OBJECTIVE -To investigate thyroid autoimmunity in a very large nationwide cohort of children and adolescents with type 1 diabetes.RESEARCH DESIGN AND METHODS -Data were analyzed from 17,749 patients with type 1 diabetes aged 0.1-20 years who were treated in 118 pediatric diabetes centers in Germany and Austria. Antibodies to thyroglobulin (anti-TG) and thyroperoxidase (anti-TPO) were measured and documented at least once in 7,097 patients. A total of 49.5% of these patients were boys, the mean age was 12.4 years (range 0.3-20.0 years), and the mean duration of diabetes was 4.5 years (range 0.0 -19.5 years). A titer exceeding 100 units/ml or 1:100 was considered significantly elevated.RESULTS -In 1,530 patients, thyroid antibody levels were elevated on at least one occasion, whereas 5,567 were antibody-negative during the observation period. Patients with thyroid antibodies were significantly older (P Ͻ 0.001), had a longer duration of diabetes (P Ͻ 0.001), and developed diabetes later in life (P Ͻ 0.001) than those without antibodies. A total of 63% of patients with positive antibodies were girls, compared with 45% of patients without antibodies (P Ͻ 0.001). The prevalence of significant thyroid antibody titers increased with increasing age; the highest prevalence was in the 15-to 20-year age group (anti-TPO: 16.9%, P Ͻ 0.001; anti-TG: 12.8%, P Ͻ 0.001). Thyroid-stimulating hormone (TSH) levels were higher in patients with thyroid autoimmunity (3.34 U/ml, range 0.0 -615.0 U/ml) than in control subjects (1.84 U/ml, range 0.0 -149.0 U/ml) (P Ͻ 0.001). Even higher TSH levels were observed in patients with both anti-TPO and anti-TG (4.55 U/ml, range 0.0 -197.0 U/ml).CONCLUSIONS -Thyroid autoimmunity seems to be particularly common in girls with diabetes during the second decade of life and may be associated with elevated TSH levels, indicating subclinical hypothyroidism.

Our data indicate a distinct role of free and bound leptin in the feedback regulating energy intake and expenditure and could have important implications for our understanding of the physiology and pathophysiology of leptin-dependent signalling.

Because 50% of children with diabetes and significant titres of anti-TPO develop thyroid problems within 3-4 years, examinations of thyroid antibodies should be performed yearly. In cases of significant antibody titres, thyroid function tests and ultrasound assessment are recommended in order to minimize the risk of undiagnosed hypothyroidism in these patients.

SUMMARYPurpose: Febrile seizures (FS) are the most common type of convulsive events in children. FS are suggested to result from a combination of genetic and environmental factors. However, the pathophysiologic mechanisms underlying FS remain unclear. Using an animal model of experimental FS, it was demonstrated that hyperthermia causes respiratory alkalosis with consequent brain alkalosis and seizures. Here we examine the acid-base status of children who were admitted to the hospital for FS. Children who were admitted because of gastroenteritis (GE), a condition known to promote acidosis, were examined to investigate a possible protective effect of acidosis against FS. Methods: We enrolled 433 age-matched children with similar levels of fever from two groups presented to the emergency department. One group was admitted for FS (n = 213) and the other for GE (n = 220). In the FS group, the etiology of fever was respiratory tract infection (74.2%), otitis media (7%), GE (7%), tonsillitis (4.2%), scarlet fever (2.3%) chickenpox (1.4%), urinary tract infection (1.4%), postvaccination reaction (0.9%), or unidentified (1.4%). In all patients, capillary pH and blood Pco 2 were measured immediately on admission to the hospital. Key Findings: Respiratory alkalosis was found in children with FS (pH 7.46 ± 0.04, [mean ± standard deviation] Pco 2 29.5 ± 5.5 mmHg), whereas a metabolic acidosis was seen in all children admitted for GE (pH 7.31 ± 0.03, Pco 2 37.7 ± 4.3 mmHg; p < 0.001 for both parameters). No FS were observed in the latter group. A subgroup (n = 15; 7%) of the patients with FS had GE and, notably, their blood pH was more alkaline (pH 7.44 ± 0.04) than in the GE-admitted group. During the enrollment period, eight of the patients were admitted on separate occasions because of FS or GE. Consistent with the view that generation of FS requires a genetic susceptibility in addition to acute seizure triggering factors, each of these patients had an alkalotic blood pH when admitted because of FS, whereas they had an acidotic pH (and no FS) when admitted because of GE (pH 7.47 ± 0.05 vs. pH 7.33 ± 0.03, p < 0.005). Significance: The results show that FS are associated with a systemic respiratory alkalosis, irrespective of the severity of the underlying infection as indicated by the level of fever. The lack of FS in GE patients is attributable to low pH, which also explains the fact that children with a susceptibility to FS do not have seizures when they have GE-induced fever that is associated with acidosis. The present demonstration of a close link between FS and respiratory alkalosis may pave the way for further clinical studies and attempts to design novel therapies for the treatment of FS by controlling the systemic acid-base status.

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