Patcharin Khlairit

Subcutaneous gonadotropin-releasing hormone agonist (triptorelin) test for diagnosing precocious puberty.

Background: A test involving 100 μg of intravenous gonadotropin-releasing hormone (GnRH) is a gold standard for confirming the diagnosis of central precocious puberty (CPP). However, intravenous GnRH for testing is commercially limited. Objective: To develop subcutaneous GnRH agonist (GnRH-A) testing and define a peak luteinizing hormone (LH) cutoff value in diagnosing CPP. Methods: A retrospective study of 101 girls with sexual precocity was undertaken. All girls underwent 100 μg subcutaneous GnRH-A (triptorelin) testing. Blood samples before and 30, 60, 90 and 120 min after GnRH-A injection were analyzed for LH and follicle-stimulating hormone levels. Criteria for diagnosing CPP include accelerated height, advanced bone age and pubertal-sized uterus and ovaries. Results: Fifty-five girls were documented as having CPP. The remaining 46 girls were diagnosed with premature thelarche (PT). Peak LH concentration in the CPP group was significantly greater than that of the PT group with a median (range) of 10.0 IU/l (2.93–65.39) and 3.04 IU/l (0.19–8.82), respectively. Peak LH was achieved within 60 min following GnRH-A injection. Peak LH of 6 IU/l provided the most appropriate cutoff level in diagnosing CPP with a sensitivity of 89.1% and a specificity of 91.3%. Conclusion: Subcutaneous GnRH-A can be used as an alternative to confirm the diagnosis of CPP.

Effects of correction of vitamin D insufficiency on serum osteocalcin and glucose metabolism in obese children

Osteocalcin (OCN) and vitamin D insufficiency (VDI) have been shown to be associated with abnormal glucose metabolism (GluMet). Whether correction of VDI affects serum OCN is unknown. This study evaluated the effects of correction of VDI on OCN and GluMet, and determined the associations of OCN with 25‐hydroxyvitamin D (25‐OHD) and GluMet.

Acute Effects of Blood Transfusion on Growth Hormone and Insulin-Like Growth Factor-1 Levels in Children with Thalassemia

Background/Aim: Children with β-thalassemia have chronic anemia and growth retardation. Impaired growth hormone (GH)-insulin-like growth factor-1 (IGF-1) axis function has been demonstrated. Growth improvement has been demonstrated following optimal blood transfusion. Whether correction of anemia by blood transfusion augments GH-IGF-1 axis function has not been established. Methods: Twenty children with thalassemia aged 11.7 years (5.3–16.3 years) were recruited. GH provocative tests were performed twice, before and 1 week after blood transfusion. IGF-1, IGF-binding protein-3 (IGFBP-3) and hematocrit were measured. Results: Median IGF-1 and IGFBP-3 concentrations were significantly increased at 1 week following transfusion: pre- versus posttransfused concentrations: 86.4 versus 143.5 ng/ml (p < 0.001) and 2.95 versus 3.75 mg/l (p < 0.001), respectively. However, median peak GH levels and areas under the curve of GH during GH testing between pre- and posttransfusion periods were not different. The pretransfused hematocrit level was correlated with pretransfused IGF-1 (r = 0.662, p < 0.001) and IGFBP-3 (r = 0.691, p < 0.001) levels. Conclusions: In thalassemics, correction of anemia by blood transfusion rapidly enhanced GH-mediated IGF-1 and IGFBP-3 secretion. This suggests thatanemia may be one of the factors causing partial GH insensitivity.

Gonadal function of beta-thalassemics following stem cell transplantation conditioned with myeloablative and reduced intensity regimens.

Abstract Gonadal dysfunction is a complication following stem cell transplantation (SCT). There have been no reports of gonadal function in stem-cell-transplanted thalassemic survivors who received a reduced intensity conditioning regimen (RIC). We evaluated gonadal function in 47 β-thalassemic patients following SCT with either myeloablative or reduced intensity regimen. Thirty-six patients received a myeloablative regimen, the remaining 11 patients had an RIC regimen. Their median (range) age was 13.2 (5.9–25.8) years. There were 29 patients (62%) with gonadal dysfunction (26 with primary gonadal dysfunction and three with gonadotropin deficiency). Comparisons between patients who received myeloablative and RIC regimens, revealed no differences in gonadal dysfunction (56% vs. 82%, p=0.113, respectively). In conclusion, our study demonstrated high frequency of gonadal dysfunction in these patients. Even after receiving RIC, gonadal dysfunction was very common. To our knowledge, this study is the first to report gonadal function in children and adolescents with β-thalassemia disease who were pre-transplanted with RIC.

Under-recognized Hypoparathyroidism in Thalassemia

Objective: Symptomatic hypoparathyroidism [symptomatic hypocalcemia without elevated serum parathyroid hormone (PTH)] in patients with thalassemia is relatively rare. Asymptomatic mild hypocalcemia without elevated PTH, which is considered hypoparathyroidism, may be more common but under-recognized. Methods: Sixty-six transfusion-dependent thalassemic patients and 28 healthy controls were enrolled. Serum calcium (Ca), phosphate (P), creatinine (Cr), albumin, intact PTH, 25-hydroxyvitamin D (25-OHD), plasma intact fibroblast growth factor-23 (FGF-23), urinary Ca, P and Cr were measured. Tubular reabsorption of P was calculated. Results: Thalassemic patients had significantly lower median serum Ca levels than the controls [8.7 (7.8-9.7) vs 9.6 (8.7-10.1) mg/dL, p<0.001]. Hypoparathyroidism was found in 25 of 66 (38%) patients. Symptomatic hypoparathyroidism was not encountered. Thalassemic patients also had significantly lower median plasma FGF-23 levels than the controls [35.7 (2.1-242.8) vs 53.2 (13.3-218.6) pg/mL, p=0.01]. In patients with hypoparathyroidism, median plasma FGF-23 level was significantly lower than that of normoparathyroid patients [34.8 (2.1-120.0) vs 43.1 (3.2-242.8) pg/mL, p=0.048]. However, serum P, Cr, intact PTH and 25-OHD levels were not significantly different in the two groups. Conclusion: Hypoparathyroidism was not uncommon in patients with transfusion-dependent thalassemia treated with suboptimal iron chelation. Plasma intact FGF-23 level in hypoparathyroid patients was lower than that of normoparathyroid patients.

Skewed X Chromosome Inactivation in Girls and Female Adolescents with Autoimmune Thyroid Disease.

Skewed X chromosome inactivation (XCI) was associated with female predominance in adult autoimmune thyroid disease (ATD). In normal females, skewed XCI is increased with age. Whether early‐onset skewed XCI is associated with childhood ATD remains unknown. This study aimed to determine XCI skewing in paediatric ATD.

Acute Effects of Blood Transfusion on Insulin Sensitivity and beta-Cell Function in Children with beta-Thalassemia / HbE Disease

Objective: To assess the acute effects of blood transfusion on insulin sensitivity and pancreatic β-cell function in thalassemia patients. Methods: Fifty children and adolescents with β-thalassemia/HbE disease were enrolled in a prospective cohort study. Hemoglobin, serum ferritin and oral glucose tolerance test (OGTT) were performed prior to, and one week after blood transfusion. Insulin sensitivity indices [homeostatic model assessment (HOMA) of insulin resistance (HOMA-IR), whole body insulin sensitivity index (WBISI)] and β-cell function indices [HOMA of β-cell function (HOMA-β), insulinogenic index (IGI), and disposition index (DI)] were calculated from glucose and insulin levels obtained during the OGTT. Results: Following blood transfusion, hemoglobin and serum ferritin increased significantly; 8.5 to 10.1 g/dL (p<0.001) and 1764 to 2160 ng/mL (p<0.001), respectively. β-Cell function indices also increased significantly [median HOMA-β: 74.3 vs. 82.7 (p=0.033); median IGI: 59.6 vs. 79.3 (p=0.003); median DI: 658 vs. 794 (p=0.01)]. However, the insulin sensitivity index (WBISI) tended to decrease and the insulin resistance index (HOMA-IR) tended to increase although this did not reach significance. Multivariate analysis showed that pre-transfusion serum ferritin was the major factor negatively associated with WBISI and positively associated with HOMA-IR, but pre-transfusion hemoglobin had no significant association with insulin sensitivity indices post-transfusion. Conclusion: This study demonstrated that acute increases in serum ferritin and hemoglobin following blood transfusion in patients with thalassemia might contribute to an increase in insulin secretion and to a trend towards increased insulin resistance.

Serum glypican 4 level in obese children and its relation to degree of obesity

Previous adult studies have demonstrated associations of serum glypican 4 (Gpc4) and obesity parameters and insulin sensitivity. However, an association of serum Gpc4 and glucose metabolism remains contradictory. Study of serum Gpc4 in obese children has not been conducted. We aimed to determine serum Gpc4 levels in obese children with various degrees of obesity.

Effect of Iron Chelation Therapy on Glucose Metabolism in Non-Transfusion-Dependent Thalassaemia.

Aims: To compare insulin sensitivity, β-cell function and iron status biomarkers in non-transfusion-dependent thalassaemia (NTDT) with iron excess during pre- and post-iron chelation. Methods: Subjects with NTDT, aged older than 10 years, with serum ferritin >300 ng/ml, were included. Iron chelation with deferasirox (10 mg/kg/day) was prescribed daily for 6 months. Results: Ten patients with a median age of 17.4 years were enrolled. The comparison between pre- and post-chelation demonstrated significantly lower iron load: median serum ferritin (551.4 vs. 486.2 ng/ml, p = 0.047), median TIBC (211.5 vs. 233.5 µg/dl, p = 0.009) and median non-transferrin binding iron (5.5 vs. 1.4 µM, p = 0.005). All patients had a normal oral glucose tolerance test (OGTT) both pre- and post-chelation. However, fasting plasma glucose was significantly reduced after iron chelation (85.0 vs.79.5 mg/dl, p = 0.047). MRI revealed no significant changes of iron accumulation in the heart and liver after chelation, but there was a significantly lower iron load in the pancreas, assessed by higher T2* at post-chelation compared with pre-chelation (41.9 vs. 36.7 ms, p = 0.047). No adverse events were detected. Conclusions: A trend towards improving insulin sensitivity and β-cell function as well as a reduced pancreatic iron load was observed following 6 months of iron chelation (TCTR20160523003).