Translational Biomedicine

Keywords

Thyroid; Goiter; Iodine; Smoking; Male

Introduction

Goitre is a major health problem in Germany with an annual cost for treatment estimated at 1 billion Euro [1]. The etiology of simple endemic or sporadic goitre depends on genetic and environmental factors. The major factor, however, remain iodine deficiency [1,2].

Despite recent improvement of iodine supplementation in Germany since 1989 [3-8], the prevalence of goitre in Germany remains substantial [9,10].

An association between smoking and the risk of goitre have been reported in several studies predominantly or exclusively including females [11-17], but none in males.

In this prospective study, we investigated the prevalence of simple goitre among healthy smoker males in west part of Germany as compared to non-smokers with respect to age, iodine status and history of goitre in the first degree relatives.

Methods

Study design

A total of 483 healthy male employees of 4 institutions in Essen (Bethesda Essen and Karstadt) and Muelheim (Siemens and Mannesmann) in western part of Germany aged between 17 and 68 years (range: 43.1 ± 9.6 y) were examined by ultrasound of the neck to determine the thyroid volume.

Ultrasound was performed by one experienced investigator (J.F.) with a Siemens Sonoline SI-400 using a 7.5 MHz linear scanner. The ultrasound was performed according to standardized criteria and the volume of thyroid was determined as the sum of p/6 X lengths X width X depth of both lobes. Goitre was defined as a thyroid volume exceeding 25 ml.

All subjects with known thyroid disorder were excluded from this analysis. Information on date of birth, date of screening, sex, daily use of iodized salt, history of previous diseases including benign diseases of thyroid, history of thyroid disorders in the first degree relatives, and type and amount of smoking were assessed by standardized questionnaires.

Smoking was defined as consuming more than 10 cigarettes daily for at least 5 years. Because of small number of cases in groups of cigar and pipe smokers, we excluded 2 cigar and 2 pipe smokers from the analyses.

Statistics

The general descriptive analysis was performed using Microsoft Excel (Version 7.0) and PASW-Statistics (version 19.0). Values for continuous variables are given as means ±SD. Statistical differences between groups and comparison of frequencies between groups were calculated with the Chi- Square test or the Fisher’s exact test for the 2 × 2 contingency tables.

Linear regression analysis was performed for continuous variables and logistic regression analysis was performed for the binary dependent variable, presence of goitre, to adjust for age, smoking, iodine status and familial history of goitre. Parameters were estimated using a least square and maximum-likelihood methods and the significance level was assessed using t-Test or Wald test respectively. A p-value below 0.05 was considered to be statistically significant.

Results

The overall thyroid volume correlated (r=0.18; p<0.001) with increasing age (Figure 1). The overall prevalence of goitre was 25.7% (124/483). Median thyroid volume among smokers (23.4 ± 10.1 ml), was higher (p<0.001) as compared with nonsmokers (19.4 ± 8.0 ml).

Figure 1: Correlation of thyroid volume and age in 483 male volunteers.

Goitre was present (Table 1 and Figure 2) in 77 out of 204 smokers (37.7%) vs. 47/279 (16.8%) in non-smokers (p<0.001) with an odds ratio of 3.0.

Figure 2: Non-smokers taking iodine vs. non-smokers taking no iodine: OR=1.2, n.s. Non-smokers taking iodine vs. smokers taking iodine: OR=2.4, p=0.008. Non-smokers taking iodine vs. smokers taking no iodine: OR=4.9, p<0.001.

	no goitre	%	goitre	%	OR (CI)	p
N=483	359	74.3	124	25.7
Age (mean) ± SD	41.8 ± 9.8		46.6 ± 8.1			p<0.001
BMI	26.1 ± 4.0		26.7 ± 3.7			n.s.
Thyroid volume ± SD	17.2 ± 3.9		33.0 ± 10.2			p<0.001
smokers non-smokers	127 232	62.3 83.2	77 47	37.7 16.8	3.0 (2.0;4.6)	p<0.001
No children children	227 132	79.4 67.0	59 65	20.6 33.0	1.9 (1.3;2.9)	p=0.003
No iodine salt Iodine salt	158 188	70.5 78.3	66 52	29.5 21.7	0.7 (0.4;1.0)	p=0.056 (n.s.) pone sided= 0.034
No family history Family history	294 65	74.2 74.7	102 22	25.8 25.3	1.0 (0.6;1.7)	n.s.
Non-smokers taking no iodine	110	82.1	24	17.9		poverall <0.001
Non-smokers taking iodine	112	84.8	20	15.2	0.8 (0.4;1.6)	n.s.
Smokers taking no iodine	48	53.3	42	46.7	4.9 (2.6;9.2)	p<0.001
Smokers taking iodine	76	70.4	32	29.6	2.4 (1.3;4.4)	p=0.008
P<0.05 was considered as significant level. OR (CI): odds ratios with the range of confidence interval

Table 1: Multivariate analyses of risk factors, age, BMI, smoking, iodized salt intake, family history of goiter on prevalence of goiter.

Smoking (<0.001) and increasing age (p<0.001) associated with goitre prevalence by the logistic regression analysis but not the history of goitre in the first degree relatives (Table 1) and the iodine status failed just to reach the significant level in this analysis (p=0.056).

Chi-square-Test shows a higher prevalence of goitre among smokers who don’t use iodine salt compared to smokers taking iodine regularly (29.6% vs. 46.7%, p=0.018, poverall<0.001). Among the non-smoking individuals the frequency of goitre stays by 15.2% with iodine intake and by 17.9% without iodine (n.s.).

Discussion

This study indicates smoking as the major risk factor for goitre in men. The median volume of thyroid in smokers was in general higher as compared to non-smokers. The risk of developing goitre in smoking men was approximately 3 times higher as compared to non-smokers. In addition, the prevalence of goitre in smokers was significantly lower in case of iodine intake.

Earlier investigations suggest that cigarette smoking may increase thyroid hormone secretion [18]. The first clinical record of association between smoking and goitre prevalence was published 1984. In this study Christensen et al. [11] evaluated the prevalence of goitre by palpation in 441 middle aged women and found higher goitre prevalence among smokers (14.8%) as compared to ex-smokers (3.8%) and nonsmokers (9.4%).

In 219 randomly selected hospital employees, Hegedus et al. [12] found a higher prevalence of goitre among smokers (30%) as compared to non-smokers (3%).

Berghout et al. [13] found no association between thyroid volume and smoking and no correlation between thyroid volume and tobacco consumption in an iodine-sufficient area.

Ericsson et al. [14] report in an epidemiological study from Sweden including more than 4000 subjects, a higher goitre prevalence among smoking females (14.2%) as compared to non-smokers (8.9%) and ex-smokers (7.0%).

Petersen et al. [15] found no increased prevalence of thyroid disease or goitre in 1154 middle-aged and older Swedish women with respect to smoking (14.3% smokers vs. 13.4% non-smokers).

Georgiadis et al. [16] investigated 187 employees of a hospital and their relatives and found goitrogen effect of smoking only in individuals with a family history of goitre.

However, these studies mostly or exclusively performed in female population, few suffer from insufficient number of subjects or inappropriate multivariate analysis of risk factors.

Knudsen et al. [17] report in a recent multivariate analysis on 4649 randomly selected sample of females and males (2002) on association between smoking and increased goitre prevalence, which was more pronounced in the most iodine deficient area.

The effects of smoking on the thyroid have been attributed to thiocyanate. Body fluid of smokers contains increased concentration of thiocyanate [19-22]. Thiocyanate inhibit iodide uptake and thyroid hormone synthesis and increase the efflux of iodide from the thyroid gland [22].

Indeed, recent improvement of iodine supplementation since 1989 reduced the prevalence of goitre especially in younger population [3-8], however, the prevalence of goitre in Germany remains substantial [9,10].

We conclude that smoking is an independent risk factor affecting the goitre prevalence in males. In addition, our study reveals that iodine intake can reduce the risk of goitre in smoker males significantly.

Acknowledgement

We thank Dr. Eberhard Heissen, Mrs. Vo and Mrs. Walschus for preparing the manuscript.

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