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Ablation of thyroid residues with 30 mCi (131)I: a comparison in thyroid cancer patients prepared with recombinant human TSH or thyroid hormone withdrawal.

The aim of the study was to assess whether stimulation by recombinant human TSH (rhTSH) may be used in patients with differentiated thyroid carcinoma for postsurgical ablation of thyroid remnants using a 30-mCi standard dose of (131)I during thyroid hormone therapy. The rate of ablation was prospectively compared in three groups of patients consecutively assigned to one of three treatment arms: in the first arm, patients (n = 50) were treated while hypothyroid (HYPO); in the second arm, patients (n = 42) were treated while HYPO and stimulated in addition with rhTSH (HYPO + rhTSH); in the third arm, patients (n = 70) were treated while euthyroid (EU) on thyroid hormone therapy and stimulated with rhTSH (EU + rhTSH). The outcome of thyroid ablation was assessed by conventional HYPO (131)I scan performed in HYPO state 6-10 months after ablation. Basal serum TSH was elevated in the HYPO and HYPO + rhTSH groups. In the EU + rhTSH group, basal serum TSH was 1.3 +/- 2.5 micro U/ml (range, <0.005-11.9 micro U/ml). After rhTSH, serum TSH significantly increased in the HYPO + rhTSH group and the EU + rhTSH group. Basal 24-h radioiodine thyroid bed uptake was 5.8 +/- 5.7% (range, 0.2-21%) and 5.4 +/- 5.7% (range, 0.2-26%) in the HYPO and HYPO + rhTSH groups, respectively. In the HYPO + rhTSH group, mean 24-h thyroid bed uptake rose to 9.4 +/- 9.5% (range, 0.2-46%) after rhTSH (P < 0.0001). The 24-h uptake after rhTSH in the EU + rhTSH group was 2.5 +/- 4.3% (range, 0.1-32%), significantly lower (P < 0.0001) than that found in the HYPO and HYPO + rhTSH groups. The rate of successful ablation was similar in the HYPO and HYPO + rhTSH groups (84% and 78.5%, respectively). A significantly lower rate of ablation (54%) was achieved in the EU + rhTSH group. Mean initial dose rate (the radiation dose delivered during the first hour after treatment) was significantly lower in the EU + rhTSH group (10.7 +/- 12.6 Gy/h) compared with the HYPO + rhTSH group (48.5 +/- 43 Gy/h) and the HYPO group (27.1 +/- 42.5 Gy/h). In conclusion, our study indicates that by using stimulation with rhTSH, a 30-mCi standard dose of radioiodine is not sufficient for a satisfactory thyroid ablation rate. Possible reasons for this failure may be the low 24-h radioiodine uptake, the low initial dose rate delivered to the residues, and the accelerated iodine clearance observed in EU patients. Possible alternatives for obtaining a satisfactory rate of thyroid ablation with rhTSH may consist of increasing the dose of radioiodine or using different protocols of rhTSH administration producing more prolonged thyroid cells stimulation.

Adenocarcinoma, Follicular↗

Potential mechanisms of thyroid disruption in humans: interaction of organochlorine compounds with thyroid receptor, transthyretin, and thyroid-binding globulin.

Organochlorine compounds, particularly polychlorinated biphenyls (PCBs), alter serum thyroid hormone levels in humans. Hydroxylated organochlorines have relatively high affinities for the serum transport protein transthyretin, but the ability of these compounds to interact with the human thyroid receptor is unknown. Using a baculovirus expression system in insect cells (Sf9 cells), we produced recombinant human thyroid receptor ss (hTRss). In competitive binding experiments, the recombinant receptor had the expected relative affinity for thyroid hormones and their analogs. In competitive inhibition experiments with PCBs, hydroxylated PCBs (OH-PCBs), DDT and its metabolites, and several organochlorine herbicides, only the OH-PCBs competed for binding. The affinity of hTRss for OH-PCBs was 10,000-fold lower (Ki = 20-50 microM) than its affinity for thyroid hormone (3,3',5-triiodothyronine, T3; Ki = 10 nM). Because their relative affinity for the receptor was low, we tested the ability of OH-PCBs to interact with the serum transport proteins--transthyretin and thyroid-binding globulin (TBG). With the exception of one compound, the OH-PCBs had the same affinity (Ki = 10-80 nM) for transthyretin as thyroid hormone (thyroxine; T4). Only two of the OH-PCBs bound TBG (Ki = 3-7 microM), but with a 100-fold lower affinity than T4. Hydroxylated PCBs have relatively low affinities for the human thyroid receptor in vitro, but they have a thyroid hormonelike affinity for the serum transport protein transthyretin. Based on these results, OH-PCBs in vivo are more likely to compete for binding to serum transport proteins than for binding to the thyroid receptor.

Binding, Competitive↗

Interrelationships between age, thyroid volume, thyroid nodularity, and thyroid function in patients with sporadic nontoxic goiter.

PURPOSE: To test the hypothesis that during the natural history of sporadic nontoxic goiter (SNG), a diffuse goiter precedes a multinodular goiter with gradual development of autonomous thyroid function. PATIENTS AND METHODS: A cross-sectional survey of 102 consecutive patients with SNG (seven male, 95 female) was performed. Thyroid volume was measured by ultrasonography, and plasma thyroid-stimulating hormone (TSH) by a sensitive assay (TSH immunoradiometric assay). RESULTS: Patients with a multinodular goiter were older and had a larger thyroid volume than patients with a diffuse or uninodular goiter. Plasma free thyroxine (T4) and total triiodothyronine (T3) were higher and plasma TSH was lower in patients than in normal subjects. Free T4 was higher in the subgroup of patients with a multinodular goiter and a decreased TSH response to thyrotropin-releasing hormone. Plasma TSH (y, in mU/L) was negatively related to thyroid volume (x, in mL): y = 8.2x-0.667 (r = 0.578, p less than 0.001). Thyroid volume (y, in mL) was positively related to age (x, in years): y = -21.8 + 2.0x (r = 0.455, p less than 0.001); and to duration of goiter (x, in years): y = 40.6 + 2.1x (r = 0.505, p less than 0.001). The annual increase in thyroid volume was calculated at 4.5%. CONCLUSION: The data suggest a continuous growth of SNG and provide support for the concept of increasing thyroid nodularity and autonomy of thyroid function--related to increasing thyroid volume--during the natural history of this disorder.

Adult↗

A cohort study of thyroid cancer and other thyroid diseases after the chornobyl accident: thyroid cancer in Ukraine detected during first screening.

BACKGROUND: The Chornobyl accident in 1986 exposed thousands of people to radioactive iodine isotopes, particularly (131)I; this exposure was followed by a large increase in thyroid cancer among those exposed as children and adolescents, particularly in Belarus, the Russian Federation, and Ukraine. Here we report the results of the first cohort study of thyroid cancer among those exposed as children and adolescents following the Chornobyl accident. METHODS: A cohort of 32 385 individuals younger than 18 years of age and resident in the most heavily contaminated areas in Ukraine at the time of the accident was invited to be screened for any thyroid pathology by ultrasound and palpation between 1998 and 2000; 13 127 individuals (44%) were actually screened. Individual estimates of radiation dose to the thyroid were available for all screenees based on radioactivity measurements made shortly after the accident and on interview data. The excess relative risk per gray (Gy) was estimated using individual doses and a linear excess relative risk model. RESULTS: Forty-five pathologically confirmed cases of thyroid cancer were found during the 1998-2000 screening. Thyroid cancer showed a strong, monotonic, and approximately linear relationship with individual thyroid dose estimate (P<.001), yielding an estimated excess relative risk of 5.25 per Gy (95% confidence interval [CI] = 1.70 to 27.5). Greater age at exposure was associated with decreased risk of radiation-related thyroid cancer, although this interaction effect was not statistically significant. CONCLUSION: Exposure to radioactive iodine was strongly associated with increased risk of thyroid cancer among those exposed as children and adolescents. In the absence of Chornobyl radiation, 11.2 thyroid cancer cases would have been expected compared with the 45 observed, i.e., a reduction of 75% (95% CI = 50% to 93%). The study also provides quantitative risk estimates minimally confounded by any screening effects. Caution should be exercised in generalizing these results to any future similar accidents because of the potential differences in the nature of the radioactive iodines involved, the duration and temporal patterns of exposures, and the susceptibility of the exposed population.

Adolescent↗

Thyroid peroxidase/microsomal antibodies are not identical with thyroid cytotoxic antibodies in autoimmune thyroiditis.

Cytotoxic activity in sera of patients with Hashimoto's thyroiditis was measured with an antibody-dependent cell-mediated cytotoxicity assay. Cytotoxicity was determined in a 51chromium release assay using human thyroid cell targets incubated with heat-inactivated serum or IgG from patients with Hashimoto's thyroiditis. Effector cells were obtained from peripheral mononuclear cells of normal subjects. Cytotoxicity was significantly increased in patients with Hashimoto's thyroiditis (median specific lysis 20.2%, range 2.1-58.8) compared with normals (median specific lysis 8.1%, range 0-19.5; p less than 0.00001). The amount of percent specific lysis did not correlate with the titres of microsomal antibodies determined by different methods: passive hemagglutination technique (r = 0.2), enzyme immunoassay with microsomal antigen (r = 0.16), and radioimmunoassay for thyroid peroxidase antibody (r = 0.02). The cytotoxic activity was located in the IgG fraction, both in microsomal antibody positive and negative sera. After pre-incubation of microsomal antibody/thyroid peroxidase antibody positive or negative sera with purified thyroid peroxidase followed by analysis in the antibody-dependent cell-mediated cytotoxicity assay, cytotoxicity decreased in only 2 cases but was unchanged in the remaining sera. Western blot experiments with solubilized thyroid membranes and immunoblotting with cytotoxic-positive/microsomal antibody negative sera showed no binding to thyroid peroxidase. Our data suggest that cytotoxicity in sera from patients with Hashimoto's thyroiditis is not mediated by antibodies against thyroid peroxidase, but by antibodies not yet identified.

Adult↗

The difference of susceptibility of target thyroid gland to autoimmune thyroiditis induced by a combination of implantation of thyroid gland and injection of lipopolysaccharide.

Autoimmune thyroiditis was induced in CBA/J mice by a newly developed method consisting of a combination of implantation of one whole syngeneic thyroid gland under the capsule of the kidney and subsequent injection of lipopolysaccharide (LPS) intravenously 6 hr after implantation. This procedure was repeated once, a week later. With this method the implanted thyroid gland, after becoming necrotic due to circulatory disturbance and regenerating, also developed definite thyroiditis, quite similar to that of the intact thyroid gland on Day 49. With respect to the H-2 haplotype of the mice, both intact and implanted thyroid glands of CBA/J (H-2k) and C3H/He (H-2k) mice showed severe thyroiditis, whereas those of BALB/c (H-2d) and C57BL/6 (H-2b) mice developed mild inflammation. With a combination of implantation of thyroid glands derived from parental good (CBA/J) or poor responder (BALB/c) mice and subsequent injection of LPS into (good X poor responder) (CBA/J X BALB/c)F1 hybrid mice, it was found that the genetic background of the target thyroid tissue itself has a strong influence on susceptibility.

Animals↗

Immunohistochemical study of papillary thyroid carcinoma and possible papillary thyroid carcinoma-related benign thyroid nodules.

Recent immunohistochemical studies have identified different antisera that have various degrees of sensitivity and specificity for papillary thyroid carcinoma (PTC). In this study, we performed immunostaining for CK, EMA, HBME, CD57 and CD15 in PTC, and benign thyroid nodular lesions to compare the sensitivity and the specificity of these antisera for PTC. In addition, we studied the patterns of immunostaining of these antisera in benign nodular thyroid lesions displaying a fine chromatin pattern, foci of cells with nuclear grooves, and optically clear nuclei. Fifty-five PTC (composed of 30 papillary variants and 25 follicular variants), 5 follicular carcinomas, 30 follicular adenomas, and 20 thyroid nodular lesions (5 papillary variants and 15 follicular variants) were submitted for immunostaining with CK, EMA, HBME, CD57, and CD15. CK and HBME showed the highest sensitivity and specificity for PTC when an arbitrary cutoff of more than 10% positive cells was considered as positive diagnostic immunostaining for these sera. The other antisera were less sensitive and less specific. One case of PTC showed negative HBME but positive CD15, whereas three papillary variants and two follicular variants of benign thyroid nodules revealed a positive diagnostic HBME immunostaining for PTC and negative CK immunostaining. Any combination of positive diagnostic immunostaining with CK+ HBME, CK+ CD57 or CK+ CD15 has a sensitivity of 95% and specificity of 90% for PTC. Thyroid nodules with a diffuse or focal fine chromatin pattern and focal areas with nuclear grooves or optically clear nuclei displayed immunoreactivity ranging from 0% to 50% of cells. Three of five follicular carcinomas showed negative reactivity for HBME, CD57, and CD15. A combination of immunostaining with CK, HBME and CD57 (or CD15) is a sensitive and specific test for PTC. This panel can be used to rule out thyroid nodules posing a diagnostic problem with PTC. Follicular adenoma and nodules of the thyroid, with a fine chromatin pattern and focal nuclear grooves or optically clear nuclei, displayed an intermediate range of reactivity between reactive thyroid tissue and PTC.

Adult↗

Postpartum thyroiditis and long-term thyroid status: prognostic influence of thyroid peroxidase antibodies and ultrasound echogenicity.

Postpartum thyroid dysfunction (PPTD) occurs in 5% of women, with hypothyroidism developing in 23% of these after 3-5 yr. We have determined the prognostic significance of thyroid peroxidase antibody (TPOAb), thyroid ultrasound morphology (U/S), human leukocyte antigen haplotype, and postpartum thyroid status on the development of thyroid dysfunction 77-81 months after PPTD. Ninety-eight TPOAb-positive [48 who had developed PPTD (group 1) and 50 without PPTD (group 2)] and 70 TPOAb-negative (group 3) women (derived from 145 TPOAb-positive and 229 TPOAb-negative cohorts at the index pregnancy), with comparable ages, parity, pregnancies after index pregnancy, and follow-up duration, were studied. Thyroid dysfunction occurred in 46% of group 1 vs. 4% of group 2 (P<0.001) and 24.5% of groups 1 and 2 vs. 1.4% of group 3 (P<0.001). Factors predictive of thyroid dysfunction included a hypothyroid form of PPTD, TSH more than 20 mU/L, and higher TPOAb levels (213.8 kIU/L in group 1 vs. 131.8 kIU/L in group 2; P<0.002) during the postpartum period. Although TPOAb was higher in group 1 than in group 2 at follow-up (166 vs. 97.7 kIU/L; P<0.03), there was no significant fall in TPOAb levels within either group during the period of follow-up. The prevalence of ultrasound hypoechogenicity was higher in group 1 than in group 2 at follow-up (76% vs. 52%; P<0.006), but U/S improved in 62.5% of group 1 during the period of follow-up. Human leukocyte antigen DR10 was lower in those who developed late thyroid dysfunction. These data, representing the longest follow-up of PPTD women, clearly show that the hypothyroid form of PPTD, high TPOAb levels, and a hypoechogenic U/S pattern lead to a high risk (relative risk, 32) of long term thyroid dysfunction. This compares with a relative risk of 12.9 for TPOAb- and PPTD-positive women, who remained euthyroid at the end of the first postpartum year, and 2.8 for TPOAb-positive but PPTD-negative women, all compared to TPOAb-negative women. Therefore, long term surveillance of TPOAb- and PPTD-positive women (group 1) is indicated.

Adult↗

Effect of thyroid-stimulating hormone and norepinephrine on cyclic AMP levels in human normal thyroids and human thyroid tumors.

The effect of TSH (100mU/ml) and norepinephrine (100 muM) on the cyclic AMP levels was studied in 10 human normal tissues, 10 thyroid adenomas and 4 thyroid carcinomas (3 papillary and 1 follicular). Normal tissues responded to TSH with a marked elevation of the cyclic AMP level. Response patterns of 10 thyroid adenomas to TSH were variable; the patterns of 6 cases resembled those of normal tissues, 3 responded mildly, and one had no response to TSH. Thyroid carcinomas had a higher basal level of cyclic AMP than those of normal tissues, although they responded only slightly to TSH. Two among 4 thyroid carcinomas had no response to TSH. Norepinephrine stimulated the accumulation of cyclic AMP in 4 thyroid adenomas and 3 thyroid carcinomas, while it had little effect on normal tissues. Responses to norepinephrine was observed only in thyroid tumors, although they had low response to TSH. It is suggested from these results that tumor cells originating from thyroid follicular cells have a modified response to hormones due to neoplastic alterations.

Adenoma↗

A unique combination of inflammatory cytokines enhances apoptosis of thyroid follicular cells and transforms nondestructive to destructive thyroiditis in experimental autoimmune thyroiditis.

Treatment of cultured primary human thyroid cells with IFN-gamma and TNF-alpha uniquely allows the induction of Fas-mediated apoptosis. To investigate the role of this cytokine combination in vivo, CBA/J mice were immunized with thyroglobulin and then injected with IFN-gamma and TNF-alpha. Compared with control animals, mice treated with IFN-gamma and TNF-alpha showed significantly sustained lymphocytic infiltration in the thyroid, which was associated with the destruction of portions of the follicular architecture at wk 6 after initial immunization. Furthermore, the number of apoptotic thyroid follicular cells was increased only in the thyroids from mice treated with the IFN-gamma and TNF-alpha. We also analyzed the function of the Fas pathway in vivo in cytokine-treated mice by using an agonist anti-Fas Ab injected directly into the thyroid. Minimal apoptosis of thyroid epithelial cells was observed unless the mice were pretreated with IFN-gamma and TNF-alpha. These data demonstrate that this unique combination of inflammatory cytokines facilitates the apoptotic destruction of thyroid follicular cells in experimental autoimmune thyroiditis, in a manner similar to what is observed in Hashimoto's thyroiditis in humans.

Animals↗

Immunohistochemical demonstration of thyroid peroxidase (TPO) in human thyroid tissues from various thyroid diseases.

Human thyroid peroxidase (hTPO) was detected immunohistochemically in 61 normal, benign and malignant thyroid tissues with a monoclonal antibody (38E) against hTPO using paraffin-embedded sections. Thyroid peroxidase was expressed intensely not only in tissues from Graves disease and hyperfunctioning adenomas, but also in those from carcinomas, adenomas and Hashimoto's thyroiditis. The staining pattern of TPO in the follicular cells was a diffuse and fine granular one in the normal thyroids, Graves' thyroids and adenomas, but abnormal coarse granular deposits of TPO were characteristically identified in most of the papillary carcinomas and Hashimoto's thyroiditis. These coarse granular deposits of TPO suggested that qualitative or structural changes in the TPO molecule are present in carcinomas and Hashimoto's thyroiditis. Consequently, these qualitative changes in TPO may be responsible for the lack of biochemically measured TPO activity in these diseases. This finding may also be useful in distinguishing between benign and malignant thyroid tumors.

Humans↗

Heterogeneity of autoantibodies against thyroid peroxidase in autoimmune thyroid disease: evidence against antibodies directly inhibiting peroxidase activity as regulatory factors in thyroid hormone metabolism.

The close relationship between thyroid microsomal antigen and thyroid peroxidase (TPO) is now well established. The present study evaluates the significance of autoantibodies against TPO (anti-TPO-Abs) in the various forms and stages of autoimmune thyroid disease with respect to a possible heterogeneous nature and particularly to their influence on TPO activity. When measured by a RIA using purified human TPO, anti-TPO-Abs were highly correlated with microsomal antibodies determined by enyzme-linked immunosorbant assay (r = 0.96; P less than 0.0001) and with the results of a TPO immunoprecipitation assay using crude microsomal preparations (r = 0.76; P less than 0.001). Relating the results of these assays to the reactivities of patients' sera with thyroid microsomes in immunoblot under nonreducing and reducing conditions, discordant results could be observed in a few cases. Further analysis of these data indicate a heterogeneous nature of anti-TPO-Abs, which react with at least two antigenic domains of the TPO molecule. The comparative analysis of patients with hyperthyroid Graves' disease, patients with Graves' disease in clinical remission, and patients with hypothyroid Hashimoto's thyroiditis revealed no significant differences in the antibody spectrum. When evaluating the direct influence of anti-TPO-Abs on the activity of TPO under a rigorous methodological approach, we found no significant inhibition of the enzymatic activity by any of the sera investigated from patients with autoimmune thyroid disease compared to that in sera from normal controls. In conclusion, the data indicate a heterogeneous nature of anti-TPO-Abs. The spectrum of antigenic epitopes recognized by anti-TPO-Abs seems not to be significantly different in the various forms and stages of autoimmune thyroid disease. The lack of an inhibitory effect of autoantibodies on TPO activity argues against direct binding of autoantibodies to the enzymatic sites of TPO and indicates that they are not important factors in producing thyroid dysfunction in autoimmune thyroid disease.

Adult↗

Thyroid hormone formation catalyzed by human thyroid peroxidase: a new and physiological measurement of thyroid peroxidase.

This report describes a method for measurement of TPO activity by the amount of thyroid hormone production. Thyroid hormone formation was accomplished by incubating purified iodine-poor Tg with human TPO for 60 min at 37 C in the presence of free DIT, KI, and an H2O2 source. Newly formed T3 and T4 were measured by radioimmunoassay of the Tg hydrolysates. With this method, TPO-catalyzed iodination of Tg and thyroid hormone formation were measured simultaneously from eight normal thyroid glands and 15 thyroid glands from MMI-treated patients with Graves' disease. Graves' disease TPO showed iodinating activity and T4 formation which was higher than that of TPO from normal thyroids, and there was a positive linear correlation between the iodinating activity and the amount of T4 formation. T3 production by highly active TPO, however, dissociates from the amount of T4 formation and the degree of Tg iodination. Thus, if the activity of TPO is to be measured by the amount of thyroid hormone production, T4 should be used rather than T3. The method of thyroid hormone formation described here provides a new and physiological measurement of TPO activity and should be useful for investigation of the role of human TPO in thyroid hormone formation.

Diiodotyrosine↗

A thyroid biopsy with histologic features of both Riedel's thyroiditis and the fibrosing variant of Hashimoto's thyroiditis.

We describe a 36-year-old woman with clinical, laboratory, and histologic features of both Riedel's thyroiditis and the fibrosing variant of Hashimoto's thyroiditis. Features of the former included a hard, fixed thyroid mass and extensive involvement of perithyroidal tissues by dense fibrosis with lymphocytes, histiocytes, and plasma cells. Features supporting Hashimoto's thyroiditis included high serum titers of antimicrosomal and antithyroglobulin antibodies and the histologic findings within the thyroid gland itself: dense fibrous bands dividing the thyroid parenchyma into nodules composed of lymphoid follicles with germinal centers, plasma cells, and oxyphilic metaplasia of follicular epithelial cells. Although Riedel's thyroiditis and the fibrosing variant of Hashimoto's thyroiditis were once considered morphologic variants of the same disease, since the 1970s these diseases have been considered as distinct clinicopathologic entities. The coexistence of both diseases in a patient is rare and is probably coincidental in this instance.

Adult↗

Autoimmune thyroiditis and exposure to iodine 131 in the Ukrainian cohort study of thyroid cancer and other thyroid diseases after the Chornobyl accident: results from the first screening cycle (1998-2000).

CONTEXT: Due to the Chornobyl accident, millions were exposed to radioactive isotopes of iodine and some received appreciable iodine 131 (131I) doses. A subsequent increase in thyroid cancer has been largely attributed to this exposure, but evidence concerning autoimmune thyroiditis (AIT) remains inconclusive. OBJECTIVE: The objective of the study was to quantify risk of AIT after 131I exposure. DESIGN/SETTING/PARTICIPANTS: Baseline data were collected from the first screening cycle (1998-2000) of a large cohort of radiation-exposed individuals (n = 12,240), residents of contaminated, iodine-deficient territories of Ukraine. Study individuals were under the age of 18 yr on April 26, 1986, and had thyroid radioactivity measurements made shortly after the accident. OUTCOMES: AIT was defined a priori based on various combinations of elevated antibodies to thyroid peroxidase (ATPO), TSH, and clinical findings; elevated ATPO were considered to be an indicator of thyroid autoimmunity. RESULTS: No significant association was found between 131I thyroid dose estimates and AIT, but prevalence of elevated ATPO demonstrated a modest, significant association with 131I that was well described by several concave models. This relationship was apparent in individuals with moderately elevated ATPO and euthyroid, thyroid disease-free individuals. CONCLUSIONS: Twelve to 14 yr after the Chornobyl accident, no radiation-related increase in prevalence of AIT was found in a large cohort study, the first in which 131I thyroid doses were estimated using individual radioactivity measurements. However, a dose-response relationship with ATPO prevalence raises the possibility that clinically important changes may occur over time. Thus, further follow-up and analysis of prospective data in this cohort are necessary.

Adolescent↗

Thyroid-infiltrating lymphocytes, thyroid function, and HLA-DR in juvenile autoimmune thyroiditis.

Eighteen patients with juvenile autoimmune thyroiditis were studied. At diagnosis 8 (44%) of the patients were euthyroid and 10 hypothyroid, whereas at the end of 6 to 12 months follow-up, 12 (66%) were euthyroid and 6 hypothyroid. All the patients were HLA-typed. The frequency of HLA-DR4 was increased in the patients when compared with the normal population, 63 vs 28% (p less than 0.01). An analysis of thyroid-infiltrating mononuclear cells revealed that the majority of the thyroid-infiltrating lymphocytes were T cells. More T lymphocytes and fewer B lymphocytes and HLA class II positive lymphocytes were found among the thyroid-infiltrating mononuclear cells in euthyroid than hypothyroid patients. The numbers of thyroid-infiltrating B lymphocytes correlated with the levels of thyroid microsomal antibodies. No correlation was found between thyroid function and thyroid antibodies.

Adolescent↗

Incidence trends for papillary thyroid carcinoma and their correlation with thyroid surgery and thyroid fine-needle aspirate cytology.

CONTEXT: Papillary thyroid carcinoma (PTC) is the most prevalent endocrine malignancy. The reported incidence of PTC has more than doubled in many countries during the past half century. In Tasmania, an island state of the Commonwealth of Australia the incidence has increased by 24.7% per annum during the last two decades. OBJECTIVE: Using the Tasmanian population as a model, this study sought to determine the relationship between changes in PTC incidence and trends for utilization of thyroid surgery and thyroid fine-needle aspiration biopsy (FNAB) cytology. DESIGN: Hospital and pathology services in Tasmania provided data relating to all thyroid surgical, cytologic, and histopathology procedures undertaken between 1988 and 1998. The accuracy of PTC case ascertainment by the Tasmanian Cancer Registry was validated and the relationship between thyroid procedures and PTC incidence assessed. RESULTS: A total of 3452 individuals underwent a thyroid procedure, comprising 1968 surgical and 1756 FNAB cytologic procedures. Of these, 184 patients were diagnosed with thyroid carcinoma, of whom 121 (65.8%) had PTC. Thyroidectomy and thyroid FNAB increased by 7.0% and 49.7% per annum, respectively. The likelihood of diagnosing PTC in thyroidectomy specimens increased by 99.7% per year in those patients preoperatively assessed by FNAB, compared to 10.1% per year in those for whom a preoperative FNAB was not performed. PTC incidence increased independently of PTC tumor size, although the greatest increase occurred for PTC 1 cm or less with a history of preoperative FNAB. CONCLUSIONS: These results suggest increasing PTC incidence is largely attributable to greater diagnosis of small PTC, many of which are likely to have been asymptomatic, identified by neck ultrasonography and subsequent FNAB. However, the incidence of PTC larger than 1 cm in patients without history of preoperative FNAB has also risen, suggesting the occurrence of clinically relevant tumors may also have increased.

Adult↗