In recent years, there has been an increasing focus on thyroid function in obese children. There is controversy concerning whether the changes in the levels of thyroid hormones and thyroid-stimulating hormone (thyrotropin - TSH) in obesity are causes or consequences of weight status and whether these subtle differences merit treatment with thyroxine. This review aimed to study the prevalence of disturbed thyroid hormone and TSH values in childhood obesity and the underlying pathophysiologic mechanisms linking obesity to thyroid function.In the past 18 months, four studies demonstrated moderate elevation of TSH concentrations in 10-23% of obese children, which was associated with normal or slightly elevated thyroxine and triiodothyronine values. Two studies reported ultrasonographic hypoechogenicity of the thyroid in obese children with hyperthyrotropinemia, which was not caused by autoimmune thyroiditis; therefore, the authors hypothesized a link to chronic inflammation in obesity. Weight loss led to a normalization of elevated TSH levels in two studies. The adipokine leptin is the most promising link between obesity and hyperthyrotropinemia since leptin stimulates the hypothalamic-pituitary-thyroid.The elevated TSH levels in obesity seem a consequence rather than a cause of obesity. Therefore, treatment of hyperthyrotropinemia with thyroxine seems unnecessary in obese children.
Meta-analyses of population-based genome-wide association studies (GWAS) in adults have recently led to the detection of new genetic loci for obesity. Here we aimed to discover additional obesity loci in extremely obese children and adolescents. We also investigated if these results generalize by estimating the effects of these obesity loci in adults and in population-based samples including both children and adults. We jointly analysed two GWAS of 2,258 individuals and followed-up the best, according to lowest p-values, 44 single nucleotide polymorphisms (SNP) from 21 genomic regions in 3,141 individuals. After this DISCOVERY step, we explored if the findings derived from the extremely obese children and adolescents (10 SNPs from 5 genomic regions) generalized to (i) the population level and (ii) to adults by genotyping another 31,182 individuals (GENERALIZATION step). Apart from previously identified FTO, MC4R, and TMEM18, we detected two new loci for obesity: one in SDCCAG8 (serologically defined colon cancer antigen 8 gene; p = 1.85x10(-8) in the DISCOVERY step) and one between TNKS (tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase gene) and MSRA (methionine sulfoxide reductase A gene; p = 4.84x10(-7)), the latter finding being limited to children and adolescents as demonstrated in the GENERALIZATION step. The odds ratios for early-onset obesity were estimated at approximately 1.10 per risk allele for both loci. Interestingly, the TNKS/MSRA locus has recently been found to be associated with adult waist circumference. In summary, we have completed a meta-analysis of two GWAS which both focus on extremely obese children and adolescents and replicated our findings in a large followed-up data set. We observed that genetic variants in or near FTO, MC4R, TMEM18, SDCCAG8, and TNKS/MSRA were robustly associated with early-onset obesity. We conclude that the currently known major common variants related to obesity overlap to a substantial degree between children and adults.
Autoimmune thyroiditis (AT) is the most common cause of nonendemic thyromegaly and acquired hypothyroidism in childhood and adolescence. Outgoing from an increasing number of newly diagnosed patients during the last years we performed a retrospective analysis including 34 patients treated between 1989 and 1998. Clinical data, laboratory and sonographical findings are described. Cases were ascertained by palpable thyroid enlargement or clinical signs of thyroid dysfunction and positive autoantibodies against thyroid tissue. Frequency of AT diagnosis has threefold increased since 1995 in our department. Age at diagnosis was 5.4 to 16.3 years (median 11.3). Palpable thyromegaly was present in 29 (85%) of our patients. Three patients had myxedema without goiter. Symptoms had been present for a period between 6 weeks and 7.5 years: median in all patients 6 months, median in hypothyroid patients 9 months. At time of diagnosis 15 patients suffered from hypothyroidism, 3 from hyperthyroidism and 7 patients showed normal levels of thyroid hormones. In 9 patients we found an isolated elevation of thyrotropin. 12 patients were prepubertal (Tanner I), 15 patients were pubertal (Tanner II-IV). 5 patients showed a dissociation of pubertal maturation. Ultrasound of thyroid gland showed an inhomogeneous and hypoechoic pattern in 32 patients. 30 patients were treated with thyroxine. Patients with persistent hyperthyroidism were treated with carbimazol. During the follow-up period enlargement of the thyroid gland decreased in one third of the patients. Thyromegaly caused by autoimmune thyroiditis gets an increasing importance. The high degree of obviously hypothyroid patients at the time of diagnosis reflects a delay of diagnosis. Early recognition and treatment of the disease should be achieved for a preventive care of hypothyroidism.
Health-related quality of life (HRQoL) is reduced in obese children and adolescents, especially in clinical samples. However, little is known regarding the HRQoL of moderately overweight youth. Moreover, several studies have indicated perceived overweight as a critical factor associated with lower HRQoL. Our main objective was to compare HRQoL between treatment-seeking overweight youth and the general adolescent population, whilst separating the effects of treatment-seeking status and perceived weight from those of objective weight status. We compared the HRQoL of a clinical sample of overweight youth (N=137 patients, mean age±s.e.=11.24±0.15 years) with that of a representative population sample (N=6354, mean age=12.75±0.03 years). The population sample was subdivided into groups based on measured and perceived weight status. We used hierarchical linear models to compare HRQoL subscale scores (self- and parent-reported) between patients and population groups, adjusted for sociodemographic characteristics and taking into account clustering of the population sample. The parent-reported HRQoL of the treatment sample was significantly lower than that of other overweight youth perceived as ‘too fat’ on two subscales: ‘self-esteem’ and ‘friends’ (effect sizes: d=0.31 and 0.34, respectively). On other subscales, patients scored lower than adolescents perceived as having a ‘proper weight’ by their parents. The patterns for self-reported HRQoL in adolescents were different: patients reported higher self-esteem than other overweight youth feeling ‘too fat’ (d=-0.39). Female patients also reported higher physical well-being (d=-0.48), whereas males scored lowest among all compared groups (d=0.42-0.95). Patients did not differ from other overweight youth who felt ‘too fat’ with respect to other HRQoL dimensions. In general, lower HRQoL was primarily associated with a perceived, rather than actual, overweight status. The treatment-seeking status of overweight youth was notably associated with low social well-being, which may therefore be the main motive for seeking treatment. Other HRQoL domains were not consistently reduced in treatment-seekers. Our results further indicate that perceived overweight rather than actual overweight impacts HRQoL in youth with a modest excess weight. These results have implications for interventions in overweight youth and in individuals who are dissatisfied with their weight. ‘Obeldicks light’ is registered at clinicaltrials.gov ( NCT00422916 ).
A moderate elevation of thyrotropin (TSH) concentrations, which is associated with triiodothyronine (T3) values in or slightly above the upper normal range, is frequently found in obese humans. These alterations seem rather a consequence than a cause of obesity since weight loss leads to a normalization of elevated thyroid hormone levels. Elevated thyroid hormone concentrations increase the resting energy expenditure (REE). The underlying pathways are not fully understood. As a consequence of the increased REE, the availability of accumulated energy for conversion into fat is diminished. In conclusion, the alterations of thyroid hormones in obesity suggest an adaptation process. Since rapid weight loss is associated with a decrease of TSH and T3, the resulting decrease in REE may contribute towards the difficulties maintaining weight loss. Leptin seems to be a promising link between obesity and alterations of thyroid hormones since leptin concentrations influence TSH release.
<b><i>Objective:</i></b> To examine whether characteristics of children and adolescents who start lifestyle intervention (LI) for obesity in Germany changed over the last decade. <b><i>Methods: </i></b>65,453 subjects (<21 years) from the APV database (Adiposity Patients Registry) with a BMI ≥ 90th percentile were included (years 2005-2015). Logistic regression models (confounders: age, sex, migration background) were created for overweight, obesity, extreme obesity, and obesity-related comorbidities. Comorbidities were further adjusted for weight category. Results were stratified by inpatient or outpatient care. <b><i>Results: </i></b>Extreme obesity was found to be more frequent at the onset of LI (2005: 11.6; 2015: 12.7%) with a similar trend in subgroups (p < 0.001). Obesity increased (2005: 50.3%; 2015: 55.1%), and overweight decreased (2005: 34.1%; 2015: 29.0%) in the whole study population. Trends were similar for inpatient or outpatient care (all p < 0.001). Hypertension increased from 45.7% to 49.2% in the whole study population, and similar data were obtained in the subgroup of inpatients (both p < 0.0001). Dyslipidemia increased in all patients (2005: 21.9%; 2015: 28.0%) and in inpatients (2005: 20.2%; 2015: 25.7%; both p < 0.0001). Abnormal carbohydrate metabolism rose in all patients (from 5.2 to 6.4%; p = 0.0002) without significant trends in subgroups. <b><i>Conclusion: </i></b>During the last decade, children and adolescents presented with higher BMI SDS at the onset of LI and the proportion with obesity-related comorbidities increased. Particularly the presence of comorbidities differed between outpatients and inpatients.
Adipositas im Kindes- und Jugendalter stellt in Deutschland ein ernst zu nehmendes Problem dar mit zum Teil schwerwiegenden Folgeerkrankungen. Häufig wird ein in der Kindheit entwickeltes Übergewicht ein Leben lang beibehalten. Dieser Beitrag beschreibt das differenzierte diagnostische Vorgehen bei adipösen Kindern und Jugendlichen sowie die therapeutischen Möglichkeiten.
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