Hydrocortisone Suspension Provides Similar Growth Outcomes as Hydrocortisone Tablets in Young Children with CAH

Background Young children with CAH require small doses (0.1-1.25 mg) of hydrocortisone (HC) to control excess androgen production and avoid the negative effects of overtreatment. The smallest commercially available HC formulation, before the recent FDA approval of HC granules, was a scored 5 mg tablet. The options to achieve small doses were limited to using a pharmacy-compounded suspension, which the CAH Clinical Practice Guidelines recommended against, or splitting tablets into quarters or eighths, or dissolving tablets into water. Methods Cross sectional chart review of 130 children with classic CAH treated with tablets versus a pharmacy-compounded alcohol-free hydrocortisone suspension to compare growth, weight, skeletal maturation, total daily HC dose and exposure over the first four years of life. Results No significant differences were found in height, weight, or BMI z-scores at 4 years, and in predicted adult height, before or after adjusting for age at diagnosis and sex. Bone age z-scores averaged 2.8 SDs lower for patients on HC suspension compared to HC tablets (p<0.001) after adjusting for age at diagnosis and sex. The suspension group received 30.4% lower (p>0.001) average cumulative HC doses by their 4th birthday. Conclusions Our data indicates that treatment with alcohol-free HC suspension decreased androgen exposure as shown by lower bone age z-scores, allowed lower average and cumulative daily HC dose compared to HC tablets, and generated no significant differences in SDS in growth parameters in children with CAH at 4 years of age. Longitudinal studies of treating with smaller HC doses during childhood are needed.

Treatment of Short Stature in Aggrecan Deficient Patients with Recombinant Human Growth Hormone: One-Year Response

Context Patients with aggrecan (ACAN) deficiency present with dominantly inherited short stature, often with advanced skeletal maturation and premature growth cessation. There is a paucity of information on the effects of growth-promoting interventions. Objective The aim of this study was to evaluate the efficacy and safety of recombinant human growth hormone (rhGH) therapy on linear growth in children with ACAN deficiency. Design and Setting Open-label, single-arm, prospective study at Cincinnati Children’s Hospital Medical Center. Patients Ten treatment-naïve patients were recruited. Inclusion criteria were: a confirmed heterozygous mutation in ACAN, age ≥ 2 years, pre-pubertal, bone age (BA) ≥ chronological age (CA), and normal IGF-I concentration. Intervention Treatment with rhGH (50 mcg/kg/day) over one year. Main Outcome Measure(s) Main outcomes measured were height velocity (HV) and change in (Δ) height SD (HtSDS). Results Ten patients (six females) were enrolled with median CA of 5.6 yrs (range 2.4 to 9.7). Baseline median HtSDS was -2.5 (range -4.3 to -1.1). Median baseline BA was 6.9 yrs (range 2.5 to 10.0), with median BA/CA of 1.2 (range 0.9 to 1.5). Median pre-treatment HV was 5.2 cm/y (range 3.8 to 7.1), increased to 8.3 cm/y (range 7.3 to 11.2) after one year of therapy (p=0.004). Median ΔHtSDS after one year was +0.62 (range +0.35 to +1.39) (p=0.002). Skeletal maturation did not advance inappropriately (median Δ BA/CA -0.1, p=0.09). No adverse events related to rhGH were observed. Conclusion Treatment with rhGH improved linear growth in a cohort of patients with short stature due to ACAN deficiency.

Transversal craniofacial development between skeletal maturation stages: A multi-center posteroanterior cephalometric study

Objectives: The aim of this study is to evaluate the dentofacial transversal norms according to the stages of skeletal maturation in growing Turkish individuals and to determine differences between the genders. Materials and Methods: In our multi-centered, cross-sectional retrospective study, in which transversal measurements were made according to skeletal maturation stages (SMSs), posteroanterior radiographs of 572 individuals (292 female, 280 male) with skeletal and dental Class I relationships and good occlusion were examined at the age range of 7–18 years. SMSs were determined using Björk, Grave and Brown hand-wrist radiography. A linear regression model was used for changes of transversal measurements between SMSs, and t-test was used to determine transverse changes between the genders. Results: There was no statistically significant difference between females and males in cranial, facial, and nasal width values up to SMS 5. In maxillary, mandibular, maxillary intermolar, and mandibular intermolar width measurements, males had higher values in most stages of skeletal maturation compared to females. Apart from nasal width and maxillomandibular ratio values in females, the regression model in which transversal measurements were dependent variables, and SMS were independent variables was found to be significant. According to cumulative growth percentages, the growth completion in transversal measurements occurred earlier in females. Conclusion: Transversal measurements determined according to the stages of skeletal maturation can be a guide for orthodontists in the clinic to determine values that deviate from normal.

Should Skeletal Maturation Be Manipulated for Extra Height Gain?

Skeletal maturation can be delayed by reducing the exposure to estrogens, either by halting pubertal development through administering a GnRH analogue (GnRHa), or by blocking the conversion of androgens to estrogens through an aromatase inhibitor (AI). These agents have been investigated in children with growth disorders (off-label), either alone or in combination with recombinant human growth hormone (rhGH). GnRHa is effective in attaining a normal adult height (AH) in the treatment of children with central precocious puberty, but its effect in short children with normal timing of puberty is equivocal. If rhGH-treated children with growth hormone deficiency or those who were born small-for-gestational age are still short at pubertal onset, co-treatment with a GnRHa for 2-3 years increases AH. A similar effect was seen by adding rhGH to GnRHa treatment of children with central precocious puberty with a poor AH prediction and by adding rhGH plus GnRHa to children with congenital adrenal hyperplasia with a poor predicted adult height on conventional treatment with gluco- and mineralocorticoids. In girls with idiopathic short stature and relatively early puberty, rhGH plus GnRHa increases AH. Administration of letrozole to boys with constitutional delay of growth puberty may increase AH, and rhGH plus anastrozole may increase AH in boys with growth hormone deficiency or idiopathic short stature, but the lack of data on attained AH and potential selective loss-of-follow-up in several studies precludes firm conclusions. GnRHas appear to have a good overall safety profile, while for aromatase inhibitors conflicting data have been reported.

Relationship between Skeletal Maturity, BMI Percentile and Dental Caries Experience among Taster and Non-taster Children

Introduction: Ability of an individual to taste phenylthiocarbamide (PTC) substance divides the population in tasters and non-tasters. The objective of this study was to investigate the relationship between the taste ability for PTC substance with BMI percentile, skeletal maturity and dental caries experience within taster and non-taster children of age 8-12 years. Hypotheses: Tasting ability for PTC affects the BMI percentile, skeletal maturity and dental caries experience and emerge as a useful caries risk assessment tool. Evaluation of Hypotheses (Materials and Method): One hundred children of 8-12 years were randomly selected and their taste perception was assessed using PTC sensitivity test. Radiovisiography (RVG) of middle phalanx was obtained to determine the skeletal maturity by using Rajgopal and Kansal modification 2005. Anthropometric measurements were recorded to obtain BMI value and then BMI percentile was calculated using CDC Pediatric growth charts. For dental caries assessment, deft/DMFT scores were recorded. Results: The non-tasters had early skeletal maturation, higher caries experience and higher BMI percentile than the tasters. Conclusion and Clinical Relevance: PTC Sensitivity is a genetically controlled trait showing strong association with dental caries. From the results of this study we can conclude that the genetic ability of tasting PTC affects the BMI percentile, skeletal maturity and dental caries experience. Thus it can emerge as a useful caries risk assessment tool helping in planning the preventive measures and interceptive orthodontics in children.

The comprehensive mechanistic insight into the effects of vitamin D on dementia – a review

Purpose This paper aims to depict the mechanistic role of vitamin D on dementia prevention, relief of the severity and the complication of the disease. All papers indexed in scientific databases, including Scopus, Elsevier, PubMed, Embase and Google Scholar between 2000 and 2021 were extracted and discussed. To present the mechanistic role of vitamin D in declining the severity of dementia, keywords including dementia, vitamin D, oxidative stress, inflammation, amyloid beta-Peptides were used. Design/methodology/approach Dementia is a prevalent cognitive disorder worldwide, especially in elderly people, which is accompanied by serious disabilities. Besides genetic, biological and lifestyle factors are involved in the incidence of dementia. An unhealthy diet along with micronutrient deficiencies are among modifiable factors. Vitamin D is one of the important micronutrients in brain health. Besides the involvement in gene expression, bone mineralization, apoptosis, inflammation, skeletal maturation, neurotropic action and hemostasis of phosphate and calcium, vitamin D also exerts neuroprotective effects via genomic and non-genomic pathways. Findings Vitamin D up-regulates the expression of various genes involved in dementia incidence via various mechanisms. Decreasing oxidative stress and the neuro-inflammatory cytokines levels, regulation of the expression of alternated Proteins including Tau and Amyloid-ß, calcium homeostasis in the central nervous system and also vascular are considered main mechanisms. Originality/value Considering the importance of diet in preventing dementia, adherence to a healthy diet that provides essential nutrients to brain function seems to be urgent. Controlling serum levels of vitamin D periodically and providing vitamin D by related sources or supplements, if there is a deficiency, is recommended. Future studies are needed to clarify other related mechanisms.

CYP11B1 variants influence skeletal maturation via alternative splicing

We performed genome-wide association study meta-analysis to identify genetic determinants of skeletal age (SA) deviating in multiple growth disorders. The joint meta-analysis (N = 4557) in two multiethnic cohorts of school-aged children identified one locus, CYP11B1 (expression confined to the adrenal gland), robustly associated with SA (rs6471570-A; β = 0.14; P = 6.2 × 10−12). rs6410 (a synonymous variant in the first exon of CYP11B1 in high LD with rs6471570), was prioritized for functional follow-up being second most significant and the one closest to the first intron-exon boundary. In 208 adrenal RNA-seq samples from GTEx, C-allele of rs6410 was associated with intron 3 retention (P = 8.11 × 10−40), exon 4 inclusion (P = 4.29 × 10−34), and decreased exon 3 and 5 splicing (P = 7.85 × 10−43), replicated using RT-PCR in 15 adrenal samples. As CYP11B1 encodes 11-β-hydroxylase, involved in adrenal glucocorticoid and mineralocorticoid biosynthesis, our findings highlight the role of adrenal steroidogenesis in SA in healthy children, suggesting alternative splicing as a likely underlying mechanism.