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PubMed1982

Thyroid xanthine oxidase and its role in thyroid iodine metabolism in the rat: difference between effects of allopurinol and tungstate.

The role of xanthine oxidase in thyroid function was studied in the rat in vivo by different approaches. Allopurinol, an inhibitor of xanthine oxidase, was administered by mixing it with a powdered diet (16 mg/100 g body wt per day for 10 days). This treatment significantly reduced the total uptake of iodide and inhibited the organification of iodide in the rat thyroid gland. Thyroid xanthine oxidase and dehydrogenase were almost completely inactivated by tungstate, which was given to rats (100 p.p.m./animal per day in drinking water for 10 days) maintained on a purified diet containing low levels of molybdenum. Under these conditions, no inhibitory effect was observed on synthesis of thyroid hormones. It therefore seemed reasonable to assume that the suppressive effect of allopurinol on the biosynthesis of thyroid hormones is not mediated by xanthine oxidase.

Allopurinol↗
PubMed1987

Inhibitory effect of various radiographic contrast agents on secretion of thyroxine by the dog thyroid and on peripheral and thyroidal deiodination of thyroxine to tri-iodothyronine.

In previous studies we have found that the cholecystographic contrast agent ipodate induced a rapid, sustained and reversible inhibition of thyroxine (T4) secretion from perfused dog thyroid lobes. This type of inhibition of thyroid secretion has not been observed previously. To evaluate whether this effect is unique for ipodate, ten other iodine-containing radiographic contrast agents were tested. The four agents used for cholecystography (iocetamate, iodipamide, ioglycamate and iotroxate) all induced rapid inhibition of T4 secretion from TSH-stimulated perfused dog thyroid lobes, while none of six agents predominantly excreted through the kidneys (amidotrizoate, metrizamid, metrizoate, iodamide, diodone and ioxithalamate) influenced T4 secretion significantly. All the cholecystographic agents inhibited T4 deiodinases from dog thyroid and liver. Diodone also inhibited the deiodinases while none of the other compounds tested had any effect. The results indicate that the structure necessary to inhibit thyroid secretion is common to a number of cholecystographic agents and that it could be related to the structure responsible for the inhibitory effect of cholecystographic agents on T4 deiodinases.

Animals↗
PubMedDate not supplied

Primary squamous cell carcinoma of the thyroid arising in Hashimoto's thyroiditis in an adolescent.

Squamous cell carcinoma is a rare thyroid neoplasm that has been described exclusively in adults. We report what appears to be the first example of a primary squamous cell carcinoma of the thyroid gland arising in a background of Hashimoto's thyroiditis in an adolescent female. The tumor was well demarcated, confined to the right thyroid lobe, and did not metastasize, although follow up has been limited. The squamous cell carcinoma was well to moderately differentiated, and the stroma contained an abundant inflammatory infiltrate rich in lymphocytes and eosinophils. The lack of goblet cells, extracellular mucin, and extensive stromal sclerosis excluded the diagnosis of sclerosing mucoepidermoid carcinoma with eosinophilia. Immunohistochemical staining revealed focal expression of cytokeratin 7 and diffuse labeling with cytokeratin AE1/AE3. The squamous cell carcinoma overexpressed p53 protein and showed increased proliferative activity, as evidenced by the high MIB-1 labeling index. In contrast, the tumor did not show immunoreactivity for thyroglobulin or thyroid transcription factor 1.

Adolescent↗
PubMed2003

Comparison of colloid, thyroid follicular epithelium, and thyroid hormone concentrations in healthy and severely sick dogs.

OBJECTIVES: To compare serum concentrations of total thyroxine (TT4), free thyroxine (fT4), and thyroid-stimulating hormone (TSH), as well as measures of thyroid follicular colloid and epithelium, between groups of healthy dogs and severely sick dogs. DESIGN: Cross-sectional study. ANIMALS: 61 healthy dogs and 66 severely sick dogs. PROCEDURE: Serum samples were obtained before euthanasia, and both thyroid lobes were removed immediately after euthanasia. Morphometric analyses were performed on each lobe, and serum TT4, fT4, and TSH concentrations were measured. RESULTS: In the sick group, serum TT4 and fT4 concentrations were less than reference range values in 39 (59%) and 21 (32%) dogs, respectively; only 5 (8%) dogs had high TSH concentrations. Mean serum TT4 and fT4 concentrations were significantly lower in the sick group, compared with the healthy group. In the healthy group, a significant negative correlation was found between volume percentage of colloid and TT4 or fT4 concentrations, and a significant positive correlation was found between volume percentage of follicular epithelium and TT4 or fT4 concentrations. A significant negative correlation was observed between volume percentages of colloid and follicular epithelium in both groups. CONCLUSIONS AND CLINICAL RELEVANCE: TT4 and fT4 concentrations are frequently less than reference range values in severely sick dogs. Therefore, thyroid status should not be evaluated during severe illness. The absence of any significant differences in mean volume percentages of follicular epithelium between healthy and severely sick dogs suggests that these 2 groups had similar potential for synthesizing and secreting thyroid hormones.

Animals↗
PubMed1990

Anti-thyroid peroxidase antibodies during pregnancy and postpartum. Relation to postpartum thyroiditis.

The frequency of autoantibodies to thyroid microsomes (MAb), thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) was studied in 736 women during and after pregnancy. The aim was to study the relationship between TPO Ab and post-partum thyroid disease, and to compare their behaviour with MAb. Seventy-five (10%) were either MAb or TgAB positive, of whom 36 were sampled serially at 18, 30 and 36 weeks of pregnancy and 1, 6 and 12 months post partum. Twenty of the antibody negative mothers were selected at random for controls. Twelve of the 36 antibody positive mothers developed post-partum thyroid dysfunction (group 1), 24 did not (group 2) compared with none of the 20 controls (group 3). Six months post partum, TPO Ab titres rose overall in both groups 1 and 2, but only in those with measurable TPO Ab during the first trimester. A TPO Ab was less frequently positive than MAb, but the difference was not statistically significant. TPO Ab are not superior to MAb for predicting post partum thyroid disease in pregnant women.

Autoantibodies↗
PubMed2006

A patient with primary squamous cell carcinoma of the thyroid intermingled with follicular thyroid carcinoma that remains alive more than 8 years after diagnosis.

Primary squamous cell carcinoma of the thyroid is an extremely rare tumor with a highly aggressive clinical course. We report here on a patient with primary squamous cell carcinoma of the thyroid who remains alive more than 8 years after diagnosis. A 56-year-old man presented with a hoarse voice and a rapidly progressing mass on the right side of the thyroid gland. The patient underwent a total thyroidectomy without neck lymph node dissection. Histopathologic findings revealed primary squamous cell carcinoma combined with follicular carcinoma of the thyroid. The tumors metastasized to the cervical lymph nodes, thoracic spine and lung. He underwent 5000 rads of adjuvant radiotherapy to the neck. TSH suppressive therapy with L-thyroxine was administered alone rather than radioactive iodine therapy or chemotherapy. The patient's clinical course has been remarkable over the first 7 years; he has remained stable except for a transient paraplegia due to nerve compression. The patient underwent colectomy for the diagnosis of a colon cancer. Recent evaluation has revealed a new lesion in the lung; this was diagnosed as metastatic follicular carcinoma originating from the thyroid. High dose radioactive iodine therapy was administered, and he remains alive in stable condition.

Adenocarcinoma, Follicular↗
PubMed1977

Thyroidal and peripheral production of thyroid hormones. Review of recent findings and their clinical implications.

There are two biologically active thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Most T3 is produced extrathyroidally, so that alterations in circulating thyroid hormone concentrations may occur as a result of both thyroidal and extrathyroidal abnormalities. Extrathyroidal T4 conversion to T3 is decreased in patients with different acute and chronic illnesses. When T4 conversion to T3 is impaired and serum T3 concentrations decline, serum concentrations of biologically inactive 3,3',5'-triiodothyronine (reverse T3) increase. In this review, we present current information on thyroidal and extrathyroidal T4 and T3 production in normal subjects and patients with various thyroid diseases and other illnesses, consider the physiologic significance of these changes, and discuss the value and interpretation of various iodothyronine measurements.

Chemical Phenomena↗
PubMed2004

[Clinical significance of serum thyroglobulin and antithyroglobulin antibody in differentiated thyroid cancer after thyroid ablation].

Serum thyroglobulin (Tg) is a suitable marker for differentiated thyroid carcinoma following total thyroid ablation. Between 1998 and 2003, serum samples from 715 papillary and 179 follicular tumor patients treated with total/nearly total thyroidectomy and radioiodine ablation therapy were collected. According to the "Guidelines for Oncotherapy in Hungary", serum Tg, antithyroglobulin antibody (TgAb), TSH and FT4 levels were measured in periods of 3 months following the first treatment and of 6 months after 2 years. In the present work the prognostic value of Tg and TgAb data of cancer patients with hormone substitution therapy were evaluated individually and retrospectively. Serum Tg and TgAb concentrations were measured with a highly sensitive immunoradiometric (IRMA) method, and with a second generation, broad epitope specificity competitive radioimmunoassay, respectively. TSH levels determined by fourth generation LIAISON kit were in a range of 0.05-0.10 mIU/L. Accuracy of measuring of Tg <1 ng/ml made it possible to select the low cut-off level (Tg <2 ng/ml) following total thyroidectomy. In the predominant part of TSH-suppressed patients (746/774, 96%) the serum Tg concentration was below the cut-off level of 2 ng/ml. The sensitivity of Tg determination in 59 TSH-suppressed thyroid cancer patients with lung and bone metastases was as high as 86 to 100%. On the contrary, the number of false negative data was high in cases with lymph node metastases of papillary cancer, and sensitivity did not exceed 62%. Specificity and sensitivity of Tg in TgAb negative patients were 91 to 100%. Based on our results it could be concluded that measuring of Tg and TgAb, using a current IRMA method and a second generation RIA kit, proved to be effective tools for the postoperative monitoring of differentiated thyroid tumours. It has to be noted that determination of TgAb is highly recommended for the adequate interpretation of serum Tg levels. Persistently high and/or increasing serum TgAb concentration with low Tg result had a diagnostic value during the follow-up and can be connected with the recurrence or persistence of the differentiated thyroid cancer.

Adult↗
PubMedDate not supplied

[Recurrences after thyroid lobectomy for benign thyroid diseases: analysis of a clinical-instrumental follow up].

The authors propose to verify the therapeutical role of lobectomy in confronting monolobar nodular thyroid disease. In a period of 4 years (1990-1993), forty-four patients (30 women, 14 men) underwent thyroid lobectomy for a benign disease and follow-up treatment for 3 years on a semestral basis. All patient were studied both before the operation and during the follow-up using US and measuring the levels of T3, T4 and TSH; 34 patients (77.2%) had undergone a scintigraphy before surgery. The indication towards surgical intervention was, in 16 patients, consequent to the diagnosis of monolobar uninodular goiter and in 28 patients to monolobar plurinodular goiter. The operation involves thyroidal extracapsular lobectomy with isthmectomy. There were no temporary and/or permanent recurrential lesions, nor there were any significant hypocalcaemic alterations. The US description of the follow-up has been classified in four groups: normal, non-homogeneity (presence of simple parenchymal non-homogeneity), recurrence/non-homogeneity (presence of both pseudonodular forms and parenchymal non-homogeneity), recurrence (presence of recurrence with nodule(s) whose diameter is greater than 5 mm.). From the US follow-up examination, it was shown that 14 out of 44 patients (31.8%) presented alterations in the residual lobe wich were not identifiable in the pre-operative US examination (3 recurrences = 6.81%; recurrence/non-homogeneity = 2.27%; 10 non-homogeneity = 22.7%). Thirteen out of 14 patients are treated with substitutive ormonal therapy Out of these 30 patients whose residual lobe shows no alterations using US, 23 (70.6%) are treated with substitutive ormonal therapy. The authors have underlined a substantial percentage difference between the incidence of normality of the residual lobe during follow-up to lobectomy due to adenoma (normality 88.8%) and to lobectomy due to goiter-related lesions (normality 60%). During US follow-up examinations, abnormality percentages equal or superior to 30%--as those noticed after lobectomy due to goiter-related lesions underline the doubts wich characterize any form of partial thyroidal asportation (4 recurrence in 35 cases of monolobar uni- or plurinodular goiter = 11.4%); also, in the authors' experience, substitutive ormonal therapy has seemingly no effect on the recurrence incidence. According to the authors, the lobectomy can occupy a therapeutical role in thyroid diseases with monolobar expression, but to avoid an elevated number of recurrences, a rigorous evaluation of the real extension of the nodular disease is indispensable.

Female↗
PubMedDate not supplied

Thyroid peroxidase (TPO) as a tumor marker in the follow-up of differentiated thyroid carcinomas with surgical and ablative radioiodine therapy. An assessment after evaluation.

The clinical significance of serum thyroid peroxidase (TPO) for differentiated thyroid carcinomas(DTA) is estimated differently. In our preliminary studies it was found that TPO presented information extending those that from hTG. For further clarification a prospective follow-up study was performed including 66 female and 14 male total thyroidectomized patients with DTA for the time course of TPO and human thyroglobulin (hTg) in relation to the ablative radioidine therapy (ART). In 34/50 evaluable cases TPO levels showed an approximately analogous time course with hTg. In relation to the extension of residues, some cases presented increasing of TPO and hTG after radioiodine treatment. 6/7 patients suffering from extended postoperative residues with high anti hTg levels but without elevated TPO concentrations showed distinctly elevated TPO values. Therefore, TPO seems to be an indicator for the destruction of normal thyroid cells or thyroid tumor cells. The clinical value of TPO seems to be in the time being limited to DTA due to false negative hTg values. However, it should be possible that TPO can did the evaluation of thyroid specific therapy.

Autoantibodies↗
PubMed1999

[Effect of iodine and thyroid hormones in the induction and therapy of Hashimoto's thyroiditis].

AIM: The effect of an iodine prophylaxis on the induction of Hashimoto's thyroiditis as well as the influence of various therapeutic approaches on the course of antithyroglobulin (TgAb) and antiperoxidase (TPOAb) antibodies in manifest diseases are evaluated. METHOD: A collective of 375 euthyroid subjects without relevant goiter received daily doses of 200 micrograms iodide, weekly doses of 1.53 milligrams iodide, or no medication. A second group of 377 patients suffering from Hashimoto's thyroiditis was treated with a non-suppressive hormone medication, a suppressive hormone administration, a combination of a non-suppressive hormone therapy with low dose iodide (50-150 micrograms/day), mere iodide in doses of 200 micrograms/day, or received no therapy. The mean observation period in these two groups was 860 and 848 days, respectively. RESULTS: There was no significant increase of the antibody levels in the subgroup with 200 micrograms iodide/day and in the non-treated subjects of the first collective. However, the group that received 1.53 milligrams iodide/week presented a distinct increase of the TgAb as well as the TPOAb, and the incidence of Hashimoto's thyroiditis was 4-fold higher than in the two other subgroups. The patients of the second collective revealed a significant decrease of the TgAb in the subgroups treated with up to 200 micrograms iodide/day, while the reduction of the TPOAb depended on the thyrotropin level and was most significant in the suppressed group (p < 0.0001). CONCLUSION: To lower the incidence of autoimmune thyroid diseases in predisposed subjects, a daily iodine supplementation seems to be superior to high-dose weekly administrations. A hormone therapy combined with a daily, low-dose iodine medication is able to reduce the TgAb and the TPOAb levels even in patients with Hashimoto's thyroiditis.

Adolescent↗
PubMed1999

The role of recombinant thyroid-stimulating hormone (rhTSH) in the detection and management of well-differentiated thyroid carcinoma: a roundtable discussion.

A Roundtable meeting of European endocrinologists and nuclear medicine physicians recently examined the role of recombinant human thyroid-stimulating hormone (rhTSH, Thyrogen, thyrotropin alfa, Genzyme Corporation, Cambridge, MA, USA) in the detection and management of well-differentiated thyroid carcinoma. The meeting sought to review clinical work to date and to provide guidance and perspective on the agent's application in everyday practice. The Roundtable included a panel discussion centering on three major topics: 1) rationale for use of exogenous versus endogenous TSH stimulation of radioiodine uptake and thyroglobulin (Tg) production; 2) impact and use of rhTSH in diagnostic follow-up; and 3) role of rhTSH in radioablation. The panel concluded that obtaining TSH stimulation of radioiodine uptake and Tg production exogenously with rhTSH obviates the weeks-long withdrawal from thyroid hormone suppression therapy (THST) needed to obtain such stimulation endogenously. rhTSH administration thereby eliminates morbidity, discomfort and uncertainties of compliance and timing associated with THST withdrawal. Thus compared to withdrawal, rhTSH administration offers important advantages in safety, quality of life, reliability, predictability and convenience to patients and care providers. rhTSH therefore represents a major advance in the diagnostic follow-up of well-differentiated thyroid cancer. By increasing the sensitivity of serum Tg testing during THST, rhTSH administration also improves the sensitivity of diagnostic follow-up. In addition, heightening the sensitivity of Tg testing may permit more selective application of iodine-131 whole body scanning, decreasing the invasiveness of diagnostic follow-up. Clinical studies are underway to confirm the preliminary promise of rhTSH as an adjunct to radioablation of normal or neoplastic thyroid tissue, with emphasis on the therapeutic setting.

Antithyroid Agents↗
PubMed2000

Follow-up regimen of differentiated thyroid carcinoma in thyroidectomized patients after thyroid hormone withdrawal.

UNLABELLED: For differentiated, nonmedullary thyroid carcinoma, postsurgical ablation of thyroid remnants and treatment of residual tumor and metastases with 131I is a potentially curative therapy. The aim of this study was to optimize the diagnostic protocol for the follow-up of thyroidectomized patients. METHODS: Two hundred fifty-four patients (187 females, 67 males; mean age, 45 y; range, 8-83 y) were studied retrospectively for a mean follow-up period of 2.7 y (range, 1-12.5 y). An evaluation study consisted of a low-dose 131I diagnostic procedure under hyperthyroid conditions (thyroid-stimulating hormone > 30 MicroU/mL), 201TI scintigraphy, and measurement of thyroglobulin (Tg) under hypothyroid conditions. A total of 254 preablation studies (1 study per patient) and 586 follow-up studies (average number of studies, 2.3 per patient) were evaluated. RESULTS: Before ablation, low-dose 131I screening was useful to estimate the size of the thyroid remnant. Low Tg levels (<10 pmol/L) indicated the absence of metastases. After ablation, undetectable Tg levels indicated the absence of tumor recurrence. When Tg levels were high (>10 pmol/L), local recurrence or metastases were always observed, providing the basis for additional high-dose 131I therapy. In these patients, 201TI imaging did not provide a significant contribution to patient management. In the case of autoantibodies against Tg, both low-dose 131I screening and 201TI scintigraphy may be advocated to allow an aggressive diagnostic work-up. CONCLUSION: Tg plays a key role in follow-up and in making decisions to treat patients with differentiated thyroid carcinoma. The role of 201TI imaging is very limited. In patients with negative low-dose 131I screening, 201TI scintigraphy can be considered when Tg is elevated or cannot be evaluated because of autoantibodies against Tg. Under such circumstances, administration of a therapeutic 131I dose without 201TI imaging can be considered.

Adenocarcinoma, Follicular↗
PubMed1979

[Lithium and thyroid function. Significance of the TRH test in the diagnosis of lithium-induced thyroid dysfunction].

The treatment by lithium is known to involve certain endocrine complications. Those concerning the thyroid function, with risk of a frank hypothyroidy, are the most important. Aiming to appreciate the frequence and the intensivity of the endocrine effects of lithium, the thyroid parameters and the steady state of the hypothalamo-pituitary-thyroid axis were tested using the TRH test in 52 patients with maniaco-depressive psychosis with special attention to TSH, prolactin and growth hormone: 24 out of them were treated for 1 month to 6 years by lithium; the 28 others were considered as controls. The lithium treatment involves a decrease in the free thyroxine index (1.78 +/- 0.09 vs 2.16 +/- 0.09; p less than 0.01), an increase in the mean baseline TSH level (5.80 +/- 1.49 vs 2.70 +/- 0.24 microU/ml; p less than 0.05) and a noteworthy increase in the TSH responsiveness to TRH (22.7 +/- 2.14 vs 9.75 +/- 1.63 microU/ml; p less than 0.005). The TSH supranormal responses were neither correlated with the length of the treatment nor with the age of the patients. They appear as the consequence of a decrease in the thyroidal hormone secretion. The basal and stimulated prolactinemias remain comparable in the two groups of patients and no response of growth hormone occured after TRH. The TRH test must be considered as a useful complement for the surveillance of the patients treated with lithium because it permits to diagnose early the lithio-induced thyroid dysfunction.

Adolescent↗
PubMed2001

Serum thyroglobulin concentrations and (131)I whole-body scan results in patients with differentiated thyroid carcinoma after administration of recombinant human thyroid-stimulating hormone.

UNLABELLED: The use of recombinant human thyroid-stimulating hormone (rhTSH) has recently become available as an alternative diagnostic tool to assess the persistence and recurrence of differentiated thyroid carcinoma (DTC) in patients on thyroid hormone-suppressive therapy (THST) after near-total or total thyroidectomy and ablative doses of (131)I. We report the results of rhTSH administration in patients who were monitored for DTC. METHODS: Thirty-three adult DTC patients (13 men, 20 women; mean age +/- SE, 45.6 +/- 2.31 y; age range, 21-65 y) underwent diagnostic follow-up after rhTSH administration at a dose of 0.9 mg once a day for 2 d. Whole-body scanning and serum thyroglobulin (Tg) measurement were performed after rhTSH administration. Patients were divided into 2 groups depending on serum Tg concentrations on THST: 29 patients had Tg concentrations of <2 ng/mL (group A) and 4 patients had Tg values of >2 ng/mL (group B). RESULTS: In group A, Tg values remained at <2 ng/mL in 25 patients and increased from 1.1 +/- 0.14 ng/mL to 22.0 +/- 5.75 ng/mL (mean +/- SE) in 4 patients after rhTSH administration. Whole-body scanning did not reveal any uptake of (131)I in the 25 patients without an increase in Tg, whereas (131)I uptake was evident in 2 of the 4 patients with a rise in Tg. In group B, Tg values increased in all 4 patients from 17.3 +/- 6.35 ng/mL to 55.3 +/- 12.75 ng/mL, and (131)I uptake was evident in 3 of the 4 patients. No major adverse effects were reported after rhTSH administration. CONCLUSION: Our results show that the measurement of serum Tg concentrations after rhTSH has a higher diagnostic value than whole-body scanning in detecting the persistence of thyroid tissue. Therefore, rhTSH should be administered in TSH-suppressed patients with basal serum Tg concentrations of <2 ng/mL because the increment in serum Tg concentrations may reveal the persistence of thyroid tissue in these patients.

Adult↗
PubMed2002

Phytoestrogens and thyroid cancer risk: the San Francisco Bay Area thyroid cancer study.

Epidemiological and pathological data suggest that thyroid cancer may well be an estrogen-dependent disease. The relationship between thyroid cancer risk and dietary phytoestrogens, which can have both estrogenic and antiestrogenic properties, has not been previously studied. We present data from a multiethnic population-based case-control study of thyroid cancer conducted in the San Francisco Bay Area. Of 817 cases diagnosed between 1995 and 1998 (1992 and 1998 for Asian women), 608 (74%) were interviewed. Of 793 controls identified through random-digit dialing, 558 (70%) were interviewed. Phytoestrogen consumption was assessed via a food-frequency questionnaire and a newly developed nutrient database. The consumption of traditional and nontraditional soy-based foods and alfalfa sprouts were associated with reduced risk of thyroid cancer. Consumption of "western" foods with added soy flour or soy protein did not affect risk. Of the seven specific phytoestrogenic compounds examined, the isoflavones, daidzein and genistein [odds ratio (OR), 0.70; 95% confidence interval (CI), 0.44-1.1; and OR, 0.65, 95% CI, 0.41-1.0, for the highest versus lowest quintile of daidzein and genistein, respectively] and the lignan, secoisolariciresinol (OR, 0.56; 95% CI, 0.35-0.89, for the highest versus lowest quintile) were most strongly associated with risk reduction. Findings were similar for white and Asian women and for pre- and postmenopausal women. Our findings suggest that thyroid cancer prevention via dietary modification of soy and/or phytoestrogen intake in other forms may be possible but warrants further research at this time.

Adult↗
PubMed2002

Reproductive and menstrual history and papillary thyroid cancer risk: the San Francisco Bay Area thyroid cancer study.

Thyroid cancer rates are three times higher in women than men during the period between puberty and menopause, suggesting that the etiology of thyroid cancer may be related to female sex hormones and reproductive function. However, the results from epidemiological studies have been mixed. To assess this hypothesis, data on menstrual history, pregnancy history, and exogenous hormone use were analyzed from a population-based, case-control study conducted in the San Francisco Bay Area. Of 817 incident thyroid cancer patients (cases), ages 20-74 years, who were diagnosed in 1992-1998 and 793 controls, identified by random-digit dialing and frequency matched to cases on age and race/ethnicity, 608 (74%) cases and 558 (70%) controls were interviewed. Of these cases, 544 were of papillary histology and included in the present analysis. Women who reported onset of menarche before age 12 or after age 14 were at about 50% increased risk for papillary thyroid cancer; however, this effect differed among age- and ethnic-specific subgroups. Among parous women younger than age 45, risk was elevated for several variables measuring recency of pregnancy. Risk was reduced for women who had ever used oral contraceptives [odds ratio (OR), 0.73; 95% confidence interval (CI), 0.52-0.97], but there was no trend with duration of use. Although it remains unclear how sex hormones influence thyroid carcinogenesis, these relationships warrant further investigation.

Adult↗
PubMed2001

Pertinence of kappa and lambda recombinant antibodies directed against thyroid peroxidase in thyroid autoimmune disease.

Forty-one single-chain variable region fragments (scFvs) directed against thyroid peroxidase (TPO) were obtained by phage display libraries constructed from thyroid-infiltrating B cells of Graves' disease patients. Among these scFvs, 24.4% used a Vkappa light chain whereas 75.6% shows a light chain of Vlamda origin. Study of light chain gene usage in the TPO antibody repertoire demonstrated a dominance of the Vkappa 1-39 and Vlambda 1-51 genes. Thyroid peroxidase probing of overlapping peptides covering the amino acid sequences of anti-TPO T2/kappa and T13/lambda variable regions demonstrated a more restricted antigen recognition on T13/lambda than on T2/kappa. These two recombinant antibodies, expressed as whole IgG1 in the baculovirus/insect cell system, inhibited the binding to TPO of serum TPO autoantibodies whatever the light chain. Our study indicates that lambda as well as kappa light chain usage are found in the TPO antibody repertoire of thyroid-infiltrating B cells and are pertinent in the pathogenesis of autoimmune thyroid disease.

Amino Acid Sequence↗