Two cases of hypokalaemia with serum potassium levels of 1.4 mmol/L and 1.9 mmol/L causing severe periodic paralysis since childhood are presented. There were associated with muscular aches and markedly raised muscle enzymes suggesting massive rhabdomyolysis. These abnormalities were due to renal tubular acidosis with markedly acidic arterial pH. The hypokalaemia and rhabdomyolysis responded to potassium and bicarbonate replacement. We postulate these patients had sporadic distal type of renal tubular acidosis and that the hypokalaemia and acidosis had caused the rhabdomyolysis.
In this paper, the islet autoimmunity status and relation to clinical characteristics, beta cell function and cardio-metabolic risk factors in young-onset Asian diabetic patients are evaluated at baseline. The study population consisted of 912 patients (from China, India, Malaysia and Singapore) with age 12-40 years and diabetes duration <12 months. Autoantibodies to glutamic acid decarboxylase (GADA) and tyrosine phosphatase (IA-2A), beta cell function and cardio-metabolic risk parameters were assessed. Among our young patient cohort, 105 (11.5%) patients were GADA and/or IA-2A positives (Ab +ve). Ab +ve patients were younger, leaner, had more severe hyperglycaemia and lower beta cell function. The frequency of metabolic syndrome was significantly lower in Ab +ve patients (27%) compared to Ab -ve patients (54%). However, a substantial proportion of patients in both groups of patients had atherogenic dyslipidaemia, hypertension and albuminuria (micro or macro). In our study cohort, only one in 10 Asian youth with new-onset diabetes had evidence of islet autoimmunity. At least 60% of Ab +ve and 50% of Ab -ve patients demonstrated classical features of type 1 and type 2 diabetes respectively. Regardless of autoimmunity status, the cardio-metabolic risk factors, in particular atherogenic dyslipidaemia, hypertension and albuminuria were common in our patients with young-onset diabetes.
Surgery for pituitary tumours at our institution was performed by rhinosurgical route by combined procedure by otolaryngologist and neurosurgeons. A retrospective review of case records of patients who had endonasal endoscopic transphenoidal approach for pituitary tumours from September 1998 to December 2004 was performed. A total of 81 trans-sphenoidal surgeries were performed during this study period. Only 68 case records with adequate information were available for review, 56 patients were included in the study and 12 were excluded. There were 24 males (42%) and 32 females (58%). The ethnic distribution, were 29 Malays, 24 Chinese, 2 Indian and 1 others. The age ranged from 16 years to 76 years, with a mean of 46 years. The majority of our patients presented with visual symptoms (38), headache (28), menstrual cycle disturbance or impotence (14) and acromegalic features (16). Forty patients had macroadenoma (71%) and 16 had microadenomas (29%). Thirty-six patients out of 40 macro-adenomas had suprasellar extensions (90%). Only eleven patients had lumbar drain inserted prior to commencement of the surgery and the majority of these were macroadenomas. The common complications encountered were diabetes insipidus (4), cerebrospinal fluid leak (2), meningitis (3), epistaxis (2), septal perforation (2), intercavernous sinus haemorrhage (3) and anterior pituitary insufficiency (2). Our study reveals that endonasal trans-sphenoidal approach is a safe and effective method of management of pituitary adenomas.
Detection of microalbuminuria is important in the management of diabetic patients since it is predictive of development of proteinuria and nephropathy. Two sensitive and specific in-house ELISAs for microalbuminuria were established and validated. One of the ELISAs was based on antigen coating while the other employed antibody coating. Recovery and linearity experiments gave acceptable results of 100 +/- 10%, while precision results were <10% for intra-assay and <12% for inter-assay coefficients of variation (CVs). The standard curve ranged from 10-625 ug/l, equivalent to 0.2-12.5 mg/l for urine samples diluted 1:20 fold. When the antibody coated ELISA was compared to antigen coated ELISA, a correlation of r=0.996 was obtained. When compared to commercial kits, the in-house ELISAs gave good correlations of r=0.961 versus the Boehringer Mannheim Micral Test strips and r=0.940 versus Ames Microalb Turbidimetry. The normal microalbumin reference ranges determined for 12h, first morning and random urine samples were 0.7-5.3 mg, 0.1-10.2 mg/l and 0.8-26.1 mg/l respectively. The normal albumin excretion rate (AER) was 1.0-7.3 ug/min while untimed urine samples gave results of 0.1-0.9 and 0.2-1.6 mg/mmol after dividing by creatinine concentrations. The ELISAs were used to detect microalbuminuria in 338 random urine samples from diabetic patients. A high percentage 47.9% was found to be positive for microalbuminuria and 18.0% had macroalbuminuria >25 mg/mmol. Thus screening for microalbuminuria together with creatinine measurements using random urine samples can be used for management of diabetic patients.
This cross-sectional study compared serum lipoprotein (a) [Lp(a)] concentrations in type 1 and type 2 diabetic subjects and examined the determinants of Lp(a) concentrations in both types of diabetes. Serum Lp(a) was measured in 26 type 1 and 107 type 2 diabetic patients and 126 non-diabetic controls. HbA(1c), fasting lipids and urinary albumin were also assayed. Lp(a) concentrations were higher in both type 1 and type 2 diabetic patients compared with controls (P<0.0001 and P<0.0001, respectively), and were higher in type 1 than type 2 diabetic patients (P<0.05). Waist-hip ratio (WHR) was an independent determinant of Lp(a) concentrations in both type 1 and type 2 diabetes.
The effect of ambient temperature on the analytical and clinical performance of a glucose meter was examined. A total of 114 venous whole blood samples were analysed for glucose by a reference method, and by a glucose meter at 21-22 degrees C, room temperatures, 26-27 degrees C and 33-34 degrees C. Glucose meter readings at each temperature were compared with the reference values and evaluated by analysis of variance, Spearman's correlation, the percentage of glucose meter readings within +/- 10% of the reference value and error grid analysis. Analysis of covariance was used to determine the effect of temperature on glucose meter readings. There were no significant differences in the glucose meter readings and in accuracy of the meter readings between different temperatures. Temperature was not a significant independent determinant of the glucose meter readings. For each glucose concentration, the precision of the meter and clinical performance were comparable between the different temperatures. In conclusion, ambient temperature does not affect the accuracy, precision and clinical performance of the Omnitest Sensor.
The objectives of this study were to: (i) evaluate the diagnostic sensitivity and specificity of the biochemical bone markers: serum total alkaline phosphatase (TALP), bone specific alkaline phosphatase (BSALP) and urinary deoxypyridinoline (Dpyr) in postmenopausal osteoporosis, (ii) compare the bone turnover of postmenopausal osteoporotic patients without and with hormone replacement therapy (HRT) against controls and (iii) identify the correlation between these bone markers and bone mineral density (BMD). We examined 42 postmenopausal women with BMD proven osteoporosis and 35 control subjects. Serum TALP, BSALP and urinary Dpyr were measured. All three biochemical bone markers showed comparable moderate diagnostic sensitivity but Dpyr had the highest diagnostic specificity. There were significantly higher serum TALP, BSALP and urinary Dpyr levels in non-HRT treated patients compared to controls (p<0.005, <0.0001 and <0.005 respectively). There were no significant differences in the levels of all three bone markers between HRT treated patients and control subjects. There was no significant correlation between TALP, BSALP or Dpyr and BMD in both controls and patients. In conclusion, the biochemical bone markers are not useful in diagnosis of postmenopausal osteoporosis but may have a role in monitoring progress and response to treatment. HRT treatment reduces bone turnover of postmenopausal osteoporosis.
Since conventional radioimmunoassays (RIA) for measurement of 17-hydroxyprogesterone (17-OHP) in serum samples require a laborious solvent extraction step, a direct and rapid in-house RIA was developed for early diagnosis and management of congenital adrenal hyperplasia (CAH). In-house rabbit anti-17-OHP antiserum, tritium labelled 17-OHP and dextran-coated charcoal were used in assay buffer with low pH 5.1 and preheated serum samples. Both inter- and intra-assay CVs were < 10% and the sensitivity was 1.2 nmol/l or 12 fmol/tube. Results from the direct assay correlated well with values from an extraction assay, r = 0.88 in samples from CAH patients, r = 0.85 in adults and children, 0.69 and 0.40 in term and preterm neonates respectively, 0.66 and 0.63 in luteal phase and third trimester pregnancy; p < 0.001 in all groups except p < 0.05 in preterm neonates. However, results from the direct assay were two to three times higher in serum samples from CAH patients, normal adults and children, but were five to seven times higher in pregnancy and term neonates and thirty times higher in preterm neonates. The markedly elevated levels measured by the direct assay are probably due to cross-reactivities with water-soluble steroid metabolites such as 17-hydroxypregnenolone sulphate and dehydroepiandrosterone sulphate (DHEAS). Although the direct assay is only useful as a screening test for preterm babies, it can be used for both diagnosis and monitoring of treatment of CAH in all other age groups.
Between January 1978 to December 1993, 130 cases of adrenal diseases were diagnosed and surgically treated at the National University of Malaysia. They were 58 cases (44.6%) of Conn's syndrome, 40 cases (30.7%) of Cushing's syndrome, 20 cases (15.3%) of phaeochromocytoma and 12 cases (9.2%) of adrenocortical carcinoma (ACC). The commonest cause of Conn's syndrome was an adenoma (96.5%) which affected the left gland four times more than the right gland. Cushing's syndrome was caused by adrenocortical adenoma (32.5%), diffuse bilateral adrenal hyperplasia (40.0%), pigmented macronodular hyperplasia (20.0%) and adrenal carcinoma (7.5%). Twenty-five percent of the phaeochromocytomas were extraadrenal in origin arising mainly from the abdominal sympathetic chain. More than 50% of ACCs were non-functioning tumours. Fifty percent of the patients with ACC had inoperable tumours. The prognosis was poor even with adjuvant chemoradiotherapy. The main surgical approach was the anterior transabdominal route. There was no operative mortality or morbidity in all operated cases.
Thyroid function and pubertal development of aborigines (Orang Asli) and Malays at different socioeconomic strata were assessed among 1136 subjects aged 7 years and above. Anthropometric measurements, goitre and pubertal staging were done. Serum thyroxine (T4), triiodothyronine (T3) and growth hormone were measured using radioimmunoassays (RIA) and serum thyroid stimulating hormone (TSH) by immunoradiometric assays (IRMA). It was found that serum T3 in children was significantly higher in Malays from rural areas, girls and children aged less than 13 years. However, in adults, T3 was significantly associated with anthropometric indices. On the contrary, serum T4 levels were higher among children from urban areas. In adults, serum T4 levels were significantly related to nutritional status and they increased according to the levels of social development, being lowest in remote areas and highest in urban areas. However, serum TSH levels were significantly higher in Orang Asli at all ages and among malnourished children. By using multiple regression, apart from age, gender and ethnicity, nutritional status was a significant predictor for T3 levels in children and adults. Presence of goitre was an important factor which determined the T4 levels in children and adults after controlling for other factors. It was also a predictor for TSH levels in children but not in adults. Fasting serum growth hormone (GH) levels were significantly higher among less privileged groups and decreased according to social development. Serum growth hormone was negatively correlated with anthropometric indices and had a significant association with malnutrition.(ABSTRACT TRUNCATED AT 250 WORDS)
1. The effects of alpha-tocopherol and gamma-tocotrienol on glutathione S-transferase (GST) and gamma-glutamyl transpeptidase (gamma-GT) activities in cultured hepatocytes prepared from rats treated with diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) were investigated. 2. Both the alpha-tocopherol and gamma-tocotrienol treated hepatocytes showed significantly higher (P < 0.05) GST activities than untreated hepatocytes prepared from the carcinogen treated rats in the first 3 days of culture. Treatment with alpha-tocopherol and gamma-tocotrienol generally resulted in a tendency to increase the GST activities above that in the untreated hepatocytes. 3. Treatment with high doses (125-250 microM) of alpha-tocopherol and low doses (12.5-25 microM) of gamma-tocotrienol generally resulted in a significant reduction in gamma-GT activities at 1-3 days. gamma-GT activities are reduced as the dose of alpha-tocopherol and gamma-tocotrienol are increased.
OBJECTIVE: To determine the prevalence of diabetes mellitus and IGT in different ethnic groups living in the same physical environment and to find their relationship to nutritional status and dietary intake.
RESEARCH DESIGN AND METHODS: The study was conducted among Malays and Orang Asli in six rural and urban locations in Malaysia. OGTTs were performed on 706 adult subjects > or = 18 yr of age. WHO criteria were used for diagnosing diabetes mellitus and IGT.
RESULTS: The overall prevalence of diabetes mellitus and IGT among Orang Asli was 0.3 and 4.4% compared with 4.7 and 11.3%, respectively, among Malays. This increased prevalence of glucose intolerance among Malays was associated with higher levels of social development. Among rural Malays, the crude prevalence of diabetes in a traditional village was 2.8% and in the land scheme was 6.7%, whereas urban Malays had a prevalence of 8.2%. In contrast, the prevalence of IGT (10.5-14.8%) was higher among rural Malays, compared with 9.6% among urban Malays. Ethnic group, > or = 40 yr of age, an income > M$250, fewer daily activity, and obesity were associated with a higher prevalence of diabetes.
CONCLUSIONS: Diabetes mellitus and IGT, which were more common among Malays than Orang Asli, were associated with more affluent life-styles and modernization.
A significant difference in the levels of thyroxine (T4), thyroid stimulating hormone (TSH) and thyroid volume among settlements at various selected Orang Asli locations is reported. The levels improved according to the level of socio-economic development. No significant difference was found in mental performance by location.
1. alpha-Tocopherol (alpha-T) and gamma-tocotrienol (gamma-T) were supplemented continuously for 8 weeks in the diets of normal rats and rats chemically induced with cancer using diethylnitrosamine (DEN), 2-acetylaminofluorene (AAF) and partial hepatectomy. Hepatocarcinogenesis was followed by determining the plasma gamma-glutamyl-transpeptidase (GGT) and alkaline phosphatase (ALP) activities as well as placental glutathione S-transferase (PGST) and GGT activities histochemically, at 4-week intervals. 2. Male Rattus norvegicus were supplemented alpha-T and gamma-T at two different doses of 30 and 300 mg/kg diet. The supplementation was started at three different times: simultaneously with DEN administration; 4 weeks; and 8 weeks after DEN administration. 3. Elevation of plasma GGT activities and formation of PGST and GGT positive foci were attenuated significantly (P < 0.05) when alpha-T and gamma-T were supplemented simultaneously with cancer induction. Supplementation begun 4 and 8 weeks after cancer induction did not affect plasma enzyme activities and formation of enzyme-positive foci. 4. alpha-T was more effective than gamma-T, and a lower dose of 30 mg/kg was found to be more effective in reducing the severity of hepatocarcinogenesis.
Fasting growth hormone (GH) level is an important reference level in dynamic tests of GH secretion. Other studies have demonstrated sex and age variation in the rate of GH secretion. We analysed fasting serum samples from 377 normal subjects (193 males and 184 females, age range 6 to 81 years old), using our in-house enzyme immunoassay. We found sex differences in fasting GH levels to be only significant in the prepubertal children (Tanner stage I), being higher in girls than in age-matched boys (p < 0.05). Both sexes showed age-dependent changes in fasting GH levels (p < 0.001); highest levels were achieved at puberty and subsequently declined with advancing age. Hence, the physiological sex difference and age-dependency in GH secretion can also be demonstrated in single fasting samples.
In order to study the effect of levothyroxine in the treatment of endemic goitre, a longitudinal study was conducted among the Aborigines in Lanai Post and Sinderut Post, situated in an iodine-deficient area located in the district of Kuala Lipis, Pahang. All subjects in the treatment group (Lanai Post) were given 100 µg of levothyroxine per day and were followed for 1 1/2 years. A total of 311 subjects were examined at baseline, 323 on the first, 256 on the second, 239 on the third and 184 on the fourth visit following levothyroxine supplementation. Goitre prevalence, thyroid hormones, thyroid volume, nutritional status, urinary iodine levels, arterial blood pressure and mental performance were determined. Following the intervention, goitre prevalence was significantly reduced in the treatment group (baseline 42.8% vs final visit 13.0%, p<0.0001); however, no significant difference was noted in the control group. Total T4 levels were increased in the treatment group (p<0.0001), while a significant reduction was noted in the control group (p<0.0001). Thyroid-stimulating hormone levels increased significantly in the treatment group following 1 year of intervention, while no significant changes were observed in the control group. As for the thyroid volume, both groups showed a significant increment following the intervention (p<0.0001). With respect to the nutritional status, the treatment group showed a significant increase in body weight following the intervention (p<0.05). In addition, the mid-arm circumference and body mass index also increased after 1 year of intervention. However, the control group showed a reduction in the waist-hip ratio (p<0.0001). Although there was no statistical difference in the waist-hip ratio in the treatment group, there has been a significant reduction observed after 1 year of intervention. At 1 year, a reduction in skinfold thickness was noted in the treatment group while only the triceps and subscapular were increased in the control group. The body fat was decreased in the treatment group following 1 year of intervention (p<0.0001). No particular trend was noted in the urinary iodine excretion in the treatment group, but surprisingly, the levels were increased in the control group (p<0.0001). A significant increase in both systolic and diastolic blood pressures was observed in the treatment group following 1 year of intervention, but the controls showed a reduction in the systolic blood pressure (p<0.0001). Both groups showed a remarkable increase in mental performance, with a more pronounced effect in the treatment group (p<0.05). The correction of iodine deficiency by levothyroxine supplementation has a short-term beneficial effect in reducing the prevalence of goitre and improving the mental ability among the Aborigines in endemic areas; however, proper monitoring and close supervision are needed to maintain compliance.
Serum concentrations of thyroid stimulating hormone (TSH) and thyroid autoantibodies in pregnant patients with thyroid disease at various stages of pregnancy were determined by in-house ELISAs. In normal pregnancy, serum TSH levels were significantly elevated (p < 0.05) from 13 weeks of gestation. The normal reference ranges for TSH for the second (0.6-5.0 mIU/l) and third trimester (0.6-5.6 mIU/l) were significantly higher (p < 0.05; p < 0.01 respectively) compared to 0.4-4.5 mIU/l for the first trimester. In pregnant thyroid patients, serum TSH levels correlated highly (p < 0.001) to T4 (r = 0.740), FT4I (r = 0.683) and MicAb (microsomal antibodies) (r = 0.825) but weaker (p < 0.01) to T3 (r = -0.512), FT3I (r = 0.520) and TgAb (thyroglobulin antibodies) (r = 0.618). Thus, measurement of TSH with the highly sensitive ELISA (enzyme linked immunosorbent assay) would form a useful first line test for thyroid dysfunction in pregnancy while measurement of thyroid autoantibodies would aid in the diagnosis of autoimmune hypothyroidism.
The effect of thyroid hormones on the renin-angiotensin-aldosterone system has not been fully resolved. Highly specific immunoassays for measurement of renin, aldosterone, free T4 (fT4), free T3 (fT3) and ultrasensitive TSH enables a direct and more accurate measurement of these hormones. We investigated the relationship between plasma renin, aldosterone and thyroid hormones in the basal state and after intravenous frusemide. This is a cross-sectional study involving 37 patients with thyrotoxicosis, 42 rendered euthyroid with normal fT4, fT3 and TSH levels, 17 with euthyroid levels of fT4 and fT3 but suppressed TSH, and 11 with hypothyroidism. Basal plasma renin was significantly higher in thyrotoxicosis (63.4 +/- 9.8 microU/ml, mean +/- SEM) compared to euthyroid (32.7 +/- 4.4 microU/ml) and hypothyroid (26.7 +/- 9.8 microU/ml). Basal plasma renin for euthyroid with suppressed TSH (41.0 +/- 7.4 microU/ml) was significantly higher than hypothyroid (p = 0.02). Basal plasma aldosterones were not significantly different except for suppressed TSH (157.7 +/- 13 pg/ml), which was higher than normal (109.9 +/- 10.4 pg/ml; p = 0.04). Following frusemide, plasma renin and aldosterone were significantly increased in all groups. Plasma renin was highly correlated to fT3 (r = 0.405, p < 0.001), total T3 (r = 0.359, p < 0.001), fT4 (r = 0.331, p < 0.001) and TSH (r = 0.300, p < 0.001) in the basal state, but less to total T4 (r = 0.248, p < 0.01). Plasma renin correlated poorly to serum aldosterone (r = 0.212, p < 0.03). This study clearly showed that regulation of renin was mainly influenced by fT3, and that aldosterone response to frusemide was blunted in thyrotoxicosis despite normal electrolytes.