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Low TSH Is Associated With Frailty in an Older Veteran Population Independent of Other Thyroid Function Tests.

ABSTRACT: Low TSH is associated with frailty in the older adult. We studied whether low TSH is an independent marker of frailty or is an indicator of subclinical hyperthyroidism, which in turn predicts frailty. Of outpatient veterans seen between January 2005 and December 2016, we identified 100 patients aged ?60?years with two low TSH (<0.5?µIU/ml) and one fT3 measurement and 50 matched controls (TSH 0.5-5.0?µIU/ml). We used a deficit accumulation approach to create a frailty index (FI). The higher the FI, the more likely (p<0.001) that patients had expired. Patients with low (0.31?±?0.11?µIU/mL) versus normal (1.84?±?0.84?µIU/mL) TSH had higher mean FI compared to controls (0.25?±?0.12 vs. 0.15?±?0.07, p?p?p?=?.13), which disappeared when adjusted for age. Similar to prior studies, low TSH was associated with frailty. However, neither fT3 nor fT4 predicted low TSH or FI, suggesting that the association of low TSH with frailty is not due to subclinical hyperthyroidism, but perhaps to effects of comorbidities on TSH secretion.

SUBMITTER: Bhalla NS

PROVIDER: S-EPMC7797567 | biostudies-literature | 2021 Jan-Dec

REPOSITORIES: biostudies-literature

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Low TSH Is Associated With Frailty in an Older Veteran Population Independent of Other Thyroid Function Tests.

Bhalla Nalini S NS Vinales Karyne Lima KL Li Ming M Bhattarai Richa R Fawcett Janet J Harman Sherman Mitchell SM

Gerontology & geriatric medicine 20210107

Low TSH is associated with frailty in the older adult. We studied whether low TSH is an independent marker of frailty or is an indicator of subclinical hyperthyroidism, which in turn predicts frailty. Of outpatient veterans seen between January 2005 and December 2016, we identified 100 patients aged ≥60 years with two low TSH (<0.5 µIU/ml) and one fT3 measurement and 50 matched controls (TSH 0.5-5.0 µIU/ml). We used a deficit accumulation approach to create a frailty index (FI). The higher the F ...[more]

PMID: 33457463

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Project description:BACKGROUND:Thyroid disorders are common in the adult German population. Little is known about guideline implementation in clinical practice and the prevalence of diagnostic procedures in ambulatory care. The study aims to investigate the use of thyroid hormone measurements, thyroid ultrasound, thyroid scintiscan and associated costs in ambulatory care at population level. METHODS:Data were derived from two independent population-based cohorts of the Study of Health In Pomerania (SHIP). Ambulatory billing data from the Association of Statutory Health Insurance Physicians Mecklenburg-Vorpommern were individually linked for the period 2002-2016 with SHIP data. The main outcomes were the frequency of outpatient ultrasound, scintiscan, serum TSH level measurement, free triiodothyronine (fT3) and free thyroxine (fT4) measurement, TSH-receptor-antibodies and microsomal antibodies measurement within 1 year and 3 years prior to the study entrance of the participants. Multinomial logistic regression models were used to assess the association of age, sex, thyroid medication intake and Charlson-Comorbidity-Index with frequency of TSH measurements and ultrasound examinations. RESULTS:A total of 5552 participants (47% male, median age 55) were included in the analysis. 25% (1409/5552) had a diagnosed thyroid disorder or treatment, 40% (2191/5552) had clinical findings based on ultrasound or laboratory testing in SHIP only and 35% (1952/5552) neither a coded thyroid disorder or clinical finding nor thyroid medication. In the total study population 30% (1626/5552) received at least one TSH measurement, 6.8% (378/5552) at least one thyroid ultrasound and 2.6% (146/5552) at least one scintiscan within the past year before the study examination. Tests were performed more frequently in patients with thyroid medication and coded thyroid disorders. Hence, this group caused the highest expenditures. CONCLUSIONS:Given the high prevalence of thyroid disorders, diagnostic and monitoring tests should be used rationally with regard to costs. TSH levels should be monitored regularly in patients on thyroid medication. A consensus on monitoring frequency and iteration of monitoring of morphological thyroid disorders with TSH and ultrasound and specific guideline recommendations are needed. TRIAL REGISTRATION:Versorgungsforschung Deutschland (VfD_17_003880).

Project description:The synergistic activation of transcription factors can lead to thyroid progenitor cell speciation. We have previously shown in vitro that mouse or human stem cells, expressing the transcription factors NKx2-1 and Pax8, can differentiate into thyroid neo-follicular structures (TFS). We now show that syngeneic mouse TFS when implanted into hypothyroid TSH receptor knockout (TSHR-KO) mice can ameliorate the hypothyroid state for an extended period. ES cells derived from heterozygous TSHR-KO blastocysts were stably transfected with Nkx2-1-GFP and Pax8-mcherry constructs and purified into 91.8% double positive cells by flow cytometry. After 5 days of activin A treatment these double positive cells were then induced to differentiate into neo-follicles in Matrigel for 21 days in the presence of 500μU/mL of TSH. Differentiated TFS expressing thyroglobulin mRNA were implanted under the kidney capsule of 4-6 weeks old TSHR-KO mice (n=5) as well as hind limb muscle (n=2) and anterior chamber of one eye (n=2). Five of the mice tested after 4 weeks were all rendered euthyroid and all mice remained euthyroid at 20 weeks post implantation. The serum T4 fully recovered (pre-bleed 0.62 ± 0.03 to 8.40 ± 0.57 µg/dL) and the previously elevated TSH became normal or suppressed (pre-bleed 391 ± 7.6 to 4.34 ± 1.25 ng/dL) at the end of the 20 week observation period. The final histology obtained from the implanted kidney tissues showed only rudimentary thyroid follicular structures but which stained positive for thyroglobulin expression. The presence of only rudimentary structures at the site of implant on these extended animals suggested possible migration of cells from the site of implant or an inability of TFCs to maintain proper follicular morphology in these external sites for extended periods. However, there were no signs of tumor formation and no immune infiltration. These preliminary studies show that TSHR-KO mice are a useful model for orthotropic implantation of functional thyroid cells without the need for thyroidectomy, radioiodine ablation or anti thyroid drug control of thyroid function. This approach is also proof of principle that thyroid cells derived from mouse ES cells are capable of surviving as functional neo-follicles in vivo for an extended period of 20 weeks.

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Low TSH Is Associated With Frailty in an Older Veteran Population Independent of Other Thyroid Function Tests.

Publications

Low TSH Is Associated With Frailty in an Older Veteran Population Independent of Other Thyroid Function Tests.

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