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.

Comparison of diagnostic accuracy of Glycated Hemoglobin [HBA1C] and 2-hour post Glucose for Diabetes using American Diabetic Association [ADA] cut offs in Pakistani population

Objectives: To determine median HbA1c level in patients screened for DM and compare the diagnostic accuracy of HbA1c with the currently recommended ADA cut off, using 2 hours [h] plasma glucose [2-h PG] post 75 grams oral glucose tolerance test [OGTT] as gold standard

Study Design: Cross sectional study

Place and Duration of Study: Aga Khan University Hospital Karachi, from Jul 2014 to Nov 2015

Patients and Methods: Consecutive subjects screened by OGTT for diabetes mellitus [DM] were included. Blood sample for plasma glucose and HbA1c were analyzed on ADVIA 1800

Results: Total 146 subjects were included with median age 45 [IQR 54.2-35] years; 53 percent [n=77] being females. Median HbA1c of the study subjects was 6 percent [IQR 6.6-5.6]. Positive correlation was observed between age and HbA1c [5.7 percent [IQR 6.2-5.3] <40 y, 6.2 percent [IQR 6.8-5.8] in >40 y subjects; r 0.34, p=0.000]. Males had higher HbA1c than females [6.1 percent [IQR 6.8-5.7] years. 5.9 percent [IQR 6.4-5.4]; r 0.17, p=0.036]. HbA1c levels were significantly different amongst the different ethnic groups residing in Pakistan [p-value<0.03]. HbA1c was positively correlated with FPG [r=0.59, p-value<0.001] and 2-h PG [r=0.56, p-value<0.001]. Sensitivity, specificity, PPV, NPV for HbA1c at cutoff of 6.5 percent in diagnosing diabetes mellitus [DM] were 70 percent, 89 percent, 72 percent and 80 percent respectively

Conclusion: High median HbA1c levels is noted in our subjects. At cut off level of HbA1c >/=6.5 percent, 70 percent of subjects with DM were diagnosed using ADA criteria of 2-h PG for diabetes as gold standard. Ethnic differences were also observed in levels of HbA1c. There is a need to define cut off for our population

High burden of subclinical lead toxicity after phase out of lead from petroleum in Pakistan

Objective: To evaluate the frequency of subclinical lead toxicity

Study Design: Cross-sectional study

Place and Duration of Study: Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from January 2011 to December 2014

Methodology: Analysis of laboratory data for blood lead levels [BLL] was performed. Lead was tested by atomic absorption spectrometer. For all subjects, only initial test results were included while the results of repeated testing were excluded. Exemption was sought from institutional ethical review committee. BLL of 2-10 ug/dl and 10-70 ug/dl in children and adults, respectively were taken as subclinical lead toxicity

Results: Amongst the total number of subjects tested [n=524], 26.5% [n=139] were children [<16 years] while rest were adults. Overall median BLLs was 6.4 ug/dl [20.9-3.1]. The median BLL was 4 ug/dl [6.7-2.6] in children and 8.3 ug/dl [27.9-3.4] in adults, respectively. The BLL increased with age; higher levels were observed in age range 21-30 years of subjects [median lead level 16.9 ug/dl [36.1-4]] and lower level [4.2 ug/dl [6.8-2.6]] in children with <10 years of age. Only 16% [n=22] children had desirable lead levels while most had either subclinical [76%, n=106] or toxic lead levels [8%, n=11]. In adults, [55%, n=212] subjects had desired lead levels, and 40% [n=154] and 4.99% [n=19] had subclinical and toxic lead levels

Conclusion: Presence of subclinical lead poisoning even after phasing out of lead petroleum in Pakistanis is alarming, especially in children. A national population-based study to determine the lead status and targeted intervention to identify potential sources is need of the time

Evaluation of 'CKD-EPI Pakistan' equation for estimated glomerular filtration rate [eGFR]: a comparison of eGFR prediction equations in Pakistani population

Objective: To evaluate the results of 24-hour urinary creatinine clearance [CrCl] with estimated glomerular filtration rate [eGFR] using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI], CKD-EPI Pakistan [CKD-EPI Pak], Cockcroft Gault [CG] and 4-variable Modification of Diet in Renal Disease [MDRD] equations

Study Design: Descriptive, cross-sectional study

Place and Duration of Study: Section of Clinical Chemistry, Department of Pathology and Laboratory Medicine, The Aga Khan University, Karachi, from June to October 2013

Methodology: Laboratory data of subjects ³18 years ordering 24-hour urinary CrCl from June to October 2013 was retrieved. Statistical comparison of eGFR using CKD-EPI, CKD-EPI Pak, CG and MDRD with the timed urine collection CrCl was done using regression analysis

Results: The mean age of the group [n=670] was 51.3 +/-15.4 years with a median of 53 [IQR:22.3] years, 55.7% being males. Median BMI of males and females was 26.98 kg/m[2] [IQR: 7.09] and 26.16 kg/m[2] [IQR: 6.97], respectively. Mean GFR using 24-hour creatinine clearance was 57.1 +/-35.9 ml/min/1.73m[2] with a median of 51 ml/min/1.73m[2]. Urinary creatinine clearance showed strong correlation with CG, MDRD, CKD-EPI and CKD-EPI Pak, showing r=0.78, r=0.79, r=0.82, and r=0.82, respectively. Sensitivity was highest for the CKD-EPI Pakistan [84.7%]. Similarly, CKD-EPI Pakistan equation showed the highest agreement [88.7%] with CrCl compared to the other formulae

Conclusion: The CKD-EPI Pak equation is more accurate and precise than the CG, CKD-EPI and MDRD in estimating GFR in Pakistani population

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

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

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

Multifocal venous thrombosis in Behcet's disease

Behcet's disease is a multisystem inflammatory vascular disorder with a chronic course characterized by recurrent oral and genital ulcers, eye lesion, arthritis and skin lesions. It has a typically waxing and waning course. The cause and pathogenesis of the disease are unclear and specific treatment is not available. A 39 years old man presented with rash, ocular manifestation and left leg swelling. He was found to have deep venous thrombosis of left leg along with recurrent cerebral venous thrombosis. He was a known case of Behcet's disease since 3 years and had been on anticoagulants since then