TY - JOUR
T1 - Excess Mortality in Treated and Untreated Hyperthyroidism Is Related to Cumulative Periods of Low Serum TSH
AU - Lillevang-Johansen, Mads
AU - Abrahamsen, Bo
AU - Jørgensen, Henrik Løvendahl
AU - Brix, Thomas Heiberg
AU - Hegedüs, Laszlo
N1 - Copyright © 2017 by the Endocrine Society
PY - 2017/7/1
Y1 - 2017/7/1
N2 - Introduction and Aim: Cumulative time-dependent excess mortality in hyperthyroid patients has been suggested. However, the effect of antithyroid treatment on mortality, especially in subclinical hyperthyroidism, remains unclarified. We investigated the association between hyperthyroidism and mortality in both treated and untreated hyperthyroid individuals. Patients and Methods: Register-based cohort study of 235,547 individuals who had at least one serum thyroid-stimulating hormone (TSH) measurement in the period 1995 to 2011 (7.3 years median follow-up). Hyperthyroidism was defined as at least two measurements of low serum TSH. Mortality rates for treated and untreated hyperthyroid subjects compared with euthyroid controls were calculated using multivariate Cox regression analyses, controlling for age, sex, and comorbidities. Cumulative periods of decreased serum TSH were analyzed as a time-dependent covariate. Results: Hazard ratio (HR) for mortality was increased in untreated [1.23; 95% confidence interval (CI), 1.12 to 1.37; P < 0.001], but not in treated, hyperthyroid patients. When including cumulative periods of TSH in the Cox regression analyses, HR for mortality per every 6 months of decreased TSH was 1.11 (95% CI, 1.09 to 1.13; P < 0.0001) in untreated hyperthyroid patients (n = 1137) and 1.13 (95% CI, 1.11 to 1.15; P < 0.0001) in treated patients (n = 1656). This corresponds to a 184% and 239% increase in mortality after 5 years of decreased TSH in untreated and treated hyperthyroidism, respectively. Conclusions: Mortality is increased in hyperthyroidism. Cumulative periods of decreased TSH increased mortality in both treated and untreated hyperthyroidism, implying that excess mortality may not be driven by lack of therapy, but rather inability to keep patients euthyroid. Meticulous follow-up during treatment to maintain biochemical euthyroidism may be warranted.
AB - Introduction and Aim: Cumulative time-dependent excess mortality in hyperthyroid patients has been suggested. However, the effect of antithyroid treatment on mortality, especially in subclinical hyperthyroidism, remains unclarified. We investigated the association between hyperthyroidism and mortality in both treated and untreated hyperthyroid individuals. Patients and Methods: Register-based cohort study of 235,547 individuals who had at least one serum thyroid-stimulating hormone (TSH) measurement in the period 1995 to 2011 (7.3 years median follow-up). Hyperthyroidism was defined as at least two measurements of low serum TSH. Mortality rates for treated and untreated hyperthyroid subjects compared with euthyroid controls were calculated using multivariate Cox regression analyses, controlling for age, sex, and comorbidities. Cumulative periods of decreased serum TSH were analyzed as a time-dependent covariate. Results: Hazard ratio (HR) for mortality was increased in untreated [1.23; 95% confidence interval (CI), 1.12 to 1.37; P < 0.001], but not in treated, hyperthyroid patients. When including cumulative periods of TSH in the Cox regression analyses, HR for mortality per every 6 months of decreased TSH was 1.11 (95% CI, 1.09 to 1.13; P < 0.0001) in untreated hyperthyroid patients (n = 1137) and 1.13 (95% CI, 1.11 to 1.15; P < 0.0001) in treated patients (n = 1656). This corresponds to a 184% and 239% increase in mortality after 5 years of decreased TSH in untreated and treated hyperthyroidism, respectively. Conclusions: Mortality is increased in hyperthyroidism. Cumulative periods of decreased TSH increased mortality in both treated and untreated hyperthyroidism, implying that excess mortality may not be driven by lack of therapy, but rather inability to keep patients euthyroid. Meticulous follow-up during treatment to maintain biochemical euthyroidism may be warranted.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Antithyroid Agents/therapeutic use
KW - Denmark/epidemiology
KW - Female
KW - Humans
KW - Hyperthyroidism/blood
KW - Male
KW - Middle Aged
KW - Registries
KW - Thyroidectomy
KW - Thyrotropin/blood
KW - Thyroxine/blood
KW - Triiodothyronine/blood
U2 - 10.1210/jc.2017-00166
DO - 10.1210/jc.2017-00166
M3 - Journal article
C2 - 28368540
SN - 0021-972X
VL - 102
SP - 2301
EP - 2309
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 7
ER -