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Primary (acute and chronic) malnutrition is still prevalent in developing countries because of inadequate nutrition and poor sanitation caused by social, economic, and environmental factors. In addition, acute malnutrition can occur secondary to an underlying disease that interferes with the intake, digestion, absorption, or assimilation of different nutrients increases nutrient loss, and/or increases energy expenditure. Immune dysfunction and infection are tightly linked to and actively contribute to the metabolic and hormonal dysregulation as well as to the progression of malnutrition. An inadequate dietary intake of macro-and micronutrients is proposed to adversely affect local intestinal and systemic immunity, intestinal mucosal integrity, and the interaction between host defense and pathogens. Lowered immunity, mucosal damage, recurrent and prolonged infections, and gut inflammation negatively affect the malnourished child growth in weight and height as well as psycho-mental development in endemic areas. Both infection and inflammation aggressively contribute to malnutrition triggering a vicious cycle. Almost all infantile and childhood malnutrition in endemic settings (unlike anorexia nervosa) results from deficient diet, infection, inflammation, and intestinal dysfunction (most children in endemic areas have environmental enteric dysfunction (EED), often with high fecal inflammatory markers. We highlight gaps in our understanding of the current interaction among immune dysfunction, infection, and inflammation in malnourished children, and evaluate the possible responsibility of pro-inflammatory cytokines in the initiation and progression of severe malnutrition. Breach of the malicious cycle between malnutrition and infection/inflammation requires innovative interferences to recover the immune defense and enforce host defense against pathogens and reduce morbidity and mortality.&nbsp

Context Intramuscular (IM) testosterone enanthate (TE) and testosterone pellets were US Food and Drug Administration approved before 1962 for pediatric use but not studied in controlled trials in adolescents. Objective An analysis using nonlinear mixed effect (NLME) modeling was designed to evaluate the adult pharmacokinetics (PK) of subcutaneous (SC) and IM TE. This model was used to simulate SC and IM TE administration in adolescents of different weight groups. Methods Data from adult male patients in a phase 2 trial were used to characterize the PK of TE using population PK modeling for SC and IM administration: Allometry was used to scale PK parameters from the adult model to simulate adolescent (aged 12 to Results The final data set included 714 samples from 15 patients receiving 100 mg SC TE and 123 samples from 10 patients receiving 200 mg IM TE. In simulated populations, average serum concentration SC:IM ratios were 0.783, 0.776, and 0.757 at steady state for weekly, EOW, and monthly dosing groups, respectively. Simulated regimens of 12.5 mg SC TE monthly produced serum testosterone levels representative of early puberty and simulated pubertal stage progression following multiple subsequent testosterone dose increases. Conclusion SC TE administration achieved a testosterone exposure-response relationship similar to IM TE in simulated adolescent hypogonadal males, which may reduce size of fluctuations in serum T and related symptoms.

Growth hormone deficiency (GHD) is a clinical syndrome that can manifest either as isolated or associated with additional pituitary hormone deficiencies. Although diminished height velocity and short stature are useful and important clinical markers to consider testing for GHD in children, the signs and symptoms of GHD are not always so apparent in adults. Quality of life and metabolic health are often impacted in patients with GHD; thus, making an accurate diagnosis is important so that appropriate GH replacement therapy can be offered to these patients. Screening and testing for GHD require sound clinical judgment that follows after obtaining a complete medical history of patients with a hypothalamic-pituitary disorder and thorough physical examination with specific features for each period of life, while targeted biochemical testing and imaging are required to confirm the diagnosis. Random measurements of serum GH levels are not recommended to screen for GHD (except in neonates) as endogenous GH secretion is episodic and pulsatile throughout the lifespan. One or more GH stimulation tests may be required, but existing methods of testing might be inaccurate, difficult to perform, and can be imprecise. Furthermore, there are multiple caveats when interpreting test results including individual patient factors, differences in peak GH cut-offs (by age and test), testing time points, and heterogeneity of GH and IGF-I assays. In this article, we provide a global overview of the accuracy and cut-offs for diagnosis of GHD in children and adults, and discuss the caveats in conducting and interpreting these tests.

This study examined the validity of two automated methods (BAUSport, BoneXpert software using Fels, Greulich-Pyle, Tanner-Whithouse III protocols) for estimating skeletal age (SA) in young athletes in comparison to a reference standard (Fels). 85 male and female athletes, nine to seventeen years of age, from multiple sports were assessed for SA as part of an annual medical and health screening programme. Intra-class correlations demonstrated high degrees of association between the automatic methods for estimating SA (BAUSport r =.98; BoneXpert r =.96-.99) and the discrepancy between SA and chronological age (SA-CA) (BAUSport r =.93; BoneXpert r =.88-.97), with the reference standard. Concordance analyses for the categorisation of participants as early, on-time and late maturing also demonstrated substantial levels of agreement for both methods (BAUSport Kappa = .71; BoneXpert Fels Kappa = .63) with the reference standard. Bland-Altman plots comparing the automatic methods with the reference standard identified statistically significant fixed biases, ranging in magnitude from small to large. Collectively, these results suggest that BoneXpert and BAUSport can provide comparable estimates of SA and SA-CA in young athletes relative to the Fels method. Biases in the estimation of SA should, however, be considered and the automatic methods should be implemented as part of a comprehensive growth and maturity screening protocol. The non-invasive nature of the BAUSport method affords particular advantages (no radiation exposure, portability) in contexts where the regular estimation of SA is recommended.

Background: People have long been fascinated with the size and growth of living things, from the giants of classic mythology and art to the little people who also have appeared in classical art, as well as the courts of European monarchs, and were exploited in “shows.” Serious medical evaluation began in the late 19th century with the description of acromegaly and its association with pituitary tumors. In the early 20th century, multiple investigators attempted to extract a growth-promoting factor from the anterior pituitary and then, over the decades, to purify it and distinguish it from other anterior pituitary hormones. With relatively pure growth hormone (GH), its biological activity in growth promotion and as a metabolic hormone were studied, and species specificity became apparent: primate GH was the only GH active in man. Human GH was prepared from cadaveric pituitaries and distributed by the NIH to treat children with GH deficiency, but there was never enough pituitary hGH for all of the children who required it. When Creutzfeldt-Jakob disease was found in some patients who received pituitary GH, the production and FDA approval of biosynthetic hGH dramatically accelerated. With a large supply, one could treat those who were GH deficient and test its efficacy in other causes of short stature; longer acting versions of hGH have now been developed, tested, and in a few instances received FDA approval. Summary: It has been a long journey from the description of over- and underproduction of GH in animals to the production and clinical use of the biosynthetic hormones. Key Messages: The efforts of basic scientists led to the extraction and purification of GH. Clinical scientists have expanded the appropriate use of hGH for short children with conditions in addition to GH deficiency.

The Pediatric Endocrine Society (PES) was initially established in 1972 as the Lawson Wilkins Pediatric Endocrine Society (LWPES), by some of Wilkins’ former fellows. As the society grew from its 37 founding members and Dr. Wilkins’ influence faded, the name of the society was changed in 2010 and now counts about 1,500 members, mostly from the US and Canada. Pediatric endocrine training programs headed by (LW)PES members have welcomed fellows from throughout the world, many of whom have gone on to leadership positions in their home countries. Starting in 1981, the (LW)PES has collaborated with pediatric endocrine societies around the world in quadrennial meetings, fostering collaborations, transfer of ideas, devising joint practice guidelines, and enjoying one another’s fellowship and counsel. The PES presently has committees and special interest groups concerned with all aspects of pediatric endocrinology, assuring that our clinical and academic resources reflect both breadth and depth. To celebrate our 50th anniversary, selected members have written the historical manuscripts featured in this special issue of Hormone Research in Pediatrics. These historical reviews delve into the origins of our specialty, sometimes deep into antiquity, provide useful background information, and illustrate the kinds of intellectual struggles that have led to the development of contemporary pediatric endocrinology, worldwide.

The 3rd International Workshop on Klinefelter Syndrome, Trisomy X, and 47,XYY syndrome was held in Leiden, the Netherlands, on September 12–14, 2022. Here, we review new data presented at the workshop and discuss scientific and clinical trajectories. We focus on shortcomings in knowledge and therefore point out future areas for research. We focus on the genetics and genomics of supernumerary sex chromosome syndromes with new data being presented. Most knowledge centre specifically on Klinefelter syndrome, where aspects on testosterone deficiency and the relation to bone, muscle and fat were discussed, as was infertility and the treatment thereof. Both trisomy X and 47,XYY syndrome are frequently affected by infertility. Transitioning of males with Klinefelter syndrome was addressed, as this seemingly simple process in practise is often difficult. It is now realized that neurocognitive changes are pervasive in all supernumerary sex chromosome syndromes, which were extensively discussed. New intervention projects were also described, and exciting new data concerning these were presented. Advocacy organizations were present, describing the enormous burden carried by parents when having to explain their child’s specific syndrome to most professionals whenever in contact with health care and education systems. It was also pointed out that most countries do not have health care systems that diagnose patients with supernumerary sex chromosome syndromes, thus pinpointing a clear deficiency in the current genetic testing and care models. At the end of the workshop, a roadmap towards the development of new international clinical care guidelines for Klinefelter syndrome was decided.

Malnutrition may be classified as acute or chronic and by severity into mild, moderate, and severe forms. Features of chronic malnutrition include diminished weight gain, stunted growth, mental apa...

Objectives Some idiopathic short stature (ISS) patients may have varying degrees of insulin-like growth factor 1 (IGFI) deficiency. Others with growth hormone deficiency (GHD) (peak GH Methods We studied the effect of GH therapy (0.035–0.06 mg/kg/day) on linear growth and weight gain per day (WGPD) in children with ISS (n=13) and those with GHD (n=10) who have low pretreatment IGFISDS (IGF SDS Results At presentation, the height standard deviation score (HtSDS) of children with ISS who had low pretreatment IGFISDS was significantly lower compared to the normal IGFI group. The age, body mass index (BMI), BMISDS, peak GH response to clonidine provocation and bone age did not differ between the two study groups. After 1 year of treatment with rhGH (0.035–0.06 mg/kg/day) IGFISDS increased significantly in both groups (p Conclusions IGFI deficiency represents a low anabolic state. Correction of IGFI level (through rhGH and/or improved nutrition) in short children (ISS and GHD) was associated with increased linear growth and WGPD denoting significant effect on bone growth and muscle protein accretion.

The growth hormone (GH)–insulin-like growth factor (IGF) cascade is central to the regulation of growth and metabolism. This article focuses on the history of the components of the IGF system, with an emphasis on the peptide hormones, IGF-I and -II, their cell surface receptors, and the IGF binding proteins (IGFBPs) and IGFBP proteases that regulate the availability of the peptide hormones for interaction with their receptors in relevant target tissues. We describe landmark events in the evolution of the somatomedin hypothesis, including evidence that has become available from experiments at the molecular and cellular levels, whole animal and tissue-specific gene knockouts, studies of cancer epidemiology, identification of prismatic human cases, and short- and long-term clinical trials of IGF-I therapy in humans. In addition, this new evidence has expanded our clinical definition of GH insensitivity (GHI) beyond growth hormone receptor mutations (classic Laron syndrome) to include conditions that cause primary IGF deficiency by impacting post-receptor signal transduction, IGF production, IGF availability to interact with the IGF-I receptor (IGF-1R), and defects in the IGF-1R, itself. We also discuss the clinical aspects of IGFs, from their description as insulin-like activity, to the use of IGF-I in the diagnosis and treatment of GH deficiency, and to the use of recombinant human IGF-I for therapy of children with GHI.

Sex chromosome aneuploidies (SCA) are relatively common as a group, perhaps 1 per 500 births, but much more common at conception. Many syndromes have been noted in those with these conditions, but not so many data are available concerning the hypothalamic-pituitary-gonadal (HPG) axis. The physiology of the HPG axis is first reviewed at four epochs in time: fetal, birth and mini-puberty, childhood, and adolescence (puberty). Those sections are followed by detailed analysis of the functioning of the HPG axis in individuals with specific SCA with chromosomal numbers ranging from 45 to 49. Robust data are available for the chromosomal complements 47,XXY and 47,XXX with fewer data available for many of the others.

Insulin is the key anabolic hormone of metabolism, with clear effects on glycaemia. Near-complete insulin deficiency occurs in type 1 diabetes (T1D), the predominant form affecting children, and uniformly fatal until the discovery of insulin. By the early 20th century, it was known that T1D was caused by the lack of a factor from pancreatic islets, but isolation of this substance proved elusive. In 1921, an unusual team in Toronto comprising a surgeon, a medical student, a physiologist and a biochemist successfully isolated a glucose-lowering pancreatic endocrine secretion. They treated an emaciated 14-year-old boy in 1922, restoring his health and allowing him to live for another 13 years. Thus began an era of remarkable progress and partnership between academia and the pharmaceutical industry to produce drugs that benefit sick people. The Toronto team received the 1923 Nobel Prize, and more Nobel Prizes for work with insulin followed: for elucidation of its amino acid sequence and crystalline structure, and for its role in the development of radioimmunoassays to measure circulating hormone concentrations. Human insulin was the first hormone synthesised by recombinant methods, permitting modifications to enable improved absorption rates and alterations in duration of action. Coupled with delivery via insulin pens, programmable pumps and continuous glucose monitors, metabolic control and quality of life vastly improved and T1D in children was converted from uniformly fatal to a manageable chronic condition. We describe this remarkable ongoing story as insulin remains a paradigm for human ingenuity to heal nature’s maladies.

Context Serum insulin-like growth factor 1 (IGF-1) levels are relatively constant in somatropin-treated children with growth hormone deficiency (GHD), and guide dose adjustments for clinical efficacy and long-term safety. IGF-1 levels following treatment with long-acting growth hormones such as lonapegsomatropin (lonapegsomatropin-tcgd, TransCon hGH), a once-weekly somatropin prodrug, exhibit a characteristic profile over the dosing interval. Objective This study aimed to develop a method to predict average IGF-1 in lonapegsomatropin-treated GHD children to interpret IGF-1 data based on a single sample obtained any time at steady state. Methods A population nonlinear mixed-effect pharmacodynamic model for IGF-1 was developed based on 2 randomized, open-label trials of TransCon hGh in GHD children and used to develop a linear mixed model with Taylor series to fit simulated IGF-1 profiles of lonapegsomatropin-treated children. A total of 49 896 IGF-1 sample data simulated from 105 lonapegsomatropin-treated GHD children were utilized for the final prediction model. The dosage range of TransCon hGh was 0.14 to 0.30 hGH mg/kg/week, and weekly average IGF-1 was calculated using IGF-1 profiles simulated from the nonlinear pharmacodynamic model. Predicted average IGF-1 was obtained by linear mixed model with Taylor series. Results The nonlinear mixed-effect model provided satisfactory model fit. The linear mixed model with Taylor series fit simulated IGF-1 data well, with a relatively straightforward prediction formula. IGF-1 values sampled at ~4.5 days post-dose coincided with weekly average IGF-1 at steady state. Conclusion A formula to predict average IGF-1 from a single sample of IGF-1 at steady state was established to aid clinicians in interpreting IGF-1 levels in GHD children administered lonapegsomatropin.

Context We characterized linear growth in infants and children with X-linked hypophosphatemia (XLH). Objective Provide linear growth curves for children with XLH from birth to early adolescence. Design Data from 4 prior studies of XLH were pooled to construct growth curves. UX023-CL002 was an observational, retrospective chart review. Pretreatment data were collected from 3 interventional trials: two phase 2 trials (UX023-CL201, UX023-CL205) and a phase 3 trial (UX023-CL301). Setting Medical centers with expertise in treating XLH. Patients Children with XLH, 1-14 years of age. Intervention None. Main Outcome Measure Height-for-age linear growth curves, including values for the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles for children with XLH compared to population norms. Results A total of 228 patients (132 girls, 96 boys) with 2381 height measurements were included. Nearly all subjects (> 99%) reported prior management with supplementation therapy. Compared to the Center for Disease Control and Prevention growth curves, boys at age 3 months, 6 months, 9 months, 1 year, and 2 years had median height percentiles of 46%, 37%, 26%, 18%, and 5%, respectively; for girls the median height percentiles were 52%, 37%, 25%, 18%, and 7%, respectively. Annual growth in children with XLH fell below that of healthy children near 1 year of age and progressively declined during early childhood, with all median height percentiles < 8% between 2 and 12 years old. Conclusion Children with XLH show decreased height gain by 1 year of age and remain below population norms thereafter. These data will help evaluate therapeutic interventions on linear growth for pediatric XLH.

“Doping” is as old as the ancient Olympics (776 BC to 394 AD) when athletes used herbal medications, animal organs (organotherapy was common to cure diseases and to improve vitality), stimulants, and hallucinogenic mushrooms to improve athletic performance. We discuss the issues of proper medical use of prohibited drugs (therapeutic use exemption) and the concept of the athlete’s biological passport to highlight disordered physiology rather than necessarily the chemical iasdentification of a banned substance. The growth hormone/IGF-1 system is used as an example of both the detection of the drugs and the consequences upon multiple analytes with the ongoing validation of a peptides module, just as hematologic and steroid modules have been used.

Pubertal maturation is a time of dramatic physical, reproductive, and psychological changes, including the development of secondary sex characteristics and changes in body composition. It requires a complex series of hormonal changes initiated by alterations in hypothalamic regulatory mechanisms that are incompletely understood, culminating in gonadal sex steroid secretion and associated maturation. While genetics play a major role in the timing and progression of pubertal maturation, other inputs such as nutrition, environmental factors, and social milieu yield individualized variations in the maturational pattern. It is likely that these factors are in part responsible for changes in timing and tempo of pubertal maturation noted over the last few decades. When a child begins to mature at the earliest or latest extremes of the normal ranges, the clinician must determine if the child is undergoing normal puberty, a non-pathologic variation, or a medically concerning condition that requires further investigation or treatment.

Delayed puberty occurs when no signs of pubertal maturation are seen by 14 years of age in boys or 13 years in girls. Although constitutional delay of growth and puberty is commonly seen and is often regarded as benign, there are many other causes of pubertal delay that ultimately result in permanent hypogonadism, and these must be differentiated from self-limited delays in maturation. Causes of hypogonadism include disorders affecting the gonads (primary hypogonadism) and abnormalities of pituitary or hypothalamic function (hypogonadotropic hypogonadism). Hypogonadotropic hypogonadism may be part of a more global set of pituitary deficiencies or may be the only endocrine axis affected. A rapidly growing array of genetic disorders accounts for isolated hypogonadotropic hypogonadism. Treatment of delayed puberty often consists of short-term administration of sex steroids to those with constitutional delay, while individuals with permanent hypogonadism require long-term testosterone or oestradiol replacement.

Context Growth hormone (GH) treatment has a generally good safety profile; however, concerns about increased mortality risk in adulthood have been raised. Objective This work aims to assess the long-term safety of GH treatment in clinical practice. Methods Data were collected from 676 clinics participating in 2 multicenter longitudinal observational studies: the NordiNet International Outcome Study (2006-2016, Europe) and ANSWER Program (2002-2016, USA). Pediatric patients treated with GH were classified into 3 risk groups based on diagnosis. Intervention consisted of daily GH treatment, and main outcome measures included incidence rates (events/1000 patient-years) of adverse drug reactions (ADRs), serious adverse events (SAEs), and serious ADRs, and their relationship to GH dose. Results The combined studies comprised 37 702 patients (68.4% in low-risk, 27.5% in intermediate-risk, and 4.1% in high-risk groups) and 130 476 patient-years of exposure. The low-risk group included children born small for gestational age (SGA; 20.7%) and non-SGA children (eg, with GH deficiency; 79.3%). Average GH dose up to the first adverse event (AE) decreased with increasing risk category. Patients without AEs received higher average GH doses than patients with more than one AE across all groups. A significant inverse relationship with GH dose was shown for ADR and SAE incidence rates in the low-risk group (P = .003 and P = .001, respectively) and the non-SGA subgroup (both P = .002), and for SAEs in the intermediate- and high-risk groups (P = .002 and P = .05, respectively). Conclusions We observed no indication of increased mortality risk nor AE incidence related to GH dose in any risk group. A short visual summary of our work is available (1).

Context There is no consensus on the effect of recombinant human GH (rhGH) therapy on skeletal maturation in children despite the current practice of annual monitoring of skeletal maturation with bone age in children on rhGH therapy. Aims To investigate the effects of long-term rhGH therapy on skeletal age in children and explore the accuracy of bone age-predicted adult height (BAPAH) at different ages based on 13 years of longitudinal data. Methods A retrospective longitudinal study of 71 subjects aged 2 to 16 years, mean 9.9 ± 3.8 years, treated with rhGH for nonsyndromic short stature for a duration of 2 to 14 years, mean, 5.5 ± 2.6 years. Subjects with syndromic short stature and systemic illnesses such as renal failure were excluded. Results Bone age minus chronological age (BA-CA) did not differ significantly between baseline and the end of rhGH therapy (-1.05 ± 1.42 vs -0.69 ± 1.63, P = 0.09). Piecewise regression, however, showed a quantifiable catch-up phenomenon in BA of 1.5 months per year of rhGH therapy in the first 6.5 years (P = 0.017) that plateaued thereafter (P = 0.88). BAPAH overestimated near-adult height in younger subjects but became more accurate in older subjects (P Conclusion Long-term rhGH therapy demonstrated an initial catch-up phenomenon in skeletal maturation in the first 6.5 years that plateaued thereafter with no overall significant advancement in bone age. These findings are reassuring and support strategic, but not the insurance company mandated reflexive annual monitoring of skeletal maturation with bone age in children receiving rhGH therapy.

Testosterone replacement therapy (TRT) is routinely prescribed in adolescent males with constitutional delay of growth and puberty (CDGP) or hypogonadism. With many new testosterone (T) formulations entering the market targeted for adults, we review current evidence and TRT options for adolescents and identify areas of unmet needs. We searched PubMed for articles (in English) on testosterone therapy, androgens, adolescence, and puberty in humans. The results indicate that short-term use of T enanthate (TE) or oral T undecanoate is safe and effective in inducing puberty and increasing growth in males with CDGP. Reassuring evidence is emerging on the use of transdermal T to induce and maintain puberty. The long-term safety and efficacy of TRT for puberty completion and maintenance have not been established. Current TRT regimens are based on consensus and expert opinion, but evidence-based guidelines are lacking. Limited guidance exists on when and how T should be administered and optimal strategies for monitoring therapy once it is initiated. Only TE and T pellets are US Food and Drug Administration approved for use in adolescent males in the United States. Despite the introduction of a wide variety of new T formulations, they are designed for adults, and their metered doses are difficult to titrate in adolescents. In conclusion, TRT in adolescent males is hindered by lack of long-term safety and efficacy data and limited options approved for use in this population. Additional research is needed to identify the route, dose, duration, and optimal timing for TRT in adolescents requiring androgen therapy.

Context Application of ultrasound (US) to evaluate attainment and morphology of glandular tissue provides a new rationale for evaluating onset and progression of female puberty, but currently no hormone references complement this method. Furthermore, previous studies have not explored the predictive value of endocrine profiling to determine female puberty onset. Objective To integrate US breast staging with hypothalamic-pituitary-gonadal hormone references and test the predictive value of an endocrine profile to determine thelarche. Design Setting and Participants Cross-sectional sample of 601 healthy Norwegian girls, ages 6 to 16 years. Main Outcome Measures Clinical and ultrasound breast evaluations were performed for all included girls. Blood samples were analyzed by immunoassay and ultrasensitive liquid chromatography–tandem mass spectrometry (LC-MS/MS) to quantify estradiol (E2) and estrone (E1) from the subpicomolar range. Results References for E2, E1, luteinizing hormone, follicle-stimulating hormone, and sex hormone–binding globulin were constructed in relation to chronological age, Tanner stages, and US breast stages. An endocrine profile index score derived from principal component analysis of these analytes was a better marker of puberty onset than age or any individual hormone, with receiver-operating characteristic area under the curve 0.91 (P

Growth is the task of children. We review the normal process of linear growth from the fetus through adolescence and note that growth is the result of age- and gender-dependent interactions among key genetic, environmental, dietary, socioeconomic, developmental, behavioral, nutritional, metabolic, biochemical, and hormonal factors. We then define the wide range of normative data at each stage of growth and note that a pattern within this range is generally indicative of good general health and that growth significantly slower than this range may lead to growth faltering and subsequent short stature. Although not often emphasized, we detail how to properly measure infants and children because height velocity is usually determined from two height measurements (both relatively large values) to calculate the actual height velocity (a relatively much smaller number in comparison). Traditionally the physiology of growth has been taught from an endocrine-centric point-of-view. Here we review the hypothalamic-pituitary-end organ axes for the GH/IGF-1 and gonadal steroid hormones (hypothalamic-pituitary-gonadal axis), both during "mini"-puberty as well as at puberty. However, over the past few decades much more emphasis has been placed on the growth plate and its many interactions with the endocrine system but also with its own intrinsic physiology and gene mutations. These latter, whether individually (large effect size) or in combination with many others including endocrine system-based, may account in toto for meaningful differences in adult height. The clinical assessment of children with short stature includes medical, social and family history, physical exam and importantly proper interpretation of the growth curve. This analysis should lead to judicious use of screening laboratory and imaging tests depending on the pre-test probability (Bayesian inference) of a particular diagnosis in that child. In particular for those with no pathological features in the history and physical exam and a low, but normal height velocity, may lead only to a bone age exam and reevaluation (re-measurement), perhaps 6 months later. he next step depends on the comfort level of the primary care physician, the patient, and the parent; that is, whether to continue with the evaluation with more directed, more sophisticated testing, again based on Bayesian inference or to seek consultation with a subspecialist pediatrician based on the data obtained. This is not necessarily an endocrinologist. The newest area and the one most in flux is the role for genetic testing, given that growth is a complex process with large effect size for single genes but smaller effect sizes for multiple other genes which in the aggregate may be relevant to attained adult height. Genetics is a discipline that is rapidly changing, especially as the cost of exome or whole gene sequencing diminishes sharply. Within a decade it is quite likely that a genetic approach to the evaluation of children with short stature will become the standard, truncating the diagnostic odyssey and be cost effective as fewer biochemical and imaging studies are required to make a proper diagnosis.

Emotional deprivation can lead to growth faltering of infants and children. The mechanism(s) involved differ in that for infants, the major metabolic problem is inadequate energy intake for growth. In young children, it is likely that the emotional deprivation causes a syndrome not only of growth faltering, but with bizarre behaviors, especially with regard to food: hoarding, gorging and vomiting, hyperphagia, drinking from the toilet, and eating from garbage pails. Other disturbed behaviors include, poor sleep, night wanderings, and pain agnosia. The pathophysiology appears to be reversible hypopituitarism, at least for the growth hormone and hypothalamic-pituitary- adrenal axes. The review begins with an historical perspective concerning stress, children and growth and then moves to the issue of hospitalism, where young infants failed to thrive (and died) due to inadequate stimulation and energy intake. Refeeding programs at the end of World Wars I and II noted that some children did not thrive despite an adequate energy intake. It appeared that in addition taking care of their emotional needs permitted super-physiologic (catch-up) growth. Next came the first notions from clinical investigation that hypopituitarism might be the mechanism of growth faltering. Studies that address this mechanism from a number of observational and clinical research studies are reviewed in depth to show that the hypopituitarism was relieved upon removal from the deprivational environment and occurred much too quickly to be due to adequate energy alone. These findings are then compared to those from malnourished children and adoptees from emerging countries, especially those from orphanages where their psychosocial needs were unmet despite adequate caloric intake. Together, these various conditions define one aspect of the field of psychoneuroendocrinology.

We provide an in-depth review of the role of androgens in male maturation and development, from the fetal stage through adolescence into emerging adulthood, and discuss the treatment of disorders of androgen production throughout these time periods. Testosterone, the primary androgen produced by males, has both anabolic and androgenic effects. Androgen exposure induces virilization and anabolic body composition changes during fetal development, influences growth and virilization during infancy, and stimulates development of secondary sexual characteristics, growth acceleration, bone mass accrual, and alterations of body composition during puberty. Disorders of androgen production may be subdivided into hypo- or hypergonadotropic hypogonadism. Hypogonadotropic hypogonadism may be either congenital or acquired (resulting from cranial radiation, trauma, or less common causes). Hypergonadotropic hypogonadism occurs in males with Klinefelter syndrome and may occur in response to pelvic radiation, certain chemotherapeutic agents, and less common causes. These disorders all require testosterone replacement therapy during pubertal maturation and many require lifelong replacement. Androgen (or gonadotropin) therapy is clearly beneficial in those with persistent hypogonadism and self-limited delayed puberty and is now widely used in transgender male adolescents. With more widespread use and newer formulations approved for adults, data from long-term randomized placebo-controlled trials are needed to enable pediatricians to identify the optimal age of initiation, route of administration, and dosing frequency to address the unique needs of their patients.

Завантажено з https://academic.oup.cOm/jcem/article-abstract/92/3/804/25968918 ЧЕРВНЯ 2018.НАДРУКОВАНО В СШАTHE JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 92(3):804 – 810PRINTED IN U.S.A.COPYRIGHT © 2007 BY THE ENDOCRINE SOCIETY DOI: 10.1210/JC.2006-2017Мета: Низька маса тіла залишається основною причиною захворюваності та смертності в ранньому віці та дитинстві. Це пов’язано з підвищеним ризиком виникнення проблем зі здоров’ям пізніше в житті, зокрема ішемічної хвороби серця та інсульту. Булa скликана нарада з метою виявлення основних проблем охорони здоров’я, що стоять перед дитиною, народженою з малою відносно гестаційного віку (МГВ) - small for gestational age (SGA), і як результат запропонувати стратегії ведення таких дітей.Учасники: були обрані 42 учасники на основі їх попередніх досліджень та обстежень в акушерстві, перинатальній та неонатальній медицині, педіатрії, педіатричній та дорослій ендокринології, епідеміології та фармакології.Докази: відбувся обмін письмовими матеріалами, вони були переглянуті, оцінені, а потім відкриті для всіх учасників. Це сформувало дискусійну базу засідання. Якщо опубліковані дані виявлялись недоступними або неадекватними, дискусія грунтувалася в такому разі на думках клінічних експертів.Процес консенсусу: кожна група питань була розглянута усіма учасниками, а потім обговорена на пленарних засіданнях за допомогою консенсусу та визначення невирішених питань. Консенсусну заяву було підготовлено на пленарному засіданні сесії, з подальшим редагуванням групами фахівців, після чого вона стала доступною для ознайомлення всім учасникам засідання.Висновки: Діагноз МГВ повинен грунтуватися на точній антропометрії при народженні, включаючи масу, довжину та об’єм голови. Ми рекомендуємо ранній нагляд у клініці росту для тих, хто не досягає необхідних параметрів. Оцінка раннього нейророзвитку та втручання у дітей ризикового віку. Ендокринні та метаболічні порушення у дитині МГВ визнаються, але рідко. Для 10%, хто не надолужує показників, лікування МГВ може збільшити лінійний ріст. Раннє втручання з GH для тих, хто має серйозну затримку в зростанні (висота за SD шкалою

Background/Aims: A meta-analysis was performed to determine the likelihood of hypothalamic-pituitary-adrenal (HPA) axis suppression following short-term cutaneous treatment of atopic dermatitis with topical corticosteroids (TCS) in pediatric patients. Methods: All published pediatric clinical trials evaluating TCS use with pre- and post-treatment HPA axis assessment by cosyntropin stimulation testing were included. Results: Of 128 eligible trials, 12 were selected for meta-analysis with a total of 522 participants. There were 20 observed cases of HPA axis suppression (3.8%, 95% CI 2.4–5.8). The percentage of HPA axis suppression with low- (classes 6–7), medium- (classes 3–5) and high-potency (classes 1–2) TCS use was 2% (3 of 148 patients, 95% CI 0.7–5.8), 3.1% (7 of 223 patients, 95% CI 1.5–6.3), and 6.6% (10 of 151 patients, 95% CI 3.6–11.8), respectively. Conclusion: There is a low rate of reversible HPA axis suppression with the use of mid- to low-potency TCS compared to more potent formulations. In pediatric clinical practice, the limited use of mid- to low-potency TCS is rarely associated with clinically significant adrenal insufficiency or adrenal crisis. In the absence of signs and symptoms of adrenal insufficiency, there is little need to test the HPA axis of these patients.

This report illustrates the links between history, sport, endocrinology, and genetics to show the ways in which historical context is key to understanding the current conversations and controversies about who may compete in the female category in elite sport. The International Association of Athletics Federations (IAAF) introduced hyperandrogenemia regulations for women’s competitions in 2011, followed by the International Olympic Committee (IOC) for the 2012 Olympics. The policies concern female athletes who naturally produce higher-than-average levels of testosterone and want to compete in the women’s category. Hyperandrogenemia guidelines are the current effort in a long series of attempts to determine women’s eligibility scientifically. Scientific endeavors to control who may participate as a woman illustrate the impossibility of neatly classifying competitors by sex and discriminate against women with differences of sex development (also called intersex by some).

Growth within the broad range of normal for age, sex and ethnicity is considered a good sign of general health and of proper living conditions. Starvation, emotional deprivation and chronic, particularly endocrine and inflammatory, diseases, impair growth; persistence of such conditions leads to stunting—long-term preventing from growing, resulting in short stature—and will raise the susceptibility to further illness and mortality. Detailed scientific observations exemplifying the close link between nutrition, living conditions, health and growth date back to the medical literature of the end 19th and early 20th centuries. Multiple observations of school physicians and paediatricians specify the impact of starvation and neglect on child growth during and after World War I,1 and recognise the significance of catch-up growth during refeeding. Catch-up growth is not limited to refeeding but systematically occurs in children whenever relieved from growth-inhibiting conditions. In 1906, Igl2 published growth patterns of Austrian boarding school children aged 7–17 years, who almost completely failed to grow during the regular school year but caught up in height during the 2 months of summer holiday at home. Mortality statistics in European orphanages since the 18th century highlight the importance of emotional care on infant survival. Scientific observations on emotional deprivation and its effect on infant and child growth became prevalent in the 20th century. Shortly after World War II, Widdowson3 investigated children in two German orphanages. Her concern with the growth of the children led her to a feeding experiment in one—to supplement the barely adequate caloric intake with additional bread and jam. This was based on …

Inter-individual differences in size, maturity status, function, and behavior among youth of the same chronological age (CA) have long been a concern in grouping for sport. Bio-banding is a recent attempt to accommodate maturity-associated variation among youth in sport. The historical basis of the concept of maturity-matching and its relevance to youth sport, and bio-banding as currently applied are reviewed. Maturity matching in sport has often been noted but has not been systematically applied. Bio-banding is a recent iteration of maturity matching for grouping youth athletes into 'bands' or groups based on characteristic(s) other than CA. The percentage of predicted young adult height at the time of observation is the estimate of maturity status of choice. Several applications of bio-banding in youth soccer have indicated positive responses from players and coaches. Bio-banding reduces, but does not eliminate, maturity-associated variation. The potential utility of bio-banding for appropriate training loads, injury prevention, and fitness assessment merits closer attention, specifically during the interval of pubertal growth. The currently used height prediction equation requires further evaluation.

Background: In adolescents, testosterone may have several effects including promotion of secondary sexual characteristics and pubertal growth, attainment of optimal muscle mass and peak bone mass, optimization of the metabolic profile, and psychosocial maturation and well-being. Summary: Testosterone therapy is a cornerstone of the management of hypogonadism in boys. Since the initial report of the chemical synthesis of testosterone, several formulations have continued to develop, and although many of these have been used in boys, none of them have been studied in detail in this age group. Given the wide ranging effects of testosterone, the level of evidence for their effects in boys and the heterogeneity of conditions that lead to early-onset hypogonadism, a standardized protocol for monitoring testosterone replacement in this age group is needed. Key Messages: In this review, we focus on the perceived benefits of androgen replacement in boys affected by pubertal delay and highlight the need to improve the health monitoring of boys who receive androgen replacement therapy, proposing different approaches based on the underlying pathophysiology.

The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international experts participated at the invitation of GRS including clinicians, basic scientists, and representatives from regulatory agencies and the pharmaceutical industry. Following plenary presentations addressing the current diagnosis and therapy of short stature in children, breakout groups discussed questions produced in advance by the planning committee and reconvened to share the group reports. A writing team assembled one document that was subsequently discussed and revised by participants. Participants from regulatory agencies and pharmaceutical companies were not part of the writing process. Short stature is the most common reason for referral to the pediatric endocrinologist. History, physical examination, and auxology remain the most important methods for understanding the reasons for the short stature. While some long-standing topics of controversy continue to generate debate, including in whom, and how, to perform and interpret growth hormone stimulation tests, new research areas are changing the clinical landscape, such as the genetics of short stature, selection of patients for genetic testing, and interpretation of genetic tests in the clinical setting. What dose of growth hormone to start, how to adjust the dose, and how to identify and manage a suboptimal response are still topics to debate. Additional areas that are expected to transform the growth field include the development of long-acting growth hormone preparations and other new therapeutics and diagnostics that may increase adult height or aid in the diagnosis of growth hormone deficiency. info:eu-repo/semantics/publishedVersion

Our objective was to assess the risk of adrenal insufficiency (AI) with short-term use of low- to moderate-potency topical corticosteroids (TCS) for treatment of atopic dermatitis. Our systematic literature search revealed 9 studies (n = 371) that evaluated AI using adrenocorticotropic hormone stimulation testing, with measures of serum cortisol levels at baseline and following at least 2 weeks of TCS application. Biochemical AI was defined by a stimulated cortisol level of ≤18.0 µg/dL (~500 nmol/L). The overall proportion of AI with low-to-moderate TCS use was 2.7% (95% confidence interval = 1.47% to 4.89%). None of the children showed any clinical evidence of AI or adrenal crisis. Short-term use of low- to moderate-potency TCS for the treatment of atopic dermatitis is associated with a low risk of adrenal suppression. General practitioners do not need to test these patients for adrenal suppression in the absence of concerning signs and symptoms of AI.