Comparison of classical and non-classical turner syndrome at NICH Karachi

Objective: to analyse chromosomal abnormalities of the patients who were referred for the screening of short stature and delayed puberty and to verify the association between karyotype and phenotype in confirmed Turner Syndrome [TS] patients

Study Design: descriptive study

Place and Duration of Study: department of Pediatric Endocrinology and Diabetes Unit-II, National Institute of Child Health, Karachi, from January 2011 to June 2016

Methodology: patients referred for the evaluation of short stature or delayed puberty were for the assessment of karyotype and phenotype correlations; standard karyotyping was executed and analysed on the basis of routine G-banding technique. Echocardiography and pelvic ultrasonography was also performed

Results: the study population consisted of 79 registered patients, with short stature and delayed puberty 48/79 [60.75%], short stature 68/79 [86.07%], and ambiguous genitalia 5/79 [6.32%]. Conferring to the karyotype analysis, classical Turner Syndrome 45, X was found in 42/79 [53.16%], isochromosomes 13/79 [16.45%], and mosaicism was present in 11/79 [14.1%]. Only 7/79 [8.86%] cases were diagnosed in infancy

Conclusion: the results of the study showed the consistency of short stature and delayed puberty in most of patients. Monosomy of X chromosome was the commonest followed by isochromosomes, mosaicism and structural abnormalities of X chromosome. No remarkable difference was found among classical and non-classical TS patients' height

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

Knowledge of integrated management of neonatal and child illness [IMNCI] in final year medical students

To assess and compare the knowledge regarding Integrated Management of Neonatal and Child Illness [IMNCI] in final year medical students of two private and two public sector universities in Karachi, Pakistan. A cross-sectional Knowledge, Attitude and Practice [KAP] study was conducted in four different medical universities of Karachi using a self administered questionnaire, comprising of 20 questions. The sample size of 240 was selected, out of which 184 students responded positively. The mean age of students was M=22.9 [S.D= 0.88]. Basic knowledge was defined as students answering at least half of the questions correctly whereas partial knowledge was defined as students who could answer at least one option correctly. The Data was analyzed using SPSS 17. The study was commenced in July 2011 and completed by September 2012. Out of the respondents, 80.4% of the students had basic knowledge [being able to answer 50% or more of the questions correctly] of IMNCI. Of both the sectors, basic content knowledge was more in the public sector universities as compared to private sector universities. The hypothesis that more than 50 percent of the students will have basic knowledge of IMNCI was proven to be correct. It was shown that students of the public sector universities had relatively more knowledge; however more students have partial knowledge then complete knowledge. Although basic knowledge was found to be more in the students of public sector institutes, knowledge of IMNCI practice was correct in more students in the two private universities