Minimal incidence of neonatal/infancy onset diabetes in Italy is 1:90,000 live births.

Until early 2000, permanent and transient neonatal diabetes mellitus (NDM), defined as diabetes with onset within 6 weeks from birth that requires insulin therapy for at least 2 weeks, were considered exceedingly rare conditions, with a global incidence of 1:500,000-1:400,000 live births. The new definition of NDM recently adopted, that includes patients with diabetes onset within 6 months of age, has prompted studies that have set the incidence of the permanent form alone between 1:210,000 and 1:260,000 live births. Aim of the present work was to ascertain the incidence of NDM (i.e. permanent + transient form) in Italy for years 2005-2010. Patients referred to the Italian reference laboratory for NDM between years 2005 and 2010 and screened for mutations in common NDM genes (KCNJ11, ABCC8, and INS) and for uniparental isodisomy of chromosome 6 (UDP6) were reviewed. A questionnaire aimed at identifying NDM cases investigated in other laboratories was sent to 54 Italian reference centers for pediatric diabetes. Twenty-seven patients with NDM born between 2005 and 2010 were referred to the reference laboratory. In this group, a mutation of either KCNJ11, ABCC8 or INS was found in 18 patients, and a case with UDP6 was identified. Questionnaires revealed 4 additional cases with transient neonatal diabetes due to UDP6. Incidence of NDM was calculated at 1:90,000 (CI: 1:63,000-1:132,000) live births. Thus, with the definition currently in use, about 6 new cases with NDM are expected to be born in Italy each year.

Growth hormone bioactivity, insulin-like growth factors (IGFs), and IGF binding proteins in obese children.

In obese children, both spontaneous and stimulated growth hormone (GH) secretion are impaired but a normal or increased height velocity is usually observed. This study was undertaken to explain the discrepancy between impaired GH secretion and normal height velocity. We evaluated the GH bioactivity (GH-BIO), GH serum level by immunofluorimetric assay (GH-IFMA), insulin-like growth factor-I (IGF-I), IGF-II, and IGF binding protein-1 (IGFBP-1), IGFBP-2, and IGFBP-3 in 21 prepubertal obese children (13 boys and eight girls) aged 5.7 to 9.4 years affected by simple obesity and in 32 (22 boys and 10 girls) age- and sex-matched normal-weight controls. The results were as follows (obese versus [v] controls): GH-IFMA, 4.84 +/- 3.54 v 23.7 +/- 2.04 microg/L (P < .001); GH-BIO, 0.60 +/- 0.45 v 1.84 +/- 0.15 U/mL (P < .001); IGF-I, 173.8 +/- 57.2 v 188.6 +/- 132.6 ng/mL (nonsignificant); IGF-II, 596.1 +/- 139.7 v 439.3 +/- 127.4 ng/mL (P < .001); IGFBP-1, 23.25 +/- 14.25 v 107 +/- 165.7 ng/mL (P < .05); IGFBP-2, 44.37 +/- 62.18 v 385.93 +/- 227.81 ng/mL (P < .001); IGFBP-3, 3.31 +/- 0.82 v 2.6 +/- 0.94 microg/mL (P < .05); and IGFs/IGFBPs, 1.32 +/- 0.32 v 1.07 +/- 0.34 (P < .05). In conclusion, in prepubertal obese children, not only immunoreactive but also bioactive GH concentrations were low. In these subjects, therefore, nutritional factors and insulin may contribute to sustain normal growth also by modulating several components of the IGF-IGFBP system.

Growth hormone-binding proteins, IGF-I and IGF-binding proteins in children and adolescents with type 1 diabetes mellitus.

Growth hormone binding proteins, insulin-like growth factor I and insulin-like growth factor binding proteins were determined in 54 children and adolescents affected by type 1 diabetes mellitus (25 prepubertal and 29 pubertal) showing reduced height velocity and the results were compared to those of 104 matched controls. Growth hormone binding proteins were similar in prepubertal and pubertal subjects but were significantly lower in the prepubertal diabetic group than in controls. Insulin-like growth factor I was low both in prepubertal and pubertal diabetic subjects. Insulin-like growth factor binding protein 3 was similar to controls, while insulin-like growth factor binding protein 1 and 2 were always high in diabetic children. Insulin-like growth factor binding protein 4 was high only in the prepubertal diabetic group. In conclusion, a low insulin-like growth factor I in diabetic children seems to depend on a GH receptor and/or a postreceptor defect. A low insulin-like growth factor I together with a normal insulin-like growth factor binding protein 3 and high levels of insulin-like growth factor binding proteins 1, 2 and 4 results in a reduced bioavailability of insulin-like growth factor I to target tissues. This could be a possible contributing factor to the reduced height velocity seen in our diabetic children.

Altered adrenal and thyroid function in children with insulin-dependent diabetes mellitus.

In 129 children, aged 12.6 +/- 3.8 years, affected by type 1 diabetes mellitus, the levels of dehydroepiandrosterone sulfate (DHEAS), cortisol, T3, fT3, T4, fT4, rT3, TSH, cholesterol, and triglycerides were evaluated and compared with those of a control group of 458 healthy age-matched children. The results were also correlated with hemoglobin HbA1C. The DHEAS-standard deviation score (DHEAS-SDS; -0.36 +/- 0.77) was significantly different from zero in diabetic children, while the cortisol serum level was higher than in control subjects (485 +/- 94 vs 359 +/- 132 nmol/l). Moreover, the DHEAS-SDS and DHEAS-SDS/cortisol ratio correlated negatively with HbA1c. Diabetic patients also showed lower T3 values (2.22 +/- 0.4 vs 2.32 +/- 0.3 nmol/l) and a higher rT3/T3 ratio (0.17 +/- 0.09 vs 0.15 +/- 0.05) than controls. There was a negative correlation between T3 and HbA1C. Cholesterol (4.77 +/- 1.08 vs 4.51 +/- 0.76 mmol/l) and triglycerides (0.82 +/- 0.53 vs 0.63 +/- 0.37 g/L) levels were higher in diabetic children and positively correlated with HbA1c, but not with DHEAS-SDS. We can therefore conclude that diabetes, particularly if poorly controlled, tends to induce a dissociation of cortisol and DHEAS secretion and a low T3 syndrome, similar to that seen in other illnesses.

[Monitoring the treatment of precocious puberty with a GnRH-analog (buserelin): comparison of the GnRH-test with nocturnal pulsatility of LH, testosterone and 17-beta-estradiol]. / Monitoraggio della terapia per la pubertà precoce con un analogo del GnRH (Buserelin): confronto fra il GnRH-test e la pulsatilità notturna di LH, testosterone e 17 beta-estradiolo.

We studied in 10 children (3 boys and 7 girls), affected by precocious puberty and treated for a period of more than 6 months with the GnRH-analog Buserelin, the efficacy of the GnRH test versus the study of spontaneous nocturnal secretion of LH, testosterone and 17 beta-estradiol as a means of testing the gonadotropin suppression. All the subjects have shown a total suppression of LH during the GnRH test as well as a nocturnal profile of LH, testosterone and 17 beta-estradiol of a prepubertal pattern. Clinically all the patients were treated successfully. Considering the effectiveness of both investigations, we conclude that the GnRH test combined with clinical observation is a single and valid means of testing the pharmacological treatment for precocious puberty.

Hypothalamic-pituitary dysfunction and Hirschsprung's disease in the Bardet-Biedl syndrome.

A child with the Bardet-Biedl syndrome associated with Hirschsprung's disease and multiple anterior pituitary hormone deficiencies is described. The importance of endocrine assessment of such patients who show disturbance of growth or puberty is emphasized.

Thyrotropin (TSH) secretion in L-thyroxine treated children: assessment by a ultrasensitive TSH immunoradiometric assay.

The clinical usefulness of the measurement of basal TSH by an ultrasensitive assay (IRMA) versus the TRH test has been challenged in 49 children treated with L-thyroxine. They were given suppressive or replacement therapy depending on the underlying disease. An absent response of TSH to TRH could be predicted from a basal TSH value less than 0.1 mU/l in 88.8% of the cases, while only in 77.7% from a basal TSH value = 0.1 mU/l. A basal TSH value found in the range of the normal children always predicted a normal TRH test. We conclude that a sensitive TSH assay has some clinical application in monitoring L-thyroxine therapy, but can not absolutely replace the TRH test.

[Leri-Weill syndrome (dyschondrosteosis). Description of 2 clinical cases]. / Sindrome di Leri-Weill (discondrosteosi). Descrizione di due casi clinici.

We describe two children with Leri-Weill syndrome (Dyschondrosteosis), one of which showed the clinical features at very early age. Stature was moderately reduced in both, due to shortening of the bones of the legs. Furthermore were evident in them the clinical and radiological features of the propositus and of their affected parents are described. The problems concerning the early recognizing of the disease and the genetic inheritance are discussed.

[Tendency to low T3 syndrome in type 1 juvenile diabetes. Comparison of treatment with human and porcine insulin]. / Tendenza alla low T3 syndrome nel diabete giovanile tipo 1. Confronto fra trattamento con insulina umana e suina.

We investigated the serum thyroid hormones an the degree of diabetic control in 30 children and adolescents suffering from type 1 insulin-dependent diabetes, first while they were being treated with porcine insulin (group A) and then while 23 of them, random selected, were being treated with human insulin (group C). The purpose of our study was to evaluate if the change to human insulin would result in better metabolic control and disappearance of the tendency to the low T3 syndrome that was evidenced in group A. If we compare group A with group C, it can be seen that the degree of diabetic control is higher in group C (decrease in HbA1C), but that the tendency to the low T3 syndrome has not disappeared. Then we selected inside the groups A and C the patients in good metabolic control, and called them respectively group B and group D. If we compare group B with group D it can be seen that there is not any significant difference at all between them and that both groups show a tendency to the low T3 syndrome if compared with the control group (group K). In conclusion, we may state that substituting porcine with human insulin has not brought about any significant metabolic improvement in our patients, as can be seen from the persistent tendency to the low T3 syndrome.

Thyroid function in type 1 juvenile diabetes mellitus: tendency to the low T3 syndrome.

We have evaluated the thyroid function in 30 children and adolescents (average age 13 2/12 +/- 3 10/12 years) suffering from type 1 insulin-dependent diabetes (average duration of illness 5 +/- 3 3/12 years). We divided them into group A (good control) and group B (poor control), according to whether they had presented an HbA1C value lower or higher than 10%. The results obtained have been compared with a group of 30 normal patients of the same age. Both groups of diabetics presented T4 values which were notably lower than the control group (P less than 0.05). T3 was appreciably diminished both in group A (P less than 0.05) and in group B (P less than 0.01) and presented a negative correlation with HbA1C, only in group A however. The rT3/T3 ratio, on the other hand, was significantly increased in group B with respect to the controls. No significant differences were found with regard to FT3 and FT4, nor any correlations among thyroid hormones, C peptide, duration of illness, and daily insulin requirement. Our results indicated that the tendency to the low T3 syndrome, already described in adult diabetics, is also identifiable in young diabetics, particularly if poorly controlled.