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Geographical distribution of subclinical autoimmune thyroid disease in Britain: a study using highly sensitive direct assays for autoantibodies to thyroglobulin and thyroid peroxidase.

In order to determine whether the geographical distribution of autoimmune thyroid disease in Britain is influenced by the pattern of iodine intake, the prevalence of subclinical disease (detectable antithyroid antibodies in biochemically euthyroid individuals) has been measured in female blood donors from seven towns in England and Wales previously characterised in terms of past and present iodine intake. Thyroglobulin antibody and thyroid peroxidase antibody were measured by highly sensitive assays which are based on the direct interaction between antibody and radiolabelled antigen. Excluding cases of overt thyroid disease (biochemically hypo- or hyperthyroid with thyroid antibodies), the overall prevalences of the antibodies in sera from the 698 female blood donors were 17.8% for thyroglobulin antibody and 17.8% for thyroid peroxidase antibody. Both antibodies were found in 12.3% of the female blood donors. In contrast, the prevalences of thyroglobulin antibody and thyroid peroxidase antibody were 41 and 43%, respectively, in the 117 female relatives of 18 probands with autoimmune thyroid disease, but the highest prevalences were observed in groups of women patients with Graves' disease (N = 39) or Hashimoto's disease (N = 39) (51, and 97% for thyroglobulin antibody, respectively, and 72 and 97% for thyroid peroxidase antibody, respectively). Antibody prevalence increased with age in the female blood donors rising from 10.6% at age 18-24 to 30.3% at age 55-64 for thyroglobulin antibody and from 14.9% at age 18-24 to 24.2% at age 55-64 for thyroid peroxidase antibody. Geographical differences in the prevalences of both antibodies were not significant and did not correlate with either the previous goitre prevalence or with current differences in iodine intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Thyroid size and thyroid function during pregnancy: an analysis.

An analysis of all available studies of thyroid size and function in pregnancy reveals that thyroid size, estimated by inspection and palpation or measured more accurately by ultrasonography, increases in pregnancy in areas of iodine deficiency but not in those with sufficient iodine. The increase in average thyroid size is within the normal range, and can partly be prevented by treatment with extra iodine or thyroxine. There is a slight transient increase in free thyroxine in the first trimester, probably as a result of physiological stimulation of thyroid function by human choriogonadotrophin. These levels then decrease by about 30% to low normal values in the second and third trimesters of pregnancy in both iodine-depleted and -replete areas. These changes resemble those of non-thyroidal illness and may well play a role in reducing energy expenditure during pregnancy. The increase in thyroid size in iodine-deficient areas is probably due to autoregulatory mechanisms of iodine on thyroid growth. The hypothesis is supported by the fact that, during pregnancy, thyroid volume and thyroid function adapt in a physiological way to meet the increased demands for iodine and energy.

Female↗

Expression pattern of the pendrin and sodium/iodide symporter genes in human thyroid carcinoma cell lines and human thyroid tumors.

OBJECTIVE: In the present study we analyzed the pattern of pendrin (PDS) and sodium/iodide symporter (NIS) gene expression in some thyroid carcinoma cell lines and a series of thyroid tumoral tissues. METHODS: Total RNA was extracted from all cell lines and from 53 tissues, and gene expression was examined by RT-PCR. Semiquantitative 'multiplex' RT-PCR was used to assess variations in PDS gene expression among various thyroid pathologies. Pendrin expression was determined in the thyroid cell lines by Western blot analysis. RESULTS: PDS mRNA was expressed in all the cells investigated; conversely, NIS mRNA was detectable only in the B-CPAP cells. Pendrin protein was expressed in B-CPAP and WRO cell lines, reduced in FRO and absent in ARO cells. PDS gene expression was not detected in 5 of 25 differentiated thyroid carcinomas (DTC) while NIS gene was not expressed in six carcinomas. A concordance expression of both PDS and NIS transcripts was found in 20 DTC. In contrast, 2 neoplastic thyroid tissues carrying undetectable PDS mRNA maintained NIS transcript, and 3 thyroid carcinomas negative for NIS mRNA retained the expression of PDS gene. A semiquantitative analysis showed that the mean PDS mRNA levels were significantly decreased in DTC tissues. CONCLUSIONS: Our data demonstrate that pendrin expression: (i) is present in the more differentiated thyroid carcinoma cell lines studied; (ii) is reduced or absent in DTC tissues; (iii) may not correlate with the NIS expression. These alterations may contribute to the loss of iodine concentration ability detected in thyroid tumors.

Adenocarcinoma, Follicular↗

The prevalence of anti-thyroid peroxidase antibodies and autoimmune thyroiditis in children and adolescents in an iodine replete area.

BACKGROUND: The iodine supply of the population in Berlin has normalized during the last 5 Years. Therefore autoimmune thyroiditis has become the most important differential diagnosis in children and adolescents with goiter. OBJECTIVE: The aim of the present study was to define the prevalence of anti-thyroid peroxidase (TPO) antibodies and autoimmune thyroiditis in children and adolescents with a normalized iodine intake. DESIGN: To enable the measurement of antibodies to thyroid peroxidase (anti-TPO-Ab) in a large cohort, a method to determine anti-TPO-Ab in dried filter paper blood spots was established. In co-operation with pediatricians the antibody prevalence was assessed and data regarding thyroid size, echostructure and the medical history concerning iodine intake and familial thyroid diseases were collected. METHODS: 660 children and adolescents participated in the study; urinary iodine, TSH and TPO-Ab were measured and an ultrasound of the thyroid gland was performed. RESULTS: The sensitivity of the newly established filter paper assay was 91.8% and specificity was 100%. The results confirmed the improved iodine supply, with a median urinary iodine concentration of 139 microg iodine/g creatinine. The prevalence of anti-TPO-Ab was 3.4% with a female to male ratio of 2.7:1. CONCLUSION: The prevalence of anti-TPO-Ab is lower or equal to data reported from other iodine sufficient areas. Data from a moderate iodine deficiency in schoolchildren range from 0.0 to 7.3%. Using the new filter paper method field studies can be implemented to monitor the effect of changes in iodine nutrition on thyroid autoimmunity. Furthermore, this study on the prevalence of anti-TPO-Ab in a cohort of healthy children and adolescents in an iodine replete area can serve as reference data for future investigations and for the comparison with other groups of patients with increased risks for thyroid autoimmunity.

Adolescent↗

Recombinant human thyroid-stimulating hormone (rhTSH) in the radioablation of well-differentiated thyroid cancer: preliminary therapeutic experience.

Iodine-131 (I-131) ablation of thyroid remnant and/or persistent, recurrent or metastatic tumour is part of the initial and subsequent management of well-differentiated thyroid carcinoma. Key to optimizing the safety and efficacy of radioablation is maximizing the selective uptake of radioiodine by normal or neoplastic thyroid tissue. This is achieved by ensuring adequate serum concentrations of thyroid-stimulating hormone (TSH). Exogenous TSH administration obviates the thyroid hormone suppression therapy withdrawal that is necessary for endogenous TSH elevation. It also avoids the marked morbidity, discomfort, and impairment in professional and educational pursuits and quality of life that often result from such withdrawal. Multicentre clinical studies have documented the safety and efficacy of recombinant human TSH (rhTSH) in promoting radioiodine uptake in the diagnostic scanning of well-differentiated thyroid cancer. Study of the use of rhTSH to facilitate radioablation of remnant and malignant thyroid tissue is at an earlier stage, with formal clinical investigation underway. Since April 1995, however, rhTSH has been employed as a radioablative adjunct in over 100 patients in the manufacturer's Compassionate Use Program. Twelve of these cases, reported or reviewed in the present paper, provide preliminary evidence that rhTSH is safe and effective in the radioablation setting. More data are needed to confirm these observations and to provide guidelines for optimal radioiodine dosing, and should be furnished by ongoing clinical investigation. rhTSH is the only acceptable treatment option in a subgroup of patients with well-differentiated thyroid cancer, including those with hypopituitarism, ischaemic heart disease, a history of "myxoedema madness," debilitation due to very advanced disease or inability to produce TSH due to continued production of thyroxine by thyroid remnant or metastatic tumour. Therapeutic use of rhTSH may be considered in an increasing number of other cases.

Adenocarcinoma, Follicular↗

Methylation of the thyroid-stimulating hormone receptor gene in epithelial thyroid tumors: a marker of malignancy and a cause of gene silencing.

Thyroid-stimulating hormone receptor (TSHR) expression is frequently silenced in epithelial thyroid cancers associated with decreased or absent TSH-promoted iodine uptake. To study the underlying molecular mechanism of decreased TSHR expression, we examined the methylation status of the TSHR gene promoter by sequencing bisulfite-treated DNA from thyroid tumors. After identification of methylated sites by sequencing bisulfite-treated DNA, we used methylation-specific polymerase chain reaction and found frequent CpG methylation in papillary thyroid cancer (23 of 39 patients; 59%) and follicular thyroid cancers (7 of 15 patients; 47%). In contrast, we saw no methylation in normal thyroid tissues and benign adenomas (0 of 8 patients; 0%). In human thyroid tumor cell lines, we observed that TSHR was normally expressed at the protein and mRNA level in cells where the TSHR gene was unmethylated, whereas it was silenced in cell lines where the TSHR promoter was hypermethylated. Treatment of the latter cells with a demethylating agent partially restored TSHR expression. We thus demonstrate aberrant methylation of human TSHR as a likely molecular pathway responsible for the silencing of this gene in thyroid cancers. We propose that methylation of TSHR may provide a novel diagnostic marker of malignancy and a basis for potential use of demethylating agents in conjunction with TSH-promoted radioiodine therapy for epithelial thyroid cancers.

Adenoma↗

[The effect of surgical treatment of benign thyroid disease on serum anti-thyroid antibodies].

The mechanisms of development of benign thyroid disease are still not entirely clarified. Immune disorders are possibly engaged in the thyroid pathological conditions. The aim of this prospective study was to follow up the dynamics of serum levels of anti-thyroid antibodies in patients with benign thyroidal disease as well as the local lymphocytic reaction. The autoantibodies to thyroglobulin and thyroid microsomes were detected prior to the surgery and on the 12th month after it using microhemaglutination test. Thyroid resection was performed depending on changes in patients. Lymphocytic infiltration of the thyroid gland from surgical histological specimens was found in various degree in the patients. Serum titres of anti-thyroid antibodies tended to fall in the majority of the patients a year after the surgical treatment. Anti-thyroglobulin antibodies were found in 60% of the patients prior to the surgery and anti-microsomal--in 31.4%. A year after surgery they were detected in 4.3% and 1.4% of the patients respectively. The described changes show that the dynamics of anti-thyroid antibodies may correlate with the effect of surgical treatment and eventual prognosis of relapse.

Adult↗

[Diagnosis and treatment of chronic lymphocytic thyroiditis coexistent with thyroid malignancy].

OBJECTIVE: To explore the principles of diagnosis and treatment of chronic lymphocytic thyroiditis (CLT) coexistent with thyroid malignancy. METHODS: The clinical data of 52 patients with CLT, including clinicopathologic features, treatment, and prognosis were retrospectively analyzed. Among these 52 patients, 40 patients had coexisting thyroid carcinoma (TC group) and 12 had coexisting thyroid lymphoma (TL group). RESULTS: These two thyroid malignancies accounted for 13.87% of all the CLT inpatients during this period, in which 10.67% were CLT with carcinoma and 3.20% were CLT with lymphoma. Significant differences existed between TC group and TL group in sex (P = 0.008) , age (P = 0.000), and B-mode ultrasound findings (P = 0.000). Most patients in TC group received total lobectomy of one lobe and subtotal lobectomy of the other side, of which some received elective lymphadenectomy. The operations varied among patients in TL group, and most of them received chemotherapy after surgery. The median follow-up was (35.51 +/- 39.84) months for 37 patients in TC group, and 36 patients survived with a median period of (34.50 +/- 39.91) months; the median follow-up was (39.50 +/- 29.00) months for 12 patients in TL group, and 10 patients survived with a median period of (44.70 +/- 28.78) months. CONCLUSIONS: CLT with thyroid malignancies are not uncommon in clinical practice. While thyroid carcinoma accounts for majority of these malignancies, its clinicopathologic features, treatment, and prognosis differs with thyroid lymphoma. Surgery may be appropriate for CLT patients with rapid thyroid enlargement or nodule, and for patients with solitary solid nodule or nodules with calcification revealed by B ultrasound.

Adult↗

Epidermal growth factor receptors on cultured neoplastic human thyroid cells and effects of epidermal growth factor and thyroid-stimulating hormone on their growth.

Epidermal growth factor (EGF) receptors on primary-cultured human thyroid cells from 27 neoplasias (nine adenomas and 18 differentiated carcinomas) were analyzed and compared with those on the cultured nonneoplastic part of human thyroid cells. Total binding of 125I-EGF to the nonneoplastic part, adenoma, and carcinoma cells did not differ significantly. Scatchard analysis showed that the neoplastic human thyroid cells, like their adjacent nonneoplastic counterparts, consistently possessed EGF receptors with two components. In a paired study of five patients, the association constant of the carcinoma cells' high-affinity component (Ka1) was found to be significantly lower than that of adjacent nonneoplastic thyroid cells (P less than 0.05). Furthermore, a study of the cells from 18 carcinomas revealed that overall their Ka1s (4.15 +/- 0.82 x 10(9) M-1, mean +/- SEM) were significantly lower than those of adenoma cells (10.34 +/- 1.51 x 10(9) M-1, n = 9) and of nonneoplastic cells adjacent to them (8.32 +/- 0.84 x 10(9) M-1, n = 23). The difference in Ka1s for adenoma and nonneoplastic thyroid cells was not statistically significant. The number of receptor sites (Cmax) per cell was not significantly different in any of the three. Incorporation of [3H]thymidine (dThd) increased significantly in all kinds of thyroid cells examined following the addition of 10 nM EGF, and the paired study showed that the size of this increase was not significantly different in neoplastic and adjacent nonneoplastic cells. The addition of 300 microunits/ml of thyroid-stimulating hormone caused a significant increase in dThd incorporation by adenoma cells but not by carcinoma or nonneoplastic cells. Furthermore, combined treatment with EGF and thyroid-stimulating hormone additively promoted adenoma cell growth only. A close inverse relationship was observed between Ka1 and the stimulatory effect of EGF on the dThd uptake in both nonneoplastic thyroid cells and adenoma cells. Carcinoma cells also showed similar profiles, but Ka1 relative to dThd increases were much smaller than the other two.

Adenoma↗

Cytotoxic mechanisms in autoimmune thyroid disorders and thyroid-associated ophthalmopathy.

Cytotoxic antibodies against thyroid cells and eye muscle cells, measured as antibody-dependent complement-mediated cytotoxicity and ADCC, have been demonstrated in sera from patients with Hashimoto's thyroiditis and thyroid-associated ophthalmopathy, respectively. Such antibodies are probably never present in the absence of target cell damage. Because cell-mediated cytotoxicity plays an important role in experimental autoimmune thyroiditis, further studies are necessary to elucidate the roles of NK cells, K cells, and cytotoxic T lymphocytes in the thyroid cell damage in AITD and orbital cell damage in ophthalmopathy. The socalled aberrant expression of HLA-DR antigens on thyroid cells and orbital cells and the gamma-interferon production by activated T cells may be both intimately associated with the development of autoimmune reactions in the thyroid and the orbit. Cytotoxic antibodies and cytotoxic T lymphocytes against antigens shared between eye muscle cells and thyroid cells may be directly responsible for the eye muscle cell damage in endocrine ophthalmopathy, and they may explain the close association of ophthalmopathy with Graves' hyperthyroidism and Hashimoto's thyroiditis.

Animals↗

Preoperative thyroid ultrasonography and fine-needle aspiration cytology in ectopic thyroid.

Ectopic thyroid tissue is a rare entity. The occurrence of a thyroid carcinoma in such aberrant thyroid tissue has been reported, but is very rare. Surgical excision is considered the treatment of choice in managing the lesions associated with ectopic thyroid. If the ectopic thyroid is excised, all the thyroid may have been ablated, resulting in permanent hypothyroidism. We report two cases of ectopic thyroid in emphasizing the importance of thyroid ultrasonography and fine-needle aspiration (FNA) cytology in evaluating ectopic thyroid before surgery.

Adult↗

[CD26/dipeptidyl peptidase IV and thyroid peroxidase as molecular markers for differentiated thyroid carcinoma].

Differential expression of two enzymes, dipeptidyl peptidase IV (CD26/DPP IV) and thyroid peroxidase (TPO), in neoplastic thyroid tissues was studied by Northern blot analysis and histochemical analysis using 31 thyroid tissue specimens of various thyroid diseases. On Northern blot analysis, all 16 differentiated carcinomas (12 papillary and 4 follicular carcinomas) overexpressed CD26/DPP IV mRNA, whereas all 14 benign tissue specimens (4 normal thyroid, 4 Graves' disease, 2 adenomatous goiters and 4 follicular adenomas) showed faint expression of CD26/DPP IV mRNA. All 14 benign tissues expressed high levels of TPO mRNA, whereas all 12 papillary carcinomas strongly underexpressed TPO mRNA. A medullary carcinoma did not show any mRNA expression of either enzyme. TPO mRNA expression in differentiated carcinomas did not always correlate with mRNA expression of thyroglobulin, thyroid stimulating hormone receptor, and thyroid transcription factor-1. Northern blot analysis also revealed that CD26/DPP IV is a more specific marker of differentiated carcinoma than three proto-oncogenes previously reported to increase mRNA expression in thyroid carcinomas: c-met, c-erbB-2, and EGF-R. Histochemically, all 14 benign tissues were CD26/DPP IV negative and strongly TPO positive, while all 12 papillary carcinomas were strongly CD26/DPP IV positive and TPO negative. Three of 4 follicular carcinomas were histochemically positive for the two enzymes. These findings suggest that the differential expression of these two enzymes can be applied to study the thyroid tumorigenesis.

Adenocarcinoma, Follicular↗

Thyroid antibodies in thyroid diseases.

The cell surface expression of the thyroid microsomal antigen is confined to the apical microvilli of the polarized cells in intact or semi-intact thyroid acini. This makes it possible to envisage a pathogenetic role for the commonest antibodies found in thyroid autoimmunity by mechanisms involving complement- and antibody-dependent cytotoxicity. TSH rereceptor antibodies can now be differentiated into those that stimulate hormone synthesis and release (TSI), and those which mimic TSH in its growth-promoting function (TGI). TGI were demonstrated in goitrous Graves' disease and in some patients with euthyroid non-toxic goitres, diffuse or nodular, defining a new variety of thyroid autoimmunity. In patients with non-toxic goitre there is hardly any lymphoid thyroiditis and a low incidence of thyroglobulin or microsomal antibodies, the main expression of autoimmunity being the impetus to thyroid hyperplasia and hypertrophy. TSH receptor antibodies of both types, TSI and TGI, can either be stimulating or have blocking effects (TSI block and TGI block). Atrophy of the thyroid gland in myxoedema is due to blocking of the normal pituitary-controlled repair mechanism. In goitrous thyroiditis cell re-growth as a result of increased TSH can occur, as there are no blocking antibodies. In some patients with 'simple' euthyroid goitres, TSI blockers prevent the onset of hyperthyroidism while growth-promoting antibodies give rise to the goitre.

Antibody Specificity↗

Gray-scale and color Doppler sonographic findings in a case of subacute granulomatous thyroiditis mimicking thyroid carcinoma.

Subacute granulomatous thyroiditis is a common disease of unknown cause and is usually self-limiting, with complete resolution of symptoms occurring spontaneously or after steroidal treatment. We report a case of subacute granulomatous thyroiditis in a 62-year-old woman whose clinical presentation was consistent with thyroid carcinoma. Gray-scale and color Doppler sonography revealed marked enlargement of the left lobe of the thyroid and markedly hypoechoic, ill-defined focal areas in both lobes. No flow was noted on color Doppler sonographic examination. Fine-needle aspiration of the thyroid was performed, and histopathologic examination of the specimen confirmed the diagnosis of subacute granulomatous thyroiditis. The patient received prednisolone therapy (20 mg/day) for 2 weeks and recovered well. This case report is the first to describe the gray-scale and color Doppler sonographic appearances of subacute granulomatous thyroiditis. This disease should be included in the differential diagnosis of patients with clinical signs and symptoms of thyroid carcinoma. Histopathologic examination is necessary to confirm the diagnosis.

Biopsy, Needle↗

Ultrasonography of the thyroid gland in pregnancies complicated by autoimmune thyroid disease.

Thyroid function and ultrasonographically determined thyroid volume were studied in nine pregnant women with diagnosed autoimmune thyroid disease at regular intervals during pregnancy and two months after delivery. The results were compared to the findings in ten healthy pregnant women. In ultrasound examinations seven of the patients showed definite morphological changes such as hypoechogeneity and inhomogeneity of the thyroid gland, which did not change during the course of pregnancy nor during the post-partum period of eight weeks. There were no morphological changes in the thyroid glands of the control group. The mean thyroid volume did not significantly change during pregnancy and after delivery in both the patient group and controls. The mean thyroid volume was smaller in the study group, with 7.55 ml (SD 6.01) compared to the controls with 11.29 ml (SD 5.61), a difference which was not statistically significant. Neither course of pregnancy nor fetal outcome was influenced by inactive autoimmune disease of the thyroid.

Adult↗

Adenoviral infection of thyroid cells: a rationale for gene therapy for metastatic thyroid carcinoma.

BACKGROUND: Patients with thyroid carcinoma experience excellent long-term survival; however, up to 16% will die of their disease. We have transformed a rat thyroid follicular cell line (FRTL-5) with a gene (TGCT) that mimics a known mutation associated with thyroid neoplasms. These cells form subcutaneous tumors that metastasize to lung in nude mice. METHODS: In anticipation of developing gene therapy against this thyroid carcinoma model, we (1) tested whether adenovirus containing the beta-galactosidase gene could infect FRTL-5 cells and neonatal rat thyroid and (2) evaluated the ability to kill FRTL-5 cells by transfecting them with a transgene in which the thyroglobulin promoter (TG) directed the expression of herpes simplex virus type I thymidine kinase (HSV1TK) and treating TG-HSV1TK-transfected cells with 5 micrograms/ml ganciclovir. RESULTS: Nearly 100% of the TG-HSV1TK but only 5% of control cells were killed by addition of ganciclovir. Histochemical staining for beta-galactosidase activity demonstrated infection of FRTL-5 cells and neonatal rat thyroid tissue by adenovirus beta-galactosidase. CONCLUSIONS: These data demonstrate the feasibility of using adenovirus as vector to infect thyroid cells in vivo and provide a rationale for development of gene therapy for treatment of thyroid cancer.

Adenoviridae↗

Occult thyroid pathology in the young adult: an autopsy study of 138 patients without clinical thyroid disease.

Thyroid glands from autopsies on 138 adults, ages 20 to 40 years, with no known clinical or laboratory evidence of thyroid disease, were serially sectioned at 2 mm intervals and microscopically examined for occult thyroid disease and anatomic variations. Occult papillary carcinoma was found in 3% of the glands, along with a single case of medullary carcinoma. The prevalence of occult thyroid carcinoma in this group of young adults is significantly less than that reported in the literature in people over forty (P less than .001). The glands demonstrated a number of other morphologic changes of importance to surgical pathologists. The thyroid capsule was incomplete in 62% of the glands. Thyroid follicles were found in the capsule in 14% of cases and thyroid follicles or nodules were outside the gland in perithyroid connective tissue in 88% of cases. Thyroid follicles were identified in 7% of cases in perithyroid strap muscles attached to the pyramidal lobe. A number of other, less common anatomic variations were also seen.

Adenoma↗

Early diagnosis and curative therapy of medullary thyroid carcinoma by routine measurement of serum calcitonin in patients with thyroid disorders.

To identify patients with medullary thyroid carcinoma (MTC) at a potentially curable stage of the disease, serum concentrations of calcitonin (hCT) were determined in 14,000 patients (including 10,158 patients with thyroid nodules) referred to a thyroid outpatient clinic. Excluding patients in whom elevated basal hCT concentrations had already been known at the time of their referral, 507 patients with thyroid nodules presented basal concentrations of hCT of more than 10 pg/ml. Following stimulation by IV pentagastrin (0.5 microg/kg BW), hCT concentrations of more than 100 pg/ml were seen in 103 patients. This group included 32 new cases of MTC (29 patients with sporadic MTC and 3 new index cases of the familial form) and 43 patients with C cell hyperplasia (CCH). Among the 3,843 patients without thyroid nodules, 2 were found to harbor sporadic MTC while 4 had CCH. As compared to 1.1 cases of MTC per 1,000 patients with nodular thyroid diseases diagnosed in our institution before hCT screening was begun, 3.2 cases of MTC per 1,000 patients were identified when hCT was determined in all patients with thyroid nodules. The determination of hCT in all patients with thyroid nodular disease facilitates the timely diagnosis of MTC, thus providing the chance of curative surgery.

Adult↗