Band 23, Heft 10

ABSTRACT Background : KF is characterized by heterogeneity in the degree of expressed phenotypes. Objective : to ascertain the variable phenotypes of Klinefelter syndrome in children. Subjects and Methods: We present eight klinefelter patients, their age ranged from 2 to 11 years (mean 6.63). Subjects were meticulously examined for evidence of dysmorphology. Intelligence quotient was estimated. Results : Cytogenetic analysis revealed 47,XXY karyotype in all patients. The following was detected: Dysmorphism in 5/8, micropenis in 4/8, the left testis was nonpalpable in 4/8, short stature in 4/8, congenital cardiac malformations in 4/8, seizures in 4/8, mental retardation in 5/8, growth hormone deficiency in 2/8, hypothyroidism and delayed bone age in 1/8. Conclusion : Our study demonstrated a variable association of mental retardation, dysmorphism, micropenis, undescended testis, seizures, congenital heart defects, and growth hormone deficiency among Egyptian patients with Klinefelter syndrome. This merits further study to facilitate earlier diagnosis and better management to improve their quality of life.

ABSTRACT Aim : Although subnormal TSH between 0.1-0.4 mIU/L is fairly common and benign, suppression of TSH to < 0.1mIU/L with normal free T4 is less common and more worrisome. We have conducted a retrospective chart review of a collection of such cases and have summarized the features and outcome on follow up. Methods : We studied 23 consecutive patients referred from 2005-07 to our pediatric endocrine clinic with TSH < 0.1 mIU/L and free T4 in the range of 0.8-2 ng/dl. We collected historical, clinical and laboratory data, and analyzed their outcome. Results : The natural evolutions of these subjects were separated into 4 groups. Group 1, 14 subjects, (61%) became euthyroid within a mean of 3.7 months. Group 2, 4 subjects, (17%) became hypothyroid within a mean of 2.8 months. Group 3, 2 subjects (9%) progressed to overt hyperthyroidism. Group 4, 3 subjects (13%) had persistently suppressed TSH, 8-14 months after initial testing, of which one had a multinodular goiter and had a thyroidectomy. Elevated thyroid peroxidase antibody (TPO) was seen in 54.5% of those tested. Conclusion : Only 2/23 in our series became overtly hyperthyroid. Substantial number of subjects had a short period of transient TSH suppression that resolved spontaneously. Markers suggestive of autoimmune thyroid disease were consistently seen in group 2 and less so in others. It is prudent to observe such cases in the short term with serial follow up TSH, free T4 and T3, and to reserve further testing and treatment for those who become symptomatic or do not resolve.

ABSTRACT Objective : To evaluate the efficacy, tolerability, and pharmacokinetics of bicalutamide plus anastrozole in young males with testotoxicosis. Methods : This was a multicenter, open-label, single-arm, 12-month, Phase II pilot trial in 14 males (2-9 years) with testotoxicosis treated with bicalutamide (12.5, 25, 50, or 100 mg) and anastrozole (0.5 or 1 mg) daily. The primary outcome was change in growth rate. Results : At 1 year, the mean (standard deviation) change from baseline in growth rate was -1.6 (± 5.1) cm/year and -0.1 (± 1.8) SD units, and in bone maturation was -2.3 (± 0.5) years. The bone age/chronological age ratio was reduced from 2.1 (± 0.6) at baseline to 1.0 (± 0.4) (p = 0.00013). Steady-state trough R-bicalutamide and anastrozole concentrations were attained by Day 21 and 8, respectively. Gynecomastia (42.9%) and breast tenderness (12.5%) were the most common treatment-related adverse events. Conclusions : Treatment of testotoxicosis with bicalutamide plus anastrozole resulted in slower growth rate.

ABSTRACT Aim : The over-expression of CB1 in adult obesity is associated with insulin resistance (IR), but it is not elucidated in childhood obesity. We studied CB1 and endocannabinoid enzymes (EE), Adiponectin (Ad), and Insulin(SI) in lean and obese pre-pubertal(PP) children. Methods : CB1 mRNA and protein (Pr) expression were studied by RT-PCR, western immunoblotting and immunohistochemistry in primary cultures of adipose tissue. The EE(NAPE-PLD, DAGL-α, FAAH, MAGL) expression was assessed by Real-Time PCR. Ad and SI were measured by ELISA and IR by HOMA-IR index. Results : In the older obese vs older lean children: (1) CB1 Pr was decreased, (2) FAAHmRNA and DAGL-α mRNA were increased. Ad was decreased and SI and HOMA-IR increased in the older PP children. Conclusions : Increased CB1 and decreased adiponectin in older lean PP children may facilitate fat deposition and “physiologic” IR necessary for the increased body growth of puberty. The reduced expression of CB1 in the older obese may be an attempt to reduce lipogenesis to avoid greater insulin resistance.

ABSTRACT Objective : To determine if pretreatment insulin and C-peptide levels together with antibody status are predictive of HbA1c levels before and during therapy in obese African-American youth with type 2 diabetes. Methods : Records of African-American patients with clinical diagnosis of type 2 diabetes were retrospectively analyzed. Insulin, C-peptide, blood glucose, HbA1c and islet autoantibodies at diagnosis were recorded. These variables were compared with HbA1c levels during therapy. Results : Eight of 45 patients were islet autoantibody positive. There was no difference in age, Body Mass Index z-score, insulin, C-peptide, glucose or HbA1c levels between antibody positive or negative patients. Insulin (r= -0.45, p<0.01 n= 45) and C-peptide (r= -0.59, p<0.001, n= 36) were correlated with HbA1c at diagnosis but not during therapy. Conclusions : Higher insulin levels were associated with lower HbA1c at presentation but not during therapy. Antibody status was not associated with differences in insulin, C-peptide levels or HbA1c level.

ABSTRACT Objective : To evaluate the cross-sectional and longitudinal relationships of morning cortisol with trunk fat and resting blood pressure (BP) in children. Methods : Participants included 72 children aged 4-10 years (mean 7.4 yrs) for the cross-sectional analysis and 58 for the longitudinal analysis. Height, weight, waist circumference, body fat by dual x-ray absorptiometry, and resting BP measures were obtained during a laboratory visit. Saliva samples were collected at home on a single morning and assayed for cortisol. Results : Approximately 21% were overweight (15.3%) or obese (5.6%). Mean morning cortisol was 0.25 ± 0.12 μg/dL (6.99 ± 3.46 nmol/L). There were no significant correlations between morning cortisol and any of the measures of fatness (r<-0.17) or BP (r<-0.10) at baseline. Cortisol at baseline was not associated with changes in body size parameters after the 1- and 2- year follow-up period. Conclusion : Morning cortisol was not associated with body fatness or BP. Future studies should examine the associations between the diurnal cortisol patterns, trunk fat, and BP by collecting samples throughout an entire day.

ABSTRACT Background : Apelin is a recently defined peptide relevant to the mechanism of obesity-related disorders. There has been no report so far about the levels of plasma apelin in obese children. Methods : In this study plasma apelin, adiponectin, and high sensitivity C reactive protein levels were investigated in obese (n=32) and nonobese (n=40) children. The effects of pubertal status on the apelin and adiponectin levels were evaluated as well. Results : When compared to nonobese controls, the obese children had significantly lower plasma apelin (p= 0.004), adiponectin and HDL cholesterol levels (p= 0.001 for both), and higher hs-CRP, triglycerides, insulin and Homeostasis Model Assessment (HOMA-IR) indexes (p< 0.001 for all). The difference between the apelin levels was present only in the pubertal period (p=0.002). Conclusions : The results of the present study indicate that plasma apelin levels are lower in child obesity and pubertal state is an important determinant of plasma apelin levels.

ABSTRACT Background : Adolescent acromegaly is a rare disorder and these patients present with tall stature/gigantism, tumor mass effects and menstrual irregularities. Patients and Methods : 34 consecutive (26 males) patients having onset of disease prior to 21 years of age were included in this retrospective analysis. Their clinical features and treatment outcome were studied. Results : Mean age and lag time at presentation were 21.6 ± 3.9 years and 5.1 ± 3.5 years respectively. Common presenting manifestations included acral enlargement, tumor mass effects and menstrual irregularities. Mean height at presentation was 174.6 ± 13.7 cms (range: 150 – 210 cm) and one third had gigantism (height ≥ 97 th percentile, WHO growth charts). Hypertension and glucose intolerance were seen in 15% and 23.5% respectively. Mean nadir GH after glucose load was 58.2± 13.7 ng/ml and IGF -1 was 534.8± 132.8 ng/ml. Half of the patients had concomitant hyperprolactinemia. Almost all (97%) had macroadenoma and anterior pituitary hormone deficiencies were frequent (75%). Patients with gigantism were younger (19.6±4.9 vs 22.6± 2.9 years; p=0.001), had higher GH values (66.68±27.22 vs 53.98± 15.99 ng/ml; p=0.04) and hypogonadism was more common (90.9% vs 56.5%, p=0.03) than those with normal stature. 32 patients (94.1%) were treated primarily with surgery, 7(21.9%) received post operative radiotherapy. Mean duration of follow up was 33.1±10.1 months. Only 30% had nadir GH values of < 1ng/ml. Conclusion : One third of adolescent patients had acrogigantism. These patients were younger, had higher GH levels and concurrent hypogonadism was more common. Cure could be achieved only in about one third of the patients.

ABSTRACT Objective : The aim of this study was to compare the LV morphology and function in adolescents with DM1 and their healthy peers. Subjects and Methods : In 59 DM1 patients (30 girls, 29 boys,aged 14-17 years), and in control group (15 girls, 15 boys) LV was assessed by M-mode, 2D and Doppler echocardiography. The metabolic control was assessed in the long- (mean HbA1c value for the entire treatment period-HbA1c1), medium- (mean HbA1c for the past two pre-study years-HbA1c2), and short-term (HbA1c on the day of the study- HbA1c3). Results : Diabetic patients presented an increase of IRT (0.062 vs. 0.056 s,p<0.05 in boys, and 0.062 vs. 0.056 s,p<0.05 in girls), A wave (56.1 vs. 53.95 cm/s in boys, and 60.3 vs. 58 cm/s in girls), and deceleration time values (0.16 vs. 0.15 s in boys, and 0.17 vs. 0.15 s in girls), decrease of E wave (97.35 vs. 104.9 cm/s in boys, and 99.67 vs. 101.8 cm/s in girls), as well as the E/A ratio (1.79 vs. 2.0 in boys, and 1.7 vs. 1.78 in girls). The systolic function was normal. In girls there was a correlation between IRT and HbA1c1 and HbA1c2 (r=0.42,r=0.46,p<0.05); between the A wave and HbA1c2 (r=0.46,p<0.05); between LV posterior wall systolic dimension and HbA1c1, HbA1c2 (r=0.45,r=0.41,p<0.05), and in boys between the A wave and HbA1c1 and HbA1c2 (r=0.48,p<0.01;r=0.37, p<0.05). Conclusions : Pubertal patients with DM1 demonstrate discrete impairment of the diastolic function beside normal systolic function of the LV. Further investigations are needed to assess the value of this observation. It seems that LV diastolic dysfunction in girls depends on the degree of insulin resistance and DM1 duration, and similarly as in boys, on the long-term metabolic control.

ABSTRACT Thirty-eight obese Korean children (21 boys, 17 girls), whose ages were between 9 and 15, were divided into either the intervention group (19 obese children: BMI>95P) or the age- and sex-matched obese control group. The intervention group performed an intensive exercise program under the supervision of educated instructors for 12 weeks (90 minutes/day, two days/week) and received lifestyle modification counseling using food diaries and phone calls. The control group participated in conventional counseling at an out-patient clinic. The intervention group appeared to have more improvement of body weight, body composition, serum lipid profiles and high-sensitivity C-reactive protein (hs-CRP) levels ( P < 0.05) but without changes in serum adiponectin level. HOMA-IR decreased from 2.3 to 1.3 in the intervention group. Maximal oxygen consumption (VO 2 max) and other physical fitness parameters were significantly improved after the intervention program ( P < 0.05).

ABSTRACT Four children; all between 10-40 days of age, were admitted with multiple episodes of multifocal seizure. After admission blood investigation was carried out and they were found to have hypocalcemia, hyperphosphatemia; kidney function tests were normal. Serum parathyroid hormone was highly elevated and serum magnesium level was found to be normal in these patients. The infants did not have any other features of pseudohypoparathyroidism. The seizure was initially resistant to intravenous calcium therapy and later responded to oral calcitriol and calcium therapy. The diagnosis of pseudohypoparathyroidism was made according to biochemical investigations. The infants were symptom-free during follow-up and the biochemistry reports were also normalized. One of the infants was also suffering from neonatal hepatitis, due to CMV infection.

ABSTRACT Bartter syndrome type IV, also known as Bartter syndrome with sensorineural deafness (BSND), is caused by loss-of-function mutations in the BSND gene, which encodes barttin, an accessory subunit of chloride channels located in the kidney and inner ear. Patients with BS IV have a highly variable clinical phenotype. This report concerns a Korean male patient with antenatal Bartter syndrome due to a homozygous BSND p.G47R mutation, who presented with severe perinatal symptoms followed by a relatively benign course with preserved renal function after early infancy. In addition, the clinical features and the laboratory data of the patient were compared with those of previously reported patients with the same mutation.

ABSTRACT Objective : A functional polymorphism at codon 55 of the small ubiquitin like modifier 4 (SUMO4) gene (methionine to valine;M55V) was recently found to be associated with type 1 diabetes mellitus mainly in Asian populations (T1D). In the present study, we aimed to investigate whether this locus also contributes to the genetic susceptiblity to type 1 diabetes in Chinese. Research design and methods : A case-control study was performed using genomic DNA samples from 165 unrelated Chinese childhood T1D subjects and 160 normal blood donors. The SUMO4 M55V single nucleotide polymorphism (SNP) was genotyped using polymerase chain reaction (PCR) amplification followed by digestion with the restriction enzyme Mse I. Results : The frequencies of SUMO4 163G allele were significantly increased in T1D patients (38. 2% vs healthy control subjects 28. 7%, P<0. 05, OR=1. 51, 95% CI 1. 03-2. 13). SUMO4 163 GG genotype was also significantly increased in the T1D patients (17% vs healthy control subjects 8%, P<0. 05). Conclusions : This study indicates that the SUMO4 gene M55V variant is associated with the genetic susceptibility of T1D in Chinese children.

ABSTRACT Mayer Rokintansky–Kuster–Hauser syndrome is characterized by the congenital absence of the vagina with a variety of Müllerian duct anomalies. Because of normal sexual development, the syndrome usually remains undetected until primary amenorrhea and/or difficulty in attempting sexual intercourse result in the diagnosis. MRKHS frequently is associated with anomalies of the urinary tract (unilateral agenesis or ectopia of one or both kidneys, horse-shoe kidney), cervico-thoracic region (asymmetric, fused or wedged vertebrae, scoliosis and Klippel-Feil anomaly), congenital cardiac defects, hearing defects, and digital anomalies of varying severity. Congenital heart diseases in the form of atrial septal defect, Holt-Oram Syndrome with or without aorticopulmonary window, pulmonary stenosis etc in association with MRKHS have been described in the literature. We present a case of MRKHS with unilateral agenesis of the kidney and atrial septal defect with partial anomalous pulmonary venous connection. This combination of anomalies has not been reported in the literature so far. The various presentations and the pathogenesis of the condition are discussed.