Ivani Novato Silva

Randomised controlled trial of growth effect of hydrocortisone in congenital adrenal hyperplasia

The influence of 15 or 25 mg/m2 of daily oral hydrocortisone with fludrocortisone 0.1 mg/day on growth and laboratory findings was evaluated in a prospective randomised crossover trial over 12 months in 26 children with 21-hydroxylase deficiency. Nine non-salt losers had fludrocortisone stopped for a further six month period. Height velocity was significantly decreased during treatment with 25 mg/m2 as compared with 15 mg/m2. This was the most sensitive indicator of corticosteroid treatment excess. A dose dependent effect upon plasma concentrations of 17-hydroxyprogesterone, testosterone, and androstenedione was found but increased values were still detected in more than half of the determinations made during the 25 mg/m2 period. Height velocity and 17-hydroxyprogesterone concentrations were positively correlated. Growth hormone response to clonidine stimulation and insulin-like growth factor-1 concentrations were both within reference values and there was no difference between treatment periods. Withdrawal of fludrocortisone did not result in any difference for the non-salt losers. It was concluded that 25 mg/m2 of hydrocortisone depressed growth in children with congenital adrenal hyperplasia, and that full suppression, or even normalisation, of plasma concentrations of 17-hydroxyprogesterone and androgens should not be considered a treatment goal, but instead an indication of corticosteroid treatment excess.

Prevalence of celiac disease in Brazilian children with type 1 diabetes mellitus

Objective: Although the relationship between celiac disease and diabetes mellitus type 1 is well recognized, there are no studies of this association in Brazil. This study aims to identify the prevalence of celiac disease in a group of children with diabetes mellitus type 1 undergoing treatment in the pediatric endocrinology division of a university hospital in Minas Gerais, Brazil. Methods: Immunoglobulin (Ig)A and IgG antigliadin antibodies (enzyme-linked immunoadsorbent assay) were measured in blood collected from 236 children and adolescents with diabetes mellitus type 1. Patients with antigliadin antibodies then had jejunal biopsy and determination of antiendomysial antibodies by indirect immunofluorescence. Results: Twenty-one patients had IgA or IgG antigliadin antibodies. Nineteen underwent jejunal biopsy. Six had mucosal alterations compatible with celiac disease; four had nonspecific histologic changes; nine had normal biopsies. Thirteen antigliadin antibody-positive patients were antiendomysial antibody-negative; one antiendomysial antibody-negative patient had celiac disease. The prevalence of celiac disease was 2.6% among 234 patients. Conclusions: Measurement of antigliadin antibodies in patients with diabetes mellitus type 1 helped in the selection of patients to undergo jejunal biopsy. Antiendomysial antibodies were highly specific and moderately sensitive in predicting celiac disease. The prevalence of celiac disease was higher in diabetics than in the general population, suggesting the need for regular screening assessment of diabetic children.

Increased prevalence of early cochlear damage in young patients with type 1 diabetes detected by distortion product otoacoustic emissions

Abstract Objective: To evaluate the hearing of adolescents with diabetes mellitus type 1(DM1) by otoacoustic emissions (OAEs), and by comparing different tests with pure-tone audiometry to identify potential early cochlear impairments. Design: Pure-tone audiometry, transient evoked otoacoustic emissions (TEOAEs), and distortion product otoacoustic emissions (DPOAEs) were performed in a group of adolescents with and without DM1. Clinical characteristics, disease duration, and glycated haemoglobin levels were studied. Study sample: Participants were 40 adolescents with DM1 and 40 healthy subjects. Results: Sensorineural hearing loss, affecting frequencies of 6000 and 8000 Hz, was found only in DM1 subjects when compared to the controls (7.7% vs. 0%, p < 0.05). A higher prevalence of cochlear damage was detected by DPOAE responses, 32% belonging from the diabetic group, vs. 3.7% in the control group. Absent TEOAE responses were observed in only three individuals, all from the diabetic group (5.1% of the tests performed in the diabetic group). Additionally, hearing thresholds were better in diabetic subjects with good control when compared to ones with regular or poor control (p = 0.00). Hearing thresholds were higher in poorly controlled diabetics when compared to subjects with good (p = 0.000) or regular control (p = 0.006). Conclusion: Early evidence of cochlear damage was detected in adolescents with DM1 leading to hearing loss at high frequencies. Abnormal DPOAEs responses were found more frequently than the alterations in TEOAEs and pure-tone audiometry, suggesting that DPOAEs evaluation is the most sensitive and it could be used for monitoring the progression of cochlear damage during the early stages of hearing impairment.

Triagem neonatal para hiperplasia adrenal congênita

OBJECTIVE: The effectiveness of neonatal screening for reducing morbimortality in children with congenital adrenal hyperplasia (CAH) is the main justification for its implementation. One of the challenges for its implementation is to determine the cutoff value for laboratory measurement of 17-hydroxyprogesterone (17OHP) with appropriate cost-effectiveness. This study identified factors affecting the results of the pilot project of newborn screening for CAH, performed in the state of Minas Gerais, Brazil. METHODS: Neonatal screening performed between September, 2007 and May, 2008, with 17OHP measurements performed in blood samples taken from the heel (filter paper), on the 5th day of life, processed by the UMELISA 17-OH Progesterona NEONATAL® method. The cutoff value was 80 and 160 nmol/L for healthy children or not, respectively. RESULTS: The incidence of CAH was 1:19,939 in 159,415 children screened. The 99th percentile (p99) of 17OHP in the first sample was 108 nmol/L. In 13,298 newborns whose weight had been reported, the p99 of 17OHP were, respectively: 344 nmol/L for weight 2,500g. The rate of recall for medical consultation was 0.31%. The test sensitivity was 100%, specificity was 99.6%, and the positive predictive value was 2.2%. By adjusting the cutoff values of 17OHP to 110 nmol/L and 220 nmol/L, a 76% decrease in consultation referrals was projected. CONCLUSION: The use of 17OHP cutoff values, considering birth weight, was a cost-effective measure to reduce false positives. The results of this pilot study suggest that screening for CAH might benefit the pediatric population.

Hipotiroidismo congênito transitório: perfil das crianças identificadas no programa estadual de triagem neonatal de Minas Gerais, Brasil

Early diagnosis and treatment of congenital hypothyroidism are the main goals of the neonatal screening programs. A retrospective analysis was carried out to assess the characteristics and etiologies of congenital transient hypothyroidism (CTH) in the Newborn Screening Program of the State of Minas Gerais, Brazil. To reach a diagnosis of CTH, altered screening and serum confirmatory T4 and TSH tests and normal serum free T4 and TSH at 4 and 8 weeks after the withdrawal of levothyroxine were used. We studied 21 children with CTH who represented 4.23% of the whole group with detected hypothyroidism and followed them up in the Screening Program. These patients received LT4 therapy for a variable period of one month to three years. Serum confirmatory TSH levels varied from 10.4 to 583.4 microUI/mL. Maternal antibodies, TRAB and anti-TPO, were associated to CTH in two children and iodine overload in one of them. We concluded that CTH is an important component in neonatal screening and hormonal treatment during the first months of the life is essential. The TSH initial levels are not relevant to determine whether the thyroid dysfunction is transient or permanent.

Risk Factors for Early Onset of Diabetic Nephropathy in Pediatric Type 1 Diabetes

ABSTRACT Aim: Diabetic nephropathy (DN) is a frequent complication in patients with long-standing type 1 diabetes mellitus (DM1). The objective of this study was to assess the prevalence of DN in DM1 patients diagnosed during childhood and its association with clinical and metabolic variables, such as age at diagnosis of DM1, glucose control, dyslipidemia, hypertension and the occurrence of diabetic retinopathy (DR). Methods: The medical records of 205 patients admitted to the Pediatric Endocrinology Division at the Hospital das Clínicas da Universidade Federal de Minas Gerais, in Belo Horizonte, Brazil, were analyzed. For the analysis of survival and prognostic factors, the Kaplan-Meyer method and the COX regression model were used. Results: The mean disease duration was 11.32 ± 4.02 years and the mean age at diagnosis was 6.10 ± 3.54 years. Microalbuminuria was present in 11.2% of them, proteinuria in 6.8% and end-stage renal disease (ESRD) in 2.9%. There was a significant association between the occurrence of microalbuminuria or proteinuria and poor glucose control (p=0.025 and p=0.005, respectively), higher LDL cholesterol levels (p=0.006 and p=0.004, respectively) and age greater than 6 years at diagnosis (p=0.049 and p=0.05, respectively). Proteinuria was also associated to the occurrence of DR (p=0.016). Conclusion: Our data showed that the prevalence of DN was higher than expected in this young population studied, especially considering the most severe forms. Clinical and laboratory factors associated to ND were: poor long-term glucose control, higher levels of LDL-C, higher age at diagnosis and the occurrence of DR.

Condição periodontal de crianças e adolescentes com diabetes melito tipo 1

OBJECTIVE To evaluate periodontal condition of diabetic children and its related factors. METHODS The plaque index (PI), sites with bleeding on probing (BOP), probing depth (PD) and clinical attachment level (CAL) were evaluated in all occlusion permanent teeth of 168 non smoking type 1 diabetic children, 13 +/- 3.5 years old. The PI and BOP evaluations were also performed in deciduous teeth. RESULTS It was observed a prevalence of 20.8% of gingivitis and 5.9% of periodontitis. Those individuals with poor metabolic control had higher percentage of affected sites on PD (p = 0.004) and on CAL (p = 0.014). Patients having more than five years with diabetes mellitus type 1 showed higher percentual of affected sites on PD (p = 0.002), on BOP (p < 0.001) and on CAL (p = 0.007). CONCLUSIONS DM1 duration and poor glycemic control were significantly associated with periodontal disturbances suggesting higher susceptibility of this population in developing DP.

Neonatal screening for congenital adrenal hyperplasia

OBJECTIVE The effectiveness of neonatal screening for reducing morbimortality in children with congenital adrenal hyperplasia (CAH) is the main justification for its implementation. One of the challenges for its implementation is to determine the cutoff value for laboratory measurement of 17-hydroxyprogesterone (17OHP) with appropriate cost-effectiveness. This study identified factors affecting the results of the pilot project of newborn screening for CAH, performed in the state of Minas Gerais, Brazil. METHODS Neonatal screening performed between September, 2007 and May, 2008, with 17OHP measurements performed in blood samples taken from the heel (filter paper), on the 5(th) day of life, processed by the UMELISA 17-OH Progesterona NEONATAL(®) method. The cutoff value was 80 and 160 nmol/L for healthy children or not, respectively. RESULTS The incidence of CAH was 1:19,939 in 159,415 children screened. The 99(th) percentile (p99) of 17OHP in the first sample was 108 nmol/L. In 13,298 newborns whose weight had been reported, the p99 of 17OHP were, respectively: 344 nmol/L for weight < 1,500 g; 260 nmol/L for weight between 1,500 and 1,999 g; 221 nmol/L for weight between 2,000 and 2,499 g; 109 nmol/L for weight ≥ 2,500g. The rate of recall for medical consultation was 0.31%. The test sensitivity was 100%, specificity was 99.6%, and the positive predictive value was 2.2%. By adjusting the cutoff values of 17OHP to 110 nmol/L and 220 nmol/L, a 76% decrease in consultation referrals was projected. CONCLUSION The use of 17OHP cutoff values, considering birth weight, was a cost-effective measure to reduce false positives. The results of this pilot study suggest that screening for CAH might benefit the pediatric population.

Final height in congenital adrenal hyperplasia: the dilemma of hypercortisolism versus hyperandrogenism

OBJECTIVE The purpose of this study was to identify factors that might interfere with reaching the final height in patients with 21-hydroxylase deficiency (21-OHD). SUBJECTS AND METHODS Thirty-one patients with classical 21-OHD who reached their FH in our Institution were evaluated in order to compare the Z score for final height (FHZ) with: (1) the target height, (2) the standard height for the population, and (3) the hydrocortisone treatment schedule. RESULTS The FHZ of -2.13 ± 1.11 had a significant negative correlation with the hydrocortisone doses used throughout the period of study. Patients who reached FH within the normal population range were those who received lower doses of hydrocortisone, as compared to those whose FH remained below -2 SDS. CONCLUSION We conclude that careful treatment adjustments have a major influence on growth of children with CAH, and that the dose range for hydrocortisone replacement that does not lead to side effects is relatively narrow. The better height outcome was achieved in 21-OHD patients who received lower doses of hydrocortisone.

Avaliação da recuperação do eixo hipotalâmico-hipofisário-adrenal após corticoterapia por meio do cortisol basal

The glucocorticoid-induced inhibition that occurs after discontinuation of treatment is the most frequent cause of adrenal insufficiency. There are yet some doubts about the best way of evaluating the hypothalamic-pituitary-adrenal (HPA) axis in those patients. The main objective of this study was to evaluate the utility of basal cortisol in diagnosing adrenal insufficiency. Thirty-five children with acute lymphoid leukemia (ALL) receiving glucocorticoid therapy (median age of 6.9 years) were evaluated. A stimulus test with corticotropin releasing hormone (CRH-1 mcg/kg) was performed before the introduction of dexamethasone (6 mg/m2/day, for 28 days), in the 8th and the 28th days of glucocorticoid therapy, and 48 hours and one month after discontinuation of therapy. Suppression of the basal secretion as well as the maximum concentration of cortisol (post-CRH) occurred during glucocorticoid therapy, which persisted for 48 hours after the steroid was removed from treatment (p< 0.01 and p< 0.0001, respectively, for the three tests). One month after ceasing the administration of the glucocorticoid, the basal secretion, as well as the maximum concentration of cortisol, were similar to that before glucocorticoid therapy. There was a positive and statistically significant correlation between basal secretion and maximum concentration of cortisol in all tests. We observed 95% of specificity for the diagnosis of adrenal insufficiency when the inferior limit of basal cortisol was 8.5 mcg/dl. According to these results we concluded that basal secretion of cortisol is a good marker of supra-renal function in evaluating children after discontinuation of glucocorticoid therapy.