particularly positive reports after octreotide use (29).

Thyroid Hormones Regulate the Basal Energy Economy of the Body

Thermogenic Action of the Thyroid Hormones. Thyroid hormones regulate the basal rate at which oxidative phos-phorylation takes place in cells. As a result, they set the basal rate of body heat production and of oxygen consumed by the body. This is called the thermogenic action of thyroid hormones. Thyroid hormone levels in the blood must be within normal limits for basal metabolism to proceed at the rate needed for a balanced energy economy of the body. For example, if thyroid hormones are present in excess, oxidative phosphorylation is accelerated, and body heat production and oxygen consumption are abnormally high. The converse occurs when the blood concentrations of T4 and T3 are lower than normal. The fact that thyroid hormones affect the amount of oxygen consumed by the body has been used clinically to assess the status of thyroid function. Oxygen consumption is measured under resting conditions and compared with the rate expected of a similar individual with normal thyroid...

Production and Action of Thyroid Hormones

The thyroid follicles actively accumulate iodide (I-) from the blood and secrete it into the colloid. Once the iodide has entered the colloid, it is oxidized to iodine and attached to a specific amino acid (tyrosine) within the polypeptide chain of a protein called thyroglobulin. The attachment of one iodine to tyrosine produces monoiodotyrosine (MIT) the attachment of two iodines produces diiodotyrosine (DIT). The transport of thyroid hormones through the blood and their mechanism of action at the cellular level was described earlier in this chapter. Through the activation of genes, thyroid hormones stimulate protein synthesis, promote maturation of the nervous system, and increase the rate of cell respiration in most tissues of the body. Through this action, thyroxine (after it is converted into T3) elevates the basal metabolic rate (BMR, discussed in chapter 19), which is the resting rate of calorie expenditure by the body. Calcitonin, secreted by the parafollicular cells of the...

Hashimotos Thyroiditis

In Hashimoto's thyroiditis, which is most frequently seen in middle-aged women, an individual produces auto-antibodies and sensitized TH1 cells specific for thyroid antigens. The DTH response is characterized by an intense infiltration of the thyroid gland by lymphocytes, macrophages, and plasma cells, which form lymphocytic follicles and germinal centers (Figure 20-1). The ensuing inflammatory response causes a goiter, or visible enlargement of the thyroid gland, a physiological response to hypothyroidism. Antibodies are formed to a number of thyroid proteins, including thyroglobulin and thyroid peroxidase, both of which are involved in the uptake of iodine. Binding of the auto-antibodies to these proteins interferes with iodine uptake and leads to decreased production of thyroid hormones (hypothyroidism).

Thyroid and Parathyroid Glands

Photomicrograph The Thyroid Gland

The thyroid secretes thyroxine (T4) and triiodothyronine (T3), which are needed for proper growth and development and which are primarily responsible for determining the basal metabolic rate (BMR). The parathyroid glands secrete parathyroid hormone, which helps to raise the blood Ca2+ concentration. The thyroid gland is located just below the larynx (fig. 11.21). Its two lobes are positioned on either side of the trachea and are connected anteriorly by a medial mass of thyroid tissue called the isthmus. The thyroid is the largest of the pure endocrine glands, weighing between 20 and 25 grams. On a microscopic level, the thyroid gland consists of numerous spherical hollow sacs called thyroid follicles (fig. 11.22). Figure 11.22 A photomicrograph (250x) of a thyroid gland. Numerous thyroid follicles are visible. Each follicle consists of follicular cells surrounding the fluid known as colloid, which contains thyroglobulin. These follicles are lined with a simple cuboidal epithelium...

Thyroid and Parathyroids

Medical Terminology

The thyroid gland consists of two lobes on either side of the larynx and upper trachea (Fig. 16-2). It secretes a mixture of hormones, mainly thyroxine (T4) and triiodothyronine (T3). Because thyroid hormones contain iodine, their levels can be measured and the activity of the thyroid gland can be studied by following the uptake of iodine. Most thyroid hormone in the blood is bound to protein, mainly thyroid binding globulin (TBG). On the posterior surface of the thyroid are four to six tiny parathyroid glands that affect calcium metabolism (Fig. 16-3). Parathyroid hormone increases the blood level of calcium. It works with the thyroid hormone thyrocalcitonin, which lowers blood calcium, to regulate calcium balance.

Synthesis Secretion And Metabolism Of The Thyroid Hormones

T4 and T3 are not directly synthesized by the thyroid follicle in their final form. Instead, they are formed by the chemical modification of tyrosine residues in the peptide structure of thyroglobulin as it is secreted by the follicular cells into the lumen of the follicle. Therefore, the T4 and T3 formed by this chemical modification are actually part of the amino acid sequence of thyroglobulin. The high concentration of thyroglobulin in the colloid provides a large reservoir of stored thyroid hormones for later processing and secretion by the follicle. The synthesis of T4 and T3 is completed when thyroglobulin is retrieved through pinocytosis of the colloid by the follicular cells. Thyroglobulin is then hydrolyzed by lysosomal enzymes

The Mechanism Of Thyroid Hormone Action

Most cells of the body are targets for the action of thyroid hormones. The sensitivity or responsiveness of a particular cell to thyroid hormones correlates to some degree with the number of receptors for these hormones. The cells of the CNS appear to be an exception. As is discussed later, the thyroid hormones play an important role in CNS development during fetal and neonatal life, and developing nerve cells in the brain are important targets for thyroid hormones. In the adult, however, brain cells show little responsiveness to the metabolic regulatory action of thyroid hormones, although they have numerous receptors for these hormones. The reason for this discrepancy is unclear. Thyroid hormone receptors (TR) are located in the nuclei of target cells bound to thyroid hormone response elements (TRE) in the DNA. TRs are protein molecules of about 50 kDa that are structurally similar to the nuclear receptors for steroid hormones and vitamin D. Thyroid receptors bound to the TRE in the...

Thyroid Hormone Deficiency Causes Nervous and Metabolic Disorders

Thyroid hormone deficiency in humans has a variety of causes. For example, iodide deficiency may result in a reduction in thyroid hormone production. Autoimmune diseases, such as Hashimoto's disease, impair thyroid hormone synthesis (see Clinical Focus Box 33.1). Other causes of thyroid hormone deficiency include heritable diseases that affect certain steps in the biosynthesis of thyroid hormones and hypothalamic or pituitary diseases that interfere with TRH or TSH secretion. Obviously, radioiodine ablation or surgical removal of the thyroid gland also causes thyroid hormone deficiency. Hypothyroidism is the disease state that results from thyroid hormone deficiency. Thyroid hormone deficiency impairs the functioning of most tissues in the body. As described earlier, a deficiency of thyroid hormones at birth that is not treated during the first few months of postnatal life causes irreversible mental retardation. Thyroid hormone deficiency later in life also influences the function of...

Thyroid Manifestations

Thyroid carcinoma occurs in 1-2 of FAP patients 138 . The relative risk of thyroid cancer has been estimated to be 7.6 (95 CL 2.5-17.7) in FAP 139 compared with the general population. FAP-associat-ed thyroid cancer is typically characterized by female predominance, young age at tumor diagnosis (usually 30 years or below), papillary differentiation, and multifocal involvement 140 . Therefore, several authors have advocated periodic thyroid evaluation in young women with FAP 139,140 . An association between FAP and thyroiditis has also been reported 141 .

Thyroid dysfunction causes goiter

A goiter is an enlarged thyroid gland, which causes a pronounced bulge on the front and sides of the neck. Goiter can be associated with either hyperthyroidism (very high levels of thyroxine) or hypothyroidism (very low levels of thy-roxine). The negative feedback loop whereby thyroxine controls TSH release helps explain how two very different conditions can result in the same symptom, but it is also necessary to understand how the thyroid makes, stores, and releases thyroxine. Each thyroid follicle consists of a layer of epithelial cells surrounding a mass of glycoprotein called thyroglobulin. The thyroglobulin, which consists of many residues of tyrosine, is made by the epithelial cells . The tyrosine residues are io-dinated as the thyroglobulin is secreted into the center of the follicle. When thyroxine is needed, the same epithelial cells that made the thyroglobulin take it back and digest it to release thyroxine molecules. If there was enough iodine available when the...

Thyroid function

Where I here is a clinical suspicion of abnormal thyroid function, this should be assessed biochemically. In thyrotoxicosis, the level of thyroid stimulating hormone (TSH) will be suppressed. Total thyroxine and free thyroxine values are usually raised but may be normal in patients with T3 thyrotoxicosis. Primary failure of the thyroid gland is associated with elevated TSH. Circulating thyroid hormones will be reduced. In secondary hypothyroidism, TSH will be low. Other investigations of the thyroid gland may be of value in assessing structure A 69-year-old lady presented with a rapidly enlarging left lobe of the thyroid gland. There was no pain in the neck and she was biochemically euthyroid, The thyroid uffrasound showed a solid nodule within the left lobe (Fig. 2.49) and the radionuclide scan showed that the nodule was non-functioning ('cold'). Fine needle aspiration (FNA) of the nodule showed no malignant cells. A left hemithyroidecfomy was performed. As a general principle, any...

Thyroid Gland

The thyroid gland appears as an epithelial proliferation in the floor of the pharynx between the tuberculum impar and the copula at a point later indicated by the foramen cecum (Figs. 15.17 and 15.18A). Subsequently the thyroid descends in front of the pharyngeal gut as a bilobed diverticulum (Fig. 15.18). During this migration, the thyroid remains connected to the tongue by a narrow canal, the thyroglossal duct. This duct later disappears. With further development, the thyroid gland descends in front of the hyoid bone and the laryngeal cartilages. It reaches its final position in front of the trachea in the seventh week (Fig. 15.18B). By then it has acquired a small median isthmus and two lateral lobes. The thyroid begins to function at approximately the end of the third month, at which time the first follicles containing colloid become visible. Follicular cells produce the colloid that serves as a source of thyroxine and triiodothyronine. Parafollicular, or C, cells derived from the...

Parathyroid Glands

Posterior View Thyroid Gland

The small, flattened parathyroid glands are embedded in the posterior surfaces of the lateral lobes of the thyroid gland, as shown in figure 11.28. There are usually four parathyroid glands a superior and an inferior pair, although the precise number can vary. Each parathyroid gland is a small yellowish-brown body 3 to 8 mm (0.1 to 0.3 in.) long, 2 to 5 mm (0.07 to 0.2 in.) wide, and about 1.5 mm (0.05 in.) deep. 1. Describe the structure of the thyroid gland and list the effects of thyroid hormones. 2. Describe how thyroid hormones are produced and how their secretion is regulated. Thyroid gland Thyroid gland parathyroids are embedded in the tissue of the thyroid gland.


Rubin Farber Pathology

Because thyroid hormone affects the growth and function of many tissues, a deficiency of this hormone in infancy causes physical and mental retardation as well as other symptoms that together constitute congenital hypothyroidism, formerly called cretinism. In the adult, thyroid deficiency causes myxedema, in which there is weight gain, lethargy, rough, dry skin, and facial swelling. Both of these conditions are easily treated with thyroid hormone. Most U.S. states now require testing of newborns for hypothyroidism. If not diagnosed at birth, hypothyroidism will lead to mental retardation within 6 months. The most common form of hyperthyroidism is Graves disease, also called diffuse toxic goiter. This is an autoimmune disorder in which antibodies stimulate an increased production of thyroid hormone. There is weight loss, irritability, hand tremor, and rapid heart rate (tachycardia). A most distinctive sign is a bulging of the eyeballs, termed exophthalmos, caused by swelling of the...


Damage to the parathyroids or their surgical removal, as during thyroid surgery, results in a decrease in blood calcium levels. This causes numbness and tingling in the arms and legs and around the mouth (perioral), as well as tetany (muscle spasms). Treatment consists of supplying calcium.

Considerations Regarding The Infectious Etiology Of Tumors

Although by the mid 1800s a contagious mode of tumor transmission had been repeatedly considered, a miasmal mechanism had not. Perhaps the only well-known author prior to the turn of the century to consider such a possibility was Theodor Billroth. Writing in his mid-century classic General Surgical Pathology and Therapeutics, he suggested that goiter (then considered a form of tumor) may be a chronic endemic-miasmatic entity. He postulated that infection occurs through the blood, and that the enlargement of the thyroid is the local expression of a general infection (73). Ironically, a true miasmal theory of cancer was not to arise until the turn of the century, as noted in a subsequent section.

Immune Dysregulation Polyendocrinopathy Enteropathy XLinked Inheritance Model for Autoaggression

Patients with the rare X-linked syndrome, immune dysregulation, polyendocrinopathy, enteropathy (IPEX) may present early in life with type I diabetes, hyperthyroidism, chronic enteropathy, villous atrophy, dermatitis, autoimmune hemolytic anemia, and antibody- induced neutropenia and thrombocytopenia. Of the reported families with IPEX, most affected boys died before the age of 3 years of malabsorbtion, failure to thrive, infections, or other complications. Characteristic findings at autopsy include lymphocytic infiltrates affecting the lungs, endocrine organs, such as pancreas and thyroid and skin, and increased lymphoid elements in lymph nodes and spleen. Although symptomatic therapy with immunosuppressive drugs provides some beneficial effects, the only curative treatment is hematopoietic stem cell transplantation.

Diagnostic Evaluation

Factors such as diabetes and hypertension, a few simple chemical assays including thyroid function tests, and a surface ECG. A transthoracic echocardiogram is also of paramount importance, as AF can be the sole presenting sign of several underlying cardiac diseases such as cardiomyopathy as discussed here. Only if all of this diagnostic evaluation is negative, should the patient be given the diagnosis of lone AF. If the patient simply has a history of hypertension, for example, this should be considered a sign of structural heart disease. These patients, regardless of age, are at a higher risk for embolic complications, and should be treated differently than patients with true lone AF. Other tests that may be useful in the diagnosis and in the management of this arrhythmia are 24-h ambulatory recordings and 30-d event monitors. These tests may help to determine the frequency and duration of asymptomatic episodes of AF which, if present, may impact on therapeutic management. In...

Abnormalities of sensation

Carpal tunnel syndrome is produced by compression of the median nerve at the wrist. As the nerve passes through the unyielding carpal tunnel, it is at risk for compression by the transverse carpal ligament. In most patients, no specific etiology can be determined, but thickening and proliferation of the peritendinous synovium is seen. This condition is very common in RA, in diabetes, during or after pregnancy, and after wrist fracture. It is also seen in postmenopausal women and in patients with the myxedema of thyroid disease.

Cardiac Growth And Hypertrophy

Thyroid hormone is generally considered the classic hormonal mediator of cardiac hypertrophy. Administration of excess thyroid hormone to experimental animals produces increased heart weight that is associated with transcriptionally mediated alterations in the myosin heavy chains (MHCs), calcium-cycling proteins, and other functional constituents of the cardiomyocyte in small animals and primates.35 Thyroid hormone-induced hypertrophy appears to be an indirect effect of the T3-mediated increased oxygen consumption and resultant augmentation of cardiac work. For example, heterotopic transplantation of a nonworking rat heart into the abdominal aorta of the hyperthyroid animal is unassociated with hypertrophy, despite the presence of the transcriptionally mediated effects of the hormone in the transplanted organ and hypertrophy and typical transcriptional events in the native working heart.36,37 In addition to the indirect effects of thyroid hormone on cardiac growth, other endocrine...

Hypogonadotropic Hypogonadism Associated With Other Pituitary Hormone Deficiencies Prop1 Gene Mutations

Combined pituitary hormone deficiency has been associated with rare abnormalities in gene-encoding transcription factors that are necessary for pituitary development (109). Prop-1 is required for the activation of genes involved in ventral differentiation and proliferation of the four ventral cell types (somatotropes, lac-totropes, thyrotropes, and gonadotropes) (110). Mutations in the gene Prop-1 (Prophet of Pit-1) are the most common cause of both familial and sporadic congenital combined pituitary hormone deficiency. Several different mutations in the Prop-1 gene have been identified and are inherited recessively. The hormonal phenotype includes deficiencies of growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH). Some subjects with Prop-1 mutations also present with LH and FSH deficiencies. However, there is variability in the clinical and hormonal expression of the cases reported thus far. Most affected patients fail to enter puberty and show consistently...

Hormones Controlling Growth Development and Metabolism

The major control of growth is carried out by so-matotropin (STH) from the anterior pituitary. STH does not act directly, however. Cells in the liver respond to STH to produce somatomedin, which stimulates bone growth and muscle production. Prolactin, a protein similar to STH, stimulates breast development in female mammals. In an interesting case of hormone evolution, thyroid hormone stimulates amphibian metamorphosis (tadpole to frog transition) however, in warmblooded vertebrates, this same hormone has evolved to stimulate metabolism for the purpose of heat production in birds and mammals. Several hormones stimulate metabolism for different reasons. Epinephrine (adrenaline), in addition to elevating blood pressure, mobilizes glucose from

Play a key role in the digestion of food and in the uptake and release of fatty acids by tissues

The fourth member of the family is known as endothelial lipase. It was discovered only in 1999 and its function is not yet clear. It is expressed by the endothelial cells in several tissues including liver, lung, kidney and placenta, and some endocrine tissues including thyroid, ovary and testis. It is more active as a phospholipase (with A1-type activity, Section 7.2) than as a TAG lipase. It has been suggested that it plays a role in lipoprotein metabolism and vascular biology.

Electron behavior determines chemical bonding

Blood Plasma Electron

Normal thyroid gland Diseased thyroid gland 2.5 A Radioisotope Used in Medicine The thyroid gland takes up iodine and uses it to make thyroid hormone. A patient suspected of having thyroid disease can be injected with radioactive iodine, which allows the thyroid gland to be visualized by a scanning device. Normal thyroid gland Diseased thyroid gland 2.5 A Radioisotope Used in Medicine The thyroid gland takes up iodine and uses it to make thyroid hormone. A patient suspected of having thyroid disease can be injected with radioactive iodine, which allows the thyroid gland to be visualized by a scanning device.

Function of Brown

Fat Beta Oxidation

The amount of brown fat in the body is greatest at the time of birth. Brown fat is the major site for thermogenesis (heat production) in the newborn, and is especially prominent around the kidneys and adrenal glands. Smaller amounts are also found around the blood vessels of the chest and neck. In response to regulation by thyroid hormone (see chapter 11) and norepinephrine from sympathetic nerves (see chapter 9), brown fat produces a unique

Mechanisms of tolerance induction

An autoimmune response is one directed against antigens expressed by the host's own tissues (auto) which leads to tissue damage. If the antigen is restricted to one particular organ or tissue (e.g. the thyroid), the resulting signs and symptoms are typical of a disease affecting that organ. However, if the antigen is expressed in several tissues or organs, the signs and symptoms will be more generalised.

Microanatomy Of The Lymphatic System

Lymphatic System Collecting Vessels

Cated along the lymphatic system so that one or several afferent lymphatic collecting vessels drain into a node, and the efferent lymphatic collecting vessels leave the nodes and drain toward major (large central) lymphatic trunks which transport the lymphatic fluid into large veins in the neck. The lymphatic collectors drain into local or sometimes remote lymph nodes which are arranged in regional groups. Nodes within a regional group are often interconnected. Lymph from most parts of the body finally drains into the venous circulation via the thoracic duct, at the junction of the left subclavian and jugular veins. In general, lymph passes through a series of lymph nodes before reaching a major collecting duct. The exceptions to this general arrangement are the lymph vessels of the thyroid gland, the esophagus, and the coronary and triangular ligaments of the liver, which drain directly to the thoracic duct without passing through lymph nodes. The flow rate in the large lymphatic...

Promoting an Optimal Response to Therapy

Support (airway, breathing, and circulation) while attempting to correct the underlying cause. Antibiotics, inotropes, hormones (eg, insulin, thyroid), and other drugs may be used to treat the underlying disease. However, the initial pharmacologic intervention is aimed at supporting the circulation with vasopressors.

Regulation of Transcription by Steroid Hormones

The large group of steroid, retinoic acid (retinoid), and thyroid hormones exert at least part of their effects by a mechanism fundamentally different from that of other hormones they act in the nucleus to alter gene expression. We therefore discuss their mode of action in detail in Chapter 28, along with other mechanisms for regulating gene expression. Here we give a brief overview.

Mononuclear Phagocytes In Specific Immunity

Changes in the cell surface expression of the MHC Class II gene product HLA-DR have been recorded in both non-organ and organ-specific autoimmune diseases. For example, epithelial cells in the thyroid of many patients with Graves' disease show high levels of HLA-DR an antigen not usually found on normal thyroid epithelium. In addition, abnormal presentation of foreign antigens (resulting from an unusual association between an antigen such as a drug or microorganism and HLA-DR) has been implicated as a cause of systemic lupus erythematosus. Such an association would appear as an altered self-antigen, thus providing a new epitope that may be recognised, and reacted to, by Th cells. As a consequence, the latter produce lymphokines that stimulate the differentiation and proliferation of activated, self-reactive, B cells. The mechanisms that cause the abnormal expression of DR antigens have not been definitively determined. It is known that interferon induces HLA-DR expression on...

Regulating Other Functions

The thyroid gland, located in the throat region, produces several hormones (examples thyroxine and triiodothyronine) that elevate the body's met abolic rate. The thyroid also secretes a hormone called calcitonin, which works antagonistically with the hormone parathormone produced by the adjacent parathyroid glands. When blood calcium is high (as in a condition called hypercalcemia), the calcitonin gene in thyroid cells begins producing the protein hormone calcitonin, which stimulates bone cells called osteoblasts to build more bone, thereby removing calcium from the bloodstream. Once blood calcium levels are back to normal, calcitonin production halts. In hypercal-cemia, the parathormone gene in parathyroid cells begins producing parathormone (also a protein hormone) that stimulates bone cells called osteo-clasts to break down bone, thereby restoring blood calcium levels but possibly contributing to osteoporosis (bones that are brittle because of calcium deficiency) and other...

Lymphatic Mapping In Other Neoplasms

With the increased experience with sentinel node technology in melanoma and breast cancer, investigators have begun to apply this technique to the staging of other solid neoplasms. Bilchik et al. reported their experience with the universal application of lymphatic mapping at the John Wayne Cancer Institute 26 . The investigators evaluated their experience with lymphatic mapping in Merkel cell tumors, squamous cell carcinoma of the head and neck, thyroid cancer, gastrointestinal malignancies (including small bowel, pancreas, and colon primaries), and vulvar neoplasms. They found the technique to be feasible for solid tumors other than breast and melanoma. Lymphatic mapping may ultimately replace conventional dissection with more accurate staging. Other investigators have confirmed the feasibility of the technique in colon and oral squamous cell carcinoma 27,28 . However, there have been no larger prospective studies in malignancies other than melanoma and breast cancer. At this point,...

Selection Of Surgical Procedure

To us have had scans previously, with the majority having negative scans. The weight rests on the surgeon, not just the nuclear medicine physician, to review the films closely and be confident that the scan is positive. Our definition of a positive sestamibi scan is one that has been performed on a patient with sporadic primary hyperparathyroidism that shows a single focus of increased radioactivity which is distinct and separate from the thyroid. In order to achieve the latter part of this definition, more than just anterior-posterior views must be obtained. We strongly believe that simple oblique views are the only other views that are needed, and in fact are essential to clearly delineate the focus of radioactivity separate from the thyroid. Interestingly, lateral views are almost universally useless.

The Importance Of Timing Between Sestamibi And Operative Exploration

Based on the relative speeds at which the thyroid and parathyroid ''wash out 99mTc-sestamibi and keeping in mind the 6.2 h halflife of 99mTc, the optimal situation to identify parathyroid adenomas with the probe occurs when the thyroid has washed out and the parathyroid remains radioactive. This window of opportunity occurs between 1.5 and 3.0 h. Figure 2 Window of opportunity. Based on the relative speeds at which the thyroid and parathyroid ''wash out 99mTc-sestamibi and keeping in mind the 6.2 h halflife of 99mTc, the optimal situation to identify parathyroid adenomas with the probe occurs when the thyroid has washed out and the parathyroid remains radioactive. This window of opportunity occurs between 1.5 and 3.0 h. This surgical window is a function of the relative speeds at which the thyroid and parathyroid ''wash out'' their nuclear tag. Because the thyroid will lose its initial uptake of 99mTc-sestamibi at a faster rate than a hyperactive...

The Glandular Systems

Several other endocrine glands provide good examples of the importance of this system in the overall functioning of the body. The thyroid gland secretes thyroxin, which regulates metabolism and influences psychological processes such as motivation and mood. The adrenal glands secrete adrenaline and noradrenaline, hormones that operate antagonistically to regulate mood, emotion, blood pressure and sugar level, and the distribution of blood between muscles and internal organs. More generally, these hormones are described as helping the organism prepare for emergencies and cope with stress. The gonads, or sex glands, secrete hormones concerned with sexual development, activity, and receptivity. EXAMPLE 3.15. Knowledge of hormonal control has allowed medical adjustments for physiological problems. Thus, the surgical necessity to remove the thyroid gland can be compensated for by appropriate doses of thyroxin (one of the gland's hormones) so that an appropriate...

Geneexpression profiles in the life cycle

Figure 5.8 Model for endocrine regulation of longevity in (a) C. elegans, (b) D. melanogaster, and (c) Mus musculus, showing how environmental cues are translated into neuroendocrine signals, acting upon an insulin IGF signalling pathway and triggering a variety of hormonal responses, including steroid responses. The ultimate effect is that different priorities are given to gonad versus soma that is, reproduction and growth versus aging. CNS, central nervous system FSH, follicle-stimulating hormone GC, germ-line cells GH, growth factor 20HE, 20-hydroxy-ecdysone INR, insulin receptor IPC, insulin-producing cells IR IGF-1R, insulin receptor IGF-1 receptor LH, luteinizing hormone SG, somatic gonad tissue TSH, thyroid-stimulating hormone T3, 3,3',5-tri-iodothyronine T4, thyroxine. Reprinted with permission from Tatar et al. (2003). Copyright 2003 AAAS.

Prolactinsecreting Pituitary Adenoma Prolactinoma

The initial treatment of prolactinomas involves the use of oral dopamine agonist therapy. Rapid reduction in PRL levels and shrinkage of both micro adenomas and macroadenomas occur in the majority of patients (3). In general, pituitary function is unaffected, but infarction has been described, which may result in loss of adenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), growth hormone (GH) and gonadotropins. Monitoring of basal levels and performance of dynamic testing, as outlined in Appendix 1 (see p. 197 et seq.), is recommended, particularly in macroadenomas.

Contraindications Precautions And Interactions

When xanthine bronchodilators are administered with sympathomimetic drugs (see Chap. 22), additive CNS and cardiovascular effects may occur. If a patient eats large amounts of charcoal-broiled foods while taking the xanthines, a decrease in the therapeutic effect of the xanthines may occur. Certain foods contain xan-thine (eg, coffee, colas, or chocolate) and may increase the risk of cardiac and CNS adverse reactions. Cigarettes, nicotine gum and patches, barbiturates, phenytoin, loop diuretics, isoniazid, and rifampin may decrease the effectiveness of the xanthines. There is an increased risk of xanthine toxicity when the drugs are administered with influenza vaccination, oral contraceptives, glucocorticoids, p-adrenergic blockers, cimeti-dine, macrolides, thyroid hormones, or allopurinol.

Additional observations

The use of interferon-alfa appears to predispose to autoimmune disease and serologic phenomena, particularly thyroid abnormalities. With its use in the treatment of Kaposi's sarcoma and as an antiretroviral agent, we might expect an increase in these features as patients live longer.

Loss of Suppression and an Increase in Autoimmune B Cells

There is evidence in humans and animals that autoimmune thyroid disorders are related to dysregulation of antigen-specific suppressor T cells. The dysregula-tion is the result of a depletion of Ts cells or an inadequate activation of suppression (Volpe, 1994). The dysregulation may allow the production of CD5+ B cells. These autoimmune B cells bind many self antigens and can be autostimu-lated to produce antibodies directed toward self antigens. There is a significant increase in CD5+ B cells in patients with Graves' disease (Afeltra etal., 1995).

Amphibian Metamorphosis

Metamorphosis in amphibians is controlled by a pair of hormones. Prolactin, a protein secreted by the anterior pituitary gland, controls the rate of growth of the tadpole and suppresses metamorphosis. Thyroxine is a modified amino acid made in the thyroid gland of the tadpole and causes metamorphosis to begin. After the tadpole has grown to a certain minimal size, the thyroid gland is stimulated by environmental conditions to produce large quantities of thyroxine, which reverses the suppression exerted by prolactin and begins metamorphosis. The hormones pass through the tadpole's circulation and instruct different tissues to activate and deactivate different sets of genes that cause some tissues to degenerate, others to change, and others to grow.

The Liver Can Modify or Amplify Hormone Action

As discussed before, the liver converts vitamin D3 to 25-hy-droxy vitamin D3, an essential step before conversion to the active hormone 1,25-hydroxy vitamin D3 in the kidneys. The liver is also a major site of conversion of the thyroid hormone thyroxine (T4) to the biologically more potent hormone triiodothyronine (T3). The regulation of the hepatic T4 to T3 conversion occurs at both the uptake step and the conversion step. Due to the liver's relatively large reserve in converting T4 to T3, hypothyroidism is uncommon in patients with liver disease. In advanced chronic liver disease, however, signs of hypothyroidism may be evident.

Bile Acid Sequestrants

The bile acids sequestrants, particularly cholestyra-mine, can decrease the absorption of numerous drugs. For this reason, the bile acid sequestrants should be administered alone and other drugs given at least 1 hour before or 4 hours after administration of the bile acid sequestrants. There is an increased risk of bleeding when the bile acid sequestrants are administered with oral anticoagulants. The dosage of the anticoagulant is usually decreased. The bile acid sequestrants may bind with digoxin, thiazide diuretics, penicillin, propranolol, tetracyclines, folic acid, and the thyroid hormones, resulting in decreased effects of these drugs.

Reduced effects of individualdifference variables

The fact that most research has failed to document a systematic relationship between onset age and different aspects of memory and other cognitive functioning in AD indicates that onset age acts much like many other potentially relevant individual-difference variables in this disease. Several studies demonstrate that variables known to influence cognitive performance in normal aging have little or no influence on performance in AD once severity of dementia is controlled. This includes education (Backman et al., 1994 Burns, Jacoby & Levy, 1991 Katzman et al., 1983), sex (e.g., Buckwalter, Sobel, Dunn, Diz & Henderson, 1993 Teri, Hughes & Larson, 1990), as well as a variety of biological variables, e.g., blood pressure, vitamin B12, folic acid, thyroid stimulating hormone (Backman et al., 1994 Hill, Backman, et al., 1995 Small & Backman, 1998 Small, Viitanen, et al., 1997). A likely reason for the lack of association between these variables and cognitive functioning in AD is that the...

Normal Physiologic Variations

Thus, a person with a protein-bound iodine of 7.8 ug. per 100 ml. would ordinarily be regarded as being within the normal range. It is conceivable, however, that this value could represent a hyper-thyroid state if the true physiologic normal for this person happened to be 4.4 *g. per 100 ml. Similar considerations illustrate the difficulty and, indeed, the undesirability of drawing sharp demarcations between normal and abnormal.

Hormones Are Chemically Diverse

Mammals have several classes of hormones, distinguishable by their chemical structures and their modes of action (Table 23-1). Peptide, amine, and eicosanoid hormones act from outside the target cell via surface receptors. Steroid, vitamin D, retinoid, and thyroid hormones enter the cell and act through nuclear receptors. Nitric oxide also enters the cell, but activates a cytoso-lic enzyme, guanylyl cyclase (see Fig. 12-10).

Evolution Of The Mhc Complex

Allelic polymorphism influences the nature of the bound antigens. Antigens will bind specifically to alleles within a certain locus. For example, lambda repressor (LR) antigen, thyroid peroxidase (TPO), and polyalanine peptide (PAP) all react with DQ molecules. However, LR binds preferentially with DQ8, TPO binds to DQ2, and LR binds strongly with DQ1 (Kwok et al., 1995).

The Leptin System May Have Evolved to Regulate the Starvation Response

Although much of the initial interest in leptin resulted from its possible role in preventing obesity, the leptin system probably evolved to adjust an animal's activity and metabolism during periods of fasting and starvation, not to restrict weight. The reduction in leptin level triggered by nutritional deficiency reverses the thermo-genic processes illustrated in Figure 23-32, allowing fuel conservation. Leptin activates AMP-dependent protein kinase (AMPK), which regulates many aspects of fuel metabolism. Leptin also triggers decreased production of thyroid hormone (slowing basal metabolism), decreased production of sex hormones (preventing reproduction), and increased production of glucocorti-coids (mobilizing the body's fuel-generating resources). By minimizing energy expenditures and maximizing the use of endogenous reserves of energy, these leptin-mediated responses may allow an animal to survive periods of severe nutritional deprivation.

Suggested Reading

The regulation of growth hormone secretion. Endocrinol Metab Clin North Am 1996 3 541-571. Fliers E, Wiersinga WM, Swaab DF. Physiological and pathophysiological aspects of thryotropin-releasing hormone gene expression in the human hypothalamus. Thyroid 1998 8 921-928. Itoi K, Seasholtz AF, Watson SJ. Cellular and extracellular regulatory mechanisms of hypothalamic corticotropin-releasing hormone neurons. Endocr J 1998 45 13-33. Reichlin S. Neuroendocrinology, In Wilson JD, Foster DW, Kronenberg HM, Larsen PR, eds. Williams Textbook of Endocrinology. 9th Ed. Philadelphia WB Saunders, 1998. Zingg HH, Bourque CH, Bichet DG, eds. Vasopressin and oxytocin. Molecular, cellular and clinical advances. Adv Exp Med Biol 1998,449 000-000.

Clinical Focus Box 331

Autoimmune Thyroid Disease Postpartum Thyroiditis Certain diseases affecting the function of the thyroid gland occur when an individual's immune system fails to recognize particular thyroid proteins as self and reacts to the proteins as if they were foreign. This usually triggers both humoral and cellular immune responses. As a result, antibodies to these proteins are generated, which then alter thyroid function. Two common autoimmune diseases with opposite effects on thyroid function are Hashimoto's disease and Graves' disease. In Hashimoto's disease, the thyroid gland is infiltrated by lymphocytes, and elevated levels of antibodies against several components of thyroid tissue (e.g., antithyroid peroxidase and antithyroglobulin antibodies) are found in the serum. The thyroid gland is destroyed, resulting in hypothyroidism. In Graves' disease, stimulatory antibodies to the TSH receptor activate thyroid hormone synthesis, resulting in hyperthyroidism (see text for details). A third,...

AGlucosidase Inhibitors

These drugs are Pregnancy Category B drugs and safety for use during pregnancy has not been established. Digestive enzymes may reduce the effect of miglitol. The effects of acarbose may increase when the agent is administered with the loop or thiazide diuretics, glucocorti-coids, oral contraceptives, calcium channel blockers, phenytoin, thyroid drugs, or the phenothiazines. Miglitol may decrease absorption of ranitidine and propranolol.

Regarding the external carotid artery and its branches

(c) False - the thyroid appears relatively homogeneous in texture and relatively hyperechoic to the superficial sternocleidomastoid muscles. (d) False - 99mTc is not metabolized in the thyroid. However, 123I is both trapped and organified, and functional data can be obtained. 99mTc provides morphological information and will reveal the presence of ectopic thyroid tissue. (e) False - the paired superior thyroid and inferior thyroid arteries are from the external carotid and thyrocervical trunk (subclavian artery) respectively. The thyroidea ima is an occasional branch of the brachiocephalic trunk on the aortic arch, which supplies the inferior portion of the right lower lobe. (b) False - superior thyroid artery is the first branch.

Case Study for Chapter

Thyroiditis A 35-year-old woman is seen in the Endocrine Clinic for evaluation of thyroid disease. The patient complains of weight loss, irritability, and restlessness. Physical examination reveals enlargement of the thyroid gland, weakness in maintaining the leg in an extended position, warm moist skin, and tachycardia. Family history indicates that the patient's mother had hypothyroidism after the birth of the patient's brother and an aunt had Hashimoto's disease. 1. The physical findings, including the presence of goiter, suggest that the patient may be hyperthyroid. However, goiter can also occur in hypothyroidism. Since autoimmune thyroid disease runs in families, the family history suggests that the thyroiditis might be due to an autoimmune response. 2. The laboratory should determine the blood levels of thyroid hormones (T4 and T3) and TSH. Thyroid hormones should be increased. TSH may be increased if it is early in the progression of Hashimoto's disease or decreased if the...


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. Levothyroxine (Synthroid) is the drug of choice for hypothyroidism because it is relatively inexpensive, requires once-a-day dosages, and has a more uniform potency than do other thyroid hormone replacement drugs. Thyroid hormones are also used in the treatment or prevention of various types of euthyroid goiters (enlargement of the thyroid gland), including thyroid nodules, subacute or chronic lymphocytic thyroiditis (Hashimoto's), and multinodular goiter and in the management of thyroid cancer. The hormone may be used with the antithyroid drugs to treat thyrotoxicosis. Thyroid hormones also may be used as a diagnostic measure to differentiate suspected hyperthyroidism from euthyroidism.

Adverse Reactions

These drugs 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 hypothy-roidism is a cause or contributing factor to a myocardial infarction or heart disease, the physician may prescribe small doses of thyroid hormone.

Ongoing Assessment

The full effects of thyroid hormone replacement therapy may not be apparent for several weeks or more, but early effects may be apparent in as little as 48 hours. During the ongoing assessment, the nurse monitors the vital signs daily or as ordered and observes the patient for signs of hyperthyroidism, which is a sign of excessive drug dosage. Signs of a therapeutic response include weight loss, mild diuresis, a sense of well-being, increased appetite, an increased pulse rate, an increase in mental activity, and decreased puffiness of the face, hands, and feet.

Gerontologic Alert

Older adults are more sensitive to thyroid hormone replacement therapy and are more likely to experience adverse reactions when taking the thyroid hormones. In addition, the elderly are at increased risk for adverse cardiovascular reactions when taking thyroid drugs. The initial dosage is smaller for an older adult, and increases, if necessary, are made in smaller increments during a period of about 8 weeks. Periodic thyroid function tests are necessary to monitor drug therapy. Dosage may need to be reduced with age. If the pulse rate is 100 bpm or more, the nurse notifies the primary health care provider before the drug is administered.

Educating the Patient and Family

Thyroid hormones are usually given on an outpatient basis. The nurse emphasizes the importance of taking the drug exactly as directed and not stopping the drug even though symptoms have improved. The nurse provides the following information to the patient and family when thyroid hormone replacement therapy is prescribed The dosage of this drug may require periodic adjustments this is normal. Dosage changes are based on a response to therapy and thyroid function tests. Therapy needs to be evaluated at periodic intervals, which may vary from every 2 weeks during the beginning of therapy to every 6 to 12 months once symptoms are controlled. Periodic thyroid function tests will be needed.

Maternal Physiology Changes Throughout Gestation

The thyroid gland enlarges, but TSH levels are in the normal nonpregnant range. T3 and T4 increase, but thyrox-ine-binding globulin (TBG) also increases in response to the rising levels of estrogen, which are known to stimulate TBG synthesis. Therefore, the pregnant woman stays in an euthyroid state. The parathyroid glands and their hormone, PTH, increase mostly during the third trimester. PTH enhances calcium mobilization from maternal bone stores in response to the fetus's growing demands for calcium. The rate of adrenal secretion of mineralocorticoids and glucocorticoids increases, and plasma free cortisol is higher because of its displacement from transcortin, the cortisol-binding globulin, by progesterone, but hypercorti-solism is not apparent during pregnancy.

Eukaryotic Gene Expression Can Be Regulated by Intercellular and Intracellular Signals

The effects of steroid hormones (and of thyroid and retinoid hormones, which have the same mode of action) provide additional well-studied examples of the modulation of eukaryotic regulatory proteins by direct interaction with molecular signals (see Fig. 12-40). Unlike other types of hormones, steroid hormones do not have to bind to plasma membrane receptors. Instead, they can interact with intracellular receptors that are themselves transcriptional transactivators. Steroid hormones too hydrophobic to dissolve readily in the blood (estrogen, progesterone, and cortisol, for example) travel on specific carrier proteins from their point of release to their target tissues. In the target tissue, the hormone passes through the plasma membrane by simple diffusion and binds to its specific receptor protein in the nucleus. The hormone-receptor complex acts by binding to highly specific DNA sequences called hormone response elements (HREs), thereby altering gene expression. Hormone binding...

Types of Endocrine Disorders

Defects And Hormone

An endocrine gland may be secreting too little hormone because the gland is not able to function normally. This is termed primary hyposecretion. Examples of primary hyposecretion include (1) genetic absence of a steroid-forming enzyme in the adrenal cortex, leading to decreased cortisol secretion, and (2) dietary deficiency of iodine leading to decreased secretion of thyroid hormones. There are many other causes infections, toxic chemicals, and so on all having the common denominator of damaging the endocrine gland. In contrast to primary hyposecretion, a gland may be secreting too little hormone not because the gland is abnormal but because there is not enough of its tropic hormone. This is termed secondary hyposecre-tion. For example, there may be nothing wrong with the thyroid gland, but it may be secreting too little thyroid hormone because the secretion of TSH by the anterior pituitary is abnormally low. Thus, the hypose-cretion by the thyroid gland in this case is secondary to...

Inappropriate Expression of Class Ii Mhc Molecules Can Sensitize Autoreactive T Cells

The pancreatic beta cells of individuals with insulin-dependent diabetes mellitus (IDDM) express high levels of both class I and class II MHC molecules, whereas healthy beta cells express lower levels of class I and do not express class II at all. Similarly, thyroid acinar cells from those with Graves' disease have been shown to express class II MHC molecules on their membranes. This inappropriate expression of class II MHC molecules, which are normally expressed only on antigen-presenting cells, may serve to sensitize TH cells to peptides derived from the beta cells or thyroid cells, allowing activation of B cells or TC cells or sensitization of TH1 cells against self-antigens. Other evidence suggests that certain agents can induce some cells that should not express class II MHC molecules to express them. For example, the T-cell mitogen phytohemag-glutinin (PHA) has been shown to induce thyroid cells to express class II molecules. In vitro studies reveal that IFN-7 also induces...

Chemical Classification of Hormones

Chemical Classes Hormones

These are hormones derived from the amino acids tyrosine and tryptophan. They include the hormones secreted by the adrenal medulla, thyroid, and pineal glands. Thyroid gland and those that are nonpolar, and thus insoluble in water. Since the nonpolar hormones are soluble in lipids, they are often referred to as lipophilic hormones. Unlike the polar hormones, which cannot pass through plasma membranes, lipophilic hormones can gain entry into their target cells. These lipophilic hormones include the steroid hormones and thyroid hormones. The major thyroid hormones are composed of two derivatives of the amino acid tyrosine bonded together (fig. 11.3). When the hormone contains four iodine atoms, it is called tetraiodothyronine (T4), or thyroxine. When it contains three atoms of iodine, it is called triiodothyronine (T3). Although these hormones are not steroids, they are like steroids in that they are relatively small, nonpolar molecules. Steroid and thyroid hormones are active...

Third Pharyngeal Pouch

Superior Parathyroid Gland

The third and fourth pouches are characterized at their distal extremity by a dorsal and a ventral wing (Fig. 15.10). In the fifth week, epithelium of the dorsal wing of the third pouch differentiates into the inferior parathyroid gland, while the ventral wing forms the thymus (Fig. 15.10). Both gland primordia lose their connection with the pharyngeal wall, and the thymus then migrates in a caudal and a medial direction, pulling the inferior parathyroid with it (Fig. 15.11). Although the main portion of the thymus moves rapidly to its final position in the anterior part of the thorax, where it fuses with its counterpart from the opposite side, its tail portion sometimes persists either embedded in the thyroid gland or as isolated thymic nests. Thyroid gland Figure 15.11 Migration of the thymus, parathyroid glands, and ultimobranchial body. The thyroid gland originates in the midline at the level of the foramen cecum and descends to the level of the first tracheal rings. Thyroid gland...

Control Systems Involving the Hypothalamus and Pituitary

Hypothalamus Blood Supply

Anterior Pituitary Hormones As shown in Table 10-1, the anterior pituitary secretes at least eight hormones, but only six have well-established functions. All peptides, these six classical hormones are follicle-stimulating hormone (FSH), luteinizing hormone (LH), growth hormone (GH), thyroid-stimulating hormone (TSH, thyrotropin), prolactin, and adrenocorticotropic hormone (ACTH, corticotropin). Each of the last four is probably secreted by a distinct cell type in the anterior pituitary, whereas FSH and LH, collectively termed gonadotropic hormones (or go-nadotropins) because they stimulate the gonads, are both secreted by the same cells. their target cells (and to maintain the growth and function of these cells) thyroid-stimulating hormone induces secretion of thyroxine and triiodothyronine from the thyroid adrenocorticotropic hormone, meaning hormone that stimulates the adrenal cortex, stimulates the secretion of cortisol by that gland. Thyroid Each hypophysiotropic hormone is named...

Case 67 Flash Pulmonary Edema Due To Upper Airway Obstruction

Negative Pressure Pulmonary Edema

The first CXR shows a normal cardiac shadow associated with bilateral perihilar alveolar infiltrates suggestive of acute pulmonary edema. The development of pulmonary edema with a normal heart size is indicative of an acute event. The rapid clearance of the pulmonary infiltrates here indicates that the process is rapidly corrected by positive pressure. In this patient, an important consideration is negative pressure pulmonary edema due to upper airway obstruction from the thyroid goiter, which is seen on the CT (Fig. 67.3).

Negative Feedback Control of Calcium and Phosphate Balance

Low Plasma Ca2 Feedback

Experiments in the 1960s revealed that high blood calcium in dogs may be lowered by a hormone secreted from the thyroid gland. This hormone thus has an effect opposite to that of parathyroid hormone and 1,25-dihydroxyvitamin D3. The calcium-lowering hormone, called calcitonin, was found to be secreted by the parafollicular cells, or C cells, of the thyroid. These cells are scattered among the follicular cells that secrete thyroxine. Although it is attractive to think that calcium balance is regulated by the effects of antagonistic hormones, the significance of calcitonin in human physiology remains unclear. Patients who have had their thyroid gland surgically removed (as for thyroid cancer) are not hypercalcemic, as one might expect them to be if calcitonin were needed to lower blood calcium levels. The ability of very large pharmacological doses of calci-tonin to inhibit osteoclast activity and bone resorption, however, is clinically useful in the treatment of Paget's disease, in...

Lower Respiratory Passageways and Lungs

Horizontal Cross Section The Lungs

The pharynx conducts air into the trachea, a tube reinforced with C-shaped rings of cartilage to prevent its collapse (you can feel these rings if you press your fingers gently against the front of your throat). Cilia in the lining of the trachea move impurities up toward the throat, where they can be eliminated by swallowing or by expectoration. At the top of the trachea is the larynx (Fig. 11-2). The larynx is shaped by nine cartilages, the most prominent of which is the thyroid cartilage at the front that forms the Adam's apple. The opening between the vocal cords is the glottis. The small leaf-shaped cartilage at the top of the larynx is called the epiglottis. When one swallows, the epiglottis covers the opening of the larynx and helps to prevent food from entering the respiratory tract.

Endocrine Functions of the Placenta

Chorionic Villi And Intervillous Space

The placenta secretes both steroid hormones and protein hormones. The protein hormones include chorionic gonadotropin (hCG) and chorionic somatomammotropin (hCS), both of which have actions similar to those of some anterior pituitary hormones (table 20.7). Chorionic gonadotropin has LH-like effects, as previously described it also has thyroid-stimulating ability, like pituitary TSH. Chorionic somatomammotropin likewise has actions that are similar to two pituitary hormones growth hormone and prolactin. The placental hormones hCG and hCS thus duplicate the actions of four anterior pituitary hormones.

The Hypocretin System In Peripheral Endocrine Tissues

Low levels of hypocretin and hypocretin receptors have been detected in other peripheral tissues. In humans prepro-Hcrt is expressed in the stomach, kidney, colon, colorectal epithelial cells and placenta.72 In the rat, Hcrtr1 mRNA has been detected in the kidney, thyroid, ovary and placenta66 (our unpublished data). In addition, Hcrtr2 mRNA has been found in rat lung, placenta66 (our unpublished data) and pineal gland.84

Lateral Folding Of The Embryo

Cephalocaudal Folding

Hence, the endodermal germ layer initially forms the epithelial lining of the primitive gut and the intraembryonic portions of the allantois and vitelline duct (Fig. 5.18 A). During further development, it gives rise to (a) the epithelial lining of the respiratory tract (b) the parenchyma of the thyroid, parathyroids, liver, and pancreas (see Chapters 13 and 15) (c) the reticular stroma of the tonsils and thymus (d) the epithelial lining of the urinary bladder and urethra (see Chapter 14) and (e) the epithelial lining of the tympanic cavity and auditory tube (see Chapter 16). The endodermal germ layer provides the epithelial lining of the gastrointestinal tract, respiratory tract, and urinary bladder. It also forms the parenchyma of the thyroid, parathyroids, liver, and pancreas. Finally, the

Suprapubic Transvesical Prostatectomy

Prostate Arterial Supply

The potential need for this maneuver should be anticipated preoperatively to permit adequate patient positioning. The adenoma should be separated with care from the bladder neck, especially posteriorly in the area of the ureteral orifices. A thyroid clamp is occasionally useful to grasp the adenoma and facilitate extraction (Fig. 5) (14). The sequence of the enucleation must be varied depending on the configuration of the adenoma and the ease of enucleation. At times, the median or subtrigonal lobe should be worked on first. In a large gland with multiple adenomas, sequential removal is preferable to the traumatic intact removal of the adenomatous growth. Obviously, unusual adherence of the adenoma to the capsule should increase suspicion of carcinoma.

Hormone Transport in the Blood

Peptide and catecholamine hormones are water-soluble. Therefore, with the exception of a few peptides, these hormones are transported simply dissolved in plasma (Table 10-2). In contrast, the steroid hormones and the thyroid hormones circulate in the blood largely bound to plasma proteins. Even though the steroid and thyroid hormones exist in plasma mainly bound to large proteins, small concentrations of these hormones do exist dissolved in the plasma. The dissolved, or free, hormone is in equilibrium with the bound hormone

Endocrine Control Systems

Blood vessel delivers the releasing hormone to the anterior pituitary gland, which in turn secretes a hormone called thyroid-stimulating hormone (TSH), or thyrotropin, into the blood. The TSH travels to the thyroid gland to stimulate the secretion of thyroid hormones, which stimulate metabolism in liver, muscle, and other cells. Heat produced as a by-product of metabolism warms the body. Some hormones are under dual control. Growth hormone (somatotropin) is stimulated by a releasing hormone called somatocrinin and inhibited by somatostatin. There are about seven anterior pituitary hormones that are controlled by similar mechanisms. Adrenocorticotropic hormone (ACTH) is controlled by corticotropin-releasing hormone. Melanocyte-stimulating hormone (MSH) and prolactin are under dual control by both releasing hormones and inhibiting hormones. The gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are under the control of a single releasing hormone called...

Contraindications To Surgery

Macroadenoma Pituitary Mri

Contraindications for surgery are very few, and most are relative rather than absolute. The most important contraindications relate to the general medical condition of the patient, which, in the face of florid CD, acromegaly, or secondary hyperthyroidism, can pose a significant anesthetic risk. In most cases, however, the medical condition of the patient can be stabilized without undue delay. Similarly, profound hypopituitarism can also be a temporary contraindication to surgery, although it should be fully responsive to steroid and thyroid replacement. Active

Preoperative Assessment Pituitary Adenoma Surgery

Gonadal hormones, 83 growth hormone, 83 prolactin, 81, 82 thyroid hormone, 82, 83 vasopressin, 83 magnetic resonance imaging, 81, 84, thyroid hormone therapy, 88, 89 radiation therapy, 85, 86, 91 somatostatin analogs, 86, 87 transsphenoidal surgery, 84, 85 Nurses, patient interactions, attitudes, 293 syndrome of inappropriate antidiuretic hormone secretion, 175, 176 thyroid-stimulating hormone tumors, 188 Pregnancy, preparations, 202, 203 replacement therapy, 89, 90, 192, 193, 203 Thyroid hormone, depression, 82, 83 replacement therapy, 88, 89, 192, 202 Thyroid-stimulating hormone (TSH), adenoma prevalence, 188 nonfunctioning pituitary tumor tumor removal, 136, 137 TRH, see Thyrotropin-releasing hormone TSH, see Thyroid-stimulating hormone

Leptomeningeal Spread Sclc

The incidence of LM from melanoma is about 23 .4 The exact incidence in genitourinary (GU) cancers (renal, bladder and prostate) is not reported but 6 of all LM patients have GU malignancies, and the incidence rate may be increasing.12'32'74'115'134 Gastrointestinal (GI) cancers were once believed to be a major cause of LM but are now rarely encountered.38 LM from gynecological cancers (ovarian, cervical, and fallopian tube adenocarcinoma) and head and neck cancers are also seen.1'7'95'128 Rare solid tumors that metastasize to the leptomeninges include thyroid cancer,10 retinoblastoma,55 neuroblastoma,65 neuroendocrine tumors,36 carcinoid,79 sarcoma,62'134 and squamous cell of the skin or larynx.11,120'140

Pituitary Gland Histology

Alpha Beta Cells Pancreas

Thyroid Gland Follicles Cuboidal epithelium surrounds endocrine follicles of the thyroid gland, the only gland that stores substantial amounts of its own hormone. (X100) Thyroid follicle Thyroid Gland Follicles Cuboidal epithelium surrounds endocrine follicles of the thyroid gland, the only gland that stores substantial amounts of its own hormone. (X100) Thyroid follicle

Feedback Control of the Anterior Pituitary

Anterior pituitary secretion of ACTH, TSH, and the gonadotropins (FSH and LH) is controlled by negative feedback inhibition from the target gland hormones. Secretion of ACTH is inhibited by a rise in corticosteroid secretion, for example, and TSH is inhibited by a rise in the secretion of thyroxine from the thyroid. These negative feedback relationships are easily demonstrated by removal of the target glands. Castration (surgical removal of the gonads), for example, produces a rise in the secretion of FSH and LH. In a similar manner, removal of the adrenals or the thyroid results in an abnormal increase in ACTH or TSH secretion from the anterior pituitary. Thyroid-stimulating hormone (TSH) Thyroid-stimulating hormone (TSH) Thyroid Figure 11.16 The hypothalamus-pituitary-thyroid axis (control system). The secretion of thyroxine from the thyroid is stimulated by thyroid-stimulating hormone (TSH) from the anterior pituitary. The secretion of TSH is stimulated by thyrotropin-releasing...

Hormone Metabolism and Excretion

Hormone Metabolism

In addition, catecholamine and peptide hormones are excreted rapidly or attacked by enzymes in the blood and tissues. These hormones therefore tend to remain in the bloodstream for only brief periods minutes to an hour. In contrast, because protein-bound hormones are less vulnerable to excretion or metabolism by enzymes, removal of the circulating steroid and thyroid hormones generally takes longer, often several hours (with thyroid hormone remaining in the plasma for days). Steroids and thyroid Protein- Cell interior Receptors directly alter Slow (hours to days)

The pituitary is closely associated with the brain

Neurohormonal Regulation

Four peptide and protein hormones released by the anterior pituitary (thyrotropin, adrenocorticotropin, luteinizing hormone, and follicle-stimulating hormone) are tropic hormones, which control the activities of other endocrine glands (see Figure 42.7). Each tropic hormone is produced by a different type of pituitary cell. We will say more about these tropic hormones when we describe their target glands (thyroid, adrenal cortex, testes, and ovaries) later in this chapter and in the next.

Complications Of Frontal Sinus Osteoma

Pyogeni Brast

Sinonasal paragangliomas exhibit no distinctive imaging feature. On both CT and MR sinonasal para-gangliomas appear as markedly enhancing lesions bone destruction can be observed (Myssiorek 2001) (Fig. 8.48). The differential diagnosis is therefore restricted to highly vascularized lesions, such as lobular capillary hemangioma, hemangiopericytoma, schwannoma, and metastases (particularly from kidney, breast, and thyroid cancer).

Common Abnormalities Eyelids

Dysthyreoid Eye Disease

Lid retraction, with widening of the palpable aperture, is obvious when sclcra is visible above and below the iris (Fig. 7.4). It occurs in hyperthyroidism, usually with a lag of Ihe upper lid on looking down (lid-lag) and when the eye is pushed forward (proplosed) by retrobulbar tumours or inflammation. Proptosis is also called exophthalmos. It is common in auto-immune thyroid disease. The periorbital (issues are loose and the lids swell easily. Periorbital oedema occurs commonly in congestive heart failure, glomerulonephritis, hypersensitiviiy reactions and thyroid

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