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Introduction: Macroprolactinaemia is defined as hyperprolactinaemia due to excess macroprolactin in the presence of normal monomeric prolactin. Failure to identify macroprolactinaemia may result in patients being subjected to unnecessary investigations and inappropriate treatment for hyperprolactinaemia. In our centre, screening for macroprolactinaemia is currently performed at the request of the treating physician. The study thus aimed to determine the frequency of macroprolactinaemia in samples with serum prolactin ≥700 mIU/L in Hospital Tengku Ampuan Rahimah (HTAR) and to determine the presence of true hyperprolactinaemia in these cases. Methods: A cross-sectional study among hyperprolactinaemic subjects in HTAR, using serum specimens received by the laboratory for measurement of prolactin between October 2018 and September 2019. Samples with prolactin ≥700 mIU/L were screened for macroprolactinaemia using the polyethylene glycol (PEG) precipitation technique. Macroprolactinaemia was present when the percentage recovery of prolactin post-PEG was <40%. Assay-specific post-PEG monomeric prolactin levels were also reported, with levels above the upper limit of reference intervals indicated the presence of true hyperprolactinaemia. Results: A total of 101 samples were subjected to PEG precipitation. Macroprolactinaemia was found in four (4%) samples, whilst eight (7.9%) were categorised as indeterminate (percentage recovery of 40-60%). The remaining 89 (88.1%) samples had a percentage recovery >60%, hence considered negative for macroprolactinaemia. All four samples with macroprolactinaemia also had raised monomeric prolactin levels indicating the co-existence of macroprolactinaemia in subjects with true hyperprolactinaemia. Similarly, in the indeterminate group, all eight had raised monomeric prolactin levels. Conclusion: In one-year period in HTAR, macroprolactinaemia was detected in 4% of subjects with prolactin ≥700 mIU/L, all of whom also had raised monome

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. 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.

Objective: To evaluate the efficacy of high-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex as a migraine prevention by conducting a systematic review and meta-analysis. Background: The efficacy of high-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex as preventive migraine treatment remains debatable. Methods: PubMed, Scopus, CINAHL, CENTRAL, and BioMed Central databases were searched from their inception until December 2020. Randomised trials comparing high-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex with sham for migraine prevention were included. The risk of bias was assessed using the Cochrane guidelines. Headache days, pain intensity, acute medication intake, and disability were extracted as study outcomes and the mean difference with a random-effects model was used to determine the effect size. Results: Meta-analysis revealed that high-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex significantly reduced acute medication intake (Mean Difference = 9.78, p = 0.02, 95%CI: 1.60, 17.96, p = 0.02) and functional disability (Mean Difference = 8.00, p < 0.05, 95%CI: 4.21, 11.79). However, no differences were found in headache days and pain intensity reduction, although there was a slight trend favouring high-frequency repetitive transcranial magnetic stimulation. Conclusion: High-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex may be effective in reducing acute medication intake and disability. However, more studies are needed to strengthen this preliminary evidence.

Objective: To evaluate the efficacy of high-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex as a migraine prevention by conducting a systematic review and meta-analysis. Background: The efficacy of high-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex as preventive migraine treatment remains debatable. Methods: PubMed, Scopus, CINAHL, CENTRAL, and BioMed Central databases were searched from their inception until December 2020. Randomised trials comparing high-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex with sham for migraine prevention were included. The risk of bias was assessed using the Cochrane guidelines. Headache days, pain intensity, acute medication intake, and disability were extracted as study outcomes and the mean difference with a random-effects model was used to determine the effect size. Results: Meta-analysis revealed that high-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex significantly reduced acute medication intake (Mean Difference = 9.78, p = 0.02, 95%CI: 1.60, 17.96, p = 0.02) and functional disability (Mean Difference = 8.00, p < 0.05, 95%CI: 4.21, 11.79). However, no differences were found in headache days and pain intensity reduction, although there was a slight trend favouring high-frequency repetitive transcranial magnetic stimulation. Conclusion: High-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex may be effective in reducing acute medication intake and disability. However, more studies are needed to strengthen this preliminary evidence.

Introduction: Glycated haemoglobin (HbA1c) is a test commonly measured in many clinical laboratories to monitor and diagnose diabetes mellitus (DM). The laboratory in Hospital Tengku Ampuan Afzan (HTAA) receives HbA1c samples internally and from several other hospitals and clinics in the state of Pahang, at which, before transportation and analysis, the samples are often stored. This study determined the stability of HbA1c samples following different storage temperatures and duration for up to 30 days. Method: Whole blood samples for HbA1c analysis were col- lected from 222 healthy blood donors and type 2 DM (T2DM) patients. Each sample was prepared into four aliquots, which were then stored at temperatures -20°C and -80°C. HbA1c analyses were performed at baseline, days 15 and 30 using ion-exchange high-performance liquid chromatography (HPLC) assay technique on Bio-Rad D-10 analy- ser. HbA1c levels following sample storage were compared to the levels at baseline. Results: The baseline HbA1c (mean±SD) was 6.6±2.2%. At -20°C of storage, the HbA1c levels decreased with a mean difference of 0.1% and 0.3% on days 15 and 30, respectively. Storage at -80°C resulted in a mean difference of 0.1% on day 15 whilst no change was noted on day 30. The number of samples that showed clinically significant HbA1c change (defined as a change of >0.5%) was less for the samples stored at -80°C (4.5%) as compared to -20°C (23%). Conclusion: HbA1c concentration is affected by temperature and duration of sample storage. In instances where prolonged storage of HbA1c samples is expected, storage at -80°C is preferable.

A 31-year-old lady presented with abnormal vaginal bleeding during her first trimester of pregnancy. Based on the ultrasound findings and the decreasing hCG trend (from 1040 mIU/mL to 759 mIU/mL), a diagnosis of missed miscarriage was made. A week later, the patient presented with heavy vaginal bleeding. Ultrasound findings showed classic snowstorm appearance suggestive of complete hydatidiform mole. The serum hCG level however, was 357 mIU/mL. In a case of hydatiform mole with inappropriately low hCG, analytical interference was suspected. Post- dilution serum hCG of 5,775,000 mIU/mL confirmed the presence of hook effect in a two-site hCG immunoassay. Discordance between serum hCG and clinical findings should be actively investigated by the laboratory to prevent delay in diagnosis and treatment. This case also highlights the need for clinicians to be aware of the hCG assay used in their hospital’s laboratory so that they may recognise false negative hCG results.

Introduction: Previous studies have revealed ethnic differences in glycated haemoglobin (HbA1c) value at the same glucose concentration. This study aimed to determine ethnic variation in HbA1c as an index of glycaemic control among type 2 diabetes mellitus (T2DM) patients. Methods: This cross-sectional, retrospective study recruited 293 T2DM patients by simple random sampling at the medical outpatient clinic of a tertiary hospital. Results: Ethnicity was equally distributed with 33.4% Malays and Indians, respectively, and 33.1% Chinese. Significant difference in ethnicity was noted between HbA1c groups 6.5% and >6.5%. Indians had the highest median HbA1c (8.3%), followed by Malays (7.7%) and Chinese (7.2%) [p=0.004]. Malays had lower HbA1c compared with Chinese at low- er fasting plasma glucose (FPG) whereas Chinese had lower HbA1c compared with Malays at higher FPG, crossing over at FPG 2.8 mmol/L. Indians had higher HbA1c compared with Chinese and Malays except at FPG cross-over of 16 mmol/L where Malays were higher than Indians. FPG and ethnicity were independent predictors of HbA1c. An increase of 1 mmol/L in FPG resulted in an increase of 0.44% in HbA1c. Indians and Malays had 0.60% and 0.47% higher HbA1c, respectively, than Chinese. Conclusion: This pilot study in Malaysia examined ethnic variation in the relationship between FPG and HbA1c among T2DM patients. Since HbA1c is higher in Indians and Malays compared with Chinese at any given FPG, the hypoglycaemia risk may be increased in Indians and Malays when treatment strategies are focussed on using similar target HbA1c values to treat them.

Objective: This study aimed to determine the prevalence of vertebral fractures (VF) in a selected urban population in Malaysia and to explore possible variables associated with VF in the study population. Methods: A cross-sectional study involving community-living, healthy subjects aged between 45–90 years from the state of Selangor, Malaysia, were invited to attend a bone health check-up. Subjects with diseases known to affect bone metabolism or were on treatment for osteoporosis (OP) were excluded. Bone mineral density (BMD) was measured using dual energy X-ray absorptiometry (DXA). Lateral and antero-posterior view lumbar spine x-rays were performed and VF was determined by the semi-quantitative Genant method. Results: A total of 386 subjects were studied. Asymptomatic morphometric VF were found in 44 (11.4%) subjects. T12 was the most common vertebrae to be fractured. The prevalence of VF was significantly higher in menopausal women (12.4%) compared to non-menopausal women, in those above the age of 60 (18.5%), in those of Chinese ethnicity (16.5%), in those with a low body fat percentage (17.1%) and among those with OP (27.0%). The mean (standard deviation) 25-hydroxyvitamin D [25(OH)D] levels were significantly higher in those with VF compared to those without VF, 67.64 (23.50) and 57.47 (21.71) nmol/L, respectively. However, after multiple regression analysis, age over 60 years and OP on DXA BMD measurement were the only significant associated factors for VF. Conclusion: Overall, 11.4% of a selected Malaysian urban population had asymptomatic morphometric VF. Age over 60 years and OP on DXA BMD measurement, but not 25(OH)D levels, were associated with VF.

Adrenal hypoplasia congenita (AHC) is a rare inherited condition due to the failure of the adult zone of the adrenal cortex to develop despite normal development of its foetal counterpart. Affected patients are usually asymptomatic at birth but will present with clinical features of acute adrenal insufficiency during early infancy. It is clinically indistinguishable from the more common congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Here, we report a case of a one-month-old male infant with primary adrenal insufficiency (PAI) whose initial laboratory investigations revealed hyponatraemia and severe hyperkalaemia. The early onset of PAI with the absence of ambiguous genitalia and low baseline and adrenocorticotropic-stimulated 17-hydroxyprogesterone and undetectable dehydroepiandrosterone sulfate levels, suggest the possibility of AHC in this infant. Genetic analysis is crucial to confirm the diagnosis of this condition and to differentiate from CAH as their prognoses and management differ.

Congenital central hypothyroidism (CCH) is a rare disorder that results from deficient biosynthesis of thyroid hormone due to defective thyroid gland stimulation by thyroid stimulating hormone (TSH). Diagnosis is typically established biochemically by low free thyroxine (fT4) and inappropriately low or normal TSH levels after excluding all other causes of discordant thyroid function test (TFT). Here, we report a case of a baby girl who presented with prolonged jaundice at day 15 of life with normal cord blood TSH performed as routine screening for congenital hypothyroidism. Serial TFT revealed declining serum fT4 with normal TSH consistent with CCH. Her jaundice resolved prior to levothyroxine replacement. CCH is commonly missed on cord blood TSH-based newborn screening leading to a delay in diagnosis, potentially resulting in neurodevelopmental delay. Hence, although CCH has a lower incidence than congenital primary hypothyroidism, a high index of suspicion is essential for timely diagnosis.

A 78-year-old male with early dementia and long-standing hypertension presented with acute, self-resolving left-sided body numbness. He was hypertensive (168/92 mmHg) but otherwise stable, euvolemic with no other clinical signs and symptoms. He was not on any other medications besides Telmisartan.

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 m

Introduction: Total calcium concentration is widely used to assess body calcium status although limited by many confounding factors. Thus, this study aimed to derive and internally validate an albumin-adjusted calcium equation for a selected Malaysian population. Method: This cross-sectional study involved 1011 adults at an emergency department of a tertiary hospital. Patients who had total calcium, ionised calcium and albumin measurements taken simultaneously were included. Derivation of the albumin-adjusted calcium equation was based on the adjustment equation obtained from the Association for Clinical Biochemistry and Laboratory Medicine 2015 position paper. Additionally, the equation was internally validated and compared with ionised calcium (gold standard) and the conventional Payne’s equation. Results: The newly derived equation = total calcium + 0.017 (41.35 – albumin). Internal validation exhibited the amount of shrinkage of 0.049. It tends to overestimate the adjusted calcium by a mean difference of 0.029 mmol/L compared to Payne’s equation. The comparison between Payne’s equation and the new equation with ionised calcium reclassified 402 and 486 patients, respectively into different calcium status. When both equations were compared, calcium status classification significantly differed in all and hypoalbuminaemic subjects by 90 and 16 patients, respectively. Conclusion: Locally derived albumin-adjusted calcium equation differed statistically in calcium status classification when compared to the Payne’s equation. However, to confirm this significance, the result must be compared to ionised calcium under strict, controlled preanalytical conditions. In terms of clinical significance, there was no difference in classification of calcium status between Payne’s and the new equation at medical decision limits.

Interpretation of thyroid function test (TFT) is often straightforward but in certain scenarios, discordance between the clinical impression and the laboratory results exists. A 50-year-old woman with a ten years history of hypothyroidism on levothyroxine presented with a recent notable change in TFT [elevated free thyroxine (FT4) and thyroid-stimulating hormone (TSH)], in an otherwise clinically euthyroid and previously stable TFT, leading to levothyroxine being withheld. This case report highlights the possibility of assay interference as a cause of discordant TFT. It also draws the importance of close collaboration between clinicians and the laboratory to avoid unnecessary investigations and inappropriate management of such a case.

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.

Introduction: The prevalence of diabetes mellitus (DM) in Malaysia is drastically increasing. Subjects with DM are more likely to have deranged liver function tests (LFT). This study aimed to determine the prevalence of abnormal liver enzymes [(alanine aminotransferase (ALT) and alkaline phosphatase (ALP)] and its associated factors among type 2 DM (T2DM) subjects visiting a referral diabetic clinic in a tertiary government hospital. Methods: This retrospective, cross-sectional study included electronic data of 300 T2DM subjects ≥18 years old in the outpatient specialist clinic from January 2011 to December 2014. Statistical analysis was performed using SPSS version 22. Results: The study population at large included Malays, of age >60 years with comparable gender percentage. Most subjects had long-standing DM, poor glycaemic control and were on treatment. The prevalence of abnormal ALT and ALP was 27.3% and 13%; with 90.2% and 97.4% having mild ALT and ALP elevations, respectively. Significant associations noted for age, body mass index (BMI) and duration of T2DM for ALT whereas for ALP, anti-diabetic medication was significant between groups of normal and abnormal levels. Deranged liver enzymes were associated significantly with dyslipidaemia. Conclusion: Our study on the crude prevalence of raised liver enzymes may help identify T2DMpatients at increased risk of non-alcoholic fatty liver disease (NAFLD). Modification of metabolic risk factors, such as weight loss, control of dyslipidaemia rather than just tighter glycaemic control should be emphasised to reduce morbidity and mortality. Liver enzymes remain a simple and non- invasive marker of liver pathology in daily medical practice.