Refractory hypothyroidism.

INTRODUCTION: Persistently elevated thyroid stimulating hormone (TSH) despite levothyroxine (LT4) treatment that exceeds the standard weight-adjusted dose is a common clinical presentation. This may lead to additional testing for LT4 malabsorption or poor LT4 adherence, the latter of which is challenging to confirm because it is predicated on accurate patient accountability. CASE REPORT: A 35-year-old lady, post-radioactive iodine therapy for Graves' disease remained euthyroid for a year on oral LT4. Two years later, she was clinically and biochemically hypothyroid despite claiming LT4 compliance. As all laboratory investigations were within the reference range, pseudomalabsorption was suspected and a LT4 absorption test was done. During the test, her free thyroxine increased significantly at 4 hours, reaching a peak of more than 50% from baseline while TSH decreased appropriately from 0 minute to 360 minutes. This was followed by normalisation of TSH with LT4 treatment under direct observation. DISCUSSION: The LT4 absorption test is a prompt and economical means to rule out true malabsorption, decrease unwarranted subspecialty referrals and validate the weight-adjusted LT4 dose reduction.

Association between bone characteristics and cardiovascular risk factors among adults in selected urban areas in Selangor, Malaysia.

INTRODUCTION: Cardiovascular disease and osteoporosis (OP) have been shown to have similar risk factors but studies have demonstrated contradictory results with regards to their associations. This study evaluated relationships between bone characteristics and cardiovascular risk factors among adults in selected urban areas in Malaysia. MATERIALS AND METHODS: A cross-sectional study was performed involving 331 subjects between 45-90 years recruited at a health screening programme. Sociodemographic and clinical characteristics were recorded. Biochemical analyses on fasting blood samples and dual energy X-ray absorptiometry scan to determine bone mineral density (BMD) were performed. RESULTS: Increased waist circumference (WC) was protective for abnormal BMD status (osteopenia and OP). Males with increased high-density lipoprotein cholesterol (HDL) were more likely to be osteoporotic. WC, fasting blood glucose (FBG) and triglyceride (TG) were positively associated with BMD at all sites but was gender specific. In contrast, WC was negatively associated with trabecular bone score (TBS) for females but this association became attenuated when adjusted for fat percentage. HDL and MetS were negatively and positively associated with BMD, respectively in males. CONCLUSION: The cardiovascular risk factors of raised WC, FBG, TG and low HDL were significantly associated with increased BMD with skeletal site and gender specific differences after adjusting for confounders. However, a higher WC was associated with a weaker skeletal microstructure reflected by lower TBS in females driven by fat percentage. A higher BMD was demonstrated among MetS individuals. These findings suggest that adiposity may have a protective effect on BMD.

Survey on serum protein electrophoresis and recommendations for standardised reporting.

INTRODUCTION: Serum protein electrophoresis (SPE) is a well-established laboratory technique. However, reporting of results varies considerably between laboratories. The variation in reporting can cause confusion to the clinician with a potential of adversely impacting patient care. The purpose of the survey was to find out the variation in reporting and to prepare recommendations to the Malaysian laboratories based on the survey to reduce both the variation in reporting between laboratories and the risk of misinterpretation of reports. MATERIALS AND METHODS: To determine the extent of variation in reporting of protein electrophoresis results questionnaires were distributed to the pathologists of various laboratories in Malaysia regarding the method, quantification of paraprotein concentrations and immunoglobulin assays, and information regarding current laboratory electrophoresis practices. RESULTS: Variation was found in the following reporting practices: (a) screening protocol; (b) reporting of serum albumin; (c) numerical reporting of protein fractions and paraprotein; (d) co-migration of a paraprotein with a normal serum protein; (e) reporting of multiple paraprotein bands (f) appearance of small abnormal band and oligoclonal bands and (g) communication about of interferences. CONCLUSION: The pathologists of the country made recommendations on the reporting of protein electrophoresis. Harmonised reporting will reduce inconsistency, variation in reporting, improve the quality of the report and most importantly improve patient care.

High sensitivity C-reactive protein (hsCRP): Its relationship with metabolic syndrome and Framingham Risk Score.

INTRODUCTION: Cardiovascular disease (CVD) remains the leading cause of death in Malaysia. Identification of asymptomatic at-risk individuals is often achieved by means of a risk prediction algorithm. Traditional CVD risk factors and their associated algorithms are, however, limited by residual CVD risk. High sensitivity C-reactive protein (hsCRP) has emerged as a novel CVD risk factor. This study aimed to evaluate hsCRP as an adjunct CVD risk marker among the adult Malaysian population by determining its correlation with the Framingham Risk Score (FRS). Comparison analyses were done according to sociodemographic, clinical and laboratory factors and between subjects with and without Metabolic Syndrome (MetS). METHOD: This cross-sectional study involved eighty-three (n=83) adults attending a health screening program at Universiti Putra Malaysia (UPM). Demographic data, anthropometric measurements and blood samples for fasting blood glucose (FBG), fasting lipid profile (FSL), glycated haemoglobin (HbA1c) and hsCRP were taken. Respondents were grouped according to FRS and the Joint Interim Statement into 10-year CVD risk categories (low, intermediate and high) and MetS, respectively. RESULTS: hsCRP was significantly increased in patients with high body mass index (BMI) (p=0.001), at-risk waist circumference (WC) (p=0.001) and MetS (p=0.009). Spearman's correlation coefficient showed a significant positive correlation between hsCRP level and total FRS score (r=0.26, p<0.05) and HDL-C score (r=0.22, p<0.05). CONCLUSION: The significant difference of hsCRP levels across obesity levels and MetS with its modest correlation with FRS scores supported the adjunctive role of hsCRP in CVD risk prediction, most likely capturing the inflammatory pathological aspect and thus partly accounting for the residual CVD risk.

Markedly raised haemolysis index with upper limit of normal serum potassium levels.

INTRODUCTION: Haemolytic specimens are a frequent occurrence in clinical laboratories, and they interfere with the analysis of many tests. CASE REPORT: We describe here an unusual case of leptospirosis complicated by haemolytic anaemia in a 70-year-old man with established kidney failure. He presented with an abrupt onset of shortness of breath, flushing and erythematous rash after completing haemodialysis. The patient's biochemistry test samples were however rejected twice as they were grossly haemolysed. The integrated auto-verification alert system implemented in the hospital's laboratory information system alerted the staff of the possibility of in vivo haemolysis. DISCUSSION: The auto-verification alert system effectively distinguishes between in vitro and in vivo haemolysis and as such can be utilised as a diagnostic aid in patients with suspected intravascular haemolysis.

Determination of salivary cortisol reference interval in a selected Malaysian population.

INTRODUCTION: Salivary cortisol is used as an indicator of stress level and a recommended screening test for Cushing syndrome. The normal reference interval for salivary cortisol is dependent on the analytical methodology and the population studied and hence, establishment of a local population-based reference interval is recommended. MATERIALS AND METHODS: A total of 129 healthy blood donors and staffs of Penang General Hospital were recruited from June 2018-May 2019. Paired (morning and late-night) saliva samples were collected from individuals aged between 18 and 60 years old with no history of chronic medical illness. Salivary cortisol was assayed using electrochemiluminescence immunoassay technique. Non-parametric statistics were used for calculation of reference interval and 90% confidence intervals (90% CIs). RESULTS: The reference interval for morning and latenight salivary cortisol was 2.09 - 22.63 nmol/L and <12.00 nmol/L, respectively. CONCLUSION: The locally-derived adult reference intervals for morning and late-night salivary cortisol concentration was determined and varied with previous studies emphasising the need in establishing individual laboratory reference interval.

Appropriateness of metformin prescription for type 2 diabetes mellitus patients with chronic kidney disease (Stages 3-5).

INTRODUCTION: Metformin is the first-line pharmacological therapy for type 2 diabetes mellitus (T2DM). Guidelines recommend metformin to be given at reduced dosages for those with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 and omitted in those with eGFR<30 mL/min/1.73m2. Lactic acidosis is a known complication of those on metformin. This study aimed to determine the appropriateness of metformin prescription in T2DM patients with chronic kidney disease (CKD) stages 3-5 in a tertiary centre in Malaysia. MATERIALS AND METHODS: A cross-sectional design using retrospective secondary data of T2DM patients on metformin attending nephrology and diabetic clinics in the year 2017. eGFR calculated using the CKD-EPI formula identified those in CKD stage 3-5 defined using the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative criteria. Metformin prescription was considered appropriate when the metformin maximum daily dosage does not exceed 1500 mg in CKD stage 3a and 1000 mg in CKD stage 3b and metformin stopped in CKD stages 4 and 5. RESULTS: A total of 143 patients were included. Majority were in the elderly age group (62.9%), male (60.8%) and had concurrent hypertension (85.3%). Median HbA1c was 8.3% (67 mmol/mol) with most patients (88.8%) having HbA1c above 6.5% (48 mmol/ mol). Majority (92.3%) were categorised as stage 3 CKD. Eleven (7.7%) subjects had inappropriate metformin prescription. Seven of nine (78%) subjects in CKD stage 4 were on metformin with a maximum daily dose of 500 mg to1000 mg. Three patients had serum lactate measured. CONCLUSION: The majority of CKD patients had appropriate metformin prescription. However, a considerable number of CKD stage 4 patients continued to be on metformin. The many benefits of metformin may be a reason why it is still continued against recommendations. Only three patients had lactate measured which, although may suggest that lactic acidosis is not a common occurrence, the potential for metformin-associated lactic acidosis especially in those at risk should be considered.

Thyroid storm: Is there a role for thyroid function test?

INTRODUCTION: Thyroid storm (TS) is an endocrine emergency. Early diagnosis for prompt treatment is essential as it has a high mortality rate. CASE REPORT: A 31-year-old lady with underlying hyperthyroidism, dilated cardiomyopathy with severe mitral regurgitation presented with shortness of breath. She was intubated and admitted due to decreasing Glasgow Coma Score. Her blood investigations revealed increased white cell count, raised free thyroxine with suppressed thyroid stimulating hormone, deranged liver, renal and coagulation profiles. As her condition did not improve with initial treatment, plasmapheresis was commenced on day 4. Biochemically, her thyroid function test (TFT) showed improvement; however, she succumbed due to multi-organ failure. DISCUSSION: Plasmapheresis is considered in TS if there is no clinical improvement within 24-48 hours of initial treatment. The improvement in patient's TFT post plasmapheresis signifies its role in treating TS. Unfortunately, there was a delay in commencing plasmapheresis due to haemodynamic instability in this patient.

Calculation of free and bioavailable vitamin D and its association with bone mineral density in Malaysian women.

INTRODUCTION: Low 25-hydroxyvitamin D [25(OH)D] levels have not been consistently associated with bone mineral density (BMD). It has been suggested that calculation of the free/bioavailable 25(OH)D may correlate better with BMD. We examined this hypothesis in a cohort of Malaysian women. MATERIALS AND METHODS: A cross-sectional study of 77 patients with rheumatoid arthritis (RA) and 29 controls was performed. Serum 25(OH)D was measured using the Roche Cobas E170 immunoassay. Serum vitamin D binding protein (VDBP) was measured using a monoclonal enzyme-linked immunosorbent assay (ELISA). Free/bioavailable 25(OH)D were calculated using both the modified Vermuelen and Bikle formulae. RESULTS: Since there were no significant differences between RA patients and controls for VDBP and 25(OH)D, the dataset was analysed as a whole. Calculated free 25(OH)D by Vermeulen was strongly correlated with Bikle (r = 1.00, p < 0.001). A significant positive correlation was noted between measured total 25(OH)D with free/bioavailable 25(OH)D (r = 0.607, r = 0.637, respectively, p < 0.001). Median free/bioavailable 25(OH)D values were significantly higher in Chinese compared with Malays and Indians, consistent with their median total 25(OH)D. Similar to total 25(OH)D, the free/bioavailable 25(OH)D did not correlate with BMD. CONCLUSION: In this first study of a multiethnic female Malaysian population, free/bioavailable 25(OH)D were found to reflect total 25(OH)D, and was not superior to total 25(OH)D in its correlation with BMD. Should they need to be calculated, the Bikle formula is easier to use but only calculates free 25(OH)D. The Vermuelen formula calculates both free/bioavailable 25(OH)D but is more complex to use.

Determination of the 99th percentile upper reference limit for high-sensitivity cardiac troponin I in Malaysian population.

Introduction of high-sensitivity cardiac troponin I (hscTn I) assays for routine clinical use in Malaysia requires determination of the 99th percentile upper reference limit (URL) for each assay to suit local context. Hence, this study aimed to determine the 99th percentile URL for hscTn I in the Malaysian population. A total of 250 (120 males and 130 females) healthy Malaysian blood donors aged 18 to 60 years old were recruited. Blood samples for hscTn I were measured using Abbott Diagnostics hscTn I assay on Architect i2000sr analyser. The 99th percentile was calculated using a non-parametric method and gender specific results were compared. The 99th percentile URL for hscTn I for the overall population was 23.7 ng/L, with gender specific values being 29.9 ng/L and 18.6 ng/L for male and female, respectively. Females had significantly lower hscTn I compared to males. This study confirms the use of gender specific 99th percentile URL for hscTn I for clinical use in a multi-ethnic Malaysian population.

Relationship between dyslipidaemia and glycaemic status in patients with Type 2 diabetes mellitus.

The risk of coronary heart disease (CHD) is dramatically increased in diabetic patients due to their atherogenic lipid profile. The severity of CHD in diabetic patients has been found to be directly associated with glycated haemoglobin (HbA1c). According to the Malaysian Clinical Practice Guidelines on diabetes mellitus (DM), HbA1c level less than 6.5% reduces the risk of microvascular and macrovascular complications. Hence, this study aimed to determine the relationship between dyslipidaemia and glycaemic status in patients with type 2 DM (T2DM) patients in Hospital Putrajaya, a tertiary endocrine centre in Malaysia. This was a cross sectional, retrospective study of 214 T2DM patients with dyslipidaemia who had visited the endocrine clinic between January 2009 and December 2012. Significant correlations were found between fasting blood glucose (FBG) and HbA1c with total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL), non-high density lipoprotein cholesterol (non-HDL), LDL/HDL ratio and TC/HDL ratio; greater correlation being with HbA1c than FBG. In patients with HbA1c ≥ 6.5%, TC, TG, non-HDL and TC/HDL ratio were significantly higher than in patients with HbA1c < 6.5%. Non-HDL, LDL/HDL ratio, TC/HDL ratio and HbA1c were significantly lower in patients on statin treatment than nontreated patients (p<0.05). This significant association between glycaemic status and dyslipidaemia emphasises the additional possible use of HbA1c as a biomarker for dyslipidaemia as well as a potential indirect predictor of cardiovascular disease (CVD) risk in T2DM patients.

An interesting case of Multiple Endocrine Neoplasia Type 2A.

We report the case of a 37-year-old Chinese man who came with a history of bilateral adrenalectomy and was admitted for recurrent phaeochromocytoma. Further investigations of an incidental finding of persistently raised carcinoembryonic antigen (CEA), fi rst observed four years ago, revealed medullary thyroid carcinoma (MTC). As such, a provisional diagnosis of Multiple Endocrine Neoplasia 2A (MEN 2A) was made. In this case, it seemed like the long-standing elevation of CEA was ignored until it was noted in a post-clinical discussion among several physicians. The present case illustrates the significance of considering a single abnormal biochemical test in an asymptomatic patient and also discusses the importance of life-long follow-up of a patient with a history of phaeochromocytoma.