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Over- and Under-Treatment of Hypothyroidism Is Associated with Excess Mortality: A Register-Based Cohort Study

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@article{87858287cea34d2fb5a3fe60e3850bfd,
title = "Over- and Under-Treatment of Hypothyroidism Is Associated with Excess Mortality: A Register-Based Cohort Study",
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.",
keywords = "Journal Article",
author = "Mads Lillevang-Johansen and Bo Abrahamsen and J{\o}rgensen, {Henrik L{\o}vendahl} and Brix, {Thomas Heiberg} and Laszlo Heged{\"u}s",
year = "2018",
month = "5",
doi = "10.1089/thy.2017.0517",
language = "English",
volume = "28",
pages = "566--574",
journal = "Thyroid",
issn = "1050-7256",
publisher = "Mary Ann/Liebert, Inc. Publishers",
number = "5",

}

RIS

TY - JOUR

T1 - Over- and Under-Treatment of Hypothyroidism Is Associated with Excess Mortality

T2 - A Register-Based Cohort Study

AU - Lillevang-Johansen, Mads

AU - Abrahamsen, Bo

AU - Jørgensen, Henrik Løvendahl

AU - Brix, Thomas Heiberg

AU - Hegedüs, Laszlo

PY - 2018/5

Y1 - 2018/5

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.

AB - 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.

KW - Journal Article

U2 - 10.1089/thy.2017.0517

DO - 10.1089/thy.2017.0517

M3 - Journal article

VL - 28

SP - 566

EP - 574

JO - Thyroid

JF - Thyroid

SN - 1050-7256

IS - 5

ER -

ID: 53794106