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Over- and Under-Treatment of Hypothyroidism Is Associated with Excess Mortality: A Register-Based Cohort Study.
Thyroid. 2018 05; 28(5):566-574.T

Abstract

OBJECTIVE

This study investigated the association between hypothyroidism and mortality in both treated and untreated hypothyroid patients, and the consequences of over- and under-treatment with respect to mortality.

PATIENTS AND METHODS

This was a register-based cohort study of 235,168 individuals who had at least one serum thyrotropin (TSH) during 1995-2011 (median follow-up 7.2 years). Hypothyroidism was defined as at least two measurements of TSH >4.0 mIU/L within a half year spaced by at least 14 days, or one measurement of TSH >4.0 mIU/L and two filled prescriptions of levothyroxine the following year. All-cause mortality rates were calculated using multivariable Cox regression analysis adjusted for age, sex, and comorbidities using the Charlson Comorbidity Index.

RESULTS

Mortality was increased in untreated hypothyroid individuals (n = 673; hazard ratio [HR] = 1.46 [confidence interval (CI) 1.26-1.69]; p < 0.001) compared to euthyroid controls. Results remained significant even when subdividing according to mild (TSH >4.0 mIU/L and ≤10 mIU/L; p < 0.001) and marked hypothyroidism (TSH >10 mIU/L; p = 0.002). Mortality was increased in both treated and untreated hypothyroid individuals for each six months a patient had increased TSH (HR = 1.05 [CI 1.02-1.07], p < 0.0001, and HR = 1.05 [CI 1.02-1.07], p = 0.0009, respectively). In patients who received levothyroxine, the HR for mortality increased by a factor 1.18 ([CI 1.15-1.21]; p < 0.0001) for each six months a patient exhibited decreased TSH. This finding was essentially unchanged after stratification by disease severity (mild or marked hypothyroidism) and age (older and younger than 65 years).

CONCLUSIONS

Mortality was increased in untreated but not in treated hypothyroid individuals, independently of age and severity of hypothyroidism. Duration of decreased TSH in treated individuals had a greater impact on mortality than did duration of elevated TSH. These results stress the need for close monitoring of treatment in individuals receiving thyroid hormone replacement therapy.

Authors+Show Affiliations

1 Department of Endocrinology and Metabolism, Odense University Hospital , Odense, Denmark . 2 Institute of Clinical Research, University of Southern Denmark , Odense, Denmark .2 Institute of Clinical Research, University of Southern Denmark , Odense, Denmark . 3 Odense Patient data Explorative Network OPEN, University of Southern Denmark , Odense, Denmark . 4 Department of Medicine, Holbæk Hospital , Holbæk, Denmark .5 Department of Clinical Biochemistry, Hvidovre Hospital , Copenhagen, Denmark . 6 Department of Clinical Medicine, University of Copenhagen , Denmark .1 Department of Endocrinology and Metabolism, Odense University Hospital , Odense, Denmark .1 Department of Endocrinology and Metabolism, Odense University Hospital , Odense, Denmark .

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29631518

Citation

Lillevang-Johansen, Mads, et al. "Over- and Under-Treatment of Hypothyroidism Is Associated With Excess Mortality: a Register-Based Cohort Study." Thyroid : Official Journal of the American Thyroid Association, vol. 28, no. 5, 2018, pp. 566-574.
Lillevang-Johansen M, Abrahamsen B, Jørgensen HL, et al. Over- and Under-Treatment of Hypothyroidism Is Associated with Excess Mortality: A Register-Based Cohort Study. Thyroid. 2018;28(5):566-574.
Lillevang-Johansen, M., Abrahamsen, B., Jørgensen, H. L., Brix, T. H., & Hegedüs, L. (2018). Over- and Under-Treatment of Hypothyroidism Is Associated with Excess Mortality: A Register-Based Cohort Study. Thyroid : Official Journal of the American Thyroid Association, 28(5), 566-574. https://doi.org/10.1089/thy.2017.0517
Lillevang-Johansen M, et al. Over- and Under-Treatment of Hypothyroidism Is Associated With Excess Mortality: a Register-Based Cohort Study. Thyroid. 2018;28(5):566-574. PubMed PMID: 29631518.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Over- and Under-Treatment of Hypothyroidism Is Associated with Excess Mortality: A Register-Based Cohort Study. AU - Lillevang-Johansen,Mads, AU - Abrahamsen,Bo, AU - Jørgensen,Henrik Løvendahl, AU - Brix,Thomas Heiberg, AU - Hegedüs,Laszlo, Y1 - 2018/04/26/ PY - 2018/4/11/pubmed PY - 2019/1/29/medline PY - 2018/4/11/entrez KW - hypothyroidism KW - mortality KW - register-based KW - thyroid KW - treatment SP - 566 EP - 574 JF - Thyroid : official journal of the American Thyroid Association JO - Thyroid VL - 28 IS - 5 N2 - OBJECTIVE: This study investigated the association between hypothyroidism and mortality in both treated and untreated hypothyroid patients, and the consequences of over- and under-treatment with respect to mortality. PATIENTS AND METHODS: This was a register-based cohort study of 235,168 individuals who had at least one serum thyrotropin (TSH) during 1995-2011 (median follow-up 7.2 years). Hypothyroidism was defined as at least two measurements of TSH >4.0 mIU/L within a half year spaced by at least 14 days, or one measurement of TSH >4.0 mIU/L and two filled prescriptions of levothyroxine the following year. All-cause mortality rates were calculated using multivariable Cox regression analysis adjusted for age, sex, and comorbidities using the Charlson Comorbidity Index. RESULTS: Mortality was increased in untreated hypothyroid individuals (n = 673; hazard ratio [HR] = 1.46 [confidence interval (CI) 1.26-1.69]; p < 0.001) compared to euthyroid controls. Results remained significant even when subdividing according to mild (TSH >4.0 mIU/L and ≤10 mIU/L; p < 0.001) and marked hypothyroidism (TSH >10 mIU/L; p = 0.002). Mortality was increased in both treated and untreated hypothyroid individuals for each six months a patient had increased TSH (HR = 1.05 [CI 1.02-1.07], p < 0.0001, and HR = 1.05 [CI 1.02-1.07], p = 0.0009, respectively). In patients who received levothyroxine, the HR for mortality increased by a factor 1.18 ([CI 1.15-1.21]; p < 0.0001) for each six months a patient exhibited decreased TSH. This finding was essentially unchanged after stratification by disease severity (mild or marked hypothyroidism) and age (older and younger than 65 years). CONCLUSIONS: Mortality was increased in untreated but not in treated hypothyroid individuals, independently of age and severity of hypothyroidism. Duration of decreased TSH in treated individuals had a greater impact on mortality than did duration of elevated TSH. These results stress the need for close monitoring of treatment in individuals receiving thyroid hormone replacement therapy. SN - 1557-9077 UR - https://www.unboundmedicine.com/medline/citation/29631518/Over__and_Under_Treatment_of_Hypothyroidism_Is_Associated_with_Excess_Mortality:_A_Register_Based_Cohort_Study_ L2 - https://www.liebertpub.com/doi/full/10.1089/thy.2017.0517?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -