Iodine Deficiency in Neonates: Where Do We Stand After a Quarter Century of Initiating Iodization Programs?

An observational study was conducted at the Section of Clinical Chemistry, Department of Pathology and Laboratory Medicine, to assess the iodine status using the World Health Organization (WHO), United Nations International Children's Emergency Fund (UNICEF), and the International Council for Control of Iodine Deficiency Disorders (ICCIDD) consensus criteria, which state that >3% prevalence of serum thyroid stimulating hormone (TSH) ≥10 mIU/L in the population is an indicator of iodine deficiency. Serum neonatal TSH was analyzed from January to December 2013. In a period of one year, a total of 11,597 neonates with the mean (25 percentile, 75 percentile value) age of 2.0 days (0.5–3.5) were tested for serum TSH. The overall mean TSH level was 3.38 mIU/L (5.63–1.96), with optimal levels (1–39 mIU/L) in 93%, <1 mIU/L in 6.3%, and ≥40 mIU/L in 0.3% neonates. Of all the neonates, 7.9% (N=916) showed TSH ≥10 mIU/L which is higher than the recommended WHO/UNICEF/ICCIDD criteria for mild endemicity for iodine deficiency in the population. These results suggest that iodine deficiency is still prevalent in our population, indicating a need for effective intervention programs and increasing awareness regarding the use of iodized salt and supplementation in all reproductive-aged women to prevent iodine deficiency in neonates.

Homeostatic model assessment for insulin resistance [HOMA-IR]: a better marker for evaluating insulin resistance than fasting insulin in women with polycystic ovarian syndrome

Objective: To assess the utility of HOMA-IR in assessing insulin resistance in patients with polycystic ovary syndrome [PCOS] and compare it with fasting insulin for assessing insulin resistance [IR]

Study Design: Observational study

Place and Duration of Study: Section of Clinical Chemistry, Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from January 2009 to September 2012

Methodology: Medical chart review of all women diagnosed with PCOS was performed. Of the 400 PCOS women reviewed, 91 met the inclusion criteria. Insulin resistance was assessed by calculating HOMA-IR using the formula [fasting glucose x fasting insulin]/405, taking normal value <2 in adults and hyperinsulinemia based on fasting insulin levels >/=12 microIU/ml

Results: A total of 91 premenopausal women diagnosed with PCOS were included. Mean age was 30 +/- 5.5 years. Mean HOMA-IR of women was 3.1 +/- 1.7, respectively with IR in 69% [n=63] women, while hyperinsulinemia was present in 60% [n=55] women [fasting Insulin 18.5 +/- 5.8 microIU/ml]. Hyperandrogenism was present in 53.8% [n=49], whereas 38.5% [n=35] women had primary infertility or subfertility, while 65.9% [n=60] had menstrual irregularities; and higher frequencies were observed in women with IR. Eight subjects with IR and endocrine abnormalities were missed by fasting insulin

Conclusion: Insulin resistance is common in PCOS and it is likely a pathogenic factor for development of PCOS. HOMAIR model performed better than hyperinsulinemia alone for diagnosing IR

Selective screening for organic acidurias and amino acidopathies in Pakistani children

Objective: To determine the frequency of organic acidurais [OA] and amino acidopathies [AA] in selected high-risk patients screened in two years

Study Design: Retrospective Observational study

Place and Duration of Study: The Aga Khan University Hospital [AKUH], Karachi, from January 2013 to December 2014

Methodology: Patients with OA and AA were included in the study and patients with IMDs other than OA and AA were excluded. Amino acids and organic acids were analyzed on high performance liquid chromatography and gas chromatography-mass spectrometry respectively. Clinical data and chromatograms of patients screened for IMDs were reviewed by chemical pathologist and metabolic physician

Results: Eighty-eight cases [4.7%] were diagnosed including 41 OA [46.5%], 28 AA [31.8%] and 19 others [21.5%] from 1,866 specimens analyzed. Median age of the patients was 1.1 years, with high consanguinity rate [64.8%]. Among OA, methyl CoA mutase deficiency was diagnosed in 9 [10.2%] and was suspected in 2 [2.3%] cases. Five [5.7%] cases of MHBD [2-methyl-3-hydroxybutyryl-CoA], 4 [4.5%] each of PPA [propionic aciduria] and HMG-CoA lyase deficiency, 3 [3.4%] cases each of IVA [isovaleric aciduria], multiple carboxylase deficiency, fructose-1, 6-biphosphatase deficiency, fumarase deficiency, GA-1 [glutaric aciduria type 1] and 2 [2.3%] cases of EMA [ethyl-malonic aciduria]. AA included 8 [9.1%] cases of MSUD [maple syrup urine disease], 6 [6.8%] cases of CBS [cystathionine beta-synthetase] and UCDs [urea cycle disorders] each, 5 [5.7%] cases of hyperphenylalaninemia and 3 [3.4%] cases of hyperprolinemia were reported. Other inherited metabolic disorders included: 9 [10.2%] cases of intracellular cobalamin defects, 2 [2.3%] cases each of alkaptonuria, Canavan's disease, SUCL [succinate CoA ligase] deficiency, and 1 [1.1%] case each of DPD [dihydropyrimidine] deficiency, GA-2, NKH [non-ketotic hyperglycinemia], AADC [aromatic amino acid decarboxylase] deficiency

Conclusion: This study presents frequency of OA and AA in the high-risk Pakistani pediatric population analyzed locally

Bone turnover markers for osteoporosis status assessment at baseline in postmenopausal Pakistani females

Objective: To assess bone turnover status in osteopenic and osteoporotic postmenopausal females

Study Design: Cross-sectional analytical study

Place and Duration of Study: The Aga Khan University Hospital, Karachi, from January to December 2013

Methodology: A cross-sectional study was conducted on 203 postmenopausal females undergoing bone mineral density testing [BMD] by DXA scan. Patients with clinical history of any disorder or medications affecting bone turnover were excluded. Bone turnover was assessed with osteocalcin and beta-CTx. Data was analyzed by SPSS version 19

Results: Mean age of the participants was 54 +/- 4.66 years with a mean BMI of 28.7 +/- 5.5 kg/m2. Mean beta-CTx [0.28 +/- 0.24 ng/ml] and osteocalcin [21.5 +/- 10.6 ng/ml] levels were within the normal reference range. Subjects were grouped into normal [26.6%], osteopenic [44.8%], and osteoporotic [28.6%] based on the t-scores. Serum levels of osteocalcin and beta-CTx between normal, osteopenic, and osteoporotic groups were not significantly different. beta-CTx was negatively and significantly associated with only lumber spine BMD [r = -0.13, p=0.04]. Positive association [< 0.0001] was noted between both markers in normal, osteopenic, and osteoporotic females. However, association of these markers with BMD in the 3 groups were not found. Multivariate linear regression showed a positive and significant effect of BMI on BMD [beta = 0.332, p= < 0.0001]. beta-CTx had negative but significant effect on BMD [beta = -0.155, p= 0.018] of postmenopausal women

Conclusion: Association between baseline levels of BTM and rate of bone loss is variable and site dependent. beta-CTx correlates better with BMD. However, role of osteocalcin in postmenopausal osteoporosis is uncertain and needs further investigation

Validation of a food frequency questionnaire for assessing macronutrient and calcium intake in adult Pakistani population

To develop and validate a food frequency table [FFQ] for use in urban Pakistani population. A validation study. The Aga Khan University, Karachi, from June to November 2008. Healthy adult females, aged >/= 18 years who consented to be included in the study were inducted, while males, unhealthy females, aged below 18 years or who did not consent were excluded. The FFQ was administered once while 4, 24 hours recalls spread over a period of one year were administered as the reference method. Daily intakes for energy, protein, fat, and calcium intake were estimated for both the tools. Crude and energy adjusted correlations for nutrient intakes were computed for the FFQ and mean of 4, 24 hours recalls and serum N-telopeptide of type-I collagen [NTx]. The correlation coefficients for the FFQ with mean of 4, 24 hours recall ranged from 0.21 for protein to 0.36 for calcium, while the correlation for nutrient estimates from the FFQ with NTx ranged from -0.07 for calcium to 0.01 for energy. Highly significant correlations were found for nutrient intakes estimated from the FFQ vs. those estimated from the mean of 4, 24 hours recalls but no correlations was found between nutrient estimates from the FFQ and serum NTx levels. FFQ was concluded to be a valid tool for assessing dietary intake of adult females in Pakistan.

Raised 17-hydroxyprogesterone levels in congenital adrenal hyperplasia

Congenital adrenal hyperplasia [CAH] refers to autosomal recessive diseases resulting from deficiency of enzymes involved in the production of cortisol by the adrenal glands. This study was designed to determine the frequency of suspected congenital adrenal hyperplasia patients by evaluating the laboratory data of blood 17-OHP. The study was conducted at Chemical Pathology Section of Department of Pathology at the Aga Khan University, Karachi. The basic demographic data of 2282 subjects was recorded, screened for blood 17-OHP levels from January 2007 to December 2010. A cutoff of >/= 4 ng/ml was considered as suggestive of CAH. The results showed 17-OHP levels >/= 4 ng/ml were found predominantly among infants [14.4%] and in females [18.2%]

Agreement between serology and histology for detection of helicobacter pylori infection

To determine the percentage agreement between serology and histology for detection of Helicobacter [H.]pylori infection. Cross-sectional analytical study. Department of Pathology and Microbiology, The Aga Khan University and Hospital, Karachi, from January to December 2009. Fifty subjects were selected by non-probability purposive sampling from laboratory data who had serological testing of H. pylori IgG antibody, prior to histological evaluation of endoscopic gastric or/and duodenal biopsies. Serological Quantification of H. pylori IgG was carried out with HpG screen ELISA kit [Genesis Diagnostics, UK], using an enzyme linked immunosorbent assay for detection of IgG antibodies against H. pylori. Manufacturer's recommended cutoff value was used and results were considered positive when greater than 7 U/ml. For histological diagnosis, an expert histopathologist characterized the presence of spiral bacteria in the mucosal layer or the surface of epithelial cells on microscopic examination, as a positive test. An agreement of 0.72 was found by Kappa statistics between serology and histopathology results and a good diagnostic accuracy [86%] of serological testing was observed for the diagnosis of H. pylori infection. A substantial agreement was found between serology and histopathology results to detect the H. pylori infection. Laboratory-based serologic testing using ELISA technology to detect IgG antibodies is inexpensive, noninvasive and convenient method to detect the H. pylori infection in primary care setting.

Illuminating the dark side - vitamin d status in different localities of karachi

This study was conducted to determine the association between place of residence [grouped into neighbourhoods], and 25-hydroxy D [25[OH]D] levels of individuals of Karachi. Addresses of 4788 individuals tested for 25[OH]D at the clinical laboratory of the Aga Khan University [AKU], Karachi, from January 2007 to June 2008 were reviewed. The neighbourhoods were categorized into ten, based on locality attributes. A high overall prevalence [74%] of vitamin D deficiency [VDD] was observed. There was a significant difference [p-value < 0.01] between mean log 25[OH]D levels amongst neighbourhoods grouped according to distinct housing structure attributes and localities. A high frequency of VDD in all the studied localities of an urban city warrant dietary vitamin D supplementation and food fortification

Response of a single 'mega intramuscular dose' of vitamin d on serum 25OHD and parathyroid hormone levels

To determine the changes produced in serum 25OHD and iPTH levels after 600,000 IU of injection cholecalciferol in volunteers. Interventional study. Section of Chemical Pathology, Department of Pathology and Microbiology, the Aga Khan University Hospital, Karachi, from June 2009 - June 2010. Volunteers of either gender aged 18-40 years with known 25OHD, calcium [Ca], creatinine [Cr] and phosphorous [P] levels were included in the study. Subjects on therapy like vitamin D and calcium supplements, corticosteroids or anti-epileptic medicines, primary hyperparathyroidism and hypercalcaemia, with co-morbidity like renal failure, liver disease and history of malabsorption, diarrhea or hyperthyroidism were excluded. All volunteers were given an intramuscular injection of vitamin D3 [cholecalciferol, 600,000 IU]. After 8 weeks, serum 25OHD, iPTH, Ca and P levels were determined again. For 25OHD level, cut-off of /= 75 as optimal level. Mean 25OHD and iPTH levels were 35.06 +/- 16.6 nmol/l and 81.15 +/- 76.78 pg/ml respectively at baseline. Seventeen volunteers were 25OHD deficient. Five had high iPTH levels [25%] [mean 156 +/- 123.7 pg/ml]. 25OHD and iPTH showed a significant inverse correlation at baseline [< 0.01]. After 8 weeks of injection vitamin D 25OHD levels became optimal in 6 subjects [35%] [mean 92.9 +/- 16.6 nmol/l]. It remained low in 5 volunteers [25%] [mean 41.6 +/- 9.6 nmol/l] while insufficient levels were seen in 9 volunteers [40%] [mean 63.3 +/- 5.8 nmol/l]. Follow-up mean Ca, P and iPTH were 2.25 mmol/l [ +/- 0.09], 1.1 [ +/- 0.1] and 47.52 pg/ml [ +/- 22.56] respectively. A significant increase in mean 25OHD level was seen at follow-up [p < 0.01], while the change in PTH was insignificant [p=0.05]. Single mega-dose of cholecalciferol achieved optimal levels of 25OHD in 35% of subjects after eight weeks of supplementation

Diagnostic utility of anti-citrullinated protein antibody and its comparison with rheumatoid factor in rheumatoid arthritis

To assess the diagnostic utility of anti-citrullinated protein antibody [anti-CCP] in rheumatoid arthritis [RA] and compare it with rheumatoid factor [RF]. Analytical study. Section of Chemical Pathology, Department of Pathology and Microbiology and Medicine, the Aga Khan University, Karachi, from January to May 2010. A review of medical records of patients presenting to the clinics with complaints of muscular or joint pains and who were tested for their serum anti-CCP was done. Inclusion criteria were presence of clinical synovitis in at least one joint and an absence of alternative diagnosis. Patients with arthralgia alone or with missing acute phase reactants information were excluded. Scoring and classification of RA was done using the 2010 RA Classification Criteria by the American College of Rheumatology [ACR]. Out of the 98 charts reviewed, ACR criteria showed 54 cases with RA. The mean age of the group was 46 +/- 15 years, 82.7% being females. High titers of anti-CCP corresponded with the ACR scores. The sensitivity and specificity of anti-CCP and RF reactivity for the diagnosis of RA were 54.7% and 95.5% versus 59.3% and 88.4% respectively. Anti-CCP is useful for the diagnosis of RA due to its higher specificity as compared to RF and can predict disease severity

Pattern of drugs of abuse identified in chemical samples

To determine the pattern of drugs of abuse in urine and blood samples processed at referral laboratory in Pakistan so that information on the type of drugs used can be identified and used for ready reference for future strategy. Observational study. Clinical Laboratory of The Aga Khan University Hospital, Karachi, from July 2006 to March 2008. Retrospective review of records were done for the common drugs that are used for screening at the Clinical Laboratory include alcohol, amphetamine, barbiturates, benzodiazepines, cannabinoids, cocaine and opiates. Alcohol was tested in blood and others were identified using urine. Percentages of tests screened positive and negative for individual drugs were computed by using SPSS 16.0. The ratio between male and female users was also established. A total of 17,714 tests were performed for drugs. The mean age of the patients whose samples were processed was 30 +/- 14.84 years. Majority used benzodiazepines 520/1317 [39.5%] among the samples tested for drug of abuse, followed by cannabinoids 423/5450 [7.8%], alcohol 75/1302 [5.8%], barbiturates 32/1148 [2.8%], opiates 137/5640 [2.4%], cocaine 5/1655 [0.3%] and amphetamine 3/1 202 [0.2%]. In all, males 15411 [87%] were tested more frequently as compared to females 2303 [13%]. Males were more frequently tested for drug abuse; however, drug abuse is increasingly seen among females. Benzodiazepines are the most frequently used. The same pattern of drugs abuse existed in different gender and age group. There is a need to explore the pattern and type of drug abuse on national scale

Work flow analysis: audit of the turn around time in chemical pathology in a tertiary care hospital

A retrospective analysis of the laboratory results was performed to explore the turnaround time [TAT] for the laboratory services. The TAT for specimens arriving at the main laboratory from wards, main laboratory and critical care areas was noted and compared with the standard set for reporting. Median TAT for results of 169 blood samples was on average 195 min [n=170], 172 min [n=169], 121 min [n=167] from main lab, wards and for STAT samples from critical care areas respectively. Median analytical time was 170 min, 105 min, and 72 min from main lab, from wards and for STAT samples respectively. This TAT is within acceptable limits according to the standard sets. However, high transport time from critical care areas [median 49 min] was noted, which can be further improved if the portering and transport arrangements of the specimens are made more effective

Vitamin D deficiency osteomalacia: the continuing challenge

Vitamin D deficiency has long been recognized to be commonest in Pakistani immigrants then in the general population in UK. We report 2 cases [patients] from our metabolic bone disease clinic in Karachi, Pakistan. The patients presented with bone deformities secondary to vitamin D deficiency. Diet, lack of sunlight exposure and wearing the veil were identified as risk factors in one case, but the other case did not have obvious risk factors. Similar cases have been identified in our clinic, confirming that despite abundant UV light, vitamin D insufficiency is a problem in people living in Pakistan. Osteomalacia presents in a clinically florid form in our population. Metabolic studies to determine the pathophysiology of vitamin D deficiency in Asian population within homeland are long overdue. It may be cost effective to pool resources inorder to setup national or regional resources to study this problem