Precocious puberty in children

To determine the etiology of precocious puberty in children and to compare the clinical and laboratory parameters of central and peripheral precocious puberty. Cross-sectional study. Endocrine Clinic at National Institute of Child Health, Karachi, from January 2009 to December 2011. Children presenting with precocious puberty were included. The age of onset of puberty was documented. Clinical evaluation, Tanner staging, height, height SDS, weight, weight SDS, body mass index, bone age, pelvic USG, plasma estradiol level and GnRH stimulation were done. Ultrasound of adrenal glands, serum level of 17 hydroxyprogesterone, ACTH, Renin, aldosterone and testosterone were performed in children with peripheral precocious puberty. MRI of adrenal glands and gonads was done in patients with suspected tumor of that organ and MRI of brain was done in patients with central precocious puberty. Skeletal survey was done in patients with Mc Cune-Albright syndrome. CAH [81.8%] indentified as a main cause in peripheral percocious puberty and idiopathic [67.74%] in central precocious puberty. Eighty five patients were registered during this period. The conditions causing precocious puberty were central precocious puberty [36.47%], peripheral precocious puberty [38.82%], premature pubarche [10.58%] and premature thelarche [14.11%]. There was a difference in the age of onset of puberty in case of central precocious puberty [mean=3, 2-6 years] versus peripheral precocious puberty [mean=5.25; 3.62 - 7.0 years]. Children with central precocious puberty showed higher height SDS, weight SDS, FSH, LH than those with peripheral precocious puberty. Etiology in majority of cases with peripheral precocious puberty was congenital adrenal hyperplasia and idiopathic in central precocious puberty. Central precocious puberty children showed higher height SDS, weight SDS, FSH, LH than peripheral precocious puberty

Etiological diagnosis of undervirilized male / XY disorder of sex development

To do clinical, hormonal and chromosomal analysis in undervirilized male / XY disorder of sex development and to make presumptive etiological diagnosis according to the new Disorder of Sex Development [DSD] classification system. Case series. Endocrine Unit at National Institute of Child Health, Karachi, Pakistan, from January 2007 to December 2012. Patients of suspected XY DSD / undervirilized male visiting endocrine clinic were enrolled in the study. Criteria suggested XY DSD include overt genital ambiguity, apparent female/male genitalia with inguinal/labial mass, apparent male genitalia with unilateral or bilateral non-palpable testes, micropenis and isolated hypospadias or with undescended testis. The older children who had delayed puberty were also evaluated with respect to DSD. As a part of evaluation of XY DSD, abdominopelvic ultrasound, karyotype, hormone measurement [testosterone, FSH, LH], FISH analysis with SRY probing, genitogram, laparoscopy, gonadal biopsy and HCG stimulation test were performed. Frequencies and percentages applied on categorical data whereas mean, median, standard deviation were calculated for continuous data. A total of 187 patients met the criteria of XY DSD. Age ranged from 1 month to 15 years, 55 [29.4%] presented in infancy, 104 [55.6%] between 1 and 10 years and 28 [15%] older than 10 years. Twenty five [13.4%] were raised as female and 162 as [86.6%] male. The main complaints were ambiguous genitalia, unilateral cryptorchidism, bilateral cryptorchidism, micropenis, delayed puberty, hypospadias, female like genitalia with gonads, inguinal mass. The karyotype was 46 XY in 183 [97.9%], 46 XX in 2 [1.1%], 47 XXY in 1 [0.5%], 45 X/46 XY in 1 [0.5%] patient. HCG stimulation test showed low testosterone response in 43 [23%], high testosterone response in 62 [33.2%], partial testosterone response in 32 [17.1%] and normal testosterone response in 50 [26.7%]. Genitogram was carried out in 86 [45.98%] patients. Presumptive etiological diagnosis of androgen sensitivity syndrome/ 5-alpha reductase deficiency, testicular biosynthetic defect/ leydig cell hypoplasia, partial gonadal dysgenesis, ovotesticular DSD, XX testicular DSD, mixed gonadal dysgenesis, testicular vanishing syndrome, klinefelter syndrome, hypogonadotropic hypogonadism, isolated hypospadias and isolated micropenis was made. Clinical, chromosomal and hormonal assessment may help in making the presumptive etiological diagnosis. Further molecular genetics analysis are needed in differentiating these abnormalities and to make a final diagnosis

Effect of intravenous pamidronate treatment in children with osteogenesis imperfecta

To assess the beneficial effect of intravenous pamidronate treatment in children with osteogenesis imperfecta [OI]. Experimental study. Endocrine Unit at the National Institute of Child Health, Karachi, Pakistan, from January 2007 to December 2011. All children diagnosed with osteogenesis imperfecta on the basis of repeated spontaneous fractures and typical radiological findings registered during the study period, were included in this study. Pamidronate therapy were offered to those with more than 3 fractures per year or had platyspondyly. Pamidronate disodium was diluted in isotonic saline and administered by slow ravenous infusion over 3 hours in a dosage 1 mg/kg/day for 3 consecutive days 3 monthly for 2 years. Fracture rate, bone mineral density [BMD], mobility score, wellbeing and pain episodes were evaluated at baseline and 2 years after the treatment. Good response was defined as less than 2 fractures per year or mobility score improvement and poor response as more than 2 fracture per year with mobility score less than 2. Seventy two patients were included in this study. There were 40 boys and 32 girls with mean age of 3.64 +/- 3.2 years. The annual fracture rate decreased overall from 5.8 +/- 1.61 to 0.6 +/- 0.93 [p < 0.001]. BMD Z-score improved from -5.3 +/- 1.74 to -1.7 +/- 0.72 [p < 0.001]. Mobility score was 0.94 +/- 1.30 at baseline and 2.5 +/- 1.02 at the end of the treatment [p < 0.001]. Wellbeing gained from 3.63 +/- 1.44 to 7.8 +/- 1.18 [p < 0.001] and pain episode improved from 24.1 +/- 8.15 to 2.7 +/- 8.31 [p < 0.001]. Good response was noted in 92% of patients and poor response in 8% patients. Bisphosphonate seems to be an effective symptomatic treatment for children with osteogenesis imperfecta irrespective of severity of mutation or clinical phenotype. Cyclical bisphosphonate therapy has a positive effect on fracture rate, BMD, mobility score, wellbeing and pain episode

Hyperinsulinemia and waist circumference in childhood metabolic syndrome

To determine the characteristics of obese children presenting at a tertiary care hospital and the frequency of metabolic syndrome [MS] in them using two paediatric definitions. Cross-sectional study. The Endocrine Clinic of National Institute of Child Health, Karachi, from November 2005 till May 2008. A total of 262 obese children aged 4-16 years, with BMI greater than 95th percentile were included Children having obesity due to syndromes, medications causing weight gain, chronic illness and developmental disability were excluded. Blood pressure, waist circumference, fasting triglycerides, HDL, insulin and glucose levels were obtained. Obesity was defined as BMI > 95th percentile for age and gender according to the UK growth reference charts. The prevalence of metabolic syndrome was estimated using to the De Ferrantis and Lambert definitions. The frequency of MS varied between 16% and 52% depending on whether insulin levels were included in the definition. There was a significant positive correlation[r] when the metabolic parameters were correlated with waist circumference and insulin levels, except HDL which was negatively correlated. All the metabolic parameters like waist circumference, triglycerides, high density lipoprotein cholesterol and systolic blood pressure increased considerably circumference, triglycerides, high density lipoprotein cholesterol and systolic blood pressure increased considerably across the insulin quartile [p< 0.05]. The most noteworthy anthropometric and metabolic abnormality were the waist circumference [46.5%] and insulin levels [58%] respectively. There was a marked difference in the frequency of metabolic syndrome according to the definition used. The waist circumference and hyperinsulinemia are significant correlates of MS in obese children. There is a need for establishing normal insulin ranges according to age, gender and pubertal status. The clinical examination and investigations ought to include waist circumference and insulin levels together as a part of the definition of MS, for early detection and intervention of childhood obesity