Doctoral Degrees (Internal Medicine)
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Item Open Access Bone health in Graves’ disease: a comparison of black and white South African women(University of the Free State, 2019) De Lange, Willem; Mollentze, W. F.; Pettifor, John M.Objectives: The negative effects of thyrotoxicosis on bone health in white populations have been widely studied. In non-South African black populations, it has been showed that the skeleton is protected against the negative effects of other endocrinopathies, for e.g.: hyperparathyroidism. The aim of the study was to determine whether black South African women are also protected against the detrimental effects of Graves’ disease (GD)? Background and motivation: The detrimental effects of thyrotoxicosis on bone health has been known for more than a century. In white females, thyrotoxicosis has been shown to increase the rate of bone resorption along with bone formation. However, the rate of bone formation is inadequate to compensate for bone resorbed, leading to a net loss of bone volume. This negatively impacts on the structural integrity of bone with an increased fracture risk. Little is known about the effect of thyrotoxicosis on bone health in black African-, and especially black South African women. Ethnic differences in bone metabolism and fat distribution do exist between black and white South African women. Dual-energy X-ray absorptiometry (DXA) studies have shown that the bone mineral density at the lumbar spine of healthy premenopausal black South African women, is equal or lower than that of their white counterparts. The bone mineral density of postmenopausal black- and white women at the lumbar spine is comparable. Vertebral fracture risk of the lumbar spine is equal for black- and white South African women. Significant differences in femoral bone density do exist when black and white South African women are compared. Black South African women have a greater bone mineral density at the femur neck site. Histomorphometric and radiometric differences between these two ethnic groups may explain the lower incidence of femoral fragility fractures in the black population. Black South African women, when compared to their white counterparts, have thicker and less porous cortices as well as thicker trabeculae. These micro architectural differences could explain the decreased number of fractures seen in black females when compared to white females. There are also ethnic differences in the abdominal adipose tissue depot distribution. White men and women have increased abdominal visceral adipose tissue and decreased subcutaneous adipose tissue when compared to black men and women. Thyrotoxicosis has detrimental effects on bone metabolism and bone structure in white women. These effects can lead to an increased risk of fracture that persists even after normalization of the bone mineral density. Study design: This was a prospective exploratory and comparative study. Methods: A convenience sample of 40 consecutive and consenting black female patients (age ≥ 25 and ≤ 65 years) and 20 consecutive and consenting white female patients (age ≥ 25 and ≤ 65 years) with confirmed GD referred to the Endocrine service at Universitas Hospital were recruited for the study. Patients were matched with 40 black and 20 white healthy control females according to age (± 5 years), body mass index (BMI) and seasonality. Black- and white South African women suffering from GD were compared with each other at baseline, 6- and 12 months according to pre-determined objectives. Women suffering from GD were also compared with healthy controls from the same ethnic group. This comparison was performed to rule out effects of ethnicity versus effects of GD on bone health. The main objectives included differences in biochemical markers, bone mineral density and body composition. Histomorphometric data on the effect of GD on bone in white ethnic groups has been published before. Therefore, bone histomorphometry was only performed in black women suffering from GD to ascertain whether ethnic differences do exist. Results: In this prospective study, 39 black women and 20 white women with newly diagnosed GD were included. The median parathyroid hormone (PTH) level of black women suffering from GD was suppressed and significantly lower when compared to white patients (p = 0.04). The suppressed PTH in black patients were accompanied by increased serum calcium levels. The markers of bone formation as well as bone resorption were increased in both patient groups. The median urine deoxypyridinoline (DPD) to creatinine ratio (Urine DPD), a marker of bone resorption, was significantly higher in black women suffering from GD compared to white patients (p = 0.026). Although the median 25-hydroxyvitamin D (25(OH)D) level of black patients with GD was lower compared to their white counterparts and suppressed below the lower limit of the laboratory threshold, it did not differ significantly. The median 1,25dihydroxyvitamin D (1,25(OH)2D) levels of black- and white patients were normal and not different. A marker of inflammation, tumour necrosis factor alpha (TNFα), was significantly higher in black patients compared to white patients (p = 0.022) while the other markers included, interleukin 6 (IL-6) and C-reactive protein (CRP), did not differ. The median insulin-like growth factor 1 (IGF-1) levels of both patient groups were lower compared to healthy controls. The median IGF-1 of black patients was significantly lower compared to that of healthy black controls (p = 0.001). The same was observed in white patients and – controls with white patients having a significantly lower median IGF-1 level (p = 0.05). There was no difference between the two patient groups. The actual bone mineral density (BMD) of white patients at the left femoral neck was significantly lower compared to black patients at baseline (p = 0.033). This difference was not observed between white patients and –controls. The BMD at the left forearm distal 3rd was lower in black patients compared to white patients (p = 0.049). Although the same pattern was observed when comparing the median Z-scores at baseline, it did not reach significance. The median Z-score at the left total hip of white patients were significantly lower when compared to white controls (p = 0.039). A greater proportion of black patients had a median Z-score of the lumbar spine ≤ -2.0 compared to white patients (p = 0.028). The difference observed of actual BMD at the left femoral neck between black- and white patients at baseline was maintained at 6- and 12 months after therapy. The difference at the left forearm distal 3rd disappeared at months 6 and 12. The actual BMD of white patients at the right femoral neck was significantly lower at 12 months compared to black patients (p = 0.030). The body composition of both black- and white patients were comparable at baseline. However, the percentage change in body mass index (BMI) did differ significantly from 0-6 and 0-12 months between the two patient groups. Black patients had a significantly higher percentage increase in BMI at 0-6 months (p = 0.042) and 0-12 months (p = 0.01) compared to white patients. The body composition of white patients and –controls did not differ significantly at baseline, 6- and 12 months. Although the body composition of black patients and –controls were comparable at baseline, black patients had a significant increase of especially fat tissue after treatment. This is confirmed by a significantly higher fat mass index (FMI) found in black patients at 12 months compared to controls (p = 0.011). The bone histomorphometry revealed a state of accelerated bone turnover, predominant stimulation of bone resorption and histological evidence of demineralization as evidenced by abundant osteoid on histology. Conclusions: Ethnic differences between black- and white South African women suffering with GD were shown. Black South African women are not protected against detrimental skeletal effects of GD. It is hoped that this study will contribute to a better understanding of bone health in the South African population in general, but especially those patients with GD. It is also envisioned that this may lead to improved management of patients once thought to be protected against the skeletal complications of GD. Further South African research is warranted.Item Open Access Radionuclide cisternography: imaging and study of the cerebrospinal fluid circulation(University of the Free State, 1975-12) Iturralde, Mario Paulino; Retief, F. P.English: English: Radionuclide cisternography performed in 200 selected patients with neurological disease has proved to be a simple and relatively safe procedure, v,rithminimal disturbing side effects, which can provide useful information about cerebrospinal fluid (eSF) flow and dynamics. Following the subarachnoid or ventricular injection of an appropiate radiopharmaceutical, the tracer flows with the eSF and demonstrates the pathways of circulation under normal and abnormal conditions with virtually no disruption of the existing eSF physiology. The eventual distribution of the tracer is complex. The range of normal varies from rapid ascent with early absorption of the radiopharmaceutical to slower ascent and absorption, frequently with laterilization of flow to one or other side intracranially and occasionally with transient ventricular reflux. In pathological states the cisternographic picture varies ac= cation (or lack of it) of the ventricles with the subarachnoid cording to the underlying disease. It may lack the ability to establish the precise anatomical features available from air encephalography. However ventricular dilatation, the communispace, and the delay or lack of absorption are only satisfactorily demonstrated by radionuclide cisternography. Repeated examinations may be readily performed to show progression of the disease or the results of surgical treatment. The abnormal flow pattern in patients with normal pressure hydrocephalus proved to be the most important criterion in their selection for extracranial neurosurgical eSF shunting. When properly selected, these patients often respond to surgical treatment. The routine use of radionuclide cisternography in the examination of patients with suspected presenile dementia and compensated hydrocephalus results in a low yield of operable patients. When operation is contraindicated conservative management of the patient is then instituted and unnecessary surgical intervention avoided. Radionuclide cisternography gained wide acceptance in the evaluation of shunt patency. The test is fast and safe in the presence of extracranial diversionary eSF shunts. The rapid flow into the cerebral ventricles and the fast disappearance of the radioactive tracer, as well as the relative size of the ventricular system, are valuable indexes for the determination of patency and efficaccy of the shunt. Another important use of radionuclide cisternography is the investigation of eSF leaks and eSF spinal flow obstruction. It may demonstrate the existence and site of eSF leakage or block and offer valuable assistance to the neurosurgeon. Radionuclide cisternographic images are usually interpreted subjectively on the basis of abnormal regional and temporal concentrations of radiopharmaceuticals in the eSF space. The evaluation of images can be improved by the use of quantitative computerized digital scanning, increasing the sensitivity and value of the measurements. The further extension of these studies involving abnormalities of cerebrospinal fluid dynamics would seem worthwhile, and the value of the methods described in this thesis and their limitations, remain a potential and challenging field for further exploration.Item Open Access Diabetes mellitus hypertension and related factors in black subjects residing in Qwaqwa and Bloemfontein(University of the Free State, 2003) Mollentze, Willem Frederik; Weich, D. J. V.; Joubert, G.; Steyn, K.; Steyn, A. F.English: BACKGROUND The black population of South Africa underwent rapid urbanisation during the last century. This process was accompanied by major changes in lifestyle including less physical activity, the moving away from traditional low-fat diets to diets high in saturated fat, and the acquiring of unhealthy habits such as the smoking of cigarettes. Previously rare chronic diseases of lifestyle such as diabetes mellitus, hypertension, obesity, dyslipidaemia and atherosclerotic cardiovascular disease started to emerge during this period. AIMS The primary aims of the study were to determine the prevalence of diabetes mellitus, hypertension, obesity, and dyslipidaemia, in a partly rural and an urban black community. The secondary objectives were to investigate the hypotheses that the metabolic syndrome existed in the black population and that hypertension was associated with hyperinsulinaemia in the study populations. STUDY DESIGN A cross-sectional study SETTING: The study was conducted in the semi-rural area of Qwaqwa and in Mangaung, the main black residential area of Bloemfontein. METHODS A representative sample of 853 subjects 25 years and older (279 males and 574 females) was selected from Qwaqwa, a partly rural community in the Free State, and a similar sample of 758 subjects (290 males and 468 females) from Mangaung, the black residential area of Bloemfontein, as the urban sample for comparison. After informed consent, the prevalence of the following conditions was determined according to standardised procedures: diabetes mellitus, impaired glucose tolerance, impaired fasting glucose, hypertension, dyslipidaemia, and overweight and obesity. In addition, anthropornetrlcal measurements including the measurement of selected skinfold thickness and body circumferences were measured. A 12- lead resting electrocardiograph was obtained from each subject and blood specimens were collected for the measurement of insulin, proinsulin and C-peptide. A trained nurse administered a questionnaire to each respondent in his or her own language to obtain demographic and biosocial information. RESULTS The response rates were 68% in Qwaqwa and 62% in Mangaung. The age-standardised prevalence rates for the chronic diseases that were studied, are provided in the Table 51. Table A1 will be attached on the full document. The prevalence rates of the risk factors that were studied did not differ significantly between the Qwaqwa and Mangaung samples. Although the metabolic syndrome was present in 31% of subjects in both samples, no electrocardiographic evidence of an increased prevalence of coronary heart disease was found in subjects with the metabolic syndrome. Hyperinsulinaemia and thus insulin resistance was not associated with hypertension in any of these two black populations with a high prevalence of obesity and hypertension. It is unlikely that a population with such a clustering of cardiovascular risk factors can much longer escape the emergence of coronary artery disease as an important public health problem. CONCLUSION The black populations of Qwaqwa and Mangaung are well advanced on the raad of urbanisation and the nutrition transition. Chronic diseases of lifestyle are as prevalent in these communities as elsewhere in the Western world. Coronary artery disease is usually the last of the typical Western diseases to emerge in a population in transition and it is unlikely that these black populations will escape this disease much longer.Item Open Access Integrating HIV care into primary health care services in the Free State : process and impact(University of the Free State, 2014-11-21) Uebel, Kerry Elizabeth; Mollentze, W. F.; Van Rensburg, H. C. J.Abstract not available