Excess Mortality in Treated and Untreated Hyperthyroidism Is Related to Cumulative Periods of Low Serum TSH

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 -