Diagnosis of growth hormone deficiency is affected by calibrators used in GH immunoassays.

Growth hormone (GH) values vary among immunoassays depending on different factors, such as the assay method used, specificity of antibodies, matrix difference between standards and samples, and interference with endogenous GH binding proteins (GHBPs). We evaluated whether the use of different calibrators for GH measurement may affect GH values and, consequently, the formulation of GH deficiency (GHD) diagnosis in children. Twenty-three short children (5 F, 18 M; age 11.4±3.1 years), with the clinical characteristics of GHD (height: -2.3±0.5 SDS; height velocity -2.3±1.5 SDS; IGF-I -1.2±0.9 SDS), underwent GH stimulation tests to confirm the clinical diagnosis of GHD. Serum GH values were measured with Immulite 2000, using 2 different calibrators, IS 98/574, a recombinant 22 kDa molecule of more than 95% purity, and IS 80/505, of pituitary origin and resembling a variety of GH isoforms. We found blunted GH secretion in 20 subjects with the Immulite assay using the IS 98/574 GH as a calibrator, confirming the diagnosis of GHD. Subsequently, using IS 80/505 GH as a calibrator, in the same samples only 14 children showed reduced GH levels. The total cost for the first year of GH therapy of patients diagnosed with IS 98/574 as a calibrator was higher than that for patients diagnosed with IS 80/505 as a calibrator. These data confirm that GH values may depend on different calibrators used in the GH assay, affecting the formulation of GHD diagnosis and the consequent decision to start GH treatment.

Efficacy of long-term growth hormone therapy in short children with reduced growth hormone biological activity.

AIM: The optimal GH regimen, in terms of cost-effectiveness, in children with normal GH immunoreactivity but reduced bioactivity is still debated. METHODS: In 12 GH-deficient (GHD) and 12 bioinactive GH children undergoing GH treatment we evaluated the increase in growth velocity, the difference between target height and final stature and the incremental cost-effectiveness ratio. RESULTS: We found a significant (p < 0.05) increase in growth velocity in both groups during the first year of GH treatment (non- GHD: from -1.7 to 5.4 SDS; GHD: from -1.46 to 4.74 SDS). There was no statistically significant variation between the two groups in the difference between final height and target height. We did not find any significant difference in cost/height gain between GHD (1925.28 ± 653.15 euro) and bioinactive GH children (1639.55 ± 631.44 euro). There were also no significant differences in cost/year of therapy between GHD (12347.68 ± 2018.1 euro) and bioinactive GH children (11355.08 ± 1747.61 euro). CONCLUSION: In children with reduced GH biological activity, confirmed by the increase of serum IGF-I levels during generation test, the cost of GH treatment is justified by the positive results obtained in growth and adult height as in classical GHD patients.

Hyperimmunoglobulinaemia in Babinga Pygmies is present from infancy.

Pygmies, a population characterized by short stature, have high immunoglobulin (Ig) concentrations. In this study, we evaluated Ig levels in Cameroons Babinga Pygmies from infancy to adulthood and the effects of a national health program on these Ig levels. We found that IgG and IgM levels were outside the normal range for Italians of the same age and were comparable to those measured in Babinga Pygmies living in the same region by Siccardi in 1975. In conclusion, the hypergammaglobulinaemia of Babinga Pygmies is already present in infants and is not affected by sanitation improvements, suggesting that it could be partly genetically-determined.

Serum IGF-I and IGFBP-3 reference values from a chemiluminescent assay in normal children and adolescents of hispanic and italian origin: presence of sexual dimorphism in IGF-I values.

Serum IGF-I and IGFBP-3 assays are used to monitor rhGH treatment. Some discrepancies in results obtained by means of different assays have been reported. The aim of this study was to establish normal ranges for circulating IGF-I and IGFBP-3 in children and adolescents of Hispanic and Italian origin. Circulating levels of IGF-I and IGFBP-3 were measured in 169 Hispanic and Italian prepubertal children and 66 adolescents of both sexes, using a chemiluminescent assay. Serum levels of IGF-I and IGFBP-3 increased from early childhood into adolescence. After pubertal peaks of IGF-I and IGFBP-3, slight decreases were observed with increasing age. Furthermore, serum IGF-I levels were significantly higher in girls than in boys, suggesting a sexual dimorphism in serum IGF-I values in late prepuberty and early puberty. Differences in IGF-I and IGFBP-3 absolute values between our study and previous studies suggest the need to establish reference ranges for each ethnic group.

[Changes in circulating levels of adiponectin and leptin in children during the first two years of life]. / Variazioni dei livelli circolanti di adiponectina e leptina nel bambino nei primi due anni di vita.

AIM: Adiponectin, leptin and insulin play an important role in the control of growth and glyco-metabolic homeostasis both during pre- and post-natal life. In order to find out markers indicative of post-natal growth, we evaluated circulating levels of these growth factors in full term small for gestational age (SGA) children, during the first 2 years of life, correlating them with the auxological parameters. METHODS: Fourteen SGA (8 males and 6 females) and 16 AGA (appropriate for gestional age) infants (7 males and 9 females) have been included in this study, recording length, weight, body mass index (BMI), adiponectin, leptin and insulin levels at birth. In SGA subjects, these biochemical and clinical parameters have also been evaluated at the first and at the second year of age. RESULTS: AGA and SGA adiponectin and insulin levels at birth did not show statistically significant differences, while leptin concentrations were significantly (P=0.011) lower in SGA children (median 418.49, range 157.68-903.67 pg/mL) in comparison with AGA ones (median 811.71, range 312.50-3085.95 pg/mL). CONCLUSIONS: In conclusion, at birth adiponectin and insulin levels do not differ between AGA and SGA subjects while leptin concentrations are significantly lower in SGA infants and positively correlated to the birthweight.