Abstract
BACKGROUND: Worldwide, iodine prophylaxis measures have improved iodine status in populations. Several studies have reported an increase in thyrotropin (TSH) levels coinciding with this prophylaxis. Whether this implies an increased risk for hypothyroidism or simply reflects a physiologic TSH adaptation mechanism is not clear. METHODS: Data on iodine and thyroid status of 6-17 year old children and adolescents (n=9175), collected between 2003 and 2006 in the German-wide Health Interview and Examination Survey for Children and Adolescents (KiGGS) Study, provided the basis for the analyses of mutual relationships of urinary iodine status (assessed by iodine/creatinine ratio in spot urines), serum TSH levels, and thyroid volume (determined by ultrasound). For data analyses (multivariable linear regression analysis), only those children were included for whom none of the available parameters (including free triiodothyronine [fT3], free thyroxine [fT4], and thyroperoxidase antibody [TPO-Ab] measurements) indicated a potential pathophysiologic thyroid status (n=6101). RESULTS: In this population-based sample of thyroid-healthy children, higher urinary iodine excretion was associated with higher TSH levels (p<0.05), adjusted for sex, age, body surface area, body mass index, fT3/fT4 ratio, and time of blood sampling. Higher TSH levels were not associated with a higher prevalence of TPO-Ab but with lower thyroid volume (p<0.001, fully adjusted). For the present study sample, one-time spot measurements of urinary iodine excretion were not related to thyroid volume, the long-term marker of iodine status. CONCLUSION: Our findings show for the first time in thyroid-healthy children that smaller thyroid volume is associated with higher normal TSH levels. A decreased thyroid cell mass and cell amount, as induced by an improved iodine status, does presumably require a higher TSH signal to maintain a constant thyroid hormone production, suggesting an underlying physiologic adaptation. Correspondingly, an increased TSH level should not be used as the single criterion to evaluate the prevalence of hypothyroidism, and the repeatedly observed parallel increases of iodine supply and TSH levels should not readily be interpreted as evidence for an increased hypothyroidism risk. These insights, contradicting conventional interpretations, may contribute to dispel uncertainties about the safety of iodine prophylaxis measures.