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ABSTRACT Introduction Methods Results Discussion Neonatal diabetes mellitus (NDM) is a rare non‐immunological monogenic disorder characterized by hyperglycemic conditions primarily occurring within the first 6 months of life. The majority of cases are attributed to pathogenic variants in genes affecting beta‐cell survival, insulin regulation, and secretion. This study aims to investigate the genetic landscape of NDM in Iran.We recruited a total of 135 patients who were initially diagnosed with diabetes at <12 months of age in Iran and referred to pediatric endocrinology clinics across the country. These patients underwent genetic diagnostic tests conducted by the Exeter Molecular Genetics Laboratory in the UK. The pathogenic variants identified were sorted and described based on type, pathogenicity (according to ACMG/AMP criteria), novelty, and the affected protein domain.Genetic defects were identified in 93 probands, presenting various pathogenic abnormalities associated with NDM and its associated syndromes. 76% of the patients were born as a result of consanguineous marriage, and a familial history of diabetes was found in 43% of the cases. A total of 58 distinct variants in 14 different genes were discovered, including 20 variants reported for the first time. Causative variants were most frequently identified in EIF2AK3, KCNJ11, and ABCC8, respectively. Notably, EIF2AK3 and ABCC8 exhibited the highest number of novel variants.These findings provide valuable insights into the genetic landscape of NDM in the Iranian population and contribute to the knowledge of novel pathogenic variants within known causative genes. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the role of systemic immune-inflammatory index and systemic inflammation response index in predicting early renal impairment in children with type 1 diabetes mellitus (T1DM). Methods: This is a retrospective cohort study which searched the electronic medical records of patients consecutively admitted to Pediatric Endocrinology Unit with the diagnosis of type 1 diabetes mellitus between August 2022 and July 2023. Results: A total of 100 children with the diagnosis of T1DM were enrolled in the study. Early stage diabetic nephropathy (DN) was found in 34 patients. Patients with DN showed significantly higher HbA1C, microalbuminuria, cholesterol, TLC, platelet, neutrophil count, NLR, PLR, SII, and SIRI than the DM without DN. It was discovered that DN was independently correlated with NLR, PLR, SII, and SIRI. Conclusions: SIRI and SII are easily available and affordable inflammatory markers that may serve as independent early predictors of diabetic nephropathy in individuals with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Introduction: Prader-Willi syndrome (PWS) is a genetic disorder characterized by hypothalamic-pituitary deficiencies including hypogonadism. In girls with PWS, hypogonadism can present early in childhood, leading to genital hypoplasia, delayed puberty, incomplete pubertal development, and infertility. In contrast, girls can present with premature activation of the adrenal axis leading to early pubarche and advanced bone age. We aim to evaluate the progression of puberty and adrenarche signals in girls with PWS. Methodology: A longitudinal retrospective cohort study included girls with PWS followed at a Pediatric Endocrinology Outpatient Clinic in a Tertiary University Hospital in Sao Paulo, Brazil from 2002 to 2022. Data collected via chart review included clinical information on birth history, breast and pubic hair Tanner stages, presence of genital hypoplasia, age at menarche, regularity of menstrual cycles, body mass index (BMI) z-score, final height, age of initiation of estrogen replacement and growth hormone replacement, as well as results for PWS genetic subtype; biochemical investigation (LH, FSH, estradiol, DHEA-S); radiographic bone age and pelvic ultrasound. Results: A total of 69 girls were included in the study and the mean age of puberty onset was 10.2 years in those who started puberty after the age of 8 years. Breast Tanner stage IV was reached by 29.1% girls at a mean age of 14.9 years. Spontaneous menarche was present in 13.8% and only one patient had regular menstrual cycles. Early adrenarche was seen in 40.4% of cases. Conclusion: Our study demonstrated in a large sample that girls with PWS often present with delayed onset of puberty despite frequent premature adrenarche. Based on our results, we suggest an estrogen replacement protocol for girls with PWS to be started at the chronological age or bone age of 12–13 years, taking into consideration the uterus size. Further prospective studies are needed. [ABSTRACT FROM AUTHOR]

Purpose The incidence of endocrine sequelae following central nervous system (CNS) infections in pediatric age is not known. We conducted this scoping review to assess the incidence of endocrinological alterations in patients with prior CNS infections in pediatric age. Methods Our screening process included both randomized and non-randomized controlled trials. All types of observational studies, prospective and retrospective, have been included. Results Ten studies were included in our review. The cumulative number of patients in all of the studies was 211, the mean age of the population study was 4.9 (±5 years). The included papers described the following acute CNS infections: meningitis (nine studies reported eighty-five cases) and encephalitis (three studies described sixty-five cases). Two case reports and one retrospective study reported hypopituitarism as a consequence of Mycobacterium tuberculosis CNS infection. In five studies the patients developed endocrine comorbidities at the time of infection. Another study analyzed 49 young adults who previously had tuberculous meningitis at a mean age of 5.9 ± 5.0 years: seven patients had growth hormone deficiency, four of whom also had gonadotropin deficiency; the other three had gonadotropin deficiency, corticotropin deficiency, and mild hyperprolactinemia. Conclusion Standardized multidisciplinary follow-up and research of patients with prior CNS infection is crucial. Although pituitary reserve screening is not commonly performed in these patients, clinical and research centers should set up an endocrinological evaluation with monitoring of auxological parameters to detect the signs and symptoms of hypopituitarism early and to initiate the appropriate care in children with previous CNS infections. [ABSTRACT FROM AUTHOR]

Background: One of the most frequent reasons for referral to pediatric endocrinology units is short stature. Children’s short height has a complicated etiology that includes genetics, race, gender, nutrition, and several endocrine hormones. Objective: To determine the etiological spectrum of short stature among children presenting to endocrinology outpatient clinics in a tertiary care hospital. Methods: This descriptive cross-sectional study was performed in the outpatient clinic of the Endocrinology Department at the National Institute of Child Health Hospital from September to December 2022. Short stature was defined as height for age

Background: Individuals with hyperinsulinemia may initially not meet any diagnostic criteria for metabolic syndrome, though displaying a higher risk of cardiovascular complications combined with obesity, diabetes, and hypertension. Aim: The main objective of our study was to assess the diagnostic accuracy of various cardiovascular risk indices in hyperinsulinemic children and adolescents; a secondary objective was to estimate the optimal cut-offs of these indices. Patients and methods: This retrospective single-center study was conducted on 139 patients aged 12.1 ± 2.9 years, managed for hyperinsulinism. Results: We found statistically significant differences in homeostasis model assessment of insulin resistance index (HOMA-IR), triglyceride glucose index (TyG), TyG-body mass index, visceral adiposity index, lipid accumulation product index, fatty liver index, and hepatic steatosis index. At the linear logistic regression assessment, we found that insulin growth factor-1 (IGF-1), HOMA-IR, and ALT/AST ratio were independently associated with confirmed hyperinsulinism. At the multivariate analysis, IGF-1 levels over 203 ng/mL and HOMA-IR higher than 6.2 were respectively associated with a 9- and 18-times higher odds ratio for hyperinsulinism. The other investigated parameters were not significantly related to hyperinsulinism, and could not predict either the presence of hyperinsulinemia or a subsequent cardiovascular risk in our patients. Conclusion: Commonly used indices of cardiovascular risk in adults cannot be considered accurate in confirming hyperinsulinism in children, with the exception of HOMA-IR. Further studies are needed to verify the usefulness of specific cardiovascular risk indices in hyperinsulinemic children and adolescents. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Rickets results from impaired mineralization of growing bone due to alterations in calcium and phosphate homeostasis. Clinical signs of rickets are related to the age of the patient, the duration of the disease, and the underlying disorder. The most common signs of rickets are swelling of the wrists, knees or ankles, bowing of the legs (knock-knees, outward bowing, or both) and inability to walk. However, clinical features alone cannot differentiate between the various forms of rickets. Rickets includes a heterogeneous group of acquired and inherited diseases. Nutritional rickets is due to a deficiency of vitamin D, dietary calcium or phosphate. Mutations in genes responsible for vitamin D metabolism or function, the production or breakdown of fibroblast growth factor 23, renal phosphate regulation, or bone mineralization can lead to the hereditary form of rickets. This position paper reviews the relevant literature and presents the expertise of the Bone and Mineral Metabolism Group of the Italian Society of Pediatric Endocrinology and Diabetology (SIEDP). The aim of this document is to provide practical guidance to specialists and healthcare professionals on the main criteria for diagnosis, treatment, and management of patients with rickets. The various forms of rickets are discussed, and detailed references for the discussion of each form are provided. Algorithms to guide the diagnostic approach and recommendations to manage patients with rare forms of hereditary rickets are proposed. [ABSTRACT FROM AUTHOR]

Multiple Endocrine Neoplasia type 1 (MEN1) is a rare genetic disease, characterized by co-occurrence of several lesions of the endocrine system. In MEN1, the pathogenic MEN1 gene mutations lead to the Abnormal expression of menin, a critical tumor suppressor protein. We here reported a case of a 14‐year‐old male with insulinoma and primary hyperparathyroidism. Genetic testing demonstrated a novel heterozygote variant c.587delA of MEN1, resulting in the substitution of the 196th amino acid, changing from glutamic acid to glycine, followed by a frameshift translation of 33 amino acids. An identical variant was identified in the proband’s father, who was further diagnosed with hyperparathyroidism. To the best of our knowledge, this is the first report of MEN1 syndrome caused by the c.587delA MEN1 variant. Observations indicated that, despite sharing the same MEN1 gene change, family members exhibited diverse clinical phenotypes. This underscored the presence of genetic anticipation within the familial context.

IntroductionInsulin is a high-risk medication, and errors can lead to patient morbidity and mortality. The American Board of Pediatrics recommends that all board-certified pediatricians be able to develop an insulin management plan for patients with diabetes. A needs assessment of pediatric residents revealed low self-efficacy at developing a new subcutaneous insulin plan despite didactic instruction on the topic.MethodsWe created a 90-minute interactive workshop that targeted resident skills in devising subcutaneous insulin plans. Learners engaged in small-group, problem-based learning and peer teaching to promote active learning and participation. We compared self-efficacy and knowledge before and after the intervention using paired t tests and evaluated learner satisfaction.ResultsTwenty-eight pediatric interns participated, with 25 completing both the pre- and postworkshop surveys. The primary outcome was self-efficacy (an individual's confidence in the ability to perform a specific task in a given domain). There was a statistically significant improvement in self-efficacy at creating a new subcutaneous insulin plan ( p < .001) as well as knowledge ( p < .001) after course completion. Learners were highly satisfied with the course, with a mean overall conference quality rating of 4.8 (SD = 0.4) based on a 5-point Likert scale (1 = poor, 5 = outstanding).DiscussionAn interactive workshop employing active learning methods resulted in improved self-efficacy and knowledge in first-year pediatric residents. Future work is needed to determine the impact of this workshop on patient care outcomes.

Introduction: A good screening tool, such as a growth chart, should distinguish between children with normal growth and those with perturbed growth. Suitability of synthetic Indian growth references for diagnosing growth-related disorders for under-five children has not been evaluated. To assess the validity of World Health Organization (WHO) 2006 standards vs synthetic Indian references (2019) (by comparing weight, height, body mass index (BMI), standard deviation scores (SDS) and the composite index of anthropometric failure (CIAF)) in differentiating normal children and children with growth-related disorders. Methods: Records of 2188 children (0-60 months) attending a tertiary centre paediatric outpatient department (OPD) were retrospectively studied; 1854 children were healthy and 334 were diagnosed with growth-related disorders as per the European Society for Paediatric Endocrinology (ESPE) classification. The anthropometric parameters converted to Z-scores for weight-for-age (WAZ), height-for-age (HAZ), BMI-for-age (BAZ) and a CIAF were computed using WHO and synthetic charts; Student's t-test was used for assessing differences and Youden's index for validity. Results: Disease status of children and anthropometric failure on WAZ, HAZ, BAZ and CIAF on both WHO and synthetic charts had a significant association (P-value <0.05). WAZ, HAZ on both charts and CIAF on synthetic chart had a fair to moderate agreement (Kappa statistics) with disease status as per diagnosis (P-value <0.05). The sensitivity and negative predictive value for all anthropometric parameters were higher for synthetic charts. Conclusion: Indian charts were more sensitive for diagnosing growth-related disorders from birth to 60 months of age when compared to WHO growth standards. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the demographic, clinical, and laboratory characteristics of children with benign transient hyperphosphatasemia (BTH) and to increase awareness of BTH. Children with BTH followed up in a tertiary pediatric endocrinology outpatient clinic were included in this retrospective study. Children who were aged under 5 years, who had no evidence of liver, kidney, or bone disease, who had serum total alkaline phosphatase (ALP) levels above 1000 IU/L, and whose ALP values resolved within 4 months, were included in the study. The study included 10 infants and children (4 females) with BTH who were referred to our clinic during 1 year for high ALP levels. The mean age was 2.4±0.5 years. The mean weight SDS was -0.24±1.27 and the mean height SDS was -0.51±0.67. The mean ALP level was 2.395±934 IU/L. The mean normalization time for serum ALP was 2.4±1.1 months. Benign transient hyperphosphatasemia is an entity that occurs in healthy infants and children without evidence of liver or bone disease and resolves without intervention. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the diagnostic value of luteinizing hormone (LH) basal values and sex hormone-binding globulin (SHBG) for rapidly progressive central precocious puberty (RP-CPP). Methods: A total of 121 girls presenting with secondary sexual characteristics were selected from the Department of Pediatric Endocrinology, Lianyungang Clinical Medical College of Nanjing Medical University, from May 2021 to June 2023. The children were followed up for 6 months andwere divided into three groups: RP-CPP group (n=40), slowly progressive central precocious puberty (SP-CPP) group (n=40), and premature thelarche (PT) group (n=41). The differences in LH basal values and SHBG among girls in the three groups were compared. ROC curves were drawn to analyze the value of LH basal values and SHBG in identifying RP-CPP. Results: Significant differences were observed in age, height, predicted adult height (PAH), weight, body mass index (BMI), bone age (BA), BA-chronological age (CA), LH basal, LH peak, FSH basal, LH peak/FSH peak, estradiol (E2), testosterone, and SHBG levels between the RP-CPP group and the SP-CPP and PT groups (P < 0.05). The LH basal value in the RP-CPP group was higher than that in the SP-CPP group and the PT group, while SHBG levels were lower than in the latter two groups, and these differenceswere statistically significant (P < 0.05). When the LH basal valuewas =0.58 IU/L and SHBG was =58.79 nmol/L, the sensitivity for diagnosing RP-CPP was 77.5% and 67.5%, and the specificity was 66.7% and 74.1%. Conclusion: Detection of basal LH and SHBG levels allows for early diagnosis of the progression of central precocious puberty. [ABSTRACT FROM AUTHOR]

Paediatric Cushing's disease (CD) is characterized by excess ACTH secretion froma pituitary adenoma, leading to hypercortisolism. It has approximately 5% of the incidence of adult CD and is a rare disorder in the paediatric age range. The four most specific presenting features of hypercortisolism are: change in facial appearance, weight gain, decreased linear growth and virilisation shown by advanced pubic hair for the stage of breast development or testicular volume. The main diagnostic priority is the demonstration of hypercortisolism followed by distinction between its ACTH-dependent and ACTH-independent origin, thus leading to identification of aetiology. All treatment options aim to resolve or control hypercortisolism. Consensus favours transsphenoidal (TSS) pituitary surgery with selective removal of the corticotroph adenoma. TSS in children with CD is now well established and induces remission in 70-100% of cases. External pituitary radiotherapy and bilateral adrenalectomy are second-line therapeutic approaches in subjects not responding to TSS. Long-term medical treatment is less frequently adopted. Recurrence in paediatric CD cases is low with factors predicting relapse being higher post-TSS cortisol and ACTH levels and rapid recovery of the hypothalamic-pituitary-adrenal axis after TSS. In summary, complete excision of the microadenoma with histological and biochemical evidence for this, predicts a low rate of recurrence of CD. Due to the need for rapid diagnosis and management to avoid the burden of prolonged exposure to hypercortisolism, tertiary university centres comprising both paediatric and adult endocrinology specialists together with experienced pituitary surgery and, eventually, radiotherapy units are recommended for referral of these patients. [ABSTRACT FROM AUTHOR]

Introduction: Type 1 pseudohypoaldosteronism (PHA) consists of resistance to aldosterone. Neonatal presentation is characterized by salt wasting, hyperkalemia, and metabolic acidosis with high risk of mortality. Type 1 PHA can be autosomal dominant (renal type 1) or autosomal recessive (systemic type 1). Renal PHA type 1 can be feasibly managed with salt supplementation; however, systemic PHA type 1 tends to have more severe electrolyte imbalance and can be more refractory to treatment. Case Presentation: We present a case of a 3-year-old girl with systemic PHA type 1, diagnosed and confirmed molecularly in infancy, who has been successfully managed with sodium polystyrene sulfonate decanted into feeds along with sodium supplementation. On day 5 of life, a full-term female infant presented to the ED for 2 days of non-bloody, non-bilious emesis, along with hypothermia to 94°F. Laboratory results were notable for hyponatremia (Na) of 127, hyperkalemia (K) of 7.9, and acidosis with bicarbonate level of 11.2. Genetic testing ordered within a week of life confirmed PHA type 1 with a homozygous pathogenic frameshift variant in SCNN1A c.575delA (p.Arg192GlyfsX57). Sodium polystyrene sulfonate and feeds were decanted until the age of 16 months, and she was also continued on NaCl supplementation. She was gradually transitioned to directly administered sodium polystyrene sulfonate without any electrolyte issues. She has overall done well after gastrostomy-tube (G-tube) placement without severe hyperkalemia even with several hospitalizations for gastrointestinal or respiratory illnesses. Discussion/Conclusion: A treatment approach to systemic PHA and sodium polystyrene sulfonate administration in neonates and infants is described. [ABSTRACT FROM AUTHOR]

This document is an editorial published in the journal Frontiers in Endocrinology. The editorial discusses a research topic called "Stars and Rising Stars in Pediatric Endocrinology: 2022." It highlights various research works in the field of endocrinology, including the genetics of rare endocrine disorders, novel applications of diabetes technology, and a new theory of dyslipidemia. The articles cover topics such as improving diagnostic approaches to endocrine disorders, expanding the understanding of classic disease phenotypes, and the impact of COVID-19 on sexual maturation. The editorial concludes that these articles will have a lasting impact on the future of endocrinology. [Extracted from the article]

The Milestones were initiated by the Accreditation Council for Graduate Medical Education (ACGME) to provide a framework for monitoring a trainee's progression throughout residency/fellowship. The Milestones describe stepwise skill progression through six core domains of clinical competency: Patient Care, Medical Knowledge, Interpersonal and Communication Skills, Practice-based Learning and Improvement, Professionalism, and Systems-based Practice. Since their introduction in 2013, several barriers to implementation have emerged. Thus, the ACGME launched the Milestones 2.0 project to develop updated specialty-specific milestones. The Pediatric Endocrinology Milestones 2.0 project aimed to improve upon Milestones 1.0 by addressing common limitations, providing resources for faculty to easily incorporate milestones into their assessment of trainees, and adding sub-competencies in health disparities, patient safety, and physician well-being. This paper reviews the development of the Pediatric Endocrinology Milestones 2.0 including the major changes from Milestones 1.0, development of the Supplemental Guide, and how Milestones 2.0 can be applied at the program level. Although use of the Milestones are required only for ACGME programs, the tools provided in Milestones 2.0 are applicable to fellowship programs worldwide. [ABSTRACT FROM AUTHOR]

A Pediatric Endocrine Society (PES) Drugs and Therapeutics Committee workgroup sought to determine the prescribing practices of pediatric endocrinologists when treating children <10 years of age with congenital adrenal hyperplasia (CAH). Our workgroup administered a 32-question online survey to PES members. There were 187 respondents (88.9% attending physicians), mostly from university-affiliated clinics (~80%). Ninety-eight percent of respondents prescribed the short-acting glucocorticoid hydrocortisone to treat young children, as per the Endocrine Society CAH Guidelines, although respondents also prescribed long-acting glucocorticoids such as prednisolone suspension (12%), prednisone tablets (9%), and prednisone suspension (6%). Ninety-seven percent of respondents indicated that they were likely/very likely to prescribe hydrocortisone in a thrice-daily regimen, as per CAH Guidelines, although 19% were also likely to follow a twice-daily regimen. To achieve smaller doses, using a pill-cutter was the most frequent method recommended by providers to manipulate tablets (87.2%), followed by dissolving tablets in water (25.7%) to create a daily batch (43.7%) and/or dissolving a tablet for each dose (64.6%). Thirty-one percent of providers use pharmacy-compounded hydrocortisone suspension to achieve doses of <2.5 mg. Our survey shows that practices among providers in the dosing of young children with CAH vary greatly and sometimes fall outside of the CAH Guidelines—specifically when attempting to deliver lower, age-appropriate hydrocortisone doses. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to explore the impact of gonadotropin-releasing hormone agonists (GnRHa) on final adult height (FAH) in girls with early and fast puberty. Methods: A retrospective study was conducted by reviewing data from the medical records of the Pediatric Endocrinology Clinics between January 1, 2010, and December 31, 2020, at MacKay Children's Hospital. The treatment group included 109 patients who received 3.75 mg monthly for at least 1 year, whereas the control group consisted of 95 girls who received no treatment. Results: The treatment group was significantly older at the time of inclusion (chronological age (CA1), treatment vs. control, 8.7 vs. 8.4 years, p < 0.001), had a more advanced bone age (BA) (BA1, 11.5 vs. 10.8 years, p < 0.001), BA1-CA1 (2.7 vs. 2.2 years, p < 0.001), and shorter predicted adult height (PAH1) (153.3 vs. 157.1 cm, p = 0.005) that was significantly lower than their target height (Tht) (PAH1-Tht, -3.9 vs. -1.3 cm, p = 0.039). The FAHs of the GnRHa and the control group were similar (157.0 vs. 156.7 cm, p = 0.357) and were not significantly different from their Tht (FAH vs. Tht in the GnRHa group, 157.0 vs. 157.0 cm; control group, 156.7 vs. 157.0 cm). In the subgroup analysis, FAH was significantly higher after GnRHa treatment in those with PAH1 less than 153 cm and Tht (154.0 vs. 152.0 cm, p = 0.041), and those whose CA1 was between 8 and 9 years (158.0 vs. 155.4 cm, p = 0.004). We defined satisfactory FAH outcome as FAH- PAH1>5 cm and significant factors were GnRHa therapy, PAH1 shorter than their Tht, age younger than 9 years, and faster growth velocity during the first year. Discussion: GnRHa is effective in restoring the Tht in some early and fast pubertal girls, especially in those with poorly PAH (PAH lower than 153 cm and shorter than their target height). A younger age at initiation of treatment and a faster growth velocity during treatment are associated with a better height gain. [ABSTRACT FROM AUTHOR]

Introduction: The standard of care for pediatric growth hormone deficiency (pGHD) is once-daily recombinant human growth hormone (rhGH). Somatrogon, a long-acting rhGH, requires less frequent, once-weekly, dosing. We describe physicians’ preference for, experiences, and satisfaction with once)weekly somatrogon vs once-daily rhGH. Methods: English-speaking investigators from somatrogon’s global phase III study (NCT02968004) with prior experience using once-daily rhGH were included. Participants answered an online survey containing 14 closed- and open-ended items. Results: Twenty-four pediatric endocrinologists (41.7% men; 79.2% practiced at public/private hospitals) from 12 countries with 25.8 ± 12.0 years’ experience treating pGHD completed the survey. In terms of the time and effort required to explain device instructions, injection regimen, procedure for missed injection, and address patients’/caregivers’ concerns, a similar proportion of physicians chose once-weekly somatrogon and once-daily rhGH; 62.5% physicians indicated that once-daily rhGH required greater effort to monitor adherence. Overall, 75% preferred once-weekly somatrogon over once-daily rhGH, 79.2% considered once-weekly somatrogon to be more convenient and less burdensome, and 83.3% were likely to prescribe somatrogon in the future. Overall, 50% felt that once-weekly somatrogon was more beneficial to patients, while 50% chose “No difference”. Most physicians (62.5%) felt both regimens were equally likely to support positive long-term growth outcomes and reduce healthcare utilization. More physicians were “very satisfied” with once-weekly somatrogon (62.5%) than with once-daily rhGH (16.7%). Reduced injection frequency, patient and caregiver burden, increased convenience, and improved adherence were reasons for these choices. Conclusion: Physicians had a positive experience with, and perception of, treating pGHD with once-weekly somatrogon. [ABSTRACT FROM AUTHOR]

β-Thalassemia is characterized by the abnormal synthesis of β-hemoglobin chains resulting in hemolytic anemia. Treatment involves frequent blood transfusions, which leads to deposition of iron in many organs, including endocrine glands. To date, several cases of papillary thyroid cancer (PTC) in patients with β-thalassemia have been reported in the adult literature, but there have been none in pediatrics. Here we report on an female adolescent with β-thalassemia who initially presented for evaluation of secondary amenorrhea. On examination, her thyroid gland was asymmetric, firm in consistency, with palpable lymph nodes along the right anterior cervical chain. A thyroid ultrasound revealed an enlarged right lobe containing 3 focal hypoechoic masses with calcific foci. Biopsy was consistent with PTC. She underwent total thyroidectomy and histological examination confirmed the diagnosis. Her postoperative course was uncomplicated and she was started on replacement therapy with levothyroxine. This is the first reported case of PTC in a pediatric patient with β-thalassemia. The incidence of thyroid cancer in patients with β-thalassemia is currently unknown; however, there may be utility in routine surveillance of this patient population. [ABSTRACT FROM AUTHOR]

Background Pediatric type 2 diabetes (T2D) is increasing in prevalence, yet it is unclear what definition of pediatric prediabetes predicts progression to T2D. Strategies are needed to better identify at risk individuals who could benefit from early intervention. Methods Retrospective chart review of a pediatric prediabetes clinic over 7 years. Inclusion criteria include hemoglobin A1c (HbA1C) and ≥1 glucose from oral glucose tolerance test. Exclusion criteria include type 1 diabetes, maturity onset diabetes of the young, or T2D on initial visit. Results A total of 552 patients were included, 6.5% (n = 36) progressed to T2D over 2.4 ± 1.5 years. At initial visit, T2D progressors had a higher body mass index (38.6 ± 6.5 vs 34.2 ± 8.4 kg/m2, P =.002), HbA1C (6.0 ± 0.3%, vs 5.7± 0.3, P <.001), 2-hour glucose (141 ± 28 vs 114 ± 29 mg/dL, P <.001), and C-peptide (4.8 vs 3.6 ng/mL, P =.001). Fasting glucose was not significantly different. In a multivariable model, male sex (hazard ratio [HR], 2.4; P =.012), initial visit HbA1C (HR, 1.3 per 0.1% increase; P <.001), and 2-hour glucose level (HR, 1.2 per 10 mg/dL increase; P =.014) were all predictive of T2D progression. Patients who progressed to T2D had an increase in body mass index of 4.2 kg/m2 and children consistently taking metformin took longer to progress (43 ± 21 vs 26 ± 16 months; P =.016). Discussion A total of 6.5% of patients with prediabetes developed T2D over a 7-year period. Initial visit laboratory values and weight trajectory may allow for risk stratification, whereas fasting plasma glucose is less helpful. Weight stabilization and metformin therapy could be important interventions for diabetes prevention in children. [ABSTRACT FROM AUTHOR]

Growth Hormone Deficiency (GHD) is one of the most important treatable endocrine causes of short stature. A problem anywhere in the Growth Hormone (GH) - Insulin-Like Growth Factor-1 (IGF-1) axis can lead to short stature. Childhood GH deficiency can be congenital, acquired, or idiopathic. Hereby, the authors present a case series consisting of five cases of short stature, aimed to provide an overview of the spectrum of GH-related disorders. All five patients presented to the Paediatric Endocrinology Outpatient Department of a tertiary care Institute with complaints of not gaining height. The patients in present case series had significant short stature (Z score for height <-3 SD (Standard Deviation) in each case). These patients were suspected of having GH deficiency based on clinical presentation and investigations. After a proper diagnostic work-up and GH stimulation tests, cases 1 to 4 were found to have GH deficiency. The 5th case was suspected of having Laron Syndrome based on high GH levels and low IGF-1. There were subtle differences in the spectrum of GH deficiency. The 1st case had Multiple Pituitary Hormone Deficiency (MPHD). Cases 2 to 4 had Isolated Growth Hormone Deficiency (IGHD). Case 2 had findings of pituitary stalk interruption on brain imaging. We found a genetic association in the 3rd case, while the 4th case had almost normal brain imaging. Cases 1 to 4 received GH therapy, and all showed appreciable height gain. These subtle differences can sometimes make the diagnosis difficult, and often a different approach to treatment is required. [ABSTRACT FROM AUTHOR]

Background: Although there are studies evaluating the psychological adjustment of healthy children when their siblings have type 1 diabetes mellitus (T1DM), no study evaluating their nutritional status exists. Thus, this study aimed to determine the nutritional status of children with T1DM and their healthy siblings. Material and methods: Data from a control group, healthy siblings, and patients who were followed and treated for T1DM in the Paediatric Gastroenterology and Paediatric Endocrinology outpatient clinics of the Health Sciences University Gülhane Medical Faculty between November 2019 and November 2020 were analysed and compared. The groups were compared in terms of nutritional characteristics, daily macro and micronutrient intakes and classified according to their body mass index (BMI) Z-scores. Results: The study population consisted of 29 children with T1DM (51.7% female, 48.3% male; age: 11.00 ±3.66 years), 36 healthy siblings of children with T1DM (50% female, 50% male; age: 9.61 ±4.84 years), and a control group of 58 healthy children (51.7% female, 48.3% male; age: 10.68 ±3.01years). The BMI Z-score of 28.6% of healthy siblings and 25% of children with T1DM was > 1 SD or overweight. All of the control group children were of normal weight. None of the children were obese; however, the overweight rate was significantly higher in the healthy siblings and diabetes groups compared to the control group (p = 0.012). Daily energy intake (%) was significantly higher in the control group than in the healthy siblings (p < 0.001). Conclusions: A quarter of the children with T1DM over five years of age were overweight. In addition, healthy siblings were found to have higher BMI Z-scores than controls. This is the first study to evaluate the nutritional status of siblings of patients with T1DM and will hopefully lead to more comprehensive studies that will also assess their daily exercise and physical activity. [ABSTRACT FROM AUTHOR]

Guidelines for screening and management of congenital hypothyroidism in neonates have been recently updated by the American Academy of Pediatrics (AAP). This article compares new AAP guideline with the Indian Society for Pediatric and Adolescent Endocrinology (ISPAE) Guidelines, 2018 and lists the changes in screening, diagnosis, and management of congenital hypothyroidism suggested in the new guidelines, along with clinical utilization in the Indian scenario. [ABSTRACT FROM AUTHOR]

IntroductionType 1 pseudohypoaldosteronism (PHA) consists of resistance to aldosterone. Neonatal presentation is characterized by salt wasting, hyperkalemia, and metabolic acidosis with high risk of mortality. Type 1 PHA can be autosomal dominant (renal type 1) or autosomal recessive (systemic type 1). Renal PHA type 1 can be feasibly managed with salt supplementation; however, systemic PHA type 1 tends to have more severe electrolyte imbalance and can be more refractory to treatment.Case PresentationWe present a case of a 3-year-old girl with systemic PHA type 1, diagnosed and confirmed molecularly in infancy, who has been successfully managed with sodium polystyrene sulfonate decanted into feeds along with sodium supplementation. On day 5 of life, a full-term female infant presented to the ED for 2 days of non-bloody, non-bilious emesis, along with hypothermia to 94°F. Laboratory results were notable for hyponatremia (Na) of 127, hyperkalemia (K) of 7.9, and acidosis with bicarbonate level of 11.2. Genetic testing ordered within a week of life confirmed PHA type 1 with a homozygous pathogenic frameshift variant in SCNN1A c.575delA (p.Arg192GlyfsX57). Sodium polystyrene sulfonate and feeds were decanted until the age of 16 months, and she was also continued on NaCl supplementation. She was gradually transitioned to directly administered sodium polystyrene sulfonate without any electrolyte issues. She has overall done well after gastrostomy-tube (G-tube) placement without severe hyperkalemia even with several hospitalizations for gastrointestinal or respiratory illnesses.Discussion/ConclusionA treatment approach to systemic PHA and sodium polystyrene sulfonate administration in neonates and infants is described.

Purpose The incidence of endocrine sequelae following central nervous system (CNS) infections in pediatric age is not known. We conducted this scoping review to assess the incidence of endocrinological alterations in patients with prior CNS infections in pediatric age. Methods Our screening process included both randomized and non-randomized controlled trials. All types of observational studies, prospective and retrospective, have been included. Results Ten studies were included in our review. The cumulative number of patients in all of the studies was 211, the mean age of the population study was 4.9 (±5 years). The included papers described the following acute CNS infections: meningitis (nine studies reported eighty-five cases) and encephalitis (three studies described sixty-five cases). Two case reports and one retrospective study reported hypopituitarism as a consequence of Mycobacterium tuberculosis CNS infection. In five studies the patients developed endocrine comorbidities at the time of infection. Another study analyzed 49 young adults who previously had tuberculous meningitis at a mean age of 5.9 ± 5.0 years: seven patients had growth hormone deficiency, four of whom also had gonadotropin deficiency; the other three had gonadotropin deficiency, corticotropin deficiency, and mild hyperprolactinemia. Conclusion Standardized multidisciplinary follow-up and research of patients with prior CNS infection is crucial. Although pituitary reserve screening is not commonly performed in these patients, clinical and research centers should set up an endocrinological evaluation with monitoring of auxological parameters to detect the signs and symptoms of hypopituitarism early and to initiate the appropriate care in children with previous CNS infections.

Background: Individuals with hyperinsulinemia may initially not meet any diagnostic criteria for metabolic syndrome, though displaying a higher risk of cardiovascular complications combined with obesity, diabetes, and hypertension. Aim: The main objective of our study was to assess the diagnostic accuracy of various cardiovascular risk indices in hyperinsulinemic children and adolescents; a secondary objective was to estimate the optimal cut-offs of these indices. Patients and methods: This retrospective single-center study was conducted on 139 patients aged 12.1 ± 2.9 years, managed for hyperinsulinism. Results: We found statistically significant differences in homeostasis model assessment of insulin resistance index (HOMA-IR), triglyceride glucose index (TyG), TyG-body mass index, visceral adiposity index, lipid accumulation product index, fatty liver index, and hepatic steatosis index. At the linear logistic regression assessment, we found that insulin growth factor-1 (IGF-1), HOMA-IR, and ALT/AST ratio were independently associated with confirmed hyperinsulinism. At the multivariate analysis, IGF-1 levels over 203 ng/mL and HOMA-IR higher than 6.2 were respectively associated with a 9- and 18-times higher odds ratio for hyperinsulinism. The other investigated parameters were not significantly related to hyperinsulinism, and could not predict either the presence of hyperinsulinemia or a subsequent cardiovascular risk in our patients. Conclusion: Commonly used indices of cardiovascular risk in adults cannot be considered accurate in confirming hyperinsulinism in children, with the exception of HOMA-IR. Further studies are needed to verify the usefulness of specific cardiovascular risk indices in hyperinsulinemic children and adolescents.

Abstract Introduction Pure androgen-secreting adrenocortical tumors are a rare but important cause of peripheral precocious puberty. Case presentation Here, we report a pure androgen-secreting adrenocortical tumor in a 2.5-year-old boy presenting with penile enlargement, pubic hair, frequent erections, and rapid linear growth. We confirmed the diagnosis through laboratory tests, medical imaging, and histology. Furthermore, genetic testing detected a pathogenic germline variant in the TP53 gene, molecularly confirming underlying Li–Fraumeni syndrome. Discussion Only 15 well-documented cases of pure androgen-secreting adrenocortical tumors have been reported so far. No clinical or imaging signs were identified to differentiate adenomas from carcinomas, and no other cases of Li–Fraumeni syndrome were diagnosed in the four patients that underwent genetic testing. However, diagnosing Li–Fraumeni syndrome is important as it implies a need for intensive tumor surveillance and avoidance of ionizing radiation. Conclusion In this article, we emphasize the need to screen for TP53 gene variants in children with androgen-producing adrenal adenomas and report an association with arterial hypertension.

Objective: To find the frequency of precocious puberty in children and to compare the clinical and laboratory parameters of central & peripheral precocious puberty. Study Design: Cross-sectional study. Setting: Karachi's National Institute of Child Health's Paediatric & endocrinology Division. Period: December 2016 and 2021. Material & Methods: All patients with precocious puberty will be taken from files through non-probability convenience sampling method. Data was analyzed on SPSS version 22.0. Results: Total 65 patients were included. The mean age was 6+3.35years. Precocious puberty was classified as peripheral precocious puberty in 38 (58.4%), central precocious puberty in 20 (30.76%), premature thelarche in 5(7.69%) and premature1pubarche in 2 (3.07%). In the peripheral precocious1puberty group, CAH was found in 22(78.5%), out of which 2 patients were of rare mutation of CAH presenting with peripheral precocious puberty (DAX mutation and 11 B hydroxylase mutation, adenocarcinoma was observed in 2(7.14%) followed by Mu-cane-Albright syndrome was in 4(14.28%) and van wykgrumbach syndrome in 10 patients. Central precocious puberty was found in 20 patients hypothalamic harmartoma in 4(20%), craniopharyngioma 3(15%), hypothalamic astrocytoma 1(5.0%), genetically proven neurofibromatosis in 1(5.0%) patient and hydrocephalus 1(5.0%) and in 10(50%) patients no cause was found. Conclusion: The conclusion of the study that Peripheral precocious puberty was more common than central precocious puberty. The common cause of peripheral precocious puberty was CAH, while central precocious puberty was idiopathic. Children with central precocious puberty had greater height SDS, weight SDS, FSH, and LH levels compared to children who had peripheral precocious puberty. [ABSTRACT FROM AUTHOR]

The Committee of Central Precocious Puberty of Korean Pediatrics and Adolescents of the Korean Society of Pediatric Endocrinology has newly developed evidencebased 2022 clinical practice guidelines for central precocious puberty in Korean children and adolescents. These guidelines provide the grade of recommendations, which includes both the strength of recommendations and the level of evidence. In the absence of sufficient evidence, recommendations are based on expert opinion. These guidelines have been revised and supplement the previous guidelines "Clinical Guidelines for Precocious Puberty 2011," and are drawn from a comprehensive review of the latest domestic and international research and the grade of recommendation appropriate to the domestic situation. This review summarizes the newly revised guidelines into 8 key questions and 27 recommendations and consists of 4 sections: screening, diagnosis, treatment, and long-term outcome of central precocious puberty. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate a potential correlation between results of the oral glucose tolerance test (OGTT) and the auxological/metabolic parameters in a cohort of overweight patients assessed for suspicion of hyperinsulinism. We analyzed 206 patients, comparing those with insulin peak below (nonhyperinsulinemic) and over 100 uIU/mL (hyperinsulinemic) at the OGTT. We found a significant difference in weight (p = 0.037), body mass index (BMI, p < 0.001) and BMI standard deviations (SD, p < 0.001), waist circumference (p = 0.001), hip circumference (p = 0.001), and waist-to-height ratio (WHtR, p = 0.016) between the two groups. Analyzing the median insulin value during OGTT in the whole population, a weakly positive correlation emerged with weight SD (p < 0.001; rho = 0.292) and a moderate positive correlation with BMI SD (p < 0.001; rho = 0.323). We also found a weakly positive correlation with waist circumference (p = 0.001; rho = 0.214), hip circumference (p = 0.001; rho = 0.217), and WHTR (p = 0.016; rho = 0.209) and a moderate positive correlation with the HOMA index (p < 0.001; rho = 0.683). The median insulin value correlates with high triglyceride (p < 0.001; rho = 0.266) and triiodothyronine values (p = 0.003; rho = 0.193) and with low HDL values (p < 0.001; rho = −0.272). In clinical practice the interpretation of laboratory and anthropometric parameters could predict the level of insulin, highlighting also a possible underlying diagnosis of insulin resistance and/or hyperinsulinemia without performing an OGTT. [ABSTRACT FROM AUTHOR]

Introduction: Algorithm‐enabled remote patient monitoring (RPM) programs pose novel operational challenges. For clinics developing and deploying such programs, no standardized model is available to ensure capacity sufficient for timely access to care. We developed a flexible model and interactive dashboard of capacity planning for whole‐population RPM‐based care for T1D. Methods: Data were gathered from a weekly RPM program for 277 paediatric patients with T1D at a paediatric academic medical centre. Through the analysis of 2 years of observational operational data and iterative interviews with the care team, we identified the primary operational, population, and workforce metrics that drive demand for care providers. Based on these metrics, an interactive model was designed to facilitate capacity planning and deployed as a dashboard. Results: The primary population‐level drivers of demand are the number of patients in the program, the rate at which patients enrol and graduate from the program, and the average frequency at which patients require a review of their data. The primary modifiable clinic‐level drivers of capacity are the number of care providers, the time required to review patient data and contact a patient, and the number of hours each provider allocates to the program each week. At the institution studied, the model identified a variety of practical operational approaches to better match the demand for patient care. Conclusion: We designed a generalizable, systematic model for capacity planning for a paediatric endocrinology clinic providing RPM for T1D. We deployed this model as an interactive dashboard and used it to facilitate expansion of a novel care program (4 T Study) for newly diagnosed patients with T1D. This model may facilitate the systematic design of RPM‐based care programs. [ABSTRACT FROM AUTHOR]

Testicular adrenal rest tumors (TARTs) are a common complication in male patients with congenital adrenal hyperplasia (CAH). The aim of our cross-sectional cohort study is to estimate the frequency of TARTs with the correlation of genotype and disease control on tumor development. Thirty-five male patients, aged 14–26 years, were included in the study, all followed by the same center of pediatric endocrinology in Bologna. We studied genotypes, hormonal profiles at different time intervals and testicular ultrasound. A logistic regression model with multivariant analysis was developed for the statistical analysis. TARTs were detected in 31.4% of the cases, 90.9% of them had a classic form with salt wasting, while 9.1% had a non-classic form. Additionally, a significant correlation between the incidence of TARTs and severity of genotype was detected. Patients with TARTs had markedly worse metabolic control on average (p = 0.027), reflected by high ACTH, 17OH progesterone, and overall delta4-androstenedione. In conclusion, a screening tool is mandatory, especially (but not exclusively) in patients with the most severe forms of CAH and poor endocrine control of the disease. [ABSTRACT FROM AUTHOR]

Introduction: Pure androgen-secreting adrenocortical tumors are a rare but important cause of peripheral precocious puberty. Case presentation: Here, we report a pure androgen-secreting adrenocortical tumor in a 2.5-year-old boy presenting with penile enlargement, pubic hair, frequent erections, and rapid linear growth. We confirmed the diagnosis through laboratory tests, medical imaging, and histology. Furthermore, genetic testing detected a pathogenic germline variant in the TP53 gene, molecularly confirming underlying Li–Fraumeni syndrome. Discussion: Only 15 well-documented cases of pure androgen-secreting adrenocortical tumors have been reported so far. No clinical or imaging signs were identified to differentiate adenomas from carcinomas, and no other cases of Li–Fraumeni syndrome were diagnosed in the four patients that underwent genetic testing. However, diagnosing Li–Fraumeni syndrome is important as it implies a need for intensive tumor surveillance and avoidance of ionizing radiation. Conclusion: In this article, we emphasize the need to screen for TP53 gene variants in children with androgen-producing adrenal adenomas and report an association with arterial hypertension. [ABSTRACT FROM AUTHOR]

Background: The present study aimed to examine the association between the conditioning intensity and height growth in pediatric patients who underwent allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Methods: We reviewed the clinical records of 89 children with malignant diseases who underwent initial allo‐HSCT between 2003 and 2021. Height measurements were standardized using standard height charts prepared by the Japanese Society for Pediatric Endocrinology to calculate standard deviation score (SDS). We defined short stature as a height SDS less than −2.0 in that reference. Myeloablative conditioning (MAC) comprised total‐body irradiation at more than 8 Gy and busulfan administration at more than 8 mg/kg (more than 280 mg/m2). Other conditioning regimens were defined as reduced intensity conditioning (RIC). Results: A total of 58 patients underwent allo‐HSCT with MAC, and 31 patients received allo‐HSCT with RIC. There were significant differences in the height SDS at 2 and 3 years after allo‐HSCT between MAC and RIC group (−1.33 ± 1.20 vs. −0.76 ± 1.12, p = 0.047, −1.55 ± 1.28 vs. −0.75 ± 1.11, p = 0.022, respectively). Multivariate logistic regression analysis with the adjustments for potential confounding factors of patients less than 10 years of age at allo‐HSCT and chronic graft‐versus host disease demonstrated that MAC regimen was associated with a markedly increased risk of a short stature at 3 years after allo‐HSCT (adjusted odds ratio, 5.61; 95% confidence interval, 1.07–29.4; p = 0.041). Conclusion: The intensity of conditioning regimen may be associated with short statures after allo‐HSCT. [ABSTRACT FROM AUTHOR]

IntroductionThe standard of care for pediatric growth hormone deficiency (pGHD) is once-daily recombinant human growth hormone (rhGH). Somatrogon, a long-acting rhGH, requires less frequent, once-weekly, dosing. We describe physicians’ preference for, experiences, and satisfaction with once-weekly somatrogon vs once-daily rhGH.MethodsEnglish-speaking investigators from somatrogon’s global phase III study (NCT02968004) with prior experience using once-daily rhGH were included. Participants answered an online survey containing 14 closed- and open-ended items.ResultsTwenty-four pediatric endocrinologists (41.7% men; 79.2% practiced at public/private hospitals) from 12 countries with 25.8 ± 12.0 years’ experience treating pGHD completed the survey. In terms of the time and effort required to explain device instructions, injection regimen, procedure for missed injection, and address patients’/caregivers’ concerns, a similar proportion of physicians chose once-weekly somatrogon and once-daily rhGH; 62.5% physicians indicated that once-daily rhGH required greater effort to monitor adherence. Overall, 75% preferred once-weekly somatrogon over once-daily rhGH, 79.2% considered once-weekly somatrogon to be more convenient and less burdensome, and 83.3% were likely to prescribe somatrogon in the future. Overall, 50% felt that once-weekly somatrogon was more beneficial to patients, while 50% chose “No difference”. Most physicians (62.5%) felt both regimens were equally likely to support positive long-term growth outcomes and reduce healthcare utilization. More physicians were “very satisfied” with once-weekly somatrogon (62.5%) than with once-daily rhGH (16.7%). Reduced injection frequency, patient and caregiver burden, increased convenience, and improved adherence were reasons for these choices.ConclusionPhysicians had a positive experience with, and perception of, treating pGHD with once-weekly somatrogon.

Introduction: This study aimed to compare the paediatric endocrinology curriculum across Southern Nigeria medical schools, using reports from learners. It also checked the learners' perceptions about different learning patterns and competency in some expected core skills. Methods: This mixed (quantitative and qualitative) study was conducted with 7 medical schools in Southern Nigeria. A multi- staged randomized selection of schools and respondents, was adopted for a focus group discussion (FGD), and the information derived was used to develop a semi-structured questionnaire, which 314 doctors submitted. The FGD discussed rotation patterns, completion rates of topics and perceptions for some skills. These themes were included in the forms for general survey, and Likert scale was used to assess competency in skills. Data generated was analysed using statistical package for social sciences, SPSS 24, and p values < 0.05 were considered significant. Results: Lectures and topics had various completion rates, 42.6% - 98%, highest being "diabetes mellitus". Endocrinology rotation was completed by 58.6% of respondents, and 58 -- 78 % perceived competency in growth measurement and charting. Significantly more learners, 46.6% who had staggered posting got correct matching of Tanner staging, versus learners who had block posting, 33.3%, p = 0.018. Conclusion: Respondents reported high variability in the implementation of the recommended guidelines for paediatric endocrinology curriculum between schools in Southern Nigeria. Variabilities were in the courses' completion, learners' skills exposure and how much hands-on were allowed in various skills acquisitions. This variability will hamper the core objectives of human capital development should the trend continue. [ABSTRACT FROM AUTHOR]

Introduction: Narcolepsy Type 1 (NT1) is a rare hypersomnia of central origin linked to hypocretin deficiency, most frequently arising at pediatric age. NT1 could be associated with endocrine comorbidities involving the neuroendocrine axis, predominantly obesity, and Central Precocious Puberty (CPP). The primary aim of this study is the evaluation of endocrine and auxological parameters at diagnosis and during follow-up in patients with NT1, treated with Sodium Oxybate (SO) or not. Methods: We retrospectively evaluated the auxological, biochemical, and radiological parameters of 112 patients referred to our Center between 2004-2022. The design of our study is cross-sectional at the time of diagnosis followed by a longitudinal follow-up. Results: Our study confirms an increased frequency of CPP and obesity in patients with NT1. At first evaluation, obesity was found in 31.3% of patients, while overweight was found in 25.0%. A diagnosis of CPP was made in 19.6% of patients. Interestingly, this group showed a significantly lower level of CSF-hypocretin (hrct-1) at diagnosis compared to others. We found an improvement in BMI SDS in the SO-treated group compared to untreated patients, and this trend persisted also at 36 months of follow-up (0.0 ± 1.3 vs 1.3 ± 0.4; p<0.03). Sixty-three patients reached their final height, with a median SDS of 0.6 ± 1.1 in boys and 0.2 ± 1.2 in girls. Discussion: To our knowledge, these are the first results regarding the final height in a large series of pediatric patients with NT1, with a normal range of IGF1-SDS levels and stature SDS. [ABSTRACT FROM AUTHOR]

Purpose: Intravenous gonadotropin-releasing hormone (IV GnRH) testing is the gold standard for confirming a central precocious puberty (CPP) diagnosis. However, this test is not widely available commercially. Therefore, our study aim was to establish cutoff values for basal gonadotropin level and gonadotrophin responses to a 100-µg subcutaneous IV GnRH test that can distinguish between CPP and premature thelarche (PT) to discover a simple method to detect CPP. Methods: Girls between the ages of 6 and 8 years who attended the pediatric endocrinology outpatient clinic at our tertiary hospital between 2019 and 2022 were included in this study. They were evaluated for breast development, and a subcutaneous 100-µg GnRH test was administered by measuring the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in blood samples at baseline and then 30, 60, 90, and 120 minutes after injection. CPP is characterized by increased height velocity, advanced bone age, and progression of breast development. The cutoff value for diagnosis of CPP was determined using a receiver operating characteristic (ROC) analysis. Results: In 86 Thai girls (56 with CPP and 30 with PT), the ROC analysis showed 71.4% and 100% sensitivity and specificity, respectively, for basal LH (cutoff = 0.2 IU/L) plus the basal LH/FSH ratio (cutoff = 0.1). The optimal cutoff values for peak LH (cutoff = 7 IU/L) demonstrated a sensitivity of 94.6% and a specificity of 100%, whereas the LH value at 30 and 60 minutes after injection (cutoff = 6 IU/L) demonstrated sensitivities of 92.9% and 94.6% and a specificity of 100%, respectively. Conclusion: Combining the basal LH (cutoff: 0.2 IU/L) and the basal LH/FSH ratio (cutoff: 0.1) can easily and cost-effectively diagnose CPP in a girl in breast Tanner stage II. [ABSTRACT FROM AUTHOR]

Background—Central precocious puberty (CPP) is characterized by clinical, biochemical, and radiological features similar to those of normal puberty, but CPP occurs before the age of eight in girls and before the age of nine in boys, subsequently leading to a reduction in the final body height in adulthood due to premature fusion of growth plates. The diagnosis of CPP is confirmed with a gonadotropin-releasing hormone (GnRH) stimulation test, which can lead to different interpretations because the diagnostic peak levels of luteinizing hormone (LH) can vary. Patients and methods—This was a single-center, retrospective observational study investigating the possible correlation between gonadotropin peaks on the GnRH test and auxological, metabolic, and radiological parameters of patients evaluated for CPP. We collected and analyzed data from the medical records of children with suspected CPP over a period from January 2019 to July 2022 who underwent a GnRH test at the Fondazione Policlinico Universitario Agostino Gemelli in Rome, Italy. Results—Our correlation analysis revealed no statistically significant differences in any auxological and radiological parameters. Among laboratory parameters, baseline levels of LH, follicle-stimulating hormone, sex hormone-binding globulin, and 17-beta estradiol were higher in children with a definitive diagnosis of CPP than in those with a negative GnRH test. In particular, the levels of LH at baseline and after the GnRH test were statistically significant in the group of CPP patients, consistent with the interpretation of the test. In the multivariate analysis, using a cut-off value of 4.1 IU/L, LH peaks showed both very high sensitivity (94%) and very high specificity (95%); all other variables showed high specificity (90%) but unsatisfactory sensitivity. Conclusion—Basal hormone dosages and, especially, basal levels of LH should be considered before performing a GnRH test as they might anticipate the final diagnosis of CPP. [ABSTRACT FROM AUTHOR]

Background: Short children born small for gestational age (SGA) often have low muscle mass. Studies on maximal isometric grip-force (MIGF) observed lower muscle strength in these children. In contrast to MIGF, jumping is an everyday muscle activity for children. Our hypothesis was that GH treatment would cause an increase in jumping strength. So, we aimed to study jumping by mechanography in short SGA children before and during GH treatment. Methods: Monocentric prospective longitudinal study in a tertiary pediatric endocrinology center. We studied 50 prepubertal short children (23 females) born SGA (mean age 7.2 y, height -3.24 SDS) during GH treatment (mean dose 45 µg/kg/d). Main outcome measures were Peak jump force (PJF) and peak jump power (PJP) measured by Leonardo® ground reaction force plate at baseline and after 12 months of GH treatment. Mechanography data were compared to sex, age and height related references (SD-Score). Fitness was estimated as PJP/kg body weight by use of the Esslinger-Fitness-Index (EFI). Results: At start of GH treatment PJP/body weight was low at -1.52 SDS and increased significantly to -0.95 SDS during 12 months of treatment (p<0.001). PJF was low-normal compared to height dependent references and remained unchanged. PJP was normal compared to height dependent references and increased only slightly from -0.34 to -0.19 SDSHT. Conclusions: Jumping performance (EFI) measured by mechanography increased during one year of GH treatment in short children born SGA. [ABSTRACT FROM AUTHOR]

INTRODUCTION: While pediatricians should receive training in the care of transgender youth, a paucity of formal educational curricula have been developed to train learners to care for this vulnerable population. METHODS: We developed a curriculum including six online modules and an in-person afternoon session observing clinic visits in a pediatric gender clinic. Learners-fourth-year medical students, interns, and nurse practitioner trainees-received protected time during an adolescent medicine rotation to complete the online modules (total duration: 77 minutes). For 20 learners, we assessed the impact of the entire curriculum-online modules and in-person observation-on self-perceived knowledge of considerations for transgender youth. For 31 learners, we assessed the effect of the online modules alone on knowledge and self-efficacy. Descriptive analyses illustrated changes in educational domains by learner group. RESULTS: On evaluations of the entire curriculum (modules and observation), median self-perceived knowledge scores (1 = not at all knowledgeable/aware, 5 = extremely knowledgeable/aware) increased within learner groups: pediatric interns (from 2.3 to 4.0), nurse practitioner trainees (from 2.9 to 4.7), fourth-year medical students (from 3.3 to 4.9), and psychiatry interns (from 2.8 to 4.4). Assessment of learners completing only the online modules demonstrated increases in median knowledge and self-efficacy scores within learner groups. All learner groups highly valued the curriculum. DISCUSSION: Our curriculum for multidisciplinary learners in the care of transgender youth was successful and well received. Increasing learner knowledge and self-efficacy is an important step towards skill development in patient care for the transgender youth population.

IntroductionWhile pediatricians should receive training in the care of transgender youth, a paucity of formal educational curricula have been developed to train learners to care for this vulnerable population.MethodsWe developed a curriculum including six online modules and an in-person afternoon session observing clinic visits in a pediatric gender clinic. Learners-fourth-year medical students, interns, and nurse practitioner trainees-received protected time during an adolescent medicine rotation to complete the online modules (total duration: 77 minutes). For 20 learners, we assessed the impact of the entire curriculum-online modules and in-person observation-on self-perceived knowledge of considerations for transgender youth. For 31 learners, we assessed the effect of the online modules alone on knowledge and self-efficacy. Descriptive analyses illustrated changes in educational domains by learner group.ResultsOn evaluations of the entire curriculum (modules and observation), median self-perceived knowledge scores (1 = not at all knowledgeable/aware, 5 = extremely knowledgeable/aware) increased within learner groups: pediatric interns (from 2.3 to 4.0), nurse practitioner trainees (from 2.9 to 4.7), fourth-year medical students (from 3.3 to 4.9), and psychiatry interns (from 2.8 to 4.4). Assessment of learners completing only the online modules demonstrated increases in median knowledge and self-efficacy scores within learner groups. All learner groups highly valued the curriculum.DiscussionOur curriculum for multidisciplinary learners in the care of transgender youth was successful and well received. Increasing learner knowledge and self-efficacy is an important step towards skill development in patient care for the transgender youth population.

Abstract Background Caregivers of children undergoing growth hormone treatment often face stress and stigma. In this regard, family-centered approaches are increasingly considered, wherein caregivers’ mental wellbeing is taken into account to optimize children’s health-related outcomes and behaviors (e.g., treatment adherence). Here, mindfulness and parenting-based programs have been developed to support the mental wellbeing of caregivers and, in turn, promote richer interactions with the children. Nevertheless, this type of program can face drawbacks, such as the scheduling and availability of family members. Recent digital health (DH) solutions (e.g., mobile apps) are showing promising advantages as self-management support tools for improving wellbeing and behaviors related to the treatments. Although, further evidence is necessary in the field of Growth Hormone Treatment (GHt). Accordingly, this study aims to examine the usability of a mobile DH solution and the feasibility of a DH intervention designed to promote emotional and mental wellbeing of caregivers of children undergoing GHt. Methods This is a prospective mixed-methods (qualitative-quantitative) exploratory study composed of two sub-studies, including caregivers of children undergoing GHt. Sub-study one (SS1; n = 10) focuses on the usability of the DH solution (detecting potential barriers and facilitators) and an ad hoc semi-structured interview will be administered to the caregivers after using the DH solution for one month. Sub-study two (SS2; n = 55) aims to evaluate the feasibility of the DH intervention on caregivers’ perceived distress, positive affectivity, mental wellbeing, self-efficacy, together with the children’s quality of life and treatment adherence. All these parameters will be assessed via quantitative methods before and after 3-months of the DH intervention. Usability and engagement will also be assessed during and at the end of the study. Results It is expected that significant amounts of data will be captured with regards of the feasibility of the DH solution. Discussion The manuscript provides a complete protocol for a study that will include qualitative and quantitative information about, on one hand, the user-friendliness of the DH solution, and on the other, the effects on caregivers’ emotional, as well as, behavioral parameters in terms of the usability and engagement to the DH solution. The findings will contribute to the evidence planning process for the future adoption of digital health solutions for caregiver support and better health-related outcomes. Trial registration ClinicalTrials.gov, ID: NCT04812665.

Introduction: Automated bone age assessment has recently become increasingly popular. The aim of this study was to assess the agreement between automated and manual evaluation of bone age using the method according to Tanner-Whitehouse (TW3) and Greulich-Pyle (GP). Methods: We evaluated 1285 bone age scans from 1202 children (657 scans from 612 boys) by using both manual and automated (TW3 as well as GP) bone age assessment. BoneXpert software versions 2.4.5.1. (BX2) and 3.2.1. (BX3) (Visiana, Holte, Denmark) were compared with manual evaluation using root mean squared error (RMSE) analysis. Results: RMSE for BX2 was 0.57 and 0.55 years in boys and 0.72 and 0.59 years in girls, respectively for TW3 and GP. For BX3, RMSE was 0.51 and 0.68 years in boys and 0.49 and 0.52 years in girls, respectively for TW3 and GP. Sex- and agespecific analysis for BX2 identified the largest differences between manual and automated TW3 evaluation in girls between 6-7, 12-13, 13-14 and 14-15 years, with RMSE 0.88, 0.81, 0.92 and 0.84 years, respectively. The BX3 version showed better agreement with manual TW3 evaluation (RMSE 0.64, 0.45, 0.46 and 0.57). Conclusion: The latest version of the BoneXpert software provides improved and clinically sufficient agreement with manual bone age evaluation in children of both sexes compared to the previous version and may be used for routine bone age evaluation in non-selected cases in pediatric endocrinology care. [ABSTRACT FROM AUTHOR]

Worldwide regulations during COVID-19 positively and negatively impacted self-management in paediatric patients with chronic medical conditions. We investigated the impact of regulations on adherence to recombinant human growth hormone (r-hGH) therapy in paediatric patients with growth disorders, using real-world adherence data extracted March 2019–February 2020 (before COVID-19) and March 2020–February 2021 (during COVID-19) from the easypod™ connect ecosystem. Data from three measures of regulations were analysed: stringency index (SI), school closure and stay-at-home. The mean SI, and the proportion of days with required school closure or stay-at-home during COVID-19 were categorised as high versus medium/low based on the 75th percentile. Adherence was categorised as optimal (≥85%) versus suboptimal (<85%). Adherence data were available for 8915 patients before and 7606 patients during COVID-19. A high SI (mean ≥68) and a high proportion of required school closure (≥88%) resulted in an increase in the proportion of optimal adherence during COVID-19 versus pre-COVID-19 (p < 0.001). Stay-at-home requirements showed no statistically significant effect (p = 0.13). Stringent COVID-19 regulations resulted in improved adherence to r-hGH therapy in patients with growth disorders, supported by connected digital health technologies. Insights into patient behavior during this time are useful to understand potential influences and strategies to improve long-term adherence to r-hGH. [ABSTRACT FROM AUTHOR]

Background: Several studies have evaluated the role of IGF-1 in the diagnosis of growth hormone deficiency (GHD). According to a recent study, an IGF-1 concentration of a −1.5 standard deviation score (SDS) appeared to be the best cut-off for distinguishing between children with GHD and normal children. This value should always be interpreted in conjunction with other clinical and biochemical parameters for the diagnosis of GHD, since both stimulation tests and IGF-1 assays have poor diagnostic accuracy by themselves. Our study was designed to evaluate the adult height (AH) in children with short stature and baseline IGF-1 concentration ≤ −1.5 SDS. Design: This retrospective analysis included 52 children and adolescents evaluated over the last 30 years for short stature and/or deceleration of the growth rate who underwent diagnostic procedures to evaluate a possible GHD. Only the patients who had baseline IGF-1 values ≤ −1.5 SDS at the time of the first test were included in the study. Patients with genetic/organic GHD or underlying diseases were not included. Method: The case group consisted of 24 patients (13 boys and 11 girls) with non-permanent, idiopathic, and isolated GHD (peak GH < 10 μg/L after two provocative tests with arginine (Arg), insulin tolerance test (ITT), and clonidine (Clo), or <20 μg/L after GHRH + Arginine (GHRH+Arg); normal MRI; normal GH; and/or normal IGF-1 concentrations at near-AH). These patients were treated with GH (25–35 μg/kg/die) until near-AH. The control group consisted of 28 patients (23 boys and 5 girls) with idiopathic short stature (ISS, normal peak GH after provocative testing, no evidence of other causes for their shortness). Both groups had basal IGF-1 ≤−1.5 SDS. Results: AH and height gain in both groups were comparable. In the group of cases, mean IGF-1 SDS at the time of diagnosis was significantly lower than the levels found at the time of retesting. Conclusions: In this study, both treated patients with idiopathic GHD and untreated patients with ISS reached similar near-AHs (within target height) and showed similar increases in SDS for their height. Thus, the efficacy of treatment with rhGH in these patients may be questionable. This could be due to the fact that children with ISS are frequently misdiagnosed with GHD. [ABSTRACT FROM AUTHOR]

X-linked hypophosphatemia (XLH) is a rare type of hereditary hypophosphatemic rickets. Patients with XLH have various symptoms that lower their QOL as defined by HAQ, RAPID3, SF36-PCS, and SF36-MCS in adult patients and SF-10 and PDCOI in pediatric patients. Early diagnosis and treatment are needed to reduce the burden, but the condition is often diagnosed late in childhood. The present review aims to summarize the symptoms, radiological and biological characteristics, and long-term prognosis of pediatric XLH. Typical symptoms of XLH are lower leg deformities (age six months or later), growth impairment (first year of life or later), and delayed gross motor development with progressive lower limb deformities (second year of life or later). Other symptoms include dental abscess, bone pain, hearing impairment, and Chiari type 1 malformation. Critical, radiological findings of rickets are metaphyseal widening, cupping, and fraying, which tend to occur in the load-bearing bones. The Rickets Severity Score, validated for XLH, is useful for assessing the severity of rickets. The biochemical features of XLH include elevated FGF23, hypophosphatemia, low 1,25(OH)2D, and elevated urine phosphate. Renal phosphate wasting can be assessed using the tubular maximum reabsorption of phosphate per glomerular filtration rate (TmP/GFR), which yields low values in patients with XLH. XLH should be diagnosed early because the multisystem symptoms often worsen over time. The present review aims to help physicians diagnose XLH at an early stage. [ABSTRACT FROM AUTHOR]

Short stature is a common concern for physicians caring for children. In traditional investigations, about 70% of children are healthy, without producing clinical and laboratory findings that justify their growth disorder, being classified as having constitutional short stature or idiopathic short stature (ISS). In such scenarios, the genetic approach has emerged as a great potential method to understand ISS. Over the last 30 years, several genes have been identified as being responsible for isolated short stature, with almost all of them being inherited in an autosomal-dominant pattern. Most of these defects are in genes related to the growth plate, followed by genes related to the growth hormone (GH)–insulin-like growth factor 1 (IGF1) axis and RAS-MAPK pathway. These patients usually do not have a specific phenotype, which hinders the use of a candidate gene approach. Through multigene sequencing analyses, it has been possible to provide an answer for short stature in 10–30% of these cases, with great impacts on treatment and follow-up, allowing the application of the concept of precision medicine in patients with ISS. This review highlights the historic aspects and provides an update on the monogenic causes of idiopathic short stature and suggests what to expect from genomic investigations in this field. [ABSTRACT FROM AUTHOR]