The Natural Thyroid Diet

Thyroid Factor

Thyroid Factor is a program that was created by Dawn Sylvester to help women deal with thyroid issues. Dawn Sylvester is a 57 years old lady that has worked with 1,000's of real women. She has over the time tried to investigate the underlying reason why majority of women lose energy and also struggle with belly fat and fatigue as they age. It is a comprehensive program thatcomprises of Thyro pause, 11 kinds of thyroid saving foods that will work to help you boost fat burning Free T3. The program also teaches you all the hidden causes of thyroid which are making you fat and later a highly reliable Thyroid reboot plan which is an excellent plan you need to tackle your weight. Additionally, there are tips to reduce bulging fat fast and eventually obtain a healthy body. You also get several bonuses all aimed at helping you solve all the problems that comes with being overweight. The three bonuses you get are 21 Day Thyroid weight loss system, 101 Thyroid boosting foods and Thyroid Jumpstart Guide. Read more here...

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Thyroid Disorders Thyrotoxicosis

The term thyrotoxicosis (TS) refers to the biochemical and physiological manifestations of excessive quantities of thyroid hormones. TS may be due to sustained hormone overproduction (hyperthyroidism) or to excessive circulating hormone levels not associated with hyperthyroidism (Table 1). The effects of TS on the major organ systems are the same regardless of the underlying origin, and weight loss is a common feature in the presence of intermediate and severe TS. Thyrotoxicosis factitia Chronic thyroiditis Subacute thyroiditis Ectopic thyroid tissue (struma ovarii, metastatic thyroid cancer) Weight loss is a common manifestation of hyperthyroidism and is present in about 90 of such patients (Table 2). TS-induced weight loss is the result of the effects of thyroid hormones on different organs and on metabolism, particularly on the cardiovascular system, the sympathetic nervous system, the alimentary system, muscle, and energy metabolism 18 . Interestingly, a direct effect of thyroid...

TABLE 524 Thyroid Enlargement and Function

A diffusely enlarged gland includes the isthmus and the lateral lobes, but there are no discretely palpable nodules. Causes include Graves' disease, Hashimoto's thyroiditis, and endemic goiter (related to iodine deficiency, now uncommon in the United States). Sporadic goiter refers to an enlarged gland with no apparent cause. This term refers to an enlarged thyroid gland that contains two or more identifiable nodules. Multiple nodules suggest a metabolic rather than a neoplastic process, but irradiation during childhood, a positive family history, enlarged cervical nodes, or continuing enlargement of one of the nodules raises the suspicion of malignancy. Symptoms of Thyroid Dysfunction Signs of Thyroid Dysfunction Evaluation of the thyroid gland includes a description of the gland and a functional assessment.

Nodular Thyroid Disease

Thyroid nodules, both solitary and multiple, are common and are often found incidentally on physical examination, ultrasonography, or computed tomography. They are more prevalent in women and increase in frequency with age. Although their pathogenesis is not clear, nodules are known to be associated with iodine deficiency, higher gravidity, and the ingestion of goitrogens. Further work-up of identified nodules is indicated, as the incidence of malignancy in solitary nodules is estimated at 5-6 . The incidence of malignancy is higher in children, adults younger than 30 or older than 60 years, and patients with a history of head or neck irradiation. Other historical risk factors include a family history of thyroid cancer, the presence of cervical lym-phadenopathy, and the recent development of hoarseness of the voice, progressive dysphagia, or shortness of breath. Initial assessment should include evaluation of thyroid function. Functional adenomas that present with hyperthyroidism are...

The parathyroid glands Fig 192

Inferior Thyroid Artery

These are usually four in number, a superior and inferior on either side however, the numbers vary from two to six. Ninety per cent are in close relationship to the thyroid, 10 are aberrant, the latter invariably being the inferior glands. Fig. 191 The relationship of the recurrent laryngeal nerve to the thyroid gland and the inferior thyroid artery. (a) The nerve is usually deep to the artery but (b) may be superficial to it or (c) pass through its branches. In these diagrams the lateral lobe of the thyroid is pulled forwards, as it would be in a thyroidectomy. Fig. 191 The relationship of the recurrent laryngeal nerve to the thyroid gland and the inferior thyroid artery. (a) The nerve is usually deep to the artery but (b) may be superficial to it or (c) pass through its branches. In these diagrams the lateral lobe of the thyroid is pulled forwards, as it would be in a thyroidectomy. Inferior thyroid artery Thyroid gland Each gland is about the size of a split pea and is of a...

Thyroid And Gonadal Dysfunction

Subclinical and clinical thyroid disease is common after treatment of HL. In a series of 151 patients, 26 cases of subclinical, 12 cases of manifest clinical hypothyroidism, and 2 cases of hyperthyroidism were documented.14 Thyroid dysfunction was more frequent in patients who underwent mantle or neck radiotherapy. Hypothyroidism was often revealed after the sixth year of follow-up. A high incidence of thy-roiditis was also reported in this group of patients. Annual monitoring of thyroid function should be incorporated in follow-up patients with HL, particularly in those treated with radiation involving neck.

Role Of Endocrine Glands In Thyroid Function

Hypothalamus Pituitary Tsh Thyroid Axis

Thyroid hormones are secreted based on a complex interaction of the hypothalamus, the adenohypophysis, and the thyroid gland. The hypothalamus has thyroid hormone receptors within many of its cells. It provides a tertiary level of control and stimulation of the thyroid gland by secreting thyrotropin-releasing hormone (TRH also known as thyrotropin-releasing factor TRF ), a peptide hormone, in response to lower than normal levels of thyroid hormone. Thyrotropin-releasing hormone may have many functions, but the primary function is to stimulate the adenohypophysis. The adenohypophysis, also known as the anterior pituitary, provides the secondary level of control and stimulation. It produces and secretes thyroid-stimulating hormone (TSH), or thyrotropin, a glycoprotein hormone. The main function of TSH is to stimulate the thyroid gland in hormonal production. Figure 11-9 depicts the hypothalamic response to subnormal levels of circulating free triiodothyronine (T3) and thyroxine (T4),...

Approach To Hyperthyroidism Definitions

Hyperthyroidism Hypermetabolic condition that results from the effect of excessive amounts of thyroid hormones produced by the thyroid gland itself. Because almost all cases of thyrotoxicosis are caused by thyroid overproduction, these terms are often used synonymously. Thyrotoxicosis Usually used as a general term for biochemical and physiologic manifestations of excessive levels of thyroid hormones from any source, for example, exogenous ingestion. Thyroid Storm Thyroid storm is a dangerous condition of decompensated thyrotoxicosis. The patient has tachycardia ( 140 bpm). fever (104-106 F), agitation, delirium, restlessness or psychosis, vomiting, and or diarrhea. It usually results from long-neglected severe hyperthyroidism to which a complicating event (intercurrent illness infection, surgery, trauma, or iodine load) is added. Treatment includes supportive care with fluids, antibiotics if needed, and specific treatment directed at the hyperthyroidism large doses of antithyroid...

Mhc Class Ii Expression On Autoimmune And Malignant Thyroid Cells

Many investigators have used the thyroid gland as a model for research of autoimmune processes. Autoimmune thyroid diseases are the archetype of organ specific autoimmune disorders, and shares with them T-cell dependency as a common characteristic. Inappropriate MHC class II expression has been first observed on thyroid cells derived from patients with Graves' autoimmune thyroid disease 40 , and lead to the hypothesis that such expression would result in antigen presentation of thyroid autoantigens to T cells, thereby starting an autoimmune response 41 . Expression of MHC class II molecules was found to be common also on malignant thyroid cells 42 , and has been recently suggested to represent local antitumor response, which prevents metastatic spread of the malignant cells 43 . We and others have shown that T and inflammatory cell products, such as IFN-Y alone or synergistically with TNF-a, induced class II expression on normal and malignant thyrocyte cell lines derived from patients...

Follicular Thyroid Cancer

This does not tend to occur as frequently as in papillary cancer. Tumours tend to be isolated, encapsulated (90 ) and unilateral. Total or near thyroidectomy is advocated to facilitate 13'I screening for metastatic disease and increase the efficacy of therapeutic 131I. An exception to total or near total thyroidectomy may be made in minimally invasive follicular where total thyroid lobectomy and isthmusectomy are regarded as sufficient surgical treatment. Extrathyroidal invasion in follicular thyroid cancer is present at initial procedure in about 25 of patients (45). As with papillary thyroid cancer local invasion into adjacent structures should be managed where technically feasible by primary en-bloc excision to include the affected organs. The RLN on the affected side may need to be sacrificed if it cannot be separated or shaved from the tumour mass. On rare occasions, follicular thyroid cancer may invade directly into the jugular vein. In this situation it may be necessary to open...

Management Of Metastatic Anaplastic Thyroid Cancer

Neck and frequently involve the overlying skin resulting in ulceration. Thyroidectomy to gain local control is rarely feasible. Lymphatic and haematogenous spread occurs early in anaplastic thyroid cancer. At presentation, cervical lymphadenopathy is present in 85 of patients and distant metastases in 75 . Metastases to lung are the most common ( 80 ), followed by the adrenals (30 ), liver (17 ), bone and brain (15 ) (48,49). Historically the most favoured method of treating the primary cancer and associated regional lymph node metastases has been with external beam radiotherapy. In early series this was coupled with thyroidectomy in an attempt to control the local disease. Both response to treatment with DXT and control of local disease following surgery are extremely disappointing with local recurrence rates between 30 and 80 (50,51).

Parathyroid Carcinoma

At operation macroscopic findings include a firm, greyish white tumour surrounded by a fibrous capsule. Adherence and invasion of adjacent structures such as the thyroid lobe, strap muscles, oesophagus or recurrent laryngeal nerve is common (82). The diagnosis should be made by the surgeon on the basis of these clinical and operative

Levothyroxine for hypothyroidism

Hypothyroidism due to panhypopituitarism requires replacement with adrenocortical as well as with thyroid hormones. Use of levothyroxine alone can cause acute adrenal insufficiency. Small doses of levothyroxine in normal subjects merely depress pituitary thyroid stimulating hormone (TSH) production and consequently reduce the output of thyroid hormone by an equivalent amount. Levothyroxine has been used in the treatment of nontoxic nodular goiter. In such patients it suppresses TSH secretion, and treatment is given on the assumption that nodular (like normal) thyroid tissue growth is dependent on TSH. The long-term value of levothyroxine in these patients remains unproven, and withdrawal of therapy leads to return of the goitre. Levothyroxine should not be used to treat obesity (see Obesity).

Treatment of hypothyroidism

Liothyronine is the most rapidly effective thyroid hormone, a single dose giving maximum effect within 24 h and passing off over 24 48 h. It is not used in routine treatment of hypothyroidism because its rapid onset of effect can induce heart failure. Its main uses are in myxoedema coma and psychosis, both rare conditions. A specialised use is during the withdrawal of levothyroxine replacement (to permit diagnostic radioiodine scanning) in patients with thyroid carcinoma. Subclinical hypothyroidism. This term refers to patients with a normal free T4 but elevated TSH. The indications for considering treatment in these patients are symptoms of hypothyrodism, presence of a goitre, detectable thyroid antibodies or hyper-cholesterolaemia. Adverse effects of thyroid hormone parallel the increase in metabolic rate. The symptoms and signs are those of hyperthyroidism. Symptoms of myocardial ischaemia, atrial fibrillation or heart failure are liable to be provoked by too...

Differentiated Thyroid carcinoma 1631 Epidemiology

In childhood, thyroid carcinoma is more a disease of teenagers, with the approximate median age of diagnosis being 15 years 4 . The incidence of DTC varies from 0.5-1.5 cases million year in children less than 15 years of age to 14.6, 36.1, and 53.2 cases per million per year in the 15-19, 20-24, and 25-29 year age groups, respectively 2, 5 . DTC is more common in females, and the female male incidence is greater than 5 1 in adolescents and young adults 1, 2 . This sex difference is not pronounced in children younger than 10 years. Although a definite increase in thyroid cancer cases has been identified in females age 20-40 years between the years 1975 and 2000, the same has not been found in males or in females less than age 20 years 2 . Incidence of thyroid cancer among males (blue) and females (pink) as a function of age at diagnosis. United States SEER 1975-2000 1 Although several prognostic scoring systems have been described for thyroid carcinoma, a thorough discussion of these...

Blood Supply Superior Inferior Thyroid

Three arteries supply and three veins drain the thyroid gland (Fig. 189) the superior thyroid artery arises from the external carotid and passes to the upper pole the inferior thyroid artery arises from the thyrocervical trunk of the 1st part of the subclavian artery and passes behind the carotid sheath to the back of the gland the thyroidea ima artery is inconstant when present, it arises from the aortic arch or the brachiocephalic artery the superior thyroid vein drains the upper pole to the internal jugular vein the middle thyroid vein drains from the lateral side of the gland to the internal jugular the inferior thyroid veins often several drain the lower pole to the bra-chiocephalic veins. As well as these named branches, numerous small vessels pass to the thyroid from the pharynx and trachea so that even when all the main vessels are tied, the gland still bleeds when cut across during a partial thy-roidectomy.

Answers To Case 19 Galactorrhea due to Hypothyroidism

Next step Check serum prolactin and thyroid-stimulating hormone (TSH) levels. Likely mechanism Hypothyroidism is associated with an elevated thyroid-releasing hormone (TRH) level, which acts as a prolactin-releasing hormone. The hyperprolactinemia then induces the galactorrhea.

Testing For Thyroid Disorders

The American Thyroid Association recommends a testing decision pathway for thyroid disorders in adult patients. Total thyroxine hormone levels should not be assessed in healthy or asymptomatic patients. In other words, total thyroxine level should not be used as a screening test to investigate for thyroid disease. If signs and symptoms of thyroid disorder are clear, the first laboratory test that should be ordered is TSH.37 If the results are abnormal compared to age- and gender-adjusted reference ranges, thyroid disease is likely present. For example, if TSH is less than 0.1 U mL in the adult, primary hyperthyroidism is most likely present.5 Free T4 (or free T4 index) can be analyzed if TSH results do not correlate with symptoms. However, due to the severe consequences of untreated thyroid disease in the neonate, particularly hypothyroidism, asymptomatic neonates are typically screened for T4 (total thyroxine) and followed up with TSH testing if abnormal results are obtained. Thyroid...

Thyroid Associated Ophthalmopathy

Orbital extracellular matrix exhibits a significant increase in tissue fractions of hyaluronan and chondroitin sulfate in patients with thyroid-associated ophthal-mopathy (TAO) (151). Immunoglobulin G of patients with TAO markedly stimulates hyaluronan secretion from retrobulbar fibroblasts (152) and such patients exhibit significantly greater antibody values against hyaluronan (153). Lymphocytes on retrobulbar fibroblasts show a tendency for TAO patients' lymphocytes to enhance the synthesis of hyaluronan (154). Hyaluronan expression is also increased at the extraocular muscle level in patients with TAO (155).


Several different conditions can cause hypothyroidism. The most common noniatrogenic condition causing hypothyroidism in the United States is Hashimoto thyroiditis, an autoimmune thyroiditis. Iatrogenic causes include post-Graves disease thyroid ablation and surgical removal of the thyroid gland. Another cause is secondary hypothyroidism related to hypothalamic or pituitary dysfunction. These conditions are primarily found in patients who have received intracranial irradiation or surgical removal of a pituitary adenoma. In primary hypothyroidism, the TSH level is elevated, indicating insufficient thyroid hormone production to meet metabolic demands. Free thyroid levels are low. In contrast, patients with secondary hypothyroidism have low or undetectable TSH levels. Once the diagnosis of primary hypothyroidism is made, further imaging or serologic testing is unnecessary if the thyroid gland is normal on physical examination. In cases of secondary hypothyroidism, however, further...

Thyroid Dysfunction

Thyroid dysfunction is a common occurrence in patients receiving IFN, with an incidence of 3-5 in patients treated for HCV (31-33), but higher incidences associated with therapy of malignancy. Both the dosage and duration of therapy with IFN are associated with an increased incidence of thyroid problems (34). Patients with antithyroglobulin or antithyroid peroxidase antibodies, prior to the start of IFN therapy, are at the highest risk of developing thyroid disease (35,36). These antibodies are present in 16 of U.S. women and 1.5-3 of U.S. males, and are also the characteristic autoantibodies seen in Hashimoto's thyroiditis (35). IFN causes an autoimmune destructive thyroiditis, which causes proteolysis and release of thyroid hormones, resulting in a clinically mild thyrotoxic state. As the gland is depleted of thyroid hormones, the persistent inflammation prevents further uptake of iodine and synthesis of thyroxine, resulting in hypothyroidism. Therefore, the commonest clinical...

The thyroid gland

Thyroid Vein

The thyroid is made up of (Fig. 189) 2 the lateral lobes each extending from the side of the thyroid cartilage downwards to the 6th tracheal ring 3 an inconstant pyramidal lobe projecting upwards from the isthmus, usually on the left side, which represents a remnant of the embryological descent of the thyroid. The gland is enclosed in the pretracheal fascia, covered by the strap muscles and overlapped by the sternocleidomastoids. The anterior jugular veins course over the isthmus. When the thyroid enlarges, the strap muscles stretch and adhere to the gland so that, at operation, they often appear to be thin layers of fascia. On the deep aspect of the thyroid lie the larynx and trachea, with the pharynx and oesophagus behind and the carotid sheath on either side. Two nerves lie in close relationship to the gland in the groove between the trachea and oesophagus lies the recurrent laryngeal nerve and deep to the Fig. 189 The thyroid and its blood vessels. Superior thyroid artery and vein...

Thyroid Cancer

Thyroid cancer is a relatively rare malignancy accounting for less than 1 of all malignancies. Only 0.5 of cancer deaths are due to thyroid cancer with one death per million in the United Kingdom and surprisingly six deaths per million in the United States (4-6). Approximately 90-95 of thyroid cancers are differentiated thyroid cancers (DTC) originating from thyroid follicular cells. A classification of thyroid cancer is shown in Table 1. This is the most common thyroid cancer, responsible for approximately 80 of cases. Patients tend to be in the 30-40 year age group with a female to male bias of 2 1 (7). Papillary cancer is the predominant thyroid malignancy in children and patients who have previously been exposed to ionising radiation of the head or neck (8). Macroscopically tumours are hard and grey white in colour and lack a tumour capsule. Multifocal disease is common (80-85 ). Tumours may erode through the thyroid capsule to invade adjacent structures such as oesophagus,...

Thyroid Hormone

BMD at the distal and 8-mm sites on the radius was measured with SPA (Nuclear Data ND 1100A) in 78 postmenopausal women who had been on thyroid hormone replacement for a minimum of 5 years (165). The average age of the women was 64 years. Hypothyroidism in these women was initially caused by idiopathic hypothyroidism or primary autoimmune hypothyroidism. Forty-four of these women had persistently suppressed thyroid stimulating hormone (TSH) values, whereas 34 did not. One hundred two women served as controls. The women with nonsuppressed TSH values had z-scores at the 8-mm and distal radial sites of -0.07 and -0.03, whereas the women with suppressed TSH had z-scores of -0.25 and -0.20, respectively. The differences between the three groups were not statistically significant. The authors estimated that a suppressed TSH was associated with at most a 5 decrease in BMD. Affinito et al. (166) also measured BMD at the distal radius in a study of 54 postmenopausal women with primary...

Thyroid hormones

L-thyroxine (T4 or tetraiodo-L-thyronine) and lio-thyronine (T3 or triiodo-L-thyronine) are the natural hormones of the thyroid gland. T4 is a less active precursor of T3, which is the major mediator of physiological effect. In this chapter T4 for therapeutic use is referred to as levothyroxine (the rINN, see p. 83) rather than levothyroxine (the former usage). For convenience, the term 'thyroid hormone' is used to comprise T4 plus T3. Both forms are available for oral use as therapy.

Thyroid storm

Thyroid crisis, or storm, is a life-threatening emergency due to liberation of large amounts of hormone into the circulation. Surgical storm is rare with modern methods of preparing hyperthyroid patients for surgery. Medical thyroid storm may occur in patients who are untreated or incompletely treated. It may be precipitated by infection, trauma, surgical emerg encies or operations, radiation thyroiditis, toxaemia of pregnancy or parturition. Treatment is urgently required to save life. Propranolol should be given immediately (i.v. slowly, 1 mg min to max of 10 mg, in severe cases, preceded by atropine 1-2 mg i.v. to prevent excessive bradycardia). Large doses of an antithyroid agent, preferably propylthiouracil 300-400 mg 4-hourly down a nasogastric tube or per rectum, are required. After this is initiated, iodide is used to inhibit further hormone release from the gland (600 mg-1.0 g iodide orally in the first 24 h) (see Potassium iodide). Large doses of adrenocorticoid, e.g....

Thyroid gland

The thyroid gland lies against the pharynx at the base of the neck. It consists of two lateral lobes connected by an isthmus. The gland produces thyroxine, a hormone that regulates the rate of metabolism in the body. It also produces a second hormone, calcitonin, which regulates the level of calcium in the blood. Thyroxine production depends on the availability of iodine. A deficiency of iodine causes thyroid gland enlargement, a condition called goiter. An undersecretion of thyroxine results in a condition known as cretinism (dwarfism with abnormal body proportions and possible mental retardation). In adults, an undersecretion results in myxedema (physical and mental sluggishness). Thyroxine oversecretion results in a high metabolic rate and Graves' disease.


Thyroid disorders occur more frequently in women than in men, occurring in up to 10 of all women. Tests for levels of TSH, free thyroxine, and free triiodothy-ronine are need by clinicians to make the diagnosis. Generally, high TSH values suggest primary hypothyroidism, while suppressed levels indicate primary hyper-thyroidism. Signs and symptoms of hyperthyroidism include goiter (enlarged thyroid gland), optic changes including exophthalmos, proximal muscle weakness, tachycardia, atrial fibrillation, hyperthermia, and weight loss or inability to gain weight. Among women, the most common etiology of thyroid disease is thyroid autoimmunity, with Graves' disease more common than Hashimoto's thyroiditis. Other causes of primary hyperthyroidism include thyroid adenoma, toxic multinodular goiter, and thyroid carcinoma. Table 11-8 summarizes the typical laboratory findings in thyroid diseases. Thyroxine or free thyroxine levels are not always necessary for diagnosis if hyper-thyroid...

Biological Basis Of Geriatric Oncology

Kirsch, Matthias Black, Peter McL. (ed.) Angiogenesis in Brain Tumors. 2003. ISBN 1-4020-7704-1. Keller, E.T., Chung, L.W.K. (eds) The Biology of Skeletal Metastases. 2004. ISBN 1-4020-7749-1. Kumar, Rakesh (ed.) Molecular Targeting and Signal Transduction. 2004. ISBN 1-4020-7822-6. Verweij, J., Pinedo, H.M. (eds) Targeting Treatment of Soft Tissue Sarcomas. 2004. ISBN 1-4020-7808-0. Finn, W.G., Peterson, L.C. (eds.) Hematopathology in Oncology. 2004. ISBN 1-4020-7919-2. Farid, N., (ed) Molecular Basis of Thyroid Cancer. 2004. ISBN 1-4020-8106-5. Balducci, L., Extermann, M. (eds.) Biological Basis of Geriatric Oncology. 2004. ISBN Leong, Stanley P.L., Kitagawa, Y., Kitajima, M. (eds.) Selective Sentinel Lymphadenectomy for Human Solid Cancer 2005. ISBN 0-387-23603-1

The common carotid artery

On the right, the brachiocephalic (innominate) artery arises from the aortic arch and then bifurcates into the subclavian artery and the common carotid artery (CCA). On the left side, both the common carotid artery and the left subclavian artery originate directly from the aortic arch. The CCA is easily assessable on the neck where it runs in parallel with the jugular vein (Figure 1.1). At approximately the level of the 4th vertebrae, which is at the level of the upper border of the thyroid cartilage, the common carotid arteries bifurcate into the internal and external carotid arteries (Figure 1.2). The carotid bulb represents dilatation at the distal common carotid artery extending into the proximal internal carotid artery. The carotid bulb bears unique flow patterns yielding a boundary separation zone and its wall has numerous baro- and chemoreceptors. The size and location of the carotid bulb are variable.

Ryanodine And Related Receptors In Calcium Mobilisation

A reference to the multifunctional receptor called megalin would not be out of place here. Megalin is a member of the low-density lipoprotein receptor family, which function as endocytic receptors. The megalin glycoprotein of rat kidney is approximately 330 kDa in size. The 550-kDa human homologue of megalin is found in the luminal surface of cells of the renal proximal tubule and epididymis. It is expressed in mammary epithelia, thyroid follicular cells, and the ciliary body of the eye (Lundgren et al. 1997). It is also found in parathyroid and trophoblast cells. Mackrill et al. (1999) raised antibodies against RyR from rabbit muscle. These antibodies recognised not only skeletal RyR but also another high-molecular-weight protein (k-HMW) in kidney microsomes thought to be a rabbit homologue of megalin. Antibodies raised against k-HMW were unable to recognise RyR. Furthermore, this protein showed partial sequence homology to RyR.

Efect Of Aging On The Susceptibility To Carcinogenesis In Vivo

Animal experiments seem to confirm that there are age related differences in sensitivity to carcinogen in some tissues. Thus, with age, susceptibility to carcinogens in murine mammary gland, small intestine and colon, thyroid, ovarian follicular epithelium decreases, in subcutaneous tissue, cervix uteri and vagina increases and in others (lung, hemopoietic tissues) it remains stable (Table 1). For details see references 1,5-6). Age-related differences in cancer susceptibility have been observed after exposure to the same carcinogens in experimental systems. For example, in female rats exposed to N-nitrosomethylurea (NMU) in doses 10, 20 or 50 mg kg at the age of 3 month developed mammary carcinomas, tumors of the kidney, ovaries and colon. In contrast to young animals, the rats exposed to the same doses of the carcinogen at the age of 15 months showed a higher frequency of tumors of the corpus and cervix uteri, and a lower frequency of mammary and intestinal adenocarcinomas and tumors...

Functional Parameters

Structural integrity of cells Fragility of erythrocytes Fragility of capillary Strength of skin tension Experimental recovery of wounds Collagen accumulation in installed sponge Lipoprotein peroxidation Defence mechanisms Leucocyte chemotaxis Leukocyte phagocyte activity Leukocyte bactericide capacity Leucocyte metabolism Opsonic activity of serum Leucocyte production of interferon Blastogenesis of T lymphocytes Delayed skin hypersensitivity Rebuck's skin window technique Transport Intestinal absorption Iron absorption Cobalt absorption Transport plasma-tissue Erythrocyte capture of Zn Erythrocyte capture of Se Dosage answer to retinol Plasmatic answer of chromium to glucose load Urinary answer of chromium to glucose load Thyroid capture of radioiodine Haemostasis Prothrombin time

HER2 gene amplification in breast cancer

It is noteworthy that many genes are included in the HER2 amplicon. These include v-erbA thyroid hormone receptor-a (THRA1), the retinoic acid receptor a (RARA), the MLNs 50, 51, 62 steroidogenic acute regulatory protein related protein (MLN 64 CAB-1), peroxisome proliferator-activated receptor binding protein (PBP PARBP TRAP-220), growth factor receptor-bound protein 7 (GRP7), homebox genes 2 and 7 (HOXB2 and HOXB7), junction plakoglobin (JUP), dopamine and cAMP-regulated phos-phoprotein (32 kDa in size) (DARPP-32), thyroid hormone receptor associated protein complex component 100 (TRAP-100), titin cap protein (TCP), CDC2 related protein kinase-7 (CrkRS), Aiolos, gastrin, 17P-hydroxy-steriod dehydrogenase type 1 (HSDl7B1), and topoisomerase IIa (topoIIa, encoded by TOP2A), all of which have been shown to be coamplified in the portion of the HER2-amplified tumors (5). High-resolution mapping of tumors with HER2 amplification with these gene-specific probes may provide additional...

Angiotensinogen Agt Gene

Experimental evidence suggests that the liver represents the primary source of plasma AGT. AGT is probably not stored in hepatocytes, but is constitutively secreted into the systemic circulation (15). Production of AGT by the liver is regulated by several hormonal factors including estrogen, glucocorticoids, thyroid hormone, insulin, and ANG II (15,16). In accordance with the local-tissue RAS concept, AGT is synthesized in many tissues other than the liver, for example the brain, kidney, heart, adrenal gland, vasculature, and adipose tissue. The AGT produced by these tissues may be converted locally or released into the bloodstream to contribute to the circulating pool of AGT. The production of AGT in these tissues may also be regulated locally, independently of the circulating system. The presence of other components of the RAS, such as renin and ACE necessary for the biosynthesis of active angiotensin peptides in most of the tissues that produce AGT, provides further evidence for...

Radiopague Indicators Of Physiological Spaces And Processes

Several layers, at different stages of mineralization, can be distinguished (10) . In some tissues there are normally fairly high concentrations of heavy elements (e.g., iodine in the thyroid, iron in hemoglobin and in the hemochromatotic liver) at concentrations which just reach a level at which a pathological increase, or

Calcium Binding And The Molecular Configuration Of Calciumbinding Proteins

Fritz et al. (1998) pointed out that Zn2+-binding cysteine residues are clustered in the C-terminal part of the S100A3 molecule that is said to be involved in the recognition of target proteins. Transcription factors recognise and bind to specific sequences in the promoter regions of genes, which initiates gene transcription. The binding of transcription factors to the DNA has been attributed to specific structural motifs that are present in the transcription factors. Many transcription factors possess Zn2+-binding domains in the form of protrusions and these are described as zinc fingers. The zinc finger motif binds to specific elements in the promoter. Zinc fingers, first identified in the transcription factor TFIIIA derived from Xenopus, are known to be present in a large family of proteins that includes the thyroid hormone receptor, vitamin D3 receptor, and retinoic acid receptors, among others. Four types of zinc finger motifs have been identified. The TFIIIA zinc finger is...

Comprehension Questions

12.1 A 42-year-old woman presents to your office for her annual physical. On examination, you note neck fullness. When you palpate her thyroid, it is enlarged, smooth, rubbery, and nontender. The patient is asymptomatic. You send her for thyroid function testing her T4, free T4. and T, are normal, but her TSH is slightly elevated. What is the most likely diagnosis B. Thyroid cancer C. Hashimoto thyroiditis A. Repeat thyroid function tests B. Thyroid ultrasound C. Nuclear thyroid scan A. Thyroid function tests 12.4 A 35-year-old woman who was diagnosed with hypothyroidism 4 weeks ago presents to your office complaining of persistent feelings of fatigue and sluggishness. After confirming your diagnosis with a measurement of the TSH. you started her on levothyroxine 50 jjg daily. She has been reading about her diagnosis on the Internet and wants to try desiccated thyroid extract instead of the medicine you gave her. On examination, she weighs 175 lb. her heart rate is 64 bpm at rest,...

Position of the Injury

The best method of pinpointing the location of an injury is to use fixed anatomical landmarks. On the head, one can use the eyes, ears, nose, and mouth on the neck, the prominence of the thyroid cartilage and the sternocleidomas-toid muscles can be used and on the trunk, the nipples, umbilicus, and bony prominences can be used as points of reference. The advantages of using simple anatomical diagrams and body charts for locating the injury are self-evident. It is a simple process to record the position of an injury accurately, yet when medical records are reviewed, it is both surprising and disappointing to find only a vague indication of location.

From GHReleasing Peptides to Ghrelin

Ghrelin, discovered in 1999 as a natural ligand of the GHS-R 1a 7 , is a 28 amino acid peptide predominantly produced by the stomach, but also expressed in bowel, pancreas, kidney, lung, placenta, thyroid, testis, ovary, pituitary and hypothalamus. Within the stomach, ghrelin is produced by enteroendocrine cells, probably the X A-like cells, a major endocrine population in the oxyntic mucosa, the hormonal product of which had not previously been clarified 3,8 .

Use in Prevention and Therapy

Ample intake of iodine (from seafood, iodized salt, or kelp supplements), especially during pregnancy, lactation, and childhood, will maintain production of thyroid hormone and prevent IDD. Inadequate iodine intake during childhood can impair learning ability and school performance.2 Hypothyroidism. If the iodine content of the diet is marginal or low, borderline hypothy-roidism may produce symptoms of fatigue, lassitude, and poor concentration. Replenishing thyroid stores of iodine can be beneficial.

N Retinal Pigment Epithelium

Hyaluronan has been identified in the media of cultured RPE (105) where it is secreted preferentially from the apical surface of RPE, suggesting that RPE is an important source of the hyaluronan present in IPM (106). Retinal glia and RPE are the principal sources of glycosaminoglycan components in retina in vitro, and endogenous neurotrophic growth factors greatly modify glycosaminoglycan synthesis (107). Human fetal RPE is a direct target for thyroid hormones shown by measuring the accumulation of hyaluronan in RPE culture media (108). Cultured human RPE cells express the standard form of CD44 (termed CD44s) and variant isoforms containing exon v6 or v10, which are preferentially expressed by proliferating human RPE cells (109).

Chromatin Versus Other Determinants Of Aging

In the mouse, several gene knockout strains have been serendipitously discovered to influence life span. For example, ablation of the ku86 locus yields mice that manifest a number of pathologies suggestive of premature senescence (18). Conversely, life span extension is observed in association with Pit1 and Prop1 mutations in the Ames and Snell dwarf mouse models, respectively. Homozygous defects at Pit1 or Prop1 loci compromise anterior pituitary development, leading to reductions in growth hormone, prolactin, and thyroid-stimulating hormone, as well as to indirect deficiencies in insulinlike growth factor-1 (IGF-1) and thyroid hormones (19).

Neuroendocrine Tumors

Neuroendocrine tumours (NET) constitute a heterogeneous group of neoplasms that originate from endocrine glands, such as the pituitary, parathyroids, and adrenals, as well as endocrine islets within glandular tissue (thyroid or pancreatic) and cells dispersed between exocrine cells, such as the endocrine cells of the digestive and respiratory tracts 31 . NET can be divided into four groups (a) carcinoid tumours, (b) islet cell tumours, (c) chromaffin cell tumours (PHs and paragangliomas), and (d) medullary thyroid carcinoma (MTC).

Enhancement of cell motility and cellmatrix interaction

Integrin receptors have been particularly implicated in tumour progression, and interaction of tumour cells and endothelial cells is likely to increase tumour cell entry into the circulation and subsequent extravasation. HGF stimulates adhesion of B-lymphoma cells to the extracellular matrix mediated via a4pi and avbl integrins, and promotes migration and invasion of the tumour cells (82). In non-transformed human thyroid epithelial cells, integrin is diffusely distributed, disconnected from the cytoskeleton, and unable to mediate adhesion to the substratum, however, in their counterpart papillary thyroid cancer cells, HGF induces recruitment of integrin molecules at focal adhesions and enhances attachment and spreading of cells via avp3 integrin (113). Likewise, HGF stimulates the expression of integrin in hepatoma cells with subsequent increases in adhesive properties of the cells to endothelial cells and to the extracellular matrix (76). On the other hand, HGF stimulates attachment...

Structure And Function Of Histone Acetyltransferases

Inantly found in proteins that function at the chromatin level (Aasland et al., 1995). The PHD finger is an integral part of the enzymatic core of the CBP HAT domain (Bordoli et al., 200la Kalkhoven et al, 2002) but is dispensable for p300 HAT activity (Bordoli et al., 200la). The HAT domain is preceded by the bromodomain, a 110 amino acid domain which is found in many chromatin-associated proteins (Jeanmougin et al., 1997 Winston and Allis, 1999). Bromodomains function as acetyl-lysine binding domains (Dhalluin et al., 1999 Jacobson et al., 2000), and could therefore play a role in tethering CBP and p300 to specific chromosomal sites (Manning et al., 2001). Interestingly, the bromodomain of p300 was recently shown to cooperate with the PHD finger in binding of hyperacetylated nucleo-somes (Ragvin et al., 2004). The preferred in vitro sites of acetylation on the N-terminal histone tails are lysine 12 (K12) and K15 in histone H2B, K14 and K18 in histone H3 and K5 and K8 in histone H4...

Hgf And Met Prognostic Significance

On the other hand, over-expression of the Met receptor was noted in a wide variety of cancer tissues (Table 3), and importantly, expression levels of the Met receptor were higher in more advanced malignant cases in many types of carcinomas (Table 4). Comparative analysis between Met receptor expression and clinicopathological features in cancer patients indicated that higher levels of Met receptor expression are an useful indicator for relapse and a poor prognosis of patients with hepatocellular carcinoma (200), endometrial carcinoma (190), breast cancer (245), pulmonary adenocarcinoma (170), and thyroid cancer (212). Therefore, expressions of HGF

Blood Sampling Conditions

Drugs such as glucocorticoids, thyroid hormones, diuretics, ACE inhibitors, -blockers, and adrenergic agonists may lower the plasma levels of natriuretic peptides. Treatment with diuretics results in a rapid drop in BNP and NT-proBNP. Therefore, blood samples intended to be used for the diagnosis of heart failure should ideally be drawn before the start of therapy. In stable chronic heart failure patients who are receiving optimized therapy, BNP and NT-proBNP concentrations may be unexpectedly low (16). As another example of confounding by treatment received, human recombinant BNP (nesiritide) is molecularly identical to endogenously released BNP and will be detected by immunoas-says for BNP. Thus, BNP should not be measured for diagnostic or monitoring purposes during infusion of nesiritide. Two hours (i.e., more than five times the half-life) after discontinuation of the infusion, therapeutically administered BNP should no longer contribute to the measured BNP concentration....

Causes Of Hyponatremia

The free water excretion is impaired (urine not maximally concentrated, 150-200 mOsm kg). If the urine is maximally dilute, it is handling free water normally but its capacity for excretion has been overwhelmed, as in central polydipsia. More commonly, free water excretion is impaired and the urine is not maximally dilute as it should be. Two important diagnoses must be considered at this point hypothyroidism and adrenal insufficiency. Thyroid hormone and Cortisol both are permissive for free water excretion, so their deficiency causes water retention. Isolated Cortisol deficiency can mimic SIADH. In contrast, patients with Addison disease also lack aldosterone, so they have impaired ability to retain sodium. Patients with adrenal insufficiency are usually hypovolemic and often present in shock. Euvolemic hyponatremia is most commonly caused by SIADH. Nonphysiologic nonosmotically mediated (therefore inappropriate ) secretion can occur in the setting of pulmonary disease, CNS disease,...

Tumor Initiation Promotion and Progression

Evidence for multistage induction of malignant tumors has also been observed for mammary gland, thyroid, lung, and urinary bladder and in cell culture systems (reviewed in Reference 9), thus it seems to be a general phenomenon. This experimental evidence is consistent with the observed clinical history of tumor development in humans after exposure to known carcinogens that is, initial exposure to a known chemical or physical carcinogen, a long lag period during which exposure to promoting agents probably occurs, and finally the appearance of a malignant tumor.

Clinical Features of Graves Disease

Conjunctival Injection Graves

Graves' disease (also called thyroid ophthalmopathy, dys-thyroid ophthalmopathy, or endocrine orbitopathy) is an autoimmune disease that commonly, though not always, is associated with hyperthyroidism. It is accompanied by a broad spectrum of signs and symptoms of orbital inflammation. Chief among these is exophthalmos. Graves' disease is the most common cause of exophthalmos among

The fascial compartments of the neck Fig 188

Carotid Sheath

Pretracheal fascia (containing thyroid, trachea, oesophagus and recurrent nerve) Pretracheal fascia (containing thyroid, trachea, oesophagus and recurrent nerve) Left lobe I of thyroid 3 The pretracheal fascia encloses the 'visceral compartment of the neck'. Extending from the hyoid above to the fibrous pericardium below, it encloses larynx and trachea, pharynx and oesophagus and the thyroid gland. A separate tube of fascia forms the carotid sheath, containing carotid, internal jugular and vagus nerve and bearing the cervical sympathetic chain in its posterior wall. (Some points of clinical significance concerning this fascia are to be found under 'The thyroid', page 267.)

Clinical features

1 The development of the thyroid accounts for the rare occurrence of the whole or a part of the gland remaining as a swelling at the tongue base (lingual thyroid) and for the much commoner occurrence of a thyroglossal cyst or sinus along the pathway of descent. Such a sinus can be dissected from the midline of the neck along the front of the hyoid (in such intimate contact with it that the centre of the hyoid must be excised during the dissection) then backwards through the muscles of the tongue to the foramen caecum (Fig. 190). Descent of the thyroid may go beyond the normal position in the neck down into the superior mediastinum (retrosternal goitre). 2 A benign enlargement of the thyroid may compress or displace any of its close relations the trachea and oesophagus may be narrowed, with resulting difficulty in breathing and swallowing, and the carotid may be displaced posteriorly. A carcinoma of the thyroid invades its neighbours rather than displacing them eroding into trachea or...

Tight Junction Its Possible Role In Cancer Invasion And Metastasis

Using freeze-fracture electron microscopy, CochandPriollet and colleagues (59) have recently studied thyroid oncocytic tumours. Both gap junctions and tight junction were found to be markedly reduced. The reduction of tight junction is particular obvious in malignant tumours.

In Human Ovarian Cancer

The presence of lymphocytes and round cells in human tumors has long been recognized (reviewed in ref. 12). In the late 1970s, several carcinomas were noted to contain mainly lymphocytes and macrophages (13,14), often with a predominance of macrophages. Alpha-napthyl esterase-positive macrophages localized to necrotic areas in addition to being found within and around the tumor parenchyma. Other cell types, particularly granulocytes, have not been found so consistently. More recent studies have used immunohistochemistry with specific monoclonal antibodies to deduce the phenotype of infiltrating cells. CD3+, CD45RO+, and CD68+ populations were all found in a series of 75 formalin-fixed, paraffin-embedded thyroid carcinomas (15), with CD3+ T-cells and macrophages occurring in comparable numbers. In colonic carcinomas, the infiltrate consisted of macrophages and CD4+ a p T-cells. CD8+ T-cells were also abundant, particularly in close association with tumor cells (16). In carcinoma of the...

Non Histone Protein Acetylation Link To Diseases

Pathways Thyroid Hormone Receptors

Nuclear protein acetylation increases dramatically immediately after UV irradiation suggesting causal relationship exists between nuclear protein acetylation and nucleotide excision repair of DNA in human cells (Ramanathan and Smerdon, 1986). Over expression of oncoprotein PU.1 inhibits erythroid cell differentiation and contributes to the formation of murine erythroleukemias (MEL) by inhibiting CBP mediated acetylation of several nuclear proteins (Hong et al., 2002) (Fig. 3b). Microtubules are formed from a protein called tubulin and have to be broken down for the cell to divide. Acetylation of tubulin leads to stabilizes micro-tubules (Maruta et al., 1986) and therefore the inhibitors of tubulin deacetylases are important for anti cancer therapy (Fig. 3b). -catenin is key component in Wnt signaling pathway, which is implicated in many human cancers (Clevers, 2004). CBP mediated acetylation of -catenin differentially regulates its function in a promoter dependent manner. The site of...

Physiological Effects Of Glucocortioids

Glucocorticoids enhance the lipolytic actions of other hormones, such as growth hormone, catecholamines, glucagon, and thyroid hormone. Gluco-corticoids also help in the mobilization of fatty acids from adipose tissues to the liver, where the metabolism of fatty acids inhibits glycolytic enzymes and promote gluconeogenesis. As a result of increased fatty acids oxidation,

The Role Of Thymosin Family Actinbinding Proteins In Actin Dynamics

Both TP10 and TP15 have been investigated for their possible relationship with cancer progression. TP 10 protein was reported to occur at high levels in the malignant cell rather than the normal tissue component of human breast cancer, and the level of expression increased with tumour grade (Verghese-Nikolakaki et al. 1996). The expression of TP 10 gene was higher in five thyroid carcinoma cell lines as compared with normal thyroid-derived primary cells. Expression of the gene was higher in anaplastic tumour tissue (Califano et al. 1998).

Answers To Case 45 Amenorrhea Primary Miillerian Agenesis

Summary A 17-year-old nulliparous female, who may have only one kidney, presents with primary amenorrhea. She denies weight loss or excessive exercise. On examination, she is 5 ft 6 inches tall and weighs 140 lb. Her blood pressure is 1 10 60. Her thyroid gland is normal. She has appropriate Tanner stage IV breast development, axillary and pubic hair, and female external genitalia.

Anionexchange resins bile acid sequestrants

About half the patients who take Colestyramine experience constipation and some complain of anorexia, abdominal fullness and occasionally of diarrhoea these effects are dose-related but may limit or prevent its use. Because the drug binds anions, drugs such as warfarin, digoxin, thiazide diuretics, phenobarbitone and thyroid hormones should be taken 1 h before or 4 h after Colestyramine to avoid impairment of their absorption.

The Team Approach

Neonatal thyroxine levels are generally elevated at birth when compared to adults, such as 11.8 to 22.6 g dL for ages 1 to 3 days, due to maternal estrogen-induced thyroid-binding globulin (TBG) levels. The medical decision limit for detecting neonatal hypothyroidism is less than 7.5 g dL.5 However, synthesis of thyroid hormones require adequate intake of proteins, so the thyroid screen should occur after adequate feedings. In preterm infants, thyroxine level is also lower and tends to rise up to typical reference ranges when term birth weight is reached. Thy-roxine levels gradually decline to the adult reference range by age 10, with some fluctuations in the values at onset of puberty. Free thyroxine is generally near adult levels but generally is tested only after repeat thyroxine levels and TSH are determined to be abnormal.

Putative New Natural Ghrelin Hormones and Companion Receptor Subtypes

Besides the GHRP ghrelin GHS type 1a receptor, the Merck group cloned another related GHS receptor designated type 1b in 1997. The type 1b receptor is a truncated version of the type 1a GHS receptor because only TM-1 through TM-5 domains are encoded. Its function is still unknown. Neither the GHRPs nor ghrelin bind to this receptor and the type 1a and 1b receptors are localised to separate chromosomes. When selective, sensitive hybridisation probes for the type 1a and 1b receptors were utilised, the mRNA distribution in normal human tissues demonstrates the truncated type 1b receptor is widely distributed while the type 1a GHRP ghrelin active receptor is much more restricted, i.e., predominantly in the pituitary gland but also in the thyroid gland, pancreas, spleen, myocardium and adrenal gland. In contrast to the distribution of the active type 1a receptor, the expression of the mRNA distribution of the ghrelin peptide is widespread in human tissues, which suggests that ghrelin may...

Extramedullary Plasmacytoma

Primary extramedullary plasmacytoma occurs rarely and involves most commonly the upper air passages and paranasal sinuses (90 ), though a variety of organ involvement has been reported.105 The clinical manifestations depend on the sites of involvement. In the head and neck region, painless or painful mass may be the first sign. Nasal obstruction, discharge, epistaxis, hoarseness, or hemoptysis may occur. Less commonly involved sites include lung, GI tract, lymph nodes, and the thyroid gland. Only about 20 of patients will have serum monoclonal proteins, and the bone marrow is not involved. Diagnosis is made by histologic or cytologic demonstration of myeloma cells in the biopsied specimen. Establishment of monoclonality, by specific antibody staining for cyto-plasmic immunoglobulin to show light-chain restriction or immunoglobulin gene rearrangement, is sometimes necessary to differentiate this entity from reactive plasmacytosis. A bone survey is necessary to exclude bone involvement,...

Answers To Case 44 Thy rotoxicosisG raves Disease

Confirm diagnosis A low serum thyroid-stimulating hormone (TSH) level and an increased free thyroxine (T,) level with this clinical presentation would be confirmatory. However, other tests that might help would be thyroid-stimulating immunoglobulins or diffusely elevated uptake of radioactive iodine on thyroid scan. Treatment options Antithyroid drugs, radioactive iodine ablation, or surgical ablation of the thyroid.

Endocrine Glands Involved In Reproduction

The hypothalamus is derived from neuroendocrine tissue in the mesencephalon, or middle section of the brain. It provides the tertiary level of control and stimulation of hormone secretion. The hypothalamus makes releasing hormones such as thyroid-releasing hormone (TRH) and Gn-RH, both peptide in nature. The primary function of these hormones is to stimulate pituitary secretion of secondary hormones such as LH and FSH. However, these hormones also respond to other hormones in a positive and negative feedback system such that a highly coordinated monthly cycle occurs in the mature female. There is a similar coordinated cycle in the mature male that spans a 24-hour cycle. Other hypothalamic hormones that play a role in sexual development and reproduction include TRH and cortisol-releasing hormone (CRH), which have the ability to stimulate secondary endocrine glands.4 The pituitary gland is composed of two unique glandular tissues, the neurohy-pophysis and the adenohypophysis, which...

The lymph nodes of the neck

Jugular Lymph Node

Along the front of the neck lies another group of vertically disposed nodes, the infrahyoid (on the thyrohyoid membrane), the prelaryngeal and the pre- and paratracheal nodes. These drain the thyroid, larynx, trachea and part of the pharynx and empty into the deep cervical group.

Approach To Thyrotoxicosis In Pregnancy Definitions

Hyperthyroidism Syndrome caused by excess thyroid hormone, leading to nervousness, tachycardia, palpitations, weight loss, diarrhea, and heat intolerance. Thyroid storm Extreme thyrotoxicosis leading to central nervous system dysfunction (coma or delirium) and autonomic instability (hyperthermia, hypertension, or hypotension).

Clinical Approach

Hyperthyroidism is rare in pregnancy, occurring in approximately 1 2000 pregnancies. Symptoms of thyrotoxicosis include tachycardia, heat intolerance, nausea, weight loss or failure to gain weight despite adequate food intake, thyromegaly, thyroid bruit, tremor, exophthalmos, and systolic hypertension. The most common cause of hyperthyroidism in pregnancy is Graves' disease, an autoimmune disorder in which antibodies are produced that mimic the function of thyroid-stinuilating hormone (TSH). These antibodies stimulate the thyroid gland to produce more thyroid hormone, leading to the symptoms responsible for thyrotoxicosis. The diagnosis of hyperthyroidism is confirmed by the presence of an elevated free T4 level and low serum TSH level. Treatment during pregnancy may be medical or surgical however, in general hyperthyroidism in pregnancy is managed medically. PTU is generally accepted as the drug of choice in pregnancy. PTU inhibits the peripheral conversion of T, to triiodothyronine...

Endocrine Abnormalities and Cytokines

Colony Abbreviations

Several endocrine abnormalities, such as low levels of testosterone and growth hormone and increased production of cytokines, have been correlated with weight loss in AIDS, while adrenal and thyroid hormones show conflicting patterns 63 . The synergic action of TNF and other cytokines is

Macroscopic And Microscopic Features Of Neoplasms

The site of the primary tumor also frequently determines the mode of, and target organs for, metastatic spread. In addition to local spread, cancers metastasize via lymphatic channels or blood vessels. For example, carcinomas of the lung most frequently metastasize to regional lymph nodes, pleura, diaphragm, liver, bone, kidneys, adrenals, brain, thyroid, and spleen. Carcinomas of the colon metastasize to regional lymph nodes, and by local extension, they ulcerate and obstruct the gastrointestinal tract. The most common site of distant metastasis of colon carcinomas is the liver, via the portal vein, which receives much of the venous return from the colon and flows to the liver. Breast carcinomas most frequently spread to axillary lymph nodes, the opposite breast through lymphatic and spleen.

Nitrogenous Biomarkers Of Nutritional Status

Filtration rate, so assessment of this protein must also be carefully evaluated. Transferrin is the protein that acts as a carrier protein for iron. It has a half-life of 8 days, which makes it a sensitive marker of recent protein-energy nutritional status. Iron concentration must be taken into consideration when evaluating nutritional status based upon transferrin concentration. Transthyretin, or TBPA, is the protein that acts as a carrier for thyroid hormones. Its short half-life of 1-2 days makes it a sensitive marker for protein-energy nutritional status. Thyroid hormone level must be taken into consideration when evaluating nutritional status based upon trans-thyretin concentration. The use of multiple biochemical markers for nutritional status gives a more accurate picture of nutritional status than relying upon the measurement of only one marker. Several indices use multiple markers for calculating nutritional status.

Steroid Receptor Superfamily

The steroid receptor superfamily comprises the glucocorticoid (GR), progesterone (PR), mineralocorticoid (MR), androgen (AR), thyroid hormone (TR),and vitamin D3 (VDR) receptors (60). These receptors bind to steroid hormones and are translocated to the nucleus where they bind to hormone responsive elements on DNApromotor regions to alter gene expression. While steroids are very effective anti-inflammatory agents, they have a multiplicity of serious side effects that limit their full use.

Coactivator Corepressor Interactions

Co-repressors in PPAR biology are less well characterized. The concept of a co-repressor was developed from other nuclear receptors such as the thyroid hormone receptor (TR) 80 . These receptors have profound repressive qualities in the absence of ligand. They can silence quite constitutively active promoters. In contrast, many PPAR reporter systems are rather inactive without PPAR and introduction of PPAR can provide transcriptional activation without the apparent addition of ligand 81 . It has been shown, however, that dominant-negative forms of PPARy bind to co-repressors such as N-COR and SMRT and are defective for their ligand-dependant dissociation 71, 72 . It has also been shown that PPARy binds to co-repressors in solution, but not when bound to DNA 82 . The binding domain for the co-repressors has recently been visualized by X-ray crystallography to residues in helix 4 and 12 of PPARa, and is mediated by overlapping yet distinct residues compared with those involved in...

Management Of Metastatic

Papillary thyroid cancer may spread via intrathyroidal lymphatic channels and at the time of the initial operation, coexisting, contralateral, intrathyroidal disease has been reported in 30 to 87.5 of patients with papillary thyroid cancer (28,29). Analysis of 576 patients followed for a median of 10 years demonstrated a recurrence rate of 11 in patients undergoing total thyroidectomy compared to 19 in patients undergoing subtotal resection (30). Local recurrence is a serious complication with a mortality rate of 50 (30-32). An exception to total or near total thyroidectomy may be advocated for the management of papillary microcarcinoma or the rare, encapsulated papillary carcinoma, when intrathyroidal spread is rare and unilateral total thyroid lobectomy deemed adequate. In patients where extrathyroidal papillary cancer invades local structures, it may be necessary to include part of the trachea or oesophagus, recurrent laryngeal nerve or jugular vein in an en-bloc excision with the...

Retinoid Receptors Belong to the Nuclear Hormone Receptor Family

NRs comprise a large and evolutionary well conserved family of transcription factors found in organisms as diverse as nematodes, flies, and mammals (reviewed in Refs 47-49 ). NRs are thought to function as ligand-activated transcription factors, exerting widely different biological functions by regulating target gene expression positively and or negatively, and include the receptors for certain small, lipophilic molecules. RARs bind both all-trans and 9-cis retinoic acids, whereas RXRs only bind 9-cRA (see Ref. 50 and references therein). Retinoid receptors activate transcription by recognizing and binding consensus sequences known as RA response elements (RAREs) in the promoters of target genes (see below). RAR binds DNA as a heterodimer with RXR, while RXR also has the ability to bind DNA as a homodimer. Additionally, RXR forms heterodimers with a number of other NRs, including the receptors for thyroid hormone (TR) and vitamin D3 (VDR) 50 , thereby coupling retinoid signaling to a...

CD36 Gene Structure and Regulation

The peroxisome proliferator activated receptors (PPARa, PPARy, and PPAR are members of the nuclear receptor family of ligand-activated transcription factors, which include the retinoid, steroid, and thyroid hormone receptors. PPARs participate broadly in the transcriptional control of genes involved in lipid and carbohydrate metabolism (reviewed in Ref. 36 ). Synthetic agonists for PPARa collectively known as fibrates, decrease serum triglyceride levels and are widely prescribed for the treatment of hypertriglyceridemia and compound lipidemia. Synthetic PPARy agonists, known as thiazolidinediones, or glitazones, act as insulin sensitizers and

Management of Recurrent or Metastatic Disease

Cervical tissues are the most common site for recurrent disease in parathyroid carcinoma. Local recurrence may result from the tumour capsule having been breached at the primary procedure. Undoubtedly the best way of decreasing the incidence of recurrent local disease rests with the surgeon recognising the possibility of parathyroid carcinoma preoperatively, confirming the diagnosis macroscopically at the initial operation for primary HPT and performing an adequate operation at the first surgical episode. This should be by performing an en-bloc excision of the tumour with the ipsilateral thyroid lobe and removing the tumour and all adherent or invaded structures without breaching the tumour capsule (81,88,89). On occasion this may necessitate sacrifice of the recurrent laryngeal (87).

Congenital Generalised Lipodystrophy Berardinelli Seip Syndrome or Lipoatrophic Diabetes

Lawrence Syndrome Lipodystrophy

CGLD can manifest with different expression of signs and symptoms and with different degrees of severity of the metabolic abnormalities (Table 3). Insulin resistance usually evolves into overt diabetes. Micro- and macroangiopathies and keto-sis are unusual in lipoatrophic diabetes. An increased resting energy expenditure without abnormalities of thyroid function has been reported. Liver steatosis, liver fibrosis, portal hypertension, and oesophageal varices are late-onset complications, possibly leading to death.

Objectives for a Clinical Trial

There is concordance of opinion amongst physicians, clinical scientists and regulatory health authorities on the value of multicentre, randomised, controlled clinical trials, with adequate statistical power and preferably double-blinded, to determine the true effects of an intervention with therapeutic intent. To evaluate treatment of a complex syndrome such as cachexia, rather than a distinct or singular abnormality, those design features may be considered requisite. Restrictive protocol eligibility criteria and stratification on prognostic factors must be used to limit the impact of various co-morbidities, concomitant medications, patient histories and physicians' treatment patterns and skills. Patients with eating disorders, infections, maldigestion, malabsorption or diarrhoea, adrenal or thyroid diseases should be excluded. Efforts to limit disparities among the patients may reduce confounding variables but also will limit the validity of generalisations about the results from the...

Treatment of Unresectable Metastatic Disease

Harness J K.Childhood thyroid carcinoma. (1977) In Textbook of Endocrine Surgery, Eds Clark O H, Dull Q-Y. W B Saunders Company, Philadelphia 1997. 3. Thompson N W, Nishiyama R H, Harness J K. Thyroid carcinoma. Current controversies. Current Problems in Surgery, 1978 15 1-67. 5. Thompson NW. (1983). The thyroid nodule - surgical management. In Endocrine Surgery p 14-24. Butterworths, London. 6. Reeve TS. (1983) Operations for non medullary cancer of the thyroid gland In Surgery of the Thyroid and Parathyroid Glands. p 63-74. Churchill Livingstone, Edinburgh 7. LiVolsi VA. (1992). Papillary neoplasms of the thyroid. Pathologic and prognostic 8. De Groot LJ. (1983). Clinical features and management of radiation associated thyroid carcinoma in Surgery of the Thyroid and Parathyroid Glands. p 4050. Churchill Livingstone, Edinburgh 9. Terry JH, St John SA, Karkowski FJ et al. (1994). Tall cell papillary thyroid cancer incidence and prognosis. American Journal of Surgery. 168(5) 459-461...

Physiology And Pharmacokinetics

Thyroid hormone synthesis requires oxidation of dietary iodine, followed by iodination of tyrosine to mono- and diiodotyrosine coupling of iodotyrosines leads to formation of the active molecules, tetraiodo-tyrosine, (T4 or L-thyroxine) and triiodotyrosine (T3 or L-thyronine). These active thyroid hormones are stored in the gland within the molecule of thyroglobulin, a major component of the intrafollicular colloid. They are released into the circulation following reuptake of the colloid by the apical cells and proteolysis. The main circulating thyroid hormone is T4. About 80 of the released T4 is deiodinated in the peripheral tissues to the biologically active T3 (30-35 ) and biologically inactive reverse T3 (45-50 ) thus most circulating T3 is derived from T4. Further deiodi-nation, largely in the liver, leads to loss of activity. In the blood both T4 and T3 are extensively (99.9 ) bound to plasma proteins (thyroxine-binding globulin, TBG, and thyroxine-binding prealbumin, TBPA)....

Nuclear Hormone Receptors

Nuclear hormone receptors belong to a superfamily of transcription factors mediating the transcriptional activity of endogenous or exogenous ligands 1-5 . This family contains approximately 50 members in humans 6 and includes the classical steroid hormone receptor family and the thyroid retinoid vitamin D receptor families. A growing number of proteins that possess the structural features of nuclear hormone receptors, but lack known ligands, have been identified. These are called orphan nuclear receptors. Identifying ligands for this class of receptors has accelerated the physiological characterization of the pathways they control.

Adverse reactions

Topical application of iodine-containing antiseptics to neonates has caused hypothyroidism. Iodide intake above that in a normal diet will depress thyroid uptake of administered radioiodine, because the two forms will compete. In the case of diet, medication and water soluble radio-diagnostic agents, interference with thyroid function will cease 2-4 weeks after stopping the source, but with agents used for cholecystography it may last for 6 months or more (tissue binding).

Guide To Further Reading

England Journal of Medicine 345 260-265 Dayan C M 2001 Interpretation of thyroid function Mazzaferri E L 1993 Management of a solitary thyroid nodule. New England Journal of Medicine 328 553-559 Pashke R, Ludgate M 1997 The thyrotropin receptor in thyroid diseases. New England Journal of Medicine 337 1675-1681 Surks M I, Sievert R 1995 Drug therapy drugs and thyroid function. New England Journal of Medicine 333 1688-1694 Toft A D 1994 Thyroxine therapy. New England

Hypothalamus and anterior pituitary

Is a tripeptide formed in the hypothalamus and controlled by free plasma T4, T3 concentration. It has been synthesised and can be used in diagnosis to test the capacity of the pituitary to release thyroid stimulating hormone (TSH), e.g. to determine whether hypothyroidism is due to primary thyroid gland failure or is secondary to pituitary disease or to a hypothalamic lesion. TRH is also a potent prolactin-releasing factor. Thyroid stimulating hormone (TSH) thyrotrophin, a glycoprotein of the anterior pituitary, controls the synthesis and release of thyroid hormone from the gland, and also the uptake of iodide. There is a negative feedback of thyroid hormones on both the hypothalamic secretion of TRH and pituitary secretion of TSH. Antithyroid drugs, by reducing thyroid hormone production, cause increased formation of TSH which is the cause of the thyroid enlargement that sometimes occurs during antithyroid drug therapy. GHRH and somatostatin both regulate growth hormone secretion.

Interferon And Autoimmunity

Given the possible effects of interferons on the immune system it is perhaps not surprising that autoimmune disorders have been reported as a consequence of interferon-a therapy. For example, autoimmune haemolytic anaemia, autoimmune thyroid disorders and thrombocytopenic purpura have all been described 18 . Interferon-a therapy is also associated with autoantibody production including antibodies to nuclear antigens 19 , thyroid antigens and epithelial cells. Ronnblom et al. 20 described a patient with a malignant carcinoid tumour who developed SLE during interferon-a therapy. Interestingly, this patient had a further course of interferon-a therapy which resulted in the recurrence of anti-DNA antibodies and clinical evidence of active lupus. This report stimulated the authors to prospectively study 135 patients with malignant carcinoid tumours treated with interferon-a and they found 25 patients who developed clinical evidence of autoimmune disorders 18 . This included 18 patients...

See also Thyroxine Thyroglobulin Aromatic Amino Acid Utilization

Figure 21.19 Biosynthesis of thyroid hormones as residues in the protein thyroglobulin. Thyroxine and triiodothyronine are thyroid hormones made by modifying tyrosine residues in the protein, thyroglobulin (Figure 21.19). Degradation of thyroglobulin yields the free hormones. Synthesis occurs in the thyroid gland, which concentrates iodide from the blood.

Phenylalanine Dihydrobiopterin O2 Tyrosine Tetrahydrobiopterin H2O

Tyrosine utilization - Tyrosine serves as a precursor to thyroid hormones, melanins (biological pigments - Figure 21.20), and catecholamines (hormones and neurotransmitters). Thyroxine and triiodothyronine are thyroid hormones made by modifying tyrosine residues in the protein, thyroglobulin (Figure 21.19). Degradation of thyroglobulin yields free hormones. Synthesis occurs in the thyroid gland, which concentrates iodide from the blood. Melanin synthesis occurs in melanocytes (Figure 21.20).

Carotenoids and Gap Junctional Intercellular Communication

Via gap junctions are involved in the regulation of tumor cell growth and differentiation (121,122). Such disturbances may also cause a predisposition for arrhythmias and therefore have a role in the pathogenesis of cardiac diseases (123). Normal cells are contact-inhibited and have functional GJIC, whereas most tumor cells exhibit dysfunctional homologous or heterologous GJIC (121). Typically, cancer cells lack growth control and are not able to terminally differentiate, which has, at least in part, been attributed to disturbed GJIC. Oncogenes like ras, raf, or src down-regulate GJIC, whereas it is up-regulated by tumor suppressor genes (116,117). Furthermore, tumor-promoting compounds such as 12-O-tetradecanoylphorbol-13-acetate or dichlorodiphenyltrichloro-ethane inhibit GJIC, whereas substances exhibiting antitumor properties, including vitamin D, thyroid hormones, flavonoids retinoids, and carotenoids, stimulate GJIC (116,117,121).

Sharyn Bord 1 Introduction

Immunohistochemistry can provide valuable information regarding protein expression in different cell types at specific stages of differentiation during bone modeling and remodeling. By combining immunohistochemistry with other techniques, it is possible for the researcher to determine protein expression, in relation to mRNA production, enzyme activity and bone remodeling, on the same sample of bone. This chapter covers the localization of protein in human bone by immunohistochemistry using an indirect immunoperoxidase method, and considers both frozen and wax-embedded sections. Methods for immunostaining of plastic embedded tissue can be found in the chapter by Van Leeuwen and Derkx, this volume. Immunohistochemistry is based on incubating high-affinity antibodies on tissue sections to detect patterns of expression for specific antigens within the tissue. This can be achieved using either an immunofluorescence-based technique in which the antibody is conjugated with a fluorochrome, or...

Alphaglucosidase inhibitor blocks hydrolysis of an

Euthyroid - showing normal clinical signs and normal thyroid function status despite the indications of dysfunction in some thyroid test results ex vivo - outside of a living being excretion - the elimination of waste products from the body glycogenesis - formation of glycogen glycogenolysis - glycogen stored in the liver and muscles is converted to glucose 1-phosphate and then to glucose 6-phosphate goiter - enlarged, usually hyperactive thyroid gland

Elements Of Signal Transduction

Abbreviations used are ACTH, adrenocorticotropic hormone FSH, follicle stimulating hormone GH, growth hormone LH, luteininzing hormone PH, parathyroid hormone TSH, thyroid stimulating hormone EGF, epidermal growth factor, PDGF, platelet derived growth factor TGF, tranforming growth factor TNF, tumor necrosis factor GM-CSF, granulocyte-moncyte colony stimulating factor GABA, y-aminobutyric acid.

Hypercalcemia Harrison

Hypercalcemia And Diagnostic Algorithm

A 63-year-old African-American woman is brought to the emergency room for upper arm pain and swelling following a fall at home. The family has noted that for approximately the past 2 months, the patient has become progressively fatigued and absent-minded, and she has developed loss of appetite and weight loss. She has been getting up to urinate several times per night and complains of thirst however, a test for diabetes in her doctor's office was negative. This morning, she lost her balance because she felt lightheaded and fell, landing on her left arm. Physical examination is notable for an elderly, thin woman in mild distress as a result of pain. She is afebrile, her blood pressure is 110 70 mmHg and heart rate 80 bpm. Her thyroid gland is normal to palpation. Her mucus membranes are somewhat dry and sticky. Heart and lung examinations are normal. and carotid auscultation reveals no bruits. Examination of her extremities is significant only for deformity of the left mid-humerus with...

Iiiiiiiiiiiimiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiismu Li Hormonal mechanisms include the following

Most hormones interacting with intracellular receptors exert their effects by controlling rates of transcription of specific genes. In this case, the hormone binds to a receptor and the complex migrates to the nucleus, where it interacts with specific DNA sites. Hormones in this class include steroids, thyroid hormones (see here), and the hormonal forms of vitamin D. In addition, retinoids, derived from retinoic acid (related to vitamin A), exert regulatory effects in embryonic development through interactions with intracellular receptors.

Us densitometry center reporting practices

The findings from Fulheihan et al. continued to be disheartening in the realm of clinical guidance. Only 57 of the responding centers recommended patient evaluations for secondary causes of bone loss. The criteria for making such recommendations also varied. A T-score of less than -2.5 was used by 25 of the centers and a z-score less than -2 was used in 18 . When specific tests were recommended, the most common recommendations included a measurement of serum calcium, parathyroid hormone (PTH) and thyroid stimulating hormone (TSH). Fifty-six percent recommended nonprescription interventions such as calcium, vitamin D, and exercise for the prevention of osteoporosis and only 52 recommended such interventions as part of therapy. Only 51 of the centers recommended prescription interventions for the prevention of osteoporosis, whereas only 58 made recommendations for prescription interventions for treatment. In contrast, 74 of the centers did recommend a follow-up bone density measurement,...

Intracellular Hormone Receptors

The steroid thyroid hormone receptor superfamily (e.g., glucocorticoid, vitamin D, retinoic acid, and thyroid hormone receptors) is a class of proteins that reside in the cytoplasm and bind the lipophilic steroid thyroid hormones. These hormones have low, intrinsic solubilities (low abundance) but are capable of freely penetrating the hydrophobic plasma membrane. Upon binding ligand, the hormone-receptor complex translocates to the nucleus and binds to specific DNA sequences, termed hormone response elements (HREs). Binding of the complex to this element results in altered transcription rates of the associated gene. Thus, most lipophilic hormone receptors are proteins that effectively bypass all of the signal transduction pathways previously described by residing intracellularly, within the cytoplasm, as opposed to on or near the cell membrane. In addition, all of the hormone receptors are bifunctional in that they are capable of binding steroid hormones of the thyroxine and retinoic...

Mechanical Stress Fluid Shear And Cell Signaling

Figure 8 The hemodynamic stress-initiated and mechanical stress signal transduction pathways activated in endothelium by mechanical-to-biochemical coupling transduced by the endothelial cell membrane via receptors such as integrins. Membrane-associated p21ras furthermore activates a number of pathways. Shown here are the MEKK-JNKK-JNK pathway (shown bold-faced in the figure), which is preferential in the fluid shear stress model over the Raf-MEK-ERK pathway in activation of AP-1 ternary complex transcription factor formation upon binding and activation of TRE promoters. Expression of chemokine MCP-1 from endothelium due to this shear stress can attract monocytes, T cells, and natural killer cells to the target endothelial cell, which has potential cancer treatment capabilities by increasing monocyte (anti-tumoral) activity (370). Abbreviations MEKK, an MAPKKK (mitogen-activated protein kinase kinase kinase) or extracellular signal-regulated kinase kinase JNKK, c-Jun NH2-terminal...

Definition and Diagnosis

Cachectic heart-failure patients are weaker and fatigue earlier, which is due to both reduced skeletal muscle mass and impaired muscle quality. A simple and fast applicable definition of 'clinical cardiac cachexia' is the following in CHF patients without signs of other primary cachectic states (e.g. cancer, thyroid disease, or severe liver disease), cardiac cachexia can be diagnosed when weight loss of 6 of the previous normal weight is observed over a period of 6 months 4 . The previous normal weight of a heart-failure patient would be the average weight prior to the onset of heart disease (before the diagnosis). It is important to document dry weight loss measured in a non-oedematous state to prove the diagnosis.

Pituitary Disorders and Weight Loss Hypopituitarism

Total or partial hypopituitarism may occur in patients with pituitary adenomas, following pituitary surgery or radiation, or after head injury. Deficiency of any or all of the six major hormones (lutheinising hormone LH , follicle stimulating hormone FSH , thyroid, GH, thyroid stimulating hormone TSH , ACTN, and prolactin) can occur. The most common symptom in both men and women is secondary hypogonadism, because of LH and FSH deficiencies or secondary to hyper-prolactinaemia. In children, cessation of growth and delayed puberty are common.

Bilateral Visual Field Obliteration

An 18-year-old college student presents to the clinic with the complaint that her heart is racing. You obtain blood for thyroid studies and diagnose her with Graves' disease (hyperthyroidism). On physical examination of her eyes, what would you expect to see (A) Thyroiditis 19. When performing posterior palpation of the thyroid gland, you should do all of the following EXCEPT (C) Palpate between the sternocleidomastoid muscle and the trachea for the thyroid isthmus. (D) Move your fingers laterally to palpate for the thyroid lobes.

Approach To Diabetes Mellitus Definitions

Glycosylated hemoglobin or hemoglobin A c (HGA c) is not recommended for diagnosis. This test is used to estimate the average glucose over the past 3 months in those who are diagnosed with diabetes. Measurement of C-peptide and insulin levels can be used to distinguish type 2 from type 1 diabetes when the history, physical examination, and other tests, such as serum ketones and osmolality, are not enough. Other tests recommended by the American Diabetes Association are fasting lipid profiles (at the time of diagnosis and. at least, annually thereafter), serum creatinine, urinalysis, urine microalbuminxreatinine ratios (at time of diagnosis in type 2 diabetics and annually thereafter in type 1 diabetics who have had disease for 5 years and annually thereafter), annual dilated eye examinations, regular foot examinations, EKG (in adults), and, in type 1 diabetics. thyroid disease screening with a thyroid-stimulating hormone (TSH).

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