Smoking in relation to thyroid metabolism and disease. Y. Taes, MD, PhD Dept. Endocrinology, Ghent University Hospital

Transcription

1 Smoking in relation to thyroid metabolism and disease Y. Taes, MD, PhD Dept. Endocrinology, Ghent University Hospital

2 Annual number of deaths attributed to tobacco in developed countries. Peto, R BMJ 1994;309: Copyright 1994 BMJ Publishing Group Ltd.

3 Thyroid disease Observational studies

4 Evidence for an effect of smoking on thyroid disease : Twin Studies

5 Proband vs. co-twin More autoimmune thyroid disease in smoking twin

6 Effects of smoking on 1. Effects on thyroid hormone concentrations 2. Auto immune thyroid disease Graves disease Graves ophtalmopathy Autoimmune hypothyroidism 3. Goiter Thyroid enlargment enlargement Toxic goiter 4. Thyroid Cancer

7 1. Circulating thyroid hormone concentrations Weak stimulating effect on thyroid function and thyroid size. Small increase in circulating thyroid hormone concentrations (T3) and thyroglobulin concentrations TSH is lower in smokers (independent from autoimmunity) MECHANISM : Nicotine stimulates sympathic nervous system and increases secretion of thyroid hormones Increase in thyroid hormone concentrations -> stimulating effect of smoking <-> intrinsic thyroid disease

8 Belin et al. J Clin Endocrinol Metab, 2004, 89:

9 Belin et al. J Clin Endocrinol Metab, 2004, 89:

10 2. Autoimmunity Graves disease Graves ophtalmopathy Autoimmune hypothyroidism

11 Graves' disease Consistent associations between Graves' disease and smoking Associations are stronger in association with opthalmopathy Interference with treatment Increase in relapse rates in men with Graves' disease upon stopping of Block & Replacement therapy

12 Graves disease without ophtalmopathy Vestergaard, Eur J Endoc 2002;146: OR : 3.3 ( )

13 Response of TSH-Receptor Antibodies and Thyroid Hormones During Treatment With Carbimazole for Graves Disease Nyirenda, M. J. et al. JAMA 2009;301:162-a-164-a.

14 Smoking and Treatment With Carbimazole T4 T3 Nyirenda, M. J. et al. JAMA 2009;301:162-a-164-a.

15 Nyirenda, M. J. et al. JAMA 2009;301:162-a-164-a.

16 The impact of smoking and TSHR-Ab on the risk of recurrence Glinoer D, European Journal of Endocrinology 2001;144:

17 Graves' ophtalmopathy Strongest associations with smoking Number of cigarettes is an independent risk factor for proptosis and diplopia Smokers : Higher risk of development / progession of ophtalmopathy after radioiodine treatment. Decreased effect of glucocorticoid treatment or external radiotherapy at the orbitae MECHANISM Hypoxia at tissue level? Immunomodulatory effects.

18 Graves ophtalmopathy Vestergaard, Eur J Endoc 2002;146: OR : 4.9 ( )

19 Smoking and Graves' disease : with or without ophtalmopathy Prummel, Wiersinga JAMA 1993;269:

20 Smokers have a more severe ophtalmopathy Prummel, Wiersinga JAMA 1993;269:

21 Thyroiditis and hypothyroidism Vestergaard, Eur J Endoc 2002;146:

22 Hypothyroidism Lower prevalence of overt (OR : 0.60 [ ]) and subclinical hypothyroidism (OR : 0.54 [ ]) in women Asvold, Ann Int Med 2007;167: NHANES III N=15592 Belin et al. J Clin Endocrinol Metab, 2004, 89:

23 TPO-Ab and Tg-Ab independent associated with smoking Pedersen IB, & Rasmussen LB. Eur J Endocrinol. 2008;158:

24 5-yr longitudinal follow-up with increased TPO-Ab or Tg-Ab conversion upon smoking discontinuation Effraimidis & Wiersinga, JCEM 2009;94:

25 Thyroid enlargement - goiter OR 1.29 ( )

26 Knudsen, Thyroid 2002;

27 Knudsen, Thyroid 2002;

28 Interaction with iodine status? Vejbjerg, Eur J Epidemiol 2008;23:

29 Mechanism Toxic components in cigarette smoke Thiocyanate and 2,3-hydroxypyridine Thiocyanate ~ goitrogen (iodine deficiency) Long half-life : t 1/2 > 6 d Thiocyanate : Inhibition of van iodide transport en organification Enhancement of iodide efflux Contrasts with lower TSH in smokers

30 Toxic goiter OR 1.27 ( )

31 Thyroid Cancer Risk of Female Papillary Thyroid Cancer in Relation to Smoking Status Rossing et al. Epidemiology 2000; 11:

32 Mack WJ, Preston-Martin S, Dal ML, et al. A pooled analysis of case-control studies of thyroid cancer: cigarette smoking and consumption of alcohol, coffee, and tea. Cancer Causes Control (2003) 14:773 85

33 Kreiger N, Eur J Cancer 2000;15:

34 Mechanism Lower TSH in smokers Anti-estrogen effect of smoking Increased metabolisation to 2-hydroxyestrogens in vitro aromatase inhibition decreased synthesis at the ovaria

35 Smoking during pregnancy Increase in serum T4 and lower TSH in children of smoking mothers, born at term Neonatal thyroid enlargement (relation to thiocyanate in cord blood) ~ weak stimulating effect of smoking at adult age Chanoine JP, Toppet V, Bourdoux P, Spehl M, Delange F. Br J Obstet Gynaecol. 1991;98:65-8 Smoking during pregnancy: a significant cause of neonatal thyroid enlargement.

36 Conclusions Increases in serum T3, T4 and lowers TSH Strong assocations with Graves' disease and especially Graves' ophtalmopathy Smokers have a more severe ophtalmopathy Effects on TPO-Ab and Tg-Ab and autoimmune thyroiditis are less clear Weak goitrogen Lower risk for (papillary / follicular ) thyroid cancer in smokers