Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy

J Clin Endocrinol Metab. 2010 Jan;95(1):186-93. doi: 10.1210/jc.2009-1625. Epub 2009 Nov 11.

Abstract

Context: For patients on T(4) replacement, the dose is guided by serum TSH concentrations, but some patients request higher doses due to adverse symptoms.

Objective: The aim of the study was to determine the safety of patients having a low but not suppressed serum TSH when receiving long-term T(4) replacement.

Design: We conducted an observational cohort study, using data linkage from regional datasets between 1993 and 2001.

Setting: A population-based study of all patients in Tayside, Scotland, was performed.

Patients: All patients taking T(4) replacement therapy (n = 17,684) were included.

Main outcome measures: Fatal and nonfatal endpoints were considered for cardiovascular disease, dysrhythmias, and fractures. Patients were categorized as having a suppressed TSH (<or=0.03 mU/liter), low TSH (0.04-0.4 mU/liter), normal TSH (0.4-4.0 mU/liter), or raised TSH (>4.0 mU/liter).

Results: Cardiovascular disease, dysrhythmias, and fractures were increased in patients with a high TSH: adjusted hazards ratio, 1.95 (1.73-2.21), 1.80 (1.33-2.44), and 1.83 (1.41-2.37), respectively; and patients with a suppressed TSH: 1.37 (1.17-1.60), 1.6 (1.10-2.33), and 2.02 (1.55-2.62), respectively, when compared to patients with a TSH in the laboratory reference range. Patients with a low TSH did not have an increased risk of any of these outcomes [hazards ratio: 1.1 (0.99-1.123), 1.13 (0.88-1.47), and 1.13 (0.92-1.39), respectively].

Conclusions: Patients with a high or suppressed TSH had an increased risk of cardiovascular disease, dysrhythmias, and fractures, but patients with a low but unsuppressed TSH did not. It may be safe for patients treated with T(4) to have a low but not suppressed serum TSH concentration.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / epidemiology*
  • Comorbidity
  • Female
  • Fractures, Bone / blood
  • Fractures, Bone / epidemiology*
  • Fractures, Bone / etiology
  • Hormone Replacement Therapy / adverse effects
  • Humans
  • Hypothyroidism / blood
  • Hypothyroidism / drug therapy*
  • Hypothyroidism / epidemiology
  • Male
  • Middle Aged
  • Osmolar Concentration
  • Osteoporosis / blood
  • Osteoporosis / complications
  • Osteoporosis / epidemiology
  • Thyrotropin / blood*
  • Thyroxine / adverse effects
  • Thyroxine / therapeutic use*
  • Time Factors
  • Young Adult

Substances

  • Thyrotropin
  • Thyroxine