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

Infectious diseases and vaccination strategies: how to protect the "unprotectable"?

Introduction. The circulation of infectious diseases puts small infants too young to be vaccinated at risk of morbidity and mortality, often requiring prolonged hospitalization. Material and Methods. We have reviewed the medical records of children not eligible for vaccination because of age, admitted to hospital for pertussis, measles, or varicella from February 1, 2010, till February 1, 2012. Results. Of the case records scrutinized, 21 were hospitalized for pertussis, 18 for measles, and 32 for varicella. Out of them, 42%, 66%, and 78% diagnosed with, respectively, pertussis, measles, and varicella had a complicated course of the disease. Discussion. To avoid infectious disease circulation, childhood immunization strategies should be adopted, such as vaccination of healthcare givers, adult household contacts, and parents planning to have, or who have had, a newborn baby

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

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

Delayed puberty versus hypogonadism: a challenge for the pediatrician

Constitutional delay of growth and puberty (CDGP) is the most common cause of delayed puberty (DP), is mainly found in males, and is characterized by short stature and delayed skeletal maturation. A family history of the subject comprising the timing of puberty in the parents and physical examination may provide clues regarding the cause of DP. Delayed onset of puberty is rarely considered a disease in either sex. In fact, DP usually represents a common normal variant in pubertal timing, with favorable outcomes for final height and future reproductive capacity. In adolescents with CDGP, a linear growth delay occurs until immediately before the start of puberty, then the growth rate rapidly increases. Bone age is often delayed. CDGP is a diagnosis of exclusion; therefore, alternative causes of DP should be considered. Functional hypogonadotropic hypogonadism may be observed in patients with transient delay in hypothalamic-pituitary-gonadal axis maturation due to associated conditions including celiac disease, inflammatory bowel diseases, kidney insufficiency, and anorexia nervosa. Permanent hypogonadotropic hypogonadism (pHH) showing low serum value of testosterone or estradiol and blunted follicle-stimulating hormones (FSH) and luteinizing hormones (LH) levels may be due to abnormalities in the central nervous system. Therefore, magnetic resonance imaging is necessary to exclude morphological abnormalities and neoplasia. Moreover, pHH may be isolated, as observed in Kallmann syndrome, or associated with other hormone deficiencies, as found in panhypopituitarism. Baseline or gonadotropin-releasing hormone pituitary stimulated gonadotropin level is not sufficient to easily differentiate CDGP from pHH. Low serum testosterone in male patients and low estradiol values in female patients, associated with high serum FSH and LH levels, suggest a diagnosis of hypergonadotropic hypogonadism. A genetic analysis can reveal a chromosomal abnormality (e.g., Turner syndrome or Klinefelter syndrome). In cases where the adolescent with CDGP is experiencing psychological difficulties, treatment should be recommended

The Emerging Role of the Autophagy Process in Children with Celiac Disease: Current Status and Research Perspectives

Celiac disease (CD) affects approximately 1% of the population in Europe and North America, but the number of patients currently undiagnosed is estimated to be far higher than that of diagnosed cases owing to the presence of prevalent forms with nonspecific symptoms. The toxicity of gliadin in children with CD is not destroyed through digestion with gastropancreatic enzymes. An innate immunity to gliadin plays a key role in the development of CD. Autophagy, a physiological catabolic process, plays also a crucial role in the pathogenesis of several inflammatory diseases. Recent studies have described functional involvement of the regulation of autophagy within a pediatric CD cohort. Furthermore, the contribution of autophagy has been highlighted in the degradation and in the reduction of extracellular release of gliadin peptides, thus suggesting novel molecular targets to counteract gliadin-induced toxicity in CD

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