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[The giant, pendulant goiter. A case report].

A 48-year-old woman with a monstrous goiter was referred to our hospital. She noticed a growth of the goiter for about 20 years, until now she did not undergo surgery because she was afraid of the operation. In September 1999 she suffered from a cardiac decompensation because of a hyperthyreosis, so she decided to be operated. The examination showed a giant goiter, placed in front of the sternum. After a detailed check of risk factors, we resected the goiter in general anaesthesia. The thyroid gland weighed 5 100 grams, in the histologic examination no signs of malignancy were found. Postoperatively, a hypocalcaemia occurred, without clinical symptoms. The patient was discharged on the 6th postoperative day.

Cardiomyopathy, Dilated↗

Differential diagnosis of hyperthyroidism: Doppler sonographic quantification of thyroid blood flow distinguishes between Graves' disease and diffuse toxic goiter.

The aim of our study was to evaluate the usefulness of color duplex sonography to distinguish Graves' disease from diffuse toxic goiter. 24 patients with Graves' disease and 13 patients with diffuse toxic goiter underwent B-mode- and color duplex sonography of the thyroid gland. All patients had hyperthyroidism and elevated (99m)Tc-uptake. Spectral Doppler recordings were obtained at all thyroid arteries. Representative color flow maps of the thyroid gland were analyzed, calculating the percentage area of the thyroid gland, occupied by color pixels (color pixel density). The B-mode ultrasound pattern was subjectively assessed on a 4-point rating scale. In patients with Graves' disease the mean peak systolic velocity (PSV) (SD) was 110 (+/- 49) cm/s, the mean volume flow rate (VFR) was 123 ( +/- 67) ml/min and the mean color pixel density (CPD) was 33 (+/- 12) %. For patients with diffuse toxic goiter mean PSV (SD) was 43 ( +/- 9) cm/s (p < 0.001), mean VFR was 23 (+/- 10) ml/min (p < 0.001) and mean CPD was 9 (+/- 6) % (p = 0.007). CPD and spectral duplex recordings were positively correlated (CPD/PSV: rs = 0.77, CPD/VFR: rs = 0.75; p < 0.0001). No significant differences were observed concerning RI values. Sensitivity was 87% and specificity 92% for CPD and VFR and 87% and 100% for PSV. We conclude, that color duplex sonography can reliably distinguish diffuse toxic goiter from Graves' disease and therefore contributes significantly to the differential diagnosis of hyperthyroidism in diffuse thyroid disease.

Adult↗

Comparison of the effects of 3,5,3'-triiodothyroacetic Acid and triiodothyronine on goiter prevention and involution and on hepatic and skeletal parameters in rats.

3,5,3'-triiodothyroacetic acid (TRIAC) has been used to suppress pituitary TSH secretion with reported attenuation of extrapituitary effects. We investigated whether equivalent doses of T (3) and TRIAC preventing the induction of goiter by methimazole (MMI) had a different or similar impact on peripheral tissues, such as liver and bone. In particular, we compared the effects of both compounds on the activity of the hepatic thyroid hormone-responsive enzymes, malic enzyme and L-glicerol-3-P dehydrogenase; bone mineral density and biochemical parameters of bone turnover, such as bone alkaline phosphatase (b-ALP) and the carboxy-terminal telopeptide region of type I collagen (beta-CTX); and the activity of thyroid ornithine decarboxylase (ODC). We also compared the effects of T (3) and TRIAC on the involution of MMI-induced goiter. Our results showed that TRIAC was more effective than T (3) to reduce MMI-induced goiter in a short-term goiter involution assay. TRIAC increased hepatic enzymes activity and beta-CTX levels, a parameter of bone resorption, more than T (3). However, bone mineral density was not altered by either treatment. Both compounds even reduced ODC activity at doses that were not effective at the pituitary level. These results demonstrate increased TRIAC hepatic and antigoitrogenic activity compared to T (3). TRIAC induces an imbalance in bone remodeling without affecting bone mineral density. Further studies are required to clarify this point.

Animals↗

The relationship between hyperthyroidism and the distribution of peripheral blood T, NK and B-lymphocytes in multinodular goiter.

Peripheral blood T, NK and B-cell subsets were analyzed in 18 patients with nontoxic multinodular goiter (NMG) and 11 patients with toxic multinodular goiter (TMG) in order to evaluate whether hyperthyroidism modifies the distribution of these cell populations. As a control group, 26 age and sex-matched healthy individuals were included in the study. Lymphoid subsets were analyzed with flow cytometry by double staining immunofluorescence techniques using a large panel of monoclonal antibodies. No differences were found in the absolute or relative numbers in any of the cell populations analyzed in both groups--NMG and TMG--, with the exception of a significant decrease in CD19+ cells in TMG. However, patients with multinodular goiter showed important abnormalities in the distribution of T, NK and B lymphocytes with respect to the control subjects. The pattern of abnormalities detected was characterized by a marked increase in the absolute and relative counts of activated T-lymphocytes (CD3+/HLA-DR+), cytotoxic T-cells (CD57+/CD8+) and of cells expressing NK-related antigens. None of these alterations were related to the serum levels of T3, T4 or TSH. Our results point to the existence of important abnormalities in the distribution of several lymphoid subsets in multinodular goiter, regardless of whether the subjects are euthyroid or hyperthyroid.

Adult↗

Color Doppler imaging of the thyroid gland in a fetus with congenital goiter: a case report.

Fetal goiter is a rare disorder, usually associated with maternal thyroid disease. Antenatal diagnosis of fetal goiter is crucial for the immediate postpartum management of these neonates. A case report is presented of an antenatally diagnosed fetal goiter induced by antithyroid medications. Color Doppler was used to demonstrate a high flow pattern that, unlike in the adult goiter, was associated with hypothyroidism in the neonate. A scan of fetal neck region is recommended in patients with current or previous history of thyroid disease, or if neck extension is noted on routine examination of fetal spine.

Adult↗

Fluorine-18-fluorodeoxyglucose positron emission tomography in the preoperative assessment of thyroid nodules in an endemic goiter area.

BACKGROUND: The aim of this study was to evaluate the usefulness of fluorine-18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in the preoperative assessment of suspicious thyroid nodules. METHODS: A total of 43 patients were examined before surgical resection. In all patients, imaging was obtained at 70 minutes after the intravenous administration of 180 MBq (18)F-FDG. Standard uptake values (SUVs) were calculated. RESULTS: A total of 16 patients with thyroid carcinomas (11 papillary, 3 follicular, 2 anaplastic), 23 thyroid adenomas (11 microfollicular, 10 Hurthle cell, 2 macrofollicular), and 4 patients with degenerative goiter were found. (18)F-FDG uptake in Hurthle cell adenoma, thyroid cancer, microfollicular adenoma, degenerative goiter, and macrofollicular adenoma was 4.4 +/- 2.2, 3.7 +/- 1.9, 1.6 +/- 0.3, 1.2 +/- 0.2, and 0.9 +/- 0.1, respectively. Significant differences were observed between thyroid carcinomas and both microfollicular adenomas and degenerative goiters (P < 0.05), and between Hurthle cell adenomas and both microfollicular adenomas as well as degenerative goiter (P < 0.05). For diagnosis of thyroid carcinoma, 100% sensitivity, 63% specificity, and 100% negative predictive value was found when a cutoff value for SUV of 2 was used. CONCLUSIONS: Our results indicate that thyroid carcinomas, in contrast to most benign thyroid nodules, demonstrate significantly increased glucose metabolism. (18)F-FDG PET is unlikely to differentiate successfully all benign tumors from malignant tumors, but it can help select patients who need surgery, especially if cytology is inconclusive or malignancy cannot be excluded.

Adenoma↗

Amyloid goiter in Familial Mediterranean Fever (FMF): a clinicopathologic study of 10 cases.

FMF Amyloidosis is an important etiological factor of end stage renal disease (ESRD) in Mediterranean Countries. Apart from major target organs as cardiovascular, respiratory and gastrointestinal system, endocrine organs can also be involved. We planned to investigate the thyroid involvement in our amyloidosis group. The aim of this study was to determine clinical characteristics of amyloid goiter in FMF patients and the abnormalities of thyroid function, as well as to identify pathologic characteristics. Twenty-two hemodialysis patients (mean age 34.1 +/- 14 years, range 17-68) whose ESRD secondary to FMF amyloidosis were evaluated with physical examination, serum levels of thyroid hormones, ultrasound examination of thyroid glands, thyroid syntigraphic studies. Goiter was found in 10 patients (4 male, 6 female) having enlarged neck mass (mean age 35 +/- 14 years, range 23-64). The serum levels of thyroid hormones and TSH were normal in 4 patients. Other four cases had euthyroid sick syndrome. Only one patient developed tender enlarged neck mass with subacute thyroiditis symptoms and one had primary hyperthyroidism. Ultrasound examination showed; hypoecoic nodules in 6 patients diffuse multinodular enlargement in 4 patients. Thyroid syntigraphic studies revealed hypoactive nodules in 7 patients and hyperactive nodules in 3 patients. After the laboratory tests were completed, in 10 patients diagnosis were made with fine needle aspiration biopsy. Of 10 patients 5 underwent subtotal thyroidectomy. Immunohistochemical evaluation demonstrated the presence of amyloid AA immunoreactivity in all cases. In conclusion fine needle aspiration from the thyroid when enlarged is useful in the diagnosis of suspected amyloidosis, especially since it is a safe, easily performed procedure. With the help of amyloid goiter diagnosis the patient's prognosis on hemodialysis and with renal transplantation can be predicted. Amyloid goiter must be searched in hemodialysis patients especially in Mediterranean Countries.

Adult↗

Familial nontoxic multinodular thyroid goiter locus maps to chromosome 14q but does not account for familial nonmedullary thyroid cancer.

Thyroid goiter is a common condition that is often associated with iodine deficiency. Familial forms of goiter in areas not known to feature iodine deficiency are much less common. We have performed a genomic search on a single large Canadian family with 18 cases of nontoxic multinodular goiter in which 2 individuals also had papillary lesions highly suggestive of papillary carcinoma. A locus on chromosome 14q (MNG1 [multinodular goiter 1]) has been identified, with a maximal two-point LOD score of 3.8 at D14S1030 and a multipoint LOD score of 4.88 at the same marker, defined by D14S1062 (upper boundary) and D14S267 (lower boundary). The gene encoding thyroid-stimulating hormone receptor (TSHR), which is located on chromosome 14q, is outside the linked region. To determine the role of this gene in familial nonmedullary thyroid cancer (NMTC), we studied 37 smaller pedigrees each containing at least two cases of NMTC. Analysis by both parametric and nonparametric methods indicates that only a very small proportion of familial NMTC (point estimate 0.001, support intervals 0-.6 under a dominant model) is attributable to MNG1.

Canada↗

The Sardinian Autoimmunity Study: 3. Studies on circulating antithyroid antibodies in Sardinian schoolchildren: relationship to goiter prevalence and thyroid function.

The relationship among iodine intake, goiter prevalence, and thyroid autoimmunity remains controversial. In the present article, we report the prevalence of antithyroid antibodies (ATA) in relation to iodine intake, frequency of goiter, and thyroid function in a large group of Sardinian schoolchildren living in areas with borderline iodine sufficiency, or mild to moderate iodine deficiency. A total of 8,040 schoolchildren (4,194 males, 3,846 females, ages 6-15 years) from 29 communities were examined between 1986-1994. Thyroid size was assessed by palpation, according to the Pan American Health Organization (PAHO) criteria. In all cases antimicrosomal (MAb) or antithyroid peroxidase antibodies (TPOAb) and thyrotropin (TSH) were assayed. Urinary iodine was determined in a subgroup of 820 children. ATA was detected in 235 (2.92%) sera (88 males, 2.12%; 147 females, 3.82%; chi2 = 20.41, p < 0.0001). ATA prevalence ranged between 0.0%-7.3% in the 29 communities without any geographical correlation with goiter prevalence and urinary iodine excretion. However, ATA was more frequently detected in goitrous children, especially in females. The presence of ATA was not age-dependent in males, whereas a significant increase of ATA was observed in females older than 11 years of age. Seventy-seven (0.96%) children showed borderline to slightly increased serum TSH (>5.2-32 mU/L). Increased serum TSH concentration was more frequently found in children with ATA, especially at higher titers. In summary, our study in Sardinian schoolchildren indicates: (1) ATA display geographical heterogeneity, which seems to be unrelated to goiter prevalence and/or to iodine supply; (2) ATA are more frequently detected in females older than 11 years of age, suggesting that puberty has a role in determining the predominance in females of thyroid autoimmunity; (3) although most goitrous children are ATA-negative, the prevalence of ATA is increased in children with enlarged glands; (4) ATA is associated with an increased prevalence of subclinical hypothyroidism.

Adolescent↗

Monoallelic deletion in the 5' region of the thyroglobulin gene as a cause of sporadic nonendemic simple goiter.

The cause of sporadic simple goiter is unknown in most cases. Family studies have suggested that this disorder may have a genetic component in some patients. We have previously demonstrated that some cases of endemic and nonendemic simple goiter are associated with a mutation within exon 10 of the thyroglobulin gene. Here we report a study of 50 cases diagnosed as having nonendemic simple goiter, and found 1 case with a large heterozygous deletion within the thyroglobulin gene. The deletion involves the promoter region and the 11 first exons of this gene and is associated with a euthyroid state. We hypothesize that the absence of thyroglobulin synthesis from the deleted allele may be responsible for a decreased level of thyroglobulin mRNA. Euthyroidism would be achieved by thyrotropin (TSH) stimulation but at the expense of goiter development.

Aged↗

Smoking as a risk factor for Graves' disease, toxic nodular goiter, and autoimmune hypothyroidism.

To study the association between smoking and thyroid disease (Graves' disease [E05.0], nodular toxic goiter [E05.2], and autoimmune hypothyroidism [E03.9]) in a low-iodine intake area a case-control study was undertaken. A self-administered questionnaire was issued to 864 consecutive patients with hyperthyroidism and 628 patients with autoimmune hypothyroidism treated at five university or regional endocrinologic clinics in Denmark between January 1, 1990 and December 31, 1998. Each respondent was compared to an age- (+/- 5 years) and gender-matched normal control person randomly drawn from the background population. A total of 621 patients with hyperthyroidism (72%) and 411 patients with autoimmune hypothyroidism (66%) responded. Of these, 617 (542 females) and 408 (364 females) could be analyzed, respectively. There was an increased risk of both Graves' disease (odds ratio [OR] = 2.5, 95% confidence interval [CI]: 1.8-3.5), toxic nodular goiter (OR = 1.7, 95% CI: 1.1-2.5), and autoimmune hypothyroidism (OR = 1.5, 95% CI: 1.1-2.1) with ever smoking compared to never smoking in women, but not in men. With the high proportion of ever-smokers among women (56%), the attributable risk of smoking in women was 45% in Graves' disease, 28% in toxic nodular goiter, and 23% in autoimmune hypothyroidism. Ever use of oral contraceptives was associated with a slightly lower risk of Graves' disease in women, but not of toxic nodular goiter or autoimmune hypothyroidism. In conclusion, smoking is a powerful risk factor for thyroid disease, especially in populations with a high smoking frequency. Oral contraceptive use is associated with a slightly lower frequency of Graves' disease.

Adult↗

Activin betaB expression in rat experimental goiter and human thyroid tumors.

Activins are dimeric proteins of the transforming growth factor beta superfamily, which exhibit multiple functions in gonadal and extragonadal tissues. Expression of activin A, composed of two betaA subunits, has been shown in the thyroid, whereas there has been no study regarding activin B (betaBbetaB) in this gland. In other tissues, such as the gonads, pancreas, and adrenal cortex, expression of both activin betaA and activin betaB has been described. In this study, we detected activin betaB mRNA and protein expression using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry in rat experimental goiter and in human thyroid, including multinodular goiter, follicular adenoma, papillary carcinoma, and follicular carcinoma. Activin betaA mRNA and protein expression was also investigated in rat and human thyroid tissue. The expression of both activin betaB and activin betaA was highest in rat methimazole-induced goiter and in human follicular adenoma, and papillary and follicular carcinomas when compared with multinodular goiter and normal thyroid tissue. The increased expression of activin betaB as well as activin betaA, observed in this study, suggests that activin B and activin A may be involved in the proliferative and neoplastic processes of the thyroid.

Animals↗

Regression of a large goiter in a patient with resistance to thyroid hormone by every other day treatment with triiodothyronine.

Resistance to thyroid hormone (RTH) is a syndrome of reduced responsiveness to thyroid hormone caused, in the majority of cases, by mutation in the thyroid hormone receptor (TR) beta gene. Partial compensation through increase synthesis and secretion of thyroid hormone is mediated through TSH and results in thyroid gland enlargement. Goiters are of variable size but are recalcitrant to surgical treatment, and tend to recur. We describe a 17-year-old girl with a very large goiter cosmetically unacceptable to the patient. She was the index case of a large Azorean family harbouring the TRbeta mutation R243Q. Complete goiter regression was achieved without significant side effects by administration of L-T3 every other day. The required dose of 250 microg suppressing TSH to values below 0.1 mU/L was derived by titration. Supraphysiological doses of L-T3 can be given safely as long-term treatment of goiter in patients RTH.

Child↗

Evidence for the segregation of three different mutated alleles of the thyroglobulin gene in a Brazilian family with congenital goiter and hypothyroidism.

We have previously reported a Brazilian family with congenital goiter, hypothyroidism, and marked impairment of thyroglobulin (Tg) synthesis. Analysis of the Tg mRNA in the goiter of one of the siblings revealed a cytosine to thymine transition creating a stop codon at position 1510. This point mutation is removed from the majority of Tg mRNA transcripts by the preferential generation in the goiter of a 171 nt deleted Tg mRNA by alternative splicing. The nonsense mutation destroys a TaqI site at this position in the mutant Tg gene. Using polymerase chain reaction (PCR) amplification and TaqI digestion we found that two siblings affected with goiter and hypothyroidism, as well as the father and three siblings with normal thyroid function, are all heterozygous for the nonsense mutation. This implies that an additional mutation must be present in the affected individuals, generating a compound heterozygote genotype. A new polymorphism within the thyroglobulin gene represented by three alleles has been detected. This was documented by the TaqI restriction enzyme and phTgM3 probe hybridization that showed a three allelic polymorphism with fragment sizes of 16.5 kb (allele A), 14.5 kb (allele B) and 11.0 kb (allele C). Segregation analysis of these alleles in the family indicated that the two affected siblings were homozygous for the allele C. In contrast the unaffected father and three other siblings, who carried the nonsense mutation, were heterozygous for alleles B and C. Analysis of the Tg genotypes implies that two additional mutations of the Tg gene must segregate in this family to account for the observed phenotypes.

Adult↗

Activating thyrotropin receptor mutations in histologically heterogeneous hyperfunctioning nodules of multinodular goiter.

Activating thyrotropin (TSH) receptor mutations have been found in toxic adenomas and in hot nodules contained in toxic multinodular goiter. The typical feature of multinodular goiter is the heterogeneity in morphology and function of different follicles within the same enlarged gland. In this report we describe a patient with a huge multinodular goiter, normal free triiodothyronine (FT3) and free thyroxine (FT4) serum values, and subnormal TSH serum concentration. Thyroid scintiscan showed two hot areas corresponding to the basal and apical nodules of the left lobe. The right lobe was poorly visualized by the radioisotope. The patient underwent thyroidectomy, and histological examination of the tissue was performed. Genomic DNA was extracted from the tissue specimen and direct sequencing of the TSH receptor and Gs alpha genes was done. At histology, one hyperfunctioning nodule had the typical microscopic structure of thyroid adenomas, and the other contained multiple macrofollicular areas not confined by a capsule. In spite of this histological difference, both hyperfunctioning nodules harbored a mutation of the thyrotropin receptor (TSHr) gene: an isoleucine instead of a threonine in position 632 (T632I) in the first nodule and a methionine instead of an isoleucine in position 486 (I486M) in the second nodule. In conclusion, our findings show for the first time that gain-of-function TSHr mutations are not only present in hyperfunctioning thyroid nodules with the histological features of the true thyroid adenomas, but also in hyperfunctioning hyperplastic nodules contained in the same multinodular goiter.

Cyclic AMP↗

Expression of transforming growth factor beta1, beta2, and beta3 in multinodular goiters and differentiated thyroid carcinomas: a comparative study.

The various isoforms of transforming growth factor-beta (TGFbeta) are growth-inhibiting cytokines for cells of epithelial origin. In malignant thyroid tumors, several studies documented a high expression of TGFbeta in the majority of thyroid follicular cells suggesting a possible role as an inhibitor of cell proliferation. In contrast to this uniform pattern of TGFbeta expression in thyroid cancer, scarce and controversial data have been reported on the expression of TGFbeta in benign multinodular goiter. In the present study, we therefore analyzed the expression of TGFbeta1, TGFbeta2, and TGFbeta3 in normal thyroid tissue, multinodular goiters and papillary thyroid carcinomas by immunohistochemistry. In normal thyroid tissue, expression of the 3 TGFbeta isoforms was barely detectable. However, in the carcinomas, almost all epithelial cells displayed immunoreactivity for the three TGFbeta isoforms. In the nodules from multinodular goiters, all 3 isoforms were found to be expressed although the immunolocalization of the 3 proteins was highly variable. TGFbeta-immunostaining was found in scattered clusters of variable size and, its expression pattern was heterogenous among individual cells within single follicles. TGFbeta-positivity was present in spite of immunostaining for proliferating cell nuclear antigen (PCNA), a marker for actively proliferating cells. In conclusion, this study shows that thyroid carcinomas and benign tumors express the TGFbeta1, TGFbeta2, and TGFbeta3 isoforms. In contrast to the abundant and homogeneous expression in differentiated thyroid carcinomas, TGFbeta expression displays a highly variable interfollicular and intrafollicular pattern in multinodular goiters, suggesting an important role of TGFbeta isoforms in tumorigenesis of thyroid cells.

Adenocarcinoma, Follicular↗

The effect of iodine administration on the development of thyroid autoimmunity in patients with nontoxic goiter.

OBJECTIVE: Previous studies, mostly performed in iodine-deficient areas, have suggested that the administration of iodine to patients with endemic goiter may be associated with the development of thyroid autoantibodies (ThAbs); however, this has not been a consistent finding. In this study, we evaluated the effect of iodine on thyroid function and on the development of indices of autoimmunity (ThAbs and lymphocytic infiltration) in an iodine replete area. METHODS: Iodized oil (1 mL) was administered intramuscularly to 40 euthyroid patients with nontoxic goiter, adequate iodine intake, and absent or normal levels of ThAbs. Blood and urinary samples were taken at time 0, 3, 6, and 12 months after iodine administration. Thyroid volume was evaluated and fine-needle aspiration (FNA) was performed at 0, 6, and 12 months. RESULTS: Seven patients developed abnormal levels of ThAbs at some time between 3 and 12 months after iodine administration (p = 0.017). Mean anti-thyroglobulin (Tg) antibody levels increased at 6 months without reaching abnormal levels, but did not reach statistical significance (p = 0.062). Lymphocytic infiltration was detected in FNA smears in 10 cases before and in 27 cases after treatment (p = 0.0003). Triiodothyronine (T3) decreased at 12 months of follow-up, while thyroxine (T4) and thyrotropin (TSH) levels did not change significantly. A decrease in the mean levels of thyroglobulin as well as a small reduction in goiter size was observed at 6 and 12 months. CONCLUSION: The administration of iodized oil to patients with small nontoxic goiter in an iodine-replete area was accompanied by the development of abnormal levels of ThAbs in some cases and by an increase in thyroid lymphocytic infiltration.

Adult↗

Preoperative embolization of thyroid arteries in a patient with large multinodular goiter and papillary carcinoma.

We herein report the case of a 51-year-old woman, who presented with a large goiter (250-300 g on palpation) with extension to the mediastinum and compression of the trachea causing dyspnea and with associated lumbar pain. Although two fine-needle aspiration biopsies of the gland were negative, a biopsy of a lesion in the spine shown on computed tomography (CT) scan was positive for metastatic papillary thyroid carcinoma. Because of the extent of the goiter and the potential of significant blood loss, total thyroidectomy was considered to be high risk. In an attempt to reduce the goiter size and try to minimize surgical risks, preoperative embolization with polyvinyl alcohol in an emulsion with histoacryl particles was performed 7 days before surgery under conventional angiography. This procedure allowed a significant reduction in blood perfusion to the gland, which resulted in a decrease on the size of the goiter facilitating surgical removal of the gland.

Angiography↗