A combined enzyme immunoassay (micro-ELISA) technique was established for measuring autoantibodies against thyroglobulin and thyroid microsome, involving the immuno-dot blot technique. Thyroglobulin and thyroid microsome antigens (1 g/L each) prepared from normal thyroids were spotted separately onto nitrocellulose membrane filter discs. Results by this method and those by immunofluorescence correlated well. The percentages of confirmed positives were 30% and 48% and the negatives were 58% and 46% (n = 50) for thyroglobulin and microsome, respectively. Testing these samples by gelatin agglutination gave a high percentage of false positives (up to 20%, n = 128) and hemagglutination testing yielded a high percentage of false negatives (up to 20%, n = 45). The titer of autoantibodies by the micro-ELISA technique was greater than by agglutination. This technique is highly specific and sensitive.
Thirty-eight normal volunteers and 10 patients with untreated thyrotoxicosis were each given 0.5 ml of Lugol's solution daily for 10 days. On days 0, 5, 10, 15 and 20, serum levels of T4, free T4, T3 and TSH (by sensitive immunoradiometric assay) were measured. In normal subjects, the serum concentrations of free T4 declined significantly at day 10 while TSH levels were significantly increased at days 5, 10 and 15. Serum levels of T4 and T3 did not change significantly. All the observed changes took place within the limits of normal ranges for the hormones mentioned. In contrast, in the thyrotoxic subjects, both T4 and T3 were significantly decreased at days 5 and 10, while serum TSH remained below detection limit (0.14 mU/l) throughout the study. Short exposure to excessive iodide in normal subjects affects T4 and T3 release and this effect could be partially overcome by compensatory increase in TSH. In thyrotoxicosis, lack of compensatory increase in TSH results in rapid decreases in T4 and T3 levels. The integrity of the hypothalamo-pituitary-thyroidal axis may be effectively assessed by measuring TSH response to iodide suppression, using a highly sensitive immunoradiometric assay.
The clinical, biochemical and immunological features of 180 patients with hyperthyroid Graves' disease managed at the Universiti Kebangsaan Malaysia (UKM) Endocrine Clinic from 1983 to 1987 were examined. The prevalence of the disease is highest in Chinese and lowest in Indians. The female: male ratio is 2.8:1. Hypokalaemic periodic paralysis and hypercalcaemia were present in 5.0% and 1.7% of the cases respectively. Pretibial myxoedema was extremely rare. Thyrotropin - binding inhibitory immunoglobulins, anti-thyroglobulin and anti-microsome antibodies were positive in 61.5%, 25.8% and 42.3% of the patients respectively. A eumetabolic state could be achieved in the majority of patients with antithyroid drugs alone. Definitive therapy with subtotal thyroidectomy or radioiodine were needed in 31.3% of cases.
Four cases of acute viral myocarditis were diagnosed within three weeks. The clinical features, electrocardiography, cardiac enzymes and other laboratory investigations are described.
62 cases of polycystic ovary syndrome (PCO) were reviewed with regards to their clinical and endocrine features. The subgroup of patients with acanthosis nigricans (AN) was further studied in detail. The prevalence of the syndrome was significantly higher in the Indian (35.5% of cases). Obesity, AN, hirsutism, non-insulin dependent diabetes mellitus (NIDDM) and raised level of serum testosterone were present in 77.1%, 74%, 79%, 21% and 48% of the cases respectively. Patients with AN was associated with higher body mass index, serum testosterone level, and prevalence of hirsutism and NIDDM than patients without AN. These observations are in keeping with the hypothesis that hyperinsulinemia may be of importance in the pathogenesis of a sub-group of PCO associated with insulin resistant states.
A 44 year old lady with primary hypothyroidism presented with massive pericardial effusion without cardiac tamponade. Pericardial tap was done twice and the effusion resolved as the hypothyroid state improved. She remained hypertensive despite the euthyroid state. She was discharged well with L-thyroxine and anti-hypertensive therapy.
A survey was done to determine the prevalence of diabetes mellitus, hypertension and renal disease, as well as extent of diabetic control, amongst the workers of Malaysian Railways. The prevalence of diabetes was high at 6.6%, with 3.8% of these being insulin dependent diabetes. The highest prevalence was in Indians (16.0%) followed by Chinese (4.9%) and Malays (3.0%). Using HbA1 measurements, diabetic control was poor in 70.6% of the diabetics. Hypertension was found in 37% and proteinuria in 35%. Renal impairment was present in 30% of the diabetics. This survey shows that diabetes, hypertension and renal disease are high amongst the railway workers in Malaysia.
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.
One hundred and six prostatic tissue samples obtained from transurethral resection were analysed for androgen and estrogen receptors. In 62 of these, progesterone and glucocorticoid receptors were also assayed. Steroid receptors were assayed using single saturation dose 3H-labelled ligand assays. Ninety percent of the 97 prostatic hyperplasia tissues and six of the nine prostatic carcinoma tissues were positive for androgen receptors. Estrogen receptors were only present in 19% and 33% respectively. Progesterone receptors were present in 70% of the tissues, but glucocorticoid receptors were present in only 16% of prostatic hyperplasia and none in prostatic carcinoma.
Adrenal histoplasmosis in Cushing's syndrome of adrenal origin is rare. A patient with Cushing's disease with bilateral nodular hyperplasia and histoplasmosis of both the adrenal glands is described. The diagnosis of histoplasmosis was only made post operatively as the constitutional manifestations, besides being partially masked by hypercortisolism also resemble those of tuberculosis.
1. The effects of corticosteroid pretreatment on acetylcholine (ACH)-induced contraction of bronchial smooth muscle (BSM) were studied. 2. ACH dose-response curves for dexamethasone (DM)- and corticosterone (B)-treated but not deoxycorticosterone (DOC)-treated BSM were significantly shifted to the right; this provides evidence that glucocorticoid treatment reduced the sensitivity of BSM to ACH. 3. Morphine enhanced BSM contraction in response to ACH by 20%. DM suppressed this enhancement. 4. These findings correlated well with the reduction of muscarinic receptor numbers in BSM by glucocorticoids in our previous study. In addition, glucocorticoids reduced the sensitivity of BSM to opioids.
1. Steroid hormones have been shown to regulate the concentration of adrenergic and muscarinic receptors in many tissues. 2. The cyclic adenosine 3',5'-monophosphate (cAMP) content in rat lung tissues in response to either dexamethasone, corticosterone, deoxycorticosterone or progesterone for 7 days were measured following intraperitoneal injection of isoprenaline just before sacrificed. 3. There was a significant increase in cAMP level (P less than 0.001) in dexamethasone and corticosterone-treated rats compared to controls that received isoprenaline alone. 4. Pretreatment with deoxycorticosterone and progesterone suppressed the increase in cAMP in response to isoprenaline. 5. The effect of glucocorticoids in causing bronchodilatation in asthmatic patients is partly due to the restoration of adenyl cyclase responsiveness to beta-agonist.
We describe the case of a 48 year old Indian female with hypercalcemia due to tuberculosis. She presented with symptoms of hypercalcemia and chest radiographs showed bilateral hilar lymphadenopathy with normal lung fields. The diagnosis of tuberculosis was made histologically from biopsy of the enlarged hilar nodes. Her hypercalcemia resolved following one month of anti-tuberculous treatment. The prevalence of hypercalcemia in tuberculosis has been reported to be high in western series. There is, however, a paucity of local data on the subject. The presence of 1-alpha-hydroxylase-like activity in pulmonary alveolar macrophages with resulting increased formation of active vitamin D metabolites is the postulated mechanism of tuberculosis associated hypercalcemia.
Thyroid eye disease is autoimmune in nature and associated with Graves' Disease. Autoantibodies to the 64 kDa antigen in thyroid membranes cross-react to the 64 kDa proteins in human eye muscle membranes. Antibody dependent cell mediated cytotoxicity against eye muscle cells are also found in patients with thyroid eye disease. The purpose of this paper is to review the treatment available and to share the authors' experience using cyclosporin A. In the majority of cases, thyroid eye disease is mild, manifest only as bilateral or unilateral proptosis, with/without grittiness of the eyes. This is usually treated conservatively with eye drops. If proptosis is more severe and there is incomplete closure of eyelids, epiphora and conjunctival injection, then lateral tarrsorrhaphy is usually effective, combined with use of eye pads and eye drops. The problem of diplopia can be treated conservatively with special lenses, or with surgical correction of tethered muscles. However when proptosis is severe, with raised intraocular pressure, severe chemosis and danger of blindness, then the choice of therapy is controversial: rapid decompression by surgical means or use of high doses of prednisolone. Most prefer prednisolone therapy initially, surgical decompression if it fails. Various other methods have been tried, aimed at the immunological nature of the disease, namely plasmapheresis, radiotherapy and immunosuppressive drugs such as cyclosporin, with variable success. Our experience with cyclosporin had been mixed and inconclusive.
Twelve cases of primary hyperparathyroidism operated by the Universiti Kebangsaan Malaysia Surgical Team from 1978 to 1989 were reviewed. There was a preponderance of Indian females in this series. The majority of the cases presented late and with complications. Renal calculi and bone disease were the commonest complications noted. Of the 12 patients, 9 had single parathyroid adenoma of which 4 were ectopically located, and 2 had hyperplasia of the parathyroids. These were all successfully operated. The remaining patient had 2 failed neck explorations. Failure at initial exploration was due to ectopic location of the glands. Meticulous surgical technique, knowledge of the anatomical variations of location of the parathyroid glands and availability of frozen section facility are essential for successful outcome.
The socioeconomic, social behaviour and dietary pattern of 100 Aborigines and Malays, aged 7 years and above from Kuala Pangsoon, Selangor Malaysia were studied by using pretested questionnaires. The individual's dietary intake was estimated using 24 hour recall for 3 days within one week which was chosen at random. The household's food consumption pattern was evaluated using food frequency questionnaires. There was no difference in the total income per month for both communities, as well as the educational attainment of the head of household and property ownership. The proportion of smokers among the Aborigines and the Malays was almost similar (33%) but the percentage of heavy smokers was higher among Aborigines compared to Malays. One third of the Aborigines regularly consume alcohol. The main energy source for both communities was rice, sugar and cooking oil whilst fish and eggs were the main sources of protein. More than 50% of the Aborigines take tapioca or tapioca leaves at least once a week compared to less than 20% among the Malays. There was no significant different in the intake of energy, protein and carbohydrate between the groups. However, the Aborigines take less fats and iron compared to the Malays. The difference in terms of smoking, drinking habit and dietary intake may determine the distribution of disease in both communities.
A filter method for collection and storage of capillary blood spots for glycated haemoglobin (gHb) has been developed. Glass fibre filters (GFB) impregnated with 0.8 M boric acid were used to collect and store capillary blood. Haemoglobin from the dried blood spots was eluted into water and determined by Drabkin's method, while gHb in the eluates was determined by the microcolorimetric method. The intraassay coefficients of variation (CVs) were 4.5, 4.5 and 3.1% at 882, 1101 and 1704 pmol HMF/mg Hb, respectively. The corresponding inter-assay CVs were 8.6, 8.6 and 6.3%, respectively. A total of 63 paired capillary and venous blood samples were measured by both the direct and GFB method. The GFB method showed excellent correlation with the direct method (r = 0.948 and r = 0.994) after 7 and 14 days' storage at room temperature. The GFB method will enable prior collection and postage of blood samples by patients.
1. Glucocorticosteroid may relieve bronchospasm by mediating changes in the muscarinic receptor concentration and/or its affinity. 2. Cholinergic muscarinic receptors were determined by using Scatchard's plots from radioligand binding assays of 0.13-3.2 nM [3H]quinuclidinyl benzylate binding to the membrane fraction of bronchial smooth muscle (BSM). 3. The concentration of muscarinic receptor in BSM of normal rat was 57 +/- 3 fmol mg protein and the dissociation constant was 0.07 +/- 0.02 nM. Dexamethasone and corticosterone reduced muscarinic receptor concentration to 50-60% of basal with no changes in receptor affinity. No changes were found in rat treated with deoxycorticosterone. 4. These findings suggest that glucocorticoids but not mineralocorticoid relieve bronchospasm at least partly by reducing the cholinergic hypersensitivity.
The clinical applications of salivary cortisol measurements were evaluated by radioimmunoassay of time-matched saliva and plasma samples. Salivary cortisol levels of normal subjects exhibited a significant (p less than 0.001) diurnal variation with a mean (+/- SD) concentration of 8.7 +/- 4.8 nmol/L at 0800-1000 h and 2.4 +/- 1.1 nmol/l at 1500-1700 h. After an overnight dexamethasone suppression test, morning salivary cortisol levels decrease to 2.7 +/- 0.7 nmol/L (p less than 0.001 vs normal). An excellent correlation (r = 0.805) of cortisol measurements with time-matched saliva and plasma samples was obtained (y = 0.03x + 0.88, p less than 0.001, n = 91). Hypercortisolism was confirmed by raised salivary cortisols in only half of patients with elevated total plasma levels, thereby indicating that salivary cortisol measurements is a better index of adrenal status.
Growth hormone (GH) levels were measured after a 75g oral glucose load (OGTT) in normal adults, patients with impaired glucose tolerance (IGT), insulin-dependent diabetes mellitus (IDDM) and acromegaly. Nadir GH levels at 2-hour post-OGTT in normal subjects ranged from 0.4 to 8.4 mIU/L, the 95% confidence interval being 0.4-4.4 mIU/L. In IGT and IDDM subjects basal fasting GH levels were not significantly different from normal and did not alter during OGTT. The high fasting GH level measured in one each of the IGT and IDDM patients was suppressible at 1-hour after glucose intake. In contrast, acromegalic patients had elevated fasting GH levels (11.8-178 mIU/L) although in 3 patients, the levels were mildly elevated and overlapped with normal. OGTT failed or only partially suppressed GH secretion in all acromegalics. Therefore, elevated fasting GH levels are not diagnostic and OGTT is required for accurate diagnosis and assessment of treatment of acromegalic patients.