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Analysis of human sodium/iodide symporter, thyroid transcription factor-1, and paired-box-protein-8 gene expression in benign thyroid diseases.

The ability to concentrate iodide, a fundamental property of normally functioning thyroid tissue, is altered in various thyroid diseases. Given the critical role of the Na+/I- symporter (NIS) in controlling iodide access to the thyroid gland, altered expression of NIS may be responsible, at least in part, for an enhanced or diminished capacity to concentrate iodide. In this study, we used Northern blot analysis, a newly established quantitative polymerase chain reaction (PCR) assay and in addition hNIS-directed immunohistochemical analysis to assess the levels of hNIS mRNA and protein expression in various localized and diffuse benign thyroid abnormalities, including Graves' disease (GD), scintigraphically cold solitary benign thyroid nodule (CBTN), nontoxic multinodular goiter (NMNG), solitary autonomously functioning thyroid nodule (AFTN), and mild diffuse iodine deficiency goiter (IDG). In addition, in view of the recent identification of putative binding sites for the transcription factors thyroid transcription factor-1 (TTF-1) and human paired-box-protein-8 (Pax-8) in the human NIS gene promoter, we used reverse transcriptase-polymerase chain reaction (RT-PCR) to assess in these same samples the levels of TTF-1 and Pax-8 gene expression. Northern blot analysis revealed high levels of hNIS gene expression in thyroid specimens derived from patients with GD and AFTN. In contrast, levels of hNIS mRNA expression were moderate in NMNG, low in diffuse IDG, and very low in CBTN. Quantitative RT-PCR analysis of hNIS mRNA transcripts revealed variable but generally low levels of hNIS gene expression in IDG and NMNG, and undetectable or very low levels of hNIS mRNA in all scintigraphically CBTN studied. In contrast, markedly elevated levels of hNIS mRNA transcripts were detected in active GD (up to 17-fold) and AFTN (up to 25-fold). Immunohistochemical analysis revealed abundant hNIS protein expression by thyroid follicular cells in GD, moderate and heterogeneous levels in NMNG, and very low levels in CBTN. hNIS mRNA levels were correlated with TTF-1 and Pax-8 gene expression in GD and, to a lesser degree, in AFTN, NMNG, and IDG, but not in CBTN. In general, hNIS gene expression was more closely correlated with TTF-1 as compared to Pax-8 gene expression. In conclusion, the abundance of hNIS mRNA and protein expression in a broad range of benign thyroid pathologies correlated well with their functional state as assessed by thyroid scintigraphy. In addition to TTF-1 and Pax-8, other transcription factors and enhancer elements may contribute to regulation of NIS gene promoter activity.

Carrier Proteins↗

Total thyroidectomy for benign thyroid disease.

BACKGROUND: The goal of this study was to evaluate the safety and efficacy of total thyroidectomy performed for benign thyroid disease. METHODS: A total of 106 consecutive patients undergoing total thyroidectomy for benign disease from October 1982 to July 1995 were reviewed. The 33 men and 73 women had an average age of 46 years (range, 16 to 82 years). Indications for total thyroidectomy were a thyroid nodule with the history of head and neck radiation in 36 patients, bilateral thyroid nodules in 35, needle biopsy of a follicular neoplasm or frozen section diagnosis of a possible malignancy in 18, and toxic goiter in 17. Total thyroidectomy was performed as the primary operation in 98 patients, and 8 patients had a completion reoperation for recurrent disease. RESULTS: Pathology findings revealed benign nodular goiter in 49 patients, follicular adenoma in 26, hyperplasia in 19, and Hashimoto's thyroiditis in 12. Postoperative hemorrhage requiring operative hemostasis occurred in two patients (1.9%). Two patients had unilateral recurrent laryngeal nerve (RLN) palsy before operation (1.9%). Three patients had unilateral postoperative RLN palsy (2.8%). Two cases resolved in 3 and 4 months. The only permanent RLN injury occurred in a patient reoperated for a compressive goiter. Early postoperative hypocalcemia (8.0 mg/dl or less) was found in nine patients (8.5%). No patient had permanent hypoparathyroidism at long-term follow-up evaluation. CONCLUSIONS: Total thyroidectomy for benign thyroid disease can avoid reoperation for nodular goiter and hyperthyroidism and eliminate any subsequent risk of malignant change in radiated thyroid glands. A low complication rate can be achieved with meticulous surgical technique. Total thyroidectomy can be performed safely for bilateral benign thyroid disease.

Adenoma↗

The scope and impact of thyroid disease.

Aspects of the incidence and demographics of common thyroid disorders in the US (and elsewhere, to a lesser extent) are reviewed. The impact of healthcare reform and the efforts of managed care organizations to impose cost-effective management for the diagnosis and treatment of thyroid disorders are bringing unusual pressures to bear on both clinical laboratories and practicing endocrinologists. I discuss the potential dangers of utilization of suboptimally focused diagnostic approaches and of the inefficiencies in clinical management by primary-care providers, who often lack sufficient expertise, as opposed to endocrinologists. More than dollars are at stake, and the suboptimal management of common thyroid disorders presents several significant risks. Finally, I propose a general blueprint for the ongoing development of a structure for continuing quality improvement of the laboratory and clinical diagnosis, treatment, and long-term follow-up of patients with thyroid disease.

Cost-Benefit Analysis↗

The clinical spectrum of postpartum thyroid disease.

The clinical and biochemical features of postpartum thyroid disease were analysed in 152 antithyroid peroxidase antibody-positive (anti-TPO+ve) women and compared with 239 anti-TPO-ve age-matched control postpartum women. All were assessed monthly for up to 12 months postpartum. Seventy three anti-TPO+ve women developed postpartum thyroiditis (PPT): 19.2% hyperthyroid alone, 49.3% hypothyroid alone, and 31.5% characterized by hyper- followed by hypothyroidism. None of the antibody-negative women developed any thyroid dysfunction. A significant increase in many of eleven symptoms of hypothyroidism and some of eight symptoms of hyperthyroidism compared to control women was observed in all anti-TPO+ve women, independent of thyroid status. This was particularly seen in women who later developed PPT when they were euthyroid, but was also observed in euthyroid anti-TPO+ve women who showed no decline of thyroid function during the postpartum period. Although PPT is usually transient, this condition, and the euthyroid antibody-positive state, may be associated with significant symptomatology, including an increased incidence of minor to moderate depression. Early recognition of this syndrome by antenatal screening of thyroid antibodies may contribute to improved management of women during the postpartum period.

Adult↗

Exophthalmos in autoimmune thyroid disease.

Protrusion of the eyes of patients with autoimmune thyroid disease was compared with that of healthy subjects. The mean values for protrusion in patients with thyrotoxic Graves' disease and Hashimoto's disease and in healthy subjects were 16.6 +/- 2.1 mm (mean +/- SD; n = 122), 14.2 +/- 1.8 mm (n = 100), and 13.9 +/- 1.9 mm (n = 558), respectively. The value of Graves' disease was significantly different from that for healthy subjects (P < 0.001). Individual values for protrusion showed a similar normal distribution in these three groups, but were displaced to higher values as a whole in Graves' disease. These results, which suggest that almost all patients with Graves' disease have exophthalmos, do not support the idea that Graves' ophthalmopathy is a distinct single autoimmune disease.

Autoimmune Diseases↗

[The role of thyroid ultrasonography in the diagnostic approach to thyroid diseases].

Echography is of increasing importance and is considered of value in the diagnostic approach to thyroid diseases. It is particularly useful for assessment of precise measurements of the thyroid gland and to the clinical physician when he has to judge the benign or malignant nature of nodular lesions, as a complement to fine-needle aspiration-biopsy.

Diagnosis, Differential↗

Influences of thyroid diseases in diabetic pregnant women.

Thyroid disorders are particularly frequent in women and, second to diabetes mellitus, are the most common endocrine diseases during pregnancy. An association between insulin-dependent diabetes mellitus and thyroid autoimmunity has long been recognized. Management of thyroid diseases in pregnancy is different than in non pregnant women, due to physiological changes of thyroid hormone economy in the childbearing period. Thyroid dysfunction may affect carbohydrate metabolism and worsen glucose control in diabetic patients. On the other hand, poorly compensated diabetes mellitus may cause alteration in the production and metabolism of thyroid hormones. Pregnant women with insulin-dependent diabetes mellitus have an increased risk of developing post partum thyroiditis. These observations have lead to the recommendation that thyroid function should be checked in diabetic women during pregnancy and in the post partum.

Adult↗

[Benign thyroid disease and cancer in our environment].

We compile our experience about the association between benign thyroid disease and thyroid carcinoma, and perform a review on the literature about this theme. We conclude on the importance of knowing this association, even not statistically significative, when it is detected modifies totally our therapeutic attitude and the vigilance of these patients.

Carcinoma↗

Studies on thyroglobulin-specific suppressor T cell function in autoimmune thyroid disease.

T cell regulation of the generation of thyroglobulin plaque-forming cells (Tg PFC) and protein A plaque-forming cells (Prot A PFC) was investigated using lymphocytes from patients with autoimmune thyroid disease. T and B cell mixed cultures (T-B MC) were carried out without mitogenic or antigenic stimulation to identify physiological T cell effects in the system. Tg PFC were found in 8 (44%) of 18 patients who had high titers of thyroglobulin antibody in their sera. Tg-specific and nonspecific immunoregulation by T cells from patients and normal subjects was studied using B cells from these eight patients in the T-B MC system. Remarkably lower values of Tg PFC induction compared to Prot A PFC induction were found after T cell addition. Normal T cells inhibited Tg PFC induction, but patient T cells did not, while the same extent of helper effects were found on Prot A PFC induction by the addition of patient and normal T cells. Irradiation (1500 rads) of T cells from patients and normal subjects significantly enhanced both TgPFC and Prot A PFC induction. Thus, Tg-specific suppressor T cells are present in all normal subjects as part of the radiosensitive suppressor T cell subset. The increase in Tg-PFC caused by irradiation-induced inhibition of Tg-specific suppressor T cell function was significantly greater in normal subjects than in patients. Histamine type 2 receptor-bearing T cells inhibited Prot A PFC induction, but not Tg PFC induction, in the autologous T-B MC system. No Tg PFC were induced from normal B cells in any combination with untreated T cells, irradiated T cells, or histamine type 2 receptor-negative T cells from patients or normal subjects. These data indicate that in vitro Tg-specific T cell regulation can be studied in the T-B MC system by using B cells from patients with autoimmune thyroid disease with high Tg antibody titers in their sera. Tg-specific suppressor T cells appear to be present in all individuals and to be involved in the regulation of Tg antibody production. The lower activity of Tg-specific suppressor T cells in patients compared to that in normal subjects may be related to Tg antibody production in vivo. This abnormality, however, is heterogeneous and is not a complete but, rather, is a relative defect of Tg-specific suppressor T cells.

Adolescent↗

IgG-class insulin autoantibodies in autoimmune thyroid disease.

We studied the incidence of insulin autoantibodies (IAA) in 97 patients with autoimmune thyroid disease with an enzyme-linked immunosorbent assay. The sera were also tested for islet cell antibodies (ICA) and thyrotropin receptor antibodies (TRAb). IAA as assessed by a standard deviation score were present in 7 patients (7.2%). None of the patients were seropositive for ICA. Data from this random sampling and a retrospective study of 12 patients on antithyroid drug treatment indicated that the presence of IAA was not associated with TRAb.

Adolescent↗

Increased sensitivity of a new assay for anti-thyroglobulin antibody detection in patients with autoimmune thyroid disease.

OBJECTIVES: To verify the cut-off values and to determine the clinical sensitivity of antithyroglobulin (TgAb) determinations using our routine RIA and the new electrochemiluminescent Elecsys assay. DESIGN AND METHODS: We used the DYNOtest anti-Tgn manual RIA from BRAHMS and the new automated Elecsys electrochemiluminescent immunoassay from Roche Diagnostics. We analyzed 452 sera from the following subjects: 193 euthyroid controls, 163 with treated and untreated autoimmune thyroid diseases (AITD) (108 Graves' disease and 55 thyroiditis), 50 with differentiated thyroid carcinoma, 13 with nonautoimmune thyroid disease and 33 with type 1 diabetes mellitus. RESULTS: As expected, using the proposed thresholds (BRAHMS 60 kIU/L, Elecsys 115 kIU/L) approximately 6% of the control subjects were positive for TgAb with both methods. In AITD patients, the sensitivity of TgAb determination was significantly higher with the Elecsys assay (51.5%) than with the BRAHMS assay (39.3%). This difference was not observed in the other patient groups. CONCLUSION: The Elecsys assay can be preferred not only because it is automated and rapid, but also because of its better clinical performance in AITD patients.

Adult↗

Detection of autoantibodies to thyroid peroxidase in autoimmune thyroid diseases by micro-ELISA and immunoblotting.

Serum autoantibodies to thyroid peroxidase (TPO) in patients with thyroid autoimmune diseases were studied by micro-ELISA and immunoblotting. Twenty-four patients, 15 with Graves' disease and 9 with Hashimoto's thyroiditis, whose serum titers were greater than 3200 on the microsomal hemagglutination test (except for 1 patient with a titer of 800) had autoantibodies to TPO. Both immunoglobulin G and M classes of autoantibodies were detected, with the former being more prominent. When TPO and thyroid microsomes were used as a target in a competitive binding inhibition test, the results suggested that TPO was a major thyroid microsomal antigen. On the other hand, immunoblotting analysis showed 3-4 bands in the 45-60K region stained by patients' sera in addition to human TPO with mol wt of 100K and 107K; only the latter 2 bands stained with antiporcine TPO antibody. In the majority of sera, TPO bands were clearer than others, although some sera showed the clearest band with a mol wt of 55K. These results indicate that patients with autoimmune thyroid disease often have autoantibodies to TPO that can be detected by micro-ELISA and immunoblotting, and that TPO is a major component of the thyroid microsomal antigen.

Animals↗

The study of thyroid diseases in a community not using iodized salt.

OBJECTIVE: To investigate the prevalence of thyroid diseases in a community which did not use iodized salt. METHODS: The survey was conducted in Panshan, Liaoning Province. 1 103 inhabitants aged 14 years or more attended the examinations, which included questionnaire, physical examination and serum analysis. Iodine in the urine and thyroid B ultrasound examination were also conducted. RESULTS: The prevalence of overt hyperthyroidism and hypothyroidism was 16.3 per thousand and 2.7 per thousand, respectively. Subclinical hyperthyroidism and hypothyroidism were detected in 37.2 per thousand and 9.1 per thousand of the subjects, respectively. Serum autoantibodies to thyroid were detected in 10.9% of the entire population. The prevalence of goiter was 20.7% (diffuse goiter 16.8% and nodular goiter 3.9%). CONCLUSION: In the iodine deficient areas, perhaps autoimmununization is not only related to the development of goiter but is also the main cause of subclinical hyperthyroidism and hypothyroidism.

Adolescent↗

[Computer tomographic differential diagnosis of thyroid diseases with special reference to scintigraphic cold spots (author's transl)].

A high proportion of carcinomas of the thyroid produce scintigraphic cold spots, this finding therefore requires further investigation in order to prevent unnecessary thyroidectomies. In order to clarify the value of computer tomography in thyroid disease, 70 patients with scintigraphic cold spots, or equivocal thyroid scans, were submitted to computer tomography of the neck. The findings in the majority of these cases have been correlated with histological results.

Diagnosis, Differential↗

[Study of thyroid function parameters and thyrotropin in general non-thyroid diseases].

The changes in the parameters of thyroid function and thyrotropin (TSH) have been evaluated in 5 groups of patients with general non-thyroid disease (GNTD): acute severe bacterial infection (16 patients), acute myocardial infarction (22 patients), diabetic ketoacidosis (24 patients), non-ketotic hyperosmolar decompensation (8 patients), protein-calorie undernutrition (12 patients), without associated conditions or drug therapies that might have modified the thyroid hormones. These patients were evaluated at the beginning of their GNTD and after recovery. Thyroxine (T4), triiodothyronine (T3) and reverse T3 (rT3) were measured by radioimmunoassay (RIA), the TBC index by competitive analysis, the free T4 by a labeled T4 analogue and T4 by immunoradiometric analysis (IRMA). In all patients similar changes in thyroid hormones and in IRMA were found, and they returned to normal after recovery; the changes were most marked in diabetic ketoacidosis, followed by hyperosmolar decompensation and by undernutrition. When the 5 groups were evaluated together, T3 was the most commonly low value (57.3%), followed by T4 and TBC index (26.8%), free T4 (20.7%) and the free T4 index (10.9%). The level of rT3 was increased in 39% of cases. Baseline TSH was, initially, 1.05 +/- 1.05 microU/ml, and 1.36 +/- 0.85 microU/ml after recovery (p less than 0.001). It was only found to be suppressed in one patient (a female with diabetes mellitus and Graves disease); in 17 cases it had borderline values between 0.1 and 0.4 microU/ml, and in the remaining patients it was normal. GNTD induces profound changes in the thyroid functional parameters, with reductions below their normal range, including the analogue measured T4 and low TSH.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗