Growth Hormone Deficiency: Diagnosis and Therapy in Children

Short stature has been defined as a height below the 2 standard deviation for age, sex and ethnicity. Growth hormone deficiency (GHD) represents a condition characterized by reduced GH secretion, isolated or associated with other pituitary hormone deficiencies. In a child with short stature and growth deceleration, after the exclusion of other causes of growth failure, the diagnosis of GHD has to be confirmed by measurement of GH secretion after at least two stimulation tests. Patients with GHD should be treated with rhGH as soon as possible, to obtain normalization of growth and normal final height. The catch-up growth in response to rhGH therapy is maximal during the first years and could be affected by many variables, such as birth-weight, age and height at start of treatment and of puberty, and duration of treatment. Overall, rhGH is believed to be safe and significant side-effects in children are very rare, including benign intracranial hypertension, hyperglycaemia, arthralgia and myalgia. Patients with childhood onset GHD are usually retested in late adolescence to confirm the GHD persistence and to continue of GH therapy. In conclusion, the present chapter provides useful and updated information about the diagnosis, treatment and follow-up of children with GHD

Late diagnosis of celiac disease in an asymptomatic infant with growth failure

The clinical spectrum for celiac disease (CD) is broad and includes cases with either typical (intestinal) or atypical (extraintestinal) features, often making the diagnosis of CD very difficult. We describe the case of a girl presenting with stunted growth and malnourishment. She was evaluated at 14 months for decreased growth rate without any signs of gastrointestinal, renal or endocrine disorders. She was evaluated for CD, but resulted negative for anti-tTG antibodies. At the age of 4.1 years, she exhibited basal dental enamel hypoplasia, iron deficiency anaemia despite repeated iron supplementation, with persistent reduced height (-2.79 SDS), BMI (-0.76 SDS), growth velocity (-1.79 SDS) and delayed bone age (1.5 year). The CD screening was repeated and very high anti-tTG-IgA (128 IU/ml, normal values 40 IELs/100 epithelial cells) confirming the diagnosis of CD. A gluten-free diet was started and after only four months, her growth velocity increased from 4.83 cm/year (-1.79 SDS) to 6.53 cm/year (-0.15 SDS). In conclusion, we report the development of a positive serology for CD in an asymptomatic child with growth retardation, who previously was investigated for CD and resulted negative. Therefore, when faced with retarded growth in young patients, after excluding other malabsorption conditions and even when CD serological markers are negative, the paediatric endocrinologist should request HLA genotyping, before the intestinal biopsy, in order to check for the presence of risk alleles

Changes in growth hormone receptor gene expression during therapy in children with juvenile idiopathic arthritis.

Background: High levels of cytokines in juvenile idiopathic arthritis (JIA) can alter target cell sensitivity to growth hormone (GH) leading to short stature in adulthood. We hypothesized that the down-regulation of GH receptor (GHR) gene expression could be involved in growth failure of children with JIA. Methods: In 18 (12 F and 6 M) prepubertal JIA patients and 13 age- and sex-matched healthy children, we evaluated serum growth-promoting factors and inflammatory indexes. We also measured GHR gene expression, by real-time PCR, in lymphocytes of patients and controls. All parameters were evaluated in patients before and after treatment of JIA. Results: The most interesting (p = 0.007) result was the increase in GHR mRNA expression in all JIA patients. Moreover, we observed a significant (p = 0.0156) decrease in IL-6 levels in JIA patients after 2 years of therapy (19.37 +/- 41.01) with respect to basal values (90.84 +/- 124.71). On the contrary, IGF-I significantly (p = 0.0005) increased to a mean SDS value of 0 (range -1.69 to +1.70 SDS) with respect to values at disease onset (-0.64 SDS). Conclusions: Our preliminary data suggest that the restoration of both GHR gene expression and IGF-I secretion correlate with inactive disease in JIA children

Heterozygous GHR gene mutation in a child with idiopathic short stature

Several monogenic defects have been reported to be associated with idiopathic short stature. Focusing on growth hormone receptor (GHR)-gene alterations, the heterozygosity of the same gene defect may be associated with a range of growth deficits. We found a heterozygous mutation (V144I) within exon 6 of the GHR gene in a patient with a low level of insulin-like growth factor I (IGF-I), normal level of GH, and severe short stature. Despite the lack of statistical difference, an overall tendency for reduced wt-GH-induction of GHR activation and Jak/Stat signalling in cells transiently expressing GHR-V144I alone or co-expressing wt-GHR compared to cells expressing only wt-GHR was found when GH doses were increased. Our results suggest that, although GHR sequence variants are responsible for some functional alterations commonly observed in children with idiopathic short stature, these changes may not explain all the height deficits observed in these subject

Role of adiponectin and leptin on body development in infants during the first year of life

<p>Abstract</p> <p>Background</p> <p>The control of growth and nutritional status in the foetus and neonate is a complex mechanism, in which also hormones produced by adipose tissue, such as adiponectin and leptin are involved. The aim of this study was to evaluate levels of adiponectin, leptin and insulin in appropriate (AGA) and small for gestational age (SGA) children during the 1^styear of life and to correlate these with auxological parameters.</p> <p>Methods</p> <p>In 33 AGA and 29 SGA infants, weight, length, head circumference, glucose, insulin, adiponectin and leptin levels were evaluated at the second day of life, and at one, six and twelve months, during which a portion of SGA could show catch-up growth (rapid growth in infants born small for their gestational age).</p> <p>Results</p> <p>Both total and isoform adiponectin levels were comparable between AGA and SGA infants at birth and until age one year. These levels significantly increased from birth to the first month of life and then decreased to lower values at 1 year of age in all subjects. Circulating leptin concentrations were higher in AGA (2.1 ± 4.1 ng/ml) than in SGA neonates (0.88 ± 1.03 ng/ml, p < 0.05) at birth, then similar at the 1^stand the 6^thmonth of age, but they increased in SGA from six months to one year, when they showed catch-up growth. Circulating insulin levels were not statistically different in AGA and SGA neonates at any study time point. Insulin levels in both AGA and SGA infants increased over the study period, and were significantly lower at birth compared to one, six and 12 months of age.</p> <p>Conclusions</p> <p>During the first year of life, in both AGA and SGA infants a progressive decrease in adiponectin levels was observed, while a difference in leptin values was correlated with the nutritional status.</p

Same Phenotype in Children with Growth Hormone Deficiency and Resistance

By definition, about 2.5% of children show a short stature due to several causes. Two clinical conditions are characterized by serum IGF-I low levels, idiopathic GH deficiency (IGHD), and GH insensitivity (GHI), and the phenotypic appearance of these patients may be very similar. We studied two children with short stature and similar phenotypes. *e first case showed frontal bossing, dollface, acromicria, and truncal obesity, with a GH peak <0.05 ng/ml after stimuli and undetectable serum IGF-I levels. After PCR amplification of the whole GH1 gene, type IA idiopathic GHD was diagnosed. *e second case had cranium hypoplasia, a large head, protruding forehead, saddle nose, underdeveloped mandible, and a micropenis. Basal GH levels were high (28.4 ng/ml) while serum IGF-I levels were low and unchangeable during the IGF-I generation test. Laron syndrome was confirmed after the molecular analysis of the GH receptor (GHR) gene. IGHD type IA and Laron syndrome is characterized by opposite circulatinglevels of GH, while both have reduced levels of IGF-I, with an overlapping clinical phenotype, lacking the effects of IGF-I on cartilage. *ese classical cases show the importance of differential diagnosis in children with severe short stature.Fil: Ioimo, Irene. University of Pavia; ItaliaFil: Guarracino, Carmen. University of Pavia; ItaliaFil: Meazza, Cristina. University of Pavia; ItaliaFil: Domene, Horacio Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Bozzola, Mauro. University of Pavia; Itali

Omitting duodenal biopsy in children with suspected celiac disease and extra-intestinal symptoms

The aim of our study is to evaluate if in children with highly positive serology and HLA-DQ2/DQ8 (triple test, TT) and only extra-intestinal symptoms, it is possible to omit performing an intestinal biopsy for celiac disease (CD) diagnosis, as suggested by the new European Society for Pediatric Gastroenterology, Hepatology and Nutrition ESPGHAN guidelines