The diagnosis of growth hormone deficiency remains a judgment call – and that is good

The diagnosis of GHD still does not reflect evidence-based and generally accepted practice, and reliance on growth hormone stimulation testing (GST) leads to a high rate of false positive diagnosis of idiopathic isolated GHD (IIGHD). While searching for more definitive indicators of GHD is attractive, it should not distract from currently available steps to reduce erroneous IIGHD diagnoses. This paper describes opportunities to improve the accuracy of the GST which include: 1) meticulous selection of candidates for GST, since a low prevalence of GHD among short children in general is a major factor undermining the test’s diagnostic accuracy; 2) departure from traditional pass/fail diagnostic GH cutoffs towards, instead, formulation of diagnoses along a continuum that spans actual GHD -> provisional GHD -> not GHD; 3) response to the provisional diagnosis of IIGHD based on GST with additional post-test observation or alternative growth-promoting interventions rather than immediate hGH treatment; 4) re-examination and often correction of a prior IIGHD diagnosis with the onset of puberty. Modern medicine is increasingly offering diagnostic tests that aim to eliminate the need for provisional diagnoses. But a pitfall of such a “definitive” test for GHD would be the temptation to respond to its results definitively. Given the nuances, variations, and fluctuations in GH axis function over time, children evaluated for growth concerns are still best served by clinical judgment that combines thoroughness, patience, flexibility, and healthy skepticism into the diagnosis of GHD.

Most Short Children with Cystic Fibrosis Do Not Catch Up by Adulthood

Poor linear growth is common in children with cystic fibrosis (CF) and predicts pulmonary status and mortality. Growth impairment develops in infancy, prior to pulmonary decline and despite aggressive nutritional measures. We hypothesized that growth restriction during early childhood in CF is associated with reduced adult height. We used the Cystic Fibrosis Foundation (CFF) patient registry to identify CF adults between 2011 and 2015 (ages 18–19 y, n = 3655) and had height for age (HFA) records between ages 2 and 4 y. We found that only 26% CF adults were ≥median HFA and 25% were <10th percentile. Between 2 and 4 years, those with height < 10th percentile had increased odds of being <10th percentile in adulthood compared to children ≥ 10th percentile (OR = 7.7). Of HFA measured between the 10th and 25th percentiles at ages 2–4, 58% were <25th percentile as adults. Only 13% between the 10th and 25th percentile HFA at age 2–4 years were >50th percentile as adults. Maximum height between ages 2 and 4 highly correlated with adult height. These results demonstrate that low early childhood CF height correlates with height in adulthood. Since linear growth correlates with lung growth, identifying both risk factors and interventions for growth failure (nutritional support, confounders of clinical care, and potential endocrine involvement) could lead to improved overall health.

GH Resistance Is a Component of Idiopathic Short Stature: Implications for rhGH Therapy

Idiopathic short stature (ISS) is a term used to describe a selection of short children for whom no precise aetiology has been identified. Molecular investigations have made notable discoveries in children with ISS, thus removing them from this category. However, many, if not the majority of children referred with short stature, are designated ISS. Our interest in defects of GH action, i.e. GH resistance, has led to a study of children with mild GH resistance, who we believe can be mis-categorised as ISS leading to potential inappropriate management. Approval of ISS by the FDA for hGH therapy has resulted in many short children receiving this treatment. The results are extremely variable. It is therefore important to correctly assess and investigate all ISS subjects in order to identify those with mild but unequivocal GH resistance, as in cases of PAPP-A2 deficiency. The correct identification of GH resistance defects will direct therapy towards rhIGF-I rather than rhGH. This example illustrates the importance of recognition of GH resistance among the very large number patients referred with short stature who are labelled as ‘ISS’.

Increased Knowledge of Pregnant Women about the Importance of Micro Minerals (Fe) During Pregnancy

Micro minerals (Fe) are indispensable for every woman, especially during pregnancy. The need for micro minerals (Fe) increases with increasing gestational age. Micro minerals (Fe) are not only important for pregnant women, they are also important for babies in the womb. Deficiency of micro minerals (Fe) can increase the risk of giving birth to babies with low body weight or premature birth and even maternal and infant mortality. If the baby is born with a normal weight, but there is still the possibility of stunting (short children). The purpose of this community service is to increase the knowledge of pregnant women about the importance of consuming micro minerals (Fe) during pregnancy. Knowledge of pregnant women in Sungai Rengit Murni village about the consumption of micro minerals (Fe) can be said to be quite good, reaching 70% of the total number of pregnant women (statement of regional midwives). We hope that as a servant, with this community service program, it is hoped that the knowledge of pregnant women about the importance of consuming micro minerals (Fe) during pregnancy will increase. So that the risk that will occur to the mother and baby is reduced. In addition, the service also supports government programs in reducing maternal problems during pregnancy until delivery.

Accelerated pubertal onset in short children with delayed bone age

Objectives Constitutional delay of growth (CDG) is usually associated with a delay in pubertal onset (CDGP) and a catch-up growth after puberty. Some individuals, however, have earlier-than-expected pubertal onset resulting in a shorter adult height. We investigated the current incidence of such individuals and that of 30 years ago. Methods The study subjects are 1,312 consecutive Japanese children referred to Osaka City General Hospital (OCGH) for short stature during 2010–2018, and a cohort of 11,256 individuals in the Ogi Growth Research (OGR, 1979–1992). Individuals with the height standard deviation score <−1.0, the bone age (BA)/chronological age (CA) ratio <0.8 at first visits, and without other identifiable causes of short stature were extracted from the record of OCGH. Similarly, individuals meeting the height and bone age criteria were extracted from the OGR record. The pubertal growth onset was auxologically determined as the upward shift from the prepubertal growth curve fitted to a quadratic function. Earlier-than-expected onset was defined as the onset earlier than the population average +1 year. Results From the OCGH cohort, 55 children (38 boys, 17 girls) met the criteria, and earlier-than-expected onset was observed in 34.2% of boys and 29.4% of girls. In the 73 short individuals with delayed bone age in the OGR cohort, earlier-than-expected onset was less common (13.0% for boys and 14.8% for girls). There was no significant association between the timing of pubertal growth onset and the BA/CA ratio, IGF-1, and midparental height. Conclusions Earlier-than-expected pubertal growth onset is common in CDG and possibly increasing.

Mengawal Tumbuh Kembang Balita dengan Optimalisasi Stimulasi Perkembangan Masa Usia Dini di Masa Pandemi Covid-19

Monitoring of growth and development is an activity to detect early growth irregularities (malnutrition or poor nutritional status, short children), developmental deviations (late speaking), and mental emotional disorders (impaired concentration and hyperactivity). The rapid growth and development in the first 1,000 days of life makes monitoring of child development very important at this age. The first 1,000 days of life are counted from the time of conception in the mother's womb until the child is 2 years old. In children aged 2 years, the height has reached half of the adult's height and the brain development has reached 80% of the adult brain. Since March 2020, Indonesia has been hit by the COVID-19 pandemic. This resulted in the temporary suspension of posyandu activities in various regions in Indonesia. Fears of a pandemic condition make parents afraid to bring toddlers to clinics and puskesmas. One of the easiest steps for mothers and caregivers to take to stimulate the growth and development of toddlers at home is baby massage. Solutions and targets The outputs offered in this activity are growth and development stimulation education, infant massage demonstrations, and assistance to mothers of toddlers for infant massage for 2x a month. The output targets are publication of articles in the journal Community Service, print media publications, and increasing community empowerment and strengthening knowledge and developing community habits in healthy behavior

MORINGA OLEIFERASEBAGAI MAKANAN PENDAMPING ASI PADA BALITA STUNTING

Specific nutrition intervention efforts for short children under five are focused on the 1,000 First Day of Life (HPK) group. Consuming Moringa Oliferadi Polewali Mandar Regency is one of the efforts taken to accelerate the growth and development of toddlers because it is found in abundance of nutrients, such as: vitamin A, vitamin C, calcium, and iron. This research is expected to be an alternative for families with stunting toddlers in order to provide adequate nutritional intake by utilizing Moringa Olifera. This research uses a Quasi Experimental design, which is an experiment that has treatment, impact measurement, experimental units but does not use random assignments to create comparisons. in order to infer changes caused by treatment. The design used was one group pre test and post test design, which is a study by comparing the nutritional status of toddlers before the intervention and after the intervention. The results showed that the Sig. (2-tailed) both variables equal to 0.000. This value is <0.05, so it can be concluded that there is an effect of giving Moringa Oliferar powder on body weight (BW) and height (TB) of toddlers. Because of this, giving Moringa Olifera powder, can increase BW and TB in toddlers.

New Horizons in Short Children Born Small for Gestational Age

Children born small for gestational age (SGA) comprise a heterogeneous group due to the varied nature of the cause. Approximately 85–90% have catch-up growth within the first 4 postnatal years, while the remainder remain short. In later life, children born SGA have an increased risk to develop metabolic abnormalities, including visceral adiposity, insulin resistance, and cardiovascular problems, and may have impaired pubertal onset and growth. The third “360° European Meeting on Growth and Endocrine Disorders” in Rome, Italy, in February 2018, funded by Merck KGaA, Germany, included a session that examined aspects of short children born SGA, with three presentations followed by a discussion period, on which this report is based. Children born SGA who remain short are eligible for GH treatment, which is an approved indication. GH treatment increases linear growth and can also improve some metabolic abnormalities. After stopping GH at near-adult height, metabolic parameters normalize, but pharmacological effects on lean body mass and fat mass are lost; continued monitoring of body composition and metabolic changes may be necessary. Guidelines have been published on diagnosis and management of children with Silver-Russell syndrome, who comprise a specific group of those born SGA; these children rarely have catch-up growth and GH treatment initiation as early as possible is recommended. Early and moderate pubertal growth spurt can occur in children born SGA, including those with Silver-Russell syndrome, and reduce adult height. Treatments that delay puberty, specifically metformin and gonadotropin releasing hormone analogs in combination with GH, have been proposed, but are used off-label, currently lack replication of data, and require further studies of efficacy and safety.

The Arginine Stimulation Test Allows Rapid Diagnosis of Central Diabetes Insipidus in Children

Introduction: Water deprivation testing (H2O-dep) is usually required to distinguish between diabetes insipidus (DI) and primary polydipsia (PP) in children with polydipsia-polyuria syndrome (PP-S). The H2O-dep is challenging for children and their families. The prolonged fasting may provoke hypoglycemia and dehydration, particularly in younger children. Serum concentrations of copeptin (COP) (a surrogate marker of AVP, which is easier to measure by a robust assay), are known to increase in adults and children undergoing IV arginine (ARG) stimulation testing (ASTT). Objective: To test the hypothesis that COP levels during ASTT would differentiate between DI and PP. Methods: Serum COP responses to ARG were measured in 13 healthy short children being tested for GH deficiency (controls); and in 4 patients with PP-S. Arginine-HCl (500 mg/Kg) was infused IV from 0 to 30 min, with blood sampling at 0, 15, 30, 45, 60 min; seven of 13 controls also received clonidine PO (150 mcg/m2) at 0 min. COP was measured with a 2-site immunometric assay (BRAHMS Platform, Quest Diagnostics). Results: A-Controls. As the COP values at each time point were similar in the ARG and ARG-Clonidine controls, the data from both groups were combined. COP peaked at 45-60 min post ARG in the 13 controls. COP (Mean+SD; pMol/l)) increased from 9.7+4.3, (range 3-17) to a peak of 12.4+5.0 (range 6-21) at 60 min; Δ% increase 47+50 % (range 0-133). The peak COP values on ASTT showed no correlation with subjects’ age or peak GH response. Results B: Subjects with PP-S: On the basis of H2O-dep, MRI findings, and long-term response to desmopressin therapy, 3 of 4 children were diagnosed with central DI, and 1 with PP. Abbreviations: S[Osm], U[Osm]= serum, urine osmolality (mOsm/Kg); values obtained at the end of the H2O Dep: Subject 1. 3 y-old male, diagnosed with PP. After H2O-dep S[Osm] / U[Osm] 286 / 615. On ASTT COP (base vs. peak) 15 vs.116 pMol/l. Subject 2. 8 y-old male, diagnosed with central DI with Langerhans cell histiocytosis (LCH). MRI: absent bright spot. After H2O-dep S[Osm] / U[Osm] 318/202; On ASTT COP (base vs. peak) 2 vs. 2 pMol/l. Subject 3. 2 y-old male. diagnosed with central DI, possible LCH; MRI: absent bright spot. No H2O-dep; On ASTT COP (base vs. peak) 3 vs 3 pMol/l. Subject 4. Male, 3 y-old. Diagnosed with partial DI with LCH. MRI: absent bright spot. After H2O-dep S[Osm] / U[Osm] 297/569. On ASTT COP (base vs. peak) 5 vs. 6 pMol/l. Comment: In all DI patients, COP concentrations remained flat in the ASTT, at 2-3 pmol/L in 2 subjects with complete DI, and 5-6 pmol/L in 1 subject with partial DI. The latter response overlapped with that of 1 of 13 control subjects. Conclusions: These preliminary data support the hypothesis that ASTT is an easy, minimally invasive test, valuable for differentiating the etiology of PP-S in children. However, patients with partial DI may have low-normal COP responses at ASTT that overlap with values in normal children.