Tags

Type your tag names separated by a space and hit enter

Thyroid replacement therapy, thyroid stimulating hormone concentrations, and long term health outcomes in patients with hypothyroidism: longitudinal study.
BMJ. 2019 Sep 03; 366:l4892.BMJ

Abstract

OBJECTIVE

To explore whether thyroid stimulating hormone (TSH) concentration in patients with a diagnosis of hypothyroidism is associated with increased all cause mortality and a higher risk of cardiovascular disease and fractures.

DESIGN

Retrospective cohort study.

SETTING

The Health Improvement Network (THIN), a database of electronic patient records from UK primary care.

PARTICIPANTS

Adult patients with incident hypothyroidism from 1 January 1995 to 31 December 2017.

EXPOSURE

TSH concentration in patients with hypothyroidism.

MAIN OUTCOME MEASURES

Ischaemic heart disease, heart failure, stroke/transient ischaemic attack, atrial fibrillation, any fractures, fragility fractures, and mortality. Longitudinal TSH measurements from diagnosis to outcomes, study end, or loss to follow-up were collected. An extended Cox proportional hazards model with TSH considered as a time varying covariate was fitted for each outcome.

RESULTS

162 369 patients with hypothyroidism and 863 072 TSH measurements were included in the analysis. Compared with the reference TSH category (2-2.5 mIU/L), risk of ischaemic heart disease and heart failure increased at high TSH concentrations (>10 mIU/L) (hazard ratio 1.18 (95% confidence interval 1.02 to 1.38; P=0.03) and 1.42 (1.21 to 1.67; P<0.001), respectively). A protective effect for heart failure was seen at low TSH concentrations (hazard ratio 0.79 (0.64 to 0.99; P=0.04) for TSH <0.1 mIU/L and 0.76 (0.62 to 0.92; P=0.006) for 0.1-0.4 mIU/L). Increased mortality was observed in both the lowest and highest TSH categories (hazard ratio 1.18 (1.08 to 1.28; P<0.001), 1.29 (1.22 to 1.36; P<0.001), and 2.21 (2.07 to 2.36; P<0.001) for TSH <0.1 mIU/L, 4-10 mIU/L, and >10 mIU/L. An increase in the risk of fragility fractures was observed in patients in the highest TSH category (>10 mIU/L) (hazard ratio 1.15 (1.01 to 1.31; P=0.03)).

CONCLUSIONS

In patients with a diagnosis of hypothyroidism, no evidence was found to suggest a clinically meaningful difference in the pattern of long term health outcomes (all cause mortality, atrial fibrillation, ischaemic heart disease, heart failure, stroke/transient ischaemic attack, fractures) when TSH concentrations were within recommended normal limits. Evidence was found for adverse health outcomes when TSH concentration is outside this range, particularly above the upper reference value.

Authors+Show Affiliations

Institute of Applied Health Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. Joint first authors.Institute of Applied Health Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. Joint first authors.Institute of Applied Health Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. NHS Greater Glasgow and Clyde, Glasgow, UK.Institute of Applied Health Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.Institute of Metabolism and Systems Research, Edgbaston, Birmingham B15 2TT, UK. Institute of Translational Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. Centre for Endocrinology, Diabetes and Metabolism, Edgbaston, Birmingham B15 2TT, UK.Institute of Applied Health Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.Institute of Applied Health Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.Institute of Applied Health Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.Institute of Applied Health Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. Department of Endocrinology, 424 General Army Training Hospital, Thessaloniki, Greece.Institute of Applied Health Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK K.Nirantharan@bham.ac.uk. Centre for Endocrinology, Diabetes and Metabolism, Edgbaston, Birmingham B15 2TT, UK. Health Data Research UK Midlands, Institute of Translational Medicine, Edgbaston, Birmingham B15 2TH, UK.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31481394

Citation

Thayakaran, Rasiah, et al. "Thyroid Replacement Therapy, Thyroid Stimulating Hormone Concentrations, and Long Term Health Outcomes in Patients With Hypothyroidism: Longitudinal Study." BMJ (Clinical Research Ed.), vol. 366, 2019, p. l4892.
Thayakaran R, Adderley NJ, Sainsbury C, et al. Thyroid replacement therapy, thyroid stimulating hormone concentrations, and long term health outcomes in patients with hypothyroidism: longitudinal study. BMJ. 2019;366:l4892.
Thayakaran, R., Adderley, N. J., Sainsbury, C., Torlinska, B., Boelaert, K., Šumilo, D., Price, M., Thomas, G. N., Toulis, K. A., & Nirantharakumar, K. (2019). Thyroid replacement therapy, thyroid stimulating hormone concentrations, and long term health outcomes in patients with hypothyroidism: longitudinal study. BMJ (Clinical Research Ed.), 366, l4892. https://doi.org/10.1136/bmj.l4892
Thayakaran R, et al. Thyroid Replacement Therapy, Thyroid Stimulating Hormone Concentrations, and Long Term Health Outcomes in Patients With Hypothyroidism: Longitudinal Study. BMJ. 2019 Sep 3;366:l4892. PubMed PMID: 31481394.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Thyroid replacement therapy, thyroid stimulating hormone concentrations, and long term health outcomes in patients with hypothyroidism: longitudinal study. AU - Thayakaran,Rasiah, AU - Adderley,Nicola J, AU - Sainsbury,Christopher, AU - Torlinska,Barbara, AU - Boelaert,Kristien, AU - Šumilo,Dana, AU - Price,Malcolm, AU - Thomas,G Neil, AU - Toulis,Konstantinos A, AU - Nirantharakumar,Krishnarajah, Y1 - 2019/09/03/ PY - 2019/9/5/entrez PY - 2019/9/5/pubmed PY - 2019/9/20/medline SP - l4892 EP - l4892 JF - BMJ (Clinical research ed.) JO - BMJ VL - 366 N2 - OBJECTIVE: To explore whether thyroid stimulating hormone (TSH) concentration in patients with a diagnosis of hypothyroidism is associated with increased all cause mortality and a higher risk of cardiovascular disease and fractures. DESIGN: Retrospective cohort study. SETTING: The Health Improvement Network (THIN), a database of electronic patient records from UK primary care. PARTICIPANTS: Adult patients with incident hypothyroidism from 1 January 1995 to 31 December 2017. EXPOSURE: TSH concentration in patients with hypothyroidism. MAIN OUTCOME MEASURES: Ischaemic heart disease, heart failure, stroke/transient ischaemic attack, atrial fibrillation, any fractures, fragility fractures, and mortality. Longitudinal TSH measurements from diagnosis to outcomes, study end, or loss to follow-up were collected. An extended Cox proportional hazards model with TSH considered as a time varying covariate was fitted for each outcome. RESULTS: 162 369 patients with hypothyroidism and 863 072 TSH measurements were included in the analysis. Compared with the reference TSH category (2-2.5 mIU/L), risk of ischaemic heart disease and heart failure increased at high TSH concentrations (>10 mIU/L) (hazard ratio 1.18 (95% confidence interval 1.02 to 1.38; P=0.03) and 1.42 (1.21 to 1.67; P<0.001), respectively). A protective effect for heart failure was seen at low TSH concentrations (hazard ratio 0.79 (0.64 to 0.99; P=0.04) for TSH <0.1 mIU/L and 0.76 (0.62 to 0.92; P=0.006) for 0.1-0.4 mIU/L). Increased mortality was observed in both the lowest and highest TSH categories (hazard ratio 1.18 (1.08 to 1.28; P<0.001), 1.29 (1.22 to 1.36; P<0.001), and 2.21 (2.07 to 2.36; P<0.001) for TSH <0.1 mIU/L, 4-10 mIU/L, and >10 mIU/L. An increase in the risk of fragility fractures was observed in patients in the highest TSH category (>10 mIU/L) (hazard ratio 1.15 (1.01 to 1.31; P=0.03)). CONCLUSIONS: In patients with a diagnosis of hypothyroidism, no evidence was found to suggest a clinically meaningful difference in the pattern of long term health outcomes (all cause mortality, atrial fibrillation, ischaemic heart disease, heart failure, stroke/transient ischaemic attack, fractures) when TSH concentrations were within recommended normal limits. Evidence was found for adverse health outcomes when TSH concentration is outside this range, particularly above the upper reference value. SN - 1756-1833 UR - https://www.unboundmedicine.com/medline/citation/31481394/Thyroid_replacement_therapy_thyroid_stimulating_hormone_concentrations_and_long_term_health_outcomes_in_patients_with_hypothyroidism:_longitudinal_study_ L2 - http://www.bmj.com/cgi/pmidlookup?view=long&amp;pmid=31481394 DB - PRIME DP - Unbound Medicine ER -