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Glandula Tiroid Problem: Literature Review
Abstract
Thyroid cancer is the most common endocrine system neoplasm.Based on the "Pathologycal Based Registration" in Indonesia, thyroidcancer is a cancer with the highest incidence in the ninth rank.According to statistics from the National Cancer Institute (NCI), theincidence of thyroid cancer in men is about 2.5 per 100.000population and women around 6.7 per 100.000 population. Thyroidcancer can affect all age groups and the frequency increases afterthe age of 50 years. Only about 5% can affect the age of 15-20 years.NCI also states that this thyroid cancer can affect 16.000 people peryear. Diagnosis is important to improve the quality of life forsufferers. Clinical diagnosis is the basis for determining furthermanagement, so that knowledge and skills are needed indetermining the diagnosis. The first treatment for a cancer is thebest chance for the patient to achieve optimal cure rates, as is thecase for thyroid cancer.
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Chromosomal translocations encoding fusion oncoproteins are common in hematological malignancies, sarcomas, and papillary thyroid carcinomas. A recent study of follicular thyroid carcinomas reported a novel chromosomal translocation, t(2;3)(q13;p25), that fused the thyroid-specific transcription factor PAX8 with a nuclear receptor, peroxisome proliferator-activated receptor gamma (PPAR gamma). Herein we report the detection of this putative oncoprotein in 6 of 17 (35%) follicular thyroid carcinomas as well as in 6 of 11 (55%) follicular thyroid adenomas. Concordant expression of protein was found in 91% of those tumors in which PAX8-PPAR gamma mRNA was detected by RT-PCR, whereas a further 20% of follicular tumors were positive for PPAR gamma immunohistochemistry alone. Our findings suggest that the PAX8-PPAR gamma fusion protein promotes differentiated follicular thyroid neoplasia, although it is not sufficient per se for carcinogenesis.
A number of molecular abnormalities have been described in association with the progression from normal thyroid tissue to benign adenomas to well-differentiated and finally anaplastic epithelial thyroid cancer. These include upregulation of proliferative factors, such as growth hormones and oncogenes, downregulation of apoptotic and cell-cycle inhibitory factors, such as tumor suppressors, disruption of normal cell-to-cell interactions, and cellular immortalization. The progression model for thyroid carcinoma has not been proven, but evidence suggests that an evolutionary molecular process is involved, especially in the development of follicular thyroid cancers for which there are distinct intermediate phenotypes. We present a comprehensive evaluation of factors involved in thyroid tumorigenesis and attempt to describe preliminary attributes of a progression model. The organization of this model should also provide a template for the incorporation of new information as it is derived from large-scale genomic studies.
Iatrogenic lesions of the external branch of the superior laryngeal nerve (EBSLN) during thyroidectomies are not infrequent due to the possibility of anatomic variations of the relationships of this nerve with the superior thyroid vessels. Therefore, based on an anatomic analysis of 30 superior thyroid poles from 15 fresh cadavers, a new classification of the EBSLN was proposed, considering the jeopardy during a thyroidectomy. Thirty-seven percent of the nerves were type 2, ie, crossing the superior thyroid pedicle less than 1 cm above the superior thyroid pole. It is notable that 20% were type 2b, ie, crossing the vessels below the upper border of the pole, having been considered "high risk." This incidence was comparable with other series, which found dangerous anatomic variations of the EBSLN in the range of 15% to 68%, confirming that a significant proportion of these nerves might be at risk during surgery on the superior thyroid pole.
The Cooperative Thyrotoxicosis Therapy Follow-up Study reported cancer mortality after use of radio-iodine (131I), surgery, and other treatments in patients with hyperthyroidism, started during 1946-1964 and followed through 1968. In 1984, the National Cancer Institute initiated a continued follow-up (FU) of the same cohort through 1990, to assess potential carcinogenic effects of 131I through 1990, a potential FU ranging from 26 to 44 years.
With an initial cohort of 35,630 hyperthyroid patients, a mean entry age of 46 years and 738,831 patient-years of FU, the 2950 observed cancer deaths were only minimally over the 2858 expected cancer deaths from US population rates, after exclusion of first-year deaths. In the 64.7% of patients receiving 131I, the total cancer deaths were significantly above expected (258 versus 208), only at durations of 1-5 years, not thereafter. Thyroid cancer deaths were significantly elevated, but the number was very small, only 24 deaths in all exposures, as compared with 5.89 expected. The overall thyroid cancer mortality was higher in cases of toxic nodular goiter than in patients with Graves' disease.
Despite the small early increase in total cancer deaths and the relatively higher increase in thyroid cancer deaths (only 18 excess deaths), the authors conclude that therapy with the doses of 131I used is a safe procedure. The interpretation of cause-specific excess mortality is greatly influenced by the prevalence of the cause of death.
The development of hyperparathyroidism after radioactive iodine (RAI) therapy has been reported in 38 cases in the literature. However, the development of a parathyroid adenoma after RAI therapy for a hyperfunctioning multinodular goiter has not been reported. This report describes the pathologic and operative finding on a patient with both hyperthyroidism and hyperparathyroidism, which was diagnosed after previous RAI therapy for a toxic, multinodular goiter. (Am J Otolaryngol 2001;22:374-375. Copyright © 2001 by W.B. Saunders Company)
Thyroglossal duct remnants are the most common midline neck masses in childhood but can be found in adults and the elderly. Sistrunk's procedure, with dissection of the tract and removal of the hyoid bone, is accepted as the main operation of choice.
Fifty-five patients were treated from January 1994 to November 2000, and these were studied. There were 29 men and 26 women, with a median age of 17 years. Diagnosis was clinical, with 13 cases of fistula and 42 of cyst. Size varied from 1.0 to 4.0 cm, with an average of 2.5 cm. Six patients presented with local abscess.
All the patients underwent Sistrunk's procedure. Serum collection occurred in three patients as complication. In one patient papillary carcinoma was identified in the cyst. Total thyroidectomy was not performed. There was only one recurrence, managed with a second operation.
We concluded that the diagnosis of thyroglossal duct is clinical. Sistrunk's procedure carries low rates of complications (9.08%) and recurrence (1.82%). Antibiotic therapy is avoidable as a rule and hospital stay is short.
Thyroid nodules can be found in up to 50% of inhabitants of iodine-deficient areas and are classified as hot or cold thyroid nodules according to their scintigraphic characteristics. Studies of hot thyroid nodules with comparable mutation detection methods and screening at least exon 10 of the TSH receptor reported frequencies for somatic TSH-receptor mutations ranging from 20 to 82% in patients with similar iodine supply. We have recently screened 75 hot thyroid nodules for somatic TSH-receptor mutations with the more sensitive DGGE method and found somatic TSH-receptor mutations in 57% and Gsalpha mutations in 3%. As 50% of the mutation-negative nodules from female patients are of monoclonal origin when tested for X-chromosome inactivation somatic mutations in other genes are likely to cause the development of hot thyroid nodules. Scintigraphically nonsuppressible areas have been identified in up to 40% of euthyroid goiters in iodine-deficient areas. We recently identified somatic TSH-receptor mutations in microscopic autonomous areas with increased 125T uptake in euthyroid goiters studied by autoradiography 20 years ago. These constitutively activating somatic TSH-receptor mutations in minute autoradiographically hot areas of euthyroid goiters are very likely starting foci which most likely lead to toxic thyroid nodules in iodine-deficient goiters. Therefore iodine deficiency does not only lead to euthyroid goiters but also to thyroid autonomy. The latter is also suggested by epidemiologic studies. Similar mechanisms induced by iodine deficiency and the subsequent hyperplasia, mutagenesis, and selection of cell clones could also lead to cold thyroid nodules by somatic mutations that only initiate growth but not hyperfunction of the affected thyroid epithelial cell. Somatic ras mutations have frequently been detected in histologically characterized thyroid adenomas or adenomatous nodules. However, they seem to be rare in cold thyroid nodules. Since the majority of these latter nodules and 60% of the cold thyroid nodules are monoclonal other somatic mutations are likely in these nodules.
The surgical therapy of Graves' disease is favored in Germany, which is an iodine-deficient area, and nodular transformation is common. The surgical methods mainly differ in their extent of resection. We examined 152 patients with regard to operative and postoperative complications in a prospective randomized study. Patients were randomized to two groups: treated either by subtotal resection on both sides (STT) or subtotal resection with contralateral hemithyroidectomy (SHT), the two most common surgical procedures. The follow-up period was 6 years; complication and recurrence rates were studied. There was no significant difference concerning mortality, recurrent laryngeal nerve palsy, hypocalcemia, secondary hemorrhage, wound infections, or recurrence rate between STT and SHT. However, SHT only requires a unilateral resection in case of a recurrence, thus reducing the risk of bilateral recurrent laryngeal nerve palsy.
Surgical damage to the inferior laryngeal nerve is one of the most feared complications of thyroid surgery. Prevention of surgical injuries requires systematic, early exposure of the inferior laryngeal nerve. A detailed knowledge of anatomical variations is necessary. Non-recurrent inferior laryngeal nerve is a rare anomaly on the right side and is exceptional on the left. Whereas the typical course of the inferior laryngeal nerve is due to the embryological development of the aortic arch and supra-aortic vessels, non-recurrence is associated with a vascular anomaly such as a right retro-oesophageal subclavian artery. The nervous anomaly on the left side is possible only with the occurrence of cardiac dextroposition (situs viscerum inversus) and a left retro-oesophageal subclavian artery. The situation is more dangerous when a non-recurrent branch of the inferior laryngeal nerve is associated with a recurrent branch. This anomaly does not appear to be associated with a vascular anomaly in all cases. The authors describe three cases of right non-recurrent inferior laryngeal nerve observed and one recent case of combined non-recurrent and recurrent nerve, highlighting the anatomical and surgical features of this anomaly.
Riedels thyroiditis is a rare chronic inflammatory disorder characterised by extensive fibrosis of the thyroid gland and sometimes the surrounding tissues. We report a case of Riedels Thyroiditis in a middle aged female presenting with goitre, stridor and dyspnoea. She initially responded to corticosteroid treatment and subsequently to tamoxifen. The rationale for these treatments are discussed.
The Chernobyl accident exposed people located hundreds of kilometres away to fallout, but increases in cancer incidence as a result of the accident seem, at present, to be restricted to one tumour type. These thyroid tumours form the largest number of cancers of one type, caused by a single event on one date, ever recorded. Epidemiological, pathological and molecular studies have provided new insights into the carcinogenic process, as well as lessons for future nuclear accidents.
The Pendred syndrome gene encodes a 780-amino acid putative transmembrane protein (pendrin) that is expressed in the apical membrane of thyroid follicular cells. Although pendrin was shown to transport iodide and chloride using Xenopus laevis oocytes and Sf9 insect cells, there is no report using mammalian cells to study its role in thyroid function. We show here, using COS-7 cells and Chinese hamster ovary cells transfected with expression vectors encoding sodium iodide symporter or human Pendred syndrome gene cDNA and by comparison with studies using rat thyroid FRTL-5 cells, that pendrin is an iodide-specific transporter in mammalian cells and is responsible for iodide efflux in the thyroid.
Rearrangement of the RET gene, also known as RET/PTC rearrangement, is the most common genetic alteration identified to date in thyroid papillary carcinomas. The prevalence of RET/PTC in papillary carcinomas shows significant geographic variation and is approx 35% in North America. RET/PTC is more common in tumors in children and young adults, and in papillary carcinomas associated with radiation exposure. There are at least 10 different types of RET/PTC, all resulting from the fusion of the tyrosine kinase domain of RET to the 5' portion of different genes. RET/PTC1 and RET/PTC3 are the most common types, accounting for >90% of all rearrangements. There is some evidence that different types of RET/PTC may be associated with distinct biologic properties of papillary carcinomas. RET/PTC1 tends to be more common in tumors with typical papillary growth and microcarcinomas and to have a more benign clinical course, whereas RET/PTC3 in some populations shows a strong correlation with the solid variant of papillary carcinoma and more aggressive tumor behavior. RET/PTC has recently been found in hyalinizing trabecular adenomas of the thyroid gland, providing molecular evidence in favor of this tumor to be a variant of papillary carcinoma. The occurrence of RET/PTC in Hashimoto thyroiditis and thyroid follicular adenomas and hyperplastic nodules reported in several studies has not been confirmed in other observations and remains controversial.
The occurrence of thyroid diseases is determined by interplay between genetic and environmental factors. The major environmental factor that determines goiter prevalence is iodine status, but other environmental factors influencing entire populations have been identified such as goitrogens in food and drinking water. Less focus has been on individual environmental factors and the interplay between factors. The goiter prevalence is higher in certain groups in the population. The variation in goiter prevalence between the genders is well known with a higher occurrence among women. The association with age is probably dependent on iodine status, because it seems that the zenith of goiter prevalence appears earlier in life the more severe iodine deficiency the population is exposed to. The association with individual risk factors has been investigated in some studies, especially the association with tobacco smoking. In iodine-deficient areas, a strong association between tobacco smoking and goiter prevalence is found, whereas the association is less pronounced in iodine-replete areas. This was predictable from experimental studies showing thiocyanate to be the mediator of the goitrogenic effect of tobacco smoke acting as a competitive inhibitor of iodine uptake. The association with alcohol intake has only been investigated in few studies, but a low occurrence of goiter among alcohol consumers has been found. The mechanism of this association is not known. Increased goiter prevalence during pregnancy has been reported, and recently a long-term goitrogenic effect of pregnancies has also been shown. As demonstrated for tobacco smoking, this association is dependent on iodine status, because the association has only been found in areas with a suboptimal iodine intake. This indicates pregnancy-induced goiter to be the result of exacerbation of existing iodine deficiency. Recently, the use of oral contraceptives has been shown to be associated with a markedly reduced prevalence of goiter, although experimental studies have previously shown proliferative effects of estrogens on thyrocytes. Some implications for prevention of thyroid disease could be suggested. Discussion of smoking habits should be included in a consultation for goiter with a motivation to quit smoking. Iodine deficiency has particularly strong goitrogenic effects during pregnancy and for the sake of the mother as well as the fetus, sufficient iodine supply should be ensured to all pregnant women. The difference in age maximum in goiter prevalence suggests that monitoring of iodine deficiency disorders should ideally include a spectrum of age groups.
This review describes the microbiology, diagnosis and management of suppurative thyroiditis (ST). Staphylococcus aureus, Streptococcus pyogenes, Streptococcus epidermidis, and Streptococcus pneumoniae, are the predominant aerobic isolates. The most common anaerobic bacteria are Gram-negative bacilli and Peptostreptococcus spp. Agents that are rarely recovered include Klebsiella spp., Haemophilus influenzae, Streptococcus viridans, Salmonella spp., Enterobacteriaceae, Mycobacterium tuberculosis, atypical mycobacteria, Aspergillus spp., Coccidioides immitis, Candida spp., Treponema pallidum, and Echinococcus spp. Viruses have been associated with subacute thyroiditis, and include measles, mumps, influenza, enterovirus Epstein-barr, adenovirus, echovirus, and St Louis encephalitis. Therapy includes administration of antibiotics effective against the causative pathogen(s). Proper selection of therapy can be guided by culture of the lesion. Surgical drainage may be necessary in case of suppuration.
Recent studies have shown that Graves' disease (GD) is linked to and associated with alleles of the cytotoxic T lymphocyte antigen-4 (CTLA4) locus. However, the true pathogenic polymorphism(s) at this locus remains uncertain. Moreover, the association studies of the promoter CTLA4(-318)C/T polymorphism in white GD populations have produced conflicting results. Therefore, we have analysed three CTLA4 single nucleotide polymorphisms, including promoter CTLA4(-318)C/T, exon 1 CTLA4(49)A/G and intron 1 CTLA4(1822)C/T in our GD cohort from the UK.
We studied 301 white patients with GD and 349 healthy ethnically matched local controls. Amongst GD probands, 129 had significant thyroid-associated orbitopathy (TAO; NOSPECS class III or worse). The CTLA4(-318)C/T, CTLA4(49)A/G and CTLA4(1822)C/T polymorphisms were genotyped by using the restriction enzymes MseI, Bst71I and HaeIII, respectively.
We found no association between GD and alleles of CTLA4(-318)C/T. GD was found to be associated with the G allele of CTLA4(49)A/G[P = 5.9 x 10(-6), odds ratio (OR) 1.65] and the T allele of CTLA4(1822)C/T (P = 7.7 x 10(-6), OR 1.64). The frequencies of these alleles were significantly higher in GD probands with significant TAO than in those without TAO (G allele: P = 0.001, OR 1.68; T allele: P = 0.001, OR 1.70).
The promoter CTLA4(-318)C/T polymorphism is not in linkage disequilibrium with the pathogenic polymorphism(s) at the CTLA4 locus. The alleles of both the exon 1 CTLA4(49)A/G and the intron 1 CTLA4(1822)C/T polymorphisms are associated with GD, which is stronger in patients with TAO.
The art and science of medicine has changed so much in the last 40 years, not only in the manner that physicians treat medical diseases but also in how they diagnose them. Technological advances have made it possible to have a test for almost anything. These technological advances, however, are important contributing factors to the rising cost of healthcare. More than ever, cost containment is an important element in all aspects of patient care. Minimizing costly diagnostic imaging and laboratory tests is essential in keeping healthcare costs reasonable but these tests should not be excluded at the risk of compromising patient care. For patients with thyroid disorders, the multiplicity of tests available do not make diagnoses more accurate or treatment more effective. A single test, the sensitive thyrotropin assay, most eloquently allows an organized, streamlined approach to the diagnoses and management of patients with thyroid disease. Even the most technologically advanced tests that are available cannot replace the clinical skills of the physician. Clinical acumen combined with the judicious use of diagnostic testing is one of the most important elements in diagnosing and treating a patient.
Thyroid nodules are common and the principal method of diagnosis is fine-needle aspiration cytology (FNAC).
To determine the value of FNAC in the diagnosis of thyroid nodules, thyroid cytology of 253 patients with definitive histology after surgery was analyzed from 1992 to 2002. FNAC was correlated with histology and the sensitivity, specificity and likelihood ratios were calculated. The method of FNAC and number of non-diagnostic aspirates were noted. The frequency of thyroid cancer was investigated in male and females who presented with a solitary thyroid nodule.
The overall sensitivity of FNAC detecting thyroid neoplasia was 55.0%, specificity 73.7% and accuracy 67.2%. Likelihood ratios indicate that a 'malignant' or 'suspicious for malignancy' cytology dramatically increase the pretest probability of thyroid neoplasia. There were no false positive 'malignant' FNAC. Ultrasound guided FNAC had a significantly lower non-diagnostic rate compared to freehand FNAC (P < 0.02). Of 22 males, 22.7% who proceeded to surgery for their solitary nodule had thyroid carcinoma compared with 11.9% of 167 females (P = 0.02).
FNAC was essential to management in this series of patients. 'Malignant' or 'suspicious for malignancy' cytology are absolute indicators for thyroidectomy. FNAC should be undertaken with ultrasound guidance and if possible with a pathologist in attendance to assess sample adequacy. We recommend a high index of suspicion of thyroid cancer in the male patient who presents with a solitary nodule. If solitary nodules are to be observed, repeat FNAC should be undertaken because of the high false negative rate.
Fluorine-18-fluorodeoxyglucose (FDG) PET has become an increasingly important functional imaging modality in clinical oncology. This article will focus primarily on the role of FDG PET during treatment and follow-up of thyroid cancer. The major role of FDG PET is in patients with elevated thyroglobulin (Tg) levels where thyroid cancer tissue does not concentrate radioiodine rendering false-negative results on I-131 scanning. FDG PET imaging takes advantage of the increased uptake of FDG in cancer cells and is sensitive (60-94%) to the detection of recurrent or metastatic cancer in patients who have negative radioiodine scans. The specificity (25-90%) of PET imaging is relatively less than its sensitivity because some inflammatory processes avidly accumulate FDG. PET can fail to localize the tumour sites in some patients with well-differentiated thyroid cancer that retain good iodine ability. This can result the well recognized phenomenon of "flip-flop" depending on the differentiation of the thyroid cancer. Several studies have documented the higher accuracy of PET, compared with other imaging modalities in the evaluation of patients with recurrent or metastatic differentiated thyroid cancer. The value of thyroid stimulating hormone stimulation for FDG PET has recently been reported. Therefore, if available, this method should be considered in all patients of differentiated thyroid cancer with suspected recurrence and/or metastasis.
To review the etiology, diagnosis, and clinical presentation of Graves disease and provide an overview of the standard and adjunctive treatments. Specifically, antithyroid drugs, beta-blockers, inorganic iodide, lithium, and radioactive iodine are discussed, focusing on current controversies.
Primary articles were identified through a MEDLINE search (1966-July 2000). Key word searches included beta-blockers, Graves disease, inorganic iodide, lithium, methimazole, and propylthiouracil. Additional articles from these sources and endocrinology textbooks were also identified. We agreed to include articles that would highlight the most relevant points, as well as current areas of controversy.
Graves disease is the most common cause of hyperthyroidism. The 3 main treatment options for patients with Graves hyperthyroidism include antithyroid drugs, radioactive iodine, and surgery. Although the antithyroid drugs propylthiouracil (PTU) and methimazole (MMI) have similar efficacy, there are situations when 1 agent is preferred. MMI has a longer half-life than PTU, allowing once-daily dosing that can improve patient adherence to treatment. PTU has historically been the drug of choice for treating pregnant and breast-feeding women because of its limited transfer into the placenta and breast milk. Adjuvant therapies for Graves disease include beta-blockers, inorganic iodide, and lithium. beta-Blockers are used to decrease the symptoms of hyperthyroidism. Inorganic iodide is primarily used to prepare patients for thyroid surgery because of its ability to decrease the vascularity of the thyroid gland. Lithium, which acts in a manner similar to iodine, is not routinely used due to its transient effect and the risk of potentially serious adverse effects. In the US, radioiodine therapy has become the preferred treatment for adults with Graves disease. It is easy to administer, safe, effective, and more affordable than long-term treatment with antithyroid drugs. Hypothyroidism is an inevitable consequence of radioiodine therapy. Radioiodine is contraindicated in pregnant women because it can damage the fetal thyroid gland, resulting in fetal hypothyroidism. Bilateral subtotal thyroidectomy, which was once the only treatment available, is now performed only in special circumstances. In addition to the normal risks associated with surgery, laryngeal nerve damage, hypoparathyroidism, and hypothyroidism can occur following that procedure.
Despite extensive experience with medical management, controversy prevails regarding choosing among the various drugs for treatment of Graves disease. None of the treatment options, including antithyroid drugs, radioiodine, and surgery, is ideal. Each has risks and benefits, and selection should be tailored to the individual patient.
Comparison of high and low dosage levels of I-131 in the treatment of thyrotoxicosis
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