ABSTRACT
Treatment outcomes for different causes of childhood dwarfism vary widely, and there are no studies on the economic burden of treatment in relation to outcomes. This paper compared the efficacy and healthcare costs per unit height of recombinant human growth hormone (rhGH) for the treatment of growth hormone deficiency (GHD) and idiopathic short stature (ISS) with a view to providing a more cost-effective treatment option for children. We retrospectively analyzed 117 cases (66 cases of GHD and 51 cases of ISS) of short-stature children who first visited Weifang People's Hospital between 2019.1 and 2022.1 and were treated with rhGH for 1 to 3 years to track the treatment effect and statistically analyzed by using paired t tests, non-parametric tests, and chi-square tests, to evaluate the efficacy of rhGH treatment for GHD and ISS children and the medicinal cost. The annual growth velocity (GV) of children with GHD and ISS increased the fastest during 3 to 6 months after treatment and then gradually slowed down. The GV of the GHD group was higher than that of the ISS group from 0 to 36 months after treatment (Pâ <â .05 at 3, 6, 9, and 12 months); the height standard deviation scores (HtSDS) of the children in the GHD and ISS groups increased gradually with the increase of the treatment time, and the changes in the height standard deviation scores (ΔHtSDS) of the GHD group were more significant than those of the ISS group (Pâ <â .05 at 3, 6, 9, and 12 months). (2) The medical costs in the pubertal group for a 1-cm increase in height were higher than those of children in the pre-pubertal group at the same stage (3 to 24 months Pâ <â .05). The longer the treatment time within the same group, the higher the medical cost of increasing 1cm height. RhGH is effective in treating children with dwarfism to promote height growth, and the effect on children with GHD is better than that of children with ISS; the earlier the treatment time, the lower the medical cost and the higher the comprehensive benefit.
Subject(s)
Body Height , Dwarfism , Human Growth Hormone , Recombinant Proteins , Humans , Human Growth Hormone/therapeutic use , Human Growth Hormone/economics , Child , Retrospective Studies , Male , Female , Dwarfism/drug therapy , Dwarfism/economics , Recombinant Proteins/therapeutic use , Recombinant Proteins/economics , Recombinant Proteins/administration & dosage , Body Height/drug effects , Treatment Outcome , Child, Preschool , Growth Disorders/drug therapy , Growth Disorders/economics , Growth Disorders/etiology , Economics, Pharmaceutical , Cost-Benefit Analysis , Health Care Costs/statistics & numerical data , AdolescentABSTRACT
Short stature with IGF-1 receptor (IGF1R) gene alteration is known as small-for-gestational-age (SGA) short stature with elevated serum IGF1 levels. Its prevalence and clinical characteristics remain unclear. No adapted treatment is available for short stature related to IGF1R gene alteration in Japan, and genetic testing is not yet widely accessible. We investigated short stature with IGF1R gene alterations and analyzed the clinical data of 13 patients using the results of questionnaires issued to the Japanese Society for Pediatric Endocrinology. Four cases were caused by a deletion of chromosome 15q26.3, and eight were caused by heterozygous pathogenic variants in the IGF1R gene. Cases with deletions showed a more severe degree of growth impairment (-4.5 ± 0.43 SD) than those caused by pathological variants (-2.71 ± 0.15 SD) and were accompanied by neurodevelopmental delay. However, cases caused by pathological variants lacked distinctive features. Only three of the 12 cases demonstrated serum IGF1 values exceeding +2 SD, and the other three had values below 0 SD. Four patients did not meet the criteria for SGA at birth. Six patients received GH therapy for SGA short stature and showed improvement in growth rate without any side effects or elevated serum IGF1 levels during treatment. Elevated IGF1 levels (over +2 SD) after GH treatment should be considered a suspicious finding. Owing to the lack of distinctive features, there was a possibility of undiagnosed cases of this condition. Promoting genetic testing and clinical trials on GH administration for this condition is recommended.
Subject(s)
Growth Disorders , Human Growth Hormone , Infant, Small for Gestational Age , Receptor, IGF Type 1 , Humans , Receptor, IGF Type 1/genetics , Female , Male , Child , Human Growth Hormone/therapeutic use , Growth Disorders/drug therapy , Growth Disorders/genetics , Child, Preschool , Infant, Small for Gestational Age/growth & development , Insulin-Like Growth Factor I/metabolism , Adolescent , Dwarfism/drug therapy , Dwarfism/genetics , Japan , Body Height/drug effects , Treatment OutcomeABSTRACT
Patients with Aarskog-Scott syndrome (AAS) have short stature, facial anomalies, skeletal deformities, and genitourinary malformations. FYVE, RhoGEF, and PH domain-containing 1 (FGD1) is the only known causative gene of AAS. However, the diagnosis of AAS remains difficult, and specific treatments are still absent. Patients suspected with AAS were recruited, and clinical information was collected. Genetic testing and functional analysis were carried out for the diagnosis. By literature review, we summarized the clinical and genetic characteristics of FGD1-related AAS and analyzed the genotype-phenotype correlation. Five patients were recruited, and four novel FGD1 variants were identified. The diagnosis of AAS was confirmed by genetic analysis and functional study. Three patients treated with growth hormone showed improved heights during the follow-up period. By literature review, clinical features of AAS patients with FGD1 variants were summarized. Regarding FGD1 variations, substitutions were the most common form, and among them, missense variants were the most frequent. Moreover, we found patients with drastic variants showed higher incidences of foot and genitourinary malformations. Missense variants in DH domain were related to a lower incidence of cryptorchidism. Conclusion: We reported four novel pathogenic FGD1 variations in AAS patients and confirmed the efficacy and safety of growth hormone treatment in FGD1-related AAS patients with growth hormone deficiency. Additionally, our literature review suggested the crucial role of DH domain in FGD1 function. What is Known: ⢠Aarskog-Scott syndrome is a rare genetic disease, and the only known cause is the variant in FGD1 gene. The typical clinical manifestations of AAS include facial, skeletal, and urogenital deformities and short stature. What is New: ⢠We reported four novel FGD1 variants and reported the treatment of growth hormone in FGD1-related AAS patients. Our genotype-phenotype correlation analysis suggested the crucial role of DH domain in FGD1 function.
Subject(s)
Abnormalities, Multiple , Face , Genetic Diseases, X-Linked , Genitalia, Male , Guanine Nucleotide Exchange Factors , Child , Child, Preschool , Female , Humans , Male , Abnormalities, Multiple/genetics , Abnormalities, Multiple/diagnosis , Dwarfism/genetics , Dwarfism/diagnosis , Dwarfism/drug therapy , Face/abnormalities , Genetic Association Studies , Genitalia, Male/abnormalities , Guanine Nucleotide Exchange Factors/genetics , Hand Deformities, Congenital/genetics , Hand Deformities, Congenital/diagnosis , Heart Defects, Congenital/genetics , Heart Defects, Congenital/diagnosis , Phenotype , Scalp Dermatoses/genetics , Scalp Dermatoses/diagnosis , Scalp Dermatoses/drug therapy , Scalp Dermatoses/congenital , Urogenital Abnormalities/genetics , Urogenital Abnormalities/diagnosisABSTRACT
BACKGROUND: This retrospective study explored the effect on adult height of a combination of recombinant human growth hormone (rhGH) and aromatase inhibitors (AIs), or rhGH and a gonadotropin-releasing hormone analog (GnRHa), and compared their effects with rhGH alone in males at advanced bone age with idiopathic short stature (ISS). METHODS: In this retrospective study, rhGH or rhGH combined with GnRHa or rhGH combined with AI therapy was given to males with advanced bone age (13-15 years) and diagnosed with ISS. The patients were followed to assess their adult height. RESULTS: (1) A total of 68 patients were reviewed; 22 males were treated with rhGH for 24.9 ± 4.47 months, 22 males were treated with GnRHa + rhGH for 34.1 ± 3.36 months, and 24 males were treated with AI + RHGH for 22.7 ± 2.49 months. (2) Before treatment, the HtSDS-CA for the three groups were -1.04 ± 0.95, -1.23 ± 1.06, and -0.85 ± 0.98, respectively, and the HtSDS-BA were -2.14 ± 0.29, -2.14 ± 0.21, and-2.26 ± 0.31, respectively. The target heights for each group were 169.7 ± 4.0 cm, 169.7 ± 3.9 cm, and 169.1 ± 3.9 cm, respectively. The predicted adult heights were 161.7 ± 3.35 cm, 162.3 ± 1.75 cm, and 161.6 ± 2.89 cm, respectively. (3) After treatment, the HtSDS-CA for the rhGH group increased by 1.30 ± 0.58, and the HtSDS-BA increased by 2.00 ± 0.27. For the GnRHa + rhGH group, the HtSDS-CA and HtSDS-BA increased by1.42 ± 0.73and 2.74 ± 0.28, respectively. The AI + RHGH group increased by1.39 ± 0.64 and 2.76 ± 0.31, respectively. (4) There was no significant difference between the adult height (170.9 ± 0.7 cm) and target height for the rhGH group (P > 0.05), but the adult heights for the GnRHa + rhGH and AI + RHGH groups (173.2 ± 1.5 cm and 173.5 ± 1.0 cm, respectively, P > 0.05) were higher than the target height (P < 0.05). (5) Compared with the predicted adult height, the adult heights for the three groups improved significantly (P < 0.05). (6) No severe adverse reactions during the treatment occurred in any of the children. However, the total incidence of side effects in the three groups was significant (χ2 = 20.433, P = 0.00). CONCLUSION: Different therapeutic approaches have been investigated to improve the final adult height of males at advanced bone ages with ISS, and the optimal strategy remains controversial. In children at advanced bone ages with ISS, clinicians should carefully consider the advantages and disadvantages prior to treatment.
Subject(s)
Dwarfism , Human Growth Hormone , Male , Child , Humans , Adult , Adolescent , Growth Disorders/drug therapy , Retrospective Studies , Body Height , Dwarfism/drug therapy , Human Growth Hormone/therapeutic use , Recombinant Proteins/therapeutic use , Recombinant Proteins/pharmacologyABSTRACT
BACKGROUND: Severe primary insulin-like growth factor-I (IGF-I) deficiency (SPIGFD) is a rare growth disorder characterized by short stature (standard deviation score [SDS] ≤ 3.0), low circulating concentrations of IGF-I (SDS ≤ 3.0), and normal or elevated concentrations of growth hormone (GH). Laron syndrome is the best characterized form of SPIGFD, caused by a defect in the GH receptor (GHR) gene. However, awareness of SPIGFD remains low, and individuals living with SPIGFD continue to face challenges associated with diagnosis, treatment and care. OBJECTIVE: To gather perspectives on the key challenges for individuals and families living with SPIGFD through a multi-stakeholder approach. By highlighting critical gaps in the awareness, diagnosis, and management of SPIGFD, this report aims to provide recommendations to improve care for people affected by SPIGFD globally. METHODS: An international group of clinical experts, researchers, and patient and caregiver representatives from the SPIGFD community participated in a virtual, half-day meeting to discuss key unmet needs and opportunities to improve the care of people living with SPIGFD. RESULTS: As a rare disorder, limited awareness and understanding of SPIGFD amongst healthcare professionals (HCPs) poses significant challenges in the diagnosis and treatment of those affected. Patients often face difficulties associated with receiving a formal diagnosis, delayed treatment initiation and limited access to appropriate therapy. This has a considerable impact on the physical health and quality of life for patients, highlighting a need for more education and clearer guidance for HCPs. Support from patient advocacy groups is valuable in helping patients and their families to find appropriate care. However, there remains a need to better understand the burden that SPIGFD has on individuals beyond height, including the impact on physical, emotional, and social wellbeing. CONCLUSIONS: To address the challenges faced by individuals and families affected by SPIGFD, greater awareness of SPIGFD is needed within the healthcare community, and a consensus on best practice in the care of individuals affected by this condition. Continued efforts are also needed at a global level to challenge existing perceptions around SPIGFD, and identify solutions that promote equitable access to appropriate care. Medical writing support was industry-sponsored.
Subject(s)
Dwarfism , Laron Syndrome , Humans , Insulin-Like Growth Factor I/therapeutic use , Quality of Life , Laron Syndrome/diagnosis , Laron Syndrome/drug therapy , Laron Syndrome/genetics , Dwarfism/drug therapy , Growth DisordersABSTRACT
BACKGROUND: The pathogenic mutation of short stature homeobox (SHOX) gene is one of the main genetic causes of short stature in children, with an incidence rate of 1/1000~1/2000 and the main clinical manifestations are short stature and (or) limb skeletal abnormalities. SHOX gene mutations are mostly large deletions of regulatory sequence genes, while exon mutations are relatively rare. The pathogenic rate of mutations occurring in exon 5 is only 1/50 000~1/100 000. This study reviewed the clinical data of a child with SHOX gene mutation in exon 5, and analyzed the clinical phenotype, pathogenesis, diagnosis, treatment and prognosis of SHOX gene mutation in combination with relevant literature at home and abroad. CASE PRESENTATION: The patient was an 8-year-old girl with a height of 105.2 cm (-4.31 standard deviations). Her sitting height/height ratio was 56.8% (>55.5%), and she exhibited high-arched palate, irregular dentition, micrognathia, short fingers, and a normal growth hormone stimulation test. Whole-exome sequencing was performed, and Sanger sequencing was used for site validation. The sequencing results revealed a heterozygous mutation of c.577Gâ >â A in exon 5 of the SHOX gene, inherited from the father. The clinical symptoms of the proband were consistent with the phenotype of short stature idiopathic familial associated with SHOX gene mutations. The father, grandfather, uncle, and sister of the proband all had the c.577Gâ >â A heterozygous mutation. Therefore, the clinical diagnosis was childhood short stature caused by SHOX gene defects. The SHOX: c.577Gâ >â A mutation is likely to be the genetic etiology of familial idiopathic short stature in this family, and this novel mutation enriches the mutation spectrum of the SHOX gene. CONCLUSION: This is the first case report of familial idiopathic dwarfism caused by mutation at the c.577Gâ >â A locus of exon 5 of SHOX gene in the world. This novel mutation enriches the mutation spectrum of the SHOX gene. It is important to emphasize genetic testing, including the SHOX gene, in patients with familial idiopathic short stature and to provide timely growth hormone therapy to individuals with short stature caused by SHOX gene mutations in order to improve their adult height.
Subject(s)
Dwarfism , Genes, Homeobox , Humans , Child , Female , Adult , Homeodomain Proteins/genetics , Short Stature Homeobox Protein/genetics , Dwarfism/genetics , Dwarfism/drug therapy , Mutation , Growth Hormone/therapeutic use , Body Height/genetics , Growth Disorders/drug therapyABSTRACT
Type 1 Insulin-like Growth Factor Receptor(IGF1R) plays a fundamental role in normal growth and development. Its disruption is usually characterized by severe intrauterine and postnatal growth retardation, microcephaly and neurodevelopmental delay.The efficacy of recombinant human growth hormone treatment remains a challenge for children with IGF1 resistance and pathogenic mutations of IGF1R, with limited data in patients carrying the most severe form of IGF1R defect, the ring chromosome 15. SUBJECT AND METHOD: We tested a high dose of rhGH in a new patient with ring chromosome 15, as confirmed by karyotype and CGH array. We performed a systematic review, and all published r(15) syndrome cases treated by growth hormone(GH) up to April 2023 were searched, and their response to GH therapy was recorded and summarized. RESULTS: Twelve patients with ring chromosome 15 received GH therapy according to a literature review. We expand the spectrum by the 13th case treated by GH, and we report an impressive improvement in intellectual performance and progressive catch-up growth after 5 and 20 months of follow-up. By introducing our new case in the analysis, the sex ratio was 3:10, and GH therapy was started at the age of 5.5 (3/9.4) (years) for an age of diagnosis of 4.75 (1.3/9.5) (years). The height before GH therapy was -5.1(-5.9/-4.1) SDS. The median duration of treatment was 1.7(0.9/2) (years), with a median height gain of 1(0.3/1.8) SDS and an improvement in growth velocity of 4.1(2.8/5.3) (cm/year). CONCLUSION: GH seems to be effective for r(15) syndrome patients with short stature.
Subject(s)
Dwarfism , Human Growth Hormone , Ring Chromosomes , Child , Humans , Child, Preschool , Human Growth Hormone/therapeutic use , Growth Hormone , Growth Disorders/drug therapy , Growth Disorders/genetics , Dwarfism/drug therapy , SyndromeABSTRACT
OBJECTIVE: Heterozygous loss-of-function variants in the NPR2 gene cause short stature with nonspecific skeletal abnormalities and account for about 2 ~ 6% of idiopathic short stature. This study aimed to analyze and identify pathogenic variants in the NPR2 gene and explore the therapeutic response to recombinant growth hormone (rhGH). METHODS: NPR2 was sequenced in three Chinese Han patients with short stature via exome sequencing. In vitro functional experiments, homology modeling and molecular docking analysis of variants were performed to examine putative protein changes and the pathogenicity of the variants. RESULT: Three patients received rhGH therapy for two years, and two NPR2 heterozygous variants were identified in three unrelated cases: c.1579 C > T,p.Leu527Phe in patient 1 and c.2842dupC,p.His948Profs*5 in patient 2. Subsequently, a small gene model was constructed, and transcriptional analysis of the synonymous variant (c.2643G > A) was performed in patient 3, which revealed the deletion of exon 17 and the premature formation of a stop codon (p.His840Gln*). Functional studies showed that both NPR2 variants, His948Profs*5 and His840Gln*, failed to produce cGMP in the homozygous state. Furthermore, the Leu527Phe variant of NPR2 was almost unresponsive to the stimulatory effect of ATP on CNP-dependent guanylyl cyclase activity. This loss of response to ATP has not been previously reported. The average age of patients at the start of treatment was 6.5 ± 1.8 years old, and their height increased by 1.59 ± 0.1 standard deviation score after 2 years of treatment. CONCLUSION: In this report, two novel variants in NPR2 gene were described. Our findings broaden the genotypic spectrum of NPR2 variants in individuals with short stature and provid insights into the efficacy of rhGH in these patients.
Subject(s)
Dwarfism , Growth Hormone , Receptors, Atrial Natriuretic Factor , Child , Child, Preschool , Humans , Adenosine Triphosphate , Body Height , Dwarfism/drug therapy , Dwarfism/genetics , Growth Hormone/genetics , Growth Hormone/therapeutic use , Molecular Docking Simulation , Mutation , Receptors, Atrial Natriuretic Factor/geneticsABSTRACT
OBJECTIVE: To analyze the clinical features of 3M syndrome and effect of growth hormone therapy. METHODS: Clinical data of four children diagnosed with 3M syndrome by whole exome sequencing at Hunan Children's Hospital from January 2014 to February 2022 were retrospectively analyzed, which included clinical manifestation, results of genetic testing and recombinant human growth hormone (rhGH) therapy. A literature review was also carried our for Chinese patients with 3M syndrome. RESULTS: The clinical manifestations of the 4 patients included severe growth retardation, facial dysmorphism and skeletal malformations. Two patients were found to harbor homozygous variants of CUL7 gene, namely c.4717C>T (p.R1573*) and c.967_993delinsCAGCTGG (p.S323Qfs*33). Two patients were found to harbor 3 heterozygous variants of the OBSL1 gene including c.1118G>A (p.W373*), c.458dupG (p.L154Pfs*1002) and c.690dupC (p.E231Rfs*23), among which c.967_993delinsCAGCTGG and c.1118G>A were unreported previously. Eighteen Chinese patients with 3M syndrome were identified through the literature review, including 11 cases (11/18, 61.1%) carrying CUL7 gene variants and 7 cases (7/18, 38.9%) carrying OBSL1 gene variants. The main clinical manifestations were in keeping with previously reported. Four patients were treated with growth hormone, 3 showed obvious growth acceleration, and no adverse reaction was noted. CONCLUSION: 3M syndrome has a typical appearance and obvious short stature. To attain accurate diagnosis, genetic testing should be recommended for children with a stature of less than -3 SD and facial dysmorphism. The long-term efficacy of growth hormone therapy for patients with 3M syndrome remains to be observed.
Subject(s)
Dwarfism , Humans , Child , Retrospective Studies , Dwarfism/drug therapy , Dwarfism/genetics , Muscle Hypotonia/genetics , Growth Hormone/therapeutic use , Cytoskeletal Proteins/geneticsABSTRACT
OBJECTIVE: Boys outnumber girls in short stature evaluations and growth hormone treatment despite absence of gender differences in short stature prevalence. Family views on short stature influence medical management, but gender-based analysis of these views is lacking. This study explored endocrine patients' and their parents' perceptions of short stature and its impact on quality of life by patient gender. METHODS: Patients aged 8 to 14 years undergoing provocative growth hormone testing and 1 parent each completed semistructured interviews. Clinical data were extracted by chart review. RESULTS: Twenty-four patient-parent dyads (6 female patients, 22 mothers; predominantly non-Hispanic White) participated. Six major themes emerged: (1) patients' perceptions of their short stature were similar by gender, (2) physical experiences of short stature were similar by gender, (3) social experiences of short stature were both similar and different by gender, (4) parental perceptions of short stature as a factor limiting their child's functionality were similar by gender, (5) concern about societal stigma related to short stature arose for both genders, and (6) patients' perceptions of parental messaging about the import of their short stature were similar by gender. CONCLUSION: Our data reveal more similarities than differences between genders in patient perceptions and patient and parent-reported experiences of short stature. Worry about stature-related stigma was noted for patients of both genders. Parental messaging about short stature emerged as an important area to explore further by patient gender. Our findings suggest that clinicians should be wary of making gender or stigma-based assumptions when evaluating children with short stature.
Subject(s)
Dwarfism , Human Growth Hormone , Child , Female , Humans , Male , Dwarfism/drug therapy , Dwarfism/psychology , Growth Hormone , Parents/psychology , Quality of Life , Social Stigma , Sexism , Body HeightABSTRACT
BACKGROUND: Herbal medicines have been used for a long time to treat idiopathic short stature (ISS) in children in East Asian countries. The aim of this study was to analyze the cost-effectiveness of 5 herbal medicines frequently used in clinical settings for children with ISS based on medical records. METHODS: Patients with ISS who had been prescribed a 60-day supply of herbal medicines in 1 Korean medicine hospital were included in this analysis. Their height and height percentile were measured before and after treatment within 6-months. The average cost-effectiveness ratios (ACERs) of 5 herbal medicines for height (cm) and height percentile were calculated for boys and girls, respectively. RESULTS: The ACERs per 1 cm height growth were USD 56.2 (Naesohwajung-Tang), USD 74.8 (Ogapi-Growth decoction), USD 86.6 (Gamcho-Growth decoction), USD 94.6 (Gwakhyangjeonggi-San plus Yukmijihwang-Tang), and USD 113.8 (Boyang-Growth decoction). The ACERs per 1 percentile height growth were USD 205 (Naesohwajung-Tang), USD 293 (Ogapi-Growth decoction), USD 470 (Gamcho-Growth decoction), USD 949 (Boyang-Growth decoction), and USD 1051 (Gwakhyangjeonggi-San plus Yukmijihwang-Tang). CONCLUSION: Herbal medicine might be a potential economical alternative treatment for ISS.
Subject(s)
Dwarfism , Human Growth Hormone , Plants, Medicinal , Male , Female , Humans , Child , Cost-Effectiveness Analysis , Dwarfism/drug therapy , Human Growth Hormone/therapeutic use , Growth Disorders/drug therapy , Body HeightABSTRACT
Idiopathic short stature (ISS) is a diagnosis of exclusion, and therefore each child with short stature or slow growth referred to a paediatrician deserves a full medical history and physical examination, as well as radiological and laboratory screening tests. In patients with an increased likelihood of a genetic cause, genetic testing is indicated. Idiopathic short stature is an approved indication for recombinant human growth hormone (rhGH) in the USA but not in most other parts of the world. In a recent article published in this journal, Luo et al reported on the 1-year's results of a multicentre randomized controlled trial (n = 360) on the efficacy and safety of two dosages of long-acting PEGylated rhGH (PEG-rhGH, Jintrolong®) (0.1 or 0.2â mg/kg body weight per week, respectively) in children with ISS compared with an untreated control group. The growth response to the higher dosage was similar to reported data on daily rhGH. In this commentary, we discuss whether the recent data on genetic causes of short stature in children who initially were labelled ISS, and data on the long-term safety of daily rhGH, may influence the balance between risks and benefits of rhGH treatment in children with ISS. We further discuss the pharmacokinetic and -dynamic profile of PEG-rhGH and its potential consequences for long-term safety.
Subject(s)
Dwarfism , Human Growth Hormone , Humans , Child , Human Growth Hormone/therapeutic use , Growth Hormone , Growth Disorders/diagnosis , Growth Disorders/drug therapy , Dwarfism/diagnosis , Dwarfism/drug therapy , Recombinant Proteins/therapeutic use , Polyethylene Glycols/therapeutic use , Body HeightABSTRACT
AIM: To estimate the association between attention-deficit hyperactivity disorder (ADHD) and relatively short stature (RSS) among adolescents. METHODS: Participants in the Israeli Youth Health and Nutrition Survey (2015-2016), a cross-sectional school-based study, completed self-administered questionnaires and underwent anthropometric measurements. Height z-score < -0.7 (<25th percentile) was defined as RSS. Multivariable logistic regression analyses assessed the relation between ADHD and RSS, controlling for age, sex, body mass index (BMI) and socioeconomic status (Basic Model), and also for lifestyle factors such as physical activity, sleep duration, dietary patterns and intakes. RESULTS: Of 4173 participants (11-18 years, 50.2% males), 654 self-reported ever being diagnosed with ADHD; 3519 participants were controls. Overweight (BMI z-score ≥1) and pubertal status were not different among groups. According to the Basic Model, ADHD was significantly associated with RSS (OR 1.25, 95% CI 1.03-1.50), and even after adjustments for lifestyle factors and dietary intake (OR 1.28, 95% CI 1.03-1.58). Stimulant-treated ADHD adolescents had similar height z-scores and lifestyles as those not treated with stimulants. CONCLUSION: Attention-deficit hyperactivity disorder was associated with RSS. Height deficit may be intrinsic to ADHD or its pharmacotherapy, rather than a consequence of lifestyle alone. Further studies are needed to determine the causal relationship between ADHD and short stature.
Subject(s)
Attention Deficit Disorder with Hyperactivity , Central Nervous System Stimulants , Dwarfism , Male , Humans , Adolescent , Female , Attention Deficit Disorder with Hyperactivity/complications , Cross-Sectional Studies , Body Mass Index , Overweight , Dwarfism/drug therapyABSTRACT
INTRODUCTION: Children with ADHD often present to pediatric endocrinologists due to growth concerns. Growth hormone stimulation testing (GHST) may be utilized as part of the workup. We evaluate whether children with ADHD and short stature or growth failure are more likely to fail GHST compared to children without ADHD. METHODS: We retrospectively studied children who underwent GHST as part of evaluation for short stature and/or growth failure and had an intact pituitary over a 16-year period (2002-2018). We performed univariate and logistic regression analyses with stratification by age. RESULTS: We included 260 children; 78 children had ADHD and were older, mean age (±SD) 12.2 (±2.6) years versus children without ADHD, mean age (±SD) 10.4 (±3.8) years. The population was largely Caucasian, and boys outnumbered the girls. Of the children with ADHD, only 9 were not medically treated. There was no difference in z-scores for height, weight, and BMI, or mid-parental height between the two groups. We found that children with ADHD were more likely to fail GHST than children without ADHD across the peak GH cut-offs of 10, 7, and 5 ng/mL (p = 0.003, p = 0.023, and p = 0.046 accordingly). The same trend persisted after regression analysis with adjustment for sex and stratification by age, and effect was more robust in the older group. DISCUSSION: The result shows higher likelihood of lower GH peaks in response to GHST in children with ADHD and short stature or impaired linear growth. Future work should evaluate possible mechanistic explanation and the role of psycho-stimulant medications.
Subject(s)
Attention Deficit Disorder with Hyperactivity , Central Nervous System Stimulants , Dwarfism , Human Growth Hormone , Male , Female , Humans , Child , Adolescent , Attention Deficit Disorder with Hyperactivity/diagnosis , Attention Deficit Disorder with Hyperactivity/drug therapy , Retrospective Studies , Central Nervous System Stimulants/therapeutic use , Human Growth Hormone/therapeutic use , Growth Hormone/therapeutic use , Dwarfism/drug therapyABSTRACT
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.
Subject(s)
Dwarfism , Familial Hypophosphatemic Rickets , Human Growth Hormone , Child , Female , Humans , Male , Body Height , Dwarfism/drug therapy , Familial Hypophosphatemic Rickets/drug therapy , Growth Disorders/drug therapy , Growth Hormone/therapeutic use , Human Growth Hormone/therapeutic use , Retrospective StudiesABSTRACT
BACKGROUND: People have long been fascinated with the size and growth of living things, from the giants of classic mythology and art to the little people who also have appeared in classical art, as well as the courts of European monarchs, and were exploited in "shows." Serious medical evaluation began in the late 19th century with the description of acromegaly and its association with pituitary tumors. In the early 20th century, multiple investigators attempted to extract a growth-promoting factor from the anterior pituitary and then, over the decades, to purify it and distinguish it from other anterior pituitary hormones. With relatively pure growth hormone (GH), its biological activity in growth promotion and as a metabolic hormone were studied, and species specificity became apparent: primate GH was the only GH active in man. Human GH was prepared from cadaveric pituitaries and distributed by the NIH to treat children with GH deficiency, but there was never enough pituitary hGH for all of the children who required it. When Creutzfeldt-Jakob disease was found in some patients who received pituitary GH, the production and FDA approval of biosynthetic hGH dramatically accelerated. With a large supply, one could treat those who were GH deficient and test its efficacy in other causes of short stature; longer acting versions of hGH have now been developed, tested, and in a few instances received FDA approval. SUMMARY: It has been a long journey from the description of over- and underproduction of GH in animals to the production and clinical use of the biosynthetic hormones. KEY MESSAGES: The efforts of basic scientists led to the extraction and purification of GH. Clinical scientists have expanded the appropriate use of hGH for short children with conditions in addition to GH deficiency.
Subject(s)
Acromegaly , Dwarfism , Human Growth Hormone , Animals , Humans , Acromegaly/history , Acromegaly/physiopathology , Dwarfism/drug therapy , Dwarfism/history , Dwarfism/physiopathology , Endocrine System Diseases/drug therapy , Endocrine System Diseases/etiology , Endocrine System Diseases/history , Endocrine System Diseases/physiopathology , Growth Hormone/physiology , Growth Hormone/therapeutic use , Human Growth Hormone/adverse effects , Human Growth Hormone/chemical synthesis , Human Growth Hormone/physiology , Human Growth Hormone/therapeutic use , Pituitary Hormones, AnteriorABSTRACT
The article presents data about short stature due to intrauterine development delay. This type of short stature - separate nosology, unites children born small for gestation age. The majority of them in the first years of life have accelerated growth rates, allowing the child to normalize their weight-growth indicators and catch up in the development of peers. In the absence of an accelerated growth rates, children have a high risk of lagging behind in physical development throughout childhood, achieving low final growth and becoming short adults. In addition, the fact of birth with small body sizes is associated with a number of hormonal and metabolic features, a risk of metabolic syndrome in adult years.It is assumed that the absence of postnatal growth acceleration is due to various damages to the GH-IGF1 axis (partial GH deficiency, partial resistance to GH, partial resistance to IGF1). Growth hormone therapy, initiated early in life, is able to normalize growth rates in childhood and ultimately significantly improve or normalize the final growth of short stature children born small for gestational age.
Subject(s)
Dwarfism , Human Growth Hormone , Infant, Newborn , Child , Adult , Female , Humans , Fetal Growth Retardation/drug therapy , Fetal Growth Retardation/metabolism , Body Height , Infant, Small for Gestational Age , Human Growth Hormone/adverse effects , Growth Hormone/therapeutic use , Growth Hormone/metabolism , Dwarfism/drug therapyABSTRACT
Objective: This study analyzed eight Chinese short stature children with aggrecan deficiency, and aimed to investigate potential genotype-phenotype correlations, differences in clinical characteristics between the Chinese and the Western populations, and effectiveness of recombinant human growth hormone therapy in patients with ACAN variants through a review of the literature. Methods: Pediatric short stature patients with ACAN heterozygous variants were identified using whole-exome sequencing. Subsequently, a literature review was carried out to summarize the clinical features, genetic findings, and efficacy of growth-promoting therapy in patients with ACAN variants. Results: We identified seven novel ACAN mutations and one recurrent variant. Patients in our center manifested with short stature (average height SDS: -3.30 ± 0.85) with slight dysmorphic characteristics. The prevalence of dysmorphic features in the Chinese populations is significantly lower than that in the Western populations. Meanwhile, only 24.24% of aggrecan-deficient Chinese children showed significantly advanced bone age (BA). Promising therapeutic benefits were seen in the patients who received growth-promoting treatment, with an increase in growth velocity from 4.52 ± 1.00 cm/year to 8.03 ± 1.16 cm/year. Conclusion: This study further expanded the variation spectrum of the ACAN gene and demonstrated that Chinese children with short stature who carried ACAN heterozygous variants exhibited early growth cessation, which may remain unnoticed by clinicians as most of these children had very mild dysmorphic characteristics and showed BA that was consistent with the chronological age. Genetic testing may help in the diagnosis.
Subject(s)
Dwarfism , Humans , Child , Aggrecans/genetics , Heterozygote , Dwarfism/drug therapy , Dwarfism/genetics , Asian People/genetics , China/epidemiologyABSTRACT
Growth hormone (GH) is an injectable medication originally used to replace the deficiency of the hormone, but has expanded to treating conditions that may reduce growth and adult height even when the body maintains endogenous GH production. In the United States, there are 8 Food and Drug Administration (FDA)-approved indications for pediatric GH therapy: GH deficiency, Prader-Willi Syndrome, small for gestational age (SGA) without catch-up growth, idiopathic short stature, Turner syndrome, SHOX gene haploinsufficiency, Noonan Syndrome, and chronic renal insufficiency. We characterize the growth patterns and effects of GH treatment in each of these indications. We also review patterns of growth that warrant referral to a pediatric endocrinologist, as well as safety updates. This review is intended to guide practitioners on the initial evaluation and management of patients with short stature, and the indications for GH therapy.
Subject(s)
Dwarfism , Human Growth Hormone , Prader-Willi Syndrome , Turner Syndrome , Adult , Child , Dwarfism/drug therapy , Growth Disorders/diagnosis , Growth Disorders/drug therapy , Growth Hormone/therapeutic use , Human Growth Hormone/therapeutic use , Humans , Prader-Willi Syndrome/diagnosis , Prader-Willi Syndrome/drug therapy , Turner Syndrome/chemically induced , Turner Syndrome/diagnosis , Turner Syndrome/drug therapy , United StatesABSTRACT
Long-acting growth hormone (LAGH) is emerging to be a new preparation for treatment of short stature. We aimed to determine whether 12-month treatment with LAGH in patients with idiopathic short stature has an effect on the nocturnal endogenous growth hormone (GH) secretion and metabolic consequences and efficacy. Participants included 10 GH-naïve prepubertal children with idiopathic short stature (ISS). One patient was withdrawn due to own decline during study. Participants were randomized on a 1:1 ratio to receive either a daily GH (0.37 mg/kg/week) or once-weekly LAGH (0.7 mg/kg/week) over a 12-month period. Nocturnal endogenous GH secretory profiles obtained from 12-h blood samplings at 30-min interval were assessed at baseline and 2 weeks after the completion of GH treatment. Post-treatment changes in height velocity, height standard deviation score (SDS), metabolic parameters, and adverse events were measured. A total of 4 patients received LAGH, and 5 patients received daily GH. Nocturnal endogenous GH secretory profiles, such as mean serum GH concentrations, frequency, amplitude, interpulse interval of spontaneous GH secretory bursts, and mass of GH released per secretory burst were similar at baseline and after 12-month treatment in both groups. The efficacy and safety after LAGH treatment for 12 months were similar to those of daily GH. In conclusions, these findings indicated that LAGH does not suppress endogenous GH secretion, and can be used for treatment of non-GH deficient short stature with similar efficacy and safety compared to daily GH. These may contribute to define and develop treatment and follow-up protocols for LAGH use in ISS patients.