Increase In Growth Velocity Research Articles

Improvement of Bone Metabolism in Prepubertal Girls with Turner Syndrome Following Long-term Pegylated Growth Hormone Treatment.

The study aims to assess the improvement in bone metabolism in prepubertal girls with Turner Syndrome (TS) after long-term polyethylene glycol recombinant human Growth Hormone (PEG-rhGH) treatment. A 12-month longitudinal prospective study was conducted with 28 prepubertal girls diagnosed with TS. Participants were divided into two groups: 18 received PEG-rhGH therapy (0.1-0.25 mg/kg/week) and 10 did not. Anthropometric measurements, bone turnover markers (BTMs), and serum levels of IGF-1, calcium, and phosphate were collected at baseline and after 12 months. BTMs included bone alkaline phosphatase (BAP), Type I collagen propeptide (CICP), Type I collagen telopeptide (CTX), and fibroblast growth factor 23 (FGF23). After 12 months of PEG-rhGH therapy, the treatment group showed significant increases in growth velocity (GV) and height standard deviation scores (HtSDS). Serum IGF-1 levels increased rapidly within one month and remained elevated. BTMs indicated enhanced bone formation, significantly increasing BAP and CICP, while CTX levels remained low. FGF23 levels initially rose slightly but declined below baseline by 12 months. Elevated blood phosphate levels were observed. PEG-rhGH therapy in children with TS significantly improves linear growth and enhances bone formation markers, benefiting bone metabolism.

Revising LH cut-off for the diagnosis of central precocious puberty via triptorelin stimulation assay.

Precocious puberty (PP) in girls is defined by thelarche before age 8. The diagnostic gold standard is an increased LH level following gonadotropin-releasing hormone (GnRH) stimulation. Alternatively, GnRH analogues like triptorelin can be used, though their interpretation varies. Since 2000, we have used a triptorelin-induced LH cut-off of 15 IU/L, 4 h post-stimulus. However, many girls showed LH values below this threshold despite evident pubertal progression. To establish a new LH threshold post-triptorelin stimulation for earlier diagnosis of central precocious puberty (CPP) in girls showing pubertal progression and to evaluate additional parameters for diagnostic accuracy. We enrolled 186 girls with thelarche onset between ages 1-8 and a GnRH analogue assay performed between 2015-2019 without signs of axis activation. Within this cohort, 62 patients repeated the triptorelin test due to rapid pubertal progression. The assay involved administering 100 mcg/m² of triptorelin and measuring LH, FSH, and estradiol levels before and four hours post-injection. Patients with axis activation at the second test had significantly higher post-stimulus LH levels at the first test compared to those below 15 IU/L. They also had higher basal LH levels, elevated LH/FSH ratio, and increased growth velocity. Statistical analysis identified a new post-stimulus LH threshold of 5 IU/L. We propose a LH value of 5 IU/L after triptorelin administration as a new threshold for early CPP diagnosis. While the LH/FSH ratio and growth velocity are associated with axis activation, they did not significantly enhance diagnostic accuracy when combined with the LH value.

7349 Identifying the Onset of Puberty in Boys Born Small for Gestational Age (SGA)

Abstract Disclosure: S.M. Suco: None. A.C. Keselman: None. M.G. Ballerini: None. M.E. Rodriguez: None. M.G. Ropelato: None. S. Rosenbrock: None. D. Braslavsky: None. R.A. Rey: None. R.P. Grinspon: None. Introduction: Some children born SGA have an earlier pubertal onset and more rapid progression. Therefore, it is essential to identify the onset of puberty to proceed in a timely and appropriate manner. As it has also been suggested that there may be some gonadal dysfunction, the classic markers of pubertal onset, for example, testicular volume ≥ 4ml, may not be appropriate in these cases. Objective: To describe the clinical and biochemical characteristics of pubertal maturation in boys born SGA and determine parameters that best identify pubertal onset. Methods: We perform a retrospective, descriptive study of a cohort of boys born SGA with longitudinal follow-up, at a tertiary pediatric public hospital in Buenos Aires, Argentina. The subjects were selected from 1997 to 2023. Main outcome measures were serum levels of LH and AMH and testicular volume (TV). Additionally, height velocity, bone age, IGF1 and HOMA-IR were also collected to analyze its association with puberty. Pubertal onset was defined as serum LH ≥ 0.3 U/L and/or a decrease in serum AMH ≥ 30%. Results: The cohort included 25 boys born SGA, 24% were born prematurely and 60% were referred for short stature. In 18 boys (72%) AMH decline occurred with testicular volume < 4ml, at a median age of 9.8 yr (IQR 8.3 – 11 yr), and with median TV of 2ml. In 5 boys, LH was ≥ 0.3 U/L when AMH decline >30%. In 14 boys (56%) TV was <4ml when serum LH was ≥ 0.3 U/L. The median age for LH ≥0.3 was 11.3yr (IQR 10.4 – 12.2 yr), with a median TV of 3ml. In 3 boys the decrease in AMH occurred concomitantly with the increase in LH, while in 6 it occurred before.Alongside with the AMH decline, acceleration of bone age was observed in 35%, increase in growth velocity in 29%, increase in IGF1 concentrations in 24% and an increase in HOMA-IR in 26% of the boys. Concomitantly with an LH ≥0.3 U/L, acceleration of bone age was observed in 19%, increase in growth velocity in 25%, increase in IGF1 concentrations in 30% and an increase in HOMA-IR in 50% of the boys. Conclusion: The increase in testicular volume to 4ml, a classic parameter used as a marker of pubertal onset, may not be appropriate in a subgroup of children born SGA. Probably other parameters such as the increase in serum LH or the decrease in AMH should be considered. Presentation: 6/1/2024

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

Directionally solidified NiCoCrFeAlW eutectic high-entropy alloy: Microstructure and mechanical properties

The NiCoCrFeAlW eutectic high-entropy alloy exhibits a balanced combination of ductility and strength. This study examines the microstructure evolution and mechanical properties of the Ni30Co30Cr10Fe10Al18W2 alloy at varying growth velocities (10, 20, 50, 100, and 200 μm/s), which in its as-cast state, features a microstructure that includes both coarse dendrites and lamellar eutectic. The structure of the coarse dendrites is characterized by an ordered body-centered cubic (B2) phase, while the lamellar eutectic, features a combination of face-centered cubic (FCC) and ordered B2 phases. The microstructure, characterized by lamellar and dendritic structures that are parallel to the growth direction after directional solidification, undergoes a morphological transition at the solid-liquid interface from a planar to a dendritic form as growth velocity increases. The tensile fracture strength initially increases with the growth velocity, reaching a peak of 1286 MPa at a velocity of 50 μm/s, and then subsequently decreases as the growth velocity continues to increase. Directional solidification results in an increase in sample elongation with increasing growth velocity, achieving an elongation of 22.5% at 200 μm/s. An examination of the deformation mechanism reveals that the lamellar structure, composed of the more ductile FCC phase and the harder B2 phase, effectively harmonizes the plasticity and strength of the alloy. Therefore, directional solidification significantly adjusts the eutectic microstructure's orientation, thereby enhancing the mechanical properties along the direction of solidification.

International expert opinion on the considerations for combining vosoritide and limb surgery: a modified delphi study

BackgroundAchondroplasia is the most common form of skeletal disorder with disproportionate short stature. Vosoritide is the first disease-specific, precision pharmacotherapy to increase growth velocity in children with achondroplasia. Limb surgery is a standard approach to increase height and arm span, improve proportionality and functionality, as well as correcting deformities. The aim of this study was to gain expert opinion on the combined use of vosoritide and limb surgery in children and adolescents with achondroplasia.MethodsAn international expert panel of 17 clinicians and orthopaedic surgeons was convened, and a modified Delphi process undertaken. The panel reviewed 120 statements for wording, removed any unnecessary statements, and added any that they felt were missing. There were 26 statements identified as facts that were not included in subsequent rounds of voting. A total of 97 statements were rated on a ten-point scale where 1 was ‘Completely disagree’ and 10 ‘Completely agree’. A score of ≥ 7 was identified as agreement, and ≤ 4 as disagreement. All experts who scored a statement ≤ 4 were invited to provide comments.ResultsThere was 100% agreement with several statements including, “Achieve a target height, arm span or upper limb length to improve daily activities” (mean level of agreement [LoA] 9.47, range 8–10), the “Involvement of a multidisciplinary team in a specialist centre to follow up the patient” (mean LoA 9.67, range 7–10), “Planning a treatment strategy based on age and pubertal stage” (mean LoA 9.60, range 8–10), and “Identification of short- and long-term goals, based on individualised treatment planning” (mean LoA 9.27, range 7–10), among others. The sequence of a combined approach and potential impact on the physes caused disagreement, largely due to a lack of available data.ConclusionsIt is clear from the range of responses that this modified Delphi process is only the beginning of new considerations, now that a medical therapy for achondroplasia is available. Until data on a combined treatment approach are available, sharing expert opinion is a vital way of providing support and guidance to the clinical community.

Over Three Decades of Growth Hormone Treatment in Children With Chronic Kidney Disease-Associated Growth Failure Before and After Kidney Transplantation.

Growth retardation and short final height is a common complication of chronic kidney disease (CKD) beginning in childhood, with profound deleterious effects on quality of life, mental health, and social achievement. Despite optimal treatments of causative factors for growth retardation in children with CKD, more than 50% of patients reach end-stage renal failure with a height >2 SD below the mean, and most do not demonstrate "catch-up" growth after receiving a kidney transplant. Four decades ago, recombinant human growth hormone (rhGH) treatment was introduced after studies showed increased growth velocity and improved height SDS in uremic subjects. Since then, an abundance of published data showed significant improvements in health-related quality of life, and most studies revealed no significant adverse effects. Clinical practice guidelines recommended rhGH treatment in CKD Stages 3-5D and after transplantation. Despite these guidelines, this therapy remained underutilized. Most commonly cited barriers to the implementation of rhGH treatment were the need for daily injections, financial challenges, physicians' unfamiliarity with guidelines, and fear of adverse events. rhGH has been shown to improve growth and final height in short children with CKD, with minimal adverse effects. Despite data of its successful use generated over 3 decades, this treatment is underutilized. More judicious utilization of the treatment should emphasize educating patients, their care givers, and members of the multidisciplinary treating team. Additional studies are needed to assess the longer-term rhGH treatment in larger cohorts of patients, leading to additional supportive data and clearer recommendations.

GH Treatment in Children of Normal Height.

The increased availability of recombinant human GH (rhGH), albeit at a relatively high cost, has increased a demand for treatment of children and adolescents of normal height to increase their adult stature. There are no scientific reports on the efficacy and safety of rhGH therapy in this condition; therefore, the authors comment on the possible causes and consequences based on their personal opinion and experience. As in gigantism, when GH action and end-organ are normal, enough GH is expected to result in increased growth velocity. Short-term adverse effects related to rhGH therapy for approved indications of short stature in children have been very rare. Data on long-term adverse effects are still scarce. A small increase in height might be statistically significant but not functionally or socially relevant. Considering that an increase in height represents more a desire than a need, physicians should emphasize the normality and qualities of these children, discuss with families the alternatives, such as counseling, and refrain from supporting the concept that taller is better.

Vosoritide treatment for children with hypochondroplasia: a phase 2 trial

Hypochondroplasia is a rare autosomal dominant skeletal dysplasia due to activating variants in FGFR3. It presents with disproportionate short stature with a wide range of clinical severity. There are currently no approved medications to treat short stature in children with hypochondroplasia. Vosoritide is a C-type natriuretic peptide analog that was recently approved for improving growth in children with achondroplasia. We aimed to evaluate the safety and efficacy of vosoritide in children with hypochondroplasia. We conducted a single-arm, phase 2, open-label trial at a single centre in the USA and enrolled 26 children with hypochondroplasia. The trial consists of a 6-month observation period to establish a baseline annualized growth velocity followed by a 12-month intervention period during which vosoritide is administered daily via subcutaneous injection at a dose of 15μg/kg/day. The trial's co-primary endpoints included the incidence of adverse events and the change from baseline in age-sex standardized annualized growth velocity and height standardized deviation score (SDS) after 12 months of treatment. This trial is registered with ClinicalTrials.gov (NCT04219007). Twenty-four participants with a mean age of 5.86 years received vosoritide therapy. The first participant was enrolled on August 4, 2020, and the final participant completed the 18-month trial on September 8, 2023. Vosoritide was well tolerated with no treatment-related serious adverse events. Injection site reactions occurred in 83.3% of participants. No participants discontinued therapy due to an adverse event. Annualized growth velocity increased by 2.26 standard deviations (SD) and height SDS increased by 0.36 SD during the treatment period versus the observation period. Hypochondroplasia specific height SDS increased by 0.38 SD. There was a 1.81cm/year increase in absolute annualized growth velocity. Vosoritide was safe and effective in increasing growth velocity in children with hypochondroplasia. Efficacy was similar to what has been reported in children with achondroplasia. This study was supported by an investigator-initiated grant from BioMarin Pharmaceutical.

The association between rapid growth and lipid profile: a systematic review and meta-analysis.

Metabolic disease prevalence has increased in many regions, and is closely associated with dyslipidemia. Rapid growth refers to a significant increase in growth velocity above the normal range, particularly in infants and children, and is highly prevalent in congenital deficiency infants. But the association between dyslipidemia and rapid growth remains controversial. We performed this meta-analysis to investigate the lipid profile in subjects with and without postnatal rapid growth, and to determine what are the confounding factors. Medline, EMBASE, China National Knowledge Infrastructure Chinese citation database and WANFANG database were searched (last search in May 2021). Publication bias was examined by constructing funnel plots, Egger's linear regression test and Begg's rank correlation test. The fixed effects model would be adopted if I2 is less than 25%, otherwise random effects model would be used. There were 11 articles involved with a total of 1148 participants (539 boys and 609 girls, mean age=7.4 years). Pooled analysis found that rapid growth was negatively associated with high-density lipoprotein cholesterol (HDL-C) (weighted mean difference=-0.068, 95%CI [-0.117, -0.020]), but not associated with triglycerides (TG), total cholesterol (TC), or low-density lipoprotein cholesterol (LDL-C). Stratified analysis suggested that increased TG were found in rapid growth subjects from developing countries. Higher TC was observed for rapid growth participants of follow-up age ≤8 years old, rapid growth duration ≤2 years, preterm, low birth weight, and from developing countries. But decreased TC was observed in small for gestational age (SGA) rapid growth subjects. Decreased LDL-C had been documented in rapid growth subjects of follow-up age >8 years old, from developed countries, and SGA. At last, rapid growth groups had lower HDL-C in infants of rapid growth duration >2 years and from developed countries. Rapid growth is associated with lipid profiles, particularly during early childhood, and this relationship is influenced by factors such as the duration of growth, the level of national development, and birth weight. These findings are significant for the development of strategies to prevent metabolic diseases.This review was registered in PROSPERO International Prospective Register of Systematic Reviews (www.crd.york.ac.uk/prospero/) with the registration number CRD42020154240.

Vosoritide Therapy in Children with Achondroplasia: Early Experience and Practical Considerations for Clinical Practice.

Vosoritide is the first precision medical therapy approved to increase growth velocity in children with achondroplasia. Sharing early prescribing experiences across different regions could provide a framework for developing practical guidance for the real-world use of vosoritide. Two meetings were held to gather insight and early experience from experts in Europe, the Middle East, and the USA. The group comprised geneticists, pediatric endocrinologists, pediatricians, and orthopedic surgeons. Current practices and considerations for vosoritide were discussed, including administration practicalities, assessments, and how to manage expectations. A crucial step in the management of achondroplasia is to determine if adequate multidisciplinary support is in place. Training for families is essential, including practical information on administration of vosoritide, and how to recognize and manage injection-site reactions. Advocated techniques include establishing a routine, empowering patients by allowing them to choose injection sites, and managing pain. Patients may discontinue vosoritide if they cannot tolerate daily injections or are invited to participate in a clinical trial. Clinicians in Europe and the Middle East emphasized the importance of assessing adherence to daily injections, as non-adherence may impact response and reimbursement. Protocols for monitoring patients receiving vosoritide may be influenced by regional differences in reimbursement and healthcare systems. Core assessments may include pubertal staging, anthropometry, radiography to confirm open physes, the review of adverse events, and discussion of concomitant or new medications-but timing of these assessments may also differ regionally and vary across institutions. Patients and families should be informed that response to vosoritide can vary in both magnitude and timing. Keeping families informed regarding vosoritide clinical trial data is encouraged. The early real-world experience with vosoritide is generally positive. Sharing these insights is important to increase understanding of the practicalities of treatment with vosoritide in the clinical setting.

Does Growth Velocity Affect Associations between Birth Weight and Neurodevelopment for Infants Born Very Preterm?

To determine how neonatal growth velocity affects the association between birth weight and neurodevelopmental outcomes in infants born preterm. This study is a secondary analysis of the Maternal Omega-3 Supplementation to Reduce Bronchopulmonary Dysplasia in Very Preterm Infants (MOBYDIck) randomized multicenter trial conducted in breastfed infants born at <29weeks of gestation, whose mothers were supplemented with docosahexaenoic acid or placebo during the neonatal period. Neurodevelopmental outcomes were assessed at 18-22months of corrected age using the Bayley-III cognitive and language composite scores. The role of neonatal growth velocity was assessed with causal mediation and linear regression models. Subgroup analyses were stratified by birth weight z-score categories (<25th, ≥25th-≤75th, and >75th percentiles). Neurodevelopmental outcomes were available for 379 children (mean gestational age, 26.7± 1.5 weeks). Growth velocity partially mediated the relationships between birth weight and cognitive (β=-1.1; 95% CI, -2.2 to -0.02; P=.05) and language scores (β=-2.1; 95% CI, -3.3 to -0.8; P=.002). An increase by 1g/kg/day in growth velocity was associated with an increase by 1.1 point in the cognitive score (95% CI, -0.03 to 2.1; P=.06) and 1.9 point in the language score (95% CI, 0.7 to 3.1; P=.001), after adjustment for birth weight z-score. For children with birth weight<25th percentile, a 1g/kg/day increase in growth velocity was associated with an increase by 3.3 points in the cognitive score (95% CI, 0.5 to 6.0; P=.02) and 4.1 points in the language score (95% CI, 1.3 to 7.0; P=.004). Postnatal growth velocity mediated the relationship between birth weight and neurodevelopmental performance, with larger effects for children with lower birth weight. Clinicaltrials.gov identifier: NCT02371460.

Ag3Sn Morphology Transitions During Eutectic Growth in Sn–Ag Alloys

Eutectic Ag3Sn can grow with a variety of morphologies depending on the solidification conditions and plays an important role in the performance of Pb-free solders. Here, we study morphology transitions in the β-Sn + Ag3Sn eutectic at increasing growth velocity using a combination of real-time X-ray imaging and analytical electron microscopy. Orthorhombic Ag3Sn grew as faceted plates or rods with [010] growth direction and (001) as the largest facet in all three eutectic growth morphologies: Irregular plate, broken-lamellar, and rod. Reproducible β-Sn + Ag3Sn orientation relationships formed for the latter two morphologies. The mechanisms of spacing adjustment and the reversible transition from plate to rod growth are studied for transient solidification after velocity changes. The transition from fully eutectic growth to β-Sn dendrites plus eutectic is reasonably reproduced using a competitive growth criterion. At the highest velocities, Ag3Sn rods developed perturbations whose break down into particles is discussed in terms of unsteady growth and pinch-off mechanisms.

Repercussão da perda de peso na velocidade de crescimento de crianças e adolescentes: um estudo de caso

Report of the longitudinal evolution of the anthropometric indices of an obese child from preschool to the end of the puberty. It is about a 4 year-old boy with history of weight gain since the first year due to carbohydrate-rich and industrialized food intake, associated with physical inactivity and familiar history of obesity. At the first appointment he had body mass index (BMI) in Z-score + 7,36 and stature above the parental target. After orientations about lifestyle changes, he reached, at 7 years old, the lowest BMI and the growth rate became reduced. At this point, other causes of growth retardation have been ruled out, therefore the hypothesis was of growth stop secondary to weight loss and recanalization of the growth curve in response to the treatment of the exogenous obesity. In the evolution, the patient regained weight maintaining the drop on the stature, staying within the parental target. When puberty started, he presented progressive fall in BMI score and increased growth velocity. At 17, he reached BMI and stature within normality and parent target. Throughout the follow-up, the importance of healthy eating and realization of physical activity was reinforced. No medications were used, and there were no alterations at physical and complementary exams. The weight loss in obese children with tall stature for the parental target, can lead to slow growth rate when secondary to change to healthy habits and increase in physical activity, however without affecting the final height.

PMON325 Rare Presentation of Precocious Puberty Secondary to LH-Secreting Adenoma

Abstract Background Normal male puberty begins after 9 years of age with a concurrent rise in luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These play distinct roles, with LH acting on Leydig cells to stimulate testosterone and secondary sex characteristics, while FSH promotes testicular growth by stimulating the maturation of seminiferous tubules. Clinical Case An 8-year 9-month-old male TV presented with a 1.5 year history of facial hair and 9 months of phallic growth, body odor and acne. Physical exam revealed phallic enlargement, Tanner stage I pubic hair and firm, borderline pubertal testes (4 cc bilaterally). Bone age was 9 years at a chronological age of 8 years 6 months. Laboratory evaluation was inconsistent with typical puberty – LH (9 mIU/mL, RR 0.0-0.3 mIU/mL) and testosterone (519 ng/dL, RR 2-8 ng/dL) were elevated while FSH was pre-pubertal (&amp;lt;0.1 mIU/mL, RR 0.0-2.8 mIU/mL) and androgens were only mildly elevated (androstenedione 0.363 ng/mL, RR 0.03-0.3; 17-OHP 155 ng/dL, RR&amp;lt;63 ng/dL). Head MRI revealed an anterior pituitary adenoma measuring 8×12×10 mm. After failing to respond to leuprolide, TV was initiated on spironolactone and anastrozole to minimize pubertal progression prior to transsphenoidal adenomectomy. Surgical pathology was positive for steroidogenic factor 1 but negative for LH, FSH and thyroid-stimulating hormone immunoreactivity. However, he had post-operative reduction of LH (0.4 mIU/mL, RR 0.0-0.3 mIU/mL) and testosterone (16 ng/dL, RR 2-8 ng/dL). Conclusions Normal male puberty follows a predictable sequence, beginning with testicular enlargement followed by body odor, pubic hair growth, phallic enlargement, voice change, and increased growth velocity. In TV, hypersecretion of LH led to testosterone production, causing secondary sex characteristics. However, his pre-pubertal FSH did not stimulate the testicular growth that typically heralds the onset of puberty. Digression from typical pubertal sequence and isolated high LH raised concern for a pathologic cause. Central precocious puberty (CPP) is most often idiopathic in females, although more commonly associated with CNS lesions in males. Rarely, precocious puberty results from a functioning gonadotroph adenoma. Less than 1% of these are hormonally active. If active, these more often secrete FSH or co-secrete FSH and LH, and typically require surgical resection given limited success of medical therapies. This case illustrates the distinct roles of FSH and LH in pubertal development. Departures from the typical sequence of development should expand one's differential to include etiologies resulting in nonconcurrent secretion of gonadotropins. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Pathology or expected morphology? Investigating patterns of cortical porosity and trabecularization during infancy and early childhood.

Increased cortical porosity is associated with a heightened risk of skeletal fragility due to bone loss and structural decay in adults. However, few studies have examined the etiology of cortical porosity in infants and children. This study examines whether age-related changes in femoral growth and locomotor development influence femoral midshaft cortical porosity in a sample of 48 individuals (fetal to 3.99 years) from the 10th-13th century cemetery of St. Étienne de Toulouse, France. Histological sections were prepared and imaged using light microscopy. Midshaft geometric variables such as total area, cortical area, and pore area were calculated using BoneJ. Increased porosity and cortical trabecularization were found to be significantly associated with age, being almost exclusively present in individuals aged 0.5-1.99 years. At approximately 6months of age infants typically begin engaging in regular femoral loading and experience an acceleration in growth. The observed increase in midshaft porosity and trabecularization, therefore, likely results from the reorganization and redistribution of cortical bone, stimulated by increased growth velocity and the onset of weight-bearing activities. The reduction in cortical porosity and trabecularization in individuals aged 2.0-3.99 years indicates that children are approaching some sort of homeostasis as growth velocity slows and their femora adapt to consistent loading. Understanding what expected skeletal development looks like is necessary when conducting bioarcheological studies and this study provides evidence for a pattern of transient midshaft porosity during infancy and early childhood.

Influence of growth velocity on fragmentation during directional solidification of Al – 14 wt.% Sn alloy studied by in-situ synchrotron X-radiography

Directional solidification of Al – 14 wt.% Sn alloy was investigated by means of synchrotron X-radiography at the European Synchrotron Radiation Facility (ESRF). The dynamics of the solidification microstructure formation was studied in-situ and in real-time. In the present manuscript, a special attention is given to the influence of increasing growth velocity on the fragmentation phenomenon of dendrite arms, which has an important role and impact on the final grain structure. Fragmentations of both secondary dendrite arms and more strikingly part of primary trunks have been observed. The experiments show that the number of fragments increases concomitantly with the solidification growth rate until it reaches a limit value after which fewer or no more fragments are observed. The possible origins of the fragmentation are discussed in detail and the likelihood of each of these potential mechanisms is estimated to understand the reason of both primary and secondary arm detachment. It is shown that the fragmentation in a transient regime is correlated to the variations of the solute accumulation, latent heat rejection and the curvature of the attachment neck during solidification. Moreover, during these experiments, Columnar-to-Equiaxed Transition (CET) induced by the fragmentation phenomenon is observed. The velocity of the dendrite fragments due to the buoyancy force is a major parameter to control the CET and our results show that a reverse Equiaxed-to- Columnar Transition can even be observed. Once the growth velocity is of the same order or higher than the fragment flotation velocity, the fragments are trapped within the columnar dendritic microstructure, and CET cannot take place or the equiaxed regime cannot be sustained.

Seaweed and Dendritic Growth in Unsaturated Fatty Acid Monolayers.

The lateral movement in lipid membranes depends on their diffusion constant within the membrane. However, when the flux of the subphase is high, the convective flow beneath the membrane also influences lipid movement. Lipid monolayers of an unsaturated fatty acid at the water–air interface serve as model membranes. The formation of domains in the liquid/condensed coexistence region is investigated. The dimension of the domains is fractal, and they grow with a constant growth velocity. Increasing the compression speed of the monolayer induces a transition from seaweed growth to dendritic growth. Seaweed domains have broad tips and wide and variable side branch spacing. In contrast, dendritic domains have a higher fractal dimension, narrower tips, and small, well-defined side branch spacing. Additionally, the growth velocity is markedly larger for dendritic than seaweed growth. The domains’ growth velocity increases and the tip radius decreases with increasing supersaturation in the liquid/condensed coexistence region. Implications for membranes are discussed.

098 McCune-Albright syndrome in a 5 years old girl with apparently central precocious puberty: a significant diagnostic delay

Objective: In girls, precocious puberty (PP) presents with breast development, increased growth velocity and bone maturation before the age of 8yrs. The cause can be Central PP (CPP; or gonadotropin (Gn) dependent) or peripheral PP (P-PP; or Gn independent). A gonadotropin releasing hormone (GnRH) test can distinguish between CPP and P-PP.

Constitutional supercooling and corresponding microstructure transition triggered by high magnetic field gradient during directional solidification of Al-Fe eutectic alloy

Directional solidification experiments of eutectic AlFe alloys were carried out under different high magnetic field gradients. High magnetic field gradient changed the microstructure selection during solidification process, induced the solidification microstructure to undergo eutectic instability, cellular transition, single-phase instability, and dendrite transition, which is similar to the planar-cellular-dendritic crystal growth pattern transition usually induced by an increasing growth velocity without magnetic field. The single phase was proved to be formed through an independent nucleation mechanism during single-phase instability. The effect of high magnetic field gradient on solidification was analyzed. Through the coupling effect of magnetic force and Lorentz force on solute migration and diffusion during solidification, high magnetic field gradient triggered a constitutional supercooling at the front of solid-liquid interface, which led to the growth pattern transition. A solidification model of eutectic alloy under high magnetic field gradient was proposed, and the microstructure selection map of AlFe alloy under gradient magnetic field was qualitatively drawn for the first time. This work proved that an alloy material with a microstructure usually obtained at high growth velocity can be obtained at a low growth velocity by applying a high magnetic field gradient, and suggested a new potential method for the future controlling of alloy structures and properties.