Height outcomes in Korean children with idiopathic short stature receiving growth hormone treatment.

Objectives: Growth hormone (GH) therapy's capacity to increase height velocity and height at the end of the study in children with idiopathic short stature (ISS) is controversial. We aimed to investigate the height standard deviation score (SDS) and height velocity of patients with ISS in Korea who received GH treatment. Methods: We retrospectively reviewed and performed linear mixed model and survival analyses on data from 12 tertiary hospitals in Korea, including subjects diagnosed with ISS from January 2009 to September 2019, treated with GH therapy for more than 6 months, and who were at a pre-pubertal state at the time of diagnosis. Results: We included 578 children (330 boys and 248 girls). The mean daily dose of GH in this study was 0.051 mg/kg, which was lower than the approved dose in Korea of 0.062 - 0.067 mg/kg. Height SDS was higher in patients who started treatment before the age of 6 years. The probability of reaching the target SDS (-1 SDS) from the beginning of treatment to 2-3 years after its start was higher in children starting treatment before the age of 6 years. The hazard ratio to reach the target SDS (-1 SDS) when using automatic pen or electronic devices was 1.727 times higher than that when using the needle and syringe device. Conclusion: ISS patients should start GH treatment at an early age, and even lower-than-recommended drug doses may be effective. The selection of automatic pen or electronic device can have a positive effect on reaching the target height SDS.

Investigating whether serum IGF-1 and IGFBP-3 levels reflect the height outcome in prepubertal children upon rhGH therapy: LG growth study database.

Serum insulin-like growth factor-1 (IGF-I) and IGF binding protein-3 (IGFBP-3) levels can be used to monitor the safety of recombinant human growth hormone (rhGH) therapy. In this study, we evaluated the changes in serum IGF-I and IGFBP-3 levels during rhGH therapy as a marker of height outcome in prepubertal children. Totally, 705 prepubertal children with short stature were enrolled from the LG Growth Study Database. Data for three groups of subjects were obtained as follows: Idiopathic GH deficiency (IGHD; n = 486); idiopathic short stature (n = 66); small for gestational age (n = 153). Serum IGF-I and IGFBP-3 levels at the baseline and after the 1st and 2nd year of rhGH therapy, as well as the Δheight standard deviation score (SDS), were obtained. Δheight SDS after the 1st and 2nd year of rhGH therapy had notably increased compared to that at the baseline for all three groups. IGF-I and IGFBP-3 levels in all three groups were significantly increased compared to those at the baseline (p <0.001). Δheight SDS was positively correlated with ΔIGF-1 SDS after the 1st year of therapy, ΔIGFBP-3 SDS after the 2nd year of therapy in the IGHD group, and ΔIGF-I SDS and ΔIGFBP-3 SDS after the 2nd year of therapy (p < 0.05), regardless of whether the height at the baseline was a covariate. The increase in IGF-I and IGFBP-3 levels during rhGH therapy was related to the growth response in children with IGHD. Therefore, it may be valuable to measure the change in serum IGF-I and IGFBP-3 levels, especially the latter, during rhGH treatment to predict the growth response upon long-term treatment.

The Impact of Perioperative Use of a Statin-Magnesium Combination on Opioid Consumption in Patients Who Underwent Cardiac Surgery: A Retrospective Study with Propensity-Score Matching.

Both statins and magnesium are associated with NMDA receptors and anti-inflammatory effect. Peripheral NMDA receptors are known to be involved in inflammation-induced pain. This study aimed to investigate the impact of perioperative use of a statin-magnesium combination on opioid consumption in patients who underwent cardiac surgery. This was a retrospective study of 542 patients who underwent cardiac surgery. The patients were divided into two groups according to statin use: the statin-magnesium group (n=375) and the magnesium-only group (n=167). Patients in the magnesium-only group received only perioperative magnesium, but no statins, to prevent atrial fibrillation following cardiac surgery. After propensity-score matching, 228 patients (n=114 in each group) were analyzed to investigate opioid consumption, visual analogue scale (VAS) pain scores over a 72-h period, and pain outcomes according to the duration of statin treatment (<1 or ≥1 yr). The consumed opioid volume was significantly smaller in statin-magnesium group than the magnesium-only group, both before (p=0.010) and after matching (p=0.017). The statin-magnesium combination did not significantly reduce the VAS pain scores compared with magnesium alone. Although the statin-magnesium combination did not significantly reduce the pain intensity compared with magnesium alone, the combination therapy was effective in reducing opioid consumption after surgery.

Predictive value of C-reactive protein for the diagnosis of meningitis in febrile infants under 3 months of age in the emergency department.

BACKGROUND: Fever is a common cause of pediatric consultation in the emergency department. However, identifying the source of infection in many febrile infants is challenging because of insufficient presentation of signs and symptoms. Meningitis is a critical cause of fever in infants, and its diagnosis is confirmed invasively by lumbar puncture. This study aimed to evaluate potential laboratory markers for meningitis in febrile infants. METHODS: We retrospectively analyzed infants aged <3 months who visited the emergency department of our hospital between May 2012 and May 2017 because of fever of unknown etiology. Clinical information and laboratory data were evaluated. Receiver operating characteristic (ROC) curves were constructed. RESULTS: In total, 145 febrile infants aged <3 months who underwent lumbar punctures were evaluated retrospectively. The mean C-reactive protein (CRP) level was significantly higher in the meningitis group than in the non-meningitis group, whereas the mean white blood cell count or absolute neutrophil count (ANC) did not significantly differ between groups. The area under the ROC curve (AUC) for CRP was 0.779 (95% confidence interval [CI], 0.701-0.858). The AUC for the leukocyte count was 0.455 (95% CI, 0.360-0.550) and that for ANC was 0.453 (95% CI, 0.359-0.547). The CRP cut-off value of 10 mg/L was optimal for identifying possible meningitis. CONCLUSION: CRP has an intrinsic predictive value for meningitis in febrile infants aged <3 months. Despite its invasiveness, a lumbar puncture may be recommended to diagnose meningitis in young, febrile infants with a CRP level >10 mg/L.

Prevalence of Pathological Brain Lesions in Girls with Central Precocious Puberty: Possible Overestimation?

BACKGROUND: Brain magnetic resonance imaging (MRI) is routinely performed to identify brain lesions in girls with central precocious puberty (CPP). We aimed to investigate the prevalence and type of brain lesions among Korean girls with CPP and evaluate the need for routine brain MRI examinations. METHODS: This retrospective cross-sectional study evaluated data on 3,528 girls diagnosed with CPP from April 2003 to December 2016, and identified 317 girls who underwent sellar MRI. Exclusion criteria were patients with a known brain tumor or who did not undergo brain MRI due to refusal or the decision of the pediatric endocrinologist. RESULTS: Normal sellar MRI findings were observed in 291 of the 317 girls (91.8%). Incidental findings were observed in 26 girls (8.2%). None of the patients had pathological brain lesions. CONCLUSION: The prevalence of intracranial lesions among girls who were generally healthy and without neurological symptoms but diagnosed with CPP was lower than that previously reported. Furthermore, none of the identified lesions required treatment. It may be prudent to reconsider the routine use of brain MRI to screen all patients with CPP, especially if they are healthy and neurologically asymptomatic, and are girls aged 6-8 years.

Glycated hemoglobin A1c as a screening test for detecting type 2 diabetes mellitus in obese children and adolescents.

BACKGROUND: The diagnostic cutoff points for indicators of type 2 diabetes mellitus (T2DM) in the pediatric population have not been defined thus far. METHODS: A retrospective, single-center study was conducted from April 2003 to May 2016. We enrolled 236 overweight or obese children and adolescents aged 4-17 years. Thirty-nine (26.9%) of 145 patients had T2DM according to the oral glucose tolerance test results. RESULTS: A glycated hemoglobin (HbA1c) level of 6.5% had a sensitivity and specificity of 87.2% and 98.5%, respectively, for detecting T2DM. The optimal HbA1c cutoff level for T2DM was >6.2% (94.7% sensitivity, 95.5% specificity). CONCLUSIONS: We observed that the use of an HbA1c level of 6.5% had a lower sensitivity for detecting T2DM than an HbA1c level of >6.2%.

The prevalence of brain abnormalities in boys with central precocious puberty may be overestimated.

Brain magnetic resonance imaging (MRI) is routinely performed to identify brain lesions in boys with central precocious puberty (CPP). We investigated the prevalence of CPP in Korean boys and the necessity for routine brain MRI examinations. This retrospective cross-sectional study was conducted from April 2003 to December 2016 at a Korean university hospital. Among 151 boys who were diagnosed with CPP, the data of 138 boys who underwent sellar MRI were evaluated. The mean age of the study subjects was 9.51 ± 0.56 years (<8 years [n = 4] and ≥8 years [n = 134]). We excluded patients who had been previously diagnosed with brain tumors and those who did not undergo a sellar MRI because of refusal or the decision of the pediatric endocrinologist. The main outcome measure was the prevalence of intracranial lesions among boys with CPP. Normal sellar MRI findings were observed in 128 of the 138 boys (93%). Mild brain abnormalities were found in 10 boys (7%), while none of the patients had pathological brain lesions. The prevalence (7%) of intracranial lesions among boys who were healthy, did not have neurological symptoms, and were diagnosed with CPP was different from that previously reported. None of the identified lesions necessitated treatment. Although this was a single country study, we found that the previously reported prevalence of brain lesions in boys with CPP is much higher than the prevalence observed in Korea. This study suggests the need to globally reevaluate the prevalence of pathological brain lesions among male pediatric patients with CPP.

Association of the urinary sodium to urinary specific gravity ratio with metabolic syndrome in Korean children and adolescents: The Korea National Health and Nutrition Examination Survey 2010-2013.

OBJECTIVES: This study aimed to evaluate the association between sodium intake and metabolic syndrome (MetS) in Korean boys. METHODS: A total of 1,738 boys aged 10-18 years were included in this study from the Korea National Health and Nutrition Examination Survey (KNHANES) during the years 2010-2013. Sodium intake was assessed using the urinary sodium excretion to urinary specific gravity ratio (U-Na to U-SG ratio). RESULTS: The median U-Na to U-SG ratio was 133.27 mmol/L (interquartile range: 95.66-178.50 mmol/L). Significant positive associations were found between the U-Na to U-SG ratio and the TG (P = 0.001 for trend) and TG concentrations, and these concentrations were significantly higher in boys with a U-Na to U-SG ratio in the highest quartile compared with those with a ratio in the lowest (P = 0.001) and second (P = 0.033) quartiles, as demonstrated through analysis of covariance (ANCOVA) after adjustment for possible confounders, including age, BMI standard deviation score, ferritin, vitamin D, house income, smoking, alcohol intake, physical activity, season, total intake, total energy intake, protein intake, fat intake, carbohydrate intake, and water intake. Significant inverse associations were found for the U-Na to U-SG ratio with the HDL-C (P = 0.033 for trend) and HDL-C levels, and these values were significantly lower in boys with a ratio in the highest quartile compared with those with a ratio in the second quartile (P = 0.020), as demonstrated through an ANCOVA. Although the trends did not reach statistical significance, a higher U-Na to U-SG ratio tended to be associated with higher SBP (P = 0.086 for trend), DBP (P = 0.063 for trend), and glucose levels (P = 0.099 for trend), as illustrated through ANCOVA. Boys with a ratio in the highest quartile exhibited a 1.73-fold increased risk for elevated TG (95% CI, 1.19-2.51) and a 2.66-fold increased risk for MetS (95% CI, 1.11-6.35) compared with those with a ratio in the lowest quartile, as demonstrated through multivariate logistic regression analyses after adjusting for confounders. CONCLUSIONS: Our results suggest that high sodium intake may be significantly independently associated with MetS in Korean boys aged 10-18 years.

Predictors of transient congenital hypothyroidism in children with eutopic thyroid gland.

PURPOSE: Congenital hypothyroidism (CH) is the most common cause of preventable mental retardation. Recently, the detection of CH cases with eutopic thyroid gland has increased due to neonatal screening programs. In this study, we aimed to identify and evaluate predictive factors that could distinguish between permanent and transient CH in patients with eutopic thyroid gland. METHODS: We retrospectively reviewed 100 children diagnosed with CH and with eutopic thyroid gland. All subjects were treated with levothyroxine and underwent re-evaluation after 3 years of age. RESULTS: Of the 100 CH patients, 35 (35.0%) were diagnosed with permanent CH (PCH) and 65 (65.0%) were diagnosed with transient CH (TCH). The initial thyroid stimulating hormone levels were significantly lower in the TCH subjects than in PCH subjects. In addition, the mean doses of levothyroxine (µg/kg/day) at the 1st, 2nd, and 3rd year of treatment were significantly lower in subjects with TCH than in PCH subjects with eutopic thyroid gland. Based on the receiver operating characteristic (ROC) curve, the optimal cutoff dose of levothyroxine at 3 years of 2.76 µg/kg/day could predict TCH, and was associated with 87.3% sensitivity and 67.6% specificity, with an area under the ROC curve of 0.769. CONCLUSION: The levothyroxine dose requirement during treatment period has a predictive role in differentiating TCH from PCH in CH patients with eutopic thyroid gland.

No association between estrogen receptor gene polymorphisms and premature thelarche in girls.

OBJECTIVE: Premature thelarche (PT) is a benign, nonprogressive condition defined as isolated breast development. While the pathophysiology of PT remains unclear, increased sensitivity to estrogen may cause PT. The aim of this study was to investigate the association between polymorphisms in the estrogen receptor alpha (ERα) gene and PT in girls. METHODS: In this case-control study, we examined 96 girls referred for early breast development (before the age of 8 years). The control group included healthy Korean females with normal pubertal progression. Anthropometric and hormonal parameters were measured and PvuII and XbaI ERα gene polymorphisms were evaluated by PCR. Out of the 96 girls, all coding exon and exon-intron boundaries of ERα were sequenced from the DNA of 46 girls. RESULTS: There was no significant difference in the distribution of PvuII and XbaI polymorphisms between patients and controls. However, the carriers of XbaI polymorphisms had more advanced Tanner stage than did the non-carriers. Also, four ERα gene polymorphisms were previously identified, but these polymorphisms had no clinical significance. CONCLUSION: No association was found between the ERα gene polymorphisms and PT in girls. However, XbaI polymorphisms may contribute to early breast budding.