Browsing by Author "Ross, Ian Louis"

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    Open Access
    9β Polymorphism of the Glucocorticoid Receptor Gene Appears to Have Limited Impact in Patients with Addison’s Disease
    (Public Library of Science, 2014) Ross, Ian Louis; Dandara, Collet; Swart, Marelize; Lacerda, Miguel; Schatz, Desmond; Blom, Dirk Jacobus
    BACKGROUND: Addison’s disease (AD) has been associated with an increased risk of cardiovascular disease. Glucocorticoid receptor polymorphisms that alter glucocorticoid sensitivity may influence metabolic and cardiovascular risk factors in patients with AD. The 9β polymorphism of the glucocorticoid receptor gene is associated with relative glucocorticoid resistance and has been reported to increase the risk of myocardial infarction in the elderly. We explored the impact of this polymorphism in patients with AD. Materials and METHODS: 147 patients with AD and 147 age, gender and ethnicity matched healthy controls were recruited. Blood was taken in a non-fasted state for plasma lipid determination, measurement of cardiovascular risk factors and DNA extraction. RESULTS: Genotype data for the 9β polymorphism was available for 139 patients and 146 controls. AD patients had a more atherogenic lipid profile characterized by an increase in the prevalence of small dense LDL (p = 0.003), increased triglycerides (p = 0.002), reduced HDLC (p<0.001) an elevated highly sensitive C-reactive protein (p = 0.01), compared with controls. The 9β polymorphism (at least one G allele) was found in 28% of patients and controls respectively. After adjusting for age, gender, ethnicity, BMI and hydrocortisone dose per metre square of body surface area in patients, there were no significant metabolic associations with this polymorphism and hydrocortisone doses were not higher in patients with the polymorphism. CONCLUSIONS: This study did not identify any associations between the 9β polymorphism and cardiovascular risk factors or hydrocortisone dose and determination of this polymorphism is therefore unlikely to be of clinical benefit in the management of patients with AD.
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    Addison's disease symptoms - a cross sectional study in urban South Africa
    (Public Library of Science, 2013) Ross, Ian Louis; Levitt, Naomi S
    BACKGROUND: Addison's disease is a potentially life-threatening disorder, and prompt diagnosis, and introduction of steroid replacement has resulted in near normal life-expectancy. There are limited data describing the clinical presentation of Addison's disease in South Africa. It is hypothesised that patients may present in advanced state of ill-health, compared to Western countries. Patients A national database of patients was compiled from primary care, referral centres and private practices. 148 patients were enrolled (97 white, 34 mixed ancestry, 5 Asian and 12 black). METHODS: Demographic and clinical data were elicited using questionnaires. Biochemical data were obtained from folder reviews and laboratory archived results. RESULTS: The majority of the cohort was women (62%). The median and inter-quartile age range (IQR) of patients at enrolment was 46.0 (32.0-61.0) years, with a wide range from 2.8-88.0 years. The median and IQR age at initial diagnosis was 34.0 (20.0-45.0) years (range 0.02-77.0) years, indicating that at the time of enrolment, the patients, on average, were diagnosed with Addison's disease 12 years previously. Hyperpigmentation was observed in 76%, nausea and vomiting occurred in more than 40%, and weight loss was noted in 25%. Loss of consciousness as a presenting feature was recorded in 20 %. with a 95% confidence interval [CI] of (14-28%) and shock occurred in 5% CI (1.5-8.5%). Case-finding was recorded at 3.1 per million. CONCLUSIONS: The usual constellation of hyperpigmentation, nausea, vomiting and weight loss suggests Addison's disease, but a significant proportion present with an advanced state of ill-health and Addisonian crises. A lower prevalence rate, compared to Western countries is suggested.
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    The aetiopathogenesis, cardiovascular and metabolic complications, and pharmacogenomics of Addison's disease in South Africa
    (2011) Ross, Ian Louis; Levitt, Dinky
    This thesis aimed to address a number of unanswered research questions in Addison's Disease: investigate whether autoimmunity is the predominant cause of Addison's disease in South Africa and if a human leukocyte (HLA) DQ antigen association exists; the extent to which lipids, lipoproteins and biochemical markers of cardiovascular disease are abnormal; the degree to which replacement doses of hydrocortisone are supra-physiological; the impact of glucocorticoid receptor (GCR) polymorphisms on risk factors, markers of cardiovascular disease and replacement doses of hydrocortisone.
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    Amiodarone-induced thyroid dysfunction
    (2005) Ross, Ian Louis; Marshall, David; Okreglicki, Andrzej; Isaacs, Sedick; Levitt, Naomi Sharlene
    Background. Little is known about the frequency of thyroid dysfunction (TD) associated with amiodarone therapy in southern Africa. Objectives. To determine the incidence of TD in a cohort of patients initiated on amiodarone therapy at a cardiac clinic in Cape Town, South Africa, believed to be an iodine-replete area. Patients. Pharmacy records were used to obtain the names of patients who received amiodarone between November 1999 and December 2002. Results. The sample size was 194, but data analysis was limited to the 163 patients for whom there were complete data. The mean age ± standard deviation (SD) was 59.0 ± 15.0 years (range 22 - 89 years). There were 67 female and 96 male patients. The indications for amiodarone therapy were supraventricular tachycardias (N = 102, 62.6%), ventricular tachycardia (N = 55, 33.7%), and prophylaxis against tachycardias (N = 3, 1.8%). The indication was uncertain in 3 patients (1.8%). The median duration of amiodarone treatment was 679.0 days (quartile deviation (QD) 1 172 days, range 3 - 6 425 days) in the whole cohort. The median duration of amiodarone therapy until new TD was 943 days (QD 1 185 days), significantly longer than in patients who remained euthyroid (547 days, QD 1 135 days) (P = 0.05). There were 45 new TD cases (27.6%): 11 patients (6.7%) were thyrotoxic, 1(0.6%) transient thyrotoxicosis, 1 (0.6%) subclinical hyperthyroidism, 13 (8.0%) had subclinical hypothyroidism, 12 (7.4%) hypothyroidism and 7 (4.3%) had minor changes in thyroid function. Conclusions. We found a high incidence of new-onset TD, similar to the highest rates reported internationally. Local factors responsible for this need to be investigated.
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    Cardiovascular risk factors in patients with Addison's disease: a comparative study of South African and Swedish patients
    (Public Library of Science, 2014) Ross, Ian Louis; Bergthorsdottir, Ragnhildur; Levitt, Naomi; Dave, Joel Alex; Schatz, Desmond; Marais, David; Johannsson, Gudmundur
    BACKGROUND: Patients with Addison's disease (AD) in Scandinavia have an increased risk for premature death due to cardiovascular disease (CVD). Serum lipids are important risk factors for CVD and vascular mortality. Replacement doses of hydrocortisone have historically been higher in Sweden than South Africa. The primary aim was to study the lipid profiles in a large group of patients with AD with the hypothesis that the lipid profile in patients in Sweden would be worse than in South Africa. METHODS: In a cross-sectional study, 110 patients with AD (55 from South Africa, 55 from Sweden) matched for age, gender, ethnicity and BMI were studied. Anthropometric measures, blood pressure, lipids, highly sensitive C-reactive protein (hs-CRP) and adiponectin were studied. RESULTS: All patients were Caucasian and the majority were women N = 36 (65.5%). Mean (standard deviation; SD) ages of the Swedish and South African patients were 52.9 (13.0) and 52.6 (14.4) years and BMI 25.3 (3.2) and 25.8 (4.1) kg/m 2 , respectively. The mean total daily hydrocortisone dose was greater in the Swedish patients than the South African patients, [33.0 (8.1) versus 24.3 (8.0) mg; p<0.0001]. South African patients had higher median (interquartilerange; IQR) triglycerides (TG) [1.59 (1.1-2.46) versus 0.96 (0.74-1.6) mmol/l; p<0.001], total cholesterol (TC) [6.02(1.50) versus 5.13 (0.87) mmol/l; p<0.001], LDL-C [4.43 (1.44) versus 2.75 (0.80) mmol/l; p<0.001] and median hs-CRP [2.15 (0.93-5.45) versus 0.99 (0.57-2.10) mg/L; p<0.003] and lower HDL-C [0.80 (0.40) versus 1.86 (0.46) mmol/l; p<0.001] than the Swedish patients. Approximately 20% of the patients in both cohorts had hypertension and diabetes mellitus. CONCLUSIONS: South African patients with AD have worse lipid profiles and higher hs-CRP compared to their matched Swedish patients, despite lower doses of hydrocortisone. It is uncertain at this time whether these are due to genetic or environmental factors.
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    Excessive weight gain following therapy for hyperthyroidism - a major problem
    (Health and Medical Publishing Group, 2003) Ross, Ian Louis; Levitt, Naomi S
    One of the most characteristic presenting features of hyperthyroidism is weight loss, despite an increased appetite. This phenomenon is easily understandable, as hyperthyroidism is accompanied by a rise in metabolic rate, energy expenditure and thermogenesis which is clearly not matched by an increased appetite and caloric intake in the vast majority of patients. Consequently a decrease in adipose tissue and muscle results. (Curiously a small proportion of hyperthyroid patients, fewer than 10%, present with weight gain owing to an increased appetite that exceeds the rise in metabolic rate.
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    Hyperthyroidism: What the generalist should know
    (2003) Ross, Ian Louis; Levitt, Naomi S
    Thyrotoxicosis is one of the more common endocrine disorders and most cases result from hyperactivity of the thyroid gland (hyperthyroidism) (Table I). Younger patients with thyrotoxicosis of any cause may present with palpitations, anxiety, easy fatigability, psychomotor activity, diarrhoea, excessive sweating, heat intolerance, preference for cold, amenorrhoea, and marked weight loss without appetite loss.