Relative Frequency of Islet Autoimmunity in Children and Adolescents with Autoimmune Thyroid Disease

Objective: The aim of the present study was to investigate islet autoimmunity and susceptibility to type 1 diabetes (T1D) in children/adolescents with autoimmune thyroid disease (AITD, and in family members of AITD patients with islet autoimmunity. Methods: Islet-cell cytoplasmic, glutamic-acid decarboxylase, and tyrosine-phosphatase autoantibodies (AAbs) were measured in 161 AITD patients [127 with autoimmune thyroiditis (AT); 34 with Graves' disease (GD)], 20 family members of AITD patients with islet autoimmunity, and 155 age-matched controls. Results: Islet autoimmunity was found in 10.6% of AITD patients, significantly more frequent than in controls (1.9%; p=0.002). A higher prevalence of islet AAbs was found in females with AITD (p=0.011) but not in males (p=0.16) and in AT (p=0.013) but not in GD patients (p=0.19), compared to corresponding controls. Two or three islet AAbs were found concurrently in six AITD patients with islet autoimmunity. They all developed T1D and had significantly higher islet AAbs titers (p=0.01) than AITD patients with single islet AAbs but normal glucose metabolism. T1D was found in 3.7% of AITD patients compared to 0.2% of the age-matched, general Croatian population. Islet AAbs were found in 5/20 family members of AITD patients with islet autoimmunity, among whom two developed T1D. None of the controls was positive for more than one islet AAb or developed T1D. Conclusion: Children/adolescents with AITD, particularly females and patients with AT, appear to represent a risk group for islet autoimmunity and T1D, as do family members of AITD patients with positive islet AAbs. However, these findings should be validated in larger studies.

[Low doses of sulphonyluria as a successful replacement for insulin therapy in a patient with neonatal diabetes due to a mutation of KCNJ11 gene encoding Kir6.2]. / Niske doze sulfonilureje kao uspjesna zamjena za inzulin u lijecenju neonatalnog dijabetesa uzrokovanog aktivirajucom mutacijom Kir6.2.

Neonatal diabetes mellitus is a rare metabolic disorder with an estimated incidence of 1:300.000 to 400.000 newborns, and less than 50% of the neonates have permanent neonatal diabetes mellitus (PNDM). Recently, activating mutation in the KCNJ11 gene encoding Kir6.2 subunit of the adenosin triphosphate-sensitive potassium (K(ATP)) channel has been described as the most frequent cause of PNDM. Under physiological circumstances K(ATP) channel closure plays a central role in glucose-stimulated insulin secretion from pancreatic beta cells. Sulphonylurea drugs stimulate insulin secretion by binding to and closing K(ATP) channels and thus bypassing beta cell metabolism stimulate the same chain of reactions as glucose. We describe a boy diagnosed with PNDM at the age of 3 months when insulin therapy was started, and at the age of 4.5 years KCNJ11 gene was sequenced and found that the boy carried a de novo activating R201H mutation. Insulin therapy was successfully switched to low doses of oral glibenclamide. Accordingly, it is important to emphasize that every person diagnosed with diabetes before six months of life, however old they actually are, should be tested for K(ATP) mutations which is offered via the website www.diabetesgenes.org.

[Duplication of the pituitary gland]. / Dvostruka hipofiza.

Duplication of the pituitary gland is a rare malformation. To the best of our knowledge, only 40 cases throughout the world have been reported previously. Due to associated severe developmental anomalies lots of these cases were diagnosed at autopsy. Only 7 patients survived beyond puberty, however, it is important to stress that none of them had major brain anomalies. We present the case of a girl with duplication of the pituitary gland (DPG), central precocious puberty and associated midline defects. Among fenestration of basilar artery, previously described in the literature, we also found, for the first time, a duplication of the M1-segment of the left median cerebral artery. Our patient is one of the 4 DPG patients with associated precocious puberty treated with gonadotropine releasing hormone agonists (GnRH), but the only one in whom this treatment was finished successfully.

[Epidemiology of congenital heart diseases in Croatia--a multicenter nationwide study, 1995-2000]. / Epidemiologija prirodenih bolesti srca u Hrvatskoj--multicentricna nacionalna studija, 1995-2000.

Congenital heart diseases (CHD) comprise a group of different conditions seen in 0.55-1% of live births. Tendency to classify CHD according to Clark's pathogenic classification is based on the assumption that relatively few pathogenic mechanisms cause a wide spectrum of phenotypic forms of CHD. The aim of this study was to classify CHD according to Clark's classification and to calculate the prevalence rates of CHD in the Croatian population. We formed the Registry including all children with CHD born between 1995 and 2000 treated in paediatric cardiology departments in Croatia. In the study were enrolled 276,565 live births, 2,204 of them with CHD, 1.126 males and 1.078 females. Total birth prevalence was 8.0@1000. A statistically significant difference was found between CHD prevalence rates in several counties. The prevalence of all main pathogenic groups of CHD was constant in time, except for cell death defects where a twofold increase in the prevalence of muscular ventricular septal defect (VSD) was noted (0.6@1000-1.3@1000). The most common diagnosis was perimembranous VSD (19.0%), followed by atrial septal defect (ASD) type II (14.4%), muscular VSD (11.1%) and pulmonary stenosis (8.5%). This four diagnoses were composing more than 50% of all CHD diagnoses. Prevalence and diagnostic possibilities weren't different from those presented in the literature. However, differences in prevalence between the counties warrant further investigation into the development and aetiology of CHD.