Mid-parental Height Research Articles

Long-term effectiveness and safety of long-acting growth hormone preparation in children with growth hormone deficiency.

To evaluate the long-term effectiveness of weekly vs. daily growth hormone (GH) administration in children with GH deficiency. This study, part of the "LG Growth Study", included a total of 996 children with GH deficiency (773 receiving daily GH and 193 receiving weekly GH). Anthropometric data were collected at baseline and every 12months; clinical and laboratory data were collected at baseline and throughout the study. At baseline, the weekly GH group was older, shorter in mid-parental height (MPH), and had more pubertal boys compared to the daily GH group (age: 8.46±3.44 vs. 7.46±2.89 years, p<0.001; MPH:-0.88±0.73 SD vs.-1.02±0.84 SD, p=0.044; pubertal boys: 34.0 vs. 16.9 %, p=0.006). Height velocity and change in height SDS during the first 12months were higher in the daily GH group (height velocity: 9.06±1.72 vs. 8.67±1.98 cm/year, p=0.028; height SDS change: 0.78±0.39 vs. 0.61±0.41, p<0.001). However, height SDS at 24 and 48months were similar between groups. No significant differences in overall height velocity, annualized treatment continuation rate, and safety profile were observed over 48months. Weekly GH therapy appears to be an effective and safe alternative to daily GH treatment in children with GH deficiency over a 4-year period. Further research with larger sample sizes and longer follow-up is needed to confirm these findings and assess the extended safety and effectiveness of LAGH.

A polygenic score for height identifies an unmeasured genetic predisposition among pediatric patients with idiopathic short stature.

Background A subset of children with short stature do not have an identified clinical explanation and are assigned a diagnosis of idiopathic short stature (ISS). We hypothesized that a polygenic score for height (PGS height ) could identify children with ISS who have an unrecognized heritable predisposition to shorter height. Methods We examined 534 pediatric participants in an EHR-linked DNA biobank (BioVU) who had undergone an evaluation for short stature by an endocrinologist. We used a previously validated PGS height and standardized it to a standard deviation (SDS) of 1. PGS height differences between short stature subtypes was estimated using Tukey's HSD. The PGS height and mid-parental height (MPH) were then used to predict adult heights for each participant and these predictions were compared using Cohen's d stratifying by short stature subtype. The ability of the PGS height to discriminate between ISS and short stature due to underlying disease was evaluated using logistic regression models with area under the ROC curve (AUC) analyses and testing the incremental benefit (ΔAUC) of adding the PGS height to prediction models. Results Among the 534 participants, 22.1% had ISS (median [IQR] PGS height SDS = -1.31 [-2.15 to -0.47]), 6.6% had familial (genetic) short stature (FSS) (-1.62 [-2.13 to -0.54]), and 45.1% had short stature due to underlying pathology (-0.74 [-1.23 to -0.19]). Children with ISS had similar PGS height values as those with FSS (ΔPGS height [95% CI] = 0.19 [-0.31 to 0.70], p = 0.75), but predicted heights generated by the PGS height were lower than the MPH estimate for children with ISS ( d = -0.64; p = 4.0×10 - 18 ) but not FSS ( d = 0.05; p = 0.46), suggesting that MPH underestimates height in the ISS group. Children with ISS had lower PGS height values than children with pathology (ΔPGS height = -0.60 SDS [-0.89 to -0.31], p < 0.001), suggesting children with ISS have a larger predisposition to shorter height. In addition, the PGS height improved model discrimination between ISS and pathologic short stature (ΔAUC, + 0.07 [95% CI, 0.01 to 0.11]). Conclusions Some children with ISS have a clinically unrecognized polygenic predisposition to shorter height that is comparable to children with FSS and larger than those with underlying pathology. A PGS height could help clinicians identify children who have a benign predisposition to shorter height.

7548 Final adult height in children with idiopathic growth hormone deficiency after growth hormone treatment

Abstract Disclosure: H. Lee: None. S. An: None. M. Cho: None. H. Nam: None. Objective: The aim of this study was to assess the final adult height (FAH) achieved through recombinant human growth hormone (GH) treatment and the factors influencing FAH. Methods: We retrospectively reviewed the charts of all patients diagnosed with IGHD who were prepubertal when they began GH treatment since August 2007. FAH was determined in 41 patients (28 males and 13 females) by July 2023. Results: 41 patients started treatment at an average age of 9.1 years and continued for 6.5 years. The mean initial height was -2.6 standard deviation scores (SDS) and the mean FAH was -0.6 SDS. GH treatment was initiated at a significantly younger age in females than in males (7.2±1.9 vs 10.0±3.2; p=0.01). The mean FAH was 169.9±4.5cm for males and 156.1±3.2cm for females. Differences between initial height and final height SDS were not significant between males and females. The mean of FAH SDS was higher compared to their mid-parental height -1.0 SDS (p=0.017). In multiple regression analysis, FAH showed a positive correlation with initial height, duration of treatment, and growth rate in the first year of treatment, and a negative correlation with BMI SDS at the start of GH (r2=0.59; p=0.000). FAH SDS was positively related to initial height SDS and growth rate in the first year of treatment. (r2=0.3; p=0.001) Conclusions: The mean FAH SDS after GH treatment was significantly higher than the mean MPH SDS in IGHD patients. Moreover, the good response of GH treatment was associated with longer treatment duration, greater height at the start of treatment, better treatment response at 1 year, and lower initial BMI SDS. Presentation: 6/3/2024

6996 Optimal Growth Hormone Response Despite Low Insulin-Like Growth Factor-1: Clinical Picture of an A67T IGF-1 Variant

Abstract Disclosure: E.M. Bomberg: Research Investigator; Self; Novo Nordisk. Z. Wu: Employee; Self; Quest Diagnostics. I. Motorykin: Employee; Self; Quest Diagnostics. J. Torkelson: None. N. Schmitz: None. A. Drilling: None. M.J. McPhaul: Employee; Self; Quest Diagnostics. B.S. Miller: Advisory Board Member; Self; Abbvie, Ascendis Pharma, Biomarin, Bristol-Myers Squibb, Eton Pharmaceuticals, EMD Serono, Endo Pharmaceuticals, GenSci, Novo Nordisk, Pfizer, Inc., Provention Bio, Sanofi, Tolmar. Consulting Fee; Self; Abbvie, Ascendis Pharma, Biomarin, Bristol-Myers Squibb, Eton Pharmaceuticals, EMD Serono, Endo Pharmaceuticals, GenSci, Provention Bio, Sanofi, Tolmar. Grant Recipient; Self; Alexion Pharmaceuticals, Inc., Abbvie, Aeterna Zentaris, Amicus, Foresee Pharmaceuticals, Lumos Pharma, Lysogene, Novo Nordisk, OPKO Health, Pfizer, Inc., Prevail Therapeutics, Sangamo Therapeutics. Research Investigator; Self; Alexion Pharmaceuticals, Inc., Abbvie, Aeterna Zentaris, Amicus, Foresee Pharmaceuticals, Lumos Pharma, Lysogene, Novo Nordisk, OPKO Health, Pfizer, Inc., Prevail Therapeutics, Sangamo Therapeutics. Speaker; Self; Biomarin, Novo Nordisk, Pfizer, Inc., Tolmar. Introduction: Insulin-like growth factor-1 (IGF-1) measurements are used for growth hormone (GH) deficiency screening and helpful in monitoring GH treatment effectiveness. However, IGF-1 variants have been reported with mass spectrometry (MS)-based assays, potentially limiting interpretation of reported results. Clinical Case: A 14-year-old male presented for short stature. Evaluation was non-revealing aside from low serum IGF-1 measured via liquid chromatography (LC)-MS assay (58 ng/mL; -3.8 standard deviation score [SDS]), and IGF-Binding Protein 3 (3.7 ug/mL; -1.7 SDS). Height was 148.2 cm (1st percentile, -2.08 SDS; mid-parental height 172.7 cm [31st percentile, -0.48 SDS]), pubertal exam Tanner stage 2, and bone age 2.5 years delayed. A GH stimulation test showed a peak GH of 8.1 ug/L; brain MRI was normal. GH was started at 0.29 mg/kg/wk. One month later, IGF-1 remained low (89 ng/mL; -3.2 SDS) and GH was increased to 0.36 mg/kg/wk, and over time to 0.52 mg/kg/wk due to persistently low IGF-1 (-2.9 to -2.3 SDS), despite reports of good compliance and significant catch-up growth (height increased to 19th percentile, -0.84 SDS). He reported no significant side effects during GH treatment. At 17.5 years old, he returned to clinic reporting self-discontinuing GH 1 month prior. Height was at the 27th percentile (171.5 cm, -0.59 SDS), he was fully pubertal, IGF-1 128 ng/mL (-3.1 SDS), and bone age 1.5 years delayed. Further review of IGF-1 linked reports accompanying lab values directly entered into the electronic health record (EHR; starting 2021) described the presence of a rare heterozygous IGF-1 functional variant with unknown clinical significance based on MS data. Concentration of the variant was expected to be identical to that reported for the wild type IGF-1 protein, potentially explaining the lower than expected values. Analysis of the raw LC-MS data (variant peak at m/z 1098.09, isotopic peak index [IP6], relative retention time [rRT]=0.00 min) was consistent with either an A67T or A70T IGF-1 variant. To resolve this ambiguity, the specimen was reanalyzed with an LC-tandem MS/MS fragmentation method, which identified distinguishing peaks at m/z 503.28 (y5 ion) and 305.18 (y3 ion) characteristic of A67T, a known benign variant. Conclusions: Benign IGF-1 variants should be considered in cases of unexplained low IGF-1 levels, including when these remain low despite increasing GH doses, good adherence, and optimal growth velocity. Presence of IGF-1 variants should not affect GH stimulation results (e.g., GH levels), however, may lower reported IGF-1 levels used to determine need for diagnostic testing and followed when monitoring GH response. Careful review of IGF-1 lab reports and full abstraction of these into the EHR should be performed. Knowing a variant is benign could help providers set lower wild-type IGF-1 targets when monitoring GH response to avoid unnecessarily high GH doses. Presentation: 6/3/2024

7726 Central Adrenal Insufficiency From Inhaled Mometasone Manifesting As Growth Deceleration

Abstract Disclosure: S. Gurnurkar: None. F.I. Cooper: None. Introduction: While long courses and/or high-doses of oral steroids have been found to cause adrenal suppression and resultant insufficiency, inhaled corticosteroids from asthma management typically do not affect cortisol production. However, in this case, we describe a patient who presented with 3 years of growth deceleration and was found to have adrenal suppression from her inhaled corticosteroid/long-acting beta agonist, Dulera (mometasone furoate and formoterol fumarate). Case Presentation: An 11-year-old female with history of moderate persistent asthma presented to our endocrinology department with growth deceleration and resultant short stature. The parent noted that the child started to decelerate in height percentiles from the 50th percentile at age 8 to the 6th percentile at age 11. BMI gradually rose from the 85th to 95th percentiles. The parent noted that the child started having worsening asthma symptoms around the start of the growth deceleration, requiring a handful of oral steroid courses and the addition of daily inhaled corticosteroid, Dulera. She had remained on the Dulera for the previous three years, with her asthma under good control. She also took cetirizine daily and albuterol as needed. The last course of oral steroids was three months prior to her first endocrinology visit. The patient’s mid-parental target height was at the 50th percentile and she denied fatigue, headache, or abdominal pain. Family history was negative for endocrine conditions and short stature. Puberty began at age 10. Further workup was recommended. A bone age was concordant with chronologic age. Initial labs including a TSH, free T4, IGF-1, IGFBP-3, CBC, ESR, and CMP were within normal limits. A growth hormone stimulation test with arginine and clonidine was performed. Growth hormone peak was 11 ng/mL, but, interestingly, cortisol resulted as &amp;lt;1.0 ug/dl throughout the test. Due to concerns of adrenal insufficiency, she underwent a high dose ACTH stimulation test. Initial ACTH was 6.3 pg/mL (ref 6-48 pg/mL) and cortisol remained at &amp;lt;1.0 ug/dl at 0, 30, and 60 mins. She was diagnosed with central adrenal insufficiency and prescribed 11 mg/m2 BSA/day of hydrocortisone divided three times daily, with stress dosing and emergency hydrocortisone injection instructions. Conclusion: The existing literature suggests that Dulera (mometasone furoate and formoterol fumarate) does not significantly influence adrenal function nor growth velocity. However, we present the case of a child with 3 years of inhaled Dulera use and significant central adrenal insufficiency. This case report is the first of its kind to detail decreased adrenal function with Dulera in particular. Presentation: 6/2/2024

7202 CPP with Rapid Pubertal Progression in a 9-Year-Old Boy with Hypothalamic Teratoma

Abstract Disclosure: R. Robilliard: None. G. Tung: None. K. Svokos: None. R. Lulla: None. J.Q. Quintos: None. Background: Central Precocious Puberty (CPP) in males is rare, with incidence of 0.01-2/10,000. The most common identifiable cause of CPP in young children is hypothalamic hamartoma. No case hypothalamic teratoma has been reported to cause CPP in males. Clinical Case: At the age of 10-years and 5-months, a boy presented to the pediatric endocrinology with signs of precocious puberty including facial hair development, voice deepening, and increased growth velocity that began at 9 years old. There was no significant past medical history and he denied headache, blurry vision, or diplopia. Physical examination showed height of 140.4 cm (47%), Tanner 4 genitalia, Tanner 3 pubic hair, and testicular volumes of 15 cc (left) and 12-15cc (right). Bone age (BA) determined by radiography was 13.5 years with a predicted adult height (PAH) of 63 inches. The mid-parental target height was 67 +/- 4 inches. Evaluation including TSH, glucose, serum and CSF β-HCG, DHEA, CSF AFP was normal. Serum LH was 2.9 IU/L and testosterone level was 109 ng/dl, consistent with CPP. MRI of the pituitary showed a small, heterogeneous and fat-containing lesion extending inferiorly from the tuber cinereum consistent with teratoma. Treatment included GnRH agonist Lupron (30mg) every 3 months. Laboratory evaluation 8 months after initial presentation showed suppressed LH of 0.9 IU/L and FSH 0.5 mIU/mL, and testosterone of 57 ng/dL. Repeat radiography for BA one year after GnRHa suppression showed BA of 14 years at CA of 11 years 6 months and PAH of 64.4 inches. Growth velocity slowed to 5.3 cm/year. At the most recent follow-up visit at CA of 12 years, height was 151.5 cm (61%), growth velocity 6.3 cm/year (74% for age), Tanner 5 penis and pubic hair, left testicular volume of 15-20cc and right testicular volume of 15 cc. Most recent radiographic BA is14 years, and PAH is 65.9 inches. Given response to GnRH agonist injections every 3 months, the absence of CNS symptoms referable to the teratoma and no change in MR imaging, no surgical intervention is recommended. Conclusion: This is the first case of a hypothalamic teratoma reported in a male associated with CPP. Despite this rare cause, the patient has responded to standard treatment with GnRH agonist therapy alone. Presentation: 6/1/2024

7795 Gender based differences in peripubertal growth patterns may offer insight into the twofold representation of boys compared to girls among children referred for growth hormone stimulation tests

Abstract Disclosure: Y. Dekel: None. L. Horowitz : None. R. Gendelman: None. M. Cohen: None. Background: Growth hormone (GH) stimulation tests are essential in the diagnostic assessment of pediatric GH deficiency (GHD). However, the tests bare multiple limitations, resulting from both intrinsic and child-related factors. Thus, referral decisions are key in making a correct diagnosis. Several studies demonstrated a gender bias in referral for short stature evaluation with a higher proportion of boys referred and diagnosed with GHD. Moreover, the boys had higher height z-scores upon referral. About 100 GH stimulation-tests are conducted annually at our pediatric endocrinology unit. We aimed to characterize the children that underwent GH stimulation-testing between 2017-2021, specifically focusing on differences based on: 1) gender 2) GH secretion status (deficient vs. sufficient). Methods: A retrospective review of charts of children aged 0-18 years that performed GH stimulation-tests at the Rambam pediatric endocrinology unit between the years 2017-2021 was conducted. Children followed at an outside clinic that had a first GH stimulation-test elsewhere, were excluded. Data was collected through the electronic database and by manually screening medical charts. The IBM SPSS statistics package 21 version was used for analysis. Results: Four-hundred children were included in the study, 266 boys (66.5%) and 134 girls (33.5%). Mean age 8.8±4.2 years, mean height z-score -2.3±0.7 and mean mid-parental height standard-deviation-scores (MPH-SDS) -0.6±0.7. The mean difference between MPH-SDS and child height-z-score was 1.7±0.8 SDS. Mean age was younger in girls compared with boys, 7.3±3.3 and 9.6±4.4 years respectively (p&amp;lt;0.001). Age distribution differed between genders, while refferals peaked between 3-4 years of age in both girls and boys, a second peak at 13-14 years of age was evident only in boys. Interestingly, there was no significant difference between boys and girls in height z-score, difference from MPH-SDS or rates of GHD. Overall, 93 (23.3%) children were diagnosed with GHD, 32 girls (24%) and 61 boys (23%). Children with GHD were younger and had higher BMI-SDSs compared to GH sufficient children, age 7.8±3.8, 9.2±4.3 years respectively (p=0.003), BMI z-score 0.17±1.38, -0.47±1.15 respectively (p&amp;lt;0.001). Conclusion: Twice as many boys than girls were referred for GH stimulation tests in our cohort. Based on differences in age distribution, the peripubertal physiologic growth deceleration that occurs later in boys, likely contributes to this finding. This male-to-female ratio is similar to ratios reported in the literature regarding short stature referrals; however, in contrast to the literature, in our cohort it could not be explained by an anthropometric bias in referral criteria. Presentation: 6/3/2024

Pattern of physical growth and pubertal changes in adolescent girls with Systemic Lupus Erythematosus

ABSTRACT Aims: To study the pattern of physical growth and pubertal changes in adolescent girls with Systemic Lupus Erythematosus (SLE). Methods and Material: Weight, height, BMI, waist and hip circumference among 50 adolescent SLE girls (aged 8–17 years) were cross-sectionally studied using standardized techniques and instruments. Breast development stage, presence or absence of pubic and axillary hair and age of attainment of menarche were also noted. Results: With the advancement of age, weight and height of SLE girls increased but they were lighter and shorter compared to normal Indian peers. 18.4% of study girls were short-statured while only one participant was underweight. As per mid-parental height, 34.3% were predicted to have shorter final heights. BMI demonstrated an inconsistent trend with 12.3% and 9.2% being obese and overweight, respectively. Interestingly, 10.7% of SLE girls were at risk of metabolic syndrome (waist circumference &gt;70th centile). About 50% of study girls had attained menarche (mean age: 13.04 ± 1.38 years). Appearance of pubic and axillary hair occurred around 1 year later than attainment of menarche. 33.80% of study subjects were in prepubertal stage of breast development and rest 66.20% were in advanced stages of breast development. SLE girls who had younger age at diagnosis and longer duration of therapy had significant delay in breast development and attainment of menarche. Conclusions: SLE girls show delayed growth and pubertal attainments compared to their normal Indian and Western counterparts. The data presented will provide an understanding of the auxological dynamics and pattern of pubertal changes among adolescent girls with SLE living in north-western India.

Nutritional Status and Growth Outcomes in Pediatric Idiopathic Growth Hormone Deficiency: A Retrospective Study in Turkey

Objective: Growth and development in children are significantly influenced by nutritional status. Nutritional deficiencies such as low hemoglobin (Hb), ferritin, vitamin B12, and vitamin D have been linked to impaired growth. This study aims to evaluate the impact of these nutritional markers on growth outcomes in children with idiopathic growth hormone deficiency (IGHD) undergoing recombinant growth hormone therapy (rhGH). Material and Methods: A cross-sectional, retrospective study was conducted on 100 children with IGHD, aged under 16, diagnosed between 2000 and 2023. Data were collected from medical records, including height, body mass index (BMI), pubertal status, bone age, and nutritional markers [Hb, ferritin, vitamin B12, 25-hydroxy-vitamin D3 (25(OH)D3]. Growth parameters were assessed at the start and end of the first year of rhGH treatment. Results: The cohort had a median age of 11.3 years; 30% were female, and 50% were prepubertal. The median height standard deviation score (SDS) was -2.8, and median BMI SDS was -0.7. Prevalence of nutritional deficiencies included 23% with low Hb, 31% with low ferritin, 44% with low 25(OH)D3, and 15% with low vitamin B12. Despite these deficiencies, no significant differences were observed in height SDS or growth velocity when grouped by nutritional markers or supplementation status. Growth velocity showed a significant positive correlation with Hb levels and mid-parental height (MPH). Conclusion: Nutritional deficiencies were common among IGHD patients; there was no significant difference in terms of growth-related metrics in the first year of the rhGH therapy in comparisons between the groups with and without common nutritional deficiencies. This finding underscores the resilience of growth in the presence of these deficiencies. In contrast, growth velocity correlated positively with Hb levels and MPH, suggesting that these factors may play a significant role in influencing growth. Further research with larger samples and extended follow-up is needed to explore the long-term impact of nutritional supplementation on growth in IGHD.

Anastrozole vs Letrozole to Augment Height in Pubertal Males With Idiopathic Short Stature: A 3-Year Randomized Trial.

Insufficient efficacy and safety data for off-label use of aromatase inhibitors to augment height in boys with short stature. To compare anastrozole and letrozole in treatment of idiopathic short stature in pubertal boys. Open-label trial with 2 treatment arms. Pediatric Endocrine Clinic at Stanford. A total of 79 pubertal males ≥10 years with bone age (BA) ≤ 14 years, predicted adult height (PAH) < 5th percentile or >10 cm below mid-parental height. Anastrozole 1.0 mg or letrozole 2.5 mg daily for up to 3 years. Annual hormone levels and growth parameters during treatment and a year posttherapy; annual BA and PAH (primary outcome measure); spine x-rays and dual energy X-ray absorptiometry at baseline and 2 years. Compared with anastrozole (n = 35), letrozole (n = 30) resulted in higher testosterone levels, lower estradiol and IGF-1 levels, and slower growth velocity and BA advance. The PAH increase observed at year 1 in both groups did not persist at years 2 and 3. Change in PAH from baseline was not different between treatment groups. In groups combined, PAH gain over 3 years vs baseline was +1.3 cm (P = .043) in linear mixed models. Letrozole caused greater deviations than anastrozole in hormone levels, growth velocity, and BA advancement, but no group differences in PAH or side effects were found. Change in PAH after 2 to 3 years of treatment was minimal. The efficacy of AI as monotherapy for height augmentation in pubertal boys with idiopathic short stature may be limited, and safety remains an issue.

Accurate Prediction of Children's Target Height from Their Mid-Parental Height.

Background: For the past 50 years, standard guidelines have recommended the use of sex-adjusted mid-parental height to predict a child's final height. Here, we studied the accuracy of this procedure. Methods: We used height data in a cohort of 23 very large nuclear families (mean = 11 adult children per family). We compared the actual final height of the children to their height predicted by the standard procedure, as well as to alternative height predictions that incorporate corrections of mid-parental height for age, sex, and regression to the mean. Results: Standard mid-parental height explained 36% of the variance in children's heights, with a heritability of 74%, and children were on average 2.7 cm taller than predicted by their target heights. When we introduced a nonlinear correction for the age of the parents, employed a multiplicative (rather than additive) correction for sex, and accounted for regression to the mean, the variance explained increased to 40%, heritability increased to 80%, and prediction bias was reduced from 2.7 cm to 0.14 cm (representing an improvement in prediction by half a standard deviation of the height distribution). We further measured the empirical distribution of the heights of adult children around their predicted height. We describe how this distribution can be used to estimate the probability that a child's height is within the normal expected range. Conclusions and Relevance: Based on these observations, we propose an improved method for predicting children's target heights. Our procedure for determining whether the deviation of a child's projected height from the target height is in the normal range can be used to assess whether the child should be tested further for potential medical abnormalities.

Final Height in Patients with Congenital Adrenal Hyperplasia

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

Short Adult Height After Rapid-tempo Puberty: When is it too Late to Treat?

A rarely reported phenomenon of rapid-tempo puberty in which the physical changes of puberty and testosterone levels increase very rapidly has not been reported outside apart from in two reviews. The resulting rapid advancement of skeletal age causes early completion of growth with shorter adult stature than expected. This appears to be genetic given its occurrence in the present report in two families, one with three brothers, one with two. We also describe potential treatments and found for the youngest that early initiation of standard therapy preserved or reclaimed adult height (AH) potential. The foreshortened AH in this situation involves rapidly advancing puberty resulting from high circulating testosterone levels leading to rapid advance in skeletal age. This was recognized earlier among younger brothers and treatment with gonadotropin-releasing analogues, growth hormone (GH) and/or aromatase inhibitor therapy (AIT) was tried. Two brothers in family A and family B were treated. Case 5 started treatment early enough so his AH was within target height (mid-parental height) range. Cases 2, 3, 4 were tried on GH and/or AIT with outcomes suggesting benefit. The prevalence and mechanism of rapid-tempo puberty requires further study. Furthermore, as illustrated by two of the current cases, this phenomenon may have a heightened prevalence, or at least may occur, in children previously diagnosed with constitutional delay of growth, underscoring the need to be cautious in assurance of a normal AH outcomes in this population, based on data from a single assessment.

Identifying factors associated with substantially reduced adult height in patients with juvenile idiopathic arthritis: a retrospective cohort study

BackgroundJuvenile idiopathic arthritis (JIA), an autoimmune disease affecting children or adolescents and causing joint or systemic symptoms, reportedly has a negative effect on the patients’ body height. This study aimed to identify factors attributable to substantially reduced adult height (SRAH) in JIA patients.MethodsThis single-center retrospective cohort study included patients from 2009 to 2019 in Taiwan. We collected JIA patients aged > 18 years at enrollment with a definite diagnosis and undergoing regular outpatient clinic follow-up or disease remission. Target height difference (THD), defined by adult height minus mid-parental height, was calculated for each patient. The calculation results yielded two groups, of which positive THD was defined as the optimal height (OH group) and those with THD below two standardized deviations as the SRAH group. Descriptive statistics and logistic regression analysis were used to analyze the data.ResultsOf 92 JIA patients, 57 and 12 were in the OH and the SRAH groups. Earlier disease onset, especially before the six-year-old, was noted in the SRAH group (p = 0.026). The distribution of JIA subtypes differed significantly between the two groups (p < 0.001); enthesis-related arthritis was the commonest subtype in the OH group, and systemic JIA was the commonest in the SRAH group. Half of the patients in the SRAH group had an active disease status at enrollment, which was higher than the OH group (50.0% vs. 21.1%, p = 0.066). More patients in the SRAH group had received orthopedic surgery due to JIA (25% vs. 3.5%, p = 0.034). Multiple logistic regression analysis showed that SRAH was independently related to systemic JIA (OR = 37.6, 95%CI 1.2-1210.5; p = 0.041).ConclusionThe subtype of systemic JIA, with its characteristics of early disease onset and active disease status, was the essential factor that significantly impacted adult height.

Endocrine Disorders in Childhood Brain Tumour Survivors: A Single-Centre Study.

The study aims to determine the prevalence and risk factors for endocrine disorders in childhood brain tumour survivors. Included in the study were 124 childhood brain tumour survivors aged 18 years old or younger with either stable disease or in remission, and had survived for at least 2 years after diagnosis. Demographic data (age at diagnosis, gender, ethnicity, socioeconomic status), clinical clues for endocrine disorders, anthropometrics (weight, height, midparental height), pubertal staging, tumour-related characteristics, treatment modalities and endocrine laboratory measurements at diagnosis and during follow up were obtained. Logistic regression was applied to evaluate risk factors for endocrine disorders in childhood brain tumour survivors. The prevalence of endocrine disorders in childhood brain tumour survivors was 62.1%. The risk factors were high BMI [adjusted odds ratio (OR) 1.29, 95% CI: 1.12 to 1.5], high-risk site [adjusted odds ratio (OR) 7.15, 95% CI: 1.41 to 36.3] and chemotherapy [adjusted odds ratio (OR) 0.18, 95% CI: 0.05 to 0.62]. The prevalence of endocrine disorders in childhood brain tumour survivors in our centre was 62.1%. The significant risk factors were high BMI, tumour location (suprasellar and intrasellar) and chemotherapy.

GH provocative tests stimulate the growth in children with idiopathic short stature

ContextGrowth hormone (GH) deficiency in a child with short stature is diagnosed by GH secretion provocative tests. When the test response is considered adequate, the short stature is considered idiopathic (ISS).ObjectiveTo determine the effect of GH provocative tests on the growth rate in children with idiopathic short stature.DesignChildren with short stature with a normal response to at least one GH provocative test were enrolled. Height and growth velocity were measured prior to and after stimulus tests during the follow-up.MethodsHeight, mid-parental height, body weight, and body mass index were measured. The height and growth rate were converted to percentiles and Standard Deviation Scores (SDS) using reference ranges standardized by age and sex. GH provocative tests employed arginine or clonidine as secretagogues.ResultsFourty-six children of both genders were enrolled. In thirty-six children, height was measured at the time of testing and on an average time prior to and after the tests of 210 days and 180 days respectively. After testing the children displayed a 3.4-fold increase in their estimated 90-day growth rate. The median (inter-quartile range, IQR) 90 days growth of children pre-and post-tests were 0.7 (0.2–1.0) cm and 2.4 (1.7–3.1) cm respectively with a mean 3,4-fold increase (p < 0.0001). The median (IQR) 90 days growth of children pre- and post-tests calculated as standard deviation scores (SDS) were −4.0 (−5.4–−2.1) SDS and 0.1 (−1.9–1.4) SDS respectively (p < 0.0001). Ten children with ISS were observed for about 5 months before the GH provocative tests. A small increase in the growth rate was seen only in 2 out of 10 children before testing while it increased in all of them after the tests. The difference in the median growth rate at the first and the second observation was not significant (p = 0.219).ConclusionsTwo sequential somatotropic axis provocative tests increase the growth rate in children with idiopathic short stature. The duration of this effect is yet to be determined.

Pubertal Suppression in Early Puberty Followed by Testosterone Mildly Increases Final Height in Transmasculine Youth.

Treatment for transmasculine youth (TMY) can involve testosterone treatment and is sometimes preceded by gonadotropin-releasing hormone agonist (GnRHa) treatment for puberty blockade. GnRHas can increase final height in birth-assigned females with central precocious puberty. Maximizing final adult height (FAH) is an important outcome for many TMY. Our objective was to determine how GnRHa treatment before testosterone impacts FAH. Retrospective cohort study at 5 US transgender health clinics. Participants were 32 TMY treated with GnRHas in early to midpuberty before testosterone (GnRHa + T group) and 62 late/postpubertal TMY treated with testosterone only (T-only group). The difference between FAH minus midparental target height (MPTH) was +2.3 ± 5.7 cm and -2.2 ± 5.6 cm in the GnRHa + T and T-only groups, respectively (P < .01). In the GnRHa + T group, FAH was 1.8 ± 3.4 cm greater than predicted adult height (PAH) (P < .05) and FAH vs initial height (IH) z-score was 0.5 ± 1.2 vs 0.16 ± 1.0 (P < .05). After adjusting for patient characteristics, each additional month of GnRHa monotherapy increased FAH by 0.59 cm (95% CI 0.31, 0.9 cm), stage 3 breast development at start of GnRHa was associated with 6.5 cm lower FAH compared with stage 2 (95% CI -10.43, -2.55), and FAH was 7.95 cm greater in the GnRHa + T group than in T-only group (95% CI -10.85, -5.06). Treatment with GnRHa in TMY in early puberty before testosterone increases FAH compared with MPTH, PAH, IH, and TMY who only received testosterone in late/postpuberty. TMY considering GnRHas should be counseled that GnRHas may mildly increase their FAH if started early.

Prediction of body mass index and skeletal maturity for early menarche risk at menarche onset: a cross-sectional study of Chinese girls

BackgroundThis study aimed to assess the predictive value of body mass index (BMI) and skeletal maturity for the occurrence of early menarche in Chinese girls.MethodsA cross-sectional analysis was conducted on...

Growth During Pubertal Induction in Girls With Turner Syndrome: A Retrospective Cohort Analysis

Abstract Context Patients with Turner syndrome (TS) often present with short stature and ovarian insufficiency. The optimal method of pubertal induction to maximize adult height (AH) is unknown. Objective To identify variables related to pubertal induction that are associated with growth and AH. Methods This retrospective cohort analysis of patients attending a specialized TS clinic at a quaternary children's hospital included patients with TS (n = 107) who attended the clinic between 2015 and 2021. Among them, 51 received estradiol for pubertal induction. Main outcome measures were changes in height SD score (ΔHeightSDS) during pubertal induction and AH. Age at pubertal induction, bone age delay, mid-parental height (MPH), growth hormone treatment, and karyotype were assessed as predictors of AH and ΔHeightSDS. Associations between karyotype and comorbidities were also assessed. Results AH was predicted by MPH (0.8 cm/cm, P = .0001) and bone age delay (−1.84 cm/year, P = .006). ΔHeightSDS was predicted by growth hormone dose (0.09 SDS/mg/m2/week; P = .017), bone age delay (−1.37 SDS/year; P = .003), and age at pubertal induction (0.44 SDS/year; P = .001). There was an interaction between bone age delay and pubertal induction age (P = .013), with the combination of younger age at pubertal induction and a less-delayed bone age associated with a lower ΔHeightSDS. Karyotype did not influence AH or ΔHeightSDS but did affect rates of other comorbidities. Conclusion Decisions around timing of pubertal induction in patients with TS should be tailored to the individual. The current approach to estrogen supplementation needs to be refined in order to facilitate pubertal induction in a physiological manner without compromising height.

Prevalence of stunting and determinants of growth failure in children with Type 1 diabetes

Objectives: India is home to the highest number of prevalent cases of Type-1 diabetes (T1D) in children. There is scarcity of data on the growth failure of children with diabetes, especially those having complications and comorbidities, thus, we conducted this study with the objective to determine the prevalence and predictors of stunting in children with T1D. Methods: This cross-sectional study included 350 children and adolescents aged 1–18 years with T1D. Demographic data, anthropometry, diet, sexual maturity rating, and biochemical measurements were performed using standard protocols. Short stature was defined as height for age Z-score &lt;−2. p&lt;0.05 was considered statistically significant. Results: We report a 15.7% prevalence of stunting in our cohort of children with T1D. Stunted children had higher cholesterol, lower hemoglobin, lower mid-parental height Z-scores, and higher urinary albumin creatinine ratio. Binary logistic regression revealed that pre-existing comorbidities, compromised renal function, longer disease duration, and short mid-parental height were significant predictors of stunting. Conclusion: A little under one-sixth of children with T1D had short stature. Monitoring growth in these patients, especially in subjects with short parents, prolonged duration of diabetes, existing comorbidities, and deteriorating renal function are critical.