Band 23, Heft 8

ABSTRACT Background : The atherosclerotic process starts at an early age and is linked to obesity. However, the exact pathophysiological mechanism is poorly understood. Objective : To investigate the relationship between serum adiponectin and metabolic syndrome and early arteriosclerosis. Subjects : 176 obese and 88 normal children. Methods : Ultrasound measurement was performed to investigate IMT, FMD, carotid artery compliance (CAC). Adiponectin was measured by enzyme-linked immunosorbent assay. Results : Adiponectin levels correlated negatively with obese markers, blood pressure, fasting insulin, high sensitive CRP, HOMA-IR and IMT; marginally positively associated with CAC and HDL-c. The risk of metabolic syndrome increased 3.43 times when adiponectin levels were less than 7060ng/ml. Heavy obesity, hypertension, low HDL-c, fasting hyperinsulin, High LDL-c and metabolic syndrome percentage were different in three groups according to the cut-off value of adiponectin. Conclusions : Low adiponectin levels are associated with a high incidence of metabolic syndrome.

ABSTRACT Neonatal reference values for serum thyrotropin are scarce and comprise only small numbers of patients. During 2006, changes were made in IMMULITE kits for TSH measurement. To validate methodological changes, 80 serum samples from patients were evaluated and to establish reference intervals, 334 neonates and infants were analyzed (divided into 4 groups). Group 1 (G1) (48-72 h of life) (n=153), group 2A (G2A) (7-10 days of life) (n =65), group 2B (G2B) (11- 14 days of life) (n= 35), group 3 (G3) (28-40 days of life) (n =81). Current kits overestimate TSH results by 26 to 37%; TSH (mIU/L) reference intervals (percentile 2.5 – 97.5) were G1 (1.1-12.7), G2A (1.8-9.8), G2B (1.1-7.1) (p<0.03 vs G2A), G3 (1.2-6.9). We suggest that during the second week of life, reference values should be divided into an early stage and a late stage, at least, for there to be an adequate interpretation of borderline measurements in newborn thyroid screening.

ABSTRACT Familial hyperlipidemia is a group of genetic disorders with a predisposition to atherosclerosis. Hyperlipidemia causes increased atherosclerotic events through increased endothelial damage. In this report we aimed to measure the plasma fibrinogen and von Willebrand factor antigen (VWf:Ag) levels in pediatric patients with familial hyperlipidemias and to investigate the effects of serum lipid levels and antihyperlipidemic agents on these parameters. Of the 41 patients analyzed, vWf:Ag level was significantly lower in antihyperlipidemic receivers (132±51%, 102±19%; p=0.010). This finding may indicate that early initiation of antihyperlipidemics in patients with familial hyperlipidemias may decrease the risk of future atherosclerotic events through not only decreasing the serum lipid levels, but also decreasing plasma vWf:Ag levels.

ABSTRACT We have prospectively assessed the influence of GHR and VDR gene polymorphisms on the response to rhGH therapy in Venezuelan children with growth hormone deficiency (GHD, n= 28) and Turner syndrome (TS, n= 25). Clinical data during rhGH treatment were compared in GH and TS patients with different genotypes. PCR amplifications were performed to obtain the genotype frequencies of the polymorphisms. Clinical data at the start of treatment and rhGH doses were indistinguishable among patients with GHD or TS with different GHR or VDR genotypes. After the first two years of rhGH treatment, clinical data in both GHD and TS patients were not different according GHR or VDR genotypes. In addition, there was no significant difference among the subjects when both these genotypes were combined. Gene polymorphisms in low penetrance genes do not contribute to the rhGH therapy response in patients with GHD and TS.

ABSTRACT We analyzed the ability of the BaF3 cell line bioassay to select patients with biologically inactive GH. We first evaluated the biological response of the Ba/F3-hGHR cells to rhGH additional doses from 10 to 5000 pg/ml. The concentration points corresponding to the linear part of the curve were selected. We then analyzed a group of sera, diluted like the standard, including the entire range of GH concentrations that can be analyzed by bioassay. The serum/standard area below the curve ratio was calculated. Serum GH immunoactivity determined by IMMULITE/GH bioactivity ratios was calculated. Our experimental data showed that GH-bioactivity/GH-immunoactivity ratios below 0.303 are indicative of a bioinactive GH molecule. This bioassay would recognize only extreme cases of GH bioinactivity, and it would not be a useful tool in the search for patients with altered forms of GH.

ABSTRACT Ongoing controversy surrounds early genital surgery for children with disorders of sex development, making decisions about these procedures extraordinarily complex. Professional organizations have encouraged healthcare providers to adopt shared decision-making due to its broad potential to improve the decision-making process, perhaps most so when data are lacking, when there is no clear “best-choice” treatment, when decisions involve more than one choice, where each choice has both advantages and disadvantages, and where the ranking of options depends heavily on the decision-maker's values. We present a 6-step model for shared decision-making in decisions about genital surgery for disorders of sex development: 1) Set the stage and develop an appropriate team; 2) Establish preferences for information and roles in decision-making; 3) Perceive and address emotions; 4) Define concerns and values; 5) Identify options and present evidence; and 6) Share responsibility for making a decision. As long as controversy persists regarding surgery for DSD, an SDM process can facilitate the increased sharing of relevant information essential for making important health care decisions.

ABSTRACT Background : Nonalcoholic fatty liver disease (NAFLD) is the accumulation of excess fat in the liver in the absence of alcohol consumption, which commonly coexists with obesity. NAFLD is associated with increased risk of atherosclerosis and insulin resistance Mean platelet volume (MPV) is a marker of platelet activation, which is a determinant of atherosclerosis. Aims : The first aim of the present study was to investigate the MPV levels in obese adolescents and compare the MPV levels in patients with and without NAFLD and also with healthy controls. The second aim of this study was to evaluate the relationship between IR and MPV. Patients and Methods : Case records of 128 exogenous obese adolescents were retrospectively evaluated. Laboratory parameters were collected by using a computerized patient database. Insulin resistance was calculated by a homeostasis model assessment (HOMA-IR) index. Patients were divided into two groups: patients with NAFLD (Group 1) and patients without NAFLD (Group 2). Forty-seven healthy children constituted the control group. Results : MPV was significantly higher in obese adolescents than their healthy peers. Group 1 had significantly higher MPV than group 2. HOMA-IR was significantly higher in group 1 than group 2. MPV was significantly higher in patients with IR than patients without IR. There was a positive correlation between MPV and HOMA-IR. MPV was inversely correlated with HDL cholesterol and platelet count. Conclusion : MPV may be used as a follow-up marker in patients with NAFLD at the point of atherosclerosis.

ABSTRACT The etiology of Congenital Hypothyroidism (CH) is important in determining its severity, prognosis, genetic counseling and clinical management. Aims : investigate the causes of CH and their severity using serum levels of FreeT4 and TSH. Patients and Methods: 243 neonates with CH (61% were girls) diagnosed by the Neonatal Screening Program of Minas Gerais between 1996 and 2003. The thyroid function was assessed through serum FreeT4 and TSH by chemilumiscence. CH etiology was evaluated by ultrasonography, scintigraphy, potassium perchlorate discharge test and serum thyroglobulin levels. Results : Out of 243 patients, dysgenesis was found in 114 (47%): 3.3% had athyreosis; 0.4% eutopic dysgenetic gland due to maternal use of 131 I; 22% ectopic glands (8.6% an isolated ectopic gland and 13% also an eutopic dysgenetic thyroid); 9% eutopic dysgenesis, 8.6% hypoplasia and 3.7% hemiagenesis. Thyroid in situ was found in 129 (52%): 23.5% had iodide organification defect; 3.7% thyroglobulin synthesis defect; 6.2% other dyshomonogenesis; 0.4% iodide transport defect; 1.2% transient CH and 18% a normal gland. Patients with dysgenesis had a more severe CH than those with thyroid in situ (TSH 248.08 vs. 18.17 μIU/mL and FT4 0.32 vs. 0.95 ng/dL, p<0.001). Conclusions : Some cases had more complex dysgenesis, presenting ectopia associated to a dysgenetic eutopic gland. The ultrasound was the best tool to detect the dysgenetic tissue, but the scintigraphy was the most effective in identifying the functioning tissue. The thyroid hormone synthesis defects were found more frequently than expected, but in some cases they could not be defined.

ABSTRACT Hyperinsulinism-hyperammonemia (HI/ HA) syndrome is the second most frequent cause of congenital hyperinsulinism (CHI) and it is characterized by recurrent symptomatic hypoglycemia and persistent hyperammonemia. We describe the familial case of a 2-year-old child and her 32-year-old mother who, having suffered from tonic-clonic seizures since infancy, had both been diagnosed with epilepsy and treated with sodium valproate . Hypoglycemia was identified in the child in routine analysis. Six days after admission, a complete study of hypoglycemia showed test results compatible with hyperinsulinemic hypoglycemia and hyperammonemia. A mutation in the GDH gene (Arg269His) confirmed the diagnosis in both the mother and the child. An important peculiarity of this case is the diagnosis of a 32-year-old woman, previously diagnosed with epilepsy through her daughter's diagnosis at a Pediatric Endocrinology Department and subsequently treated ineffectively with sodium valproate . We conclude that, as hypoglycemia may be subtle, the diagnosis of HI/HA should be considered in children or adults with seizures/epilepsy and hyperammonemia, serum ammonia being a simple screening test for the disease.

ABSTRACT Vaginal bleeding in prepuberty is an alarming symptom that must be carefully investigated. Among quite common causes of genital sanguineous discharge, there are rarer conditions responsible for bleeding at this age like Mullerian papilloma of the genital tract. In this report, we describe a case of Mullerian papilloma of the vagina in a 9 year-old girl. We believe in the importance of a correct clinical setting and histological definition to avoid wrong diagnosis and consequent inadequate treatments. Mullerian papilloma, a benign tumor, can in fact be treated only with local excision.

ABSTRACT A rare case of glycogen storage disease type III with unusually absent ketone body production during hypoglycemia is presented. A 10-month-old boy presented with asymptomatic hepatomegaly. GOT/GPT 2555/ 1160 IU/L, CK 302 IU/L, triglycerides 1223 mg/dL, cholesterol 702 mg/dL and uric acid 7.9 mg/ dL. After a 9-hour fast, glucose was 27 mg/dL and adequate lipolysis without ketogenesis was observed (total/free carnitine 34.5/20 μmol/L, free fatty acids 1620 μmol/L and β-hydroxybutyrate 172 μmol/L). Result of MCT (medium-chain triglycerides) load test: basal β-hydroxybutyrate 29 μmol/L rose to 5748 μmol/L. Treatment with a fat-restricted diet supplemented with formula containing MCT was initiated and the patient presented a satisfactory initial evolution. Three months later, CK were 3000 IU/L. Muscle biopsy was diagnostic of glycogenosis. Enzymatic activity in skin fibroblasts was 0% for amylo-1,6-glucosidase. The diagnosis of glycogenosis type III was established. Echocardiography performed at that time showed non-obstructive ventricular hypertrophy. Until now hypoketosis during hypoglycemia has only been described in glycogenosis type I.

ABSTRACT Background: McCune-Albright syndrome (MAS) is a triad of gonadotropin-independent precocious puberty (GIPP), café-au-lait spots (CALS) and fibrous dysplasia (FD) of bone. The extent of the abnormalities is variable. Patient and results: We report a 3 year old girl with CALS since infancy, FD diagnosed at age of 2.5 years, and at the age of 3 years vaginal bleeding. The ultrasound revealed a cystic mass of the ovary, surgical pathology found ovarian cyst. LHRH stimulation demonstrated GIPP (LH 9.8 mIU/ml and FSH 8.9 mIU/ml; normal LH 1.8-10, FSH 9-26 mIU/ml). Radiographs and bone scans demonstrated FD in multiple bones. Peripheral leucocytes and the ovary were negative for GNAS gene mutations. Treatment with Letrasole interrupted the pubertal development. Conclusions: We conclude that the clinical signs of MAS are telling and that timely MAS diagnosis prevents unnecessary oophorectomy. A close follow up is recommended regarding development of endocrine disorders and spreading of FD.

ABSTRACT 1,25-Dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) an important regulator of bone homeostasis, mediates its actions by binding to the vitamin D receptor (VDR), a nuclear transcription factor. Mutations in the VDR cause the rare genetic disease hereditary vitamin D resistant rickets (HVDRR). In this study, we examined two unrelated young female patients who exhibited severe early onset rickets, hypocalcemia, and hypophosphatemia. Both patients had partial alopecia but with different unusual patterns of scant hair. Sequencing of the VDR gene showed that both patients harbored the same unique nonsense mutation that resulted in a premature stop codon (R50X). Skin fibroblasts from patient #1 were devoid of VDR protein and 1,25(OH) 2 D 3 treatment of these cells failed to induce CYP24A1 gene expression, a marker of 1,25(OH) 2 D 3 action. In conclusion, we identified a novel nonsense mutation in the VDR gene in two patients with HVDRR and alopecia. The mutation truncates the VDR protein and causes 1,25(OH) 2 D 3 resistance.