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. More here...

The Natural Thyroid Diet Summary

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Benign Disorders of the Thyroid Gland

The thyroid gland, the largest endocrine organ, weighs about 20 g. It develops from an evagination in the base of the tongue at the foramen cecum and descends anterior to the larynx via the thyroglossal duct the latter usually disappears or remains as the pyramidal lobe. Congenital anomalies result from persistence of the thyroglossal duct or abnormal descent of the thyroid gland1 1. Persistent thyroglossal duct anomalies. In some patients, the epithelium of the thyroglossal cyst may persist as a fistula or a blind-ended cyst usually located above the thyroid cartilage. Thy-roglossal duct cysts, however, may present as midline structures from the base of the tongue to the suprasternal notch. Excision of the fistula or cyst should include resection of the midsection of the hyoid bone to avoid recurrence (Sistrunk operation). About 1 of thyroglossal duct cysts contain a focus of papillary thyroid cancer and about 25 of these patients have thyroid cancer elsewhere in the thyroid gland....

Differentiated Thyroid Carcinomas

The scope of this chapter is confined to differentiated thyroid follicular cell-derived carcinomas, which typically account for 80 to 95 of all thyroid cancers for the purposes of the present discussion, the term differentiated thyroid carcinomas (DTCs) will be used. Papillary thyroid carcinomas (PTCs) account for about 75 to 90 of DTCs, the remaining 10 to 25 being follicular thyroid carcinomas (FTCs) or their variant, Hurthle cell carcinomas (HCCs).1

Autoimmune Diseases of the Thyroid

Autoimmunity to thyroid antigens is the most common cause of thyroid diseases including Hashimoto's thyroiditis (HT), Graves' disease (GD), and primary myxedema (PM). Different autoimmune diseases of the thyroid share similar Fig. 14.1 Regulation of thyroid hormone production. The upper panel shows a normal hypothalamus-pituitary-thyroid axis, which maintains hormonal homeostasis and regulates normal thyroid function. The middle panel illustrates the effects of stimulatory Abs (TSAb) as seen in patients with Graves' disease. The lower panel shows the effects of blocking Abs (TSBAb) as seen in patients with primary myxedema. Fig. 14.1 Regulation of thyroid hormone production. The upper panel shows a normal hypothalamus-pituitary-thyroid axis, which maintains hormonal homeostasis and regulates normal thyroid function. The middle panel illustrates the effects of stimulatory Abs (TSAb) as seen in patients with Graves' disease. The lower panel shows the effects of blocking Abs (TSBAb) as...

Autoantibodies in Thyroiditis

Autoimmune thyroid diseases are characterized by the presence of autoantibodies to multiple thyroid antigens 1 including thyroglobulin (TG), thyroid peroxidase (TPO), and the TSHR. As mentioned above, these proteins play essential roles in the production of thyroid hormone. With respect to specific diseases, Over 90 and 80 of patients with GD have anti-TSHR and anti-TPO autoantibodies, respectively, while over 90 of patients with HT have anti-TPO and or anti-TG autoantibodies. Unlike anti-TSHR antibodies, anti-TPO and anti-TG antibodies do not play a significant role in the pathogenesis of either HT or GD. However, they are helpful in the differential diagnosis and may serve as predictors of ensuing thyroiditis. The Whickam study, an extensive population-based study, showed that after a 20-year follow-up, the odds ratio (with 95 confidence) of developing thyroiditis in individuals with thyroid autoantibodies and elevated TSH but normal free T4 was 38 (22-65) for men and 173 (81-370)...

Thyroid Hormone Suppression Therapy

The rationale for thyroid-suppressive therapy in DTC is based on many studies showing that TSH, by bind Figure 2-16. Patient with follicular thyroid carcinoma post-total thyroidectomy in whom an asymptomatic solitary left frontal bone metastasis was detected on low-dose 131I diagnostic scan (not shown). A, Total-body scan performed 72 hours after high-dose (200 mCi) radioactive iodine (131I) therapy showing avid 131I uptake (arrowheads) in the left frontal bone and a lesser degree of 131I in the thyroid remnant (arrow). B, A second dose of 200 mCi 131I was administered 6 months later. Post-therapy scan now showed minimal 131I uptake in the left frontal bone (arrowheads) as well as the thyroid remnant (arrow), indicating dramatic treatment response. C, Further diagnostic scan performed 6 months later showed no 131I uptake in the skull or thyroid bed, indicating complete treatment response (outline of the patient's head and clavicles represented by the surface marker). Courtesy of E. S....

Medullary Thyroid Cancer

Medullary thyroid cancer (MTC) is a relatively rare malignancy, accounting for 3 to 8 of all thyroid cancers however, it is responsible for up to 14 of all thyroid cancer deaths.1-3 In 1959, MTC was described as a unique clinical entity by Hazard and colleagues.4 It is distinct from other thyroid carcinomas because it originates from parafollicular cells of the thyroid gland. Furthermore, MTC has a distinct clinical behavior, hereditary occurrence, and molecular biology. The tremendous advances and application of molecular medicine to patient care parallel the advances made in understanding the pathogenesis and genetics of MTC.3 MTC has been recognized to occur in hereditary and sporadic forms because of the early contributions of Sipple. The introduction of fine-needle aspiration (FNA) cytology has allowed for accurate preoperative diagnosis of MTC, which has allowed for the selection of the appropriate initial extent of surgical resection preoperatively. Measurement of basal and...

The oesophagus and trachea and the thyroid gland

Inferior thyroid artery The thyroid and its blood supply. A large part of the right lobe has been removed Superior thyroid artery Sternothyroid Inferior thyroid artery Inferior thyroid veins Left brachiocephalic vein The thyroid and its blood supply. A large part of the right lobe has been removed

The Parathyroid Glands

The parathyroid glands are partially embedded in the posterior surface of the thyroid (fig. 17.9). There are usually four, each about 3 to 8 mm long and 2 to 5 mm wide. They secrete parathyroid hormone (PTH) in response to hypocalcemia. PTH raises blood calcium levels by promoting the synthesis of calcitriol, which in turn promotes intestinal calcium absorption by inhibiting urinary calcium excretion by promoting phosphate excretion (so the phosphate does not combine with calcium and deposit into the bones) and by indirectly stimulating osteoclasts to resorb bone. PTH and calcium metabolism are discussed in more detail in chapter 7.

Medullary Thyroid Carcinoma

Recommended surgical treatment of MTC is influenced by several factors. First, the clinical course of MTC is usually more aggressive than that of differentiated thyroid cancer, with higher recurrence and mortality rates. Second, MTC cells do not take up radioactive iodine, and radiation therapy and chemotherapy are ineffective. Third, MTC is multicentric in 90 of patients with the hereditary forms of the disease. Fourth, in patients with palpable disease, over 70 have nodal metastases. Lastly, the ability to measure postoperative stimulated calcitonin levels has allowed assessment of the adequacy of surgical extirpation. Screening for pheochromocytoma should be done before performing thyroid surgery. If patients are found to have evidence of pheochromo-cytoma, adrenal surgery with perioperative alphablockade should precede other procedures. Preventive thyroidectomy is recommended before age 6 years in patients with MEN type IIA and FMTC. Patients with MEN type IIB should undergo...

Followup Of Thyroid Cancers

Papillary thyroid carcinoma with symptomatic bone metastases. A, Plain radiograph of the thoracolumbar spine showing partial destruction of T11 and T12 vertebral bodies, resulting in scoliosis. B, Total-body scan performed 72 hours after a high-dose (200 mCi) radioactive iodine (1311) therapy showing intense 1311 uptake in vertebral bodies (arrow) and lesser degrees of 131I uptake in the ribs and the skull (shorterarrows), indicating multiple sites of bony metastases. Unlike the case shown in Figure 2-15, this patient is unlikely to achieve complete treatment response. B, (1) anterior view, (2) posterior view. Courtesy of C. H. Goh, MD, Department of Nuclear Medicine, Singapore General Hospital, Singapore. Figure 2-17. Papillary thyroid carcinoma with symptomatic bone metastases. A, Plain radiograph of the thoracolumbar spine showing partial destruction of T11 and T12 vertebral bodies, resulting in scoliosis. B, Total-body scan performed 72 hours after a high-dose (200...

Parathyroid Disease

This patient with multiple endocrine neoplasia (MEN) type IIB had recurrent elevation of calcitonin levels 20 years after total thyroidectomy for medullary thyroid cancer (MTC). Redo central neck dissection and bilateral functional neck dissections (microdissection) were performed. A, View of the trachea and dissected central and left paratracheal compartment. The photograph was taken from the patient's left side. The patient's head is to the right and the chest is to the left. CA left carotid artery IA innominate vein LJV left jugular vein LRN left recurrent laryngeal nerve T trachea VN left vagus nerve. Note markedly enlarged nerves characteristic of MEN type IIB. B, Surgical specimen from the same patient. The photograph shows central and upper mediastinal nodes (level VII), bilateral paratracheal nodes (level VI), and bilateral jugular chain and posterior triangle nodes (levels II, III, IV, and V). Microscopic foci of MTC were found in paratrachal dissection...

Steroids and Thyroid Hormone

The hydrophilic steroid and thyroid hormones easily penetrate the phospholipid plasma membrane of a target cell and enter the cytoplasm. Steroids enter the nucleus and bind to a receptor associated with the DNA. The receptor has three functional regions that explain its action on the DNA one that binds the hormone, one that binds to an acceptor site on the chromatin, and one that activates DNA transcription at that site. Transcription produces new Even though T4 constitutes 90 of the secreted thyroid hormone, it has little direct metabolic effect on the target cells. Unbound T3 and T4 enter the target cell cytoplasm, where an enzyme converts the T4 to T3 by removing one iodine. T3 binds to receptors in three sites on mitochondria, where it increases the rate of aerobic respiration on ribosomes, where it stimulates the translation of mRNA and thus increases the rate of protein synthesis and in the nucleus, where it binds to receptors in the chro-matin and stimulates DNA transcription...

Thyroid and Parathyroid Disorders

Endemic Goiter

Congenital hypothyroidism is thyroid hyposecretion present from birth it was formerly called cretinism, now regarded as an insensitive term. Severe or prolonged adult hypothyroidism can cause myxedema (MIX-eh-DEE-muh). Both syndromes are described in table 17.8, and both can be treated with oral thyroid hormone. A goiter is any pathological enlargement of the thyroid gland. Endemic goiter (fig. 17.25) is due to dietary Figure 17.25 Endemic Goiter. The thyroid gland has hypertrophied as a result of iodine deficiency, leading to TSH hypersecretion. Figure 17.25 Endemic Goiter. The thyroid gland has hypertrophied as a result of iodine deficiency, leading to TSH hypersecretion. iodine deficiency. There is little iodine in soil or most foods, but seafood and iodized salt are good sources. Without iodine, the gland cannot synthesize TH. Without TH, the pituitary gland receives no feedback and acts as if the thyroid were understimulated. It produces extra TSH, which stimulates hypertrophy of...

Thyroid Surgery

Surgery is the primary treatment for DTC and should be performed by a surgeon with expertise in thyroid surgery. In the very low-risk patients with a single small focus of PTC (s 1.0 cm) confined within the thyroid lobe, a lobectomy and isthmusectomy may be adequate as most studies do not demonstrate better survival rates after a total or near-total thyroidectomy compared with a lobectomy plus an isthmusectomy. Because PTC is a potentially multicentric and bilateral disease, one should, however, recognize a small but significant long-term risk of local recurrence after unilateral lobectomy.1518

The Thyroid Gland

The thyroid gland produces the thyroid hormone that is required to maintain normal metabolism of the body. A highly regulated feedback loop controls thyroid function and helps maintain the euthyroid status (Fig. 14.1). Thyroid-stimulating hormone (TSH) is produced in the anterior pituitary in response to stimulation by thyroid-releasing hormone (TRH) produced in the hypothalamus. The TSH binds to the thyrotropin receptor (TSHR), which then activates adeny-lyl cyclase and phosphatidyl inositol pathways and leads to the production of thyroid hormone. Hormone production begins when tyrosine residues of the thyroglobulin (Tg) are iodinated and then coupled through the catalytic action of the thyroid peroxidase (TPO), leading to the formation of the thyroid hormone precursor T4. The T4 undergoes deiodination and results in the formation of the thyroid hormone triiodothyronine (T3). The T3 binds to its cognate receptor in cells throughout the body and forms a complex, which is translocated...

Hypothyroidism

Autoimmune thyroiditis is the commonest primary cause, whilst the sequelae of surgical or radioiodine treatment of thyroid disease are also common. Deficiency of circulating thyroid hormone results in retardation of all body functions. Since thyroxine is an inotropic agent and a vasodilator, its routine use in cardiac surgery in patients without thyroid disease has been suggested. However, there is no evidence to show that it is of benefit (Bennett-Guerrero et al 1997).

Thyroid disease

Thyroid disease is associated with changes in the skin, which may sometimes be the first clinical signs. There may be evidence of the effect of altered concentrations of thyroxine on the skin, with changes in texture and hair growth. Associated increases in thyroid stimulating hormone concentration may lead to pretibial myxoedema. In autoimmune thyroid disease vitiligo and other autoimmune conditions may be present.

Thyroid Gland

Spinal Cord Nursing

The thyroid gland is just inferior to the thyroid cartilage of the larynx. It has two main lobes and a small connection between them called the isthmus. The histology of the thyroid is very distinctive. There are cells called follicular cells forming a sphere and these make up the follicle. Inside the follicle is the colloid where thyroid hormones are stored. The parafollicular cells are between the follicles. Label the main parts of the thyroid gland, the follicular cells, the parafollicular cells and the colloid and color them in. Thyroid cartilage Thyroid cartilage Answer Key a.Thyroid gland, b. Right lobe, c. Isthmus, d. Left lobe, e. Colloid, f. Follicular cells, g. Parafollicular cells

Thyroid Hyperplasia

Although thyroid neoplasms have been commonly reported in fish, most of these thyroid masses were probably goitres rather than neoplasms (Harshbarger, 1984 Hoover, 1984b Leatherland, 1994). Thyroid hyperplasia occurs most often in captive fish or in wild fish from certain geographical areas such as the Great Lakes. Prevalence of these lesions can be high, up to 93.5 in Lake Erie coho salmon (Oncorhynchus kisutch), and the lesions can occur seasonally (Leatherland and Sonstegard, 1980). Causes of goitre in fish are not always evident but can include endocrine stimulation of the thyroid, problems with iodine metabolism, or direct stimulation of the thyroid (Leatherland, 1994). Exposure to goitrogens can reduce or eliminate thyroxine (T4) synthesis or release from the thyroid without the normal negative feedback of T4 on the pituitary, thyrotropin secretion rates increase. The higher concentration of circulating thyrotropin stimulates the thyroid, resulting in hyperplasia and depletion...

Parathyroid Glands

Inferior Constrictor

There are typically four glands on the posterior of the thyroid gland and these are known as the parathyroid glands. They secrete a hormone called parathormone which regulates calcium balance in the blood. Parathormone increases blood calcium levels by causing more absorption of calcium from the digestive tract, increased osteoclast activity in the bones, and reabsorption of calcium from the kidney. The principal or chief cells secrete parathyroid hormone. The oxyphilic cells are less common and their function is poorly understood. Label the parathyroids on the posterior thyroid gland and color them in. Answer Key a. Thyroid gland, b. Parathyroid glands, c. Principal (chief) cells, d. Oxyphilic cells

Parathyroid Hormone

Pth And Renal Funciton

Parathyroid hormone (PTH) is secreted by the parathyroid glands, which adhere to the posterior surface of the thyroid gland (see fig. 17.9). These glands release PTH when the blood calcium is too low. A mere 1 drop in the blood calcium level doubles the secretion of PTH.

Classification And Staging

Until recently, the proliferation of tumor staging systems for DTC led to much heterogeneity and difficulty in comparing the results across institutions. Therefore, acceptable rules for a staging system in DTC have been adopted by the American Joint Committee on Cancer (AJCC) and the Tumor-Node-Metastasis (TNM) Committee of the International Union Against Cancer (UICC) (Table 2-1). An interesting feature of the TNM staging system is the primacy of the patient's age at diagnosis irrespective of the T and N categories, patients below 45 years and with no distant metastases have stage I disease, whereas those with distant metastases are classified as having stage II tumor. In patients aged 45 years and older, however, the staging system for papillary and follicular thyroid cancer follows the conventional paradigm and is similar to that adopted for patients with medullary thyroid

Practical Aspects Of Radioactive Iodine Imaging And Therapy

Preparation of patients with thyroid hormone withdrawal and dietary iodine restriction is essential for optimal 131I imaging or therapy. For patients currently on thyroid hormone suppression therapy, the T4 is withdrawn for 4 to 6 weeks with a substitution of triiodothyronine (T3) for 2 to 3 weeks. Then T3 is discontinued and the patient is placed on a low-iodine diet (< 50 pg d) for 1 to 2 weeks prior to the 131I uptake and scan study. This regimen will allow 90 of patients to achieve a serum TSH concentration > 30 mU L to stimulate iodide uptake by residual thyroid tissue. At the University of California-San Francisco, an outpatient dose of 30 to 50 mCi 131I is used to ablate residual thyroid tissue at 6 to 12 weeks after operation if focal uptake is detected in the thyroid bed on a 2 to 3 mCi 131I diagnostic scan. Conversely, patients It usually takes 6 to 12 months after initial therapy for 131I to achieve maximal effects. Serum TSH and Tg concentrations may be measured every...

Role Of Recombinant Human

The recent availability of clinical grade rhTSH coincided with the cessation of the production of bovine TSH (bTSH). The latter was used clinically to stimulate 131I uptake by metastatic thyroid cancer lesions however, it had a number of side effects, which were sometimes severe. Clinical trials soon demonstrated that rhTSH is able to replace the need for patients with DTC to undergo T4 withdrawal to have whole-body 131I study and serum Tg testing, while eliminating the undesirable side effects of bTSH.23 This compound has been approved by the US Food and Drug Administration for use as an adjunctive diagnostic tool for serum Tg testing and 131I imaging in the follow-up of patients with DTC. However, it must be appreciated that there remains a small risk of missing a diagnosis of residual cancer or of underestimating the extent of disease with rhTSH-mediated testing and that thyroid hormone withdrawal testing remains the standard diagnostic modality, especially in high-risk patients....

Complications And Postoperative Care

The complications and immediate postoperative care in surgery for the various endocrinopathies in MEN type II are similar to those described in more detail in the previous chapters dealing with each specific disease. In thyroidectomy for MEN type II-related MTC, the complications include injury to the recurrent laryngeal nerve, hypocalcemia secondary to parathyroid damage, and compromise of the airway secondary to hematoma formation. These complications are very unusual in the hands of an experienced thyroid surgeon. If both recurrent nerves have been injured (which may occur in a patient after multiple operations or extensive tumor involvement), a tracheostomy may be necessary. Fiberoptic laryn-goscopy is done to monitor vocal cord function. After total thyroidectomy with parathyroid autotransplantation, it is necessary to supplement calcium, vitamin D, and thyroid hormone. Calcium and vitamin D supplementation is withdrawn 4 to 8 weeks postoperatively as the parathyroid grafts begin...

Role Of Radioactive Iodine Therapy

Radioactive iodine (131I) therapy is well accepted as an adjunct to surgery for both ablation of postoperative thyroid remnants and treatment of metastatic Figure 2-12. Radiograph of the neck and upper chest of a patient following injection of iodized oil (Lipiodol) into the thyroid gland. Note the flow of contrast laterally and downward along lymphatic channels. Courtesy of O. H. Clark, MD, Department of Surgery, University of California-San Francisco Mount Zion Medical Center, San Francisco, CA. Figure 2-12. Radiograph of the neck and upper chest of a patient following injection of iodized oil (Lipiodol) into the thyroid gland. Note the flow of contrast laterally and downward along lymphatic channels. Courtesy of O. H. Clark, MD, Department of Surgery, University of California-San Francisco Mount Zion Medical Center, San Francisco, CA. disease. However, there is much debate on the selection of patients for postoperative 131I remnant ablation among those who have undergone...

Molecular Biology Of

Note the interspersed spindle and polyglonal cells sepa- Figure 3-5. Calcitonin immunohistochemistry of medullary thyroid rated by fibrinous septae (x10 original magnification). cancer with adjacent normal thyroid tissue. staining. Note the interspersed spindle and polyglonal cells sepa- Figure 3-5. Calcitonin immunohistochemistry of medullary thyroid rated by fibrinous septae (x10 original magnification). cancer with adjacent normal thyroid tissue.

Serum Thyroglobulin Measurement

Serum Tg determination after primary treatment of DTC is useful as a tumor marker to document recurrent disease on follow-up. However, current methods for serum Tg measurement remain technically challenging because significant assay interference may result from the presence of circulating thy-roglobulin autoantibodies (TgAb), as noted in up to 25 of patients with DTC. To circumvent the problem, clinical studies are ongoing to detect Tg transcripts using a reverse transcriptase polymerase chain reaction technique on blood samples from patients with DTC.26 As the presence of TgAb may invalidate Tg measurements, patients with positive TgAb may require periodic follow-up with thyroid ultrasonography, 131I scans, or other imaging modalities. Nevertheless, postablation serum TgAb levels may be used to correlate directly with the presence or absence of tumor.27 Because of assay variability, serial serum Tg measurements should be obtained using the same assay method. Table 2-2. PROTOCOL FOR...

Prognosis And Followup

The survival of patients with MTC is intermediate to that of patients with differentiated thyroid cancer of follicular cell origin and anaplastic thyroid cancer, with an overall 10-year survival rate of 75 to 85 .1,2,10 There is great variability, however, in the clinical course of patients with MTC. Some patients may survive several decades with persistent disease, whereas some will have rapidly progressive tumors and will die within months of presentation. Only early diagnosis and at least a total thyroidectomy with central neck node clearance give the patient the best chance of disease-free survival. A number of clinical, biochemical, and molecular factors have been reported to predict outcome in patients with MTC (Table 3-2). The most important prognostic factors consistently observed are the age of the patient and the stage of MTC.10 Some studies, but not all, have also suggested that male gender is associated with a worse prognosis. The presence of diarrhea, cervical node...

Epidemiology And Clinical Features

The multiple endocrine neoplasia (MEN) type II syndromes include types IIA and IIB and familial, non-MEN medullary thyroid carcinoma (FMTC). These are autosomal dominant inherited syndromes that are caused by germline mutations in the RET proto-oncogene. The hallmark of these syndromes is the development of medullary thyroid carcinoma (MTC), which is multifocal and bilateral and occurs at a young age. In patients affected by MEN types IIA and IIB or FMTC, there is complete penetrance of MTC all persons who inherit the disease allele develop MTC. Other features of the syndromes are variably expressed, with incomplete penetrance. These features are summarized in Table 17-1. FMTC is characterized by the development of MTC without any other endocrinopathies. MTC in these patients has a later age of onset and a more indolent clinical course than MTC in patients with MEN types IIA and IIB. Occasional patients with FMTC will never manifest clinical evidence of MTC (symptoms or a palpable...

Persistent Or Recurrent Disease

Distant metastatic disease in patients with medullary thyroid carcinoma (MTC). A, Radiograph of lymphangitic pulmonary spread in a child with multiple endocrine neoplasia (MEN) type IIB and MTC. B, Sonogram of solitary brain metastasis in a patient with MEN type IIA and MTC. C, Multiple skeletal metastases in a patient with sporadic MTC. Reproduced with permission from Moley JF, Lairmore TC, Phay JE. Hereditary endocrinopathies. Curr Probl Surg 1999 36 653-764. Figure 17-10. Distant metastatic disease in patients with medullary thyroid carcinoma (MTC). A, Radiograph of lymphangitic pulmonary spread in a child with multiple endocrine neoplasia (MEN) type IIB and MTC. B, Sonogram of solitary brain metastasis in a patient with MEN type IIA and MTC. C, Multiple skeletal metastases in a patient with sporadic MTC. Reproduced with permission from Moley JF, Lairmore TC, Phay JE. Hereditary endocrinopathies. Curr Probl Surg 1999 36 653-764.

Diagnosis And Staging

A, Rapidly enlarging neck mass in a patient with anaplastic thyroid carcinoma (ATC). B, Rapidly enlarging neck mass in a patient with ATC. Figure 4-1. A, Rapidly enlarging neck mass in a patient with anaplastic thyroid carcinoma (ATC). B, Rapidly enlarging neck mass in a patient with ATC. ATC. The use of serum markers is also of limited value because ATC cells do not secrete thryoglobu-lin, calcitonin, or carcinoembryonic antigen (CEA). In fact, the presence of an elevated CEA level and an elevated calcitonin level would suggest that the tumor is more likely to be a poorly differentiated medullary carcinoma of the thyroid. The presence of an elevated CEA without elevated calcitonin may be seen in a metastatic neoplasm involving the thyroid. Both of these entities may have a better prognosis than ATC so that accuracy in diagnosis is quite important. In younger patients, it is crucial to exclude tumors with much better prognosis. Young patients who present with poorly...

Positron Emission Tomography

PET has some advantages over MIBG scanning in that PET can be carried out almost immediately, whereas MIBG scanning must be delayed for 24 to 48 hours after MIBG injection to allow dissipation of background radiation. PET does not require pre-treatment with iodine to protect the thyroid, as is necessary with MIBG scanning. However, PET is

Preoperative Localization Studies

The results of both of these imaging studies are highly dependent on the expertise of the technician. The limitations of sestamibi are false-positive results from increased uptake of thyroid nodules, failure to accurately identify multiple abnormal glands, and poor visualization of hyperplastic glands.37 The limitations of ultrasonography include the inability to detect adenomas at ectopic sites, including mediastinal tumors and often those situated deep in the neck or the paraesophageal or retroesophageal area.38 It is highly operator dependent and has a successful identification rate of nearly 75 .37 If used, both of these studies should be accompanied by intraoperative PTH monitoring to allow a limited exploration with an excellent outcome.38-40 The Mayo Clinic was one of the first institutions to develop the intraoperative PTH

Vasoactive Intestinal Polypeptideproducing Tumors

The diagnosis is confirmed by demonstration of an increased serum VIP level by radioimmunoassay. An increased a-chorionic gonadotropin suggests malignancy.42 The differential diagnosis should include villous adenoma, inflammatory bowel disease, infectious diarrhea, celiac sprue, surreptitious laxative abuse, and other endocrine tumors such as gastrinoma, somatostatinoma, medullary thyroid carcinoma, and carcinoid tumors. At present, there are no known provocative or inhibitory agents to secure an otherwise equivocal diagnosis.

Persistent And Recurrent

Postoperative serum basal and stimulated calci-tonin measurement is a useful and an accurate marker for persistent or recurrent MTC.3738 Elevated postoperative CEA also indicates aggressive MTC.39 Over 50 of patients who present with clinically evident MTC have persistent MTC, manifested by elevated postoperative basal or stimulated calcitonin levels, even after initial complete surgical resection.10 Patients who have an elevated postoperative basal or stimulated calcitonin level can be grouped into two categories those patients who had incomplete initial surgical resection and those patients who had an appropriate initial surgical treatment. Patients who had less than a total thyroidectomy and central neck node clearance (incomplete) usually have residual disease and should undergo cervical re-exploration with removal of all remaining thyroid tissue and bilateral modified radical (functional) neck dissection. Table 3-3. LOCALIZING STUDIES IN PATIENTS WITH PERSISTENT OR RECURRENT...

Anterior Pituitary Tumorsnance imaging MRI with gadolinium contrast of

By pituitary tumors associated with MEN type I The diagnosis of Cushing's syndrome is made by include GH, GH-prolactin, and ACTH (Figure increased glucocorticoid levels (increased 24-hour 16-5). Rarer tumors associated with MEN type I urine cortisol excretion) or diminished response of include luteinizing hormone feedback. The feedback is most coming hormone (FSH), thyroid-stimulating hormone monly assessed by the overnight dexamethasone (TSH), and nonsecreting adenomas. Patients present suppression test (dexamethasone 1 mg orally at with symptoms and signs secondary to mass effect 11 00 pm should normally suppress cortisol to (headache, visual field loss), hypopituitarism, < 5 p,g dL at 8 00 am). The differential diagnosis and or excessive hormone production. includes pituitary-dependent ACTH excess (ade-The evaluation for pituitary tumors includes a noma or hyperplasia), ectopic ACTH from bronchial history of reproductive function (menstrual dates, carcinoid tumor, or primary...

Localization Studies For Pheochromocytoma

To block the thyroid's uptake of free 123I or 131I, Lugol's solution (potassium iodide KI , 5 drops orally three times daily) is given before the injection and daily for 7 days afterward. The 123I-MIBG is given intravenously, and gamma camera scanning may be performed between 1 and 3 days afterward.

Clinical Features Of

Frequency of MTC is equal among both sexes, unlike other thyroid neoplasms, which have a female predominance. Almost all patients with sporadic MTC or index cases of familial MTC and MEN type IIA present with a thyroid mass, thyroid mass with cervical lymphadenopathy, and, less frequently, only cervical lymphadenopathy.310 Regional lymph node metastases are common and occur in up to 75 of patients with clinically evident MTC.29 Common sites of lymph node metastases are the central neck compartment lymph nodes peritracheal and perithy-roidal nodes (level VI cervical lymph nodes) (Figure 3-8). Lymph node metastases also occur to the lateral cervical compartment and upper mediastinum (levels II, III, IV and VII) (see Figure 3-8). Because MTC usually occurs in the posterior-upper lobes of the thyroid gland, where most of the C cells reside, invasion into the trachea or recurrent laryngeal nerve or laterally into the jugular vein or carotid artery may be present. Rarely, patients with MTC...

Goiter

A goiter refers to any increase in the size of the thyroid gland as a result of excessive growth (Figure Multinodular nontoxic goiter (MNG) is the most common disease of the thyroid gland, affecting as many as 90 of the population in iodine-deficient (-endemic) areas. In the United States, about 5 of the population are affected, and the incidence of MNG is approximately 0.1 to 1.5 per year, which translates into 250,000 new cases annually. Women are five times more frequently affected than men. Goiters may reach a considerable size and could extend into the substernal region in 0.2 to 10 . Substernal goiters form 4 of all mediastinal tumors. Most substernal goiters are located anteriorly, and only 1 of them are totally intrathoracic.3 Virtually all (about 99 ) of substernal goiters may be removed via a cervical incision. This may not be possible when the substernal component is malignant, where there is no thyroid tissue in the neck, and when the patient has had previous thyroid...

Epidemiology

Although comprising less than 1 of clinically diagnosed malignancies, thyroid cancers are the most common endocrine neoplasms, and they kill more patients than all other endocrine malignancies combined. Approximately 19,500 new cases of thyroid cancer are diagnosed each year in the United States, resulting in 1,300 deaths annually. However, an estimated 500,000 patients have been treated effectively and are survivors of thyroid cancer.2 Worldwide, the annual incidence rate varies from 0.5 to 10 per 100,000 population. The incidence of thyroid cancer increases with age in adults the median age at diagnosis is 45 to 50 years, and thyroid cancer is two to four times as frequent in women as in men.1,2 Five to 36 of adults are reported to have occult thyroid carcinomas at autopsy. In contrast to clinically diagnosed malignant lesions of the thyroid, these are characteristically small (< 1 cm) and innocuous tumors that have become well recog The only established environmental risk factor...

Genetics

The genetic changes involved are likely to determine both the histologic appearance and the biologic behavior of the thyroid cancer. PTC appears to arise de novo within the thyroid gland as a result of receptor tyrosine kinase activation by RET or NTRK1 gene rearrangement. Intrachromosomal inversion of the RET proto-oncogene (chromosome 10q11.2) has been reported in 10 to 70 of PTCs, being found most commonly in tumors arising after exposure to ionizing radiation. Four types of RET rearrangements have been observed, designated RET PTC1 to RET PTC4, respectively (Figure 2-1). Constitutive RET activation occurs with these rearrangements, which is believed to play a direct role in carcinogene-sis.6 RET PTC variants are found in less than half of PTCs in the adult population, whereas the prevalence is > 70 in children with radiation-induced PTC. Children with post-Chernobyl PTC showed a striking preponderance of the RET PTC3 gene and pheno-typic association with a solid variant...

Diagnosis

Most thyroid cancers present as asymptomatic thyroid nodules, of which 80 to 95 are benign hyperplastic nodules rather than true neoplasms.9 Furthermore, most of the true neoplasms are benign adenomas rather than thyroid cancers. The task of identifying malignant nodules is therefore a challenge in itself as thyroid nodules are found in 5 to 10 of the population. Among patients with palpable thyroid nodules, the history is usually not helpful in detecting underlying thyroid malignancy. Symptoms such as hoarseness of voice, dysphagia, or shortness of breath are uncommon and suggest advanced malignancy. However, an increased risk for malignancy is recognized in individuals with a history of ionizing radiation exposure in childhood, appearance of nodules at an age younger than 20 years or older than 60 years, and the male sex in general. Virtually all patients with DTC are clini- Figure 2-1. Schematic representation of the wild-type RET proto-oncogene and activated forms of RET PTC...

Treatment

The guiding principle in managing patients with DTC is to avoid either overaggressive treatment in a patient with an excellent prognosis or inadequate therapy for the unusual patient with a high risk of tumor recurrence and possible death from thyroid cancer. However, what constitutes the appropriate therapy in patients with DTC is still a subject of intense debate because no prospective randomized clinical trials exist and none are likely to be done. Given the slow progression and good prognosis of the disease, it is difficult to demonstrate a beneficial Figure 2-10. Disease-free survival curves for patients with differentiated thyroid carcinoma by pTNM staging (p < .0001 among all stages). Reproduced with permission from Loh KC et al.15 Figure 2-10. Disease-free survival curves for patients with differentiated thyroid carcinoma by pTNM staging (p < .0001 among all stages). Reproduced with permission from Loh KC et al.15

Anatomy

Eighty-five percent of all glands are within 1 cm of where the RLN crosses the inferior thyroidal artery. Normal parathyroid glands are ovoid and peanut butter or light yellow-brown in color. Parathyroid glands are often confused with small lobules of fat, accessory nodules of thyroid tissue, or lymph nodes. When patients have mature or brown fat, identification of normal parathyroid glands is more difficult because the color is similar. In general, parathyroid glands are softer in consistency than the adjacent thyroid or lymph nodes, the latter being more glassy in appearance. Fat lobules are paler and do not have a network of surface blood vessels. Lymph nodes are, in general, more rounded, occur in groups, and are more often adherent to surrounding tissues. Thyroid nodules are harder, more reddish, and less homogeneous than parathyroid glands. Abnormal parathyroid glands move from adjacent tissues when gentle pressure is applied. This has often been referred...

Summary

Recent advances in molecular biology have significantly improved our understanding of the genetics of DTC. PTC appears to arise from tyrosine kinase activation, whereas FTC develops from RAS activation followed by the inactivation of tumor suppressor gene(s). Over the last decade, FNAB has proven to be the most reliable and cost-effective method in selecting patients with thyroid nodules for surgery. The recent availability of clinical grade rhTSH as an adjunct diagnostic tool for serum Tg testing and 131I imaging study represents yet another achievement in our management of patients with DTC. Although treatment strategies for DTC have evolved through considerable controversy among thyroid experts because of the lack of prospective controlled studies, careful analysis of patients treated by well-defined methods now gradually proves the benefit of more aggressive initial tumor management. There is now a greater consensus among experts to treat most DTC patients, except for those in the...

Pathology

Three histologic variants of anaplastic carcinoma include giant cell, spindle cell, and squamoid. Studies have clearly demonstrated that ATC labeled small cell in the past was, in fact, thyroid lymphoma (TL) or medullary thyroid carcinoma (MTC).9,13-15 TL represents an extranodal variant of non-Hodgkin's lymphoma. It is typically seen in patients with a prior history of Hashimoto's thyroiditis. It is less aggressive than true ATC, with an overall 5-year survival of 50 and a median survival of 2 years. Although most anaplastic tumors exhibit mixed morphology, the most common histologic pattern is the giant cell variant, with abundant eosinophilic, granular cytoplasm, multiple hyper-chromatic nuclei, and occasional acidophilic intracy-toplasmic hyaline globules. The spindle cell variant has spindle-shaped cells with a fascicular architecture that can mimic fibrosarcoma, occasional inflammatory infiltrates resembling malignant fibrous histiocytoma, and pronounced vascularization...

Pheochromocytoma

Photograph of left level III and IV nodes from a patient with medullary thyroid carcinoma. A large metastatic deposit can be seen in the lower portion of the nodal groups. Reproduced with permission from Moley JF and DeBenedetti MK.2 Figure 17-5. Photograph of left level III and IV nodes from a patient with medullary thyroid carcinoma. A large metastatic deposit can be seen in the lower portion of the nodal groups. Reproduced with permission from Moley JF and DeBenedetti MK.2 Pheochromocytomas rarely precede the development of C-cell abnormalities in MEN type II syndrome as nearly all patients with pheochromocy-tomas have at least biochemical evidence of C-cell hyperplasia.4 Approximately 10 of MEN type II patients present with signs or symptoms of pheochromocytomas that precede those of MTC. As with the thyroid C cells, adrenal medullary cells undergo similar, predictable, morphologic changes in the development of a pheochromocytoma. Histologi-cally, the lesion...

Outcome

With thyroid operations Unilateral injury Bilateral injury surgeon. BNE remains the standard approach because it is safe and avoids missing a second adenoma or other abnormal glands in patients with asymmetric or adenomatous hyperplasia. It also does not require intraoperative PTH assays and gamma probe localization. A unilateral, focused approach is acceptable when the prevalence of double adenoma and hyperplasia is low, a preoperative imaging study strongly suggests a solitary adenoma, thyroid disease warranting removal is absent, and intraoperative PTH assays are available. Most noninvasive studies are about 80 sensitive for single adenomas and less so for double adenomas or hyper-plasia. However, the addition of IOPTH can improve the success of surgery to 93 . The most common causes for persistent hyper-parathyroidism are an ectopic parathyroid tumor and multiple abnormal parathyroid glands. Inexperienced surgeons are often unfamiliar with the aberrant location of these glands....

Etiology

Earlier than the peak onset for benign parathyroid disease.13 Like thyroid carcinoma in which external beam radiation is a clear predisposing event, there have been a few reports of parathyroid abnormalities developing after exposure to neck radiation, more often causing benign adenoma than parathyroid carcinoma.14,15

Thyrotoxicosis

Thyrotoxicosis

Nuclear scanning can be helpful in a patient with a follicular neoplasm. A, A cold nodule has a 20 chance of being malignant, whereas a hot or autonomous thyroid nodule is rarely malignant. B, A hemithyroidectomy specimen of a follicular neoplasm. Note the smooth outer surface of the neoplasm. C, In contrast to B, the irregular appearance of a benign solitary nodule presenting as part of a multinodular architecture is demonstrated here. Figure 1-14. Nuclear scanning can be helpful in a patient with a follicular neoplasm. A, A cold nodule has a 20 chance of being malignant, whereas a hot or autonomous thyroid nodule is rarely malignant. B, A hemithyroidectomy specimen of a follicular neoplasm. Note the smooth outer surface of the neoplasm. C, In contrast to B, the irregular appearance of a benign solitary nodule presenting as part of a multinodular architecture is demonstrated here. Graves' disease is an autoimmune disease of the thyroid gland that results in a diffuse...

Cancer Treatment and Research

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. Khleif, S. (ed.) Tumor Immunology and Cancer Vaccines. 2004. ISBN 1-4020-8119-7. Balducci, L., Extermann, M. (eds) Biological Basis of Geriatric Oncology. 2004. ISBN Abrey, L.E., Chamberlain, M.C., Engelhard, H.H. (eds) Leptomeningeal Metastases. 2005.

Skull To Humeruslateral View

Mylohyoid line (medial surface of mandible) 4k. Inferior mental spine (inner surface of mandible) 9c. Mastoid notch (medial surface of temporal bone) 9d. Styloid process (temporal bone) 18a. Greater cornu of hyoid 18b. Body of hyoid 19a. Lamina of thyroid cartilage 29. Clavicle 33a. Superior border of scapula 33b. Vertebral (medial) border of scapula 33c. Axillary (lateral) border of scapula

Exposure preparation and access to the cervical esophagus

The cervical incision is made at the anterior edge of the sternocleidomastoideus muscle. The omohyoideus muscle is divided by monopolar electrocautery and the inferior thyroid artery is divided between ligatures. The recurrent laryngeal nerve must be identified and carefully preserved during the next steps of the dissection. The nerve is best located at the point where it undercrosses the inferior thyroid artery. Further dissection of the nerve should be avoided in order to prevent secondary lesions.

Experimental Models Of Human Tumor Dormancy

As early as the 1940s, experimental systems involving the transplantation of tumor pieces in isolated perfused organs and in the anterior chamber of the eyes of various species of animals have demonstrated the effects of neovascularization on tumor growth. Greene et al.,34 observed that H-31 rabbit carcinoma tumor implanted into the eyes of guinea pigs did not vascularize and failed to grow for 16-26 months. During this period, the transplants measured 2.5 mm in diameter. However, when the same tumors were reimplanted into their original host (i.e., rabbit eyes), they vascularized and grew to fill the anterior chamber within 50 days. Similarly, Folkman et al.25 showed that in isolated perfused thyroid and intestinal segment tumors, implants grew and arrested at a small size (2-3 mm diameter). This inability of neoplasms to evoke a new blood supply was later attributed to endothelial cell degeneration in the perfused organs that are perfused with platelet-free hemoglobin solution.35 In...

Production Of Am In Cultured Cells

Receptors on vascular smooth muscle cells (VSMCs) (Eguchi et al., 1994) and ECs (Kato et al., 1995) increases our confidence that AM secreted from ECs and VSMCs functions as an autocrine or paracrine regulator mediating vascular cell communication. Various humoral factors and physical stress appear to stimulate AM synthesis and secretion. Studies in cultured ECs and VSMCs demonstrated that cytokines such as TNF-a and -p, IL-la and -(5, lipopolysaccharide and various circulating hormones, including corticosteroids, thyroid hormones, angiotensin II, norepinephrine, endothelin-1 and bradykinin all strongly stimulate AM production and release (Sugo et al., 1994 Sugo et al., 1995). And shear stress and stretching, acting as a mechanical stimuli, reportedly induce expression of AM mRNA in VSMCs and cardiac myocytes (Chun et al., 1997).

Familial and Genetic Factors

Den syndrome and Li-Fraumeni syndrome, and more recently, ataxia-telangiectasia.24,25 Cow-den syndrome involves multiple hamartomatous lesions, especially of the skin, and mucous membranes, and carcinoma of the breast and thyroid. Li-Fraumeni syndrome, associated with a high incidence of p53 mutations, consists of a familial aggregation of breast carcinomas, soft tissue sarcomas, brain tumors, osteosarcomas, leukemias, and adrenocortical carcinomas.

Peroxisome proliferatoractivator receptor gamma PPARg

Peroxisome proliferator-activated receptors (PPARs) are orphan receptors belonging to the steroids thyroid retinoid receptor super family of ligand-activated transcription factors. There are three PPAR isoforms (PPARa, -p, -g), each of which is differentially expressed and displays a distinct pattern of ligand specificity 50 . PPARs are implicated in several physiological processes, such as the regulation of lipoprotein, lipid metabolism and glucose homeostasis. Recent observations indicate that PPAR activators could reduce the inflammation induced in different inflammatory pathologies including asthma, hypertensive heart disease, hepatic inflammation and cerebral ischemia 51 . In vivo, PPARg agonists have been shown to modulate inflammatory responses in the brain and to reduce infract size following transient focal ischemia 52,53 . Cerebral ischemia is frequently accompanied by inflammation, which can worsen neuronal injury 54 . Activation of PPARg reduces inflammation and the...

Application Box 41 Development of the Perfect Estrogen

Corepressor proteins mediate inhibitory actions on transcription. For example, in the absence of thyroid hormone, the thyroid-hormone receptor binds to the corepressor molecules nuclear receptor corepres-sor (N-CoR) and silencing mediator of retinoid and thyroid receptors (SMRT). These corepressor proteins attract additional complexes containing histone deacetylase (HDAC) activity. The subsequent removal of acetyl groups from lysines in histones represses transcription by inducing a more compact chromatin conformation.

Goals of Inducible Tissue Specific Ablation of Target Gene Products

In creating a strategy for suppressing the expression of a target protein in vivo, we were confronted by several formidable obstacles. Although adapted first to the elimination of a G-protein a-subunit, the approach was designed for the broader use in targeting G-protein-linked receptors and other accessory proteins. The approach of employing Gia2-specific antisense RNA is far simpler than gene disruption by homologous recombination. To ensure accumulation of the antisense RNA in vivo, the target sequence was inserted in the first exon of the rat PEPCK mRNA. The PEPCK gene was selected for this work based on three considerations (5). First, this 2.8-kb hybrid mRNA would be far more stable than a comparatively short-lived antisense RNA oligonucleotide. Second, expression of PEPCK is controlled by several hormones, including glucagon (acting via cAMP), glucocorticoids, thyroid hormone, and insulin. Insertion of the antisense sequence within the PEPCK gene confers regulated expression of...

Hypoxia And Oxidative Stress

As for the mechanism for AM expression by hypoxic stress, Garayoa et al. (2000) proposed that hypoxia-inducible factor-1 (HIF-1) mediated pathway is predominant, based on the data of cellular responses of HIF-la and HIF-lp knockout mouse, effects of HIF-1 activity stimulators and inhibitors, and activation of gene expression through putative hypoxia response elements of AM gene. Hypoxic stimulation was also reported to stabilize AM mRNA, but more data supporting the HIF-1-mediated pathway have been accumulated for the hypoxia-induced AM expression (Makino, 2003 Leonard, 2003). Thyroid hormone, a stimulator of HIF-1 expression and synthesis, is another common inducer of AM expression and secretion (Ma, 2004). In the in vivo system, more efficient augmentation can be undertaken for AM expression under the hypoxic conditions. Oxidative stress enhanced AM expression and secretion. Exposure of bovine EC to diluted hydrogen peroxide increased AM secretion rate 1.74 fold (Chun, 2000). In...

Signal Transduction via Nuclear Receptors

Finally, a third group of coactivators forms mediator complexes that link transcription factors to the GTF-polymerase complex. An example of a mediator complex is the TRAP DRIP (thyroid hormone receptor-associated protein vitamin D receptor interacting protein) complex. This mediator complex acts as an adaptor that allows transcription factors to communicate with the GTF-polymerase complex. Categorization of coactivators as histone-modifiers, chromatin-remodelers, or mediators is somewhat arbitrary because coactivators can exert multiple functions.

Vascular Endothelial Cells and Smooth Muscle Cells

Regulation profiles of AM secretion from rat EC and VSMC are summarized in Table 1. In this review, up- and down-regulation of AM expression and secretion are indicated by the direction of arrows, and the degree of alteration in the AM secretion is indicated by the number of arrows. Interleulkin 1 showed stimulatory effects on AM secretion from rat AEC, and tumor necrosis factor (TNF) and lipopolysaccharide (LPS) also augmented it. Instead, transforming growth factor (3, (TGF-f ,) and interferon y (IFN-y) inhibited AM secretion. Glucocorticoid and thyroid hormone (T3) were common stimulators of AM secretion from ECs, and aldosterone and sex steroids also increased it. Thrombin induced a strong effect, but the direction of its effect was different in each EC. In most cases, AM secretion rates correlated with AM gene expression levels in rat AECs. Based on these results, TNF-a, LPS, IL-lp, glucocorticoid and T3 are the stimulators of AM expression and secretion from the ECs. In the case...

The Thermogenic Function of the Ca2 ATPase Uncoupled Ca2 Efflux and Uncoupled ATP Hydrolysis

The general interest in this subject has increased during the past decade due to its implications in health and disease. Heat generation plays a key role in the regulation of the energy balance of the cell, and alterations of thermogenesis are noted in several diseases, such as adiposity and thyroid-hormone alterations.

Other organspecific autoimmune diseases of the skin

In this condition there is a loss of pigment as a result of antibodies developing against melanocytes in the skin in a limited area. However, the areas affected tend to gradually increase. There may be other autoimmune diseases in the same patient, causing, for example, pernicious anaemia, and thyroid disease. There is evidence that this condition may be associated with an immune reaction against the hair follicle. The increased incidence of antibodies to the thyroid gland and gastric parietal cells in patients with alopecia areata provides circumstantial support for an autoimmune aetiology.

Thyroglossal Duct Cyst

Thyroglossal duct cyst is the commonest congenital mass and is almost always located in the midline (104). This type of cyst results from embryologic anomalies in the descent of the thyroid gland. The thyroid forms high in the neck at the base of the tongue and hyoid bone and, as growth proceeds and the neck enlarges, it descends to the lower part of the neck. If the cyst retains its attachment to the tongue it is called a thyroglossal duct, and any cystic space in this duct is a thyroglossal duct cyst. The duct always joins the base of the tongue by passing behind the hyoid bone, and thus thyroglossal duct cysts are always found below the hyoid bone in the midline or occasionally just to the left of the midline. The cyst moves on swallowing and on protruding the tongue because it is attached to the thyroid gland. The cyst can become infected and cause a tender, red swelling in the midneck. When infected, the cyst is best treated with antibiotics until the acute infection subsides....

Retropharyngeal and pretracheal spaces

The retropharyngeal space includes the posterior part of the visceral compartment in which the esophagus, trachea, and thyroid gland are enclosed by the middle layers of deep cervical fasci, which extend into the superior mediastinum. This space may become infected as a result from direct extension of a pharyngeal space infection or through lymphatics from the nasopharynx. The onset of the infection is insidious, although dyspnea, dysphagia, nuchal rigidity, fever, and chills may be present. Bulging of the posterior pharyngeal wall may be present. Soft tissue radiography or computed tomography (CT) scan disclose widening of the retropharyngeal space. Hemorrhage, rupture into the airway, laryngeal spasm, bronchial erosion, and jugular vein thrombosis are the main complications. The pretracheal space that surrounds the trachea generally becomes involved following perforation of the anterior esophageal wall or from an extension of a retropharyngeal infection. Patients usually present...

Are there other substances that affect bone development What about hormones

A hormone naturally secreted by the thyroid gland that binds with osteoclasts, making them less active and allows the osteoblasts to form more bone. Secreted by the parathyroid glands (located by the thyroid gland), PTH assists in the regulation of calcium by promoting the absorption of calcium from the intestine and reducing loss of calcium from the urine by the kidney excessive amounts can lead to bone loss. Calcitonin, a hormone naturally secreted by the thyroid gland (located in the neck), binds with the osteoclasts making them less active, which allows the osteoblasts to form more bone. Parathyroid hormone (PTH), secreted by the parathyroid glands (located by the thyroid gland), assists in the regulation of calcium by promoting the absorption of calcium from the intestine and reducing loss of calcium from the urine by the kidney. Interestingly, while PTH is necessary and important at normal levels, excessive amounts can lead to bone loss. Thyroid hormones, secreted by the thyroid...

Disturbances of Serum Calcium

After thyroidectomy or parathyroidectomy Physiologic response to hypercalcemia. Hypercalcemia directly inhibits both parathyroid hormone (PTH) release and synthesis. The decrease in PTH and hypercalcemia decrease the activity of the 1-a-hydroxylase enzyme located in the proximal tubular (PT) cells of the nephron, which in turn, decreases the synthesis of 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3). Hypercalcemia stimulates the C cells in the thyroid gland to increase synthesis of calci-tonin (CT). Bone resorption by osteoclasts is blocked by the increased CT and decreased PTH. Decreased levels of PTH and 1,25(OH)2D3 inhibit Ca reabsorption in the distal convoluted tubules (DCT) of the nephrons and overwhelm the effects of CT, which augment Ca reabsorption in the medullary thick ascending limb leading to an increase in renal Ca excretion. The decrease in 1,25(OH)2D3 decreases gastrointestinal (GI) tract absorption of dietary Ca. All of these effects tend to return serum Ca to normal levels...

Tumor Escape And Future Approaches To Cancer Immunotherapy

Recent progress in tumor immunology has led to novel insights regarding the functions and interactions of immune cells (T, B, NK, M and DC) and the molecules expressed on these cells, which are linked to the development and efficacy of TA-specific immune responses. In addition, a better understanding of the molecular signals and mechanisms involved in the generation of productive immune responses in general has focused attention on those molecular events that occur or do not occur in the tumor microenvironment. The realization that immune cells undergo apoptosis in tumors has led to a search for the mechanism(s) responsible for this death and was instrumental in identifying the TNF family of receptors and ligands as instrumental in mediating tumor-induced apoptosis (165-167). This realization was prefaced by the recognition of the Fas FasL pathway and its role in maintaining the immune privilege at sites such as the anterior chamber of the eye, the brain, the testis or the thyroid...

Anaesthetic problems

Adult respiratory distress syndrome was the initial presentation in a 43-year-old woman. Asystole, from which she could not be resuscitated, occurred soon after tracheal intubation. Postmortem showed thyroid carcinoma, phaeochromocytoma, and a hypertrophied left ventricle (Van der Kleij 1999).A 65-year-old woman presented with multiple organ failure, pulmonary oedema and coma a hypertensive crisis, with VT and VF, occurred on day 8. After successful removal of a phaeochromocytoma, a thyroid carcinoma was detected (Lorz et al 1993). Treatment of thyrotoxic symptoms with propranolol precipitated a hypertensive crisis in a patient who was found to have a phaeochromocytoma (Blodgett & Reasner 1990).The family history was later elicited. Extreme levels of catecholamines were thought to have been responsible for the increased levels of thyroid hormones. et al 1993). In a pregnant patient with known Sipple's syndrome, elective Caesarean section was...

Stefan Engelhardt and Martin J Lohse 1 Introduction

The quantification of adrenergic receptor (AR) mRNAs is an important tool in the study of the physiological and pathophysiological regulation of these receptors. Alterations of the levels of these mRNA represent one of the many mechanisms that regulate receptor signaling (1,2). Such alterations can be triggered by stimulation of the receptors themselves, but also by a variety of other causes. In patients, reductions of receptor mRNA levels have been observed in response to treatment with receptor agonists in pathophysiological states, the best-known example is the downregulation of cardiac p1-ARs in heart failure. On the other hand, upregulation of receptor mRNAs has been observed in response to stimuli, such as corticosteroids and thyroid hormones.

Receptor Biochemistry And Signal Transduction

A receptor (Hulme, 1990 Strader et al., 1994) is a molecule (commonly biomac-romolecule) in on a cell that specifically recognizes and binds a ligand acting as a signal molecule. Ligand - receptor interactions constitute important initial steps in various cellular processes. The ligands such as hormones and neurotransmitters bind to plasma membrane receptors, which are transmembrane glycoproteins. These ligands include bioactive amines (acetylcholine, adrenaline, dopamine, histamine, serotonin), peptides (calcitonin, glucagon, secretin, angiotensin, bradykinin, inter-leukin, chemokine, endothelin, melanocortin, neuropeptide Y, neurotensin, somatostatin, thrombin, galanin, orexin), hormone proteins, prostaglandin, adenosine, and platelet activating factor. Other ligands such as steroids and thyroid hormones bind soluble DNA-binding proteins. The ligand-receptor interactions initiate various signal transduction (Heldin and Purton, 1996 Milligan, 1999) pathways that mobilize second...

TSHRmediated Autoimmunity

Pathogenic autoantibodies to the TSHR disturb normal hypothalamus-pituitary-thyroid regulation of thyroid function 8-10 (Fig. 14.1). GD is characterized by hyperthyroidism, which often leads to tachycardia, anxiety, excessive sweating, and acute weight loss. On the other hand, autoimmune PM is characterized by hypothyroidism that can lead to physical and mental lethargy, bradycardia, and weight gain. Pathogenic antibodies (TSAbs) from patients with GD bind to TSHR and stimulate thyroid, but in PM, pathogenic antibodies (TSBAbs) block either the binding of TSH or TSH-mediated activation of thyroid cells. Unlike in HT, the primary cause of thyroid dysfunction in GD and PM is not due to glandular destruction but rather to physiological perturbation of thyroid function mediated by anti-TSHR antibodies. The important question is how one develops pathogenic antibodies against the thyroid. Since self-tolerance prevents development of autoimmune responses, breakdown in self-tolerance must...

Preoperative abnormalities

MEN 2A.Tumours of the thyroid C cells (medullary thyroid carcinoma), with tumours of the adrenal medulla (phaeochromocytoma), and sometimes parathyroid hyperplasia or adenoma. May present at any time during adulthood, and medullary thyroid carcinoma is the commonest initial presentation (see Sipple's syndrome). 3. MEN 2B features early and aggressive medullary thyroid carcinomas, multiple mucosal ganglioneuromas (of tongue, eyelids, conjunctivae, buccal mucosa, and gastrointestinal tract), phaeochromocytomas, a Marfanoid habitus with a high arched palate, severe colonic dysfunction associated with megacolon, more aggressive thyroid carcinomas that are of earlier onset, and bilateral phaeochromocytomas.

The Role of Environmental Factors

Like other autoimmune diseases, environmental factors have long been suspected in the etiology of the disease. For example, excess iodine intake is a risk factor for developing autoimmune thyroid diseases in both humans and animal models of AITD 33, 34 . Stress, drugs, and smoking can also contribute to the development of the disease. The common mode of action of all these factors is that they place stress on the thyroid 35 . It is possible that these environmental stresses can lead to thyroid injury, which may in turn release thyroid autoantigens or alter the immunogenicity of the thyroid antigens. Another set of environmental factors linked to AITD 36 and host immune responses is microbial infections, which can cause overexpression (e.g., heat shock proteins, MHC class II molecules, costimulatory molecules, etc.) and or altered expression of certain self-proteins (altered self). Presentation of these antigens by professional APCs could provide the necessary strength of signal or be...

Growth Factors Hormones and Oncogenes

Hormones are also regulators of VEGF gene expression. Thyroid-stimulating hormone has been shown to induce VEGF expression in several thyroid carcinoma cell lines (80). Shifren et al. (81) have also shown that ACTH is able to induce VEGF expression in cultured human fetal adrenal cortical cells, suggesting that VEGF may be a local regulator of adrenal cortical angiogenesis and a mediator of the tropic action of ACTH.

Autoantibodies and Autoantigens Associated with Autoimmune Hepatitis Type

Characteristic antibodies of AIH type 2 are liver kidney microsomal antibodies (LKM-1) directed against cytochrome P450 (CYP)2D6 and, with lower frequency, against UDP-glucuronosyltransferases (UGT) 35 . In 10 of cases, LKM-3 autoantibodies against UGTs are also present 36, 37 . In contrast to AIH type 1, additional organ-specific autoantibodies are frequently present, such as anti-thyroid, anti-parietal cell, and anti-Langerhans' cell autoantibodies. The number of extrahepatic autoimmune syndromes such as diabetes, vitiligo, and autoimmune thyroid disease is also more prevalent compared to AIH type1 34 .

Hormonal Abnormalities

As would be expected, stallions with low circulating testosterone levels have depressed DSO as well as decreasing libido. As mentioned previously, testosterone, hCG and GnRH therapy have been used with mixed success to address this problem. The lack of success may well be due to the fact that depressed pituitary function is the cause of infertility in only 1 of cases (Boyle et al., 1991 Roger and Hughes, 1991). Abnormal hormone levels may be associated with hypothyroidism, resulting in delayed puberty, smaller testes, decreased spermatozoan production and decreased libido. Feminization of the genitalia may also be observed. It has been postulated that changes in thyroid function may be the cause of stallion summer infertility associated with elevated environmental temperatures (Brachen and Wagner, 1983).

Exclusion of Specific Disorders

As already mentioned, in eumenorrheic women with other hyperandrogenic features, a day 22-24 P4 level, preferably in two consecutive cycles, should be obtained. In patients demonstrating ovula-tory dysfunction, thyroid-stimulating hormone and prolactin levels may also be obtained to exclude thyroid dysfunction and hyperprolactinemia, respectively. The prevalence of these two latter abnormalities among women with hyperandrogenic features is less than 2 (12).

Cercopithecine herpesvirus 6 CeHV6 An

Unassigned species in the subfamily Alphaherpesvirinae. Genome DNA is 52 G+C. Causes a severe, often fatal, exan-thematous disease in captive vervet monkeys. Antibodies to the virus are rare among monkeys in the wild but the infection spreads rapidly when they are brought together in captivity. Sub-clinical infections are common, but in severe cases there are necrotic hemorrhagic lesions in the lungs, intestine, liver and other organs. Other monkeys, mice and rabbits are resistant to infection. Virus replicates with CPE in vervet monkey kidney cell cultures, also in human thyroid, Vero cells and many other cell lines. Produces no pocks on the CAM and does not kill the embryo. The virus is strongly cell-associated. Antigenically very closely related to Human herpesvirus 3. Synonyms Liverpool vervet monkey virus vervet monkey herpesvirus SA12 virus.

Cellular compartments in mature prostatic epithelia

Significant populations of neuroendocrine cells also reside among the more abundant secretory epithelium in the normal prostate gland. These cells are found in the epithelium of the acini and in ducts of all parts of the gland. The major type of neuroendocrine cell contains serotonin and thyroid-stimulating hormone. Neuroendocrine cells are terminally differentiated, postmitotic cell types that are androgen insensitive (23).

Serotonin Antagonists

There is no specific treatment for the fatigue of cholesta-sis at present. The methodology to study fatigue is subjective thus, there is substantial uncertainty in interpreting any data on fatigue. Some patients with PBC report that taking naps during the day facilitates the performance of their daily activities (NV Bergasa, unpublished). The examination of patients with fatigue and liver disease includes the exclusion of conditions that have a negative impact on energy level, including anemia, thyroid dysfunction, adrenal and renal insufficiencies, and depression, in order for specific treatments to be prescribed if those conditions are present.

Management options

In trophoblastic neoplastic disease, uterine evacuation may be adequate surgical management but hysterectomy may be required in more invasive disease, especially in older women. Surgery may also be required for torsion of, or haemorrhage into, ovarian cysts. Chemotherapy maybe required if human chorionic gonadotro-phin levels remain elevated or in metastatic disease. In terms of anaesthetic management, the above considerations should be taken into account and appropriate measures taken regarding investigation (including liver and thyroid function blood tests and chest radiography), monitoring and management. General anaesthesia is usually recommended since uterine bleeding may be rapid and severe, and blood should be cross-matched and ready before surgery.

[125IIododeoxyuridine 125IUdR release assay

125l is a low-energy -y- emitter, and is more easily shielded (half-value layer 0.02 mm lead) than 51Cr. The same precautions as indicated for 51Cr manipulation should be used here (Protocol 1). The incorporation of 125l into the thyroid by inhalation is its main biological risk. However, since

Autoantibodies Frequently Associated with Autoimmune Hepatitis Type

Ever, the molecular characterization of target antigen specificity does not supply important additional information to increase the diagnostic precision of AIH type 1. Although organ-specific autoantibodies are usually not observed, an association of AIH type 1 with other autoimmune syndromes is observed in 48 of cases, with autoimmune thyroid disease, synovitis, and ulcerative colitis as leading associations 18, 19 .

AAPC Also Attenuated FAP

Familial adenomatous polyposis Duodenal or peri-ampullary cancer Pancreatic cancer Thyroid cancer Gastric cancer Cowden Syndrome Thyroid cancer Breast cancer Uterine and Ovarian Upper GI endoscopy (including side-viewing exam) every 1 to 3 years, start at age 20 to 25 years Possibly periodic abdominal ultrasound after age 20 years Annual thyroid examination, start age 10 to 12 years Same as for duodenal Annual thyroid exam, start in teens

Thalidomiderelated deformities and other phocomelias

A state of thyroid overactivity, which should be controlled before elective surgery, to avoid precipitating a thyroid crisis (Pronovost & Parris 1995). If antithyroid drugs are used,preparation for thyroid surgery may take up to 2 months. With beta adrenoceptor blockers and potassium iodide alone, control can be achieved within 2 weeks, but not all are agreed on the adequacy of this method for patients who need surgery. Beta blockers only block the peripheral effects of the hormones.They do not affect their synthesis or release, and may obscure a crisis (Eriksson et al 1977). Since they are short acting, their omission in the perioperative period may lead to an unexpected crisis. Occasionally a thyrotoxic patient requires urgent surgery. Alternatively, surgery may be unwittingly undertaken in a thyrotoxic patient, because the diagnosis is obscured by other pathology. Thyrotoxicosis may also be precipitated by infections, labour, trauma, acute medical illness, and stress (Smallridge...

The Pruritis of Cholestasis

In examining patients with pruritus associated with cholestasis it is necessary to rule out contributing causes to the pruritus, including dermatological conditions, which, in contrast to the pruritus of cholestasis, manifest with pruritic skin lesions, in general. Pruritus can result from nondermatologic conditions different from cholesta-sis including medications, altered thyroid function, and malignancy. It is prudent, therefore, to rule out possible contributing factors to the pruritus, even in patients with cholestasis, by performing a well-planned investigation (eg, thyroid function tests, dermatologic examination).

How will my clinician use my test results to determine whether I have osteoporosis

A Z-score is usually not helpful in making the diagnosis of osteoporosis. However, if it is particularly low (lower than -1.5), it is important for your clinician to evaluate you for conditions and illnesses that may be causing your bone loss associated with secondary osteoporosis. Such causes of secondary osteoporosis might include thyroid or parathyroid disease, cigarette smoking, excessive alcohol intake, problems with absorption from your gastrointestinal tract, or the use of medications known to be harmful to bone.

Fathia GibrilMD and Robert T JensenMD

In this chapter, treatment of SD is briefly reviewed. Not discussed are diarrheal diseases with a secretory component included in other chapters in this volume, including (1) infectious diarrheas, (2) diarrheas owing to bile salts or fatty acids, and (3) diarrhea owing to inflammatory diseases such as inflammatory bowel disease. This chapter focuses on the treatment of the remaining causes of SD, including those owing to hormone-related diarrhea, surreptitious use of laxatives, and SD of unknown origin.The hormone-related diarrheas include vasoactive intestinal secreting tumors (VIPomas), gastrinomas causing ZollingerEllison syndrome, glucagonomas, somatostatinomas, medullary thyroid cancer, and systemic mastocytosis.

Sequestration of Other RNA Binding Proteins

In addition to MBNL proteins, the splicing regulators hnRNP H and F colo-calize with CUG foci in neurons of DM1 patient brain samples (Jiang et al. 2004). Neuron-specific c-src N1 exon is regulated by hnRNP F (Min et al. 1995) and hnRNP H regulates NF-1 exon 3, thyroid stimulating hormone beta subunit (TSH beta) genes (Buratti et al. 2004), HIV-1 tev-specific exon 6D (Caputi and Zahler 2002) and beta tropomyosin (Chen et al. 1999). The relevance of hnRNP H and hnRNP F colocalization with RNA foci is not clear since splicing of c-src is not disrupted in neurons (Jiang et al. 2004).

Clinical Manifestation Cervicofacial

This is the most common form of actinomycosis (1). The infection is generally odontogenic in origin, and evolves as a chronic or subacute painless or painful soft-tissue swelling or mass involving the submandibular or paramandibular region. However, the submental and retromandibular spaces, tempomandibullar joint and cheek can be involved. The swelling may have ligneous consistency caused by tissue fibrosis. Depending on the composition of the concomitant synergistic flora, the onset of actinomycosis may be acute, subacute, or chronic. When Staphylococcus aureus or beta-hemolytic streptococci are involved, an acute painful abscess or a phlegmatous cellulitis may be the initial manifestation. The chronic form of the disease is characterized by painless infiltration and induration that usually progress to form multiple abscesses and draining sinus tracts discharging pus that may contain sulfur granules in up to 25 of instances. Periapical infection, trismus, fever, pain, and...

Influences on the Normal Menstrual Cycle

Teriorates, its decrease in estrogen and progesterone production leads to a reduction in hypothalamic en-dorphin release. This, in turn, triggers greater GnRH, LH, and FSH production and causes follicle maturation early in the next cycle. Psychological and physical stresses may also modify the menstrual cycle through increased secretion of endorphins stimulated by increased corticotropin-releasing hormone (CRH). This leads to a decrease in GnRH release, which interferes with ovulation. Abnormalities in adrenal steroid synthesis or insufficient production of hormones by the thyroid (thyroxin) or the pancreas (insulin) may result in anovulation and infrequent menses, although the mechanisms of action are unknown. Estrogen itself is associated with increased secretion of growth hormone, prolactin, ACTH, and oxytocin controlled in concert by the hypothalamus and the anterior and posterior regions of the pituitary. Genetic syndromes affecting hormone and steroid synthesis or chemical...

Normal Menstrual Cycle

Tion and the transformation of the ovarian follicle into the corpus luteum, which is necessary for sustaining a pregnancy should fertilization and embryo implantation occur. In the absence of pregnancy, the menstrual cycle ordinarily lasts 26 to 32 days (a range of 21 to 36 days), with women between the ages of 20 and 40 having the greatest regularity in cycle length. The menstrual cycle's three distinct phases relate primarily to hormonal changes and events at the hypothalamus and pituitary regions of the brain, the ovary, and the uterus (Figures 1 and 2). The cycle is also influenced by the limbic region of the central nervous system, the adrenal and thyroid glands, the pancreas, and exogenous hormones or medications.

LEMS Lambert Eaton myasthenic syndrome

Prejunctional disturbance, with reduction of P Q Ca++ channels on presynaptic Anatomical and terminals and reduction of Ca++ dependent quantal release. Also associated functional situation with N-type Ca channel antibodies (35 ). GAD antibodies, thyroid antibodies, parietal cell antibodies, anti-Hu and muscle nicotinic AchR antibodies have been observed.

Thyrotropin Receptor Downmodulation

Lated in the thyroid is not fully understood. Although a great deal of information has been gathered on the internalization of receptors that contain a single transmembrane domain 59 , limited data exist on endocytosis of glycoprotein hormone receptors, which contain multiple membrane-spanning domains. This is particularly true of the TSHR protein upon ligand (TSH) binding, and there is no known report on the fate of this receptor upon TSAb or TSBAb binding. Milgrom's group 60 has studied TSHR trafficking. They found that the receptor was expressed on the plasma membrane and clathrin-coated pits and that a minor fraction of the expressed protein was constitutively localized to endo-somes 60 . Upon TSH addition, there was an increase in the endocytosis of the receptor. While the TSH was degraded in the lysosomes, a great majority of the internalized TSHR was recycled to the cell surface, which could be blocked by treatment with monensin. Furthermore, another study 61 provided further...

Behavioral Dysfunction

Classical antipsychotic drugs that potently block dopaminergic receptors can ameliorate psychotic symptoms but worsen parkinsonism, at times seriously enough to require levodopa (84). Better results in treating psychosis have been obtained with the atypical neuroleptics, possibly owing to their predominant antiserotoninergic rather than antidopaminergic activity. An extensive chart review revealed that 90 of DLB patients had partial to complete resolution of psychosis using long-term quetiapine, although in 27 motor worsening was noted at some point during treatment (85). A large, randomized blinded trial found that olanzapine (5 or 10 mg) reduces psychosis without exacerbating parkinsonism (86). Relatively small doses of clozapine have also been used successfully for the relief of paranoid delusions, psychosis, and agitation, albeit at the risk of agranulocytosis (84). Indeed, caution is generally warranted in using neuroleptics, since sedation, confusion, immobility, postural...

Is There an Optimal Time or Drug Dose for Normalization

Radiation therapy by increasing the concentration of reactive oxygen species created by the radiation. During the normalization window, but not before or after it, VEGFR-2 blockade was found to increase pericyte coverage of vessels in a human brain tumor grown in mice. Vessel normalization was accompanied by upregulation of angiopoietin-1 and activation of MMPs. The prevailing hypothesis is that VEGF blockade passively prunes nascent vessels that are not covered with pericytes. In contrast, this study found that pericyte coverage increased before vascular pruning. Improved understanding of the molecular mechanisms of vessel normalization may suggest new strategies for extending the normalization window to provide ample time for cytotoxic therapy. The dose of AAs also determines the efficacy of combination therapy. Although it is tempting to increase the dose of AAs or to use a more potent angiogenic blocker, as one would for chemotherapeutic agents, doing so might lead to normal...

The Role of Genetic Factors

The etiology of autoimmune thyroid disease (AITD) is unclear. Similar to other autoimmune diseases, genetic, environmental, and other endogenous factors contribute to the initiation of the disease. Increased incidence of GD among members of a family and a higher degree of disease concordance among identical twins indicate that genetic factors may play an important role in determining susceptibility to GD 15-17 . As in most other autoimmune diseases, the strongest bias in developing GD is gender women are 5-10 times more likely than men to develop the disease. Two recent reviews on genetic susceptibility to GD have summarized and discussed the implications of a large number of stud

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