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.

Growth hormone treatment in non-growth hormone-deficient short children.

The unlimited availability of GH obtained by recombinant DNA technology has allowed optimization of treatment in GH-deficient (GHD) children. At the same time it has prompted a number of studies in conditions not characterized by GHD such as Turner syndrome, intrauterine growth retardation, chronic renal failure and other chromosomal and genetic abnormalities associated with short stature. Several controlled and uncontrolled studies have now reported the adult height of patients with short stature and normal GH secretion. Critical reviewing of the data shows that some short non-GHD children may benefit from a prolonged treatment with GH. However, further studies are needed in order to be able to identify the subjects for whom treatment is really beneficial.

Evaluation of adrenal function in patients with growth hormone deficiency and hypothalamic-pituitary disorders: comparison between insulin-induced hypoglycemia, low-dose ACTH, standard ACTH and CRH stimulation tests.

OBJECTIVES: Patients with organic growth hormone deficiency (GHD) or with structural hypothalamic-pituitary abnormalities may have additional anterior pituitary hormone deficits, and are at risk of developing complete or partial corticotropin (ACTH) deficiency. Evaluation of the integrity of the hypothalamic-pituitary-adrenal axis (HPA) is essential in these patients because, although clinically asymptomatic, their HPA cannot appropriately react to stressful stimuli with potentially life-threatening consequences. DESIGN AND METHODS: In this study we evaluated the integrity of the HPA in 24 patients (age 4.2-31 years at the time of the study) with an established diagnosis of GHD and compared the reliability of the insulin tolerance test (ITT), short synacthen test (SST), low-dose SST (LDSST), and corticotropin releasing hormone (CRH) test in the diagnosis of adrenal insufficiency. RESULTS: At a cortisol cut-off for a normal response of 550 nmol/l (20 microg/dl), the response to ITT was subnormal in 11 subjects, 6 with congenital and 5 with acquired GHD. Four patients had overt adrenal insufficiency, with morning cortisol concentrations ranging between 66.2-135.2 nmol/l (2.4-4.9 microg/dl) and typical clinical symptoms and laboratory findings. In all these patients, a subnormal cortisol response to ITT was confirmed by LDSST and by CRH tests. SST failed to identify one of the patients as adrenal insufficient. In the seven asymptomatic patients with a subnormal cortisol response to ITT, the diagnosis of adrenal insufficiency was confirmed in one by LDSST, in none by SST, and in five by CRH tests. The five patients with a normal cortisol response to ITT exhibited a normal response also after LDSST and SST. Only two of them had a normal response after a CRH test. In the seven patients with asymptomatic adrenal insufficiency mean morning cortisol concentration was significantly higher than in the patients with overt adrenal insufficiency. ITT was contraindicated in eight patients, and none of them had clinical symptoms of overt adrenal insufficiency. One of these patients had a subnormal cortisol response to LDSST, SST, and CRH, and three exhibited a subnormal response to CRH but normal responses to LDSST and to SST. CONCLUSION: We conclude that none of these tests can be considered completely reliable for establishing or excluding the presence of secondary or tertiary adrenal insufficiency. Consequently, clinical judgment remains one of the most important issues for deciding which patients need assessment or re-assessment of adrenal function.

The GH/IGF-I axis in puberty.

Puberty, either spontaneous, precocious or pharmacologically induced has profound effects on the physiology of the GH/IGF-I axis. Both spontaneous and stimulated GH secretion increase with puberty. The increase in spontaneous GH secretion is the result of increased GH pulse amplitude rather than frequency, and is probably an oestrogen-dependent effect. Parallel to the increase in GH secretion at puberty, circulating IGF-I and IGF binding protein-3 also increase. The pubertal increase in IGF-I correlates with stages of puberty as well as sex steroid levels. Circulating immunoreactive GHRH also increases with puberty, while circulating GH-binding protein levels are not affected by sexual maturation. Several data suggest an important role for the GH/IGF-I axis in the pubertal growth spurt. More recent data, however, have provided evidence of an important role for gonadal hormones in promoting adolescent growth independent of GH.