M. NAUCK, F. STÖCKMANN and W. CREUTZFELDT
Till Ittermann, Rehman M Khattak, Matthias Nauck, Caio M M Cordova and Henry Völzke
Germany was iodine deficient until the mid-1990s when a nationwide iodine fortification program became effective. It is expected that after a longer period of sufficient iodine supply, median TSH values in the general population will shift to the right. Hence, the previous TSH reference range does not reflect the current TSH distribution in the general population of Germany. Thus, we aimed to establish a new reference range for serum TSH levels.
Design and methods
We used data from the Study of Health in Pomerania TREND, a population-based study including 4420 individuals. The reference population consisted of 1596 individuals without diagnosed thyroid diseases or thyroid-related findings in ultrasound and serum analysis. Serum TSH levels were measured by an immunochemiluminescent procedure on a Siemens Dimension Vista.
The overall reference range for TSH was 0.49 mIU/l (95% CI=0.44; 0.53)–3.29 mIU/l (95% CI=3.08; 3.50). The lower reference limit differed significantly by sex, whereas the upper reference limit showed no significant difference between males and females. Age was significantly associated with the 2.5th TSH percentile in males but not in females, whereas age was significantly associated in males and females for the 97.5th TSH percentile.
We demonstrate a shift toward the right of the TSH reference range in comparison with data from the same study region 10 years earlier, which is likely due to the improved iodine supply of the study region. Our study indicates that TSH reference limits are dependent on past and current iodine supply of populations.
C Meisinger, T Ittermann, H Wallaschofski, M Heier, H Below, A Kramer, A Döring, M Nauck and H Völzke
To investigate regional variations in the frequency of undiagnosed thyroid disorders among 25- to 88-year-old men and women in two communities in the northeast and the south of Germany. In addition, autoantibodies to thyroperoxidase (TPO-Abs) and urinary iodine excretion were determined.
Two population-based surveys of men and women using a common standardized protocol, the Study of Health in Pomerania (SHIP) in the northeast of Germany (2505 participants) and the Kooperative Gesundheitsforschung in der Region Augsburg (KORA) in the south of Germany (2316 participants), were compared with regard to the frequency of undiagnosed thyroid disorders.
Compared with the northeast of Germany, urinary iodine excretion and serum thyroid-stimulating hormone (TSH) levels were significantly higher in the south. The median urinary iodine concentration was 110 μg/l (64; 169 μg/l) in SHIP and 151 μg/l (97; 214 μg/l) in KORA, and the median TSH value was 0.81 mIU/l (0.56; 1.15 mIU/l) in SHIP and 1.22 mIU/l (0.84; 1.80 mIU/l) in KORA. The frequency of elevated TSH (TSH ≥2.12 mIU/l) was 4.3% in SHIP and 14.1% in KORA (P<0.001); the corresponding values for suppressed TSH (<0.25 mIU/l) were 3.5 and 1.7% (P<0.001). The proportion of ultrasonographic findings was 55.5% in SHIP and 68.0% in KORA. The frequency of serum TPO-Abs did not differ significantly between northeast and south Germany.
There were considerable regional disparities in the frequency of thyroid disorders within Germany. These differences can be explained not only by different regional histories of natural iodine deficiency but also by current differences in the iodine supply under an identical nationwide iodine fortification program.
Klaus Empen, Roberto Lorbeer, Henry Völzke, Daniel M Robinson, Nele Friedrich, Alexander Krebs, Matthias Nauck, Thorsten Reffelmann, Ralf Ewert, Stephan B Felix, Henri Wallaschofski and Marcus Dörr
IGF1 mediates multiple physiological and pathophysiological responses in the cardiovascular system. The aim of this study was to analyze the association between serum IGF1 as well as IGF-binding protein 3 (IGFBP3) levels and endothelial function measured by flow-mediated dilation (FMD).
Cross-sectional population-based observational study.
The study population comprised 1482 subjects (736 women) aged 25–85 years from the Study of Health in Pomerania. Serum IGF1 and IGFBP3 levels were determined by chemiluminescence immunoassays. FMD measurements were performed using standardized ultrasound techniques. FMD values below the sex-specific median were considered low.
In males, logistic regression analyses revealed an odds ratio (OR) of 1.27 (95% confidence interval (CI) 1.07–1.51; P=0.008) for decreased FMD for each decrement of IGF1 s.d. after adjustment for major cardiovascular confounders. In females, no significant relationship between serum IGF1 and FMD was found (OR 0.88, CI 0.74–1.05; P=0.147). After exclusion of subjects with the current use of antihypertensive medication, these findings were similar (males: OR 1.40, CI 1.12–1.75; P=0.003; females: OR 0.95, CI 0.77–1.16; P=0.595). There was no association between serum IGFBP3 levels and FMD in both sexes.
Low serum IGF1 levels are associated with impaired endothelial function in males. In women, serum IGF1 is not associated with endothelial function.
A Hannemann, M Bidlingmaier, N Friedrich, J Manolopoulou, A Spyroglou, H Völzke, F Beuschlein, J Seissler, R Rettig, S B Felix, R Biffar, A Döring, C Meisinger, A Peters, H E Wichmann, M Nauck, H Wallaschofski and M Reincke
The prevalence of primary aldosteronism in unselected hypertensive patients is currently unknown. We investigated the frequency of positive screening results for primary aldosteronism based on the aldosterone-to-renin ratio (ARR) in hypertensive subjects aged 30–79 years from two German epidemiological studies. We further examined the frequency of positive screening results in subjects with resistant hypertension or stage III hypertension and assessed possible disparities between untreated and treated hypertensive subjects.
Data were obtained from the first follow-ups of the population-based Study of Health in Pomerania (SHIP; n=1392) and the Cooperative Health Research in the Region of Augsburg (KORA; n=1052). Study-specific reference ranges for plasma aldosterone concentration (PAC), plasma renin concentration (PRC) and the ARR were applied. Confirmation tests for primary aldosteronism were not performed in these epidemiological studies. Three definitions for a positive screening for primary aldosteronism were applied: A) increased ARR; B) increased ARR and decreased PRC; and C) increased ARR and increased PAC and decreased PRC.
The frequency of positive screening results was 7.0, 3.8 and 0.2% according to definitions A–C respectively. In the subgroups of subjects with resistant hypertension (11.9, 5.5 and 0.9%) or stage III hypertension (18.3, 14.0 and 1.1%), these frequencies were markedly higher than those in the general hypertensive population. There was no difference in the frequency of positive screening results between the treated and untreated hypertensive subjects.
A maximum of 7.0% of the hypertensive population in Germany shows a positive screening result for primary aldosteronism. Thus, primary aldosteronism may be less frequent than previously expected based on data from referred hypertensive patients.