Starting Growth Hormone Therapy Research Articles

Slipped Capital Femoral Epiphysis after 2 Months from Starting Growth Hormone Therapy

AbstractRecombinant growth hormone (GH) is a widely used hormonal therapy for children and adolescents with GH deficiency or short stature related to certain conditions. Generally, GH therapy has a good safety profile; however, it could have rare but significant orthopaedic complications including slipped capital femoral epiphysis (SCFE). Pediatric endocrinologists are aware of these possible complications, and they are responsible for appropriately counseling their patients before commencing this hormone. However, the pediatric endocrinologist may not be the first clinician who encounters the orthopaedic complications of GH, as the patient may seek an emergency medical opinion from people from other specialties. Here, we report the case of a 13-year-old Iraqi adolescent boy who presented with limping that appeared only 2 months after receiving GH (0.035 mg/kg/d). He was diagnosed with SCFE in a relatively very short time after commencement of the treatment. Despite this, the patient was not considered to be at high risk of SCFE. A careful evaluation of SCFE in patients complaining of a limp or hip and knee pain during GH therapy is highly recommended.

Growth hormone therapy response in children with short stature

BackgroundShort stature is one of the main causes of children referral to pediatric endocrinologists. Common etiologies include idiopathic growth hormone deficiency (IGHD), small for gestational age (SGA), and idiopathic short stature (ISS).ObjectivesThe aim of this study was to assess and compare the response of children with IGHD, ISS, and SGA to growth hormone (GH) therapy.MethodsThis was a mixed cohort study that included 40 children with short stature (classified into IGHD, ISS, and SGA) following up at Diabetes, Endocrine, and Metabolism Pediatric Unit (DEMPU), Cairo University Children’s Hospital. Ages ranged between 3 and 18 years. Recruited cases were evaluated for their 1-year response to GH therapy. In addition to history taking, physical examination, and anthropometric measurements, serum levels of IGF-1 were assayed at recruitment.ResultsAmong the 3 groups, height gain (cm/year) was significantly higher in the IGHD group (6.59 cm/year), followed by the ISS (4.63 cm/year) and SGA groups (4.46 cm/year) (p = 0.039). Using the Bang criterion for first-year responsiveness to GH therapy, most cases (30/40, 75%) were considered poor responders.ConclusionThere is a male predominance in children seeking medical advice for short stature. Starting GH therapy at an older age was associated with poor response. Children with IGHD respond better to GH therapy than those with ISS and SGA.

Variability of the Predicted Final Height in Idiopathic Short Stature Over Time

Background: Predicting the final height in children with idiopathic short stature is essential for starting growth hormone therapy. This study was conducted to assess final height estimation variability over time. Materials and Methods: In this cross-sectional study, children with idiopathic short stature were examined. Bone age and final height were estimated through the Greulich-Pile and Bayley-Pinneau method. This process repeated in the later visits with at least six months, and the results were compared statistically. The patients were classified based on the changes in predicted final height (PFH). Results: A total of 81 patients (46 boys, 35 girls) with a mean age of 11.09 years were enrolled. The calculated PFH in the first visit was 160.15±8.79 cm, which has decreased to 159.33±9.38 cm. Based on the second evaluation, 43 patients had few changes in PFH (±3 cm), 23 patients experienced a decrease in PFH of more than 3 cm, and 15 patients experienced an increase in PFH of more than 3 cm. A change in Tanner stage, weight gain, height velocity, target height, and the interval between the two evaluations were similar in all groups. Young under ten years had more decreasing in the PFH. Conclusion: Depending on bone age velocity, predicting the final height can change over time. As bone age velocity increases, PFH decreases more. PFH is also less reliable at younger ages and requires monitoring of growth and puberty and repeating final estimations later in life.

Metabolic Changes across Tertiles of Delta Changes in Height SDS during Growth Hormone Therapy in Children with Growth Hormone Deficiency

Introduction: Obesity, dyslipidemia, hypertension, and insulin resistance are components of the metabolic syndrome and in adults are positively affected by growth hormone (GH) treatment. Few data are available on youth, especially evaluating the improvement of metabolic features after starting GH treatment. The aim of this study was to evaluate changes in metabolic profile in GHD children across tertiles of h-SDS changes after at least 20 months of GH therapy. Methods: Data from 51 normal-weight children and adolescents with GHD (age: 11.4 ± 2.3 years; h-SDS: −2.25 ± −1.94) who had performed a complete metabolic profile including IGF-1, lipid profile (total cholesterol, triglycerides, HDL cholesterol), glucose metabolism (fasting glycemia, insulin, hemoglobin A1c levels), and insulin resistance indices (HOMA, TG/HDL ratio) before and after start GH treatment were analyzed. Subjects who had received GH therapy for at least 20 months were eligible. Delta changes were calculated for each variable. Subjects were divided according to tertiles of delta changes of h-SDS (1st tertile, 2nd tertile, 3rd tertile) before and after a period of GH treatment. Results: In each tertile group, a significant increase in height SDS was documented. Delta changes in glucose metabolism, lipid profile, and insulin resistance indices significantly improved across tertiles groups, showing the highest tertile a better metabolic pattern. Discussion/Conclusions: GH therapy is associated with improvement of metabolic profile. Delta changes seem to be more evident in those children with a higher tertile of delta h-SDS after starting GH therapy. A tailored therapy aimed to reach a proper goal in h-SDS after GH treatment might be necessary in order to reduce cardiovascular risk in GHD children.

Activated phosphoinositide 3-kinase \u03b4 syndrome associated with nephromegaly, growth hormone deficiency, bronchiectasis: a case report

BackgroundActivated phosphoinositide 3-kinase (PI3K) δ syndrome (APDS) is a rare form of primary immunodeficiency with 243 known cases reported in the literature. Known findings associated with the condition include recurrent sinusitis and bronchitis, bronchiectasis, immune cytopenias, mild developmental delay, splenomegaly, and lymphadenopathy. We report the case of a child with APDS accompanied by unique clinical features: nephromegaly and growth hormone deficiency with associated pituitary anatomic abnormality.Case presentationThe patient is a nine-year-old boy with a heterozygous de novo variant in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit δ (p.E1021K), previously reported in association with APDS. Our patient, who had no family history of immunodeficiency, exhibits classic findings of this syndrome but also has unique features that extend the phenotypic spectrum of this disorder. At 5 years of age, the patient showed marked growth deceleration and was demonstrated to have growth hormone (GH) deficiency with associated pituitary anatomic abnormality. He started GH therapy with an excellent response. He additionally has bilateral nephromegaly of unclear etiology, microscopic hematuria and proteinuria, asthma, and has developed left hip pain with arthrocentesis consistent with oligoarticular juvenile idiopathic arthritis. At age nine, the patient was referred to genetics and whole exome sequencing revealed APDS. Though there was initial concern that GH may increase risk for malignancy as GH signals through the PI3K pathway, he was allowed to continue treatment as the PI3K pathway was considered constitutively active at baseline.ConclusionsOur patient’s unique presentation adds to the clinical information regarding APDS, demonstrates the utility of genetic testing and illustrates the importance of a multidisciplinary collaborative approach in managing this complex syndrome.

Effect of growth hormone therapy on thyroid function in isolated growth hormone deficient and short small for gestational age children: a two-year study, including on assessment of the usefulness of the thyrotropin-releasing hormone (TRH) stimulation test.

Background The relationship between growth hormone (GH)-replacement therapy and the thyroid axis in GH-deficient (GHD) children remains controversial. Furthermore, there have been few reports regarding non-GHD children. We aimed to determine the effect of GH therapy on thyroid function in GHD and non-GHD children and to assess whether thyrotropin-releasing hormone (TRH) stimulation test is helpful for the identification of central hypothyroidism before GH therapy. Methods We retrospectively analyzed data from patients that started GH therapy between 2005 and 2015. The free thyroxine (FT4) and thyroid-stimulating hormone (TSH) concentrations were measured before and during 24months of GH therapy. The participants were 149 children appropriate for gestational age with GHD (IGHD: isolated GHD) (group 1), 29 small for gestational age (SGA) children with GHD (group 2), and 25 short SGA children (group 3). Results In groups 1 and 2, but not in group 3, serum FT4 concentration transiently decreased. Two IGHD participants exhibited central hypothyroidism during GH therapy, and required levothyroxine (LT4) replacement. They showed either delayed and/or prolonged responses to TRH stimulation tests before start of GH therapy. Conclusions GH therapy had little pharmacological effect on thyroid function, similar changes in serum FT4 concentrations were not observed in participants with SGA but not GHD cases who were administered GH at apharmacological dose. However, two IGHD participants showed central hypothyroidism and needed LT4replacement therapy during GH therapy. TRH stimulation test before GH therapy could identify such patients and provoke careful follow-up evaluation of serum FT4 and TSH concentrations.

Treatment of the adult growth hormone deficiency syndrome with growth hormone: What are the implications for other hormone replacement therapies for hypopituitarism?

When initiating growth hormone replacement therapy, it is important to consider a patient's other pituitary hormone replacement medications, as adjustments are often necessary. Growth hormone therapy can increase the metabolism of hydrocortisone or endogenous cortisol, unmasking borderline ACTH deficiency and leading to the development of adrenal insufficiency and adrenal crisis. In addition, growth hormone can enhance the metabolism of thyroxine to triiodothyronine, uncovering borderline TSH deficiency. In many patients, thyroid hormone replacement therapy must be started, or the dose of levothyroxine must be increased. Oral estrogen replacement therapy leads to a state of relative growth hormone resistance, and the dose of GH may need to be increased substantially. Physicians have long been cognizant of the fact that adding a new prescription medication may lead to important drug-drug interactions. Starting growth hormone therapy may lead to hormone-hormone interactions that can pose serious complications for the hypopituitary patient unless the interaction of growth hormone on other pituitary hormone systems is understood.

Spectrum of Turner's syndrome: Our experience

Introduction: Turner's syndrome (TS) is the most common sex chromosome disorder in women, with an incidence of 1 in 2,500 female births. TS is characterized by distinctive features of short stature, streak gonads, increased risk of heart and renal defects and specific cognitive and psychosocial phenotype. Materials and Methods: We conducted a study in the department of endocrinology, GGH, Kurnool, for one year. 27 cases presented with short stature and primary amenorrhea, recurrent otitis media, were diagnosed as TS after detailed workup. We started growth hormone therapy for some patients with short stature. Gonadectomy was conducted for TS patients with Y component, and they were asked for regular follow-up. Results: Out of 27 cases, 12 were found to be turner mosaic, 15 were classical cases of TS. Conclusion: TS can be diagnosed with a high degree of clinical suspicion and confirmed by karyotyping. TS if identified earlier, growth can be achieved to the maximum potential. Early identification and proper management can improve the outcome and decrease the complications associated with TS.

Evaluation of Clinical Features and Growth Hormone Deficiency in Short Children Born Small For Gestational Age

Growth hormone (GH) therapy for short children born small for gestational age (SGA) has been approved in Japan. It is important to evaluate GH secretion ability before the initiation of GH therapy because there are some differences in dose and medical expenses between short children born SGA and GH deficiency (GHD). This study was designed to elucidate the incidence of GHD and to find a useful marker for detecting it in short SGA children. We retrospectively reviewed medical records to analyze the clinical features of short children born SGA and with GHD who had started GH therapy before the age of 6 in the University Hospital of Occupational and Environmental Health and Kyushu Rousai Hospital. Nine of 22 SGA subjects (41%) had GHD. There were no significant differences between two groups of short SGA children (GHD, non-GHD) in the median of height and serum insulin-like growth factors (IGF)-1 levels at birth or at the start of GH therapy. The probability of GHD was higher if the height standard deviation scores (SD) of the SGA children were lower than -3.2 (odds ratio, 11.6; 95% confidence interval, 1.52 - 89.1, P = 0.013). This study showed that there is an approximately 40% incidence of GHD in short SGA children needing GH treatment. We should do GH stimulation tests for short SGA children whose height SD is lower than -3 to determine the appropriate GH therapy.

Direct and indirect effects of Growth Hormone Deficiency (GHD) on lung function in children: A mediation analysis

Studies on pulmonary function tests (PFTs) in Growth Hormone Deficiency (GHD) children are lacking. The aims of this study were: (i) to investigate PFTs in GHD pre-pubertal children with respect to Controls, before starting Growth Hormone Therapy (GHT) (T0); (ii) to evaluate changes of PFTs in GHD vs Controls, after 1-year GHT (T1). For both aims the mediation analysis (MA) was applied to evaluate the extent to which the relationship between GHD and PFTs could be ascribed to a height-mediated (indirect) or a GH direct effect. 47 pre-pubertal GHD children (aged 5-14 years) underwent PFTs at T0 and T1. At T0, 47 healthy children matched for age and sex were enrolled as Controls. A MA was performed to assess the relationship between GHD and PFTs and height. Statistical analyses were performed using the statistical software R (https://cran.r-project.org/mirrors.html). A p-value <0.05 was considered significant. At T0, PFTs indices were significantly lower in GHD than in Controls. From T0 to T1 a significant improvement was found in PFTs. The percentages of the mediated effect on FVC, FEV1, FEF25-75% and TLC were <50% at T0, suggesting that the direct effect was prevalent. At T1, the percentages of the mediated effect for spirometry indices were ≥50%, indicating that the indirect (height-mediated) effect was the most relevant. The study shows that pre-pubertal children with GHD have an impairment of lung function not exclusively attributable to the indirect (height-mediated) effect, but also to the direct GH action which is mitigated after 1-year of GHT.

Research Article Bell’s palsy following growth hormone therapy in a patient with Prader-Willi syndrome: The first report

Prader–Willi syndrome (PWS) is a complex genetic disorder with different manifestations in infancy and childhood including obesity, type 2 diabetes mellitus, mild to moderate intellectual impairment and learning disabilities. In this syndrome, growth hormone therapy improves outcomes. For the first time, here we report a 11-year-old boy with PWS who presented with three episodes of unilateral facial palsy after starting growth hormone therapy.

Gastric Dilatation and Abdominal Compartment Syndrome in a Child with Prader-Willi Syndrome

Patient: Male, 5Final Diagnosis: Abdominal compartmentSymptoms: Abdominal distension • vomitingMedication: —Clinical Procedure: —Specialty: Pediatrics and NeonatologyObjective:Rare diseaseBackground:Prader-Willi syndrome (PWS) is a genetic disorder characterized by initial muscular hypotonia and feeding difficulties, and later an insatiable appetite, hyperphagia and obesity along with mild to moderate intellectual impairment. Affected individuals’ food-seeking behavior and suspected delayed gastric emptying can lead to gastric dilatation with subsequent necrosis and perforation.Case Report:We present the case of a 5-year-old boy diagnosed with Prader-Willi syndrome at neonatal age due to muscular hypotonia, who started growth hormone therapy at 20 months. He presented with two episodes of a rapidly progressing gastric dilatation that led to abdominal hypertension and secondary shock at the age of 2 and 5. No large amount of food was eaten before any of the episodes, and he had abdominal pain and vomiting on both occasions. On arrival at the emergency room, a nasogastric tube was placed and aspiration of food material was performed. Abdominal X-ray and CT scan revealed massive gastric dilatation. He was admitted at the Pediatric Intensive Care Unit and after a variable period of fasting, tolerated oral intake and could be discharged.Conclusions:Gastric dilatation due to gastroparesis in PWS is a rare complication. However, it is a life-threatening situation and physicians should therefore maintain a high level of suspicion for gastric dilatation when patients present with warning symptoms such as abdominal pain or discomfort and vomiting.

A Pediatric Patient with Idiopathic Short Stature Who Developed Obstructive Sleep Apnea after Starting Growth Hormone Replacement Therapy.

Growth hormone (GH) therapy has long been suspected to induce obstructive sleep apnea (OSA) in children and adults. Moreover, reports about GH-associated sudden death in children with Prader-Willi syndrome (PWS) have prompted concerns about GH worsening sleep apnea. Previous studies have supported routine polysomnography for children with PWS prior to starting GH treatments, regardless of clinical history. However, there are no established guidelines recommending routine polysomnography (PSG) prior to the commencement of GH therapy in other pediatric patients. We report a case of a 15-year-old young man with intractable headaches, referred to the sleep clinic to rule out any sleep-related variables. After an initial non-significant (mild snoring) sleep study, the patient returned with worsening snoring about one year after starting GH therapy for concerns of short stature. A second polysomnogram revealed that his obstructive apnea-hypopnea index had risen dramatically from baseline. His symptoms resolved after tonsillectomy and adenoidectomy. This interesting case highlights the need for caution with any patient eligible for GH therapy. We recommend additional research to look in the development of definitive guidelines regarding the indications for polysomnography for patients with idiopathic short stature and non-significant initial sleep history-particularly before and during the administration of GH therapy.

A case of congenital combined pituitary hormone deficiency who showed respiratory distress and hypoglycemia soon after birth

Congenital combined pituitary hormone deficiency (CCPHD) is a rare disease, presenting with respiratory distress, hypoglycemia and jaundice soon after birth. It is caused by .pituitary aplasia or hypoplasia or abnormality of transcription factor which related to pituitary development. We describe a Japanese patient with CCPHD, who presented with respiratory distress, hypoglycemia and jaundice soon after birth. The patient is now 13 months old Japanese girl. She was born by cesarean section because of fetal distress with 39 weeks and 4 days gestation after an uneventful pregnancy. Her parents were unrelated. Birth length and weight were 43.8cm (-2.2SD) and 2,100g and Apgar scores were 8 at both of 1 and 5 min. She had showed tachypnea and cyanosis since soon after birth and taken nasal-CPAP. However respiratory distress had not improved. She had also showed jaundice and hypoglycemia and was treated with phototherapy and infusion therapy. At 6 days old, we found her FT4 level was 0.4 pg/ml and TSH level was below 0.01 μIU/ml. She was suspected CPHD and anterior pituitary hormone levels were assessed. All of anterior pituitary hormones were undetectable. Anterior pituitary was not visible, posterior pituitary was detected at normal position and there were no other abnormality on brain magnetic resonance imaging. We diagnosed her as CCPHD and hydrocortisone was started since 6 days old and levothyroxine since 8 days old. After that respiratory distress and jaundice had improved rapidly. But hypoglycemia had appeared again after interrupting infusion therapy. GH level after arginine stimulation was also undetectable. She had also started growth hormone therapy since 25 days old and she has had no hypoglycemic episodes after that. Her length and weight were 70.3cm (-1.2SD) and 8,485g at 1 year old. GH replacement therapy that was started soon after diagnosis was able to prevent the severe growth retardation. She has no gene abnormalities of transcription factors, HESX1, LHX4 and OTX2, that involves pituitary development. Further studies are needed for investigating genetic basis of this patient. Careful and prompt clinical, endocrinological and neuroradiological assessment are needed for diagnosis of hypopituitarism in patients who show prolonged respiratory distress, hypoglycemia or jaundice soon after birth. Written informed consent was obtained from the patient's parent or guardian for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

Fracture risk in adult patients treated with growth hormone replacement therapy for growth hormone deficiency: a prospective observational cohort study

To our knowledge, no controlled studies of the effects of long-term growth hormone replacement on fracture risk in adult patients with growth hormone deficiency exist. We assessed the effect of growth hormone treatment on fracture risk in patients with growth hormone deficiency from the international Hypopituitary Control and Complications Study (HypoCCS) surveillance database. In this prospective cohort study, patients with growth hormone deficiency were analysed from the HypoCCS database of adults with hypopituitarism from the USA, Canada, Japan, and 14 European countries. Patients were eligible if they were aged 18 years or older and had an established diagnosis of growth hormone deficiency, either alone or with multiple pituitary hormone deficiencies, as identified by clinical history and biochemical testing. Patients were assessed over a mean follow-up period of 4·6 years (SD 3·8). The effect of growth hormone treatment on fracture risk was assessed by Cox proportional hazard modelling with adjustment for several confounders. Between Jan 3, 1996, and Dec 15, 2012, we enrolled 10,673 patients to this study. Of the enrolled patients, 1032 patients were excluded from assessment because of incomplete data, leaving 9641 in the analysis cohort. Of these patients, 8374 of received growth hormone and 1267 did not. Annual fracture incidence rate was lower in patients who received growth hormone than in those who did not (fracture incidence rate 1·19% vs 1·91%, hazard ratio [HR] 0·69, 95% CI 0·54-0·88). However, no difference in fracture risk was observed between patients who did and did not receive growth hormone treatment in the subgroup of patients with pre-existing osteoporosis (n=826; 0·97, 0·48-1·95). Our results suggest that growth hormone replacement therapy could be protective against fracture for adult patients with growth hormone deficiency without previously reported osteoporosis. Starting growth hormone therapy before the onset of osteoporosis might be optimum for bone health of adult patients with growth hormone deficiency. Eli Lilly and Co.

Initiation of growth hormone therapy in idiopathic short stature: do gender differences exist?

Growth hormone (GH) registries indicate that boys receive preferential GH treatment for idiopathic short stature (ISS). The aim was to determine whether age, auxological parameters, pubertal status, and target height differ between genders at GH initiation. Review of the computerized files of the endocrine department of a tertiary pediatric medical center identified 184 patients who started GH therapy for ISS between 2003-2011. Data on auxologic parameters, predicted height, parental height, and pubertal status were collected and compared between boys and girls. Boys accounted for a significantly higher percentage of the study group (65.8%, p<0.001). At onset of GH therapy, there were no significant differences between boys and girls in age (10.2±3.1 vs. 9.9±2.4 years), height-standard deviation score (SDS) (-2.64±0.5 vs. -2.79±0.5), body mass index-SDS[(-0.65±1.01) vs. (-0.80±1.13)], or pubertal status (66% vs. 63.5% prepubertal). Predicted height-SDS was significantly higher in boys (-1.95±1.05 vs. -2.56±0.73, p<0.001). Midparental height-SDS was similar in the two groups, as were paternal and maternal height. The similar age, height deficit, and pubertal status at onset of GH treatment in boys and girls suggests that gender differences do not exist. Male predominance may stem from family preferences to treat boys. Future studies are warranted to assess the psychosocial aspects in the decision to initiate therapy.

An audit of growth hormone replacement for GH‐deficient adults in Scotland

Guidelines on the clinical use of growth hormone therapy in adults were issued by the UK National Institute for Clinical Excellence (NICE) in August 2003. We conducted a retrospective clinical audit on the use of growth hormone (GH) in Scotland to evaluate the use of these guidelines and their impact on clinical practice. The audit had two phases. In phase I, the impact of NICE criteria on specialist endocrine practice in starting and continuing GH replacement was assessed. In phase II, the reasons why some adults in Scotland with growth hormone deficiency were not on replacement therapy were evaluated. A retrospective cross-sectional case note review was carried out of all adult patients being followed up for growth hormone deficiency during the study period (1 March 2005 to 31 March 2008). Phase I of the audit included 208 patients and phase II 108 patients. Sellar tumours were the main cause of GH deficiency in both phases of the audit. In phase I, 53 patients (77%) had an AGHDA-QoL score >11 documented before commencing GH post-NICE guidance, compared with 35 (25%) pre-NICE guidance. Overall, only 39 patients (18%) met the full NICE criteria for starting and continuing GH (pre-NICE, 11%; post-NICE, 35%). Phase II indicated that the main reasons for not starting GH included perceived satisfactory quality of life (n = 47, 43%), patient reluctance (16, 15%) or a medical contraindication (16, 15%). Although the use of quality of life assessments has increased following publication of the NICE guidelines, most adults on GH in Scotland did not fulfil the complete set of NICE criteria. The main reason for not starting GH therapy in adult GH-deficient patients was perceived satisfactory quality of life.

Prader-Willi syndrome and growth hormone therapy: effect on sleep

Because of reports that growth hormone therapy causes increased severity of obstructive sleep apnea in Prader-Willi syndrome, a retrospective review was performed of polysomnograms performed in children with Prader-Willi syndrome before onset of therapy and 6 weeks, 6 months, 1 year, and 2 years after starting growth hormone therapy. The results from Al-Saleh et al are published in this issue of The Journal, which show that 13 of 15 children did well with no adverse sleep outcomes. However, 2 of the 15 had growth hormone therapy discontinued because of the development of severe obstructive sleep apnea after 6 weeks. The authors recommend that growth hormone therapy appears to be a safe treatment after an initial period of increased risk with regards to sleep-related breathing, but they recommend that children selected for treatment should be evaluated very carefully. This issue of growth hormone related-obstructive sleep apnea in Prader-Willi syndrome is discussed in the accompanying Editorial by Whitman and Myers. They propose recommendations for how to manage children with Prader-Willi syndrome with regards to starting growth hormone therapy. Article page 263▶ Editorial page 224▶ Longitudinal Evaluation of Sleep-Disordered Breathing in Children with Prader-Willi Syndrome during 2 Years of Growth Hormone TherapyThe Journal of PediatricsVol. 162Issue 2PreviewTo review longitudinal polysomnography data to assess sleep-related disordered breathing (SRDB) before and up to 2 years after initiation of growth hormone (GH) therapy in children with Prader-Willi syndrome (PWS). Full-Text PDF Prader-Willi Syndrome and Growth Hormone Therapy: Take a Deep Breath and Weigh the DataThe Journal of PediatricsVol. 162Issue 2PreviewPrader-Willi syndrome (PWS), a complex neurogenetic disorder originally described in 1956,1 was relatively unknown outside genetics and developmental clinics until the late 1990s when growth hormone replacement therapy (GHRT) emerged as an effective intervention. The cardinal feature is the early onset, unrelenting, treatment-refractory hyperphagia leading to morbid obesity and attendant comorbidities. In addition, however, PWS is characterized by infantile hypotonia and failure to thrive, followed by short stature, hypogonadism, abnormal body composition, sleep and respiratory abnormalities (including impaired ventilatory control, central and obstructive apnea, and excessive daytime sleepiness), and behavioral difficulties. Full-Text PDF

Résultats du traitement précoce par hormone de croissance dans les hypopituitarismes de l'enfant

Hypopituitarism is an interesting pathological model because it allows us to examine the long-term effects of hormone replacement therapy in this population. However, the impact of growth hormone replacement therapy started before 1 year of age on final height has not been studied. The France-Hypophyse database contains the files of 59 children who started growth hormone therapy before one year of age between 1977 and 1992, and the complete growth profile of 49 patients could be analyzed Twenty girls (age at diagnosis: 6.1 +/- 3.8 months) and 29 boys (4.5 +/- 3.3 months) were treated with growth hormone for an average of 16 +/- 1.6 years. Catch-up growth was maximal during the first 3 years. At 10 years of age the patients had reached or even exceeded their target size Puberty was spontaneous (14 children) or stimulated (33 children), and occurred at an estimated bone age of 11.7 +/- 1.8 years. During puberty we observed an acceptable growth spurt but no further catch-up growth. Final height was 159 +/- 8 cm in girls and 173 +/- 7 cm in boys. No adverse effects of growth hormone therapy were reported Thanks to early GH treatment, children with hypopituitarism had a mean gap between final size and parental target size of only 0.1 +/- 1.1 SD. Early diagnosis and treatment are therefore essential in this setting.

A polymorphism in the growth hormone receptor is associated with height in children with Prader–Willi syndrome

The exon-3 deletion polymorphism (d3, Database of Genomic Variants ID: Variation_64191) in the growth hormone receptor (GHR) gene is associated with increased growth response to growth hormone (GH) therapy in GH-deficient patients. However, an association of the GHR genotype with height has not yet been reported in Prader-Willi syndrome (PWS). The aim of this study was to assess the association of GHR alleles with height before starting GH therapy in patients with PWS. Seventy-four patients with PWS were genotyped and their medical records were retrospectively reviewed (45 males and 29 females, median age 8.7 years). One hundred normal controls, with known final height, were also genotyped. The GH-exon 3 locus was genotyped using a PCR multiplex assay. The distribution of alleles in the patients with PWS was not different from controls [(fl/fl n = 53 (72%), fl/d3 n = 21 (28%)) in PWS vs. (fl/fl n = 72(72%), fl/d3 n = 26(26%), and d3/d3 n = 2(2%)]. However, patients with PWS carrying a d3 allele had significantly greater height standard deviation scores (SDS) (P = 0.025) and higher insulin-like growth factor I (IGF-I) level (P = 0.041), although the age at the start of GH therapy, weight, BMI, and body fat were not different. The d3 allele was associated with height and IGF-I levels before GH therapy and suggests that even before GH therapy, d3 allele may influence height through GH secretion.