Type IV collagen is the principal component of glomerular basement membrane and messangial matrix. Studies have shown increased levels of urinary type IV collagen (uIV) in diabetic patients compared to healthy controls. The concentration of uIV increases gradually as diabetic nephropathy progresses. Aim and method: This study was carried out to determine whether urinary type IV collagen (uIV) can serve as an indicator of diabetic nephropathy. Using a sandwich enzyme immunoassay technique, uIV excretion was determined in 30 type 2 diabetic patients with normoalbuminuria and 20 patients with microalbuminuria. Results: uIV excretion was signifi cantly increased in type 2 diabetics, in both normoalbuminuric and microalbuminuric patients, compared with healthy controls. The increase in urinary type IV collagen was well correlated with the amount of urinary albumin but not with HbA1C. Conclusion: Our fi ndings that uIV is higher in those with microalbuminuria and correlates with albuminuria, support uIV as an indicator of diabetic nephropathy. Whether the increased uIV excretion would predict the impending renal failure needs further confi rmation.

Thyrotoxic periodic paralysis (TPP) is a medical emergency characterised by sudden onset of muscle weakness with hypokalemia that resolves with the treatment of hyperthyroidism. We report three cases of thyrotoxic periodic paralysis seen at the Accident and Emergency Care Department, University of Malaya Medical Centre in a period of four months. We also review the clinical presentation, pathophysiology, biochemical features and management of TPP. All three patients were young Asian males, presenting with muscle weakness of sudden onset. The first patient presented with lower limb weakness and had symptoms of thyrotoxicosis and goitre. He had a previous similar episode which resolved spontaneously. The second patient presented with quadriplegia, respiratory acidosis and had no signs and symptoms of thyrotoxicosis. The electrocardiogram of this patient showed normal sinus rhythm with U wave in V3 and a flat T wave, which are characteristic of hypokalaemia. The third patient, who was a known case of thyrotoxicosis, was admitted thrice for hypokalemic paralysis during the study period. All cases had low serum potassium, suppressed TSH and elevated T4 confirming thyrotoxic periodic paralysis. Potassium therapy was useful during the crisis; however prophylactic potassium has not been shown to prevent attacks as seen in one of our cases. Conclusion: Thyrotoxic periodic paralysis should be considered in the differential diagnosis of sudden onset paralysis in young male patients. Determination of the plasma potassium levels and thyroid hormones help in the diagnosis. The definitive treatment for TPP is the achievement of euthyroid state.
Thyrotoxic periodic paralysis ; Patients ; Paralysis ; Review [Publication Type] ; Thyrotoxicosis

Pleural effusion is a common diagnostic problem. The analysis of serum and pleural fluid for tumour markers is widely used as a diagnostic aid in clinical practice. The aim of the present study was to determine the usefulness of simultaneous quantification of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA-125) in distinction of malignant from benign effusion. Data from a total of 78 patients including 53 patients with benign and 25 patients with malignant effusion was evaluated. The cut-off values for differentiating benign from malignant effusions were determined using results obtained from patients with known benign effusions (mean + 2 SD, 95% confidence interval). The cut-off for CEA and CA-125 were 5.1 ng/ml and 1707 IU/ml respectively. CEA assay in pleural fluid had an acceptable sensitivity and good specificity of 64% and 98% respectively. CA-125 had a sensitivity of 36% and specificity of 94%. The combination of the two tumour markers gave a sensitivity of 72% and specificity of 92.4%. We suggest a good clinical strategy may be to begin with CEA measurement (assay specificity 98%); if CEA is below the cut-off value (negative), CA-125 could then be measured to improve the sensitivity of detection of malignant effusions. However, measurement of these tumour markers is not cost effective from the point of view that it does not give information on the type of malignancy present. The latter has to be determined either by histological or cytological study.
CA-125 Antigen ; Carcinoembryonic Antigen ; Malignant Neoplasms ; Benign ; Pleural Effusion

The aim of this study is to assess tissue and serum prostate-specific antigen (PSA) in breast lesions; to compare tissue PSA with serum PSA; to compare tissue PSA in benign and malignant lesions and to compare PSA with known prognostic factors in breast carcinoma. Tissue PSA immunoreactivity in twenty women with breast carcinoma was compared with PSA in twenty-three women with benign breast lesions. Tissue PSA was also compared with known prognostic indicators such as tumour size, axillary nodal status, histological type, histological grade, oestrogen receptor status, progesterone receptor status and c-erbB-2 oncoprotein over-expression. Serum free PSAlevels from these women were measured pre- and post-operatively and an attempt was made to correlate serum PSA with tissue PSA expression. 40% and 43% of malignant and benign breast lesions respectively showed tissue PSA immunoreactivity. No significant difference was observed in the tissue PSA expression between these two groups as also between tissue PSA and known prognostic indicators. As serum PSA levels were below the detection limit (< 0.004 ng/ml) in all except two benign cases, no statistical evaluation was done for the latter. Tissue PSA expression did not correlate with other prognostic markers and detectable serum PSA levels were present in too few cases for statistical analysis. Although no definitive conclusion is possible in this preliminary study regarding the role of PSA in breast disease, it stimulates interest in further research in this direction.
public service announcement ; Tissues ; Serum ; Breast ; seconds

Aim: Autoantibodies against cyclic citrullinated peptide (anti-CCP) are considered to be a sensitive and specifi c marker for rheumatoid arthritis (RA). This study evaluated the diagnostic and analytical performances of the automated anti-CCP assay. Materials and Method: Sera from 80 patients with established RA, 65 from other rheumatic diseases (non-RA) and 55 from healthy controls were studied using second generation anti-CCP. Rheumatoid factor (RF) was also assayed in each sample, and the results were compared to the anti-CCP fi ndings. Serum pools were used to determine the precision and linearity. Results: At a cut-off of 7.4 U/ml for anti-CCP, the sensitivity and specifi city for RA were 65% and 98% respectively. RF had a sensitivity of 58% and a lower specifi city of 93 % than anti-CCP. Conclusion: The high specifi city of the assay suggests that anti-CCP is useful in the diagnosis of rheumatoid arthritis and in our cohort of study population anti-CCP exhibits a better diagnostic value than RF. A considerable proportion (28%) of RF-negative RA patients were anti-CCP positive. Based on analytical performance of the assay, we conclude that full automation and high throughput features of AxSYM makes it an ideal platform for routine testing of anti-CCP.

Introduction: The objective of the study is to determine the level of agreement between measured total carbon dioxide (TCO2) and calculated bicarbonate (HCO3–) in our laboratory. Materials and Methods: TCO2 and HCO3– values of 1820 samples drawn at the same time from the patient were compared. TCO2 from venous samples was measured on Dimension RxL while HCO3 – was obtained from arterial blood gas samples analyzed on Radiometer ABL 700. Results: The TCO2 and HCO3– values correlated well (r = 0.977, p<0.001), with the correlation given by the equation, y = 0.986x – 0.5335. Using Bland-Altman analysis, the bias was 0.87 mmol/L (SD 1.42 mmol/L), and the limits of agreement (LOA) were -1.92 to 3.67 mmol/L. Story and Poustie’s criteria were applied to study the agreement between these two methods. Based on the fi rst criterion that the bias between TCO2 and HCO3– should be less than ±1 mmol/L, the results for the two methods appear to be in good agreement. The second criterion requires that the LOA between the two methods should range between a bias of ± 2 mmol/L or a total span of 4 mmol/L; the LOA was exceeded in our study. Using the total allowable error in the Bland Altman plot also showed that the two values cannot be used interchangeably especially at the lower values. Conclusions: TCO2 did not show good agreement with HCO3–. Clinicians should be aware of this discrepancy and hence should be cautious when using HCO3– for management of acid-base disorders.

Introduction: The Malaysian Association of Clinical Biochemists (MACB) established a Task Force for Chronic Kidney Disease. A survey was undertaken by the Task Force on the reporting of estimated glomerular filtration rate (eGFR) and urine albumin by hospital laboratories in Malaysia in both the government and private sectors. Materials and Methods: An e-mail invitation to participate in an online survey was sent to hospital laboratories in Malaysia (n=140). Questions regarding methods for measuring creatinine, equations for calculating eGFR, eGFR reporting, the terminology used in reporting urine albumin, types of samples and the cut-off values used for normal albuminuria. Results: A total of 42/140 (30%) laboratories answered the questionnaire. The prevalent method used for serum creatinine measurement was the Jaffé method (88.1%) traceable to isotope-dilution mass spectrometry. eGFR was reported along with serum creatinine by 61.9% of laboratories while 33.3% of laboratories report eGFR on request. The formula used for eGFR reporting was mainly MDRD (64.3%) and results were reported as exact numbers even when the eGFR was >60 ml/min/1.73m2 . The term microalbumin is still used by 83.3% of laboratories. There is a large heterogeneity among the labs regarding the type of sample recommended for measuring urine albumin, reference interval and reporting units. Conclusion: It is evident that the laboratory assessment of chronic kidney disease in Malaysia is not standardised. It is essential to provide a national framework for standardised reporting of eGFR and urine albumin. Recommendations developed by the MACB CKD Task Force, if adopted by all laboratories, will lead to a reduction in this variability.

Introduction: Prolactin (PRL) exists in different forms in human serum. The predominant form is monomeric PRL (molecular mass 23 kDa) with smaller amounts of big PRL (molecular mass 50–60 kDa) and at times macroprolactin (molecular mass 150–170 kDa). Macroprolactin, generally considered to be biologically inactive, accounts for the major part of prolactin in some patients. Different immunoassays for prolactin differ in reactivity with this macromolecular complex. Aim: The present study was undertaken to assess the incidence of macroprolactinaemia in our cohort of hyperprolactinemic patients. Method: 204 samples with hyperprolactinemia were evaluated for macroprolactinemia by polyethylene glycol (PEG) precipitation and gel fi ltration chromatography (GFC). Recoveries <60% after PEG precipitation were considered to have macroprolactinaemia. Results: A total of 43 (21%) of these patients had less than 60% recovery after PEG precipitation. GFC confi rmed that in seven of these patients macroprolactin was the major part of the prolactin. Recoveries were < 40% PEG precipitation in these samples. Combined macro and hyperprolactinemia was observed in two samples and the recovery after PEG precipitation was >40% but 50%. The incidence of macroprolactinemia in our cohort of hyperprolactinaemic patients was noted to be 4.4%. Conclusion: Macroprolactin is a signifi cant cause of misdiagnosis, unnecessary investigation, and inappropriate treatment and hence it is useful to screen all patients with high PRL levels with PEG precipitation and to apply GFC to samples with recoveries <50%.

Hypophosphataemia is a metabolic disorder that is commonly encountered in critically ill patients.Phosphate has many roles in physiological functions, thus the depletion of serum phosphate could leadto impairment in multiple organ systems, which include the respiratory, cardiovascular, neurologicaland muscular systems and haematological and metabolic functions. Hypophosphataemia is defined asplasma phosphate level below 0.80 mmol per litre (mmol/L) and can be further divided into subgroupsof mild (plasma phosphate of 0.66 to 0.79 mmol/L), moderate (plasma phosphate of 0.32 to 0.65mmol/L) and severe (plasma phosphate of less than 0.32 mmol/L). The causes of hypophosphataemiainclude inadequate phosphate intake, decreased intestinal absorption, gastrointestinal or renal phosphateloss, and redistribution of phosphate into cells. Symptomatic hypophosphataemia associated withhaematological malignancies has been reported infrequently. We report here a case of asymptomaticsevere hypophosphataemia in a child with acute T-cell lymphoblastic leukaemia.A 14-year-old Chinese boy was diagnosed to have acute T cell lymphoblastic leukaemia (ALL).His serum biochemistry results were normal except inorganic phosphate and lactate dehydrogenaselevels. The serum inorganic phosphate level was 0.1mmol/L and the level was low on repeatedanalysis. The child had no symptoms related to low phosphate levels. The possible causes of lowphosphate were ruled out and urine Tmp/GFR was normal. Chemotherapy regime was started andthe serum phosphate levels started to increase. Hypophosphataemia in leukaemia was attributed toshift of phosphorus into leukemic cells and excessive cellular phosphate consumption by rapidlyproliferating cells. Several reports of symptomatic hypophosphataemia in myelogenous andlymphoblastic leukaemia in adults have been reported. To our knowledge this is the first case ofsevere asymptomatic hypophosphataemia in a child with ALL.

Introduction: Hyperandrogenism remains as one of the key features in Polycystic Ovarian Syndrome (PCOS) and can be assessed clinically or determined by biochemical assays. Hirsutism is the most common clinical manifestation of hyperandrogenism. The clinical assessment is subjected to wide variability due to poor interobserver agreement and multiple population factors such as ethnic variation, cosmetic procedures and genetic trait. The difficulty in resolving the androgen excess biochemically is due to a lack of consensus as to which serum androgen should be measured for the diagnosis of PCOS. The aim of the study was to compare and establish the diagnostic cut off value for different androgen biomarker for the diagnosis of PCOS. Materials and Methods: A total of 312 patients classified to PCOS (n = 164) and non PCOS (n = 148) cohorts were selected from the Laboratory Information System (LIS) based on serum total testosterone (TT) and sex hormone binding globulin (SHBG) from the period of 1st April 2015 to 31st March 2016. PCOS was diagnosed based on Rotterdam criteria. Clinical hyperandrogenism and ultrasound polycystic ovarian morphology were obtained from the clinical records. The other relevant biochemical results such as serum luteinizing hormone (LH), follicle stimulating hormone (FSH) and albumin were also obtained from LIS. Free androgen index (FAI), calculated free testosterone (cFT) and calculated bioavailable testosterone (cBT) were calculated for these patients. Receiver Operating Characteristic (ROC) curve analysis were performed for serum TT, SHBG, FAI, cFT, cBT and LH: FSH ratio to determine the best marker to diagnose PCOS. Results: All the androgen parameters (except SHBG) were significantly higher in PCOS patients than in control (p<0.0001). The highest area under curve (AUC) curve was found for cBT followed by cFT and FAI. TT and LH: FSH ratio recorded a lower AUC and the lowest AUC was seen for SHBG. cBT at a cut off value of 0.86 nmol/L had the highest specificity, 83% and positive likelihood ratio (LR) at 3.79. This is followed by FAI at a cut off value of 7.1% with specificity at 82% and cFT at a cut off value of 0.8 pmol/L with specificity at 80%. All three calculated androgen indices (FAI, cFT and cBT) showed good correlation with each other. Furthermore, cFT, FAI and calculated BT were shown to be more specific with higher positive likelihood ratio than measured androgen markers. Conclusions: Based on our study, the calculated testosterone indices such as FAI, cBT and cFT are useful markers to distinguish PCOS from non-PCOS. Owing to ease of calculation, FAI can be incorporated in LIS and can be reported with TT and SHBG. This will be helpful for clinician to diagnose hyperandrogenism in PCOS.