Physical growth in children with reflux nephropathy with normal or mildly impaired renal function.

Ten children aged 11 months to 10 years (means 5.7 years) with reflux nephropathy, vesicoureteric reflux (VUR) and normal or mildly impaired renal function having GFR more than 50 ml/min/1.72 m2, were included in the study. The hematological and biochemical parameters were within normal limits. Height standard deviation score (HZ score) was reduced at entry and, decreased further during follow-up (-2.2 and -2.6 at 0 and 12 months, respectively). Weight for height index (WHI) improved significantly (p=0.0004) during follow-up. The basal and stimulated peak growth hormone levels of these patients were found to be elevated, 18.53 ± 11.36 μg/L and 34.20 ± 5.86 μg/L, respectively. The IGF-1 levels were low ranging from 45.00 to 84.40 ng/dl (mean ± SD 61.54 ± 10.21 ng/dl) compared to 51.80 to 247.50 ng/dl (mean ± SD111.20 ± 70.24 ng/dl) in age and sex matched controls, indicating partial insensitivity to growth hormone.

Central diabetes insipidus: clinical profile and factors indicating organic etiology in children.

OBJECTIVE: To evaluate the profile of children with central diabetes insipidus (DI) and identify factors indicating organic etiology. DESIGN: Retrospective chart review. SETTING: Tertiary referral hospital. SUBJECTS: Fifty-nine children with central DI (40 boys, 19 girls). METHODS: Features of organic and idiopathic central DI were compared using students t test and chi square test. Odds ratio was calculated for factors indicating organic etiology. RESULTS: Diagnosis included post-operative central DI (13, 22%), central nervous system (CNS) malformations (5, 8.6% holoprosencephaly 4 and hydrocephalus 1), histiocytosis (11, 18.6%), CNS pathology (11, 18.6%; craniopharyngioma 3, empty sella 2, germinoma 2, neuro-tuberculosis 2, arachnoid cyst 1 and glioma 1) and idiopathic central DI (19, 32.2%). Children with organic central DI were diagnosed later (7.8+/- 3.1 years against 5.3+/-2.4 years, P=0.03) and had lower height standard deviation score (-2.7+/-1.0 versus -1.0+/- 1.0, P<0.001) compared to idiopathic group. A greater proportion of children with organic central DI had short stature (81.8% against 10.5%, P <0.001, odds ratio 38.25), neurological features (45.5% against 0%, p 0.009) and anterior pituitary hormone deficiency (81.8% against 5.3%, P<0.001, odds ratio 81) compared to idiopathic group. A combination of short stature and onset after five years of age led to discrimination of organic central DI from idiopathic group in all cases. CONCLUSION: Organic central DI should be suspected in children presenting after the age of five years with growth retardation and features of anterior pituitary deficiency.

Characterization of adult onset growth hormone deficiency syndrome in patients with hypothalamopituitary diseases: Asian Indian data.

BACKGROUND: Hardly any data is available on Adult onset growth hormone deficiency (AOGHD) in Patients with hypothalamopituitary diseases in India. AIMS: To characterize Asian Indian AOGHD syndrome in hypothalamopituitary diseases. SETTINGS AND DESIGN: Cross-sectional analysis of data from a tertiary care hospital. MATERIALS AND METHODS: Thirty patients with AOGHD were compared with 30 age-, sex-, body mass index-matched controls with respect to endocrine evaluation, biochemistry, body composition (BC), bone mineral density (BMD), cardiovascular risk profile and quality of life (QoL). STATISTICAL ANALYSIS USED: Comparisons were performed using two-tailed Student's test (SPSS Software version 10.0). RESULTS: Most of the patients had abnormal BC with central obesity [Truncal FM (%): males {33.9+/-4.4 (patient) vs. 29.31+/-6.2 (control); P -0.027}; females {39.87+/-5.93 (patient) vs. 35.76+/-3.16 (control); P - 0.025}] and poor QoL. Patients aged over 45 years did not show low bone mass or lipid abnormalities as compared to controls. Low BMD and abnormal lipid profile {Triglycerides [mg/dl]:170.55+/-72.5 (patient) vs101.24+/-31.0 (control); P -0.038}; {very low density lipoprotein cholesterol [mg/dl]: 33.54+/-14.9 (patient) vs. 20.25+/-6.18 (control); P - 0.05} was seen in female patients less than 45 years of age. Conclusions: Male and female (more than 45 years) AOGHD patients have increased cardiovascular risk factors and poor QoL while BMD is unaffected. Females less than 45 years of age have the major characteristics of AOGHD and would be the group to benefit maximally with recombinant human Growth Hormone treatment, which is similar to that in the western literature.

Growth pattern and final height in 21-hydroxylase deficiency.

Growth pattern and final height were evaluated in 47 children with 21-hydroxylase deficiency to identify factors influencing growth. The subjects were followed-up from the age of 0.6 +/- 1.2 years for 8.8 +/- 3.9 years. Final height SDS was significantly below target height SDS (- 2.5 +/- 1.4 versus - 1.0 +/- 1.0, P < 0.001). Laboratory monitoring and type of disease (salt-wasting or simple virilizing) significantly influenced age-specific height SDS. Age at treatment, frequency of laboratory monitoring and dose of glucocorticoid during infancy influenced final height on univariate analysis; the effect was not sustained on multivariate analysis. Our study emphasizes the need for regular laboratory monitoring and lower glucocorticoid dose during infancy in 21-hydroxylase deficiency.

Serum leptin levels in obese Indian children relation to clinical and biochemical parameters.

OBJECTIVE: To evaluate serum leptin levels in obese Indian children and its correlation to anthropometric and biochemical parameters. DESIGN: Cohort study. SETTING: Referral tertiary hospital. METHODOLOGY: Leptin levels were measured in 36 children (26 boys, age 1.5 to 15 years) and 37 adults (21 men, age 25 to 69 years) with obesity and 29 normal weight controls (15 children and 14 adults). RESULTS: Leptin levels were higher than controls in obese children (19.4 +/- 6.4 ng/mL against 5.4 +/- 1.7 ng/mL, p = 0.0001) and obese adults (18.9 +/- 6.4 ng/mL against 7.8 +/- 5.6 ng/mL, p = 0.0001). Leptin levels were higher than males in obese girls (23.5 +/- 1.7 ng/mL against 18.0 +/-7.6 ng/mL, p = 0.040) and women (21.3 +/- 4.4 ng/mL against 15.8 +/- 7.4 ng/mL). Leptin levels correlated with body mass index, waist circumference and waist to-hip ratio. A positive correlation was observed between serum leptin and cholesterol, triglycerides and LDL-cholesterol. No correlation was seen with fasting blood glucose and HDL-cholesterol. CONCLUSIONS: Leptin levels correlate significantly with anthropometric and laboratory parameters in obese children. There is a need for further studies on the role of leptin in childhood obesity and metabolic syndrome.

Growth pattern and skeletal maturation following growth hormone therapy in growth hormone deficiency: factors influencing outcome.

OBJECTIVE: To evaluate pattern of growth and skeletal maturation following growth hormone (GH) therapy in children with GH deficiency (GHD) with special emphasis on factors influencing outcome. METHODS: Records of ninety-six children (67 boys, 29 girls) with GHD treated with GH for 2.3 +/-2.1 years were reviewed. RESULTS: Height SDS at the end of treatment was significantly higher than that at initiation (-3.4 +/- 1.7 versus -4.8 +/-1.6, P < 0.001); it was however lower than target height SDS (corrected height SDS (1.8 +/- 1.6, P < 0.001). The greatest increase in height SDS was observed during the first two years of treatment. Kaplan Meier survival analysis showed that 92%; of all subjects achieving end height SDS in the target height range did so within the first two years of treatment. Height SDS for bone age increased by 0.7 +/-0.9 during treatment (from -2.5 +/- 1.0 to -1.8 +/- 1.5, P < 0.001); the increase was however lower compared to that for height SDS for chronological age (P < 0.01) suggesting inadvertent skeletal maturation. End height SDS was influenced by duration of treatment and corrected height SDS on multivariate analysis. CONCLUSION: GH treatment improves growth parameters in GHD; height however still remains compromised. Most of the catch-up growth occurs within two years of treatment emphasizing the need of optimal treatment during this period. Inadvertent skeletal maturation during treatment indicates a need for evaluating the role of agents effective in retarding skeletal maturation.

Insulin like growth factors axis and growth disorders.

The growth hormone-insulin like growth factor (GH-IGF) axis plays a crucial role in the regulation of growth. Initially considered to be a mediator of growth hormone actions, IGF axis has been established as an independent endocrine system with wide array of actions. Recent advances have led to tremendous increase in the clinical utility of the IGF axis. IGF-based investigations (IGF1 and IGF binding protein 3) are now replacing GH-based investigations for evaluation and monitoring of disorders of the GH-IGF axis. IGF therapy has been successfully utilized in growth hormone insensitivity syndrome and GHD type 1B. The possibility of IGF axis as therapeutic options is being explored in wide variety of disorders like hypoxic-ischemic encephalopathy, Alzheimer's disease and psoriasis.

Familial combined hyperlipidemia in a North Indian kindred.

Familial combined hyperlipidemia is the most common genetic hyperlipidemia and is responsible for premature coronary artery disease. It is genetically heterogenous and no single diagnostic marker exists. The authors report an affected North Indian kindred spanning three successive generations with a possible autosomal dominant pattern of inheritance and all of them had combined dyslipidemia [elevated total cholesterol, predominantly the low density lipoprotein (LDL) fraction and elevated triglycerides]. The proband, a 4-month-old male baby, was incidentally discovered to have a lipaemic serum and so further evaluated. Both the index case and his maternal grandmother, a non-obese diabetic (type 2) with hypertension, had an atherogenic lipoprotein phenotype. Lipaemia retinalis was documented in this baby but xanthomas and coronary artery disease were not noted in the kindred. The present case report highlights the failure of dietary therapy in the proband and explores new options.

Cytogenetic causes for recurrent spontaneous abortions - An experience of 742 couples (1484 cases).

BACKGROUND: First trimester pregnancy loss is a very common complication and a matter of concern for couples planning pregnancy. Balanced chromosomal rearrangements in either parent is an important cause of recurrent pregnancy loss particularly in the first trimester. AIMS: In this study an evaluation of the contribution of chromosomal anomalies in causing repeated spontaneous abortions was made. METHODS AND MATERIALS: A review of the cytogenetic data in 742 couples (1484 individuals) with recurrent spontaneous abortions who were examined for chromosomal aberrations in the period 1990-2003 is presented. Women who had at least two abortions, or spontaneous abortions preceded or followed by fetal deaths or birth of a malformed child, and patients who had recurrent spontaneous abortions (> 3) with normal live issue/s were studied. RESULTS: Chromosomal rearrangements were found in 31 individuals (2%). These abnormalities included 22 (2.9%) structural aberrations, 9 (1.2%) numerical anomalies. In addition to these abnormalities, 21 (3.2%) chromosomal variants were also found. CONCLUSION: Chromosomal analysis is an important etiological investigation in couples with repeated spontaneous abortions as it helps in genetic counseling and deciding about further reproductive options.

21-Hydroxylase deficiency: clinical features, laboratory profile and pointers to diagnosis in Indian children.

We evaluated clinical features, laboratory profile and pointers to diagnosis of 21-hydroxylase deficiency in children presenting to the Pediatric Endocrine Clinic of our hospital from 1990 to 2002. Of the 94 patients included in the study 46 had salt wasting form (SW, 21 girls), 44 simple virilizing form (SV, 34 girls) and 4 non-classical form of the disease (NC, all girls). No difference was observed in the mean (95% confidence interval) age at diagnosis in boys and girls with salt wasting (2.3 mo (0.7-3.9 mo) against 1.3 mo (0.9-1.7 mo), p not significant) despite the presence of genital ambiguity in all girls at birth. Diagnosis of salt wasting was missed at admission in 18 boys (72%) and 3 girls (14.3%) highlighting the need for high index of suspicion for the disorder. Eight patients with 46 XX karyotype (14.5%) had male-like external genitalia with cryptorchidism emphasizing the need for evaluation of boys with cryptorchidism for female pseudohermaphroditism. Our study reiterates the need for early recognition and management of 21-hydroxylase deficiency in children in countries where neonatal screening programs are not feasible.

Familial hypercholesterolemia.

Abnormalities in the lipid profile though uncommon in pediatric practice pose an increased risk for developing heart disease. Studies suggest that adult cardiovascular disease has its roots in children and young adults. A significant correlation between atherosclerotic changes in children and young adults and total and LDL cholesterol levels also exists. The association is particularly true for Familial Hypercholesterolemia. We report a young boy aged 14 years who presented with all the features of Familial Hypercholesterolemia.

Evaluation of low dose ACTH stimulation test in suspected secondary adrenocortical insufficiency.

BACKGROUND: Several studies in the last few years have shown that the standard 250 micro g dose used in ACTH stimulation test may be very high and have suggested that a dose of 1 micro g may be sufficient for evaluating hypothalamo-pituitary adrenal (HPA) axis. AIMS: To evaluate the role of low dose ACTH stimulation test in patients with suspected Secondary Adrenal Insufficiency (SAI). SUBJECTS AND METHODS: Thirty-one patients of suspected SAI with a documented pituitary lesion and seven normal healthy controls were included in the study. All the subjects underwent ACTH stimulation test with standard high dose (HD= 250 microg) and low dose (LD= 1 microg) ACTH. Insulin Induced Hypoglycaemia (IIH) test was done in 7 out of 9 patients in whom the results of the two tests were discordant. The cut off for normal HD stimulation test was taken as peak cortisol response > 18 microg/dl and for LD test, either a cortisol response of > 18 microg/dl or an increment of more than 7 micro g/dl over the basal value at any time during the test, on the basis of response observed in controls. RESULTS: 22/31 patients (74%) in SAI group showed concordant results with both tests, whereas nine patients had discordant results. These nine patients showed AI with LD ACTH, but HD ACTH test showed a normal response. In 7 of these 9 patients who underwent IIH, AI was confirmed in 6. CONCLUSION: The LD ACTH stimulation test seems to be better than HD ACTH stimulation test for evaluating HPA axis in patients with suspected SAI. When basal cortisol is normal, LD ACTH stimulation test detects subtle SAI.

Long-acting GnRH analogue triptorelin therapy in central isosexual precocious puberty.

OBJECTIVE: To evaluate the efficacy of long acting GnRH analogue in improving the auxological outcome of patients with central isosexual precocious puberty (CIPP) and to determine the factors influencing the response. METHODS: Thirty-five patients (30 girls, 5 boys) with CIPP were treated with a long acting GnRH analogue, triptorelin. Final height outcomes and factors affecting treatment were analyzed. RESULTS: Treatment was started at the chronological age (CA) of 6.5 1.8 years in girls and 4.4 1.5 years in boys and continued for a period of 3.7 1.8 years in girls and 6 1.8 years in boys. Follow-up period after discontinuation of treatment was 2.2 0.5 years in girls and 2.6 0.3 years in boys. Treatment led to regression of precocious puberty and reversal of secondary sexual characteristics. There was decline in growth rate reflected by a fall in heightSD of 0.8 0.8 in girls and 2.3 0.9 in boys (p = 0.014), an even greater retardation in bone age (BA) advancement with a decrease in BA-CA of 1.7 1 years in girls and 2.7 1 years in boys and a fall in heightSDBA of 1.5 1.1 in girls and 2.1 1.6 in boys. Final height (149.8 6.9 cm in girls and 161.9 3.9 cm in boys) exceeded projected height at the onset of treatment (143.4 8.3 cm in girls and 154.3 2.7 cm in boys) by 6.4 2.4 cm in girls and 7.6 1.5 cm in boys ( p < 0.001 in both the groups). Factors influencing height gain included age at start of therapy (r = 0.715), BA-CA at the time of initiation of treatment (r = 0.734), heightSDBA at the onset of treatment ( r = 0.566) and the duration of treatment (r = 0.711). Girls treated at an age of less than 6 years (n = 9) had a greater height gain (8.7 1.6 cm versus 5.3 1.9 cm, p < 0.001) and achieved similar final height (148.7 8 cm versus 150.2 6.6 cm) in those treated after this age (n = 21). No side effects of GnRH therapy were observed in the study. CONCLUSION: Long acting GnRH therapy is effective in improving the auxological outcome of patients with CIPP. Maximum benefit is observed in girls with greater bone age advancement treated at a younger age and for a longer duration of treatment. These girls had lower bone age advance at discontinuation of treatment.