Prevalence of Type 1 diabetes autoantibodies (GAD and IA2) in Sardinian children and adolescents with autoimmune thyroiditis.

AIMS: Type 1 diabetes and autoimmune thyroiditis are common autoimmune diseases characterized by the presence of autoantibodies against tissue-specific components. Non-thyroid-specific autoantibodies are frequent in patients with autoimmune thyroiditis. The prevalence of Type 1 diabetes autoantibodies in patients with autoimmune thyroiditis is unknown. METHODS: The prevalence of Type 1 diabetes autoantibodies (GAD and IA2) was analysed in 236 Sardinian children and adolescents with autoimmune thyroiditis. GAD and IA2 antibodies were measured at the time of the diagnosis of autoimmune thyroiditis and re-evaluated after 1 year in the children who were shown to be positive. Autoantibody prevalence was evaluated in 949 healthy age-matched controls. RESULTS: The prevalence of GAD and/or IA2 antibodies was 8% in the children and adolescents with autoimmune thyroiditis and 4.1% in control subjects (P = 0.017). When Type 1 diabetes autoantibodies were separately analysed, the difference remained significant for IA2 (3.39% in autoimmune thyroiditis vs. 1.16% in control subjects, P = 0.012), but not for GAD (5.1% in autoimmune thyroiditis vs. 3.79% in control subjects, P = 0.367). Seven of 10 children with autoimmune thyroiditis and detectable Type 1 diabetes autoantibodies at the diagnosis remained positive after 1 year. In the course of 2 years of follow-up, two patients who were positive for Type 1 diabetes autoantibodies at the time of diagnosis of autoimmune thyroiditis developed diabetes. CONCLUSIONS: This is the first study reporting the prevalence of Type 1 diabetes autoantibodies in a selected cohort of genetically homogeneous children and adolescents with autoimmune thyroiditis. The main finding was that the prevalence of Type 1 diabetes autoantibodies and of newly diagnosed Type 1 diabetes in patients with autoimmune thyroiditis was significantly higher than that observed in the general paediatric population, suggesting that children with autoimmune thyroiditis are at increased risk of developing Type 1 diabetes.

The effect of puberty on insulin resistance in obese children.

OBJECTIVE: Insulin resistance (IR) increases during puberty in normal children. IR is the first adverse metabolic event of obesity, and the marker of the metabolic syndrome. We aimed to study the effect of puberty on IR in obese and normal-weight children. DESIGN: Cross-sectional evaluation of fasting glucose, insulin concentrations, and homeostasis model assessment of IR (HOMA-IR) in obese and control children throughout puberty. PATIENTS AND METHODS: We recruited 424 obese children (207 pre-pubertal and 217 pubertal divided in Tanner stages 2-3, 4, and 5) and estimated IR using the HOMA-IR index. Data were compared to those obtained in 123 healthy normal-weight children (40 pre-pubertal and 83 pubertal divided in Tanner stages 2-3, 4, and 5). RESULTS: In the obese children mean HOMA-IR increased progressively across Tanner stages, and was significantly higher in all groups (pre-pubertal and Tanner stages 2-3, 4, and 5) of obese than in control children. HOMA-IR was significantly correlated with BMI. CONCLUSIONS: HOMA-IR in obese children increases at puberty more than in normal-weight children and does not return to pre-pubertal values at the end of puberty.

Somatostatin infusion withdrawal: studies in normal children and in children with growth hormone deficiency.

Withdrawal of a somatostatin infusion (SSIW) is followed by a rebound rise of GH in both animals and normal adult men, a phenomenon likely mediated by endogenous GHRH function. In the present study, we have evaluated the GH response to SSIW in a group of 28 prepubertal children (18 boys and 10 girls; aged 3.7-11.1 yr). Six children had GH deficiency [GHD; GH responses to pyridostigmine (PD)+GHRH and to clonidine <20 and <7 microg/L, respectively], 4 children had GH neurosecretory dysfunction (GHND; GH responses to PD+GHRH and to clonidine > or =20 and >7 microg/L, respectively; mean integrated nighttime GH concentrations <3 microg/L), and 18 children were short normal children [normal controls (NC)]. All children received a constant infusion of SS at the dose of 3 microg/Kg x h for 90 min. SSIW elicited a clear-cut GH rise in NC children (13.7+/-1.0 microg/L), but not in GH-deficient children, regardless of the underlying etiology (GHD, 1.6+/-0.4 microg/L; GHND, 2.4+/-0.3 microg/L). The GH response to SSIW was similar between GHD and GHND children. There was no overlapping of the maximum SSIW-stimulated GH peaks between NC and GHD or GHND children. In conclusion, we have demonstrated that SSIW elicits a significant GH rise in NC children, but not in GH-deficient children, regardless of the underlying etiology (GHD or GHND). This resulted in complete discrimination of NC from GHD or GHND children. Were these present findings confirmed on a larger number of children, SSIW, because of its testing efficaciousness and safety, procedural simplicity, and economy holds promise of being a useful diagnostic tool for GH-dependent growth disorders.

The growth hormone response to hexarelin in patients with different hypothalamic-pituitary abnormalities.

We evaluated the GH-releasing effect of hexarelin (Hex; 2 microg/kg, i.v.) and GHRH (1 microg/kg, i.v.) in 18 patients (11 males and 7 females, aged 2.5-20.4 yr) with GH deficiency (GHD) whose hypothalamic pituitary abnormalities had been previously characterized by dynamic magnetic resonance imaging (MRI). Ten patients had isolated GHD, and 8 had multiple pituitary hormone deficiency. All patients were receiving appropriate hormone replacement therapy. Twenty-four prepubertal short normal children (11 boys and 13 girls, aged 5.9-13 yr, body weight within +/-10% of ideal weight) served as controls. MRI studies revealed an ectopic posterior pituitary at the infundibular recess in all patients. A residual vascular component of the pituitary stalk was visualized in 8 patients with isolated GHD (group 1), whereas MRI showed the absence of the pituitary stalk (vascular and neural components) in the remaining 10 patients (group 2), of whom 8 had multiple pituitary hormone deficiency and 2 had isolated GHD. In the short normal children, the mean peak GH response to GHRH (24.8 +/- 4.4 microg/L) was significantly lower than that observed after Hex treatment (48.1 +/- 4.9 microg/L; P < 0.0001). In the GHD patients of group 2, the mean peak GH responses to GHRH (1.4 +/- 0.3 microg/L) and Hex (0.9 +/- 0.3 microg/L) were similar and markedly low. In the patients of group 1, the GH responses to GHRH (8.7 +/- 1.3 microg/L) and Hex (7.0 +/- 1.3 microg/L) were also similar, but were significantly higher that those observed in group 2 (P < 0.0001). In the whole group of patients, a significant correlation was found between the GH peaks after Hex and those after GHRH (r = 0.746; P < 0.0001). In this study we have confirmed that the integrity of the hypothalamic pituitary connections is essential for Hex to express its full GH-releasing activity and that Hex is able to stimulate GH secretion in patients with GHD but with a residual vascular component of the pituitary stalk.

The effect of atenolol on the growth hormone response to growth hormone-releasing hormone in obese children.

We have evaluated the effect of acute administration of atenolol, a selective beta-adrenergic antagonist, on the GH response to GHRH in nine obese children and in eight age-matched controls. The GH response to GHRH (1-29, 1 microgram/kg iv), evaluated both as the GH peak and as integrated area under the curve, was significantly lower in the obese children than in the controls. Pretreatment with atenolol (50 or 100 mg orally in subjects with body weight less than or greater than 40 kg, respectively, administered 120 min before the GHRH injection) significantly increased the GH response to GHRH in the obese subjects, such that their mean peak GH levels and mean integrated area under the curve after atenolol plus GHRH were similar to those of the control children after GHRH. Also in control children, atenolol caused a significant augmentation of the GH response to GHRH. Mean peak GH levels and mean integrated area under the curve after atenolol plus GHRH were significantly higher in the controls than in the obese children given the same treatment. These data show that inhibition of central beta-adrenergic receptors counteracts the blunted GH response to GHRH present in the obese children. In view of the alleged mechanism of action of beta-adrenergic blockade (inhibition of endogenous SRIH release), our data suggest that the somatostatinergic system is intact in obesity, and that the suppressed GH secretion is due to other causes.

[Usefulness and limitations of determination of lactate dehydrogenase enzymes in the diagnosis of liver diseases]. / Utilità e limiti del dosaggio degli enzimi della latticodeidrogenasi (LDH) nella diagnostica epatologica.

Serum LDH isoenzyme electrophoretic pattern was evaluated in forty-four patients affected by acute or chronic liver diseases. Moreover, the correlation between LDH4, LDH5, and various parameters of liver function (particularly SGOT and SGPT) were examined. The authors believe that LDH4 and LDH5 are useful parameters for the differential diagnosis between chronic persistent hepatitis and chronic active hepatitis.