Subclinical Thyroid Dysfunction and Fracture Risk

Blum, Manuel R.; Bauer, Douglas C.; Collet, Tinh‐Hai; Fink, Howard A; Cappola, Anne R.; Costa, Bruno R. da; Cj, Wirth; Peeters, Robin P.; Åsvold, Bjørn Olav; Elzen, Wendy P. J. den; Luben, Robert; Imaizumi, Misa; Bremner, Alexandra; Gogakos, Apostolos; Eastell, Richard; Kearney, Patricia M.; Strotmeyer, Elsa S.; Wallace, Erin; Hoff, Mari; Ceresini, Graziano; Rivadeneira, Fernando; Uitterlinden, André G.; Stott, David J.; Westendorp, Rudi G.J.; Khaw, Kay Tee; Langhammer, Arnuf; Ferrucci, Luigi; Gussekloo, Jacobijn; Williams, Graham R.; Walsh, John P.; Jüni, Peter; Aujesky, Drahomir; Rodondi, Nicolas

doi:10.1001/jama.2015.5161

Cited by 282 publications

(195 citation statements)

References 59 publications

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“…5,6,[16][17][18] Even the subclinical form of hypothyroidism and hyperthyroidism are associated with poor bone quality. TSH even moderately below or above the reference range is an independent predictive factor for vertebral fractures.…”

Section: Discussionmentioning

confidence: 99%

The impact of thyroid autoimmunity (TPOAb) on bone density and fracture risk in postmenopausal women

Polovina

Miljić

Zivojinović³

et al. 2017

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ObJeCTIVe: Skeletal development, linear growth, cartilage biology and bone turnover are highly dependent on the activity of thyroid hormones. Thyroid dysfunction affects the skeleton, and autoimmune thyroid disease, manifesting as a chronic inflammatory condition, may be an important contributing factor to impaired bone quality in these patients. MATeRIAlS AND MeTHODS: Measurement of TSH, FT4, TPOAb and bone mineral density and FRAX score calculations were performed in 189 postmenopausal women (110 euthyroid women and 79 women diagnosed with subclinical hypothyroidism) divided into subgroups according to the presence of TPOAb. ReSUlTS: In multivariate logistic regression analysis only TPOAb were found to be significantly related to fracture, independently of TSH values (p=0.018; OR=7.800; 95% CI 1.424-42.721). Lower bone mineral density and FRAX score for hip and for major osteoporotic fractures were associated with the presence of TPOAb in euthyroid postmenopausal women in an unadjusted logistic regression model, as well as in a model adjusted for age, bMI and smoking. TSH was a better predictive factor for fractures in women with subclinical hypothyroidism (FRAX main p <0.001; 95% CI for SE 0.858-0.959 and FRAX hip p <0.001; 95% CI for SE 0.628-0.854). CONCLUSION: Autoimmune thyroid disease is associated with decreased bone mineral density at both spine and hip and risk of future fracture incidence in euthyroid postmenopausal women. Presence of TPOAb is a potential marker of higher fracture risk in these patients. However, in subclinical hypothyroidism, TSH is a better indicator of future fragility fractures than TPOAb.

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Section: Discussionmentioning

confidence: 99%

The impact of thyroid autoimmunity (TPOAb) on bone density and fracture risk in postmenopausal women

Polovina

Miljić

Zivojinović³

et al. 2017

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“…In 2014, a meta-analysis by Wirth et al (85) reported a 2.2 higher risk for hip fractures and a 1.4 higher risk for non-vertebral fractures in subclinical thyrotoxicosis. In 2015, a meta-analysis comprising more than 70 000 participants revealed a 3.57 (1.88-6.78) higher risk for spine fractures among subjects with serum TSH lower than 0.10 U/L (86). Sensitivity analyses of the latter study showed a 1.79 (1.04-3.09) higher risk for spine fractures in endogenous thyrotoxicosis.…”

Section: European Journal Of Endocrinologymentioning

confidence: 97%

MANAGEMENT OF ENDOCRINE DISEASE: Subclinical thyrotoxicosis: prevalence, causes and choice of therapy

Carlé¹,

Andersen

Boelaert

et al. 2017

European Journal of Endocrinology

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Subclinical thyrotoxicosis is a condition affecting up to 10% of the population in some studies. We have reviewed literature and identified studies describing prevalences, causes and outcomes of this condition. Treatment should be considered in all subjects if this biochemical abnormality is persistent, especially in case of symptoms of thyrotoxicosis or in the presence of any complication. In particular, treatment should be offered in those subclinically thyrotoxic patients with a sustained serum TSH below 0.1 U/L. However it is important to recognise that there are no large controlled intervention studies in the field and thus there is no high quality evidence to guide treatment recommendations. In particular, there is no evidence for therapy and there is weak evidence of harm from thyrotoxicosis if serum TSH is in the 0.1-0.4 IU/L range. In this review, we describe the different causes of subclinical thyrotoxicosis, and how treatment should be tailored to the specific cause. We advocate radioactive iodine treatment to be the first-line treatment in majority of patients suffering from subclinical thyrotoxicosis due to multinodular toxic goitre and solitary toxic adenoma, but we do generally not recommend it as the first-line treatment in patients suffering from subclinical Graves' hyperthyroidism. Such patients may benefit mostly from antithyroid drug therapy. Subclinical thyrotoxicosis in early pregnancy should in general be observed, not treated. Moreover, we advocate a general restriction of therapy in cases where no specific cause for the presumed thyroid hyperactivity has been proven. Allan Carlé, MD, PhD, is a senior researcher, Aalborg University Hospital, Aalborg, Denmark. His research has focused on nosological classification of various subtypes of hypothyroidism. He has explored the field of hypoand hyper-thyroidism with special focus on the occurrence in the population, biochemical findings at diagnosis, the symptom presentation across gender and age, the magnitude of avoiding referral bias in population-based studies, and he has studied several risk factors for both hyper-and hypo-thyroidism. The research frame has been DanThyr (The Danish Investigation on Iodine Intake and Thyroid Diseases).

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“…A very recent meta-analysis, including IPD from 13 prospective cohorts, confirmed that Endo SHyper is associated with an increased risk of fractures with an HR of 1.52 (95% CI: 1.19-1.93) for hip fracture, 1.42 (95% CI: 1.16-1.74) for any fracture and 1.74 (95% CI: 1.01-2.99) for spine fracture [109]. Grade 2 SHyper was associated with higher fracture rates with an HR of 1.61 (95% CI: 1.21-2.15; 47 events in 510 participants) for hip fracture, 1.98 (95% CI: 1.41-2.78; 44 events in 212 participants) for any fracture, 1.61 (95% CI: 0.96-2.71; 32 events in 185 participants) for non-spine fracture and 3.57 (95% CI: 1.88-6.78; 8 events in 162 participants) for spine fracture [109].…”

Section: Risks Associated With Persistent and Untreated Endo Subclinimentioning

confidence: 99%

The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism

Biondi¹,

Bartalena²,

Cooper³

et al. 2015

Eur Thyroid J

235

143

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Endogenous subclinical hyperthyroidism (SHyper) is caused by Graves' disease, autonomously functioning thyroid nodules and multinodular goitre. Its diagnosis is based on a persistently subnormal serum thyroid-stimulating hormone (TSH) level with free thyroid hormone levels within their respective reference intervals. In 2014 the European Thyroid Association Executive Committee, given the controversies regarding the treatment of Endo SHyper, formed a task force to develop clinical practice guidelines based on the principles of evidence-based medicine. The task force recognized that recent meta-analyses, including those based on large prospective cohort studies, indicate that SHyper is associated with increased risk of coronary heart disease mortality, incident atrial fibrillation, heart failure, fractures and excess mortality in patients with serum TSH levels <0.1 mIU/l (grade 2 SHyper). Therefore, despite the absence of randomized prospective trials, there is evidence that treatment is indicated in patients older than 65 years with grade 2 SHyper to potentially avoid these serious cardiovascular events, fractures and the risk of progression to overt hyperthyroidism. Treatment could be considered in patients older than 65 years with TSH levels 0.1-0.39 mIU/l (grade 1 SHyper) because of their increased risk of atrial fibrillation, and might also be reasonable in younger (<65 years) symptomatic patients with grade 2 SHyper because of the risk of progression, especially in the presence of symptoms and/or underlying risk factors or co-morbidity. Finally, the task force concluded that there are no data to support treating SHyper in younger asymptomatic patients with grade 1 SHyper. These patients should be followed without treatment due to the low risk of progression to overt hyperthyroidism and the weaker evidence for adverse health outcomes.

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Subclinical Thyroid Dysfunction and Fracture Risk

Cited by 282 publications

References 59 publications

The impact of thyroid autoimmunity (TPOAb) on bone density and fracture risk in postmenopausal women

The impact of thyroid autoimmunity (TPOAb) on bone density and fracture risk in postmenopausal women

MANAGEMENT OF ENDOCRINE DISEASE: Subclinical thyrotoxicosis: prevalence, causes and choice of therapy

The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism

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