Search

Introduction: Congenital adrenal hyperplasia (CAH) due to 21α-hydroxylase deficiency results in inadequate cortisol and aldosterone synthesis and concomitant overproduction of adrenal androgens. Despite adequate replacement, impaired growth and overweight remain a clinical challenge. The main objective was to investigate the differences in growth, final height (FH), and body mass index (BMI) between different CYP21A2 genotype groups and glucocorticoid treatment strategies during the different phases of growth. Methods: This is a population-based observational cohort study from diagnosis to FH. A total of 86 subjects were diagnosed with CAH in Sweden during 1989–1994. Eighty subjects were followed until FH. There were no interventions apart from the clinical standard of care treatment for CAH. The main outcome measure was the corrected FH standard deviation score (cFH SDS) and its correlation with genotype, accumulated total glucocorticoid dose, and treatment strategy. In addition, BMI and growth trajectories during infancy, childhood, and adolescence were studied. Results: FH was shorter in patients with the more severe CYP21A2 genotypes. Treatment doses of glucocorticoid were within the international treatment recommendations (10–15 mg/m2). Patients with the null and I2 splice genotypes lost approximately 1 SD in FH, whereas patients with the milder genotypes (I172N, P30L, and V281L) were within 0.5 to 0 SDS from target height. cFH SDS was negatively affected by the use of prednisolone but did not correlate with overall glucocorticoid treatment dose calculated as hydrocortisone equivalents. BMI at 18 years was higher in patients treated with prednisolone but did not correlate with genotype. Conclusions: Corrected FH was more affected in patients with severe CYP21A2 genotypes. The addition of a low dose of prednisolone to the hydrocortisone treatment, despite an equivalent total dose of glucocorticoids, was associated with shorter FH and higher BMI in growing subjects with CAH. [ABSTRACT FROM AUTHOR]

Aim: Tall stature, defined as a height greater than 2 standard deviation score (SDS), affects 2.3% of children. Our study aimed to explore the causes of tall stature in children and assess the long-term outcomes for these cases. Materials and Methods: This study included 393 children with tall stature who applied to a pediatric endocrinology clinic between 2015-2024. The patients' medical histories, physical examinations, laboratory findings and hormonal profiles were recorded. Results: Two hundred and forty-seven girls (62.8%) and 146 boys (37.2%) with a mean age of 9.0±2.8 (0.7-16.8) years were included. The majority of the cases presented with obesity and tall stature (25.2%), early onset of puberty signs and tall stature (18.8%), and early onset of puberty signs (12%). Tall stature was not reported as a complaint in 32.7% of the patients. At the initial visit, the height SDS was 2.6±0.5 (2.0-6.2), the mid parenteral height (MPH) SDS was 0.1±0.8 [(-1.9)-3.6] and the predicted adult height (PAH)-MPH was 8.5±7.8 [(-8.5)-39.0] cm. Considering their diagnoses, the majority were familial tall stature (39.9%), obesity + tall stature (32.3%), and central precocious puberty (13.5%). Cranial imaging was performed in 33 cases, and pathology was detected in 10. 95 of the cases had reached their final height. There was a statistically significant difference between the final height SDS and the patients' initial height SDS and MPH SDS values (p<0.001). There was no difference between their PAH and final height values (p=0.481). Conclusion: Those individuals with tall stature required fewer hospital admissions than those with short stature. Obesity, precocious puberty, and genetic potential were found to be the most significant triggering factors, so they should not be overlooked. [ABSTRACT FROM AUTHOR]

Introduction: Direct comparisons of both short-term and long-term auxological outcomes of growth hormone therapy (GHT) between growth hormone deficiency (GHD) and small for gestational age (SGA) are scarce. Methods: One hundred three patients with GHD and 53 patients with SGA treated at our tertiary center were investigated. Short-term and long-term outcomes were compared between these groups using multivariable linear regression models with adjustment for age, sex, and height at therapy start, also allowing for sex-specific group comparisons. Results: Mean delta height standard deviation scores (SDS) after 1 year of treatment were significantly higher in GHD (0.90, CI: 0.82–0.99) compared to SGA (0.67, CI: 0.54–0.79) (p = 0.003) with no sex difference. As expected, the mean increase in height SDS at final height (FH) was significantly higher in GHD (2.21, CI: 2.00–2.42) compared to SGA (1.05, CI: 0.75–1.35) (p < 0.001), leading to a target height corrected FH of −0.39 SDS (CI: −0.62 to −0.15) in GHD and −1.22 SDS (CI: −1.57 to −0.87) in SGA (p < 0.001). Girls with GHD had a better long-term outcome, as did boys with SGA when compared to the respective opposite sex. The cut-off of delta height of 0.5 SDS during the first year had a low sensitivity to detect long-term non-responders. We found a relation between short-term and long-term outcomes in GHD but not in SGA (adjusted R2 = 0.66 vs. 0.01). Conclusion: In contrast to GHD, we observed practically no relationship between 1st-year and long-term outcomes in SGA patients treated with GH. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study is to analyze height after cessation of growth (final height [FH]) and its evolution over the last decades in X-linked hypophosphatemia (XLH) patients in France, as the data on natural history of FH in XLH are lacking. Design: We performed a retrospective observational study in a large cohort of French XLH patients with available data on FH measurements. Materials and methods: We divided patients into 3 groups according to their birth year: group 1 born between 1950 and 1974, group 2 born between 1975 and 2000, and group 3 born between 2001 and 2006, respectively, and compared their FHs. Results: A total of 398 patients were included. Mean FHs were the following: for group 1, −2.31 ± 1.11 standard deviation score (SDS) (n = 127), 156.3 ± 9.7 cm in men and 148.6 ± 6.5 cm in women; for group 2, −1.63 ± 1.13 SDS (n = 193), 161.6 ± 8.5 cm in men and 153.1 ± 7.2 cm in women; and for group 3, −1.34 ± 0.87 SDS (n = 78), 165.1 ± 5.5 cm in men and 154.7 ± 6 cm in women. We report a significant increase in mean FH SDS over 3 generations of patients, for both men and women (P < .001). Final height SDS in male (−2.08 ± 1.18) was lower than in female (−1.70 ± 1.12) (P = .002).Conclusion: The FH of XLH patients in France increased significantly over the last decades. Even though men’s FHs improved more than women’s, men with XLH remain shorter reflecting a more severe disease phenotype. While the results are promising, most patients with XLH remain short leaving room for improvement. [ABSTRACT FROM AUTHOR]

Background: Early puberty suppression (ePS; Tanner stages 2 and 3) through gonadotropin-releasing hormone agonists (GnRHas) and genderaffirming hormones (GAHs) interferes with growth and may impact final height (FH). Aim: To investigate the impact of ePS and GAH on FH in trans boys and trans girls. Methods: Retrospective study, including 10 trans boys and 22 trans girls at FH. Bone age (BA) was determined at the start of ePS and at the start of GAH according to Greulich and Pyle; predicted adult height (PAH) was calculated according to Bayley and Pinneau's tables; target height (TH) was calculated as adjusted mean of maternal and paternal height. Target height, PAH, and BA were determined according to sex registered at birth (SRAB) and experienced gender (EG). Results: The age at the start of PS was 12.37 ± 0.74 years in trans boys and 13.10 ± 1.12 years in trans girls. Total height gain since the start of ePS in trans boys was 14.62 ± 4.08 cm, with 70% achieved before the start of GAH. In trans girls, it was 20.68 ± 7.66 cm, with 61% achieved before GAH. Target height for SRAB was the most accurate predictor for FH in both trans boys and girls: the difference with FH was 1.57 cm ± 3.1 (P = .168) and -0.98 cm ± 4.17 (P = .319), respectively. Also the difference between FH and PAH at the start of PS for SRAB was nonsignificant in both trans boys and girls (2.62 cm ± 3.79, P = .056 and -2.35 cm ± 5.2, P = .051, respectively). Conclusion: Early puberty suppression and GAH do not impact FH, supporting the safety of the treatment; however, trans adolescents achieve a FH in line with SRAB, rather than EG. [ABSTRACT FROM AUTHOR]

Background: Growth hormone deficiency (GHD) is the commonest endocrine cause of short stature and may occur in isolation (I-GHD) or combined with other pituitary hormone deficiencies. Around 500 children are diagnosed with GHD every year in the UK, of whom 75% have I-GHD. Growth hormone (GH) therapy improves growth in children with GHD, with the goal of achieving a normal final height (FH). GH therapy is given as daily injections until adult FH is reached. However, in many children with I-GHD their condition reverses, with a normal peak GH detected in 64–82% when re-tested at FH. Therefore, at some point between diagnosis and FH, I-GHD must have reversed, possibly due to increase in sex hormones during puberty. Despite increasing evidence for frequent I-GHD reversal, daily GH injections are traditionally continued until FH is achieved. Methods/design: Evidence suggests that I-GHD children who re-test normal in early puberty reach a FH comparable to that of children without GHD. The GHD Reversal study will include 138 children from routine endocrine clinics in twelve UK and five Austrian centres with I-GHD (original peak GH < 6.7 mcg/L) whose deficiency has reversed on early re-testing. Children will be randomised to either continue or discontinue GH therapy. This phase III, international, multicentre, open-label, randomised controlled, non-inferiority trial (including an internal pilot study) will assess whether children with early I-GHD reversal who stop GH therapy achieve non-inferior near FH SDS (primary outcome; inferiority margin 0.55 SD), target height (TH) minus near FH, HRQoL, bone health index and lipid profiles (secondary outcomes) than those continuing GH. In addition, the study will assess cost-effectiveness of GH discontinuation in the early retesting scenario. Discussion: If this study shows that a significant proportion of children with presumed I-GHD reversal generate enough GH naturally in puberty to achieve a near FH within the target range, then this new care pathway would rapidly improve national/international practice. An assumed 50% reversal rate would provide potential UK health service cost savings of £1.8–4.6 million (€2.05–5.24 million)/year in drug costs alone. This new care pathway would also prevent children from having unnecessary daily GH injections and consequent exposure to potential adverse effects. Trial registration: EudraCT number: 2020-001006-39 [ABSTRACT FROM AUTHOR]

Background/aim: Despite optimal conventional treatment (oral phosphate supplements and active vitamin D analogs), about 40–50% of children with well-controlled X-linked hypophosphatemia (XLH) show linear growth failure, making them less likely to achieve an acceptable final height. Here, we studied the hypothesis that rhGH treatment improves final height in children with XLH and growth failure. Methods: Two cohorts of children with XLH were included in this retrospective longitudinal analysis: (1) a cohort treated with rhGH for short stature (n = 34) and (2) a cohort not treated with rhGH (n = 29). The mean duration of rhGH treatment was 4.4 ± 2.9 years. We collected the auxological parameters at various time points during follow-up until final height. Results: In rhGH-treated children, 2 years of rhGH therapy was associated with a significant increase in height from − 2.4 ± 0.9 to − 1.5 ± 0.7 SDS (p < 0.001). Their mean height at rhGH discontinuation was − 1.2 ± 0.9 SDS and at final height was − 1.3 ± 0.9 SDS corresponding to 165.5 ± 6.4 cm in boys and 155.5 ± 6.3 cm in girls. Notably, the two groups had similar final heights; i.e., the final height in children not treated with rhGH being − 1.2 ± 1.1 SDS (165.4 ± 6.8 cm in boys and 153.7 ± 7.8 cm in girls), p = 0.7. Conclusion: Treatment with rhGH permits to improve final height in children with XLH and growth failure, despite optimal conventional treatment. We propose therefore that rhGH therapy could be considered as an option for short stature in the context of XLH. [ABSTRACT FROM AUTHOR]

Introduction: In this retrospective study, it was aimed to examine the effect of gonadotropin-releasing hormone (GnRH) analogue treatment on final height in girls diagnosed with early puberty (EP) between the ages of 8 and 10. Materials and Methods: In the study, 87 girls who were diagnosed with EP and reached the final height were included. Two groups, those who received GnRH analogue treatment and those who did not, were formed. The average age, bone age, average height, height standard deviation score (SDS), body mass index SDS, target height, predicted adult height of the groups at the time of admission were calculated. The final height they reached and their menarche ages were noted. Results: No difference was found between the groups in terms of average age, average height, height SDS, bone age, body mass index SDS at the time of admission. The target height, predicted adult height, final height and the SDS of these were similar in both groups. All cases in both groups reached the target height. Conclusion: It was determined that the GnRH analogue treatment did not make a positive contribution to the final height in the EP group, who were between the ages of 8 and 10. Therefore, it can be recommended to use GnRHa treatment in EP patients with psychosocial problems and for delaying menarche. [ABSTRACT FROM AUTHOR]

Background: The final adult height of patients with congenital adrenal hyperplasia (CAH) is usually less than the target height (TH). This could be attributed to androgen excess or treatment with steroids. Androgen excess can occur at any age leading to accelerated growth, early epiphyseal closure and compromised final adult height (Webb and Krone, 2015), (Charmandari et al., 2004). Aim: evaluate growth and final height in children and adolescents with CAH. Methodology: This retrospective study was conducted on 36 patients diagnosed with CAH, data was collected from patients' records within endocrinology clinic, Children's Hospital, Ain Shams University. Result: Our patients had a mean final height and final height SDS of (161.68±6.48cm and -0.41) and (151.03±6.1cm and -0.67) for males and females respectively. Final adult height was less than target height (mean target heights were 168.8± 3.54 cm and 157.1± 6 cm for males and females respectively). The median target height in our study was 158.4cm and mean target height SDS corrected to mid-parental target height was -0.43 ± (1.26). The mean daily hydrocortisone was 15.67 (± 3.26 SD) mg/m2 per day with range (9.9 - 24) mg/m2. There was no correlation between final heights and the cumulative doses and mean daily doses of hydrocortisone. There was no correlation between final height SDS in both sexes and age of starting steroid therapy. The bone age of our patients was advanced on average by 2 years compared to chronological age at final height. Conclusion: the final height of CAH patients treated with glucocorticoids is lower than the population norms and is lower than what would be predicted based on parental height. [ABSTRACT FROM AUTHOR]

Objective: Multiple endocrine neoplasia 2B (MEN2B) is characterised by early‐onset medullary thyroid carcinoma (MTC), pheochromocytoma and several nonendocrine manifestations. Unfortunately, MEN2B is often diagnosed late, after the development of clinically significant MTC. Marfanoid habitus is considered an important related feature, which may lead to the assumption that patients with MEN2B have tall stature. Here, we describe the longitudinal growth and body proportions of eight MEN2B patients during childhood. Design: It is a retrospective case series. Methods: Patients were under the care of a Dutch MEN expertise centre. Growth patterns were assessed and interpreted in relation to body mass index (BMI), age at diagnosis and at thyroidectomy, extensiveness of disease manifestations and parental height. Results: Seven patients were short during childhood, of whom four showed growth below target height range (THR) and three at the lowest margin of THR. Only one patient grew well within THR. All patients who attained final height (n = 4) ended within THR, despite short stature during childhood. Arm span/height ratio was not increased and upper segment/lower segment ratio was not reduced in any patient. Short stature in childhood in this study did not seem to be associated with age at diagnosis, age at thyroidectomy, extensiveness of MTC, endocrine deficiencies or BMI. Conclusions: This study shows that children with MEN2B may well present with short rather than tall stature. Thereafter, final height within THR was attained in those who already reached adulthood, but none had tall stature. Finally, body proportions were normal in all children and adults in this case series, not underlining a 'marfanoid' body habitus. [ABSTRACT FROM AUTHOR]

Growth retardation is a major complication in children with chronic kidney disease (CKD) and on kidney replacement therapy (KRT). Conversely, better growth in childhood CKD is associated with an improvement in several hard morbidity–mortality endpoints. Data from pediatric international registries has demonstrated that improvements in the overall conservative management of CKD, the search for optimal dialysis, and advances in immunosuppression and kidney transplant techniques have led to a significant improvement of final height over time. Infancy still remains a critical period for adequate linear growth, and the loss of stature during the first years of life influences final height. Preliminary new original data from the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry confirm an association between the final height and the height attained at 2 years in children on KRT. [ABSTRACT FROM AUTHOR]

Background: In patients with growth hormone (GH) deficiency, the prediction of adult height before initiation of GH treatment can be helpful to guide clinicians and families. However, data regarding the effectiveness of prediction methods in such patients are limited. Objective: We aimed to investigate the accuracy of the three most used adult height prediction methods [Bayley-Pinneau (BP), Roche-Wainer-Thissen (RWT), and Tanner-Whitehouse 2 (TW2)] by comparing their results with the near-adult height (NAH) data of children treated with GH. Methods: A single-center retrospective study was conducted including patients treated with somatotropin due to GH deficiency. Bone age radiographs were reread by three authors. Adult height predictions were made using BP, RWT, and TW2 methods for each patient. Results: Forty-nine patients with GH deficiency [median age at diagnosis 10.8 (9.2–12.0) years, 63.3% girls, 69.4% prepubertal] were included. Median differences between predicted adult height (PAH) and NAH standard deviation (SD) scores were −0.5, 0.0, and 0.3 for BP, RWT, and TW2 methods, respectively. The rates of PAH within ±1 SD score of NAH were 54.7%, 62.3%, and 77.4% for BP, TW2, and RWT methods, respectively. RWT was the most accurate method in girls, however, it showed a similar efficiency with TW2 in prepubertal patients or those with delayed bone age between 1–2 years, independent of gender. Conclusions: We found that RWT and TW2 methods may be preferable rather than the BP method for predicting adult height in patients with a diagnosis of GH deficiency. [ABSTRACT FROM AUTHOR]

The objective of the study is to determine the risks and benefits of treating idiopathic short stature (ISS) with aromatase inhibitors (AIs). We comprehensively searched PubMed, Embase, and the China National Knowledge Infrastructure between establishment year and January 31, 2020. Mean difference (MD)/Standardized mean differences (SMD) with 95% confidence intervals (CI) of individual studies were pooled using fixed or random effects models. Subgroup and sensitivity analyses were also performed. Publication bias was estimated using funnel plots and Egger tests. Fourteen studies including 388 participants were included. The meta-analysis results showed that AIs significantly increased final height (MD=2.46, 95% CI: 0.8–4.12) and predicted adult height (MD=0.34, 95% CI: 0.11–0.57). Changes in bone age (MD=–0.1, 95% CI: –0.86–0.66) and bone mineral density (MD=–0.05, 95% CI: –0.19–0.1) were not different between intervention and control group. AI significantly increased testosterone level (SMD=2.01, 95% CI: 0.8–3.23) and reduced estradiol level (SMD=–1.13, 95% CI: –1.87 to –0.40); The intervention and control group had no significant differences in the levels of high-density lipoprotein-cholesterol (SMD=–0.31, 95%CI: –0.68–0.06) and IGF-1 (SMD=0.7, 95% CI: –0.66–2.06) levels. Adverse events were more frequent in the intervention group than in the control group (odds ratio=3.12, 95% CI: 1.44–6.73). In conclusion, both AI monotherapy and AI combination therapy can increase predicted adult height and testosterone levels. [ABSTRACT FROM AUTHOR]

Objective: To retrospectively evaluate the follow-up data in patients with 46,XX congenital adrenal hyperplasia (CAH) who were raised male. Methods: A national database was created. The data of patients were asked to be recorded in the data form. Results: The median (range) age of diagnosis was three (0.1-18.3) years in 44 patients. Twenty nine cases were diagnosed after the age of two years. Most (95.4%) cases were stage 4-5 virilized. Hysterectomy and bilateral salpingoopherectomy, at a median age of 7.25 (2.4-25.3) years, was performed in 35 cases. Testicular prostheses were placed in 11 (25%) cases at a median age of 11.2 (2.8-17) years. The median final height was 149.2 (132.8-172) cms in 38 patients, including simple virilizing (n=18), salt-wasting (n=6), and 11-beta hydroxylase (n=12). Of the 16 patients above the age of eighteen, university education was completed in 25%. Conclusion: It was seen that most (65.9%) of the 46,XX CAH cases raised male were diagnosed after two years of age. In these cases, hysterectomy and bilateral salpingoopherectomy, genital corrective surgeries and testicular prosthesis operations were performed in a very wide age rage. [ABSTRACT FROM AUTHOR]

Objectives: Sex steroids, administered as a priming before GH stimulation tests (GHST) to differentiate between growth hormone deficiency (GHD) and constitutional delay of growth and puberty (CDGP) or as growth‐promoting therapy using low‐dose sex steroids (LDSS) in CDGP, are much debated. We aimed to compare auxological outcomes of CDGP or GHD children undergoing primed or unprimed GHST and to evaluate LDSS treatment in CDGP. Design: Retrospective study among three paediatric University Hospitals in Italy and UK. Methods: 184 children (72 females) aged 12.4 ± 2.08 years underwent primed (/P+) or unprimed (/P−) GHST and were followed up until final height (FH). CDGP patients were untreated (CDG P−) or received LDSS (CDGP+). The cohort included 34 CDG P−/P+, 12 CDGP+/P+, 51 GHD/P+, 29 CDG P−/P−, 2 CDGP+/P− and 56 GHD/P−. FH standard deviation score (SDS), Δ SDS FH‐target height (TH) and degree of success (−1 ≤ Δ SDS FH‐SDS TH ≤ +1) were outcomes of interest. Results: GHD/P+ had better FH‐SDS (−0.87 vs −1.49; P =.023) and ΔSDS FH‐TH (−0.35 vs −0.77; P =.002) than CDGP−/P+. Overall, GHD/P+ showed the highest degree of success (90%, P =.006). Regardless of priming, both rhGH and LDSS improved degree of success compared to no treatment (89% and 86% vs 63%, P =.0009). GHD/P+ showed a trend towards a higher proportion of permanent GHD compared to GHD/P‐ (30.43% vs 15.09%; P =.067). Conclusion: In peripubertal children, priming before GHST improves diagnostic accuracy of GHST for idiopathic GHD. LDSS treatment improves auxological outcomes in CDGP. [ABSTRACT FROM AUTHOR]

Introduction: In the randomized "Toddler Turner" study, girls who received growth hormone (GH) starting at ages 9 months to 4 years (early-treated [ET] group) had marked catch-up growth and were 1.6 ± 0.6 SD taller than untreated (early-untreated [EUT]) control girls after 2 years. However, whether the early catch-up growth would result in greater near-adult height (NAH) was unknown. Therefore, this extension study examined the long-term effects of toddler-age GH treatment on height, pubertal development, and safety parameters. Methods: Toddler Turner study participants were invited to enroll in a 10-year observational extension study for annual assessments of growth, pubertal status, and safety during long-term GH treatment to NAH for both ET and EUT groups. Results: The ET group was taller than the EUT group at all time points from preschool to maturity and was significantly taller at the onset of puberty (p = 0.016), however, the difference was not significant at NAH. For the full cohort (ET + EUT combined, n = 50) mean (± SD) NAH was 151.2 ± 7.1 cm at age 15.0 ± 1.3 years. NAH standard deviation score (SDS) was within the normal range (>−2.0) for 76% of ET and 60% of EUT subjects (68% overall) and correlated strongly with height SDS at GH start (r = 0.78; p < 0.01), which in turn had a modest inverse correlation with age at GH start (i.e., height SDS declined with increasing age in untreated girls [r = −0.30; p = 0.016]). No new safety concerns arose. Conclusion: Although the ET group was taller throughout, height SDS at NAH was not significantly different between groups due to catch-down growth of ET girls during lapses in GH treatment after the Toddler study and similar long-term GH exposure overall. Early initiation of GH by age 6 years, followed by uninterrupted treatment during childhood, can prevent ongoing growth failure and enable attainment of height within the normal range during childhood, adolescence, and adulthood. [ABSTRACT FROM AUTHOR]

Introduction: About 8% of children born small for gestational age (SGA) do not reach a final height within the normal range. Recombinant human growth hormone (rhGH) has been shown to be effective in increasing the final height in children born SGA. Our objective was to identify predictive factors of final height in children born SGA treated with rhGH. Materials and Methods: In this retrospective study, conducted in a tertiary pediatric endocrinology referral center, we recruited all patients born SGA (defined as birth length or weight <10th percentile) treated with rhGH for more than 12 months for whom final height data were available. Some patients had received gonadotropin-releasing hormone (GnRH) analog therapy. Results: We included 252 patients with an average birth length of −2.0 ± 0.7 SD and birth weight of −1.7 ± 1.0 SD. After 4.6 ± 2.8 years of rhGH treatment, their height increased from −2.2 ± 0.9 SD to −1.5 ± 0.9 SD. In multivariate analysis, we identified 8 factors that predict 46% of the final height, namely, cause of SGA (p < 0.0001), GnRH analog therapy >2 years (p = 0.006), birth length (p < 0.02), height at the start of rhGH (p < 0.0001), IGF-1 level at the start of rhGH (p = 0.0002), growth velocity during the 1st year of treatment (p = 0.0002), and age and height at the onset of puberty (p < 0.0001, p = 0.0007, respectively). Conclusion: In this large cohort of SGA patients who had reached their final height, we were able to confirm that growth hormone increases final height in short SGA children. In addition, we identified several factors associated with a better response to growth hormone treatment. [ABSTRACT FROM AUTHOR]

Context. GnRHa treatment has been a standard of care in progressive early puberty (EP). Choice of the GnRHa formulation is dependent on the preference of the clinician. Objective. To compare the effects of triptorelin acetate (TA) and leuprolide acetate (LA) on anthropometry in girls with EP. Design. A descriptive observational study. Subjects and Methods. Girls diagnosed with central EP and treated with GnRHa at least for one year were included; treated with TA (n=46) and LA (n=35). First year anthropometric response and final height were evaluated. Results. The mean age at the initiation of GnRHa treatment of girls was 8.5±0.5 years. The ratio of obesity and of overweight was 7.4 and 25.9%, respectively. In both TA and LA groups, anthropometric data of the patients at initiation and at the first year of treatment were similar. Although growth velocity was similar in each group, in LA group height SDS at the first year of the treatment showed a significant decrease (p=0.045), but not in TA group (p=0.317). No significant ΔBMI was observed with treatment. The differences between FH -- PAH at initiation (height gain) in TA and LA groups were 2.9±4.7 and 4.0±5.8 cm, respectively (p=.316). Height gain per treatment year was 1.7±3.0 cm. Conclusions. There was a significant decrease in height SDS at the first year of leuprolid treatment, but not in triptorelin. Although these two analogs show similar effects on treatment, a not significant but slightly better benefit in leuprolide was observed. [ABSTRACT FROM AUTHOR]

Aim: To determine the effects of gonadotropin-releasing hormone analog treatment on final height and body mass index in girls with central precocious puberty. Material and Methods: All cases with diagnosis age <8 years constituted group 1 (n=19) and those with ≥8 years constituted group 2 (n=35). Results: There was no significant difference in height standard deviation score, body mass index standard deviation score, bone age/chronologic age, predicted final height at the time of diagnosis, and follow-up between group 1 and group 2. There was no significant difference in final height (standard deviation score) between the groups. The number of obese and overweight cases at diagnosis and final height was similar. The target height (standard deviation score), predicted final height (standard deviation score), and final height (standard deviation score) were similar in both Group 1 and Group 2. Conclusion: We found that between the ages of 6--9.8 years, girls with central precocious puberty who received gonadotropin-releasing hormone analog treatment reached a final height within their target height range. It is concluded that gonadotropin-releasing hormone analog treatment increases body mass index during treatment and when patients reach the final height, they return to their pretreatment body mass index. Younger age and greater height at the time of diagnosis are the positive factors on final height. [ABSTRACT FROM AUTHOR]

Objective: Adverse prenatal conditions can exert a long‐lasting impact on growth up to final height (FH). Due to different prenatal nutrient availability, monozygotic twin pairs with discordant birth weight (bw) provide an excellent model to examine the impact of genes and environment and to analyse the predictive value of bw, birth length (bl) and cord blood (cb) concentration of IGF‐I on FH. Patients and Methods: Twenty eight monozygotic twin pairs with intra‐twin bw‐/bl‐differences were studied at birth and longitudinally until FH. Intra‐twin bw difference >1 SDS was defined "discordant" (n = 10 pairs). IGF‐I was analysed in cord blood in all twins. Intra‐twin differences (∆) in bw, bl and cord blood IGF‐I were correlated with ∆FH. Results: Throughout growth and up until FH intra‐twin length/height differences remained for all but two (26/28) twins and for all (10/10) discordant twins. In the discordant group, a highly significant intra‐twin difference for FH‐SDS was found with a mean intra‐twin Δheight‐ SDS of 1.23 (range, 0.29‐2.34). This corresponds to a mean Δintra‐twin difference at FH of 7.9 cm (3.1 inch; range, 2‐15 cm [0.79‐5.9 inch]). Correlation coefficients were calculated to identify factors predicting FH: ∆bw (r =.678; P =.0005), ∆bl (r =.333; P =.0002) and ∆IGF‐I in cb (r =.418; P =.0023). Interaction terms showed that IGF‐I is an additional factor to the auxological data, leading to an improvement of the ∆FH modelling. Conclusion: Prenatal environment leading to bw‐/bl‐ and cbIGF‐I differences in monozygotic twins had a long‐lasting impact on growth until FH. Both, anthropometric data at birth and cbIGF‐I are predictive of FH. [ABSTRACT FROM AUTHOR]

Objective: The aim was to determine the final adult height (FAH) achieved by recombinant human growth hormone (rhGH) treatment, the factors affecting FAH and the success of attaining the genetic potential. Methods: Data of 133 patients treated with rhGH therapy were reviewed retrospectively. Patients were grouped according to diagnosis, either isolated GH deficiency (IGHD) or multiple pituitary hormone deficiency (MPHD), and by sex, and pubertal status at the beginning of treatment. Results: The mean age of initiation of treatment was 12.3±2.18 years, and the mean duration of rhGH treatment was 3.65±1.5 years. The mean height standard deviation score (SDS) at diagnosis was -3.11±0.75 SD. All patients received a standardized GH dose of 0.033 mg/kg/day. Mean FAH-SDS was -1.8±0.77 and delta height-SDS (the change in height SDS between the beginning and end of treatment) was 1.28±0.94 SD. FAH-SDS was -1.79±0.86 SD in males; -1.82±0.64 in females (p=0.857); -1.94±0.71 at the beginning of treatment in pubertal patients and -1.68±0.81 in prepubertal patients (p=0.056); -1.84±0.89 in patients with IGHD and -0.47±0.2 in patients with MPHD (p=0.05). In multiple regression analysis, First year delta height-SDS was the most predictive factor for both FAHSDS and delta height-SDS. Conclusion: The majority of our patients achieved a final height compatible with their genetic potential as well as population standards when treated with rhGH even having started at a relatively late age. First year delta height-SDS was a predictive factor for FAH. [ABSTRACT FROM AUTHOR]

Introduction: Loss-of-function mutation of MKRN3 represents the most frequent genetic cause of familial central precocious puberty (CPP). The outcomes of gonadotropin-releasing hormone analog (GnRHa) treatment in CPP patients with MKRN3 defects are unknown. Objective: To describe the clinical and hormonal features of patients with CPP with or without MKRN3 mutations after GnRHa treatment. Anthropometric, metabolic and reproductive parameters were evaluated. Patients and Methods: Twenty-nine female patients with CPP due to loss-of-function mutations in the MKRN3 and 43 female patients with idiopathic CPP were included. Their medical records were retrospectively evaluated for clinical, laboratory, and imaging study, before, during, and after GnRHa treatment. All patients with idiopathic CPP and 11 patients with CPP due to MKRN3 defects reached final height (FH). Results: At the diagnosis, there were no significant differences between clinical and laboratory features of patients with CPP with or without MKRN3 mutations. A high prevalence of overweight and obesity was observed in patients with CPP with or without MKRN3 mutations (47.3 and 50%, respectively), followed by a significant reduction after GnRHa treatment. No significant differences in the values of mean FH and target height were found between the 2 CPP groups after GnRHa treatment. Menarche occurred at the expected age in patients with or without CPP due to MKRN3 mutations (11.5 ± 1.3 and 12 ± 0.6 years, respectively). The prevalence of polycystic ovarian syndrome was 9.1% in patients with CPP due to MKRN3 mutations and 5.9% in those with idiopathic CPP. Conclusion: Anthropometric, metabolic, and reproductive outcomes after GnRHa treatment were comparable in CPP patients, with or without MKRN3 mutations, suggesting the absence of deleterious effects of MKRN3 defects in young female adults' life. [ABSTRACT FROM AUTHOR]

A retrospective evaluation of growth in 112 patients (68 males, 44 females) with Hb E (HBB: c.79G>A)/β-thalassemia (β-thal), classified as 88 transfusion-dependent thalassemia (TDT) and 24 non transfusion-dependent thalassemia (NTDT), is reported. Patients with TDT have received regular transfusions of red blood cells (RBCs) 15 mL/kg every 4 weeks to maintain pre transfusion hemoglobin (Hb) levels of at least 9.0 g/dL and were categorized according to age at initiation of regular RBC transfusion as subgroup 1, <4 years; subgroup 2, 4–10 years, and subgroup 3, >10 years. Iron chelation was initiated at the mean age of 7 years. The results revealed that patients in subgroups 1 and 2, receiving RBC transfusions at a young age (2.9 and 6.9 years, respectively), had normal prepubertal growth at enrollment and last follow-up. Patients in subgroup 3, with the lowest initial height Z-score of −2.10, were able to achieve comparable final adult height as those in subgroups 1 and 2. The mean final height of 21 males and 13 females with TDT at the ages of 18.9 and 18.7 years was 168.1 and 157.7 cm, respectively, which did not significantly differ from their midparental height and those with NTDT. Early initiation of optimal transfusion and iron chelation promoted normal prepubertal growth. However, delayed initiation of transfusion at age 12 years impaired prepubertal growth but they could achieve normal final adult height. [ABSTRACT FROM AUTHOR]

Aim: We analysed near final height (NFH) data in children with growth hormone deficiency (GHD) treated with recombinant human GH (rhGH).Methods: We divided the idiopathic GHD patients into two groups, isolated GHD (IGHD) and multiple pituitary hormone deficiency, to evaluate NFH. Then, data were grouped according to gender, pre-pubertal/pubertal status and spontaneous or induced puberty. The trial was performed as a retrospective study. Median values are given, and measurements are expressed as standard deviation scores (SDSs).Results: rhGH therapy was started at a median age of 12.1 (range 9.1-14.9) years in the IGHD group (n = 162, 83 males) and 9.1 (range 4.9-13.4) years in the multiple pituitary hormone deficiency group (n = 33, 22 males) at a median dose of 0.20 mg/kg/week. Height SDSs at the onset of therapy were -3.2 (range -4.4 to -2.6) and -3.9 (-6.8 to -2.8) in the two groups, respectively (P < 0.001). NFH SDSs were -1.8 (-2.9 to -1) and -1.6 (-3.1 to -0.4) (P = 0.139), and delta height SDSs (finish - start) were 1.4 (0.3-2.5) and 2.6 (1.5-4.6) (P < 0.001), respectively. Total delta height was 1.4 SDS (0.4-3.1) in patients who started rhGH treatment in the pre-pubertal period and 1.3 SDS (0.3-2.4) (P = 0.106) in those who started rhGH in the pubertal period.Conclusions: About 85% of the cases reached their genetic height potential. Delta height SDSs were higher than expected in cases that started treatment during the pubertal period. Therefore, it is possible to achieve NFH within the mid-parental height range in patients who start therapy during puberty. [ABSTRACT FROM AUTHOR]

Background/Aims: To describe characteristics, auxological outcomes and safety in paediatric patients with growth disorders treated with growth hormone (GH), for cohorts from the USA, Germany and France enrolled in GeNeSIS, a post-authorisation surveillance programme. Methods: Diagnosis and biochemical measurement data were based on reporting from, and GH treatment was initiated at the discretion of, treating physicians. Auxological outcomes during the first 4 years of GH treatment and at near-adult height (NAH) were analysed. Serious and treatment-emergent adverse events were described. Results: Children in the USA (n = 9,810), Germany (n = 2,682) and France (n = 1,667) received GH (dose varied between countries), most commonly for GH deficiency. Across diagnostic groups and countries, mean height velocity standard deviation score (SDS) was > 0 and height SDS increased from baseline during the first 4 years of treatment, with greatest improvements during year 1. Most children achieved NAH within the normal range (height SDS >−2). No new or unexpected safety concerns were noted. Conclusion: GH treatment improved growth indices to a similar extent for patients in all three countries despite variations in GH doses. Data from these three countries, which together contributed > 60% of patients to GeNeSIS, indicated no new safety signals and the benefit-risk profile of GH remains unchanged. [ABSTRACT FROM AUTHOR]

Purpose: Congenital hypothyroidism (CH) is the most common endocrine disorder in children. Thyroid hormone deprivation results not only in mental retardation but also growth retardation. This study investigates the final height (FH) in Korean patients with CH detected by newborn screening and examines factors that may affect the FH. Methods: The medical records of Korean CH patients (n=45) were reviewed. The FH was examined and target height (TH) was calculated based on mid-parental height. The FH z score (FHZ) and TH z score (THZ) were computed using the 2007 Korean National Growth Chart. The FHZ and THZ were compared with a Student t test. The impact of the etiology of CH (athyreosis, dyshormonogenesis, ectopic thyoid, hypoplastic thyroid), initial serum thyroid stimulating hormone (TSH) level, initial free thyroxine (T4) level, and time of therapy initiation based on FH was assessed. Results: The mean FHZ was 0.10±1.01 for male patients and -0.11±1.09 for female patients. There were no significant differences between FHZ and THZ for both female (P=0.356) and male patients (P=0.237). No significant relationship was found between FH and the etiology of CH, initial TSH level, initial free T4 level, and the time of therapy initiation. Conclusion: Early intervention and satisfactory management do not appear to impede growth in Korean patients with CH. Thus, early detection and proper management of patients with CH detected by newborn screening program are necessary. [ABSTRACT FROM AUTHOR]

Aim: This study investigated whether substantial body mass index (BMI) reductions in Swedish schoolchildren aged seven years to 19 years, caused by disease, healthy or unhealthy behaviour, had any impact on their final height.Methods: We used height and weight data on 6572 subjects from two nationally representative longitudinal samples of Swedish children born in 1973 and 1981. These provided information on their final height and any BMI reduction episodes.Results: Of the 6572 subjects (50.9% boys), among individuals with information on final height, 1118 had a BMI reduction of 5% and <10%, and 346 had at least one substantial BMI reduction of 10% or more. On a group level, there was no statistically significant difference in the final height of individuals with BMI reductions of 10% or more and those without. The findings were independent of age and the subject's BMI at the start of the reduction episode. However, there were a number of cases where a substantial BMI reduction probably had an impact on the subject's final height.Conclusion: Our study found no evidence that a substantial BMI reduction had any impact on final height on a group level, but further analyses of specific case studies are necessary to determine whether substantial BMI reduction might have an impact on final height. [ABSTRACT FROM AUTHOR]

Background: Linear growth was reported to be negatively affected by type 1 diabetes mellitus (T1DM), in relation to disease duration and poor metabolic control. It is unclear whether a subtle growth failure still persists despite the optimization of therapy. Our aim was to analyse pubertal growth, adult height, and metabolic profile in a cohort of children with T1DM undergoing intensive insulin treatment by multiple daily injections or continuous subcutaneous insulin infusion (CSII). Methods: One-hundred and four children (51 males) with prepubertal onset of T1DM were prospectively followed up to final height attainment. Results: Age at puberty onset was 11.7 ± 1.1 years in males and 10.9 ± 1.3 in females. Age at adult height attainment was 16.4 ± 1.6 years in males and 14.1 ± 1.8 years in females. Pubertal height gain was 24.4 ± 4.9 cm in males and 19.0 ± 3.8 cm in females. HbA1c, HDL cholesterol, and triglyceride levels increased during puberty. HDL cholesterol levels were higher in patients treated with CSII. Height standard deviation score (SDS) at diagnosis (0.52 ± 1.04) was higher than target height SDS (0.01 ± 1.07), but declined afterwards, and both height SDS at puberty onset (0.22 ± 1.1) and adult height SDS (–0.1 ± 1.02) were not significantly different from target height SDS. BMI SDS showed a positive trend from diagnosis to puberty onset and stabilized later (–0.04 ± 1.4 at T1DM onset, 0.55 ± 2.1 at puberty onset, and 0.53 ± 2.1 at adult height attainment). Conclusions: Although subtle abnormalities of growth still persist, the modern advancements of insulin therapy are able to normalize puberty and final height of children with T1DM. [ABSTRACT FROM AUTHOR]

Background: Hypothalamic hamartoma (HH) represents the commonest cause of organic central precocious puberty (CPP). Follow-up of these patients in adulthood is scarce. Objective: To describe the anthropometric, metabolic, and reproductive parameters of patients with CPP due to HH before and after treatment with gonadotropin-releasing hormone analog (GnRHa). Methods: We performed a retrospective and cross-sectional study in a single tertiary center including 14 patients (7 females) with CPP due to HH. Results: The mean duration of GnRHa treatment was 7.7 ± 2.4 years in boys and 7.9 ± 2.1 years in girls. GnRHa treatment was interrupted at the mean chronological age (CA) of 12.1 ± 1.1 years in boys and 10.7 ± 0.5 years in girls. At the last visit, the mean CA of the male and female patients was 21.5 ± 3.2 and 24 ± 3.9 years, respectively. Eleven of the 14 patients reached normal final height (FH) (standard deviation score -0.6 ± 0.9 for males and -0.6 ± 0.5 for females), all of them within the target height (TH) range. The remaining 3 patients had predicted height within the TH range. The mean body mass index and the percentage of body fat mass was significantly higher in females, with a higher prevalence of metabolic disorders. All patients presented normal gonadal function in adulthood, and 3 males fathered a child. Conclusion: All patients with CPP due to HH reached normal FH or near-FH. A higher prevalence of overweight/obesity and hypercholesterolemia was observed in the female patients. Finally, no reproductive disorder was identified in both sexes, indicating that HH per se has no deleterious effect on the gonadotropic axis in adulthood. [ABSTRACT FROM AUTHOR]

Purpose: Predicted adult height (PAH) is often crucial to decision-making about treatment with human growth hormone (GH) or gonadotropin-releasing hormone agonist in children with short stature. This study compares final adult height (FAH) with different methods used to determine PAH and assesses the clinical utility and analytical validity of height prediction for children not treated with GH. Methods: Clinical findings were retrospectively analyzed, and the heights of 44 children (22 males and 22 females) who visited our clinic between August 2006 and June 2017 and reached near final adult height (NFAH) were evaluated. Children treated with GH were excluded. We compared measured NFAH to PAH using the Bayley-Pinneau (BP), Tanner-Whitehouse Mark 2, and Roche-Wainer-Thissen (RWT) methods. Results: Pearson correlation between all 3 prediction methods and NFAH showed high positive correlations in males and females (P<0.05). The average difference between PAH and NFAH for the BP method (0.4±3.9 cm) was significantly lower than those for the RWT and TW 2 methods in females (P=0.000, analysis of variance). Furthermore, only PAH by the BP method in females was very close to measured NFAH (paired t-test). A Bland-Altman plot verified that 95% of the differences between the PAH and NFAH exist between limits of agreement (mean±1.96 standard deviation). Conclusion: The BP method is more useful to predict NFAH in females than other methods. Careful attention is still required when using such tools because PAH can be inaccurate. Therefore, a more accurate FAH prediction model for Korean children is needed. [ABSTRACT FROM AUTHOR]

Introduction: Patients with low stature normal variant growth have peculiar evolutionary patterns making it difficult to precisely define when final stature will be reached, since prediction methods are based on parameters of difficult quantification, such as bone age. Objective: To assess the agreement between two methods for prediction of final height based on family target range regarding the final height reached by adolescents with a diagnosis of normal variant short stature. Methods: Thirty-three subjects were evaluated using height of parents for the calculation of family target range and Bayley-Pinneau and Tanner-Whitehouse methods for prediction of final height. Spearman correlation coefficient was calculated to correlate final height with the mean of the family target range, and the St. Laurent concordance coefficient was used to assess concordance between final stature and predictive methods. Results: 87.9% (29/33) subjects kept short stature at the end of growth and 90.9% (30/33) had a final height within family target range. A very strong positive correlation (Cs = 0.77; p < 0.01) was observed between parental mean and final height. Bayley-Pinneau method showed a 0.47 concordance coefficient with final height (95% CI: 0.34; 0.57), and Tanner-Whitehouse 3 method showed a concordance coefficient of 0.58 (95% CI: 0.41; 0.75). Conclusion: The strong positive correlation observed demonstrates the significant influence of parental height on final height. Neither method showed good concordance when used as a predictor of final height, with height values being overestimated. [ABSTRACT FROM AUTHOR]

Introduction: Patients with low stature normal variant growth have peculiar evolutionary patterns making it difficult to precisely define when final stature will be reached, since prediction methods are based on parameters of difficult quantification, such as bone age. Objective: To assess the agreement between two methods for prediction of final height based on family target range regarding the final height reached by adolescents with a diagnosis of normal variant short stature. Methods: Thirty-three subjects were evaluated using height of parents for the calculation of family target range and Bayley- Pinneau and Tanner-Whitehouse methods for prediction of final height. Spearman correlation coefficient was calculated to correlate final height with the mean of the family target range, and the St. Laurent concordance coefficient was used to assess concordance between final stature and predictive methods. Results: 87.9% (29/33) subjects kept short stature at the end of growth and 90.9% (30/33) had a final height within family target range. A very strong positive correlation (Cs = 0.77; p < 0.01) was observed between parental mean and final height. Bayley-Pinneau method showed a 0.47 concordance coefficient with final height (95% CI: 0.34; 0.57), and Tanner-Whitehouse 3 method showed a concordance coefficient of 0.58 (95% CI: 0.41; 0.75). Conclusion: The strong positive correlation observed demonstrates the significant influence of parental height on final height. Neither method showed good concordance when used as a predictor of final height, with height values being overestimated. [ABSTRACT FROM AUTHOR]

The GnRH-A therapy is the treatment of choice for CPP, with the main objective to increase height potential, which is compromised by the premature fusion of growth cartillages. We assessed in a retrospective longitudinal unicenter study the impact of treatment with GnRH-A on growth velocity, SDSh, SDS ba, the final height and eventual adverse effects in 18 girls with idiopathic CPP. We follow-up in a long-term study, from 1992 until 2003, 16 girls with CPP, treated by Decapeptyl-Depot or Diferilin Depot, in dose of 3,75 mg every 28 days. Duration of treatment was from 1y 11mo to 8y 8mo. The middle age of onset of PP was 3,17, the age of diagnosis - 3,78 and the age of therapy 6,25. The diagnosis was based on clinical and paraclinical parameters like the degree of thelarche and pubarche, SDSh, SDSba, growth velocity (which were rapidly progressing), the positive LH-RH test.The results of the treatment were good. The accelerated growth velocity decreased as well as SDSh an SDSba, degree of thelarche and pubarche fall dawn.There was positive correlation between SDSh at the onset of therapy and the height in the end of observation, which was about 10 cm bellow the midparental height. At the end of observation and after cessation of the treatment, gradually the pubertal symptoms developed again. After cessation of the therapy, menses appeared in an interval of 10 mo to 2 yrs. The GnRH-A treatment appears to improve height potential, especially when PP is diagnosed and the therapy begins before the age of 6 and SDSh is not very high.The growth outcomes and the real final height, after pubertal growth spurt, would be better [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the gain in final height of achondroplasia (ACH) patients with long-term growth hormone (GH) treatment. We analyzed medical data of 22 adult patients (8 males and 14 females) treated with GH at a dose of 0.05 mg/kg/day. Optionally, tibial lengthening (TL) was performed with the Ilizalov method in 15 patients and TL as well as femoral lengthening (FL) in 6 patients. Concomitant gonadal suppression therapy with buserelin acetate was applied in 13 patients. The mean treatment periods with GH were 10.7 ± 4.0 and 9.3 ± 2.5 years for males and females, respectively. GH treatment augmented the final height +0.60 ± 0.52 SD (+3.5 cm) and +0.51 ± 1.29 SD (+2.8 cm) in males and females compared to non-treated ACH patients, respectively. Final height of ACH patients that underwent GH and TL increased +1.72 ± 0.72 SD (+10.0 cm) and +1.95 ± 1.34 SD (+9.8 cm) in males and females, respectively. GH, TL, and FL increased their final height +2.97 SD (+17.2 cm) and +3.41 ± 1.63 SD (+17.3 cm) in males and females, respectively. Gonadal suppression therapy had no impact on final height.Conclusions: Long-term GH treatment contributes to 2.6 and 2.1% of final adult height in male and female ACH patients, respectively. [ABSTRACT FROM AUTHOR]

Introduction. The diagnosis of growth hormone (GH) deficiency is based on the results of GH stimulation tests. Growth hormone therapy in children with normal GH secretion is a matter of discussion. Recently, GH deficiency has been defined as a secondary insulin-like growth factor-I (IGF-I) deficiency. Objective. The aim of the study was to assess GH therapy efficacy in short children with respect to GH peak in stimulation tests and IGF-I secretion before treatment. Material and methods. The retrospective analysis comprised 182 children with partial GH deficiency (GH peak in stimulation tests 5-10 ng/ml), qualified to pGHD Group, and 75 children with normal GH peak in stimulation tests (>10 ng/ml), qualified to normGH Group. According to IGF-I secretion, expressed as IGF-I SDS for age and sex, the patients were qualified to the following subgroups: pGHD-1 and normGH-1 - IGF-I SDS <-2.0; pGHD-2 and normGH-2 - IGF-I SDS between -2.0 and -1.0; pGHD-3 and normGH-3 - IGF-I SDS =-1.0. The increase of the final height SDS with respect to the height SDS before treatment (DHSDS) was calculated as the main index of the GH therapy effectiveness. Results. The best DHSDS was in pGHD-1 (1.65±0.89) and normGH-1 (1.86±0.93), the worse in normGH-3 (0.99±0.71), with insignificant differences between pGHD-1 and normGH-1, pGHD-2 and normGH-2, as well as pGHD-3 and normGH-3. Conclusions. The effectiveness of the GH therapy was the best in the patients with the most severe IGF-I deficiency but almost independent from either decreased or normal GH secretion in stimulation tests before treatment. [ABSTRACT FROM AUTHOR]

This review focuses on the evidence for the efficacy and safety of recombinant human growth hormone (rhGH) therapy in children with all stages of chronic kidney disease (CKD) and at all ages. It describes the improving height prognosis for our patients both with and without rhGH; explains the underlying hormonal abnormalities that provide the rationale for rhGH use in CKD and the endocrine changes that accompany treatment; and views on who warrants treatment, with what dose, and how long for. [ABSTRACT FROM AUTHOR]

Introduction. The diagnosis of growth hormone (GH) deficiency is based on the results of GH stimulation tests. Growth hormone therapy in children with normal GH secretion is a matter of discussion. Recently, GH deficiency has been defined as a secondary insulin-like growth factor-I (IGF-I) deficiency. Objective. The aim of the study was to assess GH therapy efficacy in short children with respect to GH peak in stimulation tests and IGF-I secretion before treatment. Material and methods. The retrospective analysis comprised 182 children with partial GH deficiency (GH peak in stimulation tests 5-10 ng/ ml), qualified to pGHD Group, and 75 children with normal GH peak in stimulation tests (>10 ng/ml), qualified to normGH Group. According to IGF-I secretion, expressed as IGF-I SDS for age and sex, the patients were qualified to the following subgroups: pGHD-1 and normGH-1 - IGF-I SDS <-2.0; pGHD-2 and normGH-2 - IGF-I SDS between -2.0 and -1.0; pGHD-3 and normGH-3 - IGF-I SDS ≥-1.0. The increase of the final height SDS with respect to the height SDS before treatment (DHSDS) was calculated as the main index of the GH therapy effectiveness. Results. The best DHSDS was in pGHD-1 (1.65±0.89) and normGH-1 (1.86±0.93), the worse in normGH-3 (0.99±0.71), with insignificant differences between pGHD-1 and normGH-1, pGHD-2 and normGH-2, as well as pGHD-3 and normGH-3. Conclusions. The effectiveness of the GH therapy was the best in the patients with the most severe IGF-I deficiency but almost independent from either decreased or normal GH secretion in stimulation tests before treatment. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of treatment with gonadotropin-releasing hormone analog (GnRHa) on final height in girls who experienced moderately early puberty with symptoms beginning at 7-8.5 years of age. Methods: Female cases diagnosed with moderately early puberty which had started between ages 7 to 8.5 years were included in the study. In the treatment groups, all cases with a bone age ≤10.5 years constituted group 1 (n=18) and those with a bone age >10.5 years constituted group 2 (n=23). The 8 patients for which treatment approval could not be obtained constituted group 3. The 49 cases in all three groups were observed until they reached their final height. Results: Target height, target height standard deviation score (SDS), final height, and final height SDS values were similar in all 3 groups. Final height showed a significant positive correlation with target height (p=0.000, r=0.54) and height at diagnosis (p=0.003, r=0.467) in all groups. Linear regression analysis revealed that a 1 cm longer height at diagnosis increased the final height 0.213 fold, and a 1 cm longer target height at diagnosis increased the final height 0.459 fold. Conclusion: We found that GnRHa did not make a positive contribution to final height in cases of moderately early puberty. [ABSTRACT FROM AUTHOR]

Background: Growth hormone (GH) has a strong positive influence on bone, stimulating both bone elongation and increase in size. The aim of the study was to compare the effect of two different GH dosages on final height and bone geometry in two groups of GH-deficient children. Methods: We evaluated 121 children (86 m, 35f). Group 1 (77 patients) treated with GH at a mean dose of 0.16 mg/kg/week and group 2 (44 patients) at 0.3 mg/kg/week. Bone geometry was evaluated at final height from a digitalized X-ray of the left hand considering the following parameters: metacarpal index (MI), cross-sectional area (CSA), cortical area (CA) and medullary area (MA). Results: At baseline, group 2 was shorter than group 1 (-1.54 vs -1.01 SDS; p < 0.005), while at final height there was no difference. Height gain was significantly greater in group 2 than in group 1 (1.62 vs 1.13 SDS; p < 0.001). Bone geometry: MI was significantly greater in group 2 (0.62 vs 0.55; p < 0.001) as well as CA (46.87 vs 42.69 cm²; p < 0.005), while MA was significantly lower in group 2 (8.48 vs 11.65 cm²; p < 0.002). Conclusion: Higher GH doses elicit a significantly greater statural gain and a greater bone cortical area. [ABSTRACT FROM AUTHOR]

Objective: Idiopathic short stature (ISS) constitutes a heterogeneous group of short stature which is not associated with an endocrine or other identifiable cause. Some ISS patients may have varying degrees of insulin-like growth factor-1 (IGF-1) deficiency. Recombinant growth hormone (rGH) treatment has been used by some authors with variable results. Reports on long-term rGH treatment are limited. Methods: In this study, 21 slowly growing, non-GH-deficient ISS children who received rGH treatment for 3.62±0.92 years were evaluated at the end of a 5.42±1.67-year follow-up period. The study group included patients with low IGF-1 levels who also responded well to an IGF generation test. The patients were divided into two groups as good responders [height increment >1 standard deviation (SD)] and poor responders (height increment <1 SD) at the end of the follow-up period. Results: The height of the patients improved from -3.16±0.46 SD score (SDS) to -1.9±0.66 SDS. At the end of the follow-up period, mean height SDS was -1.72. Eleven of the patients showed a good response to treatment. Clinical parameters were essentially similar in the good responders and the poor responders groups. A female preponderance was noted in the good responders group. Conclusion: rGH treatment can safely be used in ISS children. Long-term GH treatment will ameliorate the height deficit and almost 40% of patients may reach their target height. [ABSTRACT FROM AUTHOR]

Background: Linear growth and final height are reported as normal in congenital hypothyroid patients in the neonatal screening era. Methods: We evaluated the final height in 215 patients with congenital hypothyroidism to assess if it improved over the last 2 decades. Results: Final height (-0.1 ± 1.0 SDS) was higher than target height (-0.8 ± 1.0 SDS, p < 0.001) and not different among the 4 quartiles for birthdate. It was correlated with target height (r² = 0.564, p < 0.001) and height at puberty onset (r² = 0.685, p < 0.001), but not with age at diagnosis or the starting LT4/kg/day dose. The curve fitting analysis showed that the age at diagnosis progressively decreased during the 20-year study period, while the target height and the starting LT4/kg/day increased. Final height was not affected by the birthdate, the age at diagnosis, the starting LT4 dose. Conclusions: The final height is higher than the target height, but despite the improvement in the screening and the treatment, it did not improve over the last 20 years. These findings are in keeping with the described secular trend and suggest that earlier diagnosis and replacement therapy do not significantly modify final height in these patients. [ABSTRACT FROM AUTHOR]

Objective: Growth hormone (GH) deficiency (GHD) has recently been classified as secondary IGF-I deficiency but the significance of IGF-I measurement in diagnosing GHD is still discussed. The aim of the study was to assess the relationships between IGF-I secretion and GH therapy effectiveness in children with GHD. Patients and methods: The analysis comprised 300 children with isolated, non-acquired GHD (GH peak below 10 μg/l) who completed GH therapy and attained final height (FH). In all patients IGF-I concentration was measured before the treatment and IGF-I deficiency was diagnosed if IGF-I SDS for age and sex was below − 1.0. The following auxological indices were assessed: patients' height SDS before treatment (H0SDS), FH SDS and improvement of FHSDS vs. H0SDS (ΔHSDS). Results: In the patients with IGF-I deficiency when compared with those with normal IGF-I secretion before treatment, significantly better FH SDS ( − 1.42 ± 0.90 vs. − 1.74 ± 0.86, p = 0.004) and ΔHSDS (1.64 ± 1.01 vs. 1.32 ± 1.05, p = 0.010) were observed, despite similar H0SDS (− 3.07 ± 0.78 vs. − 3.11 ± 0.77, p = 0.63) and GH peak (7.0 ± 3.1 μg/l vs. 6.8 ± 2.1 μg/l, p = 0.55). The patients who achieved FH over 10th centile had significantly lower IGF-I SDS before treatment than those with FH below 10th centile (− 1.59 ± 1.54 vs. − 1.20 ± 1.64, p = 0.04), despite similar GH peak (7.0 ± 2.3 μg/l vs. 6.7 ± 3.1 μg/l, p = 0.45). The patients with ΔHSDS over the median value had significantly lower IGF-I SDS than those with ΔHSDS below the median value (− 1.59 ± 1.71 vs. − 1.09 ± 1.47, p < 0.0001), despite similar GH peak (6.8 ± 2.5 μg/l vs. 7.0 ± 2.7 μg/l, p = 0.86). Conclusion: In children with isolated, nonacquired GHD, secondary IGF-I deficiency is an important predictor of better GH therapy effectiveness. [ABSTRACT FROM AUTHOR]

Objective- To evaluate the efficiency of recombinant growth hormone for increasing adult height in children treated for idiopathic growth hormone deficiency and to evaluate the prognostic factor for height at the end of treatment. Design- Observational follow up study. Setting- Population based registry. Participants- All Albanian children diagnosed with idiopathic growth hormone deficiency who had attained final height. Their treatment started between 2001 and 2011. Main outcome measures- Annual changes in height, and change in height between the start of treatment and adulthood; the importance of the factors that influence on final height. Results- Adult height was obtained for 83 (55%) patients. The mean dose of growth hormone at start of treatment was 0.21 IU/kg/week for 29 patients and 0.24 IU/week for 54 patients. Height gain was 2.41±1.19 z-scores, resulting in an adult height of - 1.98±1.12 z-score (girls, -2.05±1.27 z-score; boys, -1.95±1.20 z-score). Patients who completed the treatment gained 2.40±1.13 z-score of height in 4.0±2.0 years. Most of the variation in height gain was explained by regression towards the mean, patients' characteristics, and delay in starting puberty. Conclusion- Nearly all our patients with idiopathic growth hormone deficiency treated with growth hormone were able to achieve their genetic height potential. Despite starting treatment late, they managed to gain 2.40±1.13 HAZ score in height and the final height for majority of them (61.5%) was within the target height range. It was found that the final height had good correlation with the prediction height, HAZ score at beginning of treatment, change of HAZ score during the puberty, duration of treatment with GH, and pubertal stage at the start of therapy. [ABSTRACT FROM AUTHOR]

Growth hormone (GH) deficiency (GHD) is currently defined as secondary IGF-I deficiency. In the patients with normal GH secretion, significant increase of IGF-I during generation test excludes primary IGF-I deficiency, however is not an approved indication for GH therapy. The aim of the study was to assess GH therapy effectiveness in children with IGF-I deficiency which turned to be out non-primary, despite normal GH secretion. Patients and methods. Analysis comprised 42 patients with spontaneous (after falling asleep) and stimulated GH peak >10.0 ng/ml, and IGF-ISDS for age and sex <-1.0, in whom IGF-I concentrations increased significantly during generation test, suggesting that IGF-I deficiency is non-primary (npIGFD Group). All patients were subjected to GH therapy. First-year response to treatment: height velocity (HV) increase and IGF-I SDS increase were assessed in all of them, final height (FH) - in 28 patients. The therapy efficacy was compared with 110 children with isolated, partial GHD (pGHD Group), including 42 treated up to FH. Results. In npIGFD Group, height SDS before treatment (H0SDS) was -2.87±0.72, in 1st year of treatment HV increased from 3.8±0.9 to 9.4±1.9 cm/year, IGF-I SDS increased from -2.19±0.78 to 0.34±1.07, FHSDS was -1.14±0.82. In pGHD Group, H0SDS was -2,79±0.59, HV increased from 3.8±1.4 to 9.8±2.1 cm/year, IGF-ISDS increased from -1.76±0.88 to 0.52±0.87, FH SDS was -1.20±0.80. The differences in all the analysed indices of GH therapy effectiveness between the Groups were insignificant. Conclusions. Children with short stature, normal spontaneous and stimulated GH secretion and non-primary IGF-I deficiency may benefit during GH therapy similarly to children with partial GHD. It seems worth considering not diagnose idiopathic short stature in such patients. [ABSTRACT FROM AUTHOR]

There has been no consensus regarding the efficacy and safety of oxandrolone (Ox) in addition to growth hormone (GH) in girls with Turner syndrome (TS), the optimal age of starting this treatment, or the optimal dose. This collaborative venture between Dutch, UK and US centers is intended to give a summary of the data from three recently published randomized, placebo-controlled, double-blind studies on the effects of Ox. The published papers from these studies were reviewed within the group of authors to reach consensus about the recommendations. The addition of Ox to GH treatment leads to an increase in adult height, on average 2.3-4.6 cm. If Ox dosages <0.06 mg/kg/day are used, side effects are modest. The most relevant safety concerns are virilization (including clitoromegaly and voice deepening) and a transient delay of breast development. We advise monitoring signs of virilization breast development and possibly blood lipids during Ox treatment, in addition to regular follow-up assessments for TS. In girls with TS who are severely short for age, in whom very short adult stature is anticipated, or in whom the growth rate is modest despite good compliance with GH, adjunctive treatment with Ox at a dosage of 0.03-0.05 mg/kg/day starting from the age of 8-10 years onwards can be considered. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: Medulloblastoma is a highly malignant childhood brain tumor. Survival from medulloblastoma is increasing. This study was performed to examine growth outcomes, insulin-like growth factor-1(IGF-1), and response to growth hormone (GH) treatment in children with medulloblastoma. Methods: Retrospective analysis of 34 children treated with GH for medulloblastoma was performed. We evaluated serum IGF-1 and insulin-like growth factor binding protein-3 concentrations. Further, we examined growth status and changes with GH treatment according to treatment modality. Results: GH deficiency was observed in 28 patients (82 %). The initial height at the start of GH treatment was −2.35 ± −1.53 standard deviation score (SDS) and increased to −1.85 ± −1.28 SDS by 1 year, −1.64 ± −1.46 SDS by 2 years, and −1.42 ± −1.49 SDS by 3 years after GH treatment. The final height was −1.54 ± −1.06 SDS. Gender, surgical method, tumor location, tumor size, and type of radiation did not correlate with height gain. A younger age at the initiation of GH treatment correlated with height gain. The initial serum IGF-1 concentration was −1.73 ± −0.42 and increased significantly to −0.74 ± −0.21 SDS by 1 year after GH treatment. The serum IGF-1 SDS increment correlated significantly with height gain. Conclusions: Beginning GH treatment at a younger age was an important prognostic factor for growth outcome. Serum IGF-1 increment correlated with height gain during GH treatment. Thus, early GH treatment and analysis of serum IGF-1 might be helpful for improving final height or growth outcome. [ABSTRACT FROM AUTHOR]

Congenital adrenal hyperplasia (CAH) describes a group of autosomal recessive disorders where there is impairment of cortisol biosynthesis. CAH due to 21-hydroxylase deficiency accounts for 95% of cases and shows a wide range of clinical severity. Glucocorticoid and mineralocorticoid replacement therapies are the mainstays of treatment of CAH. The optimal treatment for adults with CAH continues to be a challenge. Important long-term health issues for adults with CAH affect both men and women. These issues may either be due to the disease or to steroid treatment and may affect final height, fertility, cardiometabolic risk, bone metabolism, neuro-cognitive development and the quality-of-life. Patients with CAH should be regularly followed-up from childhood to adulthood by multidisciplinary teams who have knowledge of CAH. Optimal replacement therapy, close clinical and laboratory monitoring, early life-style interventions, early and regular fertility assessment and continuous psychological management are needed to improve outcome. [ABSTRACT FROM AUTHOR]

Background Our study aimed to evaluate final height in a cohort of Dutch childhood cancer survivors (CCS) and assess possible determinants of final height, including height at diagnosis. Patients and methods We calculated standard deviation scores (SDS) for height at initial cancer diagnosis and height in adulthood in a cohort of 573 CCS. Multivariable regression analyses were carried out to estimate the influence of different determinants on height SDS at follow-up. Results Overall, survivors had a normal height SDS at cancer diagnosis. However, at follow-up in adulthood, 8.9% had a height ≤−2 SDS. Height SDS at diagnosis was an important determinant for adult height SDS. Children treated with (higher doses of) radiotherapy showed significantly reduced final height SDS. Survivors treated with total body irradiation (TBI) and craniospinal radiation had the greatest loss in height (−1.56 and −1.37 SDS, respectively). Younger age at diagnosis contributed negatively to final height. Conclusion Height at diagnosis was an important determinant for height SDS at follow-up. Survivors treated with TBI, cranial and craniospinal irradiation should be monitored periodically for adequate linear growth, to enable treatment on time if necessary. For correct interpretation of treatment-related late effects studies in CCS, pre-treatment data should always be included. [ABSTRACT FROM PUBLISHER]

Background: Growth retardation is a considerable clinical problem in children with chronic kidney disease (CKD). Optimization of metabolic and nutritional parameters does not always lead to improved growth. Recombinant human growth hormone (rhGH) treatment has been used to improve height. Several studies in the literature have shown increased growth velocity, although data on the final height (FH) reached are scarce. Aims: We assessed the effect of rhGH on FH standard deviation score (SDS) in children with CKD following renal transplantation (RTx), comparing it with patients who did not receive rhGH (control group) but were treated with the same protocol and followed up in a single Center. Methods: Thirty-three patients received rhGH treatment until FH. Fourteen who refused rhGH therapy were included in the controls. Prognostic factors for FH and changes in glomerular filtration rate (GFR) during follow-up were also analyzed Results: FH SDS in rhGH-treated patients was significantly higher than in controls (−1.88 ± 1.14 vs −3.48 ± 1.19 SDS, respectively, p <0.05). In both groups, a similar reduction in GFR was observed. Height (SDS) at onset of rhGH treatment was the only statistically significant variable useful to predict response to treatment ( p = 0.001). Conclusion: Our findings confirm that rhGH is effective to improve FH in CKD RTx patients, without affecting kidney function. [ABSTRACT FROM AUTHOR]

Impaired linear growth has been reported in patients treated during childhood with allogeneic stem cell transplantation and fractionated total body irradiation (fTBI). The objective of this study was to determine the final height and body mass index (BMI) achieved. Forty-nine patients with leukemia were included and surveyed for more than 5 years. Median age at follow-up was 24.3 years (range, 18.9-35.8) and median follow-up time from allograft was 14.4 years (range, 4.5-21.9). Mean height standard deviation score (s.d.s.) at final examination (−1.1 ± 1.3,) was significantly lower than at fTBI (0.3 ± 1.2; P = .001). Final height s.d.s. was significantly correlated with age at diagnosis, age at fTBI, and target height ( P = .001; P < .001; P < .001, respectively). Final height was significantly lower in children transplanted before age 5 ( P = .006). Growth hormone treatment ( n = 6) had only a modest effect on growth velocity. Mean BMI at follow-up was normal at 19.6 kg/m2 for boys and 21.2 for girls, but with a significant decrease since allograft only for boys (−1.2 ± 1.5 s.d.s.) ( P = .003). In conclusion, final height is decreased; BMI is normal but decreased from fTBI in boys. [ABSTRACT FROM AUTHOR]