Impaired action of thyroid hormone associated with smoking in women with hypothyroidism

N Engl J Med. 1995 Oct 12;333(15):964-9. doi: 10.1056/NEJM199510123331503.


Background: The effect of smoking on thyroid function is controversial, and its effect on thyroid hormone action is unknown. We investigated the effects of cigarette smoking in women with various grades of hypothyroidism and in normal women.

Methods: We studied 138 normal women and 135 women with primary hypothyroidism, of whom 84 had subclinical hypothyroidism and 51 overt hypothyroidism. Sixty of the women with hypothyroidism were reevaluated during thyroxine therapy. The women were categorized as smokers or nonsmokers according to their responses to a questionnaire. Thyroid function was evaluated by measurements of serum thyrotropin, free thyroxine, and triiodothyronine. Peripheral thyroid hormone action was assessed by a clinical score and measurements of ankle-reflex time and serum lipids and creatine kinase.

Results: Among the women with subclinical hypothyroidism, the smokers had a higher mean (+/- SD) serum thyrotropin concentration (21.3 +/- 16.6 vs. 12.7 +/- 7.2 mU per liter, P = 0.004) and a higher ratio of serum triiodothyronine to serum free thyroxine (by 30 percent, P = 0.003) than the nonsmokers. Their serum concentrations of total cholesterol and low-density lipoprotein (LDL) cholesterol were higher (by 16 percent, P = 0.013; and 28 percent, P = 0.003, respectively). Among the women with overt hypothyroidism, the serum concentrations of thyrotropin, free thyroxine, and triiodothyronine were similar in the smokers and nonsmokers. As compared with the nonsmokers, the smokers had a clinical score indicating a greater degree of hypothyroidism (P < 0.001), higher serum concentrations of total and LDL cholesterol (by 25 percent, P < 0.001; and 24 percent, P = 0.002, respectively), longer ankle-reflex time (by 25 percent, P < 0.001), and higher serum concentrations of creatine kinase (by 236 percent, P < 0.001). There were dose-response relations between smoking and serum concentrations of total and LDL cholesterol, serum creatine kinase concentrations, and ankle-reflex time in the women with overt hypothyroidism, and between smoking and serum concentrations of total and LDL cholesterol in the women with subclinical hypothyroidism.

Conclusions: Smoking increases the metabolic effects of hypothyroidism in a dose-dependent way. This may be explained by alteration of both thyroid function and hormone action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Cholesterol / blood
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Hypothyroidism / blood
  • Hypothyroidism / drug therapy*
  • Hypothyroidism / physiopathology
  • Middle Aged
  • Smoking / adverse effects
  • Smoking / blood
  • Smoking / physiopathology*
  • Thyroid Gland / drug effects*
  • Thyroid Gland / physiology
  • Thyroid Gland / physiopathology
  • Thyrotropin / blood
  • Thyroxine / blood
  • Thyroxine / therapeutic use*
  • Triiodothyronine / blood


  • Triiodothyronine
  • Thyrotropin
  • Cholesterol
  • Thyroxine