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Competing Interests: Disclosure The author has no conflicts of interest to disclose.

Competing Interests: Disclosure The author has no conflicts of interest to disclose.

Introduction: We present the evolution of GHD in adolescent males with persistent growth failure, in whom the diagnosis was established after a second GH stimulation test (GST)., Methods: We performed a retrospective chart review of children who presented for short stature (height less < 2SD for mean/mid-parental height) and/or growth failure (sustained growth velocity < 0 SD) to pediatric endocrinology at Mount Sinai Kravis Children's Hospital, New York and who had 2 GSTs. Data collected from electronic medical records were analyzed using SPSS v28.0., Results: Of 53 patients included, 42 were males. Average GH peak on initial GST was 15.48 ± 4.92 ng/ml, at 10.07 ± 2.65 years, mean height -1.68 ± 0.56SD(28% had <2SD), IGF-1 -1.00 ± 0.88SD. After 2.23 ± 1.22 years, at 12.04 ± 2.41years, height SDs decreased to -1.82 ± 0.63SD and IGF-1 was -1.08 ± 0.84SD. At repeat GST, average GH peak was 7.59 ± 2.12 ng/dL, with 36% ≤7 ng/dl and 32% in puberty. 12 males reached adult height of 0.08 ± 0.69 SD with a mean height gain of 1.83 ± 0.56SD(p<0.005), IGF-1 of -1.15 ± 0.81SD after 4.64 ± 1.4 years of GH., Conclusion: We offer evidence for Evolving Growth Hormone Deficiency (EGHD) through repeat GST in children with persistent growth slowdown, even with pubertal progression; emphasizing the need for careful longitudinal follow-up to make accurate diagnosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chimatapu, Sethuram, Samuels, Klomhaus, Mintz, Savage and Rapaport.)

Introduction: Growth hormone (GH) and the immune system have multiple bidirectional interactions. Data about the acute effects of GH on the immune system are lacking. The objective of our study was to evaluate the acute effects of GH on the immune system using time-of-flight mass cytometry., Methods: This was a prospective study of pediatric patients who were being evaluated for short stature and underwent a GH stimulation test at a tertiary care center. Blood samples for immunologic markers, i.e., complete blood count (CBC) and time of flight mass cytometry (CyTOF), were collected at baseline (T0) and over the course of three hours (T3) of the test. Differences in immune profiling in patients by timepoint (T0, T3) and GH response (growth hormone sufficient (GHS) versus growth hormone deficient (GHD)) were calculated using a two-way ANOVA test.  Results: A total of 54 patients (39 boys and 15 girls) aged five to 18 years were recruited. Twenty-two participants tested GHD (peak GH <10 ng/ml). The CyTOF analysis showed a significant increase from T0 to T3 in granulocyte percentage, monocyte count, and dendritic cell (DC) count; in contrast, a significant decrease was seen in T lymphocytes (helper and cytotoxic) and IgD+ B lymphocytes. The CBC analysis supported these findings: an increase in total white blood cell count, absolute neutrophil count, and neutrophil percentage; a decrease in absolute lymphocyte count, lymphocyte percentage, absolute eosinophil count, and absolute monocyte count. No significant differences were found between CBC/CyTOF measurements and GH status at either time., Conclusions: This study provides the first high-resolution map of acute changes in the immune system with GH stimulation. This implies a key role for GH in immunomodulatory function., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Gujral et al.)

Type 1 diabetes (T1D) management has evolved over the last decade. Innovations and groundbreaking research have paved the way for improved outcomes for people with T1D. One of the major T1D focused research network that has supported real-world research studies in the United States is the T1D Exchange Quality Improvement Collaborative (T1DX-QI) Network.T1DX-QI is a large multicenter network of 55 T1D clinics that uses quality improvement, health equity framework, and population health principles to improve outcomes for people with T1D. This article summarizes insights from T1DX-QI clinical and population health improvement studies., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Phelan-McDermid syndrome (PMS) is a genetic condition caused by SHANK3 haploinsufficiency and characterized by a wide range of neurodevelopmental and systemic manifestations. The first practice parameters for assessment and monitoring in individuals with PMS were published in 2014; recently, knowledge about PMS has grown significantly based on data from longitudinal phenotyping studies and large-scale genotype-phenotype investigations. The objective of these updated clinical management guidelines was to: (1) reflect the latest in knowledge in PMS and (2) provide guidance for clinicians, researchers, and the general community. A taskforce was established with clinical experts in PMS and representatives from the parent community. Experts joined subgroups based on their areas of specialty, including genetics, neurology, neurodevelopment, gastroenterology, primary care, physiatry, nephrology, endocrinology, cardiology, gynecology, and dentistry. Taskforce members convened regularly between 2021 and 2022 and produced specialty-specific guidelines based on iterative feedback and discussion. Taskforce leaders then established consensus within their respective specialty group and harmonized the guidelines. The knowledge gained over the past decade allows for improved guidelines to assess and monitor individuals with PMS. Since there is limited evidence specific to PMS, intervention mostly follows general guidelines for treating individuals with developmental disorders. Significant evidence has been amassed to guide the management of comorbid neuropsychiatric conditions in PMS, albeit mainly from caregiver report and the experience of clinical experts. These updated consensus guidelines on the management of PMS represent an advance for the field and will improve care in the community. Several areas for future research are also highlighted and will contribute to subsequent updates with more refined and specific recommendations as new knowledge accumulates., (© 2023 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Background: We used real-world electronic health record (EHR) data to examine HbA1c levels among children and adults with type 1 diabetes (T1D) who are classified as continuous glucose monitor (CGM) users after T1D diagnosis and switch to self-monitoring of blood glucose (SMBG) during follow-up, versus people who opt for SMBG after T1D diagnosis and switch to CGM during follow-up visits., Methods: We conducted an observational, case-crossover study using electronic medical record (EMR) data from the T1D Exchange Quality Improvement Collaborative. The primary outcome in this study was HbA1c. Baseline HbA1c levels were taken at the index date, corresponding to initial device classification, and compared with HbA1c value recorded at the clinic visit following device switch., Results: Of all patients classified in the SMBG group, 7,706 switched to CGM use within the 5-year study time frame, and 5,123 of all initial CGM users switched to SMBG within the study time frame and were included in this analysis. At baseline, median (interquartile range [IQR]) HbA1c for SMBG use was 8.1 (2.4), whereas postcrossover to CGM use, there was a decline in median (IQR) levels to 7.7 (1.9) ( P < .001). For baseline CGM users, median (IQR) HbA1c levels were 7.9 (2.0), and postcrossover to SMBG, median (IQR) HbA1c levels increased to 8.0 (2.9) ( P < .001)., Conclusion: We found that people who switched to CGM use had significantly improved HbA1c levels compared to those who switched to glucose monitoring with SMBG., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: NN is PI on Dexcom and Vertex funded research projects through her organization T1D Exchange. GN is employed at Dexcom. OE is PI on Dexcom, MannKind, Medtronic, Vertex, Abbott funded research projects through his organization T1D Exchange. OE is an advisor for Medtronic Diabetes and Vertex Pharmaceuticals.

This International Consensus Guideline was developed by experts in the field of small for gestational age (SGA) of 10 pediatric endocrine societies worldwide. A consensus meeting was held and 1300 articles formed the basis for discussions. All experts voted about the strengths of the recommendations. The guideline gives new and clinically relevant insights into the etiology of short stature after SGA birth, including novel knowledge about (epi)genetic causes. Further, it presents long-term consequences of SGA birth and also reviews new treatment options, including treatment with gonadotropin-releasing hormone agonist (GnRHa) in addition to growth hormone (GH) treatment, as well as the metabolic and cardiovascular health of young adults born SGA after cessation of childhood GH treatment in comparison with appropriate control groups. To diagnose SGA, accurate anthropometry and use of national growth charts are recommended. Follow-up in early life is warranted and neurodevelopment evaluation in those at risk. Excessive postnatal weight gain should be avoided, as this is associated with an unfavorable cardiometabolic health profile in adulthood. Children born SGA with persistent short stature < -2.5 SDS at age 2 years or < -2 SDS at 3 to 4 years of age, should be referred for diagnostic workup. In case of dysmorphic features, major malformations, microcephaly, developmental delay, intellectual disability, and/or signs of skeletal dysplasia, genetic testing should be considered. Treatment with 0.033 to 0.067 mg GH/kg/day is recommended in case of persistent short stature at age of 3 to 4 years. Adding GnRHa treatment could be considered when short adult height is expected at pubertal onset. All young adults born SGA require counseling to adopt a healthy lifestyle., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Health disparities are a significant cause of concern globally and in the United States. Disparities have been additionally highlighted throughout the ongoing COVID-19 pandemic during which populations of color have been the most affected by the disease. Social determinants of health, race, ethnicity, and gender have all contributed to disparate outcomes and disparities spanning all age groups. Multiple socio-ecological factors contribute to disparities and different strategies have been proposed. The purpose of this paper is to provide an overview of disparities in pediatric treatment and outcomes, with a focus on children with endocrine disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Beliard, Wu, Samuels, Lipman and Rapaport.)

Context: The impact of the COVID-19 pandemic on individuals with type 1 diabetes remains poorly defined., Objective: We examined United States trends in diabetic ketoacidosis (DKA) among individuals with type 1 diabetes (T1D) during the COVID-19 pandemic at 7 large US medical centers and factors associated with these trends., Methods: We compared DKA events among children and adults with T1D during COVID-19 surge 1 (March-May 2020) and COVID-19 surge 2 (August-October 2020) to the same periods in 2019. Analysis was performed using descriptive statistics and chi-square tests., Results: We found no difference in the absolute number of T1D patients experiencing DKA in 2019 vs 2020. However, a higher proportion of non-Hispanic Black (NHB) individuals experienced DKA in 2019 than non-Hispanic White (NHW) individuals (44.6% vs 16.0%; P < .001), and this disparity persisted during the COVID-19 pandemic (48.6% vs 18.6%; P < .001). DKA was less common among patients on continuous glucose monitor (CGM) or insulin pump in 2020 compared to 2019 (CGM: 13.2% vs 15.0%, P < .001; insulin pump: 8.0% vs 10.6%, P < .001). In contrast to annual DKA totals, a higher proportion of patients had DKA during COVID-19 surges 1 and 2 compared to the same months in 2019 (surge 1: 7.1% vs 5.4%, P < .001; surge 2: 6.6% vs 5.7%, P = .001)., Conclusion: DKA frequency increased among T1D patients during COVID-19 surges with highest frequency among NHB patients. DKA was less common among patients using CGM or insulin pumps. These findings highlight the urgent need for improved strategies to prevent DKA among patients with T1D-not only under pandemic conditions, but under all conditions-especially among populations most affected by health inequities., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

The evaluation of children with short stature includes monitoring over a prolonged period to establish a growth pattern as well as the exclusion of chronic medical conditions that affect growth. After a period of monitoring, evaluation, and screening, growth hormone stimulation testing is considered when the diagnosis of growth hormone deficiency (GHD) is entertained. Though flawed, growth hormone stimulation tests remain part of the comprehensive evaluation of growth and are essential for the diagnosis of growth hormone (GH) deficiency. Variables including testing length, growth hormone assay and diagnostic cut off affect results. Beyond the intrinsic issues of testing, results of GH stimulation testing can be influenced by patient characteristics. Various factors including age, gender, puberty, nutritional status and body weight modulate the secretion of GH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yau and Rapaport.)

Introduction: The known markers of insulin resistance in obese children are well studied. However, they require serial measurements and complicated calculations. The objective is to study IGFBP-1 and its relation with other known risk measures., Materials and Methods: The study included 98 New York City school students of diverse ethnic/racial backgrounds (57 males and 41 females), 11-15 years of age. Subjects were enrolled in a cross-sectional study, and anthropometric measures were collected. They underwent fasting intravenous glucose tolerance tests (IVGTT), and glucose, insulin, lipids, IGFBP-1, adiponectin and inflammatory markers were collected., Results: The subjects were stratified into 3 groups based upon the BMI Z-score. Out of all the subjects, 65.3% were in the group with a BMI Z-score <1 SDS, 16.3% subjects were in the group with a BMI Z-score of 1 to 2 SDS, and 18.4% of the subjects were in the group with a BMI Z-score of more than 2 SDS. The group with a BMI Z-score of more than 2 SDS had increased waist circumference (WC), body fat, increased fasting insulin, and triglycerides (TG). This group had decreased levels of adiponectin and HDL and low IGFBP-1 as compared to the group with BMI <1 SDS. The group with a BMI Z-score of 1 to 2 SDS had a decreased level of IGFBP-1 as compared to the group with a BMI Z-score less than 1 SDS. IGFBP-1 inversely correlated with age, WC, BMI, body fat, TG, and insulin levels. IGFBP-1 positively correlated with adiponectin and HDL levels., Conclusion: IGFBP-1 in children can identify the presence of insulin resistance in the group with BMI 1 to 2 SDS, even before the known markers of insulin resistance such as elevated triglycerides and even before decreased HDL and adiponectin levels are identified., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer EG declared a shared affiliation with the author RR to the handling editor at the time of review., (Copyright © 2022 Bhangoo, Gupta, Shelov, Carey, Accacha, Fennoy, Altshuler, Lowell, Rapaport, Rosenfeld, Speiser, Ten and Rosenbaum.)

Purpose: This study aimed to evaluate the time interval to menarche after gonadotropin-releasing hormone agonist (GnRHa) treatment in females with central precocious puberty (CPP) and to identify factors contributing to timing of menarche., Methods: We retrospectively reviewed medical records of 39 females with CPP who reached menarche after GnRHa treatment (leuprolide or histrelin). CPP diagnostic criteria were breast development at &lt;8 years old, measurable pubertal luteinizing hormone and/or estradiol concentrations, and bone age advancement. Indications to treat were advanced bone age and psychosocial concerns. Descriptive summaries were reported as frequency and proportion for categorical variables and mean and standard deviation for continuous measures. Linear regression models were developed to evaluate the associations of clinical factors with the time interval to menarche., Results: Mean age was 9.4±1.6 years at treatment onset, and treatment duration was 2.2±1.4 years. Menarche occurred at 12.6±1.1 years, which was 1.04±0.5 years after treatment discontinuation. This was negatively associated with Tanner stage of breast development and bone age at treatment onset and change in bone age during treatment. No association was seen between time interval to menarche and treatment duration, medication, or body mass index., Conclusion: We found the average time interval to menarche after GnRHa treatment in our population of female patients with CPP to be 1.04±0.5 years; this is in agreement with other reports. Tanner stage of breast development, bone age at treatment onset, and change in bone age were negatively associated with time interval to menarche. These data provide clinical correlates that assist providers during anticipatory guidance of patients with CPP after GnRHa treatment.

Background: Diabetes is a risk factor for poor COVID-19 outcomes, but pediatric patients with type 1 diabetes are poorly represented in current studies., Methods: T1D Exchange coordinated a US type 1 diabetes COVID-19 registry. Forty-six diabetes centers submitted pediatric cases for patients with laboratory confirmed COVID-19. Associations between clinical factors and hospitalization were tested with Fisher's Exact Test. Logistic regression was used to calculate odds ratios for hospitalization., Results: Data from 266 patients with previously established type 1 diabetes aged <19 years with COVID-19 were reported. Diabetic ketoacidosis (DKA) was the most common adverse outcome (n = 44, 72% of hospitalized patients). There were four hospitalizations for severe hypoglycemia, three hospitalizations requiring respiratory support (one of whom was intubated and mechanically ventilated), one case of multisystem inflammatory syndrome in children, and 10 patients who were hospitalized for reasons unrelated to COVID-19 or diabetes. Hospitalized patients (n = 61) were more likely than nonhospitalized patients (n = 205) to have minority race/ethnicity (67% vs 39%, P < 0.001), public insurance (64% vs 41%, P < 0.001), higher A1c (11% [97 mmol/mol] vs 8.2% [66 mmol/mol], P < 0.001), and lower insulin pump and lower continuous glucose monitoring use (26% vs 54%, P < 0.001; 39% vs 75%, P < 0.001). Age and gender were not associated with risk of hospitalization. Higher A1c was significantly associated with hospitalization, with an odds ratio of 1.56 (1.34-1.84) after adjusting for age, gender, insurance, and race/ethnicity., Conclusions: Higher A1c remained the only predictor for hospitalization with COVID-19. Diabetic ketoacidosis is the primary concern among this group., (© 2021 Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Summary: We describe a case of an infant who presented with clinical features of hyperthyroidism. The child was found to be tachycardic, hypertensive and diaphoretic, she was noted to have poor weight gain and difficulty in sleeping. The child was admitted to the pediatric intensive care unit for care. She was found to have biochemical evidence of hyperthyroidism with positive thyroid stimulating immunoglobulin. She responded well to methimazole and propranolol and had a remarkable recovery. She is the youngest patient to be diagnosed with Graves disease in the English literature, at 12 months of life., Learning Points: Hyperthyroidism must always be considered even at very young age, for patient presenting with poor weight gain and hyperdynamic state. Autoimmune diseases are becoming more common in infancy. Craniosynostosis and increased height for age are well-documented consequences of untreated hyperthyroidism in developing children.

Cerebral edema (CE) is a potentially devastating complication of diabetic ketoacidosis (DKA) that almost exclusively occurs in children. Since its first description in 1936, numerous risk factors have been identified; however, there continues to be uncertainty concerning the mechanisms that lead to its development. Currently, the most widely accepted hypothesis posits that CE occurs as a result of ischemia-reperfusion injury, with inflammation and impaired cerebrovascular autoregulation contributing to its pathogenesis. The role of specific aspects of DKA treatment in the development of CE continues to be controversial. This review critically examines the literature on the pathophysiology of CE and attempts to categorize the findings by types of brain injury that contribute to its development: cytotoxic, vasogenic, and osmotic. Utilizing this scheme, we propose a multifactorial pathway for the development of CE in patients with DKA., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

The terms 'idiopathic short stature' (ISS) and 'small for gestational age' (SGA) were first used in the 1970s and 1980s. ISS described non-syndromic short children with undefined aetiology who did not have growth hormone (GH) deficiency, chromosomal defects, chronic illness, dysmorphic features or low birth weight. Despite originating in the pre-molecular era, ISS is still used as a diagnostic label today. The term 'SGA' was adopted by paediatric endocrinologists to describe children born with low birth weight and/or length, some of whom may experience lack of catch-up growth and present with short stature. GH treatment was approved by the FDA for short children born SGA in 2001, and by the EMA in 2003, and for the treatment of ISS in the US, but not Europe, in 2003. These approvals strengthened the terms 'SGA' and 'ISS' as clinical entities. While clinical and hormonal diagnostic techniques remain important, it is the emergence of genetic investigations that have led to numerous molecular discoveries in both ISS and SGA subjects. The primary message of this article is that the labels ISS and SGA are not definitive diagnoses. We propose that the three disciplines of clinical evaluation, hormonal investigation and genetic sequencing should have equal status in the hierarchy of short stature assessments and should complement each other to identify the true pathogenesis in poorly growing patients.

Background/aims: Studies are lacking regarding the timing of peak growth hormone (PGH) response. We aim to elucidate the timing of PGH response to arginine and levodopa (A-LD) and evaluate the influence of body mass index (BMI) and other metabolic parameters on PGH., Methods: During growth hormone (GH) stimulation testing (ST) with A-LD, serum GH was measured at baseline and every 30 min up to 180 min. The PGH cut-off was defined as &#x3c;10 ng/mL. IGF-1, IGF BP3, BMI, and metabolic parameters were obtained in a fasting state at baseline., Results: In the 315 tested children, stimulated PGH levels occurred at or before 120 min in 97.8% and at 180 min in 2.2%. GH area under the curve (AUC) positively correlated with PGH in all patients and with IGF-1 in pubertal males and females. BMI negatively correlated with PGH in all subjects. GH AUC negatively correlated with HOMA-IR and total cholesterol., Conclusion: We propose termination of the GH ST with A-LD at 120 min since omission of GH measurement at 180 min did not alter the diagnosis of GH deficiency based on a cut-off of &#x3c; 10 ng/mL. BMI should be considered in the interpretation of GH ST with A-LD. The relationships between GH AUC and metabolic parameters need further study., (© 2019 S. Karger AG, Basel.)

Growth hormone (GH) is used to treat short stature and growth failure associated with growth disorders. Birth size and GH status variably modulate response to GH therapy. The aim of this study was to determine the effect of birth size on response to GH therapy, and to determine the impact of GH status in patients born small for gestational age (SGA) on response to GH therapy. Data from the prospective, non-interventional American Norditropin® Studies: Web-Enabled Research (ANSWER) Program were analyzed for several growth outcomes in response to GH therapy over 3 years. GH-naïve children from the ANSWER Program were included in this analysis: SGA with peak GH ≥10 ng/mL (20 mIU/l), SGA with peak GH <10 ng/mL (20 mIU/l), isolated growth hormone deficiency (IGHD) born SGA, IGHD not born SGA, and idiopathic short stature. For patients with IGHD, those who did not meet criteria for SGA at birth showed greater improvements in height SDS and BMI SDS than patients with IGHD who met criteria for SGA at birth. For patients born SGA, response to GH therapy varied with GH status. Therefore, unlike previous guidelines, we recommend that GH status be established in patients born SGA to optimize GH therapy.

Context: Weaver syndrome is characterized by tall stature, advanced bone age, characteristic facies, and variable intellectual disability. It is caused by heterozygous mutations in enhancer of zeste homolog 2 (EZH2), a histone methyltransferase responsible for histone H3 at lysine 27 (H3K27) trimethylation. However, no early truncating mutations have been identified, suggesting that null mutations do not cause Weaver syndrome., Objective: To test alternative hypotheses that EZH2 variants found in Weaver syndrome cause either a gain of function or a partial loss of function., Design: Exome sequencing was performed in a boy with tall stature, advanced bone age, and mild dysmorphic features. Mutant or wild-type EZH2 protein was expressed in mouse growth plate chondrocytes with or without endogenous EZH2, and enzymatic activity was measured. A mouse model was generated, and histone methylation was assessed in heterozygous and homozygous embryos., Results: A de novo missense EZH2 mutation [c.1876G>A (p.Val626Met)] was identified in the proband. When expressed in growth plate chondrocytes, the mutant protein showed decreased histone methyltransferase activity. A mouse model carrying this EZH2 mutation was generated using CRISPR/Cas9. Homozygotes showed perinatal lethality, whereas heterozygotes were viable, fertile, and showed mild overgrowth. Both homozygous and heterozygous embryos showed decreased H3K27 methylation., Conclusion: We generated a mouse model with the same mutation as our patient, found that it recapitulates the Weaver overgrowth phenotype, and demonstrated that EZH2 mutations found in Weaver syndrome cause a partial loss of function.

Context: Pituitary stalk interruption syndrome (PSIS, ORPHA95496) is a congenital defect of the pituitary gland characterized by the triad of a very thin/interrupted pituitary stalk, an ectopic (or absent) posterior pituitary gland, and hypoplasia or aplasia of the anterior pituitary gland. Complex genetic patterns of inheritance of this disorder are increasingly recognized., Objective: The objective of this study was to identify a genetic cause of PSIS in an affected child., Methods: Whole exome sequencing (WES) was performed by using standard techniques, with prioritized genetic variants confirmed via Sanger sequencing. To investigate the effects of one candidate variant on mutant WDR11 function, Western blotting and coimmunofluorescence were used to assess binding capacity, and leptomycin B exposure along with immunofluorescence was used to assess nuclear localization., Results: We describe a child who presented in infancy with combined pituitary hormone deficiencies and whose brain imaging demonstrated a small anterior pituitary, ectopic posterior pituitary, and a thin, interrupted stalk. WES demonstrated heterozygous missense mutations in two genes required for pituitary development, a known loss-of-function mutation in PROKR2 (c.253C>T;p.R85C) inherited from an unaffected mother, and a WDR11 (c.1306A>G;p.I436V) mutation inherited from an unaffected father. Mutant WDR11 loses its capacity to bind to its functional partner, EMX1, and to localize to the nucleus., Conclusions: WES in a child with PSIS and his unaffected family implicates a digenic mechanism of inheritance. In cases of hypopituitarism in which there is incomplete segregation of a monogenic genotype with the phenotype, the possibility that a second genetic locus is involved should be considered., (Copyright © 2017 Endocrine Society)

Normal growth is a complex dynamic process dependent on the coordination of multiple factors including genetics, nutrition and hormones that are all working in balance. This chapter will review selected features of commonly utilized genetic techniques such as chromosomal analysis, microarray analysis, targeted gene screening and whole exome sequencing that are being used to identify genes influencing growth. As genetic technologies continue to improve and become more accessible many of these techniques will help to provide a better understanding of mechanisms underlying abnormal growth and will eventually lead to novel management approaches for abnormal growth., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Growth is a good indicator of a child's health. Growth disturbances, including short stature or growth failure, could be indications of illnesses such as chronic disease, nutritional deficits, celiac disease or hormonal abnormalities. Therefore, a careful assessment of the various requirements for normal growth needs to be done by history, physical examination, and screening laboratory tests. More details will be reviewed about the GH-IGF axis, its abnormalities with special emphasis on GH deficiency, its diagnosis and treatment. GH treatment indications in the US will be reviewed and a few only will be highlighted. They will include GH deficiency, as well as the treatment of children born SGA, including the results of a US study using FDA approved dose of 0.48mg/kg/week. GH deficiency in adults will also be briefly reviewed. Treatment of patients with SHOX deficiency will also be discussed. Possible side effects of GH treatment and the importance of monitoring safety will be highlighted., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Congenital hypothyroidism is the most common preventable cause of mental retardation. It is important to know the cause of each patient's thyroid dysfunction to foresee the course of therapy and outcomes. Imaging methods, such as ultrasound and thyroid scan, help determine the anatomy and function of the thyroid gland. Although thyroid scan is considered superior in detecting ectopic thyroid tissue, ultrasound is able to detect the presence of thyroid tissue not otherwise visualized in 15% of patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)