Overdiagnosis of adrenal insufficiency in children with biliary atresia.

Serum cortisol mainly binds to the cortisol-binding globulin (CBG). Children with biliary atresia (BA) may have low serum CBG levels; thus, low serum total cortisol (TC) levels and adrenal insufficiency (AI) may be overdiagnosed. This study aimed to assess adrenal function in children with BA. All the patients underwent adrenocorticotropic hormone (ACTH) stimulation tests. Plasma ACTH, serum TC, and CBG levels were measured at baseline, with additional TC measurements at 30 and 60 min during testing. Free cortisol (FC) index (FCI) and calculated FC (cFC) were also calculated. AI was defined as peak TC <500 nmol/L (<18 µg/dL), peak FCI <12 nmol/mg, or peak cFC <33 nmol/L (<1.2 µg/dL). This study enrolled 71 children with BA. The Median (IQR) age of the patients was 5.5 (1.7-11.4) years. Twenty-five (35%) patients were diagnosed with AI based on the peak TC. In the AI group, the median serum CBG level was significantly lower than that in the non-AI group (481 vs. 533 nmol/L, p = 0.03). Only eight patients (11%) met all three AI criteria (six secondary AI and two primary AI). In conclusion, low serum CBG levels contribute to reduced peak TC and, consequently, overdiagnosing AI. Peak FCI and cFC could help reduce the overdiagnosis of AI.

Glucose metabolism in systemic juvenile idiopathic arthritis.

BACKGROUND: Systemic juvenile idiopathic arthritis (SJIA) is a chronic systemic inflammatory disease in children. Overproduction of inflammatory cytokines in SJIA resembles that in adult onset Still disease. Chronic inflammation causes insulin resistance and consequently leading to abnormal glucose metabolism. Adults with rheumatoid arthritis (RA) have increased risks of abnormal glucose metabolism and diabetes. To date, glucose metabolism in patients with SJIA has not been elucidated. METHODS: Patients with SJIA aged 4-25 years were recruited. All patients underwent an oral glucose tolerance test (OGTT). Indices of insulin sensitivity [homeostasis model assessment for insulin resistance (HOMA-IR) and whole-body insulin sensitivity index (WBISI)] and ß-cell function [insulinogenic index (IGI) and disposition index (DI)] were calculated. Obese children with normoglycemia who underwent the OGTT were served as a control group. RESULTS: A total of 39 patients with SJIA, aged 4-25 years, median (IQR) BMI SDS was 0.1 (-0.5 to 1.7). Patients were divided into 2 groups, overweight/obese (OW/OB) (n = 11) and lean (n = 28). Only one obese patient had prediabetes and none had diabetes. In comparison with sex- and age-matched OW/OB controls (n = 33), OW/OB patients with SJIA had higher insulin resistance [median (IQR) HOMA-IR: 2.6 (2.1-3.3) vs 1.5 (0.8-2.0), p = 0.001], lower insulin sensitivity [median (IQR) WBISI: 3.7 (2.7-5.9) vs 5.4 (4.5-8.7), p = 0.024], and higher insulin secretion [median (IQR) IGI: 2.5 (2.0-3.5) vs 1.0 (0.8-1.9), p = 0.001]. In lean patients with SJIA, insulin sensitivity indices seemed to be comparable with those of lean controls. CONCLUSIONS: Overweight/obese children with SJIA seemed to have increased insulin resistance and thus may have an increased risk for developing diabetes.

Beta cell function, incretin hormones, and incretin effect in obese children and adolescents with prediabetes.

BACKGROUND: Defects of incretin hormones and incretin effect may be underlying mechanisms of abnormal glucose metabolism in youth. OBJECTIVE: To assess incretin hormone dynamics during an oral glucose tolerance test (OGTT) and incretin effect in obese children with prediabetes in comparison with those with normal glucose tolerance (NGT). METHODS: Overweight and obese children were enrolled and classified according to OGTT results as NGT and prediabetes. Insulin sensitivity, insulin secretion, incretin hormone concentrations during OGTT; and incretin effect derived from OGTT and intravenous glucose tolerance test were determined and compared between NGT and prediabetes groups. RESULTS: Sixty-three patients (43 NGT and 20 prediabetes) were enrolled. Their median (interquartile range) age was 12.5 (11.1, 13.8) years. Peak glucagon-like peptide-1 (GLP-1) was demonstrated at 30 min during OGTT and was higher in the prediabetes group (49.2 [35.6, 63.6] versus 36.5 [27.6, 44.2] pmol/L, p = 0.009). However, incremental areas under the curves (iAUCs) of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) were not different between the two groups. There was no difference in incretin effect between NGT and prediabetes (NGT: 66.5% [60.2%, 77.5%] vs. prediabetes: 70.0% [61.5%, 75.0%], p = 0.645). Incretin effect had positive correlations with iAUCs of both GLP-1 and GIP (GLP-1: r = 0.40, p = 0.004 and GIP: r = 0.37, p = 0.009). CONCLUSIONS: Comparing between obese children with prediabetes and NGT, there were no differences in overall incretin hormone changes during OGTT and incretin effect. Incretin effect was positively correlated with iAUCs of GLP-1 and GIP.

Short-term effects of gonadotropin-releasing hormone analogue treatment on leptin, ghrelin and peptide YY in girls with central precocious puberty.

OBJECTIVES: To determine appetite-regulating hormone levels in girls with central precocious puberty (CPP) before and after 20 weeks of gonadotropin-releasing hormone analogue (GnRH-A) treatment. METHODS: Eighteen newly diagnosed CPP girls were enrolled. Body composition measured by bioelectrical impedance analysis and GnRH-A test were performed with fasting serum leptin, ghrelin and peptide YY (PYY) measurements at baseline (before) and after 20 weeks of GnRH-A treatment. RESULTS: Following GnRH-A treatment, all patients had prepubertal gonadotropin and estradiol levels. Mean (SD) fat mass index (FMI) was significantly increased from 4.5 (1.7) to 5.0 (1.8) kg/m2 after treatment. Also, median (IQR) serum leptin level was significantly increased from 6.9 (4.2-8.6) to 7.4 (5.3-13.1) ng/mL. FMI had a positive correlation with serum leptin level (r=0.64, p=0.004). In contrast, no significant changes of serum ghrelin and PYY levels were observed. CONCLUSIONS: Decreased estrogen following short-term GnRH-A treatment in CPP girls may cause an increase in appetite and consequently an elevation of FMI. Increased serum leptin may be a result of having increased FMI secondary to an increase in appetite.

Masked hypertension and its associations with glycemic variability metrics in children and adolescents with type 1 diabetes.

BACKGROUND: Masked hypertension defined as having normal office blood pressure (BP) but hypertension detected by continuous BP monitoring has been observed in children and adolescents with type 1 diabetes (T1D). However, no study has evaluated whether masked hypertension is associated with glycemic variability (GV) in these patients. We hypothesized that masked hypertension might be associated with high GV in patients with T1D. METHODS: This cross-sectional study performed continuous glucose monitoring (CGM) in parallel with ambulatory blood pressure monitoring (ABPM) in T1D patients aged 6-21 years. Patients who had known hypertension were excluded. CGM data from the same day as ABPM was calculated for GV including standard deviation (SD), coefficient of variation (CV) of glucose levels, and unstable glycemia which was defined as having a CV of glucose levels ≥ 36%. RESULTS: Thirty-three patients had complete ABPM and CGM data. Mean (SD) age was 13.8 (3.8) years and mean (SD) duration of T1D was 5.4 (3.6) years. All patients had normal office BP, but ABPM showed masked hypertension in 9 patients (27%). In comparison with normotensive patients, patients with masked hypertension had longer duration of T1D (7.4 vs. 4.6 years, p = 0.049), higher insulin requirement (1.2 vs. 0.9 units/kg/day, p = 0.049), and higher SD of glucose (70.3 vs. 47.9 mg/dl, p = 0.038). Masked hypertension group had a greater number of patients (71% vs. 19%, p = 0.02) with unstable glycemia. Multivariate analysis revealed that unstable glycemia was associated with masked hypertension. CONCLUSIONS: The presence of unstable glycemia in children and adolescents with T1D is associated with masked hypertension. Graphical abstract.

DUOX2 variants are a frequent cause of congenital primary hypothyroidism in Thai patients.

OBJECTIVE: To identify the genetic etiologies of congenital primary hypothyroidism (CH) in Thai patients. DESIGN AND METHODS: CH patients were enrolled. Clinical characteristics including age, signs and symptoms of CH, pedigree, family history, screened thyroid-stimulating hormone results, thyroid function tests, thyroid imaging, clinical course and treatment of CH were collected. Clinical exome sequencing by next-generation sequencing was performed. In-house gene list which covered 62 potential candidate genes related to CH and thyroid disorders was developed for targeted sequencing. Sanger sequencing was performed to validate the candidate variants. Thyroid function tests were determined in the heterozygous parents who carried the same DUOX2 or DUOXA2 variants as their offsprings. RESULTS: There were 118 patients (63 males) included. Mean (SD) age at enrollment was 12.4 (7.9) years. Forty-five of 118 patients (38%) had disease-causing variants. Of 45 variants, 7 genes were involved (DUOX2, DUOXA2, TG, TPO, SLC5A5, PAX8 and TSHR). DUOX2, a gene causing thyroid dyshormonogenesis, was the most common defective gene (25/45, 56%). The most common DUOX2 variant found in this study was c.1588A>T. TG and TPO variants were less common. Fourteen novel variants were found. Thyroid function tests of most parents with heterozygous state of DUOX2 and DUOXA2 variants were normal. CONCLUSIONS: DUOX2 variants were most common among Thai CH patients, while TG and TPO variants were less common. The c.1588A>T in DUOX2 gene was highly frequent in this population.

Serum Kisspeptin and Its Relation to Metabolic Parameters and Glucose Metabolism in Prepubertal and Pubertal Obese Children.

OBJECTIVE: Kisspeptin, a puberty control neuropeptide, has been discovered to have an additional role in metabolism and glucose homeostasis regulation. This study aimed to determine the association of serum kisspeptin with metabolic parameters and glucose metabolism in obese children. Design, Patients and Measurements. A cross-sectional study of 270 obese children was conducted. All children underwent an oral glucose tolerance test and had serum kisspeptin, glycated hemoglobin (HbA1c), and lipid profile measurements. Body fat mass was assessed by bioelectrical impedance analysis. Serum kisspeptin levels of both prepubertal and pubertal children with two HbA1c ranges, <5.7% (normal range) and 5.7-6.4% (prediabetes range), were analyzed and correlated with metabolic parameters and glucose metabolism status. RESULTS: The median (IQR) serum kisspeptin level of only pubertal (not prepubertal) children with prediabetes HbA1c was higher than those with normal HbA1c (53.2 (33.9, 69.8) and 37.8 (29.6, 67.5) pg/mL; p = 0.015, respectively). There were no differences in serum kisspeptin levels among children with different glucose metabolism status. During pubertal progression, serum kisspeptin reached the highest level at Tanner stage II only in obese boys. Additionally, there was a positive correlation between serum kisspeptin and HbA1c after adjusting for puberty (ß = 12.87; p = 0.001). No correlations between serum kisspeptin and insulin sensitivity indices, insulin secretion indices, lipid profile, blood glucose, as well as percentage of body fat were demonstrated. CONCLUSIONS: Serum kisspeptin levels in pubertal obese children with prediabetes HbA1c were greater than those with normal HbA1c. Serum kisspeptin was positively associated with HbA1c, but not with glucose metabolism status.

Skewed X chromosome inactivation in girls and female adolescents with autoimmune thyroid disease.

OBJECTIVE: 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. DESIGN, PATIENTS AND MEASUREMENTS: Ninety-one female ATD patients, aged 3-20 years and 57 age-matched, female controls were enrolled. XCI was analysed by enzymatic digestion of DNA with methylation-sensitive enzymes followed by PCR of the polymorphic CAG repeat in the androgen receptor gene. Skewed XCI was defined as having 80% or greater of the cells preferentially inactivated on the same X chromosome. XCI pattern of the enrolled patients and parental origin of the skewed XCI were determined. RESULTS: After exclusion of samples with homozygous CAG repeats, skewed XCI was analysed in 83 patients (57 Graves' disease and 26 Hashimoto thyroiditis) and 52 controls. There was an increased frequency of skewed XCI in ATD patients as compared with the controls (23% vs 8%, P = 0.022). Patients with Hashimoto thyroiditis had greater frequency of skewed XCI than patients with Graves' disease (38% vs 16%, P = 0.023). There were no differences in clinical parameters between patients with skewed and random XCI. Analysis of 7 patients with skewed XCI showed a preferential inactivation of paternal X chromosome in 6 patients (86%). CONCLUSIONS: Frequency of skewed XCI was increased in childhood ATD. This observation suggests a possible association of skewed XCI in the development of paediatric ATD.

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.

Acute Effects of Blood Transfusion on Insulin Sensitivity and Pancreatic ß-Cell Function in Children with ß-Thalassemia/Hemoglobin E Disease.

OBJECTIVE: To assess the acute effects of blood transfusion on insulin sensitivity and pancreatic ß-cell function in thalassemia patients. METHODS: Fifty children and adolescents with ß-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 ß-cell function indices [HOMA of ß-cell function (HOMA-ß), 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. ß-Cell function indices also increased significantly [median HOMA-ß: 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.

OBJECTIVE: 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. DESIGN, PATIENTS AND MEASUREMENTS: Up to 370 overweight and obese children, aged 6-18 years were enrolled in this cross-sectional study. Oral glucose tolerance test (OGTT) was performed with fasting serum Gpc4, lipid profiles, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) measured. Insulin sensitivity and ß-cell function indices were calculated from plasma glucose and serum insulin levels derived from the OGTT. Bioelectrical impedance analysis was performed for body fat determination. Comparisons of serum Gpc4 levels among the groups of children with various degrees of obesity were performed. RESULTS: Serum Gpc4 levels progressively increased in children with increasing body mass index standard deviation score (BMI SDS) tertiles [median (interquartile range, IQR): 2.3 (1.8, 3.2), 2.6 (1.9, 3.4) and 3.2 (2.4, 3.8) µg/L, P<.001]. There were no differences in serum Gpc4 levels among children in the different glucose metabolism categories. Log serum Gpc4 levels were positively correlated with SDSs of weight and BMI, cholesterol, AST and ALT. No associations of log serum Gpc4 and insulin sensitivity and ß-cell function indices were demonstrated. CONCLUSIONS: Serum Gpc4 levels were increased with increasing degrees of obesity. There were no differences in serum Gpc4 levels among glucose metabolism categories.

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

AIMS: To compare insulin sensitivity, ß-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 ß-cell function as well as a reduced pancreatic iron load was observed following 6 months of iron chelation (TCTR20160523003).

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

OBJECTIVES: 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. DESIGN, PATIENTS AND MEASUREMENTS: This study involved 230 obese children in a cross-sectional part and 72 participants in a prospective part in which children with VDI were treated with vitamin D2 at a dose of 20 000 IU daily for 28 days. All 230 children underwent an oral glucose tolerance test and had their serum total and undercarboxylated OCNs and 25-OHD measured. Forty of 72 children were reassessed for the GluMet and serum total and undercarboxylated OCNs and 25-OHD after the vitamin D2 treatment. RESULTS: In the prospective part, correction of VDI by raising mean (SD) 25-OHD of 51·5 (12·3) to 141·8 (40·8) nmol/l resulted in an improvement of their GluMet and increase in their whole-body insulin sensitivity index with no changes in their OCN measures. In the cross-sectional part, after adjustments for age, sex and puberty, the total (ß = 0·322) and undercarboxylated OCNs (ß = 0·315) were positively associated with insulinogenic index, which is an index of insulin secretion (P = 0·034 and 0·037, respectively) in the group of prediabetic and diabetic children. CONCLUSIONS: Correction of VDI increased insulin sensitivity and improved GluMet, but had no effect on serum OCN measures. OCN was associated with increased insulin secretion in children with abnormal GluMet.

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

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 ß-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 ß-thalassemia disease who were pre-transplanted with RIC.

Acute effects of blood transfusion on growth hormone and insulin-like growth factor-1 levels in children with thalassemia.

BACKGROUND/AIM: Children with ß-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.

High prevalence of "biochemical" adrenal insufficiency in thalassemics: is it a matter of different testings or decreased cortisol binding globulin?

CONTEXT: High prevalence of "biochemical" adrenal insufficiency (AI) in thalassemics has been reported. However, "clinical" AI is rare. AIM: The aim was to determine whether cortisol binding globulin (CBG) or tests used in assessing adrenal function contributed to the abnormally high prevalence of biochemical AI. SETTING: The study was conducted at Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. PARTICIPANTS: Participants included 56 children and adolescents with thalassemia and 44 controls. MAIN OUTCOME MEASURES: Serum CBG and adrenal function test results assessed by 1 µg cosyntropin test and insulin tolerance test (ITT) were measured. Free cortisol index (FCI) calculated by total cortisol (TC)/CBG and calculated free cortisol (cFC) were determined. RESULTS: Mean (sd) CBG levels were comparable between patients and controls [45.2 (11.0) vs. 47.0 (8.6) mg/liter]. Peak TC, FCI, and cFC after cosyntropin test were lower in thalassemics [TC, 15.2 (4.0) vs. 18.9 (3.1) µg/dl; FCI, 3.4 (0.8) vs. 4.2 (1.2) µg/mg, P <0.001; and cFC, 1.03 (0.38) vs. 1.44 (0.61) µg/dl, P = 0.008]. Thirty of 56 thalassemics (53.6%) had AI, defined as having peak TC of less than 16 µg/dl. ITT was performed in 26 of those 30 patients. Five of 26 patients had peak TC after an ITT of at least 20 µg/dl. As a result, the estimated frequency of AI in the entire patient group was reduced by approximately 10%. CONCLUSION: The 1 µg cosyntropin test could be an adrenal function screening test in thalassemics. However, for definite diagnosis, ITT should be performed in those having peak total cortisol of less than 16 µg/dl after the 1 µg cosyntropin test.

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

BACKGROUND: A test involving 100 microg 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 microg 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.

Childhood virilization and adrenal suppression after ingestion of methandienone and cyproheptadine.

We report a combination of precocious pseudopuberty and adrenal insufficiency in a 4 year-old boy who had received an off-label 'appetite stimulant' syrup and excessive virilization in a 2 year-old girl who had received the same medication. Both patients presented with excessive virilization for a period of approximately 1-2 years. The syrup contains cyproheptadine and methandienone, a derivative of testosterone. Both cyproheptadine and methandienone were responsible for severe adrenal suppression in the boy. Methandienone undoubtedly caused precocious virilization in both children. Cessation of the syrup led to partial regression of virilization in both children and normalization of adrenal reserve function in the boy.

Serum free cortisol index, free cortisol, and total cortisol in critically ill children.

BACKGROUND: In critical illness, serum total cortisol (TC) may not adequately reflect adrenal function because of reduced cortisol-binding globulin (CBG). AIM: To evaluate adrenal function of critically ill children, using free cortisol index (FCI), calculated free cortisol (cFC), and TC levels. METHODS: Thirty-two critically ill and 36 healthy children were included. All children underwent the 1 microg cosyntropin test. TC and CBG levels were measured. Basal and peak TC, FCI, and cFC were determined. RESULTS: Basal and peak TC, FCI, and cFC of critically ill children were significantly higher than those of the controls. Compared with TC, both basal and peak FCI and cFC of the patients were higher than those of controls to a greater degree. Use of FCI or cFC to diagnose adrenal insufficiency (AI) reduced the frequency of diagnosis of AI by 50%. CONCLUSION: FCI and cFC better reflect the dynamic changes of adrenal function of critically ill children.