Multiparametric ultrasound-based assessment of overt hyperthyroid diffuse thyroid disease.

Introduction: Hyperthyroidismis a prevalent condition affecting global populations, with an overall prevalence of 1.2%. Our research aimed to establish a systematic diagnostic approach using multiparametric ultrasound (MPUS) to diagnose hyperthyroid diffuse thyroid disease (DTD). Methods: We conducted a retrospective study from June 2021 to June 2023 at a specialized endocrinology center in Timisoara, Romania, enrolling subjects presenting with clinical hyperthyroidism. Using the Mach 30 Aixplorer ultrasound equipment, evaluations were performed initially in B-mode US, followed by Color Doppler and Spectral Doppler measurements, and finally, 2D Shear wave elastography (SWE). Results: From the 218 patients analyzed, the diagnosis of DTD with hyperthyroidism was confirmed through biochemical assessment, subgrouping various pathologies such as subacute thyroiditis, Graves' disease, painless thyroiditis, Hashimoto's thyroiditis, iatrogenic, as well as healthy controls. In the first step, B-mode hypoechogenicity had an AUC of 0.951 for DTD detection. In the second step, the peak systolic velocity differentiated Graves' disease with a median of 42.4 cm/s and an AUC of 1. Lastly, the third step consisted of SWE evaluation, revealing a mean elasticity index in the SAT subgroup significantly higher from other subgroups (p<0.001) with an AUC of 1. Conclusion: Our study offers a step-by-step evaluation algorithm for DTD diagnosis, with a very good overall diagnostic performance (AUC of 0.946).

Assessment of thyroiditis risk associated with HPV vaccination among girls aged 9-18 years: A time-varying cohort study.

BACKGROUND: Previous studies have suggested a relationship between human papillomavirus vaccine and autoimmune diseases, including thyroiditis. Thus, we aimed to evaluate the risk of thyroiditis associated with HPV vaccination among girls using the Primary Care Database For Pharmacoepidemiological Research (BIFAP) in Spain. METHODS: In this retrospective cohort study, girls in BIFAP aged 9-18 years from 2007 to 2016, free of past thyroiditis and HPV vaccination, were included. Hazard Ratios (HRs; 95% CI) of thyroiditis were calculated within exposed periods (up to 2 years of vaccination) and post-exposed periods (from 2 years after vaccination onwards) compared with non-exposed periods, overall, by dose and by type of vaccine, adjusted for potential confounders collected at different times. In a post-hoc analysis, we moved back the thyroiditis date (30 days) as a theoretical delay in diagnosis. RESULTS: Out of the 388,411 girls included in the cohort, 153,924 were vaccinated against HPV and 480 thyroiditis (253 autoimmune) cases were identified (334 non-exposed; 103 exposed; 43 post-exposed). Adjusted HR was 1.18 [95% CI: 0.79-1.76] for exposed (1.25 [0.77-2.04] for bi- and 1.15 [0.76-1.76] for quadri-valent vaccines) and 1.26 [0.74-2.14] for post-exposed periods. HR was 1.50 [0.87-2.59] for the 1st dose, 1.13 [0.66-1.91] for the 2nd and 1.11 [0.71-1.72] for the 3rd one. When the diagnosis date was moved back, the risk was 1.14 [0.76-1.70] for exposed period, being 1.80 [0.86-3.76] and 1.40 [0.74-2.66] after 1st dose of bi- and quadri-valent, respectively. CONCLUSIONS: We did not observe an increased risk of thyroiditis following HPV vaccination (whether bi- or quadri-valent). Even though the point estimate was higher after 1st HPV vaccination dose than after subsequent doses, a dose-effect was not confirmed. Results remained similar after applying a lag time.

[Dynamics of epidemiological indicators of thyroid pathology in the population of the Russian Federation: analytical report for the period 2009-2018].

BACKGROUND: The level of iodine consumption by the population largery determines the spectrum of thyroid pathology. To date, in the Russian Federation, iodine-deficiency disorders (IDD) occupy a leading position in the structure of all thyroid diseases. Chronic ID leads to adverse health consequences and significant economic costs for their elimination on a national scale. However, the spectrum of thyroid pathology is not limited to the problem of ID, and the study of other thyroid diseases is also of interest. AIMS: to assess the dynamics of prevalence and incidence of IDD and other thyroid diseases in the entire population of the RF for the period 2009-2018, using official state statistics. MATERIALS AND METHODS: the main epidemiological indicators (incidence and prevalence) of thyroid diseases in the entire population of the RF were analyzed using official state statistics. The analyzed period is 2009-2018. There was no medical intervention. To assess the dynamics of prevalence and incidence, a linear regression models were constructed, the slope of the trend line was calculated. RESULTS: the data were analyzed in accordance with the structure of diseases presented in the statistical reporting: goiter, thyroiditis, hypothyroidism, thyrotoxicosis, congenital iodine deficiency syndrome. For the ten-year period 2009-2018 there is a statistically significant increase in the prevalence of various forms of goiter, thyrotoxicosis, congenital iodine deficiency syndrome in the entire population of the Russian Federation. During the observation period, an increase in the incidence of thyrotoxicosis was revealed. With regard to the incidence of congenital iodine deficiency syndrome, only an upward trend was revealed. Despite the fact that during the observation period the number of new cases of various forms of goiter decreased, the prevalence of goiter among the population of the Russian Federation remains high: 1.2% of the population by January 1, 2019. with the growth of autoimmune pathology, improvement of the level of diagnosis, and also, in some cases, with overdiagnosis (for example, when diagnosing autoimmune thyroiditis in individuals with asymptomatic carriage of antithyroid antibodies). The current approaches to iodine prophylaxis are not effective enough. CONCLUSIONS: the results of the analysis indicate mainly an increase in the high prevalence of thyroid pathology among the population of the RF against the background of regional events. The problem of ID remains unresolved, which dictates the need to introduce universal mandatory salt iodization in the territory of the RF.

The assessment of autoimmunological status and prevalence of different forms of celiac disease among children with type 1 diabetes mellitus and celiac disease.

This study aims to assess the autoimmunological status and forms of celiac disease (CD) among children with type 1 diabetes mellitus (T1DM). The study group comprises 27 patients at the mean age of 12.30 years (+/-SD 3.12). The measurement of the level of diabetes-specific antibodies and organ-specific antibodies was gained at the T1DM-onset and repeated annually. The following risk factors influencing time of CD diagnosis were analyzed: age, sex, T1DM duration, autoantibodies, and HLA-haplotype. The prevalence of antibodies was GADA-74%, IAA-63%, IA2A-67%, ATA-11%, and ATG-4%. The intestinal biopsy revealed in 19% no changes and in 77% stage 3 (Marsh scale). In most cases, no clinical manifestation of CD was observed. The diagnosis of Hashimoto's disease was made twice. The negative correlation between the age at T1DM-onset and the interval between onset of T1DM and CD (r = -0.35, p < .05) was noted. The high-comorbidity ratio of CD and thyroiditis with T1DM demands regular screening tests especially in the first years after T1DM-onset.

[Spectrometric assessment of thyroid depth within the radioiodine test]. / Spektrometrisches Verfahren zur Tiefenbestimmung der Schilddrüse im Rahmen des Radioiodtests.

UNLABELLED: Aim of this study is the validation of a simple method for evaluating the depth of the target volume within the radioiodine test by analyzing the emitted iodine-131 energy spectrum. PATIENTS, METHODS: In a total of 250 patients (102 with a solitary autonomous nodule, 66 with multifocal autonomy, 29 with disseminated autonomy, 46 with Graves' disease, 6 for reducing goiter volume and 1 with only partly resectable papillary thyroid carcinoma), simultaneous uptake measurements in the Compton scatter (210 +/- 110 keV) and photopeak (364-45/+55 keV) windows were performed over one minute 24 hours after application of the 3 MBq test dose, with subsequent calculation of the respective count ratios. Measurements with a water-filled plastic neck phantom were carried out to perceive the relationship between these quotients and the average source depth and to get a calibration curve for calculating the depth of the target volume in the 250 patients for comparison with the sonographic reference data. Another calibration curve was obtained by evaluating the results of 125 randomly selected patient measurements to calculate the source depth in the other half of the group. RESULTS: The phantom measurements revealed a highly significant correlation (r = 0,99) between the count ratios and the source depth. Using these calibration data, a good relationship (r = 0,81, average deviation 6 mm corresponding to 22%) between the spectrometric and the sonographic depths was obtained. When using the calibration curve resulting from the 125 patient measurements, the overage deviation in the other half of the group was only 3 mm (12%). There was no difference between the disease groups. CONCLUSION: The described method allows on easy to use depth correction of the uptake measurements providing good results.

Cost-effectiveness of prenatal screening for postpartum thyroiditis.

Five percent of all pregnant women and 25% of pregnant women with insulin-dependent diabetes mellitus (IDDM) develop postpartum thyroiditis (PPT) during the first year after delivery. PPT has significant morbidity and can be predicted prenatally by the presence of thyroid peroxidase (TPO) antibody. Our objective was to estimate the cost-effectiveness of screening pregnant women for the TPO antibody versus the current strategy of no screening test or an alternative strategy of a thyroid-stimulating hormone (TSH) test 6 weeks postpartum. We performed cost-effectiveness analysis using a decision tree model that accounted for cases of PPT detected, medical outcomes of screening, and costs of screening and care. Hypothetical cohorts of 1000 pregnant women with uncomplicated pregnancies and 1000 pregnant women with IDDM were used to determine direct medical costs, quality-adjusted life years, and cases of PPT detected. The cost of testing 1000 pregnant women for TSH at the 6 week postpartum visit was $75,000, with an effectiveness of 995.2 quality-adjusted life years resulting in a cost-effectiveness ratio of $48,000 per quality-adjusted life year. Checking a TPO antibody was more effective (995.5 quality-adjusted life years) but also more expensive ($93,000). The incremental cost-effectiveness ratio of the TPO antibody strategy was $60,000 per quality-adjusted life year. Results were most sensitive to changes in the test characteristics, incidence of disease, and percentage of women with PPT who were symptomatic. A separate analysis for women with IDDM resulted in an incremental cost-effectiveness ratio of $13,000 per quality-adjusted life year for the TSH strategy and $32,000 per quality-adjusted life year for the TPO strategy. Screening for PPT is likely to be reasonably cost-effective and should be considered for inclusion as part of routine pregnancy care.

Association of autoimmune thyroid disease with a microsatellite marker for the thyrotropin receptor gene and CTLA-4 in a Japanese population.

To examine the genetic contribution of the thyroid-stimulating hormone receptor (TSHR, or thyrotropin receptor) gene to autoimmune thyroid disease (AITD), we identified a dinucleotide repeat polymorphism near the TSHR gene that mapped to an 8.6 cM interval between D14S74 and D14S55 on the long arm of human chromosome 14. Association studies revealed a significant difference (p = 3.8 x 10(-5) between the TSHR microsatellite allele frequency distribution in 81 unrelated Japanese AITD patients and 113 Japanese controls, with a significant increase in the 180 pb allele (allele 1) of the microsatellite sequence (p = 5.8 x 10(-7). The risk for AITD with the 180 bp allele was 3.5, with association highly significant in female patients (p = 1.1 x 10(-5) and less dramatic, but still significant, in male patients (p = .02). These results suggest that the 180 bp allele of the TSHR microsatellite is associated with a susceptibility locus for AITD in Japanese patients. Two additional genetic markers have been evaluated for association in the Japanese AITD patients. The TSHR codon 52 (C52-->A52) transition mutation was not observed in the Japanese. A polymorphism for the CTLA-4 gene was genotyped and, while association with AITD was not observed (p = .15), a significant association was observed between CTLA-4 alleles of 110 bp (p = .01) and 106 bp (p = .004) and susceptibility to primary hypothyroidism or idiopathic myxedema, respectively.

To operate or not to operate? The value of fine needle aspiration cytology in the assessment of thyroid swellings.

AIMS: To evaluate all thyroid fine needle aspirations (FNA) done over a six year period to assess the accuracy and value of the technique. METHODS: There were 335 FNAs of which 184 had subsequent histology and 49 others had clinical follow up, providing 233 patients for analysis. All cytology and histology was reviewed with no significant alterations in diagnosis. The FNAs were classified into three groups: benign, suspicious (recommend excision), and malignant. The histology and medical records were reviewed to determine whether the cytology was accurate. RESULTS: There were 130 benign FNAs, 126 had non-malignant histology or normal clinical follow up, and four had malignancies on histology (two lymphomas, one follicular carcinoma, and one carcinoma not otherwise specified). There were 45 suspicious FNAs. Of these five had either follicular or papillary carcinoma, 14 had follicular adenomas, and 26 had colloid nodular goitres or normal clinical follow up. Of the 21 malignant FNAs, 11 had carcinoma and 10 had either a non-malignant histology or normal follow up. There were 126 true negatives, 30 true positives, 4 false negatives, and 36 false positives. This gives a sensitivity of 88%, a specificity of 78%, a positive predictive value of 46%, a negative predictive value of 97%, and an accuracy of 80%. CONCLUSIONS: FNA cytology of the thyroid has a high negative predictive value, which is useful to reassure the majority of patients presenting with thyroid enlargement. However, a negative FNA should never exclude malignancy if there is a strong clinical suspicion. If this rule is adhered to a large number of patients will be spared unnecessary surgery and no malignant nodule will go untreated.

Role of nuclear grooves in the diagnosis of papillary thyroid carcinoma. A quantitative assessment on fine needle aspiration smears.

Thirty-four cases of papillary thyroid carcinoma and 69 control cases consisting of 17 follicular neoplasms, 5 Hürthle cell neoplasms, 7 medullary carcinomas, 6 thyrotoxic goiters, 19 chronic lymphocytic thyroiditis cases, 3 subacute thyroiditis cases and 12 colloid goiter cases were studied for nuclear grooves. Such grooves were seen in 100% of papillary carcinoma and in 75-100% of other thyroid disorders, but their number was strikingly higher in papillary carcinoma. A quantitative assessment for nuclear grooves was made based on counting 500 follicular cells in hematoxylin and eosin (H&E)-stained and May-Grünwald-Giemsa (MGG)-stained smears. In H&E-stained smears of papillary carcinoma the number of cells with nuclear grooves (227.3 +/- 99.96 SD) was significantly higher as compared to other thyroid disorders (P < .01 to < .001). Eighty-eight percent of papillary carcinoma had nuclear grooves in > or = 20% tumor cells, whereas none of the other thyroid diseases exceeded this level. In MGG-stained smears the number of cells with nuclear grooves (40.7 +/- 32.83 SD) was also significantly higher as compared to other thyroid disorders (P < .05 to < .001). Of papillary carcinomas, 67.6% had > or = 4% cells with nuclear grooves, whereas 0-40% of other thyroid diseases exceeded this level. Nuclear grooves were significantly higher in H&E-stained smears of papillary carcinoma as compared to MGG-stained smears (P < .001). Based on this objective assessment, nuclear grooves were a useful criterion in the diagnosis of papillary thyroid carcinoma in H&E-stained smears but were not as reliable in MGG-stained smears.

Soluble CD antigen (cytokine) expression in various hyperthyroid states and use in the assessment of propylthiouracil treatment.

The soluble CD antigens sCD8, sCD23, and sCD25 are increased in untreated Graves' hyperthyroidism. These levels remain elevated when euthyroidism is established in response to propylthiouracil (PTU) therapy but decrease to control values after PTU treatment is discontinued, when euthyroidism has been established and maintained. Neither sCD8 nor sCD23 are elevated in patients with euthyroid Graves' ophthalmopathy nor in the hyperthyroid phase of subacute thyroiditis. sCD25 is increased to an intermediate degree in these disorders. Soluble CD8 > or = 450 U/ml is sensitive, specific, and predictive of PTU success as sole therapy or need for definitive therapy in untreated and PTU-treated Graves' hyperthyroidism, exceeding the predictive values of thyroid-stimulating hormone receptor antibody, thyroid peroxidase antibody, and T3 radioimmunoassay.

Fine-needle aspiration biopsy of the thyroid. Superior diagnostic tool.

Fine-needle aspiration biopsy of thyroid nodules is an easily performed office procedure that has the highest sensitivity and specificity and the lowest cost of all evaluation methods. Interpretation requires an experienced cytologist or endocrinologist, or both. Patient acceptance has been high. With use of fine-needle aspiration biopsy, many unnecessary operations have been avoided.

Needle biopsy in the assessment and management of hypofunctioning thyroid nodules.

Needle biopsy of hypofunctioning solitary thyroid nodules provides direct diagnostic information which would be otherwise obtainable only by surgery. The technique is safe and cost-effective. It provides a high diagnostic yield. It is also useful in planning surgery and reducing dependence on frozen-section diagnosis, which is often difficult with thyroid nodules. Technical and interpretative precautions are discussed. Of 192 patients undergoing this procedure, a satisfactory specimen was obtained in 95 percent. Needle aspiration biopsy (fine needle) was done in 110 patients with good cytologic correlations. Of 52 glands subsequently excised, carcinoma was present in 22 (42 percent). The preoperative diagnosis had been made in 19 (86 percent) of the latter group. This procedure is recommended for consideration in the assessment and management of hypofunctioning thyroid nodules.

[Measurement for serum thyroxine-binding globulin (TBG) and its clinical assessment in diagnosis of thyroid states (author's transl)].

Serum levels of thyroxine (T4)-binding globulin (TBG) were determined by a radioimmunoassay using cellulose-linked antibody to TBG. Values obtained in healthy young adults averaged 1.62 +/- 0.25 (SD) mg/100 ml, and no significant difference wwas detected between males and females. The TBG levels remained within the normal limit in hyperthyroidism while they were significantly increased in hypothyroidism. Interestingly enough, TBG levels were significantly elevated in chronic thyroidities with no overt hypothyroidism. In normal pregnancy, TBG was increased slightly in the first trimester, and markedly in the second and third trimesters. In one case of congenital TBG deficiency, no immunoreactive TBG was detected. It was demonstrated, further, that an inverse relationship (r = -0.7593) existed between the TBG level and serum triiodothyronine uptake index, and that a direct relation (r = +0.6557) was present between the TBG level and T4 in sera from normal subjects and pregnancy. Ratios of T4/TBG were markedly increased in hyperthyroidism, and decreased in hypothyroidism, showing no overlap with the normal subjects, whereas they were below the normal limit in half the cases in the second and third trimesters of pregnancy. The radioimmunoassay for TBG was useful in evaluating hypothyroid states, because it could differentiate the increase in T4 associated with elevated TBG from hyperthyroidism.

Susceptibility of inbred rat strains to experimental thyroiditis: quantitation of thyroglobulin-binding cells and assessment of T-cell function in susceptible and non-susceptible strains.

Ten inbred strains of rats were immunized with crude homologous thyroglobulin emulsified in Freund's complete adjuvant in order to investigate strain susceptibility to the induction of both thyroiditis and antibody to thyroglobulin. Two strains (LH and AUG) were found to be extremely susceptible and had 100% incidence of thyroid lesions which in general varied from moderate to very severe (mean index of pathology+/-SE, 2-5+/-0-2 and 2-1+/-0-4 respectively). One other strain (HL) also had 100% incidence of lesions but there were consistently mild in character (1-1+/-0-1). Two strains (DA and SD) were variable, with thyroid change varying from negative to severe. Three strains (LEW, WAG and PVG/c) had occasional lesions and the remaining two strains (AS and CAM) showed no thyroid change. Four strains (LH, AUG, HL and DA) consistently produced good antibody responses to thyroglobulin (mean titres+/-SE 7-3+/-0-3, 9-5+/-0-4, 6-9+/-0-3 and 6-6+/-0-5 respectively). In contrast WAG and CAM rats failed to develop autoantibody and the responses of AS, PVG/c and SD strain rats were quite variable. Although the autoantibody response generally correlated well with the presence of thyroiditis in a particular strain, LEW, AS and PVG/c rats often had good antibody levels with minimal thyroid lesions. Females of the most susceptible strains (LH and AUG) were found to have significantly more severe thyroid lesions and higher antibody titres to thyroglobulin than males. The most susceptible strains were all found to be of the Ag-B5 major histocompatibility genotype whilst the least susceptible were of the Ag-B2 genotype. However, wide interstrain variability was noted within the Ag-B5 genotype particularly with respect to the induction and extent of thyroid lesions. It was not found possible to relate the divergence in susceptibility between rat strains of Ag-B5 and Ag-B2 genotypes to differences in respective numbers of thyroglobulin-binding cells within the circulation of the non-immunized animal. Similarly, there were no differences in response between a susceptible (LH) and non-susceptible (CAM) strain to the phytomitogens PHA and Con A.