Focal choroidal excavation in patients with central serous chorioretinopathy.

PURPOSE: To evaluate the prevalence and clinical features of focal choroidal excavation (FCE) in patients presenting with central serous chorioretinopathy (CSC). METHODS: This is a retrospective consecutive case series of consecutive patients with CSC who were referred for spectral domain optical coherence tomography (SD-OCT) between January 2010 and December 2011. Medical records were reviewed and clinical features including presence of FCE in SD-OCT, fluorescence angiography (FA), and indocyanine green angiography (ICGA) were studied. RESULTS: Among the 116 CSC patients assessed, FCE was found in 11 eyes of 7 (6.0%) patients. FCE was associated with subretinal fluid in six eyes of six patients and serous pigment epithelial detachment in three eyes of two patients. The mean central subfield retinal thickness of CSC eyes with FCE was 283.7 µm, compared with 377.5 µm for CSC eyes without FCE (Mann-Whitney U-test, P=0.020). Five FCE eyes of five patients had focal leakage on FA. Choroidal hyperpermeability on ICGA was found in seven CSC eyes with FCE, with four eyes showing hypofluorescent spot corresponding to the FCE. After a mean follow-up of 16 months, visual acuity of all 11 eyes with FCE remained stable or improved at the last follow-up. CONCLUSION: FCE is not an uncommon feature in patients with CSC and might be associated with choroidal hemodynamic disturbances.

The effect of a 5-month supervised program of physical activity on anthropometric indices, fat-free mass, and resting energy expenditure in obese male military recruits.

Studies using mainly dietary restriction have shown that weight loss is associated with a decrease in fat-free mass (FFM) and resting energy expenditure (REE). The aim of this study was to investigate the effects of a weight-loss program relying solely on increased physical activity on FFM and REE. Forty-two overweight male military recruits (12 with initial body mass index [BMI] between 25.0 and 29.9 kg/m2, group 1; 14 with BMI between 30.0 and 34.9 kg/m2, group 2; and 16 with BMI of at least 35 kg/m2, group 3) completed a 5-month program of supervised physical activity that included both aerobic and muscle-strengthening components. All subjects lost significant amounts of weight (group 1, 8.6 kg; group 2, 15.7 kg; group 3, 22.0 kg). This weight loss was accompanied by a significant reduction in the waist to hip ratio (WHR) in all groups. FFM was maintained in all groups. REE tended to decline in all groups (group 1, from 1,595.0 +/- 46.9 to 1,511.7 +/- 53.2 kcal/d; group 2, from 1,751.4 +/- 56.0 to 1,680.0 +/- 63.1 kcal/d; group 3, from 1,901.9 +/- 93.7 to 1,740.0 +/- 67.3 kcal/d), but this decline reached statistical significance only when all 42 subjects were considered. REE normalized for FFM did not decrease except in group 1. Furthermore, differences between the slopes and intercepts of the regression lines relating REE with FFM before and at completion of the 5-month program were not statistically significant, suggesting that the relationship between REE and FFM was maintained after weight loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyrotoxicosis due to the simultaneous occurrence of silent thyroiditis and Graves' disease.

Silent thyroiditis (ST) and Graves' disease (GD) are two clinical entities belonging to the wide spectrum of autoimmune thyroid diseases (AITD). The two diseases are closely linked because sequential development of GD followed by ST, or the reverse course of events, ie, ST followed by GD, have been documented. However, the pathogenetic basis of the above association remains unknown. Some authors have suggested that the concomitant existence of ST and activation of GD can occur in thyrotoxic postpartum women with normal radioiodoine uptake. The simultaneous occurrence of the two diseases in different parts of the same thyroid gland has, however, to our knowledge, not been documented. We report the case of a 40-year-old thyrotoxic female with atypical presentation of GD. The titers of the antithyrotropin receptor antibodies were elevated and her initial 99mTc-pertechnetate thyroid scan showed the coexistence of ST and GD in different parts of the thyroid gland. Through serial thyroid scans, we document the recovery from ST in parts of the gland and demonstrate the progression to Graves' hyperthyroidism in the entire gland.

The combination of absent thyroid peroxidase antibodies and high thyroid-stimulating immunoglobulin levels in Graves' disease identifies a group at markedly increased risk of ophthalmopathy.

Among Graves' Disease (GD) patients, we have observed an unexpectedly high prevalence of antithyroperoxidase antibody (TPOAb) and antithyroglobulin antibody (TgAb) negativity in those with severe ophthalmopathy. To study the possible role of thyroid autoantibodies in the pathogenesis of Graves' ophthalmopathy (GO), TPOAb, TgAb, thyroid-stimulating immunoglobulin (TSI), and thyrotropin-binding inhibitory immunoglobulin (TBII) levels were measured, and the presence or absence of GO was assessed by a single observer in 100 consecutive patients with newly diagnosed, untreated GD who were nonsmokers. Ophthalmopathy was present in 43 patients. TSI levels (p = 0.001), and the prevalence of TPOAb-negativity (p = 0.002) were significantly higher in patients with ophthalmopathy compared to those without. Logistic regression analysis showed that TSI levels (p = 0.005) and the absence of TPOAb (p = 0.0025) were independent predictors of GO. No correlation between TBII or TgAb and eye disease was found. The prevalence of GO increased with each quartile of TSI levels. The prevalence was 20%, 36%, 52%, and 64% in the first, second, third and fourth quartiles of TSI, respectively. The odds ratio of GO (with 95% confidence intervals) when TSI levels were above the median level (1640%) was 3.6 (1.5-8.0), when TPOAb was negative it was 5.0 (1.7-14.4), and with both risk factors it was 36.6 (4.3-313.5). The prevalence of ophthalmopathy in this last group was 92.9%. The combination of negative TPOAb and high TSI levels appears to be associated with a markedly increased risk of clinically evident ophthalmopathy.

Overnight (1 mg) dexamethasone suppression testing reliably distinguishes non-cushingoid obesity from Cushing's syndrome.

To determine the sensitivity of the overnight 1-mg dexamethasone suppression test in diagnosing Cushing's syndrome, we evaluated the cortisol responses of 55 subjects (25 non-obese individuals with body mass index less than 25 kg/m2, 20 obese individuals with body mass index greater than 30 kg/m2, and 10 patients with surgically proven Cushing's syndrome) following ingestion of 1 mg dexamethasone at midnight. The basal 8 AM plasma cortisol levels among non-obese and obese individuals and patients with Cushing's syndrome were 310 +/- 85, 377 +/- 91, and 813 +/- 270 nmol/L, respectively. Following 1 mg of dexamethasone, Cushing's syndrome patients showed minimal suppression of cortisol to 609 +/- 180 nmol/L (P = 0.79). Non-obese and obese individuals suppressed to 18.7 +/- 6.0 nmol/L (P less than 0.001) and 22 +/- 7.1 nmol/L (P = 0.003), respectively. The results demonstrated similar cortisol responses to overnight dexamethasone suppression in obese and non-obese groups, and clearly distinguished these subjects from those with Cushing's syndrome. Obesity is not a confounding factor in the 1-mg dexamethasone suppression test.

Cushing's syndrome in a patient with a corticotropin-releasing hormone-producing pheochromocytoma.

OBJECTIVE: To present the first case of Cushing's syndrome attributable solely to ectopic production of corticotropin-releasing hormone by a pheochromocytoma. METHODS: We summarize the clinical features and results of laboratory investigations in a patient with symptoms characteristic of Cushing's syndrome. RESULTS: Although Cushing's syndrome is usually caused by ectopic production of adrenocorticotropic hormone (ACTH), our current patient had clinical and biochemical evidence of hypercortisolism in conjunction with "normal" ACTH levels and nonsuppressible serum and urinary cortisol levels on low-dose and high-dose dexamethasone suppression testing. An abdominal computed tomographic scan revealed a 7.7-cm mass in the left adrenal gland. Light microscopic examination and immunohistochemical staining showed a pheochromocytoma with mild cortical hyperplasia. Immunostaining was positive for corticotropin-releasing hormone but negative for ACTH. CONCLUSION: To our knowledge, this is the first case of Cushing's syndrome in a patient with pheochromocytoma caused only by ectopic secretion of corticotropin-releasing hormone without accompanying secretion of ACTH.

Patient outcome and intensive care resource allocation using APACHE II.

A prospective study of seventy consecutive admissions to the Medical Intensive Care Unit (MICU) of a local hospital over a five-month period was conducted with the aim of developing objective criteria for critical care resource allocation. Patients gaining admission were subjected to APACHE II scoring and their progress followed till they recovered from their illness or perished. The mean APACHE II score of patients who recovered from their illness or perished were 12.96 and 28.52 respectively (p < 0.001). 91.5% of all patients who recovered had an APACHE II score of below 21 whereas 82.6% of those who died had an APACHE II score of more than 23. Males generally had poorer outcome than females [47% mortality vs 8% (p < 0.001)] although their mean ages were comparable [47.6 years vs 46.6 years respectively (p = 0.85)]. The mean APACHE II scores of male and female patients were significantly different [male = 20.6 vs female = 13.6 (p < 0.005)] and this partly accounted for the poorer outcome of males. The APACHE II score has considerable predictive value on the final outcome of patients admitted to the MICU. When ICU beds are short, the allocation of such beds may be made with consideration of the APACHE II Score which identifies the patient who is most likely to benefit from ICU care.

Medical intensive care unit utilization in an acute teaching hospital.

To ascertain the profile of medical intensive care unit (MICU) utilization in the Singapore General Hospital, a prospective survey studying 162 consecutive patients admitted to MICU was conducted over a four-month-period spanning September through December 1990. While there was no racial predilection, male admissions (n = 98) outnumbered female (n = 64) by a ratio of 3:2. Male admissions averaged 56.7 +/- 1.9 years (mean +/- SEM) vs 56.4 +/- 2.69 years in female (p = 0.98). Sepsis comprised 25.3% (n = 41) of admissions during this period of which chest infection (n = 26) made up 63%. The superinfection rate was 3% comprising colonization of endotracheal and peritoneal dialysis tubes by Candida and Acinetobacter. There was a surprisingly high number of culture negative infections. These amounted to 43.9% (n = 18) out of 41 admissions for sepsis as the primary indication and 57.1% of admissions in which sepsis was an accompaniment of the main indication. The mean duration of ICU stay was 7.17 +/- 1.5 days for sepsis vs 4.7 +/- 0.5 days for admissions other than sepsis. Although this did not reach statistical significance (p = 0.79) it corroborates the prevalent impression that patients with sepsis tend to require longer intensive care. The overall mortality was 37% (n = 60). The mortality for septic patients (42.5%) is alarmingly high. This contrasts with a mortality rate of 34.7% for non-septic patients. The issue of culture negative sepsis needs to be addressed. As it stands, septic patients stay longer than non-septic ones.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnostic difficulties associated with phaeochromocytoma--4 case illustrations.

The diagnosis of phaeochromocytoma can be extremely difficult with 40%-76% of cases escaping diagnosis during life. Until recently, the only available biochemical test for the detection of phaeochromocytoma in Singapore has been the 24-hour urinary vanillyl mandelic acid (VMA). Urinary VMA has been reported to have a high specificity (85%-100%) but variable sensitivity (28%-90%) in the diagnosis of this disease. In 1993, high performance liquid chromatography (HPLC) assays for the measurement of urinary catecholamines and metanephrines were introduced at the Singapore General Hospital. Since 1993, 4 cases of phaeochromocytoma have been detected at our institution. We report here, the diverse clinical presentations of these patients. The urinary-free catecholamine and catecholamine metabolite levels of these patients were compared with corresponding levels from 12 non-phaeochromocytoma patients. Using the reference value of 65.6 mumol/day, we found the urinary VMA to be a highly sensitive (100%) test with a specificity of only 31%. In contrast, a urinary total metanephrine level > or = 9,000 nmol/day was both sensitive (100%) as well as specific (100%).

In the absence of dietary surveillance, chitosan does not reduce plasma lipids or obesity in hypercholesterolaemic obese Asian subjects.

OBJECTIVE: To investigate the effects of Absorbitol on body weight, anthropometry, body composition, blood pressures and lipid profiles in obese, hypercholesterolaemic subjects without dietary restriction. DESIGN: A randomised, double blind. Placebo-controlled study. SUBJECTS: Normal volunteers with no history of chronic illnesses (n=88) who were obese (body fat percentage > 20% in males and > 30% in females) and hypercholesterolaemic (total cholesterol > 5.20 mmol/L). Sixty-eight (72.3%) subjects completed the study. INTERVENTION: After a 4 week run in phase, 4 placebo/Absorbitol (250 mg) capsules were prescribed 3 times a day before meals. Subjects received written information on healthy lifestyle but there was no dietary restriction or monitoring. MAIN OUTCOME MEASURES: Weight, body mass index, lean body mass, waist, hip, blood pressure, fasting lipids and insulin levels were taken at baseline, 4th and 16th week of the study. STATISTICAL ANALYSIS PERFORMED: Analyses were on an intention-to-treat basis. Comparisons between groups were made using Student's t and Mann-Whitney tests for parametric and non-parametric data respectively. RESULTS: There was no significant change in the measured parameters in Absorbitol treated subjects compared to those on placebo, with exception of HDL-cholesterol which increased in the absorbitol group and decreased in the placebo group (p=0.048). The side effects of Absorbitol were also comparable to that of placebo. CONCLUSIONS: In the absence of dietary surveillance, Absorbitol does not bring about improvement in weight, anthropometry, body composition, blood pressure or lipid profile.

A study to assess the effect of dietary supplementation with soluble fibre (Minolest) on lipid levels in normal subjects with hypercholesterolaemia.

Hypercholesterolaemia is one of the major risk factors in the development of coronary artery disease. In recent years, many nonprescription treatments have become available for cholesterol lowering. Minolest is a product that contains guar gum and psyllium as the principal active ingredients. We conducted a randomised, placebo-controlled, double-blind, parallel-group study to assess the efficacy of Minolest as a lipid-lowering agent. Secondary aims included assessment of the effect on blood pressure and obesity. We also looked at the acceptability of the product and side effects associated with its ingestion. After a 4-week run-in period, 83 subjects were randomised to receive placebo or Minolest (16.5 g/day) for 3 months. Seven subjects defaulted follow up, 5 in the placebo group and 2 in the active treatment group. In addition, 9 subjects (5 on active treatment and 4 on placebo) had total cholesterol fall into the optimal range (< 5.2 mmol/l) during the run-in phase and were removed from the study. At baseline in the active treatment group, total cholesterol was 6.1 (5.43 to 8.06) mmol/l, triglyceride 1.54 (0.56 to 4.19) mmol/l, HDL cholesterol 1.32 +/- 0.43 mmol/l and LDL cholesterol 4.1 (3.10 to 6.27) mmol/l. In the placebo group, total cholesterol was 5.84 (5.32 to 8.38) mmol/l, triglyceride 1.47 (0.69 to 11.0) mmol/l, HDL cholesterol 1.15 +/- 0.33 mmol/l and LDL cholesterol 3.87 (2.46 to 5.14) mmol/l. The differences in the baseline characteristics were not statistically significant except the LDL-cholesterol. Minolest produced a 3.24% (SD = 7.85%, P = 0.020) decrease in total cholesterol and 5.45% decrease in LDL cholesterol (SD = 10.25%, P = 0.0034) but no significant difference in serum triglyceride, weight, body mass index or blood pressure. This was not seen in the placebo group. The percentage fall in LDL cholesterol increased to 7.16% and 7.37% in subjects who consumed at least 50% and 70% of the treatment respectively. There were few side effects. The authors conclude that this product has a small impact on the lipid profile and may be useful only in subjects with mild hypercholesterolaemia and a low risk of coronary artery disease.

Metabolic abnormalities in young non-obese males with hypertension.

Essential hypertension has been shown by various studies to be an insulin-resistant state. However, most of these studies have included obese and elderly patients. We were interested to know the extent of insulin resistance in a group of young, non-obese patients with hypertension. A total of 59 male patients with essential hypertension and 31 controls matched for age, sex and body mass index were studied. All the subjects were under 35 years old and had a body mass index of less than 27 kg/m2. Our results showed that such patients with hypertension had significantly higher fasting insulin, total insulin after glucose challenge, insulin/glucose ratio and higher triglycerides than the control subjects.

Thyroid storm presenting as jaundice and complete heart block.

Thyroid storm is a difficult diagnosis in "apathetic" variant of hyperthyroidism. The clinical features may not be evident. Abnormal atrioventricular (AV) conduction, such as complete heart block, in thyrotoxicosis is uncommon. We report a case of a 16-year-old girl presenting with fever, jaundice, heart failure and complete heart block in whom the diagnosis of thyroid storm was initially missed because of the unusual presenting features. Prompt resolution of the conduction abnormality occurred when treatment with carbimazole, intravenous iodide and dexamethasone was instituted.

Measurement of obesity by anthropometry and bioelectric impedance analysis: correlation with fasting lipids and insulin resistance in an Asian population.

Obesity is associated with increased coronary artery disease risk. This is at least partially mediated by increased prevalence of other risk factors such as dyslipidaemia and insulin resistance. Various anthropometric indices have been used to quantify generalised and central obesity. Correlations between these measurements and risk factors are specific to the population and findings cannot be extrapolated to other ethnic groups. Bioelectric impedance analysis (BIA) is a simple means of estimating percentage body fat. We compared body mass index (BMI), waist circumference, waist-hip ratio (WHR) and percentage body fat measure by BIA as predictors of fasting lipid profiles and insulin resistance in 109 Singaporean Chinese. BMI was significantly correlated with insulin resistance and there appeared to be a threshold at 26 kg/m2 above which the regression line became more steep. WHR best predicted fasting triglyceride in both men and women. In women, it was inversely correlated with high density lipoprotein cholesterol. A similar association was seen in men but this did not reach statistical significance. We conclude that measurement of BMI and WHR should be part of the assessment of cardiovascular risk in our population as they connote different aspects of risk. BIA was not found to be a useful tool for the prediction of coronary artery disease risk factors in our population.

Abnormal thyroid and adrenocortical function test results in intensive care patients.

A prospective, cohort study of 75 consecutive patients requiring management in the medical intensive care unit (MICU) of the Singapore General Hospital was carried out over a five-month period to determine thyroid and adrenocortical profiles and evaluate their use in predicting patient outcome. Up to 88% of patients had at least one abnormal thyroid function and 77% had abnormal adrenocortical function test results. There were significantly lower triiodothyronine, thyroxine and free thyroxine, but not thyrotropin levels, and higher cortisol levels in non-survivors compared to survivors (all P < 0.01). Of the endocrine parameters, triiodothyronine and cortisol concentrations were independent predictors of outcome. The overall predictive accuracy of combining these two variables on admission into the MICU was 74%. The APACHE II (acute physiology and chronic health evaluation II) score alone predicted outcome with 71% accuracy, and in combination with triiodothyronine and cortisol levels improved accuracy to 84%. The use of dopamine alone predicted outcome with 74% accuracy, and in combination with triiodothyronine and cortisol levels, improved accuracy to 84%. Measurements of total triiodothyronine and cortisol concentrations on admission to the MICU, and consideration of the use of dopamine improve on the APACHE II score in outcome prediction.

Thyroid stimulating hormone receptor antibody levels in Singaporean patients with autoimmune thyroid disease.

Stimulating thyrotrophin receptor antibodies (TRAbs) have been identified as the antibodies responsible for the pathogenesis of Graves' disease (GD) while blocking TRAbs have been implicated as the cause of hypothyroidism in some patients with chronic lymphocytic thyroiditis (CLT). TRAb positivity in patients with other thyroid disorders such as silent thyroiditis, toxic multinodular goitre and subacute thyroiditis has been reported but the role of TRAb in these disorders is unclear. A study was carried out to determine the prevalence of TRAb positivity in Singaporean patients with a spectrum of thyroid diseases. TRAb levels were measured in 181 patients with GD, 54 patients with CLT (37 goitrous and 17 agoitrous), 16 patients with thyroid nodules, 11 patients with subacute thyroiditis, 1 patient with hyperthyroidism due to a human chorionic gonadotrophin (HCG)-secreting tumour, 2 patients with thyroid stimulating hormone-secreting tumours and 2 patients with amiodarone-induced dysthyroidism. Using a cut-off of 10.0 U/L, TRAb levels were found to be positive in 79.0% of GD patients, 9.2% of CLT patients (euthyroid and hypothyroid) and no patients with other thyroid disorders. TRAb was a more sensitive marker of GD than anti-thyroglobulin antibodies (53.2%) but not anti-microsomal (78.3%) antibodies. TRAb levels > 10.0 U/L appear to be highly specific for autoimmune thyroid disease.

Hyperinsulinaemia in non-obese subjects with hypertriglyceridaemia: a preliminary report.

It has been known for some time that hyperinsulinaemia is associated with hypertriglyceridaemia. However, previous studies looking at the relationship between hyperinsulinaemia and hypertriglyceridaemia have included overweight subjects. The effect of obesity on the insulin status of hypertriglyceridaemic patients is uncertain. We investigated the insulin status of hypertriglyceridaemic subjects in the absence of confounding factors such as obesity, hypertension and diabetes mellitus. Our results demonstrate that basal insulin levels as well as the insulin response after an intravenous glucose challenge are higher in moderately hypertriglyceridaemic patients when compared to age and body mass index matched controls. Hyperinsulinaemia may have pathogenetic significance for hypertriglyceridaemia as well as other features of a constellation of metabolic derangements such as obesity, hypertension and glucose intolerance.

Aldosterone to renin ratios in the evaluation of primary aldosteronism.

Primary aldosteronism, though an uncommon cause of hypertension, causes significant morbidity, making it important to diagnose and treat this condition. Its evaluation requires complex and time consuming investigative procedures in order to confirm the diagnosis and to differentiate between the subtypes of aldosterone producing adenoma and idiopathic hyperaldosteronism. Often, the values of renin and aldosterone are equivocal, and the diagnosis of primary aldosteronism is in doubt. In this study, we examine the use of aldosterone to renin ratios in confirming the diagnosis of primary aldosteronism when the usual criteria of suppressed renin and elevated aldosterone are not met. We have found that an aldosterone to renin ratio of 50 has a 100% specificity and 92% sensitivity for detecting primary aldosteronism. Also, an aldosterone to renin ratio of > 2000 is suggestive of an aldosterone producing adenoma.