Factors Affecting Growth Velocity during Gonadotropin-Releasing Hormone Agonist Treatment in Girls with Idiopathic Central Precocious Puberty

PURPOSE: In some girls with central precocious puberty (CPP), growth velocity (GV) decreases below the age-appropriate normal range during gonadotropin-releasing hormone agonist (GnRHa) treatment. The purpose of this study was to investigate clinical and laboratory factors related to changes in GV during GnRHa treatment in girls with CPP. METHODS: We analyzed clinical and laboratory data of 49 girls (aged 7.8+/-0.5 years) with idiopathic CPP who were treated with GnRHa. GV, height standard deviation score (SDS), hormonal parameters, pubertal stage, chronological age and bone age (BA) were evaluated. RESULTS: GV during the first year of GnRHa treatment was 5.9+/-1.0 cm/yr and decreased significantly to 5.4+/-1.1 cm/yr during the second year of treatment (P = 0.005). GV during the third year (5.0+/-1.0 cm/yr) was not different from GV during the second year. During the second year of treatment, 8.2% and 36.7% of the girls had a GV or = 11 yr) at 1 year (55.6% vs. 19.4%; odds ratio [OR], 5.2; P = 0.022). In multivariate logistic regression analysis, more advanced BA at 1 year (OR, 6.1; 95% confidence interval [CI], 1.57-23.87) and lower height SDS for BA at 1 year (OR, 0.24; 95% CI, 0.06-0.94) were associated with relatively decreased GV (< 5 cm/yr) during the second year of GnRHa treatment. CONCLUSION: GV during and after the second year of GnRHa treatment in girls with idiopathic CPP remains within the normal prepubertal range, and relatively low GV during GnRHa treatment is associated with more advanced BA and lower height SDS for BA.

Factors Affecting Growth Velocity during Gonadotropin-Releasing Hormone Agonist Treatment in Girls with Idiopathic Central Precocious Puberty

PURPOSE: In some girls with central precocious puberty (CPP), growth velocity (GV) decreases below the age-appropriate normal range during gonadotropin-releasing hormone agonist (GnRHa) treatment. The purpose of this study was to investigate clinical and laboratory factors related to changes in GV during GnRHa treatment in girls with CPP. METHODS: We analyzed clinical and laboratory data of 49 girls (aged 7.8+/-0.5 years) with idiopathic CPP who were treated with GnRHa. GV, height standard deviation score (SDS), hormonal parameters, pubertal stage, chronological age and bone age (BA) were evaluated. RESULTS: GV during the first year of GnRHa treatment was 5.9+/-1.0 cm/yr and decreased significantly to 5.4+/-1.1 cm/yr during the second year of treatment (P = 0.005). GV during the third year (5.0+/-1.0 cm/yr) was not different from GV during the second year. During the second year of treatment, 8.2% and 36.7% of the girls had a GV or = 11 yr) at 1 year (55.6% vs. 19.4%; odds ratio [OR], 5.2; P = 0.022). In multivariate logistic regression analysis, more advanced BA at 1 year (OR, 6.1; 95% confidence interval [CI], 1.57-23.87) and lower height SDS for BA at 1 year (OR, 0.24; 95% CI, 0.06-0.94) were associated with relatively decreased GV (< 5 cm/yr) during the second year of GnRHa treatment. CONCLUSION: GV during and after the second year of GnRHa treatment in girls with idiopathic CPP remains within the normal prepubertal range, and relatively low GV during GnRHa treatment is associated with more advanced BA and lower height SDS for BA.

A Single-Arm, Phase III Study to Assess Efficacy and Safety after 6-Month-Treatment of Eutropin(TM) Inj. (Recombinant Human Growth Hormone) in Prepubertal Children with Short Stature due to Small for Gestational Age / 대한소아내분비학회지

PURPOSE: Recombinant human growth hormone is an effective therapy for short-statured children born small for their gestational age (SGA). This single-arm, multicenter, phase III clinical study of such children was designed to assess the efficacy and safety of treating them with recombinant human-growth-hormone (Eutropin(TM) Inj.) for 6 months. METHODS: Between 2005 and 2007, 30 treatment naive, prepubertal, short-statured SGA-born children were recruited as participants. Eutropin(TM) Inj. was administered for 6 months with a subcutaneous dose of 0.48 mg/kg/wk. The primary endpoint was the change in height velocity from the baseline to month 6. Various parameters were checked to obtain secondary outcome measures and to meet safety criteria. RESULTS: Height velocity significantly increased from 5.36 +/- 1.59 cm/yr at baseline to 10.66 +/- 2.03 cm/yr at month 6 (P < 0.0001). Secondary outcome measures (height velocity at month 3, height SDS for chronological age (CA), weight SDS for CA, bone maturation, and IGF-I and IGFBP-3 levels) were also significantly increased. Eutropin(TM) Inj. was well tolerated and safe over 6 months of treatment. CONCLUSION: The clinical efficacy and safety of Eutropin(TM) Inj. was demonstrated for the 6 month treatment of prepubertal children with short stature due to SGA. Further long-term study is needed.

Blockade of Vascular Endothelial Growth Factor (VEGF) Aggravates the Severity of Acute Graft-versus-host Disease (GVHD) after Experimental Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT)

BACKGROUND: Recent clinical observation reported that there was a significant correlation between change in circulating vascular endothelial growth factor (VEGF) levels and the occurrence of severe acute graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the action mechanisms of VEGF in GVHD have not been demonstrated. METHODS: This study investigated whether or not blockade of VEGF has an effect on acute GVHD in a lethally irradiated murine allo-HSCT model of B6 (H-2b)-->B6D2F1 (H-2b/d). Syngeneic or allogeneic recipient mice were injected subcutaneously with anti-VEGF peptides, dRK6 (50 microg/dose) or control diluent every other day for 2 weeks (total 7 doses). RESULTS: Administration of the dRK6 peptide after allo-HSCT significantly reduced survival with greaterclinical GVHD scores and body weight loss. Allogeneic recipients injected with the dRK6 peptide exhibited significantly increased circulating levels of VEGF and expansion of donor CD3+ T cells on day +7 compared to control treated animals. The donor CD4+ and CD8+ T-cell subsets have differential expansion caused by the dRK6 injection. The circulating VEGF levels were reduced on day +14 regardless of blockade of VEGF. CONCLUSION: Together these findings demonstrate that the allo-reactive responses after allo-HSCT are exaggerated by the blockade of VEGF. VEGF seems to be consumed during the progression of acute GVHD in this murine allo-HSCT model.

Pelvic Ultrasonography Findings in Girls with Precocious Puberty / 대한소아내분비학회지

PURPOSE: We analyzed pelvic ultrasonography (USG) findings in girls with central precocious puberty (CPP) and assessed the role of uterine and ovarian measurements in discriminating between CPP and other pubertal conditions. METHODS: Seventy-four girls (chronological age 7.8 +/- 0.5 years, bone age 9.9 +/- 0.8 years) with precocious pubertal signs were enrolled. Measurements of uterine and ovarian parameters by pelvic USG included antero-posterior diameters of the uterine fundus and cervix, diameter of each ovary, number of follicles, and maximal diameter of the largest follicle. The pelvic USG parameters were compared between girls with CPP (n = 49) and girls with atypical premature thelarche (PT) (n = 25). RESULTS: Antero-posterior diameter of uterine fundus (1.05 +/- 0.34 vs. 0.74 +/- 0.78 cm, P = 0.001), maximal ovarian diameter (2.13 +/- 0.48 vs. 1.84 +/- 0.74 cm, P = 0.048) and mean ovarian area (2.31 +/- 0.79 vs. 1.69 +/- 0.71 cm, P = 0.002) were significantly greater in girls with CPP than in girls with atypical PT. For the diagnosis of CPP, the sensitivity and specificity of A-P diameter of uterine fundus (> 0.9 cm) was 65.3% and 84.0%, the sensitivity and specificity of maximal ovarian diameter (> 2.0 cm) was 55.1% and 76%, and the sensitivity and specificity of mean ovarian area (> 2.0 cm2) was 62.9% and 80.0%. CONCLUSION: Girls with CPP had significantly higher dimensions of the uterus and ovary measurements compared to girls with atypical PT, but sensitivity and specificity were not high enough to differentiate CPP from atypical PT. Pelvic USG may help the diagnosis of CPP in girls.

Endocrine Complications after Hematopoietic Stem Cell Transplantation during Childhood and Adolescence

Long-term survivors of hematopoietic stem cell transplantation (HSCT) during childhood and adolescence are at risk of developing endocrine complications. The purpose of this study was to evaluate the long-term endocrine complications and their associated risk factors among such patients. We reviewed the data from 111 patients (59 males and 52 females) who underwent HSCT at the mean age of 8.3+/-4.1 yr. Thirty patients (27.0%) had growth impairment, and seven (21.2%) out of 33 patients who attained final height reached final height below 2 standard deviation (SD). The final height SD score of the patients conditioned with total body irradiation (TBI) was significantly lower than that of the patients conditioned without TBI (-1.18+/-1.14 vs. -0.19+/-0.78, P=0.011). Thirteen patients (11.7%) developed hypothyroidism (11 subclinical, 2 central) 3.8+/-1.8 (range 1.6-6.2) yr after HSCT. Nineteen (65.5%) out of 29 females had evidence of gonadal dysfunction, and 18 (64.3%) out of 28 males had evidence of gonadal dysfunction. The risk for gonadal dysfunction was significantly higher in females conditioned with busulfan/cyclophosphamide (P=0.003). These results suggest that the majority of patients treated with HSCT during childhood and adolescence have one or more endocrine complications. Therefore, multiple endocrine functions should be monitored periodically after HSCT until they reach adult age.

Association of Cytotoxic T Lymphocyte Antigen-4 Gene Polymorphisms and HLA Class II Alleles with the Development of Type 1 Diabetes in Korean Children and Adolescents

We studied the association of cytotoxic T lymphocyte antigen-4 gene (CTLA4) polymorphisms with the development of type 1 diabetes (T1D) in Korean children and adolescents. A total of 176 Korean subjects (92 females and 84 males) with childhood-onset T1D were studied. The A/G polymorphism at position 49 in CTLA4 exon 1 and the C/T polymorphism at position -318 in the CTLA4 promoter were analyzed by PCR-RFLP methods. The genotype and allele frequencies of the CTLA4 polymorphisms in the T1D patients were not different from those in the controls. These polymorphisms were not associated with the clinical characteristics or the development of autoimmune thyroid disease in the T1D patients. The frequency of the A allele was significantly higher in the patients that did not have two out of the three susceptible HLA-DRB1 alleles, which were DRB1*0301, *0405 and *09012, compared to the controls (P<0.05). These results suggest that CTLA4 polymorphisms do not directly confer any susceptibility to T1D. However, a CTLA4-mediated susceptibility effect on the development of T1D might be significant in children and adolescents that do not have susceptible HLA class II alleles.

Analysis of gonadotropin-releasing hormone (GnRH) test results in girls with precocious puberty / 소아과

PURPOSE: The gonadotropin-releasing hormone (GnRH) test results of girls with precocious puberty were analyzed to determine whether this test can efficiently and clearly differentiate between central precocious puberty (CPP) and other disorders. METHODS: Clinical and laboratory data of 54 girls with precocious pubertal signs were reviewed. Intravenous GnRH test was performed with blood samples obtained at 0, 30, 60, and 90 minutes. A peak luteinizing hormone (LH) level of > or =5.0 IU/L was indicative of CPP. RESULTS: Of the 40 girls with CPP, 36 (90.0%), 3 (7.5%), and 1 (2.5%) showed peak LH levels at 30, 60, and 90 minutes, respectively. A percentage of girls whose peak LH > or =5.0 IU/L up to 30, 60, and 90 minutes was 92.5%, 100%, and 100%, respectively. The peak LH/follicle stimulating hormone (FSH) ratio of girls with CPP was 0.89+/-0.49 and was 1.0 showed higher chronological age (CA) (8.3+/-0.6 vs. 7.7+/-1.0 years, P=0.033), bone age (BA) (10.9+/-0.8 vs. 9.7+/-1.1 years, P=0.001), and BA-CA difference (2.6+/-0.7 vs. 2.0+/-0.7 years, P=0.009) than those of girls with peak LH/FSH ratio of 1.0 showed advanced breast development (> or =Tanner III) (93.7% vs. 41.7%, P=0.001). CONCLUSION: LH levels after 30 and 60 minutes of intravenous GnRH administration are the most useful for diagnosing CPP in girls.

The Effect of Growth Hormone Therapy on Bone Mineral Density in Young Adults with Childhood-onset Growth Hormone Deficiency / 대한소아내분비학회지

PURPOSE: Growth hormone (GH) has multiple beneficial effects in addition to its promotion of linear growth. Therefore adults with GH deficiency (GHD) have abnormal body composition, altered lipid metabolism, increased cardiovascular disease, and decreased bone mineral density (BMD). We evaluated the effect of GH therapy on BMD in young adults with childhood-onset GHD. METHODS: 17 childhood-onset GHD adults (10 male, 7 female, mean age 24.5+/-5.5 yr) with or without continuous GH treatment after final height were studied. All subjects divided two groups; GH-treated group (n=6) and GH-untreated group (n=11). BMD in lumbar spine and proximal femur was measured by dual energy X-ray absorptiometry. RESULTS: The mean serum level of IGF-I concentration in the GH-untreated group was lower than in the GH-treated group (88.4+/-55.9 ng/mL vs. 358.7+/-196.8 ng/mL, P<0.05). The BMD of lumbar spine in the GH-treated group and GH-untreated group was 1.02+/-0.13 g/cm2 and 0.82+/-0.09 g/cm2 and the BMD of femur was 1.15+/-0.14 g/cm2 and 0.82+/-0.10 g/cm2 respectively. The BMD of the GH-treated group was significantly higher than the GH-untreated group (P<0.05). CONCLUSION: These findings support the need of continuous GH treatment after completion of growth and careful evaluation of BMD in adult patients with childhood-onset GHD.

A case of adrenocortical adenoma following long-term treatment in a patient with congenital adrenal hyperplasia / 소아과

As a result of the widespread use and enhanced quality of high-resolution radiological techniques, a recent report has revealed a relatively high prevalence of small adrenal tumors in patients with untreated congenital adrenal hyperplasia due to 21-hydroxylase deficiency. However, there are scarcely any pediatric cases of adrenocortical tumor following long-term treatment in patients suffering with congenital adrenal hyperplasia. We report here on a pediatric female case of adrenocortical adenoma despite adequate long-term treatment for the salt-losing type of congenital adrenal hyperplasia.

The Genotype and Clinical Phenotype of Korean Patients with Familial Hypokalemic Periodic Paralysis

Familial hypokalemic periodic paralysis (HOPP) is a rare autosomal-dominant disease characterized by reversible attacks of muscle weakness occurring with episodic hypokalemia. Mutations in the skeletal muscle calcium (CACNA1S) and sodium channel (SCN4A) genes have been reported to be responsible for familial HOPP. Fifty-one HOPP patients from 20 Korean families were studied to determine the relative frequency of the known mutations and to specify the clinical features associated with the identified mutations. DNA analysis identified known mutations in 12 families: 9 (75%) were linked to the CACNA1S gene and 3 (25%) to the SCN4A gene. The Arg528His mutation in the CACNA1S gene was found to be predominant in these 12 families. Additionally, we have detected one novel silent exonic mutation (1950C>T) in the SCN4A gene. As for a SCN4A Arg669His mutation, incomplete penetrance in a woman was observed. Characteristic clinical features were observed both in patients with and without mutations. This study presents comprehensive data on the genotype and phenotype of Korean families with HOPP.

Serum ghrelin and leptin concentrations in children with cancer: comparisons with normal children / 소아과

PURPOSE: Ghrelin, being secreted from the stomach, stimulates growth hormone secretion and controls energy homeostasis by increasing appetite. Leptin, being secreted from the adipocytes, controls weight and energy homeostasis by decreasing appetite. Leptin concentration is reported to increase after childhood cancer therapy. This study was aimed to compare ghrelin and leptin concentrations in normal children and children who received cancer therapy. METHODS: We enrolled forty-three patients who were diagnosed with cancer and received radiotherapy or chemotherapy during Dec. 2004 through Dec. 2005 in St. Marys hospital and Kangnam St. Marys hospital. Forty-five healthy children were selected as a control group whose age, gender, weight and height were similar to those of cancer group. The serum leptin and ghrelin concentrations were also measured by radioimmunoassay. RESULTS: The cancer group showed higher BMI and leptin concentrations. The control group showed higher concentrations of ghrelin. Both control and cancer groups revealed positive correlations between leptin concentrations and BMI. Ghrelin concentrations in the control group showed negative correlations with age, height, weight and BMI but no significant correlation was found in the cancer group. All the parameters in the group treated with chemotherapy only were not different from those in the group treated with chemotherapy and irradiation. But the level of ghrelin in the acute myeloid leukemia group was much higher than those in the acute lymphoblastic leukemia group. CONCLUSION: Patients with pediatric cancer treatment have presented higher BMI and leptin concentrations but lower ghrelin concentrations than those in healthy children. Because of the relatively short duration and cross sectional method of the study, however, further long term and prospective study will be required in the future.

Final Adult Height of Children with Normal Endocrine Function after Hematopoietic Stem Cell Transplantation / 대한소아내분비학회지

PURPOSE: We analyzed the final adult height of patients without endocrine dysfunction who underwent hematopoietic stem cell transplantation (HSCT) during the childhood. METHODS: We evaluated the final height of 28 long term survivors (13 males, 15 females) who underwent HSCT at the mean age of 12.3 years. Patients who had solid tumors, inherited diseases and endocrine dysfunction before or after HSCT were excluded. The mean age at last visit was 18.8 years. Height values were expressed in standard deviation score (SDS). Height at HSCT was compared with final height as well as mid-parental height. We analyzed the risk factors for affecting final adult height of patients. RESULTS: There was a decrease in final height SDS compared to pre-transplantation height SDS (P= 0.003). All patients except one reached an adult height above -2.0 SDS of normal population. The difference between the height SDS at HSCT and the final height was -0.98+/-0.5 SDS in boys and -0.10+/-0.6 SDS in girls (P<0.01, and P=0.53 respectively). A significant decrease in height SDS was found in male (Mann-Whitney U test, P=0.001). The type of primary diseases, age at HSCT, total body irradiation, acute graft-versus-host disease did not influence the final height. CONCLUSION: Despite the decrease in final height SDS after HSCT during childhood, the majority of patients without endocrine dysfunction spontaneously reached on a normal adult height range (above -2.0 SDS). Therefore, careful monitoring of growth after HSCT during childhood is warranted to detect the growth velocity decrease.

The Effect of Gonadotropin Releasing Hormone Agonist with or without Growth Hormone Treatment on Predicted Adult Height in Girls with Early Puberty / 대한소아내분비학회지

PURPOSE: Many recent studies have been performed to improve adult height in short normal girls with early puberty by arresting rapid pubertal progression. We evaluated the effect of combined therapy with growth hormone (GH) and gonadotropin releasing hormone agonist (GnRHa) on predicted adult height in girls with early puberty, comparing them with a group treated with GnRHa alone. METHODS: Twenty eight girls with early puberty were classified into two groups and treated for an average 18 months. Group I of 18 girls was treated with GnRHa alone (leuprolide acetate; dosage: 30-90 mcg/kg, s.c. every 28 days) and group II of 10 girls was treated in combination with GH (dosage: 0.1 IU/kg, s.c. 5-7 days/week). Two groups were compared in terms of bone age, height, sexual maturity, and predicted adult height at the start and after the treatment. RESULTS: Two groups were not significantly different from each other in chronologic age, bone age, weight, target height, and sexual maturity before and after treatment. After treatment, group I showed predicted adult height (157.1+/-6.2 cm) which was comparable to target height (157.1+/-3.7 cm) and was not significantly higher than predicted adult height before treatment (156.0+/-6.5). On the contrary, group II showed predicted adult height (158.5+/-4.6 cm) which was comparable to target height (156.2+/-3.6 cm), but significantly higher than predicted adult height before treatment (154.2+/-7.4 cm) (P<0.05). CONCLUSIONS: GH and GnRHa combination treatment is more effective than GnRHa treatment alone to improve predicted adult height in girls with early puberty.

Short-term follow up of thyroid function after pediatric hematopoietic stem cell transplantation / 소아과

PURPOSE: In this study, we analyzed the short term changes of thyroid function, incidence and risk factors of thyroid dysfunction soon after allogeneic hematopoietic stem cell transplantation (HSCT) in children. METHODS: We enrolled 80 pediatric patients following allogeneic HSCT, at the Catholic HSCT center between January, 2004 and February, 2006. Serum TSH (thyroid stimulating hormone), total serum thyroxine and total serum triiodothyronine levels were systematically measured in 80 patients before the HSCT, and at 1 month, 6 months and 12 months after HSCT. RESULTS: Thyroid function statistically decreased at 1 month after HSCT(P or = II) were risk factors for ETS (P=0.04, 0.01 respectively). In multivariate analysis, we could not detect an independent risk factor for ETS (P=0.19, 0.06 respectively). CONCLUSION: The present study suggests that the incidence of thyroid dysfunction is high after allogeneic HSCT. Therefore, regular monitoring of thyroid hormone levels after HSCT is required.

Serum IGF-I and IGFBP-3 Concentrations in Children with Cancer: Comparisons with Normal Children / 대한소아내분비학회지

PURPOSE: Since insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) are often used as markers for growth assessment, we compared the serum IGF-I and IGFBP-3 levels in children diagnosed with cancer with those in the healthy children. METHODS: Forty-nine children who were diagnosed with cancer and treated with radiotherapy or chemotherapy were enrolled in the study. Sixty-four healthy children without any medical problems were enrolled as controls. Height, weight, body mass index (BMI), height standard deviation score (HTSDS), serum IGF-I, serum IGFBP-3 and molar ratio of IGF-I/IGFBP-3 were compared between the two groups. RESULTS: The mean age of children in the control group was 9.3+/-2.9 years and that of children in the cancer group was 8.8+/-3.3 years. There were no significant differences in mean height, weight, BMI and HT SDS between in the two group. Serum IGF-I levels increased with age in both groups, and the mean level of the control group was significantly higher than that of the cancer group. The mean serum level of IGFBP-3 in the control group was higher than that of the cancer group. IGF-I/IGFBP-3 molar ratio also increased with age in both groups and the mean level of molar ratio of the control group was higher than that of the cancer group. IGF-I, IGFBP-3, and IGF-I/IGFBP-3 molar ratio in the leukemia group and the solid tumor group were not significantly different. Mean age, IGF-I and IGFBP-3 concentrations in the chemotherapy group were higher than those in the chemotherapy and radiation therapy group. CONCLUSION: The serum levels of IGF-I and IGFBP-3 in children diagnosed with cancer, treated with radiotherapy or chemotherapy, were lower than those of the control group. In conclusion, the serum levels of IGF-I and IGFBP-3 can possibly be used as early markers of growth assessment in children with cancer treatment.

Effect of Potent Aromatase Inhibitor (Letrozole) on Bone Maturation and Predicted Adult Height in Boys with Early Puberty / 대한소아내분비학회지

PURPOSE: We evaluated the effect of potent aromatase inhibitor (Letrozole) on the rate of bone maturation and an increase in predicted adult height (PAH) in boys with early puberty. METHODS: Nine boys, aged 10.9-12.9 years, with early puberty were studied. The boys were treated with the aromatase inhibitor, letrozole, 2.5 mg/day for 1 year. The main outcome parameters were the change in bone age and predicted adult height. Also, serum LH, FSH, testosterone and estradiol concentrations were measured and sexual maturation before and after 12 months of treatment were evaluated. RESULTS: PAH significantly increased by 3.3 cm (P<0.05) and PAH standard deviation score significantly increased by 0.6 (P<0.05). Bone age before therapy advanced by 0.72+/-0.93 year, but bone age after therapy decreased by 0.07+/-0.90 year compared to chronological age (P<0.01). Whereas, sexual maturation of the subjects progressed normally. CONCLUSION: These results suggest that treatment with the potent aromatase inhibitor, letrozole, delays bone maturation and improves PAH in boys with early puberty.

Incidence and Clinical Characteristics of Diabetes Mellitus in Aplastic Anemia Patients Treated with Multiple Transfusions / 대한소아내분비학회지

PURPOSE: We investigated the epidemiological and clinical characteristics of diabetes mellitus developed in aplastic anemia patients who have had many blood transfusions. METHODS: We retrospectively reviewed medical records of 170 patients with aplastic anemia who were diagnosed before 15 years of age in Department of Pediatrics, The Catholic University of Korea from 1987 to 2001. We obtained their medical history, family history of diabetes mellitus, clinical onset of diabetes mellitus and the successive history, and coexistence of other disorders. RESULTS: Diabetes mellitus was diagnosed in 8 of 107 patients (7.5%) with severe aplastic anemia in childhood. The mean age of diagnosis of diabetes mellitus was 18.5+/-5.2 years, and the mean duration from the start of blood transfusion to the diagnosis of diabetes mellitus was 7.7+/-2.9 years. Duration of multiple blood transfusions was a major risk factor for the development of diabetes mellitus in severe aplastic anemia patients. There was a wide range of symptoms at clinical onset of diabetes mellitus from asymptomatic hyperglycemia to diabetic ketoacidosis. Incidence of other complications, such as hepatic impairment (88%) and cardiac dysfunction (75%), was high in patients who developed diabetes mellitus. CONCLUSION: Severe aplastic anemia patients treated with prolonged, multiple transfusions have a significant risk of developing insulin-deficient diabetes mellitus. These patients are at risk for other complications, such as hepatic, cardiac, or thyroid disorders. Early prevention of iron overload and screening for transfusion-related complications are very important in these patients.

Puberty and Gonadal Function after Bone Marrow Transplantation During Childhood / 대한소아내분비학회지

PURPOSE: Bone marrow transplantation (BMT) involving high dose chemotherapy and irradiation can seriously affect the gonad and reproductive axis. We studied puberty and gonadal function in the subjects who underwent BMT during childhood for the treatment of acute leukemia. METHODS: 25 females (age at examination:15.7+/-3.1 years; age at BMT:10.3+/-3.0 years) and 22 males (age at examination:16.4+/-2.0 years; age at BMT:11.1+/-2.2 years) who underwent BMT for acute leukemia were included. We evaluated their pubertal status and gonadal function before and after BMT, and investigated the clinical factors influencing disturbances of gonadal function in these patients. RESULTS: Of the 13 females who were prepubertal before BMT, two had no breast development by 13 years of age, and the others entered puberty spontaneously. Of the 8 females who were older than 16 years at the last evaluation, 5 had primary amenorrhea, and 3 developed secondary amenorrhea. Sixteen (64.0%) out of 25 pubertal females had abnormally elevated serum concentrations of luteinizing hormone (LH), and 23 (92.0%) had abnormally elevated serum concentrations of follicle-stimulating hormone (FSH). Abnormal elevation of LH was more frequent in the females who had entered puberty at BMT compared with those before puberty (91.7% vs 45.5%, OR=13.2, P<0.05). Of the 19 males who were prepubertal before BMT, 3 did not enter puberty spontaneously by 14 years of age, and the others entered puberty spontaneously. Four (18.2%) out of 22 pubertal males had abnormally elevated plasma concentrations of LH, and 9 (42.9%) had abnormally elevated plasma concentrations of FSH. Abnormal elevation of FSH was more frequent in males who underwent BMT after relapse than those without relapse (87.5% vs 20.0%, OR=28.0; P<0.05). CONCLUSION: More than 40% of the girls who underwent BMT cannot retain adequate ovarian function to complete puberty and menstruate regularly. The ovaries of the pubertal girls seem to be more vulnerable to BMT. The majority of the boys experience normal pubertal development after BMT, but about 40% of the boys had abnormally elevated levels of FSH, which is indicative of germ cell dysfunction.

Cord Blood Adiponectin Concentrations in Relation to Newborn Birth Weight, Length and Gender / 대한소아내분비학회지

PURPOSE: Adiponectin is an adipocyte-derived plasma protein with various metabolic effects that include increasing insulin sensitivity, antiatherogenic, and antiinflammatory properties. The purpose of this study was to investigate the association of cord plasma adiponectin levels with body size, ponderal index, and gender in newborns and also age and body mass index in their mothers. METHODS: The cord blood was obtained from 99 healthy newborns (male 46, female 53, gestational age of 32-41 weeks) and the concentrations of adiponectin were analyzed by a radioimmunoassay kit. Anthropometric parameters of the newborns including birth weight and length were measured. Maternal weight and height were identified, and their body mass index was calculated. RESULTS: The cord plasma adiponectin levels of the newborns whose gestational age was longer than 39 weeks were significantly higher compared with those of gestational age shorter than 39 weeks (15.0+/-9.9 vs 8.4+/-8.9 microgram/mL, P=0.001). The cord plasma adiponectin concentrations were positively correlated with gestational age and length at birth of the newborns. There was no correlation between cord plasma adiponectin levels and sex, birth weight or ponderal index of the newborns. Any significant correlation was not found between cord plasma adiponectin levels and maternal age or body mass index. CONCLUSION: These findings indicate that cord plasma adiponectin concentrations are positively associated with gestational age and length at birth of neonates. However there is no correlation between cord plasma adiponectin levels and maternal age or body mass index.