Achievement Of Adult Height Research Articles

Accuracy of Glucagon Testing Across Transition in Young Adults with Childhood-Onset Growth Hormone Deficiency.

The 2019 AACE guidelines suggested peak GH-cutoffs to glucagon test (GST) of ≤3 µg/L and ≤1 µg/L in the diagnosis of permanent GH deficiency (GHD) during the transition phase. Aim of the study was to evaluate the accuracy of GST compared to insulin tolerance test (ITT) in the definition of GHD at adult height achievement. Ninety-seven subjects with childhood-onset GHD (median age, 17.39 years) underwent ITT, GST and IGF-1 testing; 44 subjects were idiopathic (isolated GHD), 35 moderate organic GHD (0-2 hormone deficiencies-HDs) and 18 severe organic GHD (≥3 HDs). Bland and Altman analysis showed a high consistency of GH peak measures after ITT and GST. Receiver operating characteristic analysis-ROC- identified 7.3 μg/L as the optimal GH peak cutoff to GST (95% CI 4.15-8.91; sensitivity 95.7%, specificity 88.2%, positive predictive value-PPV-88.0%, negative predictive value-NPV-95.7%), able to correctly classify 91.8% of the entire cohort while 5.8 μg/L was the best GH peak cutoff able to correctly classify 91.4% of moderate organic GHD patients (95% CI 3.16-7.39; sensitivity 96.0%, specificity 80.0%, PPV 92.3%, NPV 88.9%). Patients with ≥3HDs showed a GH peak <5μg/L at ITT and <5.8μg/L at GST but one. The optimal cutoff for IGF1 was -1.4 SDS (95% CI -1.94-0.77; sensitivity 75%, specificity 94%, PPV 91.7%, NPV 81.0%) that correctly classified 85.1% of the study population. A GH peak to GST <5.8 μg/L represents an accurate diagnostic cutoff for young adults with childhood-onset GHD and high pre-test probability of permanent GHD.

THU172 Accuracy Of The Glucagon Testing In The Diagnosis Of Growth Hormone Deficiency During Transition

Abstract Disclosure: N. Di Iorgi: None. D. Guglielmi: None. N. Flavia: None. A. Allegri: None. D. Fava: None. E. Casalini: None. G. Patti: None. M. Maghnie: None. Objectives: To evaluate the accuracy of the Glucagon test (GST) compared with the Insulin Tolerance test (ITT) as the gold standard in the diagnosis of Growth Hormone deficiency (GHD) in young adults with childhood-onset GHD (COGHD). Methods: Eighty-six subjects with COGHD (33F, 55M) were evaluated by ITT and GST stimulation tests and IGF-1 SDS at adult height achievement (median age of 17.5; IQR 13.9-18.4 years). Subjects were recruited from a single Center and based on the AACE 2019 Guidelines [1] classified as 1. idiopathic isolated GHD (I-GHD n=40 with normal brain MRI); 2. organic moderate GHD (omGHD with less than 3 pituitary deficiencies-PD and IGF-1&amp;lt;0 SDS, total n=40; n=12 midline defects, n=2 ALL, n=26 CNS tumors); 3. congenital/genetic defects/organic severe GHD (osGHD ≥3 PD and IGF-1 &amp;lt;-2 SDS, total n=6; n=1 midline defect, n=5 CNS tumors). ROC analyses were performed in order to analyze the Sensitivity (Se) and Specificity (Sp) of the GH peak after GST and of IGF-1 SDS compared to ITT. A peak GH value &amp;lt;6μg/L after ITT was suggestive of permanent GHD [2]. Results: Median GH peak to ITT (0.2; IQR 0.01-0.7 μg/L) and GST (0.1; IQR 0.01-1.4μg/L) were lower in osGHD compared to I-GHD subjects (15.0; IQR 8.6-21.9 to ITT and 12.6; IQR 10.5-18.8 μg/L to GST, P’s &amp;lt;0.0001); similarly, GH peak to ITT (2.1; IQR 1.1-6.8 μg/L) and GL (2.7; IQR 1.2-5.8) were lower in omGHD compared to I-GHD subjects (P’s &amp;lt;0.0001). Mean IGF-1 were also lower in osGHD (-3.2 SDS; IQR -7.4- -2.9, P&amp;lt;0.0001) and in omGHD (-2.0 SDS; IQR -2.8 - -0.7; P&amp;lt;0.0001) compared to I-GHD subjects (0,1; IQR -0.6-1.1SDS). A GH peak value to GST of 7.59 mcg/L (Se 92.3%, Sp of 87.2%; AUC=0.94; 95% CI, 0.89-0.99) correctly classified 89.5% of the entire cohort while an IGF-1 cut-off of -1.45 SDS (Se 73%; Sp 93.5%; AUC=0.84; 95% CI, 0.75 - 0.94) correctly classified 83,1%. A GH peak value to GST of 5.81 mcg/L (Se 96.6%, Sp of 81.8%; AUC=0.95; 95% CI, 0.88-1.02) correctly classified 92.5% of omGHD patients while an IGF-1 cut-off of -1.64 SDS (Se 72.3%, Sp of 90.9%; AUC=0.94; 95% CI, 0.89-0.99) correctly classified 77.5% omGHD patients. Median BMI SDS was higher in patients with osGHD (1.8; IQR 1,6- 2.2, P&amp;lt;0.001) and omGHD (0.6; IQR 0.1- 1.8, P&amp;lt;0.001) compared to I-GHD (0.2; IQR -0.7- 1.1). GH peak to GST correlated with BMI SDS only in the total cohort (r -0.313, P=0.0031). Conclusions: Our results suggest that a peak value &amp;lt;6 μg/L after GST is accurate in detecting permanent GHD during transition in a cohort of patients with organic GHD with less than 3 pituitary defects and IGF-1 values &amp;lt;0 SDS; the GH response to GST could be affected by BMI SDS, but further studies are needed. [1] Yuen KCJ et al. Endocr Pract 2019; 25 (11):1191-1232. [2] Maghnie M et al, EJE 2005; 152:589-596. Presentation: Thursday, June 15, 2023

Accuracy and Limitations of the Growth Hormone (GH) Releasing Hormone-Arginine Retesting in Young Adults With Childhood-Onset GH Deficiency.

Background: Re-testing for GH secretion is needed to confirm the diagnosis of GH deficiency (GHD) after adult height achievement in childhood-onset GHD (COGHD).Aim: To define the cut-off of GH peak after retesting with GH-releasing hormone plus arginine (GHRHarg) in the diagnosis of permanent GHD in COGHD of different etiology.Patients and methods: Eighty-eight COGHD (median age 17.2 y), 29 idiopathic GHD (IGHD), 44 cancer survivors (TGHD) and 15 congenital GHD (CGHD) were enrolled in the study; 54 had isolated GHD (iGHD) and 34 had multiple pituitary hormone deficiencies (MPHD). All were tested with insulin tolerance test (ITT) and GHRHarg. IGHD with a GH response to ITT ≥6μg/L were considered true negatives and served as the control group, and patients with a GH response <6μg/L as true positives. Baseline IGF-I was also measured. The diagnostic accuracy of GHRHarg testing and of IGF-I SDS in patients with GHD of different etiologies was evaluated by ROC analysis.Results: Forty-six subjects with a GH peak to ITT ≥6μg/L and 42 with GH peak <6 μg/L showed a GH peak after GHRHarg between 8.8–124μg/L and 0.3–26.3μg/L, respectively; 29 IGHD were true negatives, 42 were true positives and 17 with a high likelihood GHD showed a GH peak to ITT ≥6μg/L. ROC analysis based on the etiology indicated the best diagnostic accuracy for peak GH cutoffs after GHRHarg of 25.3 μg/L in CGHD, 15.7 in TGHD, and 13.8 in MPHD, and for IGF-1 SDS at −2.1 in CGHD, −1.5 in TGHD, and −1.9 in MPHD.Conclusions: Our findings indicate that the best cut-off for GH peak after retesting with GHRHarg changes according to the etiology of GHD during the transition age. Based on these results the diagnostic accuracy of GHRHarg remains questionable.

SUN-250 Natural History of Growth in Patients with SHOX Gene Haploinsufficiency and Impact of Treatment with rhGH in Adult Height

Introduction: The SHOX gene haploinsufficiency is the main monogenic cause of short stature, being observed in 56% to 100% of patients with Leri-Weill dyschondrosthosis (LWD) and in 1% to 14% of children with idiopathic short stature (ISS). The diagnosis allows the establishment of a suitable prognosis for adult height, indication of rhGH treatment and genetic counseling. Objectives: To describe a cohort of 45 children (24 female) with molecular diagnosis of heterozygous SHOX defects, focusing on achievement of adult height. Materials and Methods: We analyzed retrospective data from 37 families in that defects in the SHOX gene were identified. The molecular study was performed by MLPA followed by gene sequencing. Results: In 64% of the families there was deletions in SHOX gene, 20% deletions in SHOX expression regulatory region and 16% point mutations. Among the 45 patients diagnosed during childhood, 14 were identified by family screening and 31 were index case. The mean age at diagnosis was 10.2 ± 3.2y, BMI SDS = 0.9 ± 0.8, height SDS of affected parent -2.4 ± 1.1 and height SDS of non-affected parent was -1.1 ± 1.2. The index cases were shorter than the children diagnosed by screening (Height SDS of -2.2 ± 1.0 vs. -1.5 ± 0.7, respectively; p 0.038). The majority (80%) of these children had disproportionate short stature (Sitting height by total height SDS = 3.5 ± 1.7), and 47% had Madelung deformity. Twenty-six patients reached adult height, 16 of them were treated with rhGH (mean duration of treatment = 4.8 ± 3.0 y, mean dose: 50 µg/kg/d). Eight patients (3 boys and 5 girls) were also treated with GnRH analog due to a low predicted adult height (mean duration of GnRHa was 3.1 ± 1.7y). At the first evaluation, treated patients were shorter than untreated ones (Height SDS = -2.3 ± 1.1 vs. -1.5 ± 0.6, respectively; p = 0.059). Mean adult height SDS was similar between treated and non-treated patients (height SDS -2.0 ± 1.2 vs. -2.6 ± 0.7, respectively, p = 0.179). Treated patients showed a slighted improvement of height SDS from the start the therapy to adult height (∆Height SDS = 0.3 ± 0.7), while untreated patients had loss of height SDS (∆Height SDS -1.2 ± 0.7 p <0.001). Of the treated patients 63% reached normal height (Height SDS >-2) whereas 75% of untreated patients had short stature at adult height (Z <-2). Conclusion: Treatment with rhGH promotes stature gain in patients with SHOX haploinsufficiency. Genetic screening in children with short stature allows the identification of new carriers of SHOX defect and precocious rhGH therapy can avoid the lost of 1 SDS of height between childhood and adult life.

Growth Hormone Deficiency in the Transition Age.

Growth hormone (GH) is essential not only for normal growth during childhood, but also for the acquisition of bone mass and muscle strength in both sexes. This process is completed after the achievement of adult height in the phase of transition from adolescence to adulthood. Adolescents with childhood onset GH deficiency (GHD) show reduction of bone mineral density, decrease in lean body mass, increase in fat mass, and deterioration of the lipid profile. For this reason, continuation of GH replacement therapy in the transition age is recommended in all patients with a confirmed diagnosis of GHD. To confirm the diagnosis of GHD, GH treatment should be discontinued for at least 1 month after the attainment of adult height, and the patient should be re-evaluated for GH secretion. Current guidelines indicate that retesting is not required for those with a transcription factor mutation, more than 3 pituitary hormone deficits, or isolated GHD associated with an identified mutation. The key predictors of persistent GHD are its severity, the presence of additional pituitary hormone deficits, low insulin-like growth factor I (IGF-I) concentration, and the presence of structural hypothalamic-pituitary abnormalities Treatment should be initiated with a low dose (0.2-0.5 mg/day s.c.) and then adjusted according to IGF-I concentrations.

Central Precocious Puberty: Adult Height in Girls Treated with Quarterly or Monthly Gonadotropin-Releasing Hormone Analog Triptorelin

Background/Aims: Treatment with quarterly gonadotropin-releasing hormone (GnRH) analogs may improve compliance and optimize outcome in girls with central precocious puberty (CPP), but long-term comparative data between the new and the monthly formulations are very scarce. Methods: A group of girls with idiopathic CPP (n = 13; age 7.9 ± 0.6 years) were treated from the beginning with quarterly triptorelin (11.25 mg/90 days) and followed up to the achievement of adult height (AH). A group of girls with idiopathic CPP (n = 12; age 8.0 ± 0.6 years) treated with monthly triptorelin (3.75 mg/28 days) served as controls. Results: The AH (157.1 ± 4.9 cm) of girls treated with quarterly triptorelin was not significantly different from their mid-parental height (159.7 ± 3.8 cm) and significantly increased in comparison with predicted AH (average tables) at the beginning of GnRH analog therapy. The AH of girls treated with quarterly triptorelin was not significantly different in comparison with that of girls treated with the monthly formulation (158.1 ± 6.6 cm; mid-parental height 158.4 ± 5.0 cm). Conclusion: Treatment with quarterly triptorelin formulation permitted to achieve an AH adequate for mid-parental height in girls with CPP. Significant differences of AH between girls with CPP treated with quarterly or monthly formulations were not found.

Successful Treatment With Sirolimus of a Patient With Blue Rubber Bleb Nevus Syndrome

Introduction: The bean syndrome, or “blue rubber bleb nevus” (BRBN) is a rare disease (about 200 reported cases) characterized by the presence of multiple cutaneous and vascular malformations of the digestive tract and is associated with difficult to control chronic intestinal hemorrhage and consequent iron deficiency anemia. Case Report: A male patient, 18 year-old, was diagnosed with BRBN at the age of 3 years. The patient had multiple visceral, muscular, and subcutaneous vascular lesions, complicated with chronic gastrointestinal bleeding. The patient was initially treated by endoscopic ablation (argon-plasma) and surgical resection of the larger lesions, with temporary clinical improvement. Due to RBC-transfusion dependence (total of 74 transfusions since diagnosis), despite oral and intra-venous iron therapy (ferric hydroxide, iron dextran, and ferric carboxymaltose), the digestive tract was evaluated by endoscopy and capsule enteroscopy, which revealed the small bowel as the main source of bleeding. Treatment with propranolol was initiated, as so various endoscopic treatments (balloon-assisted enteroscopy with thermal argon ablation and sclerosis), but only with temporary improvement. The most recent therapy (propranolol and ferric carboxymaltose) provided symptomatic improvement without significant improvement of anemia and blood loss. The use of anti-angiogenic drugs has been delayed due to concerns of possible growth adverse effects. At 18 years old, with achievement of adult height, it was the treatment with sirolimus was proposed. After 5 months of anti-angiogenic therapy, the patient showed improvement of blood loss, asthenia, and subcutaneous/muscular lesions sensitivity and size. Sirolimus was well-tolerated and anemia also resolved (recovery of 5g/dL in 5 months). Disclosure - Helder Cardoso - Advisory committee: Abbvie, Janssen; Speaking and Teaching: BMS, Bayer, Roche.

Effects of Growth Hormone (GH) Therapy Withdrawal on Glucose Metabolism in Not Confirmed GH Deficient Adolescents at Final Height

Context, objectiveGrowth hormone deficiency (GHD) is associated with insulin resistance and diabetes, in particular after treatment in children and adults with pre-existing metabolic risk factors. Our aims were. i) to evaluate the effect on glucose metabolism of rhGH treatment and withdrawal in not confirmed GHD adolescents at the achievement of adult height; ii) to investigate the impact of GH receptor gene genomic deletion of exon 3 (d3GHR).Design, settingWe performed a longitudinal study (1 year) in a tertiary care center.Methods23 GHD adolescent were followed in the last year of rhGH treatment (T0), 6 (T6) and 12 (T12) months after rhGH withdrawal with fasting and post-OGTT evaluations. 40 healthy adolescents were used as controls. HOMA-IR, HOMA%β, insulinogenic (INS) and disposition (DI) indexes were calculated. GHR genotypes were determined by multiplex PCR.ResultsIn the group as a whole, fasting insulin (p<0.05), HOMA-IR (p<0.05), insulin and glucose levels during OGTT (p<0.01) progressively decreased from T0 to T12 becoming similar to controls. During rhGH, a compensatory insulin secretion with a stable DI was recorded, and, then, HOMAβ and INS decreased at T6 and T12 (p<0.05). By evaluating the GHR genotype, nDel GHD showed a decrease from T0 to T12 in HOMA-IR, HOMAβ, INS (p<0.05) and DI. Del GHD showed a gradual increase in DI (p<0.05) and INS with a stable HOMA-IR and higher HDL-cholesterol (p<0.01).ConclusionsIn not confirmed GHD adolescents the fasting deterioration in glucose homeostasis during rhGH is efficaciously coupled with a compensatory insulin secretion and activity at OGTT. The presence of at least one d3GHR allele is associated with lower glucose levels and higher HOMA-β and DI after rhGH withdrawal. Screening for the d3GHR in the pediatric age may help physicians to follow and phenotype GHD patients also by a metabolic point of view.

Central Diabetes Insipidus in Children and Young Adults: Etiological Diagnosis and Long-Term Outcome of Idiopathic Cases

Central diabetes insipidus (CDI) is considered idiopathic in 20% to 50% of affected subjects. The purpose of this study was to determine whether a systematic diagnostic workup could achieve better etiologic diagnosis in children and adolescents presenting with polyuria and polydipsia. This is a prospective study conducted at a tertiary referral center. Patients underwent clinical and endocrine evaluations every 6 months and neuroimaging every 6 months for 2 years and yearly for 3 years. Endocrine function and neuroimaging were also reassessed after adult height achievement. A total of 85 consecutive patients with CDI were enrolled at a median age of 7.5 years; those with idiopathic CDI were stratified based on pituitary stalk thickness. To establish the etiology of CDI, we determined the time lag between its onset and the specific diagnosis, the long-term impact on pituitary function, and the overall long-term outcomes. Of the subjects, 24 (28.2%) received an etiologic diagnosis at presentation and 11 (13%) within 2.5 years (n = 7 germinomas and n = 4 Langerhans cell histiocytosis), 7 (8.2%) were lost to follow-up, and 43 (50.6%) were considered to have idiopathic disease and were followed until the median age of 17.3 years. Neuroimaging identified 40 of 43 patients with self-limited inflammatory/autoimmune pituitary stalk thickness within the first 6 months, the severity of which was significantly correlated to pituitary dysfunction. The probability of >10-year-survival without an anterior pituitary defect was related to the severity of pituitary stalk thickness, and 53% showed permanent anterior pituitary defects. Three patients developed Langerhans cell histiocytosis and 1 developed Hodgkin lymphoma after a median of 9 and 13 years, respectively. A diagnostic etiology was achieved in 96% of patients with CDI. Risk stratification based on the degree of pituitary stalk thickness is of prognostic value for long-term outcomes including permanent pituitary dysfunction. New guidance is provided for the management of these patients.

Adult height in girls with Turner syndrome treated from before 6 years of age with a fixed per kilogram GH dose

To evaluate adult height (AH) in 25 girls with Turner syndrome (TS) who were treated from before 6 years of age for 10.0 ± 1.7 years with a fixed GH dose of 0.33 mg/kg per week. After a 6-month pretreatment assessment all patients were measured 6-monthly under therapy to assess height SDS (H-SDS) and height velocity (HV) until AH achievement. Following initial acceleration, HV declined after the first 4 years of therapy. At the end of the sixth year of therapy, H-SDS gain was 1.9 ± 1.1. Thereafter, H-SDS gain from baseline decreased, becoming 0.9 ± 0.9 SDS at AH achievement. Bone maturation velocity did not significantly change throughout the prepubertal period. According to Lyon standards for TS, mean AH SDS was significantly higher than pretreatment H-SDS (P<0.0001), with a mean H-SDS change of 0.9 ± 0.9. However, the prevalence of patients with AH <-2 SDS (according to Sempé standards) was close to those recorded at the start of therapy (16/25 vs 18/25). No significant differences in terms of AH were found between patients with either X monosomy or X-chromosomal abnormalities and between girls with either spontaneous or induced puberty. We infer that the therapeutic regimen adopted in this prospective study is sufficient to induce a significant growth acceleration during the first year, but the response waned after 6 years of treatment.

Mechanisms and management of growth impairment in children affected by inflammatory bowel disease

Growth failure is a typical complication of pediatric inflammatory bowel disease. Factors responsible for stunting are multiple, and proinflammatory cytokines such as TNF-α and IL-6 play a pivotal role. Other determinants are disease severity and location, malnutrition, increased nutritional needs, genetics and drugs. The achievement of optimal linear growth and the remission of gastrointestinal symptoms are the principal targets of pediatric inflammatory bowel disease treatment. Thus, it is very important to assess and monitor linear growth at diagnosis and during follow-up of disease until final adult height achievement. The main strategies for management or prevention of growth impairment in these children are aimed to ensure optimal nutrition, obtain a rapid and complete remission of the disease avoiding or minimizing steroid usage and consider surgical resection, in particular in case of localized ileo or ileocecal disease, to achieve remission in early or mid-puberty. In the last few years, some authors have evaluated the effects of recombinant human growth hormone treatment in children and adolescents with inflammatory bowel disease. However, further studies are needed to better assess its efficacy.

The use of neuroimaging for assessing disorders of pituitary development

Magnetic resonance imaging (MRI) is the radiological examination method of choice for evaluating hypothalamo-pituitary-related endocrine disease and is considered essential in the assessment of patients with suspected hypothalamo-pituitary pathology. Physicians involved in the care of such patients have, in MRI, a valuable tool that can aid them in determining the pathogenesis of their patients' underlying pituitary conditions. Indeed, the use of MRI has led to an enormous increase in our knowledge of pituitary morphology, improving, in particular, the differential diagnosis of hypopituitarism. Specifically, MRI allows detailed and precise anatomical study of the pituitary gland by differentiating between the anterior and posterior pituitary lobes. MRI recognition of pituitary hyperintensity in the posterior part of the sella, now considered a marker of neurohypophyseal functional integrity, has been the most striking finding in the diagnosis and understanding of certain forms of 'idiopathic' and permanent growth hormone deficiency (GHD). Published data show a number of correlations between pituitary abnormalities as observed on MRI and a patient's endocrine profile. Indeed, several trends have emerged and have been confirmed: (i) a normal MRI or anterior pituitary hypoplasia generally indicates isolated growth hormone deficiency that is mostly transient and resolves upon adult height achievement; (ii) patients with multiple pituitary hormone deficiencies (MPHD) seldom show a normal pituitary gland; and (iii) the classic triad of ectopic posterior pituitary, pituitary stalk hypoplasia/agenesis and anterior pituitary hypoplasia is more frequently reported in MPHD patients and is generally associated with permanent GHD. Pituitary abnormalities have also been reported in patients with hypopituitarism carrying mutations in several genes encoding transcription factors. Establishing endocrine and MRI phenotypes is extremely useful for the selection and management of patients with hypopituitarism, both in terms of possible genetic counselling and in the early diagnosis of evolving anterior pituitary hormone deficiencies. Going forward, neuroimaging techniques are expected to progressively expand and improve our knowledge and understanding of pituitary diseases.

Guidelines for Pubertal Suspension and Gender Reassignment for Transgender Adolescents

Pubertal suppression at Tanner stage 2 should be considered in adolescents with persistent gender identity disorder (GID). Issues related to achievement of adult height, timing of initiating sex steroid treatment, future fertility options, preventing uterine bleeding, and required modifications of genital surgery remain concerns. Concerns have been raised about altering neuropsychological development during cessation of puberty and reinitiation of puberty by the sex steroid opposite those determined by genetic sex. Collaborative assessment and treatment of dysphoric adolescents with persistent GID resolves these concerns and deepens our understanding of gender development.

Growth hormone treatment in adults with growth hormone deficiency: The transition

The approval of GH treatment of adults with GH deficiency (GHD) raises issues regarding continuation of GH treatment in the GH-deficient child following achievement of near adult height. The transition period begins in late puberty and ends with full adult maturation and includes hormonal and many lifestyle changes. Children treated with GH should be retested near the time of reaching adult height to determine if they have persistence of GHD. Although most children with organic causes of GHD will again be found to have GHD on retesting, most of those with idiopathic GHD will not. Retesting usually involves measurement of IGF-I and stimulation with insulin-induced hypoglycemia or arginine-GHRH, but important questions remain about adjustment of established cut-offs for age and body mass index. Most studies have shown the benefit of GH treatment in young adults with GHD in body composition, especially the achievement of peak bone mass. It is important for pediatric endocrinologists to discuss the potential need for continued treatment beyond achievement of adult height at the time of initiation of GH treatment, especially in those children with organic causes of GHD.

Impact of Growth Hormone Therapy on Adult Height of Children Born Small for Gestational Age

Use of growth hormone (GH) therapy to promote growth in short children born small for gestational age (SGA) was recently approved in the United States and Europe, but there is still disagreement about the magnitude of effectiveness of GH. To determine the impact of GH therapy on adult height in short SGA children by a meta-analysis of randomized, controlled trials (RCTs). We performed a systematic review of controlled studies using as data sources the Cochrane Central Register of Controlled Trials, Medline, and the bibliographic references from all retrieved articles describing RCTs up to November 2008. A meta-analysis of all RCT studies conducted up to the achievement of adult height was performed. Inclusion criteria were birth weight and/or length below -2 SD score (SDS), initial height less than -2 SDS, and GH dose range of 33 to 67 microg/kg per day. Adult height SDS and overall height gain SDS were the primary outcome measures. Four RCTs (391 children) met the inclusion criteria. The adult height of the GH-treated group significantly exceeded controls by 0.9 SDS. Mean height gain was 1.5 SDS in treated versus 0.25 SDS in untreated SGA subjects. No significant difference in adult height was observed between the 2 GH dose regimens. GH therapy seems to be an effective approach to partially reduce the adult height deficit in short SGA children. However, the response to therapy is highly variable, and additional studies are needed to identify the responders.

Growth and Endocrine Function in Long-term Adult Survivors of Childhood Stem Cell Transplant.

The number of long-term surviving stem cell transplant (SCT) recipients has increased steadily, and attention has now extended to the late complications of this procedure. The objective of this study was to investigate relationship among growth and endocrine functions in long-term adult survivors of childhood SCT. The inclusion criteria of this study were survival at least 5 yr after SCT and achievement of adult height. Fifty-four patients (39 males) fulfilled these criteria and were included in this study. Growth was mainly evaluated by height standard deviation score (SDS) and individual longitudinal growth curves. Among the 54 patients, those that received SCT before 10 yr of age showed significantly greater reductions in changes in height SDS (mean –1.75, range –4.80 to –0.10) compared with those that received SCT at or after 10 yr of age (mean –0.50, range –1.74 to 1.20; P<0.001). The mean loss of height for all patients who received SCT during childhood was estimated to be approximately 1 SDS/6.5 yr (r=0.517). Individual longitudinal growth curves indicated that a significant growth spurt was absent in severe short stature patients during the pubertal period without severe endocrine dysfunctions including GH deficiency. The incidence of growth disorder in long-term adult survivors depends on the age at SCT and whether they received radiation therapy. Life-long follow-up is necessary for survivors to detect, prevent and treat the late endocrine complications in SCT survivors.

OR7,5 The diagnosis of growth hormone deficiency after adult height achievement

OR7,5 The diagnosis of growth hormone deficiency after adult height achievement

Pubertal correlates in black and white girls

Since pubertal maturation is an important covariate in studies that evaluate physical and social changes that occur during the teen years, we examined pubertal parameters in a group of US girls. Black and white girls recruited at age 9 were followed annually for 10 years. Preece-Baines model 1 was used to estimate tempo and growth parameters. The temporal trend between age of menarche and onset of puberty was calculated. The study included 615 (77.2% prepubertal) white and 541 (49.4% prepubertal) black participants. Mean onset of puberty was 10.2 and 9.6 years in white and black girls, respectively, menarche was 12.6 and 12.0, achievement of Tanner growth stage 5 was 14.3 and 13.6, and achievement of adult height was 17.1 and 16.5 years. The Pearson's correlation coefficient between menarche and onset of puberty was .37. Menarche is often used as a marker for onset of puberty and for timing of puberty. Data gathered over the past 20 years suggest only moderate correlation between menarche and onset of puberty (.37-.38), which has decreased significantly during the last 50 years. This suggests the existence of both similar and unique factors that impact the age at onset of puberty and age at menarche.

Growth hormone binding protein, insulin-like growth factor-I and short stature in two pygmy populations from the Philippines.

The molecular basis and biochemical mediators of genetic growth propensity and adult height achievement in the general population are largely unknown. Pygmies represent one extreme of the height spectrum that may provide important clues regarding this issue. Previous studies in pygmies from Africa and Papua-New Guinea have shown decreased serum levels of growth hormone binding protein (GHBP), the circulating ectodomain of the growth hormone receptor (GHR). By inference, a similar limitation in tissue GHR expression has been assumed to be responsible for the partial growth hormone (GH) resistance observed in African pygmies. It is not clear how generalizable this concept is to other populations. To address this question, we studied two pygmy populations from the Philippines (Aeta and Mamanwa people) that are unrelated to the African pygmies. Serum GHBP and IGF-I levels were significantly decreased in both pygmy populations, compared to normal-statured Philippino controls. The results, together with previous observations in African and New Guinean pygmies, indicate that short stature is associated with low serum GHBP levels in pygmy populations of diverse origins and in different parts of the world. This strengthens the tentative postulate that the GHBP/GHR system plays an important role in the genetic and perhaps nutritional determination of adult stature in humans. Molecular genetic studies of the GHR gene in various pygmy populations may shed further light on the mystery of pygmy short stature.

Growth hormone secretion and effects of growth hormone therapy on growth velocity and weight gain in children with Prader-Willi syndrome.

Obesity, short stature, decreased growth rate and delayed skeletal maturation are common features of children with Prader-Willi syndrome (PWS). In contrast to PWS, children with simple exogenous obesity have normal or increased growth rate and normal or advanced skeletal maturation. Decreased growth hormone (GH) secretion evaluated by pharmacological or physiological testing associated with increased plasma insulin-like growth factor (IGF-I) and GH-binding protein (GH-BP) levels are also characteristic of simple obesity. In order to understand whether the suboptimal GH secretion in PWS is an artifact of the obesity, we studied 33 obese and 11 non-obese PWS children, aged 2-16 years.GH secretion was evaluated with three pharmacological stimuli (insulin, clonidine and L-dopa) and by spontaneous 24-hour GH secretion. Skeletal maturation was delayed in 70% whereas plasma IGF-I and GH-BP were either low or normal. Forty subjects, including ten non-obese children, had GH deficiency by standard testing (failure to respond to two pharmacological stimuli), and all but one had blunted spontaneous 24-h GH secretion. No significant correlation between body mass index (wt/ht2) and spontaneous 24-h GH secretion (r = 0.145), p > 0.06) or GH-BP levels (r = 0.19, p > 0.07) was found. Thirty documented GH deficient children have completed at least two years of GH therapy. With treatment the overall mean height SD and weight SD changed from -2.2 to -0.8 and from 3.5 to 2.4 respectively (p < 0.0001). No patient has developed diabetes mellitus. In conclusion, growth velocity, skeletal maturation, GH secretion and GH dependent proteins in PWS resemble GH deficiency more than simple obesity. Our ongoing study suggests that GH deficiency in PWS is not an artifact of obesity. Although it is unlikely that GH deficiency is the only cause of decreased growth velocity and increased adiposity in PWS, it is a common feature and significant contributory factor. Long term observation will be required until achievement of adult height to determine whether GH therapy actually improves final height.