Is annual surveillance of all treated hypothyroid patients necessary?

Peer reviewedPublisher PD

Description and validation of a Markov model of survival for individuals free of cardiovascular disease that uses Framingham risk factors

BACKGROUND: Estimation of cardiovascular disease risk is increasingly used to inform decisions on interventions, such as the use of antihypertensives and statins, or to communicate the risks of smoking. Crude 10-year cardiovascular disease risk risks may not give a realistic view of the likely impact of an intervention over a lifetime and will underestimate of the risks of smoking. A validated model of survival to act as a decision aid in the consultation may help to address these problems. This study aims to describe the development of such a model for use with people free of cardiovascular disease and evaluates its accuracy against data from a United Kingdom cohort. METHODS: A Markov cycle tree evaluated using cohort simulation was developed utilizing Framingham estimates of cardiovascular risk, 1998 United Kingdom mortality data, the relative risk for smoking related non-cardiovascular disease risk and changes in systolic blood pressure and serum total cholesterol total cholesterol with age. The model's estimates of survival at 20 years for 1391 members of the Whickham survey cohort between the ages of 35 and 65 were compared with the observed survival at 20-year follow-up. RESULTS: The model estimate for survival was 75% and the observed survival was 75.4%. The correlation between estimated and observed survival was 0.933 over 39 subgroups of the cohort stratified by estimated survival, 0.992 for the seven 5-year age bands from 35 to 64, 0.936 for the ten 10 mmHg systolic blood pressure bands between 100 mmHg and 200 mmHg, and 0.693 for the fifteen 0.5 mmol/l total cholesterol bands between 3.0 and 10.0 mmol/l. The model significantly underestimated mortality in those people with a systolic blood pressure greater than or equal to 180 mmHg (p = 0.006). The average gain in life expectancy from the elimination of cardiovascular disease risk as a cause of death was 4.0 years for all the 35 year-old men in the sample (n = 24), and 1.8 years for all the 35 year-old women in the sample (n = 32). CONCLUSIONS: This model accurately estimates 20-year survival in subjects from the Whickham cohort with a systolic blood pressure below 180 mmHg

Comprehensive Genotyping in Two Homogeneous Graves' Disease Samples Reveals Major and Novel HLA Association Alleles

BACKGROUND: Graves' disease (GD) is the leading cause of hyperthyroidism and thyroid eye disease inherited as a complex trait. Although geoepidemiology studies showed relatively higher prevalence of GD in Asians than in Caucasians, previous genetic studies were contradictory concerning whether and/or which human leukocyte antigen (HLA) alleles are associated with GD in Asians. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a case-control association study (499 unrelated GD cases and 504 controls) and a replication in an independent family sample (419 GD individuals and their 282 relatives in 165 families). To minimize genetic and phenotypic heterogeneity, we included only ethnic Chinese Han population in Taiwan and excluded subjects with hypothyroidism. We performed direct and comprehensive genotyping of six classical HLA loci (HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1) to 4-digit resolution. Combining the data of two sample populations, we found that B*46:01 (odds ratio under dominant model [OR]  = 1.33, Bonferroni corrected combined P [P(Bc)]  = 1.17 x 10⁻²), DPB1*05:01 (OR  = 2.34, P(Bc) = 2.58 x 10⁻¹⁰), DQB1*03:02 (OR  = 0.62, P(Bc)  = 1.97 x 10⁻²), DRB1*15:01 (OR  = 1.68, P(Bc) = 1.22 x 10⁻²) and DRB1*16:02 (OR  = 2.63, P(Bc)  = 1.46 x 10⁻⁵) were associated with GD. HLA-DPB1*05:01 is the major gene of GD in our population and singly accounts for 48.4% of population-attributable risk. CONCLUSIONS/SIGNIFICANCE: These GD-associated alleles we identified in ethnic Chinese Hans, and those identified in other Asian studies, are totally distinct from the known associated alleles in Caucasians. Identification of population-specific association alleles is the critical first step for individualized medicine. Furthermore, comparison between different susceptibility/protective alleles across populations could facilitate generation of novel hypothesis about GD pathophysiology and indicate a new direction for future investigation

cDNA Immunization of Mice with Human Thyroglobulin Generates Both Humoral and T Cell Responses: A Novel Model of Thyroid Autoimmunity

Thyroglobulin (Tg) represents one of the largest known self-antigens involved in autoimmunity. Numerous studies have implicated it in triggering and perpetuating the autoimmune response in autoimmune thyroid diseases (AITD). Indeed, traditional models of autoimmune thyroid disease, experimental autoimmune thyroiditis (EAT), are generated by immunizing mice with thyroglobulin protein in conjunction with an adjuvant, or by high repeated doses of Tg alone, without adjuvant. These extant models are limited in their experimental flexibility, i.e. the ability to make modifications to the Tg used in immunizations. In this study, we have immunized mice with a plasmid cDNA encoding the full-length human Tg (hTG) protein, in order to generate a model of Hashimoto's thyroiditis which is closer to the human disease and does not require adjuvants to breakdown tolerance. Human thyroglobulin cDNA was injected and subsequently electroporated into skeletal muscle using a square wave generator. Following hTg cDNA immunizations, the mice developed both B and T cell responses to Tg, albeit with no evidence of lymphocytic infiltration of the thyroid. This novel model will afford investigators the means to test various hypotheses which were unavailable with the previous EAT models, specifically the effects of hTg sequence variations on the induction of thyroiditis

Identification of Novel Genetic Loci Associated with Thyroid Peroxidase Antibodies and Clinical Thyroid Disease

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