Clinical practice guidelines for optimizing bone health in Korean children and adolescents

The Committee on Pediatric Bone Health of the Korean Society of Pediatric Endocrinology has newly developed evidence-based clinical practice guidelines for optimizing bone health in Korean children and adolescents. These guidelines present recommendations based on the Grading of Recommendations, which includes the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. These guidelines include processes of bone acquisition, definition, and evaluation of low bone mineral density (BMD), causes of osteoporosis, methods for optimizing bone health, and pharmacological treatments for enhancing BMD in children and adolescents. While these guidelines provide current evidence-based recommendations, further research is required to strengthen these guidelines.ope

Commentary on "Effect of gonadotropin-releasing hormone agonist treatment on near final height in girls with central precocious puberty and early puberty"

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The mediating effects of parenting style on the relationship between parental stress and behavioral problems in girls with precocious puberty in Korea: a cross-sectional study

Background: This study aimed to examine the mediating effects of parenting style on the relationship between parental stress and behavioral problems of girls with precocious puberty. Methods: This cross-sectional study analyzed a convenience sample of 200 mothers of girls with precocious puberty at a university hospital located in a metropolitan area. The Parental Stress measurement, Parents as Social Context Questionnaire, and Korean version Child Behavior Checklist (K-CBCL) 6-18 were measured via self-report questionnaires. Descriptive, t-test, Pearson correlation, and bootstrapping analyses were used to analyze the data. Results: Negative parenting styles had a full mediating effect on the relationship between parental stress and internalizing and externalizing behavioral problems. Conclusions: Care plans for parents of girls with precocious puberty should be designed and applied in health care settings to reduce internalizing and externalizing behavioral problems by decreasing negative parenting styles.ope

Clinical Characteristics of Hypoparathyroidism and Pseudohypoparathyroidism

PURPOSE: Insufficient production of the parathyroid hormone (PTH) by the parathyroid glands known as hypoparathyroidism, or a resistance against its action on target organs known as pseudohypoparathyroidism, cause PTH-related hypocalcemia associated with hyperphosphatemia. Signs and symptoms are caused by hypocalcemia. This study aimed to assess clinical characteristics, treatment, severity, onset time, and therapeutic responses of hypoparathyroidism and pseudohypoparathyroidism. METHODS: From January 2000 to February 2010, 21 hypoparathyroid and 10 pseudohypoparathyroid children were selected from Severance Hospital. Clinical manifestations and laboratory data were analyzed retrospectively. RESULTS: In hypoparathyroid patients, there were 14 with idiopathic hypothyroidism (66%) and 7 with 22q11.2 deletion syndrome (33%). Patients with hypoparathyroidism had more frequent neurologic symptoms compared to those with pseudohypoparathyroidism (2.89 +/- 1.75 vs. 1.25 +/- 1.67, P = 0.01). Required amounts of calcium to control hypocalcemia were larger in hypoparathyroidism than in pseudohypoparathyroidism (37.98 +/- 26.64 vs. 15.64 +/- 7.87 mg/day/kg, P = 0.034). After treatment, neurologic symptoms decreased significantly in hypoparathyroidism (P < 0.05) from 2.01 +/- 1.68 to 0.89 +/- 0.96. CONCLUSION: Hypoparathyroidism presented more severe symptoms than pseudohypoparathyroidism. Larger amounts of calcium were required to correct hypocalcemia in hypoparathyroidism than in pseudophypoparathyroidsm. These differences may be explained by the findings that distal tubules respond to PTH, in contrast to proximal tubules, in pseudohypoparathyroidism, because the GNAS gene coding is not imprinted at the distal tubular cells responsible for calcium reabsorption.ope

A novel compound heterozygous mutation of the AIRE gene in a patient with autoimmune polyendocrine syndrome type 1

Autoimmune polyendocrine syndrome type 1 (APS-1), or autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is a rare, autosomal recessive autoimmune disease caused by a mutation of the autoimmune regulator (AIRE) gene. The main symptom triad in APS-1 comprises chronic mucocutaneous candidiasis, adrenal insufficiency, and hypoparathyroidism. Various autoimmune diseases and ectodermal abnormalities are also commonly associated with the syndrome. The treatment of APS-1 includes hormone replacement and symptom control. It is important to monitor such patients for clinical manifestations of their disease through regular follow-up. We report the case of a 10-year-old Korean girl with APS-1 due to a novel compound heterozygous mutation of the AIRE gene. This patient's main clinical manifestations were adrenal insufficiency and chronic mucocutaneous candidiasis. The patient had a previously known pathogenic variant of c.1513delG (p.Ala505ProfsTer16), and a newly discovered variant of c.1360dupC (p.His454ProfsTer50).ope

Fructose-1,6-bisphosphatase deficiency presented with complex febrile convulsion

Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare inborn error of metabolism affecting gluconeogenesis caused by FBP1 gene mutations. It could be more fatal to infants and children when glycogen reserves are insufficient. A 4-year-old girl was admitted with complex febrile convulsion. Initial laboratory results showed hypoglycemia, metabolic acidosis, and hyperlactatemia. Plasma amino acid and urine organic acid analyses showed increased levels of alanine and tricarboxylic acid cycle intermediates. However, she had similar clinical features, including confusion under severe hypoglycemia, two additional times over 6 months. Correct diagnosis could not be made because of nonspecific symptoms, and mitochondrial disorder was initially suspected. Clinical exome sequencing was performed, and compound heterozygous mutations of c.960_961insG and c.490G>A (p. Ser321ValfsTer13 and p. Gly164Ser) in the FBP1 gene were identified. This is the first Korean pediatric case of FBPase deficiency that initially presented with neurologic clinical features. Despite its very low prevalence in Far-East Asian countries, FBPase deficiency should be considered in children with repeated clinical features of metabolic acidosis with hypoglycemia.ope

Sex hormone binding globulin, free estradiol index, and lipid profiles in girls with precocious puberty

Purpose: Sex hormone-binding globulin (SHBG) modulates the availability of biologically active free sex hormones. The regulatory role of SHBG might be important in the relationship between hormone levels and the modification of lipid profiles in girls with precocious puberty. However, few studies have evaluated the relationship of SHBG, free estradiol index (FEI), and lipid levels in these girls. Methods: One hundred and nine girls less than 8 years of age with pubertal development were enrolled. FEI was calculated with SHBG and estradiol (E2). We analyzed SHBG between peak luteinizing hormone (LH)≥5 (IU/L) (group 1) and LH＜5 (IU/L) (group 2) through a gonadotropin releasing hormone stimulation test. Results: Body mass index (BMI) standard deviation score (SDS) was higher in group 2 than in group 1 (P =0.004). Serum SHBG levels did not differ and FEI was not higher in group 1 (P =0.122). Serum cholesterol, HDL, and LDL did not differ; however, triglyceride levels were higher in group 2 (P =0.023). SHBG was negatively correlated with bone age advancement, BMI, BMI SDS, and FEI, and was positively correlated with HDL. However, SHBG was not correlated with E2 or peak LH. Conclusion: Serum SHBG itself might not be associated with precocious puberty in girls, but it might be related to BMI and lipid profiles. Further studies are needed to reveal the relationship between sex hormone and obesity in girls with precocious puberty.ope

A Case of Primary Focal Segmental Glomerulosclerosis in an Adolescent Patient with Type 1 Diabetes

Diabetic nephropathy is a common and serious complication in diabetic patients. Renal diseases other than diabetic nephropathy (non-diabetic nephropathy) can occur in diabetic patients with nephrosis. The presence of non-diabetic nephropathy is noted in type 2 diabetes patients, but no data exists for type 1 diabetes. In this report we describe the case of a 15-year-old girl with type 1 diabetes mellitus, who presented with an acute elevation of urinary microalbumin excretion, general edema, and liver enzyme elevation. She had shown microalbuminuria about 3 years earlier, as well as an uncontrolled hemoglobin A1c level, but she had no diabetic retinopathy and neuropathy. A renal biopsy was conducted, and she was diagnosed with primary focal segmental glomerulosclerosis. She was treated with corticosteroids and an angiotensin converting enzyme inhibitor.ope

Effect of the Orally Active Growth Hormone Secretagogue MK-677 on Somatic Growth in Rats

PURPOSE: Growth hormone secretagogues (GHSs) possess the ability to release growth hormone (GH) in the body. This study aimed to investigate the effects of MK-677, an orally active GHS, on somatic growth in rats. MATERIALS AND METHODS: The serum levels of GH were measured after oral administration of MK-677 to confirm GH stimulatory effects. Body weight, body length, tibia length, epiphyseal plate width, and serum levels of insulin-like growth factor (IGF)-I were measured after oral administration of 4 mg/kg of MK-677 for 6 weeks to investigate growth-promoting effects. RESULTS: Oral administration of MK-677 at 4 mg/kg increased peak GH concentrations by 1.8-fold, compared to baseline. However, oral administration of MK-677 for 6 weeks did not increase body growth or serum levels of IGF-I. At 6 weeks after treatment, the GH response to MK-677 was abolished. Pituitary GH mRNA and hypothalamic GH-releasing hormone mRNA, and GH secretagogue receptor (GHSR) mRNA expression in the pituitary and hypothalamus did not differ between the control and treatment group. Somatostatin (SST) mRNA expression in the hypothalamus was markedly increased in the treatment group, whereas SST receptor (SSTR)-2 mRNA expression in the pituitary gland was decreased. Protein expression of hypothalamic GHSR, SST, and pituitary SSTR-2 showed patterns similar to those for mRNA expression. CONCLUSION: Our results suggest that prolonged administration of MK-677 in rats does not promote growth despite the GH stimulatory effect of MK-677, which may be related to increased expression of SST in the hypothalamus. Further studies are needed to overcome the observed desensitization to GHS.ope

Efficacy of Growth Hormone Treatment in Patients with Noonan syndrome and Growth Hormone Deficiency

Purpose: Noonan syndrome (NS) is characterized by short stature, congenital heart defects, mild mental retardation, and characteristic faces. We investigated the efficacy of growth hormone (GH) treatment and the adverse effect compared to sex and age-matched patients with growth hormone deficiency (GHD). Methods: We included patients whose Noonan scores were over 60, treated with GH in Severance Children’s Hospital. We analyzed height and height velocity before and during GH treatment in 14 NS patients (0.81 ± 0.13 U/kg/wk) and also in 42 patients with sex- and age-matched GHD as a control group (0.78 ± 0.17 U/kg/wk) at intervals of 3 months. Results: At the start of GH treatment, mean age was 10.0 ± 2.4 years, and mean height was 123.3 ± 13.5 cm, and the height SDS was -2.79 ± 0.85 in NS, while the mean age was 10.3 ± 2.6 years, mean height was 119.6 ± 13.5 cm, and the height SDS was -3.43 ± 1.56 in GHD. Mean duration was 3.8 ± 2.1 years in NS and 4.9 ± 2.4 years in GHD. Mean height SDS increased from -2.79 SDS to -1.94 SDS in NS (P = 0.007) and from -3.43 SDS to -1.82 SDS in GHD (P ˂ 0.0001). Growth velocity increased from 3.7 ± 1.2 cm/yr to 8.5 ± 2.5 cm/yr (P ˂ 0.0001) and 6.5 ± 2.9 cm/yr (P = 0.016) during the first and second years of GH treatment, respectively, in NS and from 3.4 ± 1.5 cm/yr to 8.8 ± 2.3 cm/yr (P ˂ 0.0001) and 8.1 ± 3.2 cm/yr (P ˂ 0.0001) in GHD. No severe adverse effects were observed during treatment. Conclusion: GH treatment in the NS patients increased growth velocity significantly, especially during the 1st year of treatment. GH treatment in NS is thought to be effective and relatively safe.ope