Evaluation Of Short Stature Research Articles

Pragmatic Evaluation of Growth Hormone Stimulation Tests in Short Stature.

To assess the performance of growth hormone stimulation tests (GHSTs) in the evaluation of short stature. It was a single-centre retrospective study carried out in children evaluated for short stature between January 2005 to March 2020. The clonidine stimulation test (CST) and glucagon stimulation test (GST) were used to assess growth hormone (GH) reserve (GST was performed only when peak GH levels were between 5 to ≤10 ng/mL on CST). A GH level of <5 ng/mL on CST or ≤10 ng/ml on both was used to corroborate GH deficiency. A total of 556 children were eligible for this study. The mean (SD) age was 12.9 (3.5) years, and 66.3% were male. The peak GH level [median (IQR)] was 5.50 ng/ml (1.90 - 7.50) on CST (at 60 minutes) and 7.45 ng/ml (2.15 - 10.77) on GST (at 120 minutes). On restricting sampling to two time points, the false positive rate was 13.6% on CST (60, 90 minutes) and 11.5% on GST (120, 150 minutes). Similarly, restricting to three time points was associated with a false positive rate of 8.5% on CST (60, 90, 120 minutes) and 3.8% on GST (90, 120, 150 minutes). Using the treating clinician-determined diagnosis of GHD as a reference standard, the optimal cut-off of peak GH on CST was 7.79 ng/ml (sensitivity: 83.8%; specificity: 89.4%). Restricting the GH sampling to fewer time points is associated with an increase in the false positivity rate (FPR).

A Genetic Approach in the Evaluation of Short Stature.

Short stature is considered a condition in which the height is 2 standard deviations below the mean height of a given age, sex, and population group. Human height is a polygenic and heterogeneous characteristic, and its heritability is reported to be approximately 80%. More than 600 variants associated with human growth were detected in the genome-wide association studies. Rare and common variants concurrently affect human height. The rare variations that play a role in human height determination and have a strong impact on protein functions lead to monogenic short stature phenotypes, which are a highly heterogeneous group. With rapidly developing technologies in the last decade, molecular genetic tests have begun to be used widely in clinical genetics, and thus, the genetic etiology of several rare diseases has been elucidated. Identifying the genetic etiology underlying idiopathic short stature which represents phenotypically heterogeneous group of diseases ranging from isolated short stature to severe and syndromic short stature has promoted the understanding of the genetic regulation of growth plate and longitudinal bone growth. In cases of short stature, definite molecular diagnosis based on genetic evaluation enables the patient and family to receive genetic counseling on the natural course of the disease, prognosis, genetic basis, and recurrence risk. The determination of the genetic etiology in growth disorders is essential for the development of novel targeted therapies and crucial in the development of mutation-specific treatments in the future.

Prevalence of Vitamin D Deficiency in Children with Fractures: Before and during the COVID-19 Outbreak.

Background Although it is generally agreed that vitamin D is important for bone health, the role of vitamin D in preventing fractures in children and adolescents remains unclear. Therefore, this study aimed to investigate the prevalence of vitamin D deficiency and insufficiency in healthy Korean children with fractures. Our secondary aim was to compare serum vitamin D levels before and during the coronavirus disease 2019 (COVID-19) outbreak. Methods We evaluated 334 patients with fractures who were surgically treated at our institution between 2018 and 2019 before the onset of COVID-19 (group I). In addition, we collected data on the serum 25(OH)D levels of 210 patients who visited our pediatric department for evaluation of short stature (group II) and the serum 25(OH)D levels of the patients with fractures during the COVID-19 pandemic period (group III). A serum 25(OH)D level of <20 ng/mL was considered deficient, between 20 and 32 ng/mL was insufficient, and ≥32 ng/mL was considered sufficient. Results The mean age was 8.1 ± 3.5 years in group I, 8.2 ± 3.7 years in group II, and 8.6 ± 3.5 years in group III. The prevalence of vitamin D deficiency was 53.0% in group I and 32.9% in group II. The mean serum 25(OH)D level was lower in group I than in group II (20.0 ± 7.3 ng/ml vs. 23.2 ± 6.9 ng/ml, p < 0.001). The mean serum 25(OH)D level of younger patients (<10 years) in group III was lower than that of the younger patients in the prepandemic period (21.4 ± 7.2 ng/mL vs. 19.2 ± 6.8 ng/mL, p=0.037). Conclusions We observed a high prevalence of vitamin D deficiency/insufficiency in children with fractures who required surgical treatment. During the COVID-19 pandemic, the serum vitamin D levels became even lower, especially in younger children.

Ten year analysis of the clinic profile of the tertiary paediatric endocrine service in Western Australia.

There is a paucity of information regarding the profile of entire paediatric endocrine clinics and how they are changing. This study aimed to analyse the clinic profile of the Western Australian tertiary paediatric endocrine outpatient service over 10 years and compare to national and international data. Retrospective analysis of the Western Australian Paediatric Endocrine Database (WAPED) between 2007 and 2017 looking at the frequency, proportion andlongitudinal change of diagnosis categories, specific diagnoses, and gender breakdown. In total, 2,791 endocrine diagnoses were recorded for 2,312 patients. The most frequent reason for referral (22.1% of patients), was for evaluation of abnormalities in thyroid function. The most common diagnosis being hypothyroidism (76.7%). Evaluation of short stature was the reason for referral in 19.2% of patients, 14.6% of whom were diagnosed with growth hormone deficiency. Evaluation of puberty disorders, syndromes with endocrine features and disorders of calcium and phosphate metabolism were other common reasons for clinic referral, seen in 11.3,9.8 and 8.2% of patients respectively. Between 2007 and 2017, the odds ratio of a thyroid diagnosis increased by 1.07 per year (95% CI: 1.02-1.12), whilst the odds ratio of a short stature diagnosis decreased by 0.91 per year (95% CI: 0.87-0.95). The profile of the WAPED is similar to previously published national and international data. The analysis of the profile of diagnoses and its longitudinal change over a ten-year period offer a unique opportunity to guide clinic planning, resource allocation and future research.

Is the fear from insulin tolerance test in the evaluation of short stature justified?

A nationwide survey in Israel revealed a high rate of reluctance to perform ITT. The rationale behind this attitude was a sense of fear of performing the test by many endocrinologists. We discuss the preferences for choosing GH stimulation tests and the pros and cons of alternatives to ITT. The fear of not performing ITT was not always justified. • ITT test is considered a gold standard in the evaluation of short stature to diagnose GH deficiency by many endocrinologists. • High reluctance rate found in Israel to perform ITT, prompted us to evaluate the attitudes of pediatric endocrinologists around the world showing conflicting ideas. • The role of a single paper sometimes misquoted also contributed to these conflicting results.

Causes of Short Stature in Children Referred to a Tertiary Care Center in Southeast of Iran: 2018-2020

Background: Short stature is a common problem encountered by endocrinologists. Short stature may be due to normal variations of growth or pathologic process. Evaluation of short stature and its causes in any community can be effective in reducing physical and mental illness in children. Objectives: The objective of this study was to evaluate the frequency of common causes of short stature in children referring to the endocrinology clinic. Methods: This prospective and descriptive study was carried out between August 2018 and September 2020. Included criteria were age below 18 years, height more than 2 SD below the mean for age (&lt; 3rd percentile), growth failure (&lt; 4 cm/year), small for mid-parental height, and adequate follow-up. They were evaluated by anthropometric measurements, biochemical panel, hormonal tests, radiological studies, and hormonal provocative tests. Results: A total of 509 cases, including 238 males (46.8%) and 271 females (53.2%) had short stature. The age of participants varied from 2-18 years. The mean chronological age was 11.83±3.44 years. Most study participants were over 10 years old (68%). Normal variants of growth with 271 (53.34%) children, were the most prevalent causes. These causes were in three subgroups: familial short stature: 133 (26.14%), constitutional delay of growth and puberty: 112 (22%), and idiopathic short stature: 26 (5.12%). Totally 238 cases (46.66%) were due to pathologic types of short stature. The leading cause of short stature in this group was growth hormone deficiency, which was seen in 70 (13.76%) patients. Conclusions: The normal variants of short stature as a group were the most common cause of short stature, followed by endocrinological causes of short stature and non-endocrinological causes.

Growth Hormone Stimulation Testing Patterns Contribute to Sex Differences in Pediatric Growth Hormone Treatment

Introduction: Males are twice as likely as females to receive pediatric growth hormone (GH) treatment in the USA, despite similar distributions of height z (HtZ)-scores in both sexes. Male predominance in evaluation and subspecialty referral for short stature contributes to this observation. This study investigates whether sex differences in GH stimulation testing and subsequent GH prescription further contribute to male predominance in GH treatment. Methods: Retrospective chart review was conducted of all individuals, aged 2–16 years, evaluated for short stature or poor growth at a single large tertiary referral center between 2012 and 2019. Multiple logistic regression models were constructed to analyze sex differences. Results: Of 10,125 children referred for evaluation, a smaller proportion were female (35%). More males (13.1%) than females (10.6%) underwent GH stimulation testing (p < 0.001) and did so at heights closer to average (median HtZ-score −2.2 [interquartile range, IQR −2.6, −1.8] vs. −2.5 [IQR −3.0, −2.0], respectively; p < 0.001). The proportion of GH prescriptions by sex was similar by stimulated peak GH level. Predictor variables in regression modeling differed by sex: commercial insurance predicted GH stimulation testing and GH prescription for males only, whereas lower HtZ-score predicted GH prescription for females only. Conclusions: Sex differences in rates of GH stimulation testing but not subsequent GH prescription based on response to GH stimulation testing seem to contribute to male predominance in pediatric GH treatment. That HtZ-score predicted GH prescription in females but not males raises questions about the extent to which sex bias – from children, parents, and/or physicians – as opposed to objective growth data, influence medical decision-making in the evaluation and treatment of short stature.

Focused Revision: ACMG practice resource: Genetic evaluation of short stature

Focused Revision: ACMG practice resource: Genetic evaluation of short stature

The role of delayed bone age in the evaluation of stature and bone health in glucocorticoid treated patients with Duchenne muscular dystrophy

BackgroundLow bone mineral density and an increased risk of appendicular and vertebral fractures are well-established consequences of Duchenne muscular dystrophy (DMD) and the risk of fractures is exacerbated by long-term glucocorticoid treatment. Monitoring of endocrine and skeletal health and timely intervention in at-risk patients is important in the management of children with DMD.MethodsAs part of the Norwegian Duchenne muscular dystrophy cohort study, we examined the skeletal maturation of 62 boys less than 18 years old, both currently glucocorticoid treated (n = 44), previously treated (n = 6) and naïve (n = 12). The relationship between bone age, height and bone mineral density (BMD) Z-scores was explored.ResultsThe participants in the glucocorticoid treated group were short in stature and puberty was delayed. Bone age was significantly delayed, and the delay increased with age and duration of treatment. The difference in height between glucocorticoid treated and naïve boys was no longer significant when height was corrected for delayed skeletal maturation. Mean BMD Z-scores fell below − 2 before 12 years of age in the glucocorticoid treated group, with scores significantly correlated with age, duration of treatment and pubertal development. When BMD Z-scores were corrected for by retarded bone age, the increase in BMD Z-scores was significant for all age groups.ConclusionOur results suggest that skeletal maturation should be assessed in the evaluation of short stature and bone health in GC treated boys with DMD, as failing to consider delayed bone age leads to underestimation of BMD Z-scores and potentially overestimation of fracture risk.

Evaluation of short stature in paediatric age group in rural medical college

Evaluation of short stature in paediatric age group in rural medical college - IJMPO- Print ISSN No: - 2581-4699 Online ISSN No:- 2581-4702 Article DOI No:- 10.18231/2581-4702.2018.0036, IP International Journal of Medical Paediatrics and Oncology-IP Int J Med Paediatr Oncol

Application of Chromosomal Microarray for Evaluation of Idiopathic Short Stature in Asian Indian Children: A Pilot Study.

Background:Human height is a classic polygenic trait and currently available data explains only 10% of the phenotypic variation in height. Almost 60%–80% of the children coming to pediatric and endocrinology outpatient department for the evaluation of short stature are still labeled as idiopathic.Objectives:The aim of this study is to identify various chromosomal alterations causing idiopathic short stature (ISS) and short stature with dysmorphic features not pertaining to known genetic syndromes.Materials and Methods:After exclusion of all nutritional, systemic, endocrine, and syndromic causes of short stature, 19 patients with height <2 standard deviation scores were subjected to chromosomal microarray (CMA) study using Affymetrix CytoScan 750K array and CMA Scanner 3000 platform.Results:We identified total 61 copy-number variant (CNV) and polymorphs (33 gains, 11 loss, and 17 gain-mosaics) not described as normal variants in database of genomic variations. We identified SHOX haploinsufficiency as a cause of short stature in two patients, whereas one patient was gain-mosaic for SHOX. All three had normal conventional karyotype. One of these patients also had deletion of PAX3, which could be the cause of both short stature and associated mild intellectual impairment in this patient. We also found a long noncoding RNA, namely, KIAA0125 and a pseudogene ADAM6 in 18 out of our 19 patients which might have a regulatory role.Conclusion:This study shows that CMA is a very promising tool for the identification of pathogenic CNVs in patients with ISS. It can also help to identify novel genes controlling height and can open up new insight into pathophysiologic mechanisms underlying ISS, and thus may help to unfold new therapeutic targets for treatment of this condition. The association of CNV having genes for long noncoding RNAs, such as KIAA0125 and pseudogene such as ADAM6 with ISS suggest that they may play a role in controlling the expression of height-related genes and it needs further investigations.

Short stature in association with Cornelia de Lange syndrome – it is useful to administrate rhgh?

Cornelia de Lange syndrome (CdLS) is a very rare genetic disorder that is apparent at birth (congenital). Since children with CdLS are often compared to a typical child’s grow rate, many are incorrectly diagnosed.In the absence of the genotyping, the diagnosis would be clinical: a range of criteria would be required, such as the facial features and criteria related to at least one of the following : development, behaviour or growth. Short-stature associated with CdLS is usually due to GH deficiency or GH resistance. However the response to GH administration in patients with CdLS was reported in a limited number of cases.We present the case of a female child 4,11 years old reffered for endocrinological evaluation of short stature. From her medical history we mention: language delay and a pulmonary valve regurgitation. At the time of evaluation, she presented short stature (-2,32 SDS) with a -3 SDS growth velocity during the past year, bone age was more than 2 years delayed compared to the chronological age (2,5 years), weight and head circumference below 5th percentile for age, synophrys, oral dystrophy, micrognathism and thin upper lip, down-turned corners of mouth, hypertrichosis, pulmonary systolic murmur, partial elbow extension.Facial findings and criteria met for two major categories confirm the CdLS. The endocrinological evaluation revealed short-stature with GH deficiency based on two GH values below 10 ng/mL during two stimulation tests . The patient began treatment with somatropin 0,04 mg/kg/day and the patient grew 3,5 cm in 6 months (-2,7 SDS for height).This case suggests that adequate evaluation of patients with CdLS and short stature could identify patients that are good candidate for GH treatment in order to improve final height.

Early Identification of Pituitary Dysfunction in Congenital Nasal Pyriform Aperture Stenosis: Recommendations Based on Experience in a Single Centre

Background: Congenital nasal pyriform aperture stenosis (CNPAS) is an increasingly recognised cause of upper airway obstruction associated with midline abnormalities. Studies have described pituitary dysfunction in 40% of patients. We aimed to develop guidelines for: (a) the early identification of pituitary insufficiency to minimise surgical risk and (b) to stratify patients for follow-up. Methods: Retrospective case note review of patients with CNPAS between 2000 and 2014 in a tertiary paediatric unit. Results: 20 patients (12 female:8 male) were analysed; 16 were diagnosed during the neonatal period while 4 were diagnosed later. There was no consistent approach in the evaluation of the pituitary axis at diagnosis. Pituitary dysfunction was identified in 3 (15%) patients, 2 of whom were found during evaluation of short stature in mid-late childhood. Hypoglycaemia and conjugated hyperbilirubinaemia, but not the degree of stenosis, were highly predictive of pituitary dysfunction (p < 0.05). Available height standard deviation score (SDS) data at 1 year of 70% of our patients identified both of the late-diagnosed growth hormone-deficient patients, with SDS of -2.6 and -3.6, respectively. Conclusion: All CNPAS patients should have MRI of the brain and baseline endocrine investigations at diagnosis. Growth monitoring for at least 1 year is recommended as low, or falling, height SDS at 1 year is a good predictor of pituitary dysfunction.

Evaluation of Short Stature in Children

Normal growth in children is a reflection of general health and is the result of a complex interaction between genetic, nutritional, and hormonal factors. From conception through infancy, growth is mostly driven by maternal nutrition and the in utero environment. Genetic factors, growth and thyroid hormones, ghrelin, and sex steroids have a more prominent influence later. Normal growth is not linear; it is marked by periods of growth spurts, particularly during puberty, separated by periods of slow or immeasurable growth. There is often a period of growth deceleration observed before the onset of puberty, with maximal pubertal growth spurts occurring at Tanner stage III for girls and Tanner stage IV for boys. This is caused primarily by the combined effect of the increased amplitude of growth hormone pulses and sex steroids. Short stature (SS), which is the subject of this review, is defined as a length or height more than 2 standard deviations below the mean for age and gender, which corresponds to a percentile below 2.5%. Taking a thorough patient history and completing a comprehensive physical examination are some of the most important diagnostic tools for pediatricians to use in the diagnosis of SS, and in making appropriate referrals as needed.

Turner Syndrome, Uncommonly Diagnosed Cause of Short Stature: Case Report and Review of Literature

Many children are frequently brought to the paediatric clinic for evaluation of short stature. Evaluation for these children does not go beyond x-ray for bone age estimation and growth hormone analysis. Most of them are considered having constitutional or genetic cause for their short stature. However, shuttle dysmorphic features could be missed in many of them. Hence, many children might be having chromosomal anomaly as an underlying cause. We report a case of 40 months who had been evaluated several times in the past for pneumonia, otitis media and short stature is finally diagnosed to have Turner syndrome. DOI: http://dx.doi.org/10.3126/jnps.v33i1.8174 J Nepal Paediatr Soc. 2013;33(1):74-76

Re-emergence of a rare syndrome: A case of mauriac syndrome

Mauriac syndrome is a rare syndrome associated with type 1 diabetes (T1DM) in children presenting with growth retardation, hepatomegaly, and cushingoid features. Recently, there has been re-emergence of this syndrome, especially with the use of premix insulin. A 15-year old type 1 diabetic boy, who was on premix insulin with erratic blood glucose, was referred to us for evaluation of short stature. He had significant short stature, hepatomegaly, and cushingoid features. His growth hormone (GH) stimulation was normal, and so was the overnight dexamethasone suppression test, based on which the diagnosis of Mauriac syndrome was reported. He was made to switch over to basal bolus regime, and was advised to follow-up for 6 months. He had reduction in hepatomegaly and a height gain of 3 cms.

Too short and too poor: A tale of two siblings

Two short siblings who were brought for evaluation of short stature are described with emphasis on availability of resources in the diagnosis and management of the cause of short stature in them.

Short Stature Work-up Influenced by Gender

Source: Grimberg A, Feemster KA, Pati S, et al. Medically underserved girls receive less evaluation for short stature. Pediatrics. 2011; 127(4): 696– 702; doi: 10.1542/peds.2010-1563Investigators from the University of Pennsylvania sought to determine the influence of gender on the evaluation of poor growth in children. A previous report by this group noted that referred girls were shorter than referred boys relative to the population mean and midparental height, and were more likely to have an underlying disease.1In the current study, growth records of 33,476 children aged 6 months to 20 years who attended four urban pediatric primary care offi ces from July 2002 to June 2005 were examined. Criteria for growth-faltering (GF) included: a) height below the 5th percentile, or b) a decrease of 1 to 1.5 standard deviations (SD) on the height Z-score chart. Surrogate markers of socioeconomic status were collected from United States Census data and included median income, employment, and education level. Subjects in these urban practices were predominantly African American (87%) and Medicaid-insured (70%). They lived in census tracts with median household incomes of $24,600; a median of 29% of inhabitants were below the federal poverty line.Nine percent of children met criteria for GF (mean height −1.5 SD) and 1.6% were below −2.25 SD. The racial distribution did not differ significantly between boys and girls. Only 8% of children with GF were referred to a subspecialist. Some children had multiple subspecialty referrals. Subspecialty referral was not significantly associated with gender. Of interest, 6% of GF children were referred to gastroenterology (compared with 1.5% of others; P<.0001) while 2.8% of those with GF were referred to endocrinology (compared with 0.8% of others; P<.005). Race differences were nonsignificant after multivariate analysis.Primary care pediatricians were more likely to order diagnostic tests in children with GF than those without. Thyroid tests were the most frequently obtained endocrine study (9%) and CBC (60%) was the most commonly ordered test. A measure of growth hormone production (GH or IGF-1) was obtained in only 1.4% of tested subjects and was ordered twice as often in short boys compared with short girls. Similarly, chromosome testing was obtained in only 1.4% of girls with GF, and 35% of them were at least 12 years of age. The authors conclude that current practices of diagnostic testing of urban underserved children with growth impairment may lead to underdiagnosis of Turner syndrome and growth hormone deficiency in girls.Dr Heinze has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The findings of this retrospective case review will come as no surprise to pediatric endocrinologists, and serve to remind our primary care colleagues of the critical importance of both identifying and properly evaluating children with growth impairment. This may be especially true of families of lower income whose members may not consistently raise short stature as a concern with their pediatrician or who have limited access to primary care physicians. The limited laboratory testing performed by providers in this study was particularly striking; IGF-1 measurements, for example, are an essential part of any pediatric growth evaluation as is chromosome analysis in girls with short stature.While concerns have been raised regarding the cost of using growth hormone in some populations of short children,2 this study identifies our shortcomings in the identification and evaluation of short children. In the end, treatment with growth-promoting therapies is reserved for a small percentage of children.The number of children who are small relative to their family and are slow-growing — below the 5th percentile — is considerable and not all of these children will require referral to a pediatric endocrinologist. This report is a reminder of the benefits of detailed tracking of growth velocity and the need for selective comprehensive laboratory investigation.The negative physical and psychosocial consequences of delayed etiologic diagnosis (eg, Turner syndrome) cannot be overemphasized. It is important to note that this study is limited to data from urban clinics whose patients are primarily African American Medicaid recipients. Examination of a more socioeconomically diverse population is the obvious next step.

Arginine extravasation leading to skin necrosis

Arginine hydrochloride is used in the evaluation of short stature and in the management of urea cycle disorders. In recent times, it has been used in the treatment of stroke-like episodes of MELAS (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes). We want to highlight the need for good intravenous access and monitoring the drip site to prevent extravasation injuries that can be caused by arginine, which is a hyperosmolar solution.

Medically underserved girls receive less evaluation for short stature.

To determine if gender is associated with diagnostic evaluation by primary care pediatricians caring for children with growth-faltering. This was a retrospective study of children who were attending 4 urban pediatric primary care practices affiliated with a tertiary pediatric hospital. Growth-faltering was defined as height at the <5th percentile or a z-score decrease of ≥ 1.5 SDs before 18 months of age or ≥ 1 SD thereafter. For each child, height z score, age, gender, race, insurance, diagnostic tests, and subspecialist appointments were examined. Of 33 476 children, 3007 had growth-faltering (mean height: -1.5 ± 1.0 vs 0.3 ± 0.9 SDs in those without growth-faltering). Boys comprised 53% of the growth-faltering group (vs 51% of the nonfaltering group; P < .01). Among children with growth-faltering, 2.8% had endocrinology appointments (vs 0.8% of others; P < .0001) and 6% had gastroenterology appointments (vs 1.5% of others; P < .0001). Subspecialty care was not associated with gender. Pediatricians ordered diagnostic tests for a significantly greater proportion of children with growth-faltering than others. In multivariate analysis of height z score among children with growth-faltering, tests for chromosomes (1.4% of short girls vs 0.4% of short boys; P < .005) and growth hormone/insulin-like growth factor axis (0.9% of short girls vs 1.8% of short boys; P < .05) were associated with gender. Thirty-five percent of the girls for whom chromosome testing was performed were 12 years old or older. Patterns in diagnostic testing of children with growth-faltering by their pediatricians may lead to underdiagnosis of Turner syndrome and growth hormone deficiency among girls.