The Natural Thyroid Diet

The Natural Thyroid Diet

The Natural Thyroid Diet is a guide written to show people suffering from thyroid how to treat it the most natural and effective way. The guide was put together to be something that can be done at home without a need to visit an expert as regards its use. This program is a proven home method useful in eliminating Thyroid rapidly and permanently. It is a combination of useful diets system to help you permanently get rid of your thyroid within 4 weeks. The foods have been tested and have been proven to solve this problem for you. The book is a quick fix that has been designed to help you get a cure for your Thyroid in 4 Weeks. The methods employed in this book are natural ones that have been proven by many specialists. The book is in a digital format (PDF) and has been created at a very affordable price. There are a lot of stress, frustrations and disappointments that come with trying programs after programs. This is one thing that happens in the name of fighting Thyroid; however, this program has been designed to help you stop worrying about programs after programs. The creator is assured of its work that you are allowed to ask for a refund if nothing happens after 4 weeks of its usage. Read more here...

The Natural Thyroid Diet Summary

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CASE 4 Thyroid Storm Case Description

A 25-yr-old woman presented to her physician two yr previously with weight loss, palpitations, and tremulousness. She was diagnosed with hyperthyroidism due to Graves' disease and started on therapy with an antithyroid drug. Because of a variety of circumstances, including an inability to afford the medication, she became increasingly symptomatic. Over the next two yr, she lost approximately 40-50 lbs, and developed significant proximal muscle weakness. When referred to the Endocrine Clinic, she was severely debilitated. The patient had no other medical problems. There was a positive family history of thyroid disease her mother had had an overactive thyroid treated surgically many years earlier. She smoked two packs of cigarettes daily and was unemployed. On physical exam, pulse was 130 bpm, BP 150 60 mmHg, weight 110 lbs, height 67 inches. The patient was emaciated and had severe temporal muscle wasting. There was a stare, lid lag, and mild bilateral proptosis. Extraocular movements...

CASE 1 Recurrent Painful Hashimotos Thyroiditis Case Description

Case 1 presented to us in 1982, at age 67, after taking levothyroxine (T4) for 10 yr. Her thyroid was nontender, quite firm, and diffusely enlarged, with an estimated size of 50 g. Her antithyroid microsomal antibody titer was 1 1 600,000 and her antithyroglobulin antibody level was 50 radioimmunoassay (RIA) units*. On a T4 dose of 150 g daily, her serum thyrotropin thyroid stimulating hormone (TSH) level was 3.5 mU L (normal 0.5-5.2). The presumed diagnosis was chronic lymphocytic (Hashimoto's) thyroiditis. T4 was continued. In 1987, because her thyroid size had not decreased, she had a fine-needle aspiration biopsy (FNAB), that produced only a few groups of oxyphilic follicular cells (Hurthle cells), consistent with Hashimoto's thyroiditis, but insufficient for a definite diagnosis. Her goiter was stable until May 1995, when she reported 2 wk of severe anterior neck pain that radiated to her ears and jaw. Thyroid size was still about 50 g, the erythrocyte sedimentation rate (ESR)...

CASE 2 Localized Thyroid Pain Case Description

Case 2 is a 19-yr-old man who presented to us with 10 d of marked anterior neck pain and swelling. Two days earlier, he had been started on 60 mg of prednisone daily, which had improved the pain and reduced the neck swelling. Examination showed a 4-cm firm, tender mass in the lower right thyroid lobe and isthmus, which was hypofunctional by per-technetate scintiscanning (see Fig. 2). Free T4 and TSH levels were normal, the erythrocyte sedimentation rate (ESR) was elevated at 32 mm h, and the leukocyte count was elevated at 14,800 with 84 neutrophils. FNAB with 22- and 25-gauge needles was quite TC THYROID 19 1993 at 11 06 Fig. 2. Technetium-99m pertechnetate scan showing the large hypofunctional mass that seems to arise from the lower right thyroid lobe and isthmus. There is a faint suggestion of a rim of activity surrounding the mass. The projections are anterior, right anterior oblique (RAO) and left anterior oblique (LAO). TC THYROID 19 1993 at 11 06 Fig. 2. Technetium-99m...

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).

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...

Thyroid Eye Disease

Thyroid eye disease is an immunological disorder that affects the orbital muscles and fat. Hyperthyroidism is observed with orbitopathy at some point in most patients, although the two are commonly synchronous. Histological examination of the retroocular connective tissues in thyroid eye disease reveals lymphocytic infiltration and accumulation of glycosaminoglycans produced locally by fibro-blasts, which contribute to the pathogenesis of ophthalmopathy. Effective parameters involving glycosaminoglycans to indicate the activity of thyroid eye disease have been reported. The concentrations of glycosaminoglycans were determined in patients with thyroid eye disease and control subjects (68). The orbital extracellular matrix glycosaminoglycans exhibited a significant increase in the tissue fractions containing chondroitin sulfate A and hyaluronan in patients with thyroid eye disease in comparison to those from control subjects. Patients with increased glycosaminoglycan concentrations...

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.

Differentiated Thyroid carcinoma 1631 Epidemiology

Epidemiology Thyroid Cancer

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...

CASE 5 Postirradiation Insular Thyroid Cancer Case Description

A 69-yr-old man with a history of external beam radiation therapy for acne as a teenager presented in July 1991 with superior vena cava syndrome thought owing to an enlarged thyroid. Although he could not date the onset of his symptoms precisely, his arm swelling seemed to have appeared over a few weeks. He underwent neck surgery at his local hospital where the surgeon found an invasive thyroid tumor that he considered unresectable and merely performed a wedge biopsy. The pathologists thought the tumor was an anaplastic thyroid carcinoma and he was referred to our medical center. In August 1991, our initial examination disclosed a hoarse, but robust muscular man who had a large asymmetrical and very hard goiter that was adherent to surrounding tissues on the right. There was facial suffusion and edema, and dilatation of his neck veins and those of his right arm and thorax consistent with a superior vena cava syndrome. He had stridor with forced deep inspiration. Upon our review of the...

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...

Functional Anatomy of White Adipose Tissue

Flyer, noting that its administration restored plasma levels of thyroid, adrenal and gonadal hormones in fasting mice, hypothesised a prominent role for leptin in controlling the endocrine secretion in relation to food intake 19 . Accordingly, leptin functional receptors were identified in several peripheral organs 20 , considerably broadening its role.

Risk Factors and Cancer

Ionizing radiation is a universal but weak carcinogen.1,39 However, cumulative exposures from medical diagnostic and treatment procedures, commercial, occupational sources, or waste increase the risk of cancer. Leukemias and cancers of the breast, lung, and thyroid are typical but cancers of the stomach, colon, and bladder, and potentially any human tumor may be seen. Radiation can cause most types of cancer, especially myelogenous leukemia and cancers of the breast, thyroid, and lung. Some cancers that have not been linked to radiation include chronic lymphocytic leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, and cancers of the cervix, testis, prostate, and pancreas. Despite the massive radiation contamination resulting from the nuclear reactor accidents at Chernobyl and Chelyabinsk thus far the only well-documented increase in cancer is childhood thyroid cancer.40 Finally, genetic predisposition can increase the risk of developing cancer by exposure to radiation, as in the...

Cancer Screening Diagnosis and Prevention

Thus far, biological markers (biomarkers) have been used to diagnose cancer, and to monitor disease progression and recurrence after therapy.59-62 Biomarkers have substantially improved the understanding of the molecular mechanism of action of carcinogenesis and risk, although they are more useful for monitoring the consequences of the disease and therapy rather than assessing the effects of risk factors on the onset of the disease. For example the serum-based markers calcitonin, prostate-specific antigen, and CA-125 are all elevated in medullary thyroid, prostate cancer, and a small subset of ovarian cancers, respectively.63-65 Urine-based biomarkers like bladder tumor antigen, survivin, and calreticulin have been recently used as diagnostic marker for bladder cancer.66 Therefore improved modern molecular screening approaches may identify (1) high-risk patient groups who might benefit from more intensive screening as well as inclusion in trials of preventive agents and (2) indicators...

Etiology and Risk Factors

Lymphoma, sarcoma, melanoma, and cancer of the breast, thyroid, colon, and liver may also occur at higher frequency during this period of life in persons with inherited conditions (see Chaps. 9, 11, 12, 16-18, and 20). On aggregate, however, these cancers account for only a small proportion of the cancers that occur during adolescence and early adulthood.

Aberrant Cav1 Expression Complexity and Context

In accordance with that notion, some reports have documented down-regulation of Cav-1 in various malignant human tissues, including osteosarcomas 7 , fibrosarcomas 98 , colon cancer 6 , follicular thyroid cancer 1 , ovarian cancer 17, 98 , mucoepidermoid carcinoma of the salivary gland 79 , lung adenocarcinoma 46, 99 , and relatively small, estrogen receptor-positive breast cancer 73 . Numerous studies have not revealed any inactivating Cav-1 mutations in tumors with Cav-1 down-regulation, but the recent identification of a dominant-negative mutation, a proline-to-leucine substitution at position 132 in human breast cancer tissues, may lead to further information about tumor-suppressor functions of Cav-1 31 . Although there is not a perfect correlation, it is remarkable that many of these malignancies are of stromal cell origin. A recent novel and somewhat surprising observation is the reduction of Cav-1 levels in human cancer-associated fibroblasts from breast cancers and PCa 20, 60...

The Antigen Specificity of Naturally Arising TR

The presence of the corresponding organ, as adoptive transfer of T cells from male mice were more effective at preventing neonatal thymectomy-induced autoimmune prostatitis than oophoritis, and vice versa for T cells from female mice (Taguchi et al. 1994). Studies from Mason's group extended this observation by demonstrating that ablation of the thyroid gland resulted in the selective functional loss of T cells within the CD4+ population capable of preventing radiation-induced autoimmune thyroiditis, but not diabetes (Seddon and Mason 1999). Curiously, thyroid ablation did not result in the loss of protective thymic CD4+ T cells. Although the CD4+ T cell population was not fractionated in these studies to ensure that the suppressing cells were indeed CD25+ TR, these data support the hypothesis that tissue-specific antigen recognition by TR is necessary for their survival, development, and or expansion in the periphery, as the tissue-protective CD4+ T cell population is functionally...

Estrogen Receptors ERa and ER

Although estrogens are mainly produced locally by the ovaries, they exert systemic effects on selected target tissues. The action of the estrogens is mediated by two different estrogen receptors (ERs), ERa and ER 11 . ERa and ERjS are products of different genes and exhibit a tissue- and cell type-specific expression. The ERa is expressed primarily in the uterus, liver, kidney and heart, and sometimes it is co-expressed with the ER in mammary, thyroid and adrenal glands, in bone, and in the brain, where they can form functional heterodimers and where ER in many instances opposes the actions of ERa 11 . ERjS in contrast, is expressed specifically in the ovaries, in prostate, lung, in the gastrointestinal tract, bladder, and in the hematopoietic and central nervous system 11 .

CASE 1 Tshsecreting Pituitary Adenoma Case Description

A 54-yr-old African-American woman was seen at an urgent care facility because of the recent development of palpitations. When examined, she was noted to have a pulse of 100 bpm. Her thyroid was normal in size, and the rest of the physical examination was normal. Thyroid function tests were as follows T4 14 lg dL, T3RU 43 (25-35), thyroid-stimulating hormone (TSH) 1.6 mU L. These results were interpreted as indicating that the patient was euthyroid, and she was started on a P-blocker for symptomatic relief. However, one of the physicians in the urgent care center felt that the thyroid function tests were somewhat inconsistent, and called for further advice. Two weeks later, the patient presented for an evaluation. Since starting on atenolol 50 mg twice daily, her palpitations had resolved. She denied nervousness, tremor, hyper-defecation, insomnia, weakness, shortness of breath, chest pain, or symptoms of ophthal-mopathy. she had not noticed anterior neck discomfort, dysphagia,...

All cancers154118231980

Table 3.7 reports incidence rates for carcinomas. In 13- to 14-year-olds and 15- to 19-year-olds, the head and neck forms the most common primary site group for carcinomas, making up 46 and 41 , respectively, of all carcinomas among these two age groups, but in 20- to 24-year-olds, carcinomas of the head and neck region make up only 25 of all carcinomas. The thyroid is by far the most common primary site for carcinomas in the head and neck, and rates for carcinoma of the thyroid steadily increase across the three age groups. Nasopharyngeal carcinoma (NPC), which is extremely rare in the population in Britain in general, 19 makes up more than 10 of all carcinomas in 13-to 14-year-olds, but represents only 2 among 20- to 24-year-olds, although the rate is similar to that seen in the younger age group. There are also marked differences in the incidences of certain cancers in this age group by gender, ethnicity, and country that are described in more detail elsewhere 23, 24 . Ethnic...

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.

Temporal Trends in incidence

Marked increases in incidence were also seen for gonadal germ cell tumors (accounted for primarily by testicular tumors), melanoma, and carcinoma of the thyroid (in all cases p< 0.0001) (Fig 3.6). There was no corresponding significant increase in ovarian germ cell tumors. Colorectal carcinomas showed a significant trend, which was accounted for by an increase between the second and third time periods (p< 0.001) (Fig 3.6).

Histologic Grade of Malignancy

The histologic grading of malignancy is based on the degree of differentiation of a cancer and on an estimate of the growth rate as indicated by the mitotic index. It was generally believed that less differentiated tumors were more aggressive and more metastatic than more differentiated tumors. It is now appreciated that this is an oversimplification and, in fact, not a very accurate way to assess the degree of malignancy for certain kinds of tumors. However, for certain epithelial tumors, such as carcinomas of the cervix, uterine endometrium, colon, and thyroid, histologic grading is a fairly accurate index of malignancy and prognosis. In the case of epidermoid carcinomas, for example, in which keratinization occurs, keratin production provides a relatively facile way to determine the degree of differentiation. On the basis of this criterion, and others like it, tumors have been classified as grade I (75 to 100 differentiation), grade II (50 to 75 ), grade III (25 to 50 ), and grade...

Etiology and Pathogenesis 361 Etiology

Whereas cancers in infants and young children are likely to be influenced strongly by congenital and prenatal factors, and cancers in the elderly are most strongly linked with environmental causes, the cancers in adolescent and young adult patients may be an interesting combination of both. It has been possible to attribute only very few cancers in this age group directly to single environmental or inherited factors. An exception is clear-cell adenocarcinoma of the vagina or cervix in adolescent females, with most cases caused by diethylstilbestrol taken prenatally by their mothers in an attempt to prevent spontaneous abortion 42 . Radiation-induced cancer may occur in adolescents and young adults after exposure during early childhood rates of thyroid cancer in children and adolescents have increased in Eastern European and Slavic countries since the Chernobyl accident in 1986 43 . In fact, many of the adolescent and young adult cancers that have been linked to etiologic factors are...

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

Tissue distribution and ontogenic development

As described above, reductase activity is distributed amongst a host of different enzymes, and systematic studies on many aspects of this diverse enzymology, including tissue distribution and developmental studies of the human enzymes, are lacking. However, carbonyl-reducing enzyme activity is generally present in most human tissues, including the liver, lung, brain, heart, kidney, spleen, testis, and blood, and intracellularly, with a few exceptions, most of these enzymes are cytosolic in origin.73 Interestingly, NQO1, which has been associated with protection against carcinogenesis and mutagenesis, is expressed in many tissues, including epithelium of the thyroid, breast, colon, and eye, but is expressed at very low levels in the human liver. This contrasts with rat liver, which contains high levels of NQO1 and has been the enzyme's major source for purification.82

CASES 3 AND 4 Malabsorption Of Levothyroxine Case Descriptions

A 45-yr-old female had a 3-yr history of hypothyroidism. For the past year she had taken 300 g T4 tablets 6 d a week. She was intermittently fatigued and sometimes needed excessive sleep. She took no other medication. On examination, her height was 66 in and her weight was 198 lb. Her thyroid gland was small. Her serum free T4 was 1.7 ng dL (normal 0.8-1.8) and her TSH was 4.0 mU L, both normal. T4 was continued. One year later, she returned and was now ingesting her T4 tablets simultaneously with multiple supplements including St. John's wort, Kava-Kava, a natural energy tablet, vitamin B-12, vitamin E, and a multivitamin preparation. She reported that she took her thyroid tablets faithfully, 6 d a week as prescribed. Her tablets were inspected and they were the same brand tablets she was taking the year before. Her serum free T4 was normal at 1.3 ng dL, but her TSH was elevated to 11.38 mU L. She was instructed to take her T4 dose 4 h apart from her supplements. Nine weeks later,...

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

Deregulated Cytosolic Signaling Pathways

Different growth factors and cytokines transduce their growth-promoting signals through the activation of the small G protein Ras (Figure 4). This leads to activation of members of the Raf family of serine threonine kinases (c-Raf, A-Raf, and B-Raf) and its downstream effector, the mitogen-activated protein kinase (MAPK) kinase (MEK). This protein then phosphorylates and activates MAPK, the so-called extracellular signal-regulated kinase (ERK). The Ras-Raf-MEK-MAPK pathway controls the growth and survival of a broad spectrum of cancers. Thus, it has been shown by the expression of dominant negative or activated forms of MEK that the expression of cyclin D1, which leads to transition from G1 to S phase, is controlled by MEK signaling.287 Activating mutations in Ras and Raf are present in a large percentage of solid tumors. For example, the Ras oncogene is found mutated in its oncogenic form in 15 of human cancers, with subsequent activation of the MAPK pathway.288 The MEK and ERK...

Factors That Shape the Repertoire of CD25 Suppressor T Cells in the Periphery

For several reasons, it is unlikely that the composition of the suppressor T cell pool as it exists in a normal immune system is a linear projection of the intrathymically generated pool. First, extrathymic conversion of conventional, naive CD4 T cells into suppressor T cells may modulate the composition of the peripheral suppressor T cell pool. Although this has at present only been demonstrated in certain experimental systems (see preceding section), it appears reasonable to assume that the normal immune system in the steady state exploits similar pathways. Furthermore, there is accumulating evidence that the repertoire of suppressor T cells undergoes dynamic changes that are dictated by competition for survival factors such as access to cognate antigen or niches in the immune system. Among polyconal (non-TCR-transgenic) model systems, the most straightforward evidence in favor of interplay between an intra- and extrathymic encounter of self-antigen in the shaping of the repertoire...

Hypoglycaemic stimuli for research Insulin tolerance test

Prior to performing an insulin tolerance test, it is important to rule out complete deficiency of counterrgulatory hormones and establish cardiovascular status. A 9 am cortisol, baseline thyroid function and ECG should be checked as being normal before proceeding. In its simplest form, the insulin tolerance test comprises intravenous injection of soluble insulin

Telomeres And Direct Proof Of Their

Many reports have appeared suggesting a telomere-independent mechanism of cellular senescence is present in epidermal keratinocytes (39,40) and in mammary (39), adenoid (41), thyroid (42), and prostate (43) epithelial cells. The investigators who reported these findings found that inactivation of the p16 pRB pathway (by methylation of the p16 gene or by expression of viral oncogenes such as the human papilloma virus protein E7) was required before telomerase could immortalize these epithelial cells. Many of these epithelial cells were grown in a chemically defined medium in which the proliferative life span of 10-20 doublings is much less than the approximately 50 doublings that are seen when keratinocytes are grown on feeder layers (44). We have shown that keratinocytes can be immortalized by telomerase alone without inactivating p16 when grown in the more hospitable environment provided by feeder layers (which produce additional growth factors, extracellular matrix and or epithelial...

CASE 1 Child With Sclerosing Papillary Cancer Case Description

A 9-yr-old girl was referred to an endocrinologist in November 1995 after her pediatrician found a goiter. Her paternal grandmother and paternal uncle (who also had Down syndrome) both had thyroidectomies by age 20 yr for unknown reasons. The endocrinologist found the patient had high titers of antithyroid peroxidase antibodies, diagnosed Hashimoto's thyroiditis, and initiated thyroxine suppression therapy. In January 1996 her mother noted a swollen gland in the left posterior neck and in July 1997 found another swelling in the patient's anterior neck. Thyroid ultrasound and 123I scan showed a solid, cold, left thyroid nodule. Her endocrinologist found an enlarged thyroid, left cervical lymphadenopathy, and a firm nodular mass involving the right thyroid lobe. The preoperative chest X-ray showed a diffuse interstitial nodular pattern consistent with metastases. She was referred to surgery and underwent open biopsy of a slightly enlarged Delphian lymph node and the thyroid isthmus. The...

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.

CASE 2 Graves Disease And Papillary Cancer Case Description

In March 1997, a 41-yr-old white woman presented with a recent onset of hoarseness and the history of a knot in her neck. She had heat intolerance and weight loss despite a normal appetite, and fatigue and muscle weakness. Her mother had undergone a thyroid lobectomy in the past for a thyroid mass. On examination she was clinically thyrotoxic, showing resting tachycardia, fine tremor, stare, lid lag, and a diffusely enlarged thyroid with increased fullness in the left lobe that seemed adherent to surrounding tissues. Her serum free T4 was 3.6 ng dL (normal 0.8-2.4) and TSH was undetectable. A thyroid scan showed a diffusely enlarged gland with uniform uptake of radioiodine except for a cold area in the left lower lobe. Thyroid ultrasound revealed a 2.7-cm echogenic solid mass with an internal 1-cm hypoechoic area in the left lobe. Her chest X-ray was normal. FNA revealed PTC and she was referred to surgery after control of her thyrotoxicosis with methimazole. At time of surgery done...

Biological Background and Rationale

There are three members of the Raf family A-Raf, B-Raf, and C-Raf (Raf-1). C-Raf was first identified as the cellular homolog of the v-Raf oncogene and has been the subject of extensive study over the last two decades. However, in recent years, the focus has shifted to B-Raf after it was discovered that point mutations in B-Raf are prevalent (approximately 65 ) in human melanomas 16 . Subsequently, point mutations in B-Raf have been identified in other cancers including 40-70 of papillary thyroid cancers, 60 of low-grade ovarian tumors, and 4-16 of colorectal cancers 17 . The most prevalent point mutation in B-Raf, V600E, results in a constitutively active B-Raf. Presumably, the negatively charged glutamate mimics the phosphory-lation of a neighboring serine or threonine residue required for activation. Conversely, mutations in A-Raf and C-Raf are rare in human cancer 18,19 . Unlike A-Raf and C-Raf, B-Raf is primed for activation because the other critical residues that need to be...

Endocrine Disorders Associated with Myofascial Pain

Hypothyroidism is secondary to a lack of thyroid hormone production levothyroxine (T4) and liothyronine (T3) secondary to a problem with the hypotha-lamic-pituitary-thyroid (HPT) axis. Clinically, the patients are frequently overweight. Their eyelids may be puffy, their voice hoarse. The thyroid gland may be enlarged. Their muscles are stiff, tender, and, on occasion, weak. They may display muscle hypertrophy. TrPs are common. Their primary complaint may be diffuse muscle tenderness. The Achilles reflex may show delayed relaxation. Laboratory testing typically shows low serum thyroxine (T4), free thyroxine index, and a high thyroid-stimulating hormone (TSH) level.

CASE 3 Persistent Papillary Cancer Case Description

A 45-yr-old woman who had been treated for primary hypothyroidism from age 29 noted a thyroid mass in August 1994 that was cold by 123I scan and yielded indeterminate cytology by fine-needle aspiration (FNA) biopsy. At surgery done shortly after the FNA, frozen section biopsy revealed PTC and total thyroidectomy was performed. The final histologic sections showed this to be a multifocal bilateral PTC, the largest focus of which was 1.8 cm in the left lobe amidst a background of severe Hashimoto's thyroiditis. She was treated with 29 mCi of 131I in October 1994 when her thyroglobulin (Tg) was 73 ng mL (Table 3) and her 131I whole body scan (WBS) at 48 h showed an uptake of 0.4 in a thyroglossal duct remnant and bilateral thyroid bed. Fourteen months later, because of a persistent elevation in serum Tg and a nearly identical uptake and WBS, she was treated with 150 mCi of 131I. Ten-day posttherapy images demonstrated no uptake in the left thyroid bed, suggesting thyroid stunning or...

Tamoxifens Legacy A Menu of Medicines

The discovery of SERM action with tamoxifen227 has opened the door to discovering selective activity for all members of the steroid hormone receptor superfamily. A huge effort is under way to discover agonist and antagonists drugs for the androgen receptor, progesterone receptor, glucocorticoid receptor, thyroid hormone receptor, and the peroxisome proliferator-activated receptor (PPAR).

Congenital Generalised Lipodystrophy Berardinelli Seip Syndrome or Lipoatrophic Diabetes

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.

Pyridinium crosslinks

In both healthy individuals and in patient groups with osteoporosis, thyroid disorders, hyperparathyroidism and arthritic diseases. These observations paved the way for the development of direct immunoassays that initially measured both Pyd and Dpd along with small molecular weight substances (Mr < 1000). This was followed by the commercial development of specific monoclonal antibody-based assays that measure the more bone-specific crosslink, Dpd 9 . More recently, immunoassays for free urinary Dpd have become widely available on several types of automated immunoassay analyzers in reference laboratories and clinical laboratories.

CASE 2 Ectopic Acth Syndrome Case Description

Examination showed a mildly cushingoid man whose blood pressure was 142 98 mmHg, pulse 96, height 69-3 4'', weight 191 lbs. There was some mild facial rounding but no real plethora. He did have a slight increase in supraclavicular fullness. There was no proptosis or abnormal eye findings. His thyroid gland was not enlarged. He had

Diagnosis of Graves Disease

The diagnosis of Graves' disease, aside from a history of thyroid problems, uses measures of visual acuity, pupillary light responses, and ocular motility. The configuration and movement of the lid margins should be carefully studied. The slit-lamp examination should include the measure of intraocular pressure by applanation tonometry both in downgaze and in the primary position. Because of the foreshortened rectus muscle's traction on the globe, attempts to force the eye into the primary position often result in a marked, though transient, elevation of the intraocular pressure. Visual field testing and a sonographic determination of rectus muscle thickness by A-scan complete the workup. Echographic confirmation of rectus muscle thickening in the midportions of muscle belly, but with no thickening at the tendinous insertions, is characteristic of Graves' disease and differentiates it from orbital myositis, in which the inflammatory swelling extends all the way to the point of...

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.

CASE 3 Cushings Syndrome In A Child Case Description

Examination showed a cushingoid-appearing 11-yr-old girl whose height was 130.7 cm (52'') and weight 85 lbs. Her blood pressure was 104 70 mmHg, pulse 68 bpm. She had facial rounding with plethora and generalized obesity with increases in supraclav-icular fullness. There were no abnormal eye findings and her thyroid gland was normal. She had good muscle strength and no peripheral edema. Transsphenoidal pituitary surgery was performed and complete exploration of the pituitary revealed no evidence of a microadenoma. Based on the results of the IPSS, a right hemi-hypophysectomy was performed. Despite the fact that no definite tumor was identified during surgery or even in the histological specimen submitted to the laboratory, the patient promptly developed secondary adrenal insufficiency, which persisted for 2 yr following surgery. The patient had a significant weight loss of 10 lbs and gained 8 cm in height within 6 mo of surgery. Menarche occurred 20 mo following surgery. She had...

Balancing the Risk and Benefits of RT in Adolescent and young adult Patients

The same balance of risks concerning efficacy versus toxicity must be considered for the adolescent and young adult population, even though the neurocogni-tive toxicity of conventional RT doses at this age is not clear-cut due to the scarcity of good evidence from long-term follow-up studies. There is concern that, although early estimates of neurocognitive function after cranial radiation may be acceptable, long-term survival may reveal progressive accelerated cognitive decline in a proportion of the population, representing a hidden toxicity 100 . The risk of ovarian radiation from spinal fields is an important consideration, worthy of ovarian ultrasound for assessment and consideration of oophoropexy to a location outside the planned radiation fields. These concerns are greatest for those diagnosed in this young age group, as they have the longest time to live and to experience the tox-icity. The endocrine consequences of cranial RT are considerable. However, the availability of...

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...

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 .

The essential role of supportive care

With more aggressive interventions in controlling locoregional and recurrent disease, patients require close surveillance. The importance of a teamwork approach to treating HNC patients cannot be underestimated. The expertise of a radiation oncologist, speech therapist, pathologist, otolaryngologist, nurse, and oncologist is fundamental in the care of these patients. Evaluating the quality of life in these patients is also essential when determining the nature of such aggressive chemoradiotherapy that may alter the daily lifestyle of these patients physically, including physical appearance and loss of their voice, and psychologically patients may have to sacrifice simple capabilities such as their swallowing ability and appreciation of the texture of food. Additionally, the lifestyle of these patients has placed these patients at increased risk of developing a second malignancy of the aerodigestive tract. Consequently, we encourage monthly clinical exams on our patients following the...

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.

Leptin and Congenital Leptin Deficiency

Congenital leptin deficiency due to mutations in the leptin gene or receptor is a rare, but treatable, cause of severe early-onset obesity and various endocrine disturbances in both rodents and humans 74, 75 . According to the lypostatic theory, a state of 'perceived starvation' might exist in these subjects and results in a chronic stimulation of excessive food intake 39 . Leptin therapy has shown to have dramatically beneficial effects on weight, fat mass and appetite, hyperinsulinaemia and lipid levels, as well as on neuroendocrine phe-notypes and immune functions in these subjects 76, 77 . Leptin treatment blunts the changes in circulating thyroid hormone and corticosterone levels that are normally associated with food deprivation. It has been suggested that the inhibition of thyroid hormone secretion may have evolved to limit energy expenditure and prevent protein catabolism during starvation 78 . The effect of leptin on circulating thyroid hormone can be explained at least in...

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).

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).

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).

Basic Concepts for Assignment of the Reference Range

These statistical treatments are applicable for tests that have clinical significance at both high and low concentrations, for example, thyroid-stimulating hormone (TSH) for detection of hypo- and hyperthyroidism, respectively. For cardiac markers, only high results are significant, and therefore only an upper reference range limit is necessary. This is calculated as the mean plus 2 SD (Gaussian distribution) or the lower 97.5 of the test results (non-Gaussian). Use of the 99th percentile results in the mean plus 3 SD or the lower 99.5 of test results.

CASE 4 Its All In The Genes Case Description

The patient was taken to surgery where she underwent a bilateral total adrenalectomy. The right adrenal contained a pheochromocytoma with a diameter of 3 cm and the left adrenal contained a pheochromocytoma with a 6.5 cm diameter. She recovered well postoperatively and was discharged home, relieved of the adrenergic symptoms, with a normal blood pressure. Six weeks later, she underwent total thyroidectomy. At surgery, hard nodules were found in both lobes of the thyroid gland. Two superior parathyroid glands

Diagnosis and Clinical Presentation

In childhood, DTC usually presents as an asymptomatic neck mass 34, 35 . Occasionally, the diagnosis may be made incidentally after the discovery of pulmonary nodules on a chest radiograph. In any individual younger than 20 years of age presenting with a solitary thyroid nodule, there is a higher likelihood of malignancy 10, 36 . The overall prevalence of thyroid carcinoma is about 20-25 of thyroid nodules in children, compared to 5 in adults 10, 12, 37, 38 . Symptomatic thyroid cancers (i.e., those associated with hoarseness, dysphagia, or cough, thus suggesting more locally advanced disease) are rare in young individuals. Uncommonly, thyroid carcinoma arises ectopically in a thyroglossal duct remnant or cyst. Arguably, this would be an unusual presentation of childhood thyroid carcinoma, but it must be kept in mind for patients presenting with a midline mass in the region of the hyoid. Finally, although most patients are euthyroid at the time of diagnosis, rare cases of...

Radioimmunotherapy RIT

I-131 tositumomab I-131 tositumomab is a conjugate of the murine anti-CD20 antibody tositumomab and I-131. It is approved for use in patients with relapsed refractory follicular or transformed NHL. As with Y-90 ibritumomab tiuxetan, treatment occurs over about a week. Thyroid protection is required with I-131 tositumomab because of the radioactive iodine. I-131 is a gamma emitter, and dosimetry is required to provide patient-specific dosing. In a multicenter pivotal trial,86 65 of the 60 heavily pretreated patients with NHL responded including 20 CR. The response rate in the subset with follicular histologies was 81 . Response rates and response duration were significantly higher than from the last chemotherapy. The response rate has been 63 with 29 complete responses in rituximab-refractory patients.

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,

Differential Diagnosis

Mood and anxiety disorders, learning disorders, mental retardation, pervasive developmental disorders, organic mental disorders, and psychotic disorders may all present with impairment of attention, as well as hyperactive impulsive behaviors. The diagnosis of ADHD in DSM-IV-TR requires that the symptoms of inattention cognitive disorganization and impulsivity hyperactivity are not better accounted for by one of the above conditions. Differentiating ADHD from bipolar disorder in childhood is complicated by the low base rate of bipolar disorder and the variability in clinical presentation. Even though there are phenomenological similarities between the two disorders, there is little evidence to suggest that most children with externalizing symptoms are at risk for bipolar disorder. A positive family history of bipolar disorder is especially helpful in diagnosing bipolar disorder in children. In addition, a variety of medical conditions such as epilepsy, Tourette's disorder, thyroid...

Constitutive Androstane Receptor

Using a cell-based transfection assay, Negishi and colleagues screened a number of known nuclear receptors, such as RXR, CAR, LXR, thyroid receptor-a, hepatocyte nuclear factor 4 (HNF4), and chicken ovalbumin upstream promoter-transcription factor (COUP-TF), for their capacity to bind and transactivate the PBREM in reporter assays. The results indicated that CAR alone was able to stimulate the PBREM reporter gene expression 60 . Further NR1-affinity chromatography was used to purify the protein that bound to PBREM, and both binding assays and Western blot analysis proved that CAR was the protein mediating the PB induction response. Thereafter a group of structurally diverse compounds was identified to induce CYP2B through activation of CAR and thus was referred to as phenobarbital-type inducers. The most potent member from among these compounds is (TCPOBOP), which was originally identified as a pesticide contaminant 69 .

Genetic abnormalities

The most common aberration is the t(11 18)(q21 q21), which results in a fusion of the apoptosis inhibitor gene API2 with the MALT1 gene.27-29 The t(11 18) is present in 30-50 of extranodal MZL of MALT type, but not in nodal MZL lymphoma and splenic MZL.30 It is usually the sole cytogenetic alteration. The frequency of the t(11 18) in MALT lymphoma is site related more frequent in the GI tract and in the lung, less common in conjunctiva and orbit, and absent or almost absent in salivary glands, thyroid, liver, and skin.2631

Management of nongastric localizations

The stomach is the most common and best studied site of involvement, but MALT lymphomas have also been described in various non-GI sites, such as salivary gland, thyroid, skin, conjunctiva, orbit, larynx, lung, breast, kidney, liver, prostate, and even in the intracranial dura.53 5480 One-fourth of non-GI MALT lymphomas have been reported to present with involvement of multiple mucosal sites or nonmucosal sites such as bone marrow.53 54 Nevertheless, despite presenting so often with stage IV disease, they usually have a quite indolent course regardless of treatment type (5-year survival of 90 ). The rate of histologic transformation seems much lower than that in follicular lymphomas. Patients at high risk according to the IPI, and those with lymph node involvement at presentation, but not those with involvement of multiple MALT sites, have a worse outcome. Localization may have prognostic relevance. In a radiotherapy study from Toronto,70 gastric and thyroid MALT lymphomas had better...

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.

Autoimmunity in chronic hepatitis C

Hepatic infection with HCV is known to induce several hepatic and extrahepatic autoimmune manifestations. Extrahepatic manifestations include mixed cryoglo-bulinaemia, membranoproliferative glomerulonephritis, porphyria cutanea tarda, Sjorgen syndrome and autoimmune thyroid disease 4 . Not surprisingly, numerous autoantibodies are found to be associated with chronic hepatitis C, i.e. antinuclear antibody (ANA), smooth muscle antibody (SMA), LKM-1 and antithyroid autoantibodies 5 . However, in the majority of cases, these antibodies are not markers of real autoimmune diseases. LKM1 autoantibodies, for example, are detected in patients with AIH-2 and in 0-7 of patients with chronic hepatitis C

Causes of Malnutrition in the Elderly

These studies, most diagnoses were made from standard evaluations that included a careful history, physical examination, and basic screening lab tests (complete blood count, electrolyte, renal, liver and thyroid function test, stool haemoccult, chest radiograph, and urinalysis) 4-8 . The most interesting findings indicated that 10-36 of weight loss was due to an unknown aetiology 5, 6, 8 , 6-36 was due to neoplasm 4-6, 8 , 9-42 to depression and related psychiatric problems 4-6, 8 , and 14-19 to gastrointestinal and swallowing-related problems 4-6, 8 . Although it may be informative, from a clinical standpoint, to review all of the aetiologies that have been noted in case series and respective studies of weight loss in the elderly, Morley et al. 38 have devised a simple mnemonic for remembering the major causes of weight loss (Table 2).

Emmprin Stimulation of Fibroblasts

The mechanism whereby EMMPRIN upregulates transcription of the interstitial collagenase gene in fibroblasts is another interesting question yet to be solved. The interstitial collagenase promotor region contains a TATA box, a TPA responsive element (TRE), and a binding motif for the transcription factor PEA31,111 (see chapter 4). The TRE alone or in combintion with the PEA3 site, and possibly other upstream elements, controls the transcription of this gene. These regulatory sequences are recognized by transcription factors which are composed of proto-oncogene products. The PEA3 binding site interacts with the c-Ets protein, whereas the TRE element binds AP-1, a protein complex of homodimers and heterodimers of the fos and jun family. Thus, agents that modulate the expression of these proto-oncogenes also influence the transcription of the collagenase gene.1 Recently it has been shown that c-Ets-1 is expressed in mesenchymal cells adjacent to epithelial structures during morphogenetic...

The osteoporosis selfassessment tool

The final model included 11 variables that were significantly and independently associated with femoral neck bone density age, weight, current estrogen use, current thyroid hormone use, any fracture after age 45, spine fracture after age 45, Chinese or Thai ethnicity, and being from Malaysia, Hong Kong, or Taiwan. Each of these variables was assigned a value based on the regression coefficient for that variable in the statistical model. The index values for all 11 variables were then added for each woman. The sensitivity and specificity for an OSTA cutpoint of -1 were 95 and 47 , respectively. The AUC was 0.85. When thyroid hormone use and the three countries were dropped from the model, the AUC was still 0.83. Dropping Chinese and Thai ethnicity and current estrogen use lowered the AUC to only 0.80. Finally, dropping a history of any fracture or spine fracture after age 45 still resulted in an AUC of 0.79. This left only age and weight in the final index. Using an OSTA cutpoint of -1...

Glycosaminoglycans in Eye Diseases A Macular Corneal Dystrophy

Figure 1 Schematic diagram of the eye in horizontal section indicating each ocular component. a, corneal epithelium b, keratocyte c, corneal endothelium d, aqueous humor e, conjunctiva f, sclera g, trabecular meshwork h, iris i, lens j, ciliary zonule and body k, vitreous l, retina m, interphotoreceptor matrix n, retinal pigment epithelium o, Bruch's membrane p, choroid q, optic nerve head r, lamina cribrosa s, extrao-cular muscles and tissues. The candidate glycosaminoglycans involved in the ocular components of each eye disease described in this chapter are as follows macular corneal dystrophy (b, c KS, CS DS, HA), glaucoma (d HA g CS DS, HS, HA q, r CS, HS, HA), cataract (i CS DS, HS, HA), diabetic retinopathy (k HA l HS), retinal detach-ment proliferative vitreoretinopathy (k, l, m, n CS DS, HS, HA), myopia (f, p CS), thyroid eye disease (s CS, HA), pseudoexfoliation syndrome (c, d, g, h, i, j KS, CS DS, HA). KS, keratan sulfate CS DS, chondroitin sulfate dermatan sulfate HS,...

Current Treatment

Perhaps the earliest pharmacologic treatment of obesity that had a scientific basis was the use of thyroid extract, which dates from the late 1800s.4 Also of historical interest was the use of dinitrophenol, which came to be used after the observation in the early 1900s that textile workers lost weight after on-the-job exposure.5 Needless to say, this uncoupler of oxidative phosphorylation was discontinued due to serious side effects.

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....

Classification of Diabetes Mellitus and the Metabolic Syndrome

Immune-mediated diabetes, previously referred to as insulin-dependent diabetes, type I diabetes, and juvenile-onset diabetes, accounts for 5-10 of all cases of diabetes. Immune-mediated diabetes typically develops in childhood and adolescence, but has a variable age of onset ranging from infancy to the eighth and ninth decades of life. Abnormalities in glucose homeostasis result from severe insulin deficiency due to cell-mediated autoimmune inflammation (insulitis) and subsequent destruction of the b-cells of the pancreas. In T1DM, daily exogenous insulin administration is a life-sustaining intervention, and the absence of insulin can result in a state of acute metabolic decompensation known as diabetic ketoacidosis (DKA). Individuals with T1DM are at increased risk for other autoimmune disorders such as Graves' disease, Hashimoto's thyroiditis, Addison's disease, vitiligo, celiac sprue, autoimmune hepatitis, myasthenia gravis, and pernicious anemia. Thyroid hormone

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.

Other Conditions That Increase Natriuretic Peptides

Concentrations of BNP and NT-proBNP may be elevated in settings other than acute heart failure. Such increases do not represent analytic false positives but may cause false positive clinical diagnostic results, if other etiologies for abnormal BNP results are not considered. Disease processes other than heart failure (e.g., renal and thyroid function) have been shown to influence the concentration of natriuretic peptides (37). As an example, hyperthyroidism increases and hypothyroidism decreases natriuretic peptide concentrations (38). Renal impairment has been shown to increase NT-proBNP concentrations substantially and BNP to a lesser extent (39,40). In severe renal impairment (glomerular filtration rate of < 60 mL min1.73 m2 ) and end-stage renal diseases, testing of BNP or NT-proBNP may be difficult to interpret because decision limits for the diagnosis of heart failure or risk stratification were developed almost solely in patients without significant renal dysfunction....

CASE 1 Hirsutism Case Description

On examination, this patient was 65 in (1.67 m) tall and weighed 125 lbs (56.7 kg) (body mass index 21). She had 3+ out of 4+ facial hair noted on her chin, upper lip, and sideburn area. Hair growth was also noted on her midline chest and abdomen. There were no signs of thyroid disease or glucocorticoid excess. Breast development was Tanner stage 4 and there were no masses or galactorrhea. A pelvic exam revealed Tanner stage 5 pubic hair external and internal genitalia were normal, and there was no clitoromegaly. There were no other pertinent findings.

Assessment of Proptosis

Once thyroid disease and trauma have been excluded, the patient would require further investigations including systemic examination, full blood picture, orbital ultrasound, CT scan, magnetic resonance imaging (MRI) scan, possibly carotid angiography and sometimes orbital biopsy.

Endocrine Abnormalities and Cytokines

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

CASE 2 Amenorrhea And Pituitary Neoplasm Case Description

On examination, she had normal vital signs. She was 62 in tall and weighed 104 lbs. There were no signs of thyroid disease, glucocorticoid imbalance, or androgen excess. Breast development was Tanner stage 3 and there were no masses or galactorrhea. A pelvic exam revealed Tanner stage 3 pubic hair development. Her vagina was hypoestro-genic she had an unremarkable uterus and cervix. Neurologic exam was normal and there were no other pertinent findings.

Radiolabeled Antibodies

Adverse events included fatigue (43 ), fever (30 ), nausea (25 ), infection (25 ), chills (15 ), vomiting (13 ), pruritis (13 ), anorexia (10 ), and hypotension (10 ). The hematologic nadir occurred on days 43, 46, and 34 for red cells, white cells, and platelets, and median recovery occurred at 74, 78, and 73 days, respectively. In this study, five patients developed myelodysplastic syndrome 1.2-7.5 years after treatment, but all had previously received alkylating agents.25 Two patients later developed bladder cancer, but both had previously received cyclophosphamide. An elevation of Thyroid stimulating humane (TSH) was noted in five patients, but was asymptomatic in all five.

Rsk Reduction in Women with Inherited Predisposition to Breast cancer

Affected patients have a 50 risk of developing cancer by age 35 years and a 90 lifetime risk. The syndrome is characterized by pediatric bone or soft tissue sarcoma, early-onset breast cancer, and other cancers including those affecting the brain, lung, and adrenals, and leukemia. Cowden's syndrome is caused by a mutation in the PTEN gene on chromosome 10 84 . Affected patients have multiple hamartomas and an increased risk of developing breast or thyroid carcinoma at a young age.

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...

Posttranslational Modification Of Nonhistone Proteins Involved In Cancer

NRs are highly conserved transcriptional regulators known to control home-ostasis, development, reproduction, metabolism, and disease progression 59 . Hormones such as estrogen (E2), dihydroxytestosterone (DHT), retinoic acid, thyroid hormone, and or vitamins stimulate the activity of these receptors. Upon cellular exposure to a hormone, the activated receptor may bind directly to DNA, resulting in transcription of target genes. NRs such as the estrogen receptor (ER) and the androgen receptor (AR) are major contributors to cancer cell proliferation and overall tumor metastasis. More specifically, the ER's presence is crucial in breast cancer development and progression, while the AR is functional throughout all stages of prostate cancer. Other NRs such as the peroxisome-proliferating activating receptor gamma (PPARy) and the progesterone receptor (PR) have also been implicated in the onset and progression of breast, thyroid, and colon cancers and are also suggested to be highly...

Guidelines And Recommendations

The optimal management of patients with NLPHL is uncertain and controversial. The NCCN guidelines for patients with NLPHL are complex and distinctly different than for patients with CHL these recommendations are based on lower-level evidence including clinical experience, and are not always with uniform agreement among the panel members.62 For patients with CS IA NLPHL confined to the high neck (above the hyoid bone), the NCCN guidelines recommend IF or regional RT. For patients with CS I-IIA disease at other locations, the guidelines generally recommend IF or regional RT (with or without initial chemotherapy), while for patients with more advanced disease, the guidelines recommend chemotherapy with or without RT. For patients with CS III-IVA, observation is also offered as a management option. The National Cancer Institute Physician's data query (NCI PDQ) website suggests that patients with nonbulky, stage I LPHL presenting in a unilateral high neck (above the thyroid notch),...

Solid Tumors Incidence And Risk Factors

Radiation therapy is the most significant risk factor for developing solid tumors after lymphoma, with the majority of second cancers arising either within or at the edges of radiation fields. In the aforementioned series, temporal trends and treatment group distribution for cancers of the esophagus, stomach, rectum, breast, bladder, and thyroid all suggested a radiogenic effect. Three case-control studies have carefully evaluated the dose-response relationship between exposure to radiation therapies and the development of breast cancer and lung cancer, and demonstrated a significant trend of increasing risk of tumor development with increasing radiation dose.4-6

Hyaluronan in the Stroma of Epithelial Malignancies

The connective tissue stroma that surrounds most epithelial cancers is enriched in hyaluronan. Examples of tumors with a hyaluronan 'halo' include breast (27), prostate (53), ovarian (54), lung (33), gastric (29), colon (36), thyroid (55), and skin squamous cell (56) carcinomas. These hyaluronan deposits can serve as strong indicators of unfavorable prognosis for the patients (27,33,53-55,57) and probably contribute to the spreading of the malignant epithelial cells. Several mechanisms are likely to contribute to the hyaluronan accumulation. The malignant epithelial cells secrete (growth) factors, like TGFb (58), that stimulate the synthesis of hyaluronan by the stromal cells in a paracrine manner (59,60).

Hormonal regulation of bone remodeling

Calcitonin is a product of the thyroidal C cells. Its secretion is stimulated by high serum calcium levels. The peptide has been shown to inhibit osteoclast activity rapidly and thus decreases serum calcium levels. While calcitonin is an important clinical marker of medullary thyroid cancer, its relevance in human calcium homeostasis and bone metabolism has not been well established.11

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,...

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,...

Second Primary Neoplasms after Hodgkin Lymphoma

In contrast to radiotherapy for Hodgkin lymphoma being, at most, weakly leukemogenic, it is associated with an increased risk of several solid cancers including breast, lung, thyroid, stomach, bone, soft tissue, skin, and possibly colon and pancreas 12 . These excess risks of solid tumors tend to emerge by about a decade after Hodgkin lymphoma, and again, in contrast to leukemia, the excess risk is still increasing after 15 years of follow-up. Excesses of cancers of several other sites have been observed after Hodgkin lymphoma including thyroid, stomach, bone, non-Hodgkin lymphoma (NHL), and melanoma 12 .

Second Primary neoplasms after Breast cancer

As noted in a review 12 , before the implementation of breast-conserving surgery and localized radiotherapy to treat node-negative breast cancer, the principal method of local control was radical mastectomy and extensive radiotherapy to the chest wall and lymph nodes. Consequently, such women have experienced an excess risk of leukemias and cancers of the contralateral breast and lung, and possibly of esophagus, bone, connective tissue, and thyroid gland 22-26 . The risk of second primary leukemia is associated with radiotherapy (relative risk 1.8), alkylating agents (relative risk 6.5), and both (relative risk 17.4) 23 . The radiation dose to the contralateral breast can amount to several Grays and a review 12 has inferred that women irradiated in young adulthood are probably at increased risk of contralateral breast cancer, based mainly on one study 22 . However, another review 27 suggests no convincing evidence of such an effect. As the dose and effect appear to be less than...

Other Endocrinopathies

Radiation may affect the thyroid gland. Patients that received radiation to the neck or craniospinal irradiation are at risk of thyroid dysfunction. This may take the form of hypothyroidism, thyrotoxicosis, or thyroid nodules, which may be malignant. Patients at risk should have regular thyroid function tests performed and their thyroid should be examined by palpation on an annual basis. Endocrine dysfunction of the thyroid should be managed as for any patient with hypo- or hyperthyroidism. The presence of nodules should be treated seriously and referral for thyroidectomy made where appropriate 88 .

Exposures from Nuclear Medicine Studies

Radionuclides such as iodine-131 cross the placenta and can pose fetal risks. After 10 weeks gestational age, the fetal thyroid accumulates iodine. High fetal thyroid doses from radioiodine can result in permanent hypothyroidism. If pregnancy is discovered within 12 hours of radioiodine administration, prompt oral administration of stable potassium iodine (60-130 mg) to the mother can reduce the fetal exposure.

Recommendations for Screening

The Scottish Intercollegiate Guidelines Network (SIGN) has also released an evidence-based guideline (Long-Term Follow-up of Survivors of Childhood Cancer A National Clinical Guideline). The SIGN guideline is targeted to provide a framework for the follow-up of young people who have survived cancer and covers five key areas, including growth, puberty and fertility, cardiac function, thyroid function, and neurodevelopment and psychological health. At this time, the guideline does not address long-term follow-up of the renal, pulmonary, gastrointestinal, ocular, auditory, or musculoskeletal systems and does not provide guidance regarding surveillance for second malignancies. The guideline can be downloaded in its entirety from www.sign.ac.uk.

Delirium Due to a General Medical Condition

Metabolic and Endocrine Disturbances. Metabolic causes of delirium include hypoglycemia, electrolyte disturbances, and vitamin deficiency states. The most common endocrine causes are hyperfunction and hypofunction of the thyroid, adrenal, pancreas, pituitary, and parathyroid. Metabolic causes may involve consequences of diseases of particular organs, such as hepatic encephalopathy resulting from liver disease, ure-mic encephalopathy and postdialysis delirium resulting from kidney dysfunction, and carbon dioxide macrosis and hypoxia resulting from lung disease. The metabolic disturbance or endocrinopathy must be known to induce changes in mental status and must be confirmed by lab

Collagenases in Carcinomas

A number of tumors become encapsulated by fibrillar collagens. A good example of this is seen in thyroid cancer, which is not typically invasive, but is associated with the expression of collagenase by host cells, not by tumor cells.64 Liver tumors, which are often delimited by collagen fibrils, also express interstitial collagenase. Terada et al showed that all cholangiocarcinoma biopsies studied expressed collagenase as detected by immunostaining.21 In all cases, expression was localized to both tumor cells and tumor stroma. Interestingly, Okazaki et al recently demonstrated that, in hepatocellular carcinoma, only early lesions with well-differentiated tumor cells expressed collagenase mRNA, as detected by in situ hybridization.22 More advanced lesions showed no collagenase expression. Early lesions were characterized by tissue destruction and the lack of a fibrous capsule. In more advanced tumors, cells were less differentiated, showed high proliferative rates, and demonstrated...

Risk Based Healthcare of Survivors

Faced with these risks and challenges, how can the healthcare delivered to survivors be optimized It is important to recognize that there is a window of opportunity to modify the severity of health outcomes by prevention or early intervention. Early diagnosis and intervention or preventive care targeted at reducing risk for late effects can benefit the health and quality of life of survivors 6 . The outcomes of the following late effects can be influenced by early diagnosis and early intervention second malignant neoplasms following radiation therapy (breast, thyroid, and skin), altered bone metabolism and osteoporosis, obesity-related health problems (dyslipidemia, hypertension, diabetes mellitus, cardiovascular disease), liver failure secondary to chronic hepatitis C following blood transfusion, and endocrine dysfunction following chest mantle or cranial radiotherapy. Primary, secondary, and tertiary prevention, including tobacco avoidance cessation, physical activity, low-fat diet,...

Erick J Richmond MD and Alan D Rogol MD PhD

The initial laboratory exams showed the following Na 141 mEq L, K 4.2 mEq L, T4 8.3 mcg dL thyroid-stimulating hormone (TSH) 1.2 IU mL, luteinizing hormone (LH) 0.03 IU L, follicle-stimulating hormone (FSH) 0.38 IU L, testosterone 83 ng dL (normal < 10 ng dL), dehydroepi-androsterone sulfate (DHEAS) 281 mcg dL (normal 5-57 mcg dL), plasma renin activity 610 ng dL h (normal 100-650 ng dL h). Bone age 11 yr.

Development Of Endodermderived Organs

The digestive system develops from an early endodermal structure known as the primitive gut. In the human, the primitive gut forms at about 16 days following the conception and is composed of three parts in the early stage the foregut, the midgut, and the hindgut. At about 22 days, the liver bud forms from the foregut and is the presumptive structure for the formation of the liver. At about 28 days, the anterior end of the foregut opens up to form the oral opening, which is the presumptive structure of the mouth. The foregut also gives rise to the pharynx, esophagus, thyroid bud, and lung bud, and stomach at about the

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...

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...

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