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Netherton syndrome (NS) is a rare autosomal recessive disorder characterized by ichthyosiform scaling, hair abnormalities, and variable atopic features. Mutations in the serine protease inhibitor Kazal type 5 (SPINK5) gene leading to lymphoepithelial Kazal-type-related inhibitor (LEKTI) deficiency cause NS. Growth retardation is a classic feature of NS, but growth hormone (GH) deficiency with subsequent response to GH therapy is not documented in the literature. It is proposed that a lack of inhibition of proteases due to a deficiency of LEKTI in the pituitary gland leads to the overprocessing of human GH in NS. Herein we report three patients with NS who had growth retardation associated with GH deficiency and responded well to GH therapy., (© 2013 Wiley Periodicals, Inc.)

Aim: It was the aim of this study to evaluate adult height (AH) and different methods used for estimation of target height (TH) in children with idiopathic short stature (ISS)., Methods: Eighty-five ISS children (36 female, 49 male) were followed until AH was evaluated retrospectively. TH was calculated according to the following 4 methods: (1) as +/-6.5 cm to the mean parental heights for boys or girls, respectively, (2) as the mean standard deviation score (SDS) of the parents' heights, (3) as the sum of the SDS of the parents' heights divided by 1.61, and (4) as the mean SDS of the parents' heights multiplied by 0.72. ISS was classified as familial short stature (FSS) if the height was within the TH range and as nonfamilial short stature (NFSS) if it was below the TH range., Results: The number of FSS and NFSS children differed by the method chosen. The mean AH SDS was lower than the TH SDS in FSS in all methods, except in method 3. NFSS children did not attain their TH in either of the methods., Conclusions: Classification of ISS depends on the method of the TH range chosen. ISS children reach a mean AH SDS lower than the mean TH SDS. Only FSS children classified by method 3 reached a mean AH SDS close to the mean TH SDS., (Copyright 2009 S. Karger AG, Basel.)

This retrospective study evaluated clinical characteristics of patients with constitutional delay of growth and puberty (CDGP) at presentation, during puberty and at final height. The records of 151 children (105 boys, 46 girls) with CDGP were reviewed and the results were evaluated with respect to findings in healthy Turkish schoolchildren. CDGP was twice as frequent in boys as in girls. Height and weight deficit and short sitting height of the children were evident at presentation and continued up to final height. Mean age of onset of puberty was retarded by 2.5 years in girls and by 3 years in boys. The time between onset of puberty and pubertal growth spurt was shorter in both girls and boys than in the controls. Peak growth velocity was compromised in both girls and boys. Forty-one patients (30 boys, 11 girls) reached final height (FH). Mean FH was shorter than both target height and predicted adult height. The Bayley-Pinneau method was found to be a better predictor of FH than either the Tanner-Whitehouse method or target height. FH also showed correlation with the father's height. There was no effect of testosterone treatment on final height. Height deficit at onset of puberty, shorter duration between onset of puberty and pubertal growth spurt, compromised peak growth velocity and short upper segment due to delayed puberty, are findings which may explain the decreased final height of children with CDGP.

Retesting of patients with growth hormone (GH) deficiency (GHD), especially those with idiopathic GHD, has yielded normalization of the results in several studies. The aim of this study was to reevaluate patients diagnosed as GHD at completion or reconfirm the diagnosis before completion of GH treatment by retesting with provocative tests, and to evaluate the value of IGF-I and IGFBP-3 levels in the diagnosis of GHD. Fifty (33 M, 17 F) patients with GHD (peak GH level <0.46 pmol/l (10 ng/ml]) in two pharmacological tests were retested and IGF-I and IGFBP-3 levels measured. The age of the patients at retest was 15.2+/-5.0 yr. Thirteen of 50 patients (26%) normalized their GH secretion. According to the initial diagnosis, 69% of those with partial GHD (peak GH level 0.32-0.46 pmol/l [7-10 ng/ml]), 43% with isolated GHD, 33% idiopathic and 11% of those with complete GHD (peak GH level <0.32 pmol/l [7 ng/ml]) normalized their GH level at retesting. None of the patients with multiple hormone deficiency and none with small pituitary on MRI normalized GH levels at retest. The sensitivities of IGF-I and of IGFBP-3 were 70% and 67%, respectively, and the specificities were 100%, when peak GH cutoff is taken as 0.46 pmol/l (10 ng/ml) for the diagnosis of GHD. The sensitivities of IGF-I and IGFBP-3 increased to 76.5% and 73.5% when the cutoff level for GHD is taken as 0.32 pmol/l (7 ng/ml). Those patients who normalized their GH levels at retest showed a satisfactory height velocity when GH therapy was discontinued. In conclusion, reevaluation of GH status may also be undertaken while patients are still on treatment as well as at completion of treatment, especially in patients with idiopathic, partial and isolated GHD, by retesting and by IGF-I and IGFBP-3 measurements. Lowering the cutoff level of GH peak at pharmacological tests to 0.32 pmol/l (7 ng/ml) will lower the number of false positive results in the diagnosis of GHD.

This study was planned to search for the presence of possible tubular bone abnormalities in familial short stature (FSS) as has been previously noted in some reports. Twenty-five (17 male, 8 female) children with FSS aged 10.0 SD 3.6 years were taken as the study group, and 23 (14 male, 9 female) children of normal stature aged 10.6 SD 2.7 years comprised the control group. FSS was defined as height of the child and mean parental height below 3rd centile line, normal growth velocity and bone age within 2 years of chronological age. Other causes of short stature were ruled out. Height, weight, sitting height and arm, forearm and upper arm length measurements were taken by standard methods. A left hand and wrist X-ray was taken to evaluate the length of the 5th metacarpal. Children with FSS had a significantly higher prevalence of brachymetacarpia V (64%) than the children with normal stature (21.7%) (p < 0.001). Other tubular bone parameters, however, were normal. Sitting height/height ratios were in normal ranges and comparable in FSS and the control group. Similarly arm to height and upper arm to forearm ratios were comparable in the two groups excluding disproportionate shortening of the limbs. The finding of increased incidence of brachymetacarpia V in FSS may suggest an underlying tubular bone abnormality, which may explain the short stature in FSS.

To assess the growth-promoting effect of different doses of growth hormone-releasing hormone(1-29)-NH2 (GHRH(1-29)-NH2) in GH deficiency (GHD) of hypothalamic origin, 43 prepubertal children aged between 4.3 and 18.9 years (mean 10.4 +/- 2.9 years) were randomly assigned to three treatment regimens: low-dose GHRH(1-29)-NH2 (LD group; n = 15), high-dose GHRH(1-29)-NH2 (HD group; n = 12) and GH (GH group; n = 16). The LD group received GHRH(1-29)-NH2 at 30 micrograms/kg/day s.c. in three daily doses, the HD group received 60 micrograms/kg/day s.c. in three daily doses and the GH group received GH, 0.1 IU/kg/day s.c. once daily. All children were treated for a period of 6 months. Evaluation included anthropometry, bone age, intravenous and subcutaneous GHRH(1-29)-NH2 tests and determination of insulin-like growth factor I (IGF-I) levels. An increase in height velocity of 2 cm/year or more was observed in all except two children. Height velocity during treatment was lowest in the LD group, but comparable in the HD and GH groups. An increase in height SDS for bone age occurred only in the GH-treated group. GH responses to intravenous GHRH(1-29)-NH2 showed a priming effect of the LD GHRH(1-29)-NH2 treatment, while a decrease in response occurred in the GH-treated group. Following a subcutaneous test dose of one-third of the daily dose of GHRH(1-29)-NH2, GH levels remained unchanged in both the LD and HD groups. There was accumulation of GHRH immunoreactivity over time in the HD group, but there was no correlation between measured GHRH and GH levels.(ABSTRACT TRUNCATED AT 250 WORDS)