Endocrine disturbances, notably diabetes, have been well described as a complication of iron overload due to hereditary hemochromatosis and beta-thalassemia. Dysfunction of the ...hypothalamic-pituitary-adrenal (HPA) axis has also been well documented. The pattern of iron loading in African iron overload with saturated transferrin is similar to that seen in hereditary hemochromatosis. In addition, many symptoms ascribed to pituitary dysfunction are common to both conditions. The present study was undertaken to assess whether a similar pattern of endocrine dysfunction occurs in African iron overload. Thirty subjects with African iron overload and transferrin saturation >50%, plus 30 age and sex matched normal controls were studied. An iron profile, fasting plasma glucose, cortisol, DHEA-S, LH, FSH, growth hormone, prolactin, TSH, and FT4 levels were measured in all 60 subjects as well as testosterone in the males and estradiol in the females. Iron loading in the subjects with increased transferrin saturation ranged from moderate to severe. No significant differences were found in the mean testosterone, estradiol, LH, DHEA-S, growth hormone, prolactin, or TSH levels between the subjects and normal controls. In female subjects, although within the normal range, the mean FSH level was significantly higher, probably due to their being somewhat older and in a more advanced stage of menopause than the control females. Mean cortisol concentrations were increased in both genders in the patient group, significantly so in the females; however, values were within the reference range. We conclude therefore that there appears to be no major impairment of endocrine function in the basal state in African iron overload subjects with moderate to severe degrees of iron loading.
Objective. To assess whether adrenocortical function was compromised in patients with active tuberculosis (TB) during the first 5 days of therapy with either a rifampicin-based or ciprofloxacin-based ...regimen.
Design. Patients were randomised into two groups of 10 each. Adrenocortical function was compared in both groups by the measurement of biochemical indices, electrolytes, osmolality and pituitary-adrenocortical hormones. Adrenal reserve was assessed by intravenous 250 μg adrenocorticotropin hormone (ACTH) stimulation tests.
Setting. Department of Medicine, Johannesburg Hospital.
Subjects. Twenty hospitalised patients who were diagnosed with TB.
Outcome measures. Respiratory rate, pulse rate and blood pressure were recorded, and urinary sodium and osmolality were measured. Serum ACTH, cortisol, dehydroepiandros-terone-sulphate (DHEA-S) and aldosterone were assayed.
Results. None of the patients demonstrated biochemical evidence of overt adrenal insufficiency. There were no significant differences between the two groups before or during therapy for any biochemical indices, electrolytes, hormones or calculated osmolality. Mean basal cortisol concentrations were substantially elevated and DHEA-S levels were consistently subnormal, resulting in a high cortisol/DHEA-S ratio. In the ciprofloxacin group, cortisol responses to ACTH stimulation on day 1 were not significantly lower than on day 5. In the rifampicin group, cortisol concentrations decreased at each time point on day 5 compared with day 1 (p = 0.001). However, a significantly higher mean incremental rise from the basal cortisol concentration was measured on day 5 at 60 minutes (p = 0.04). In the entire cohort of 20 patients, 40% demonstrated an incremental cortisol rise of < 250 nmol/l after ACTH stimulation on day 1.
Conclusions. Rifampicin did not additionally impair adrenocortical function during the initial period of therapy. The high cortisol/DHEA-S ratio might be of clinical relevance.
To assess whether moderate dietary protein restriction can delay the progression of overt diabetic nephropathy, 22 subjects with insulin-dependent diabetes mellitus were randomly assigned to an ...unrestricted protein diet (> 1.6 g.kg body wt-1.d-1) or a moderately protein-restricted diet (0.8 g.kg body wt-1.d-1) and followed prospectively for six mo. Direct isotope methods were used to assess renal function. Protein intake was assessed by measurement of urinary urea nitrogen. The two groups were well-matched for age, sex, duration of diabetes, glycemic control, blood pressure, and degree of renal insufficiency. Patients consuming the unrestricted protein diet (n = 11) showed a progressive decline in glomerular filtration rate of 1.3 mL.min-1.mo-1 with no change in proteinuria. Patients consuming the moderately protein-restricted diet showed a marked decrease in the degree of proteinuria (2.15-1.13 g/d, P = 0.036) and a stabilization of glomerular filtration rate. This occurred independently of changes in blood pressure or glycemic control. Moderate dietary protein restriction can ameliorate progression of overt diabetic nephropathy.
The peak age specific prevalence occurs earlier in HIV/AIDS than type 2 diabetes, but correspondingly fewer infected people will survive to middle age. ...our calculation of 3% fewer cases, ...reflecting the expected decrease in population growth due to HIV/AIDS, represents a small but substantial reduction, irrespective of the prevalence of diabetes selected.
Objective. To assess whether adrenocortical function was compromised in patients with active tuberculosis (TB) during the first 5 days of therapy with either a rifampicin-based or ciprofloxacin-based ...regimen. Design. Patients were randomised into two groups of 10 each. Adrenocortical function was compared in both groups by the measurement of biochemical indices, electrolytes, osmolality and pituitary-adrenocortical hormones. Adrenal reserve was assessed by intravenous 250 µg adrenocorticotropin hormone (ACTH) stimulation tests. Setting. Department of Medicine, Johannesburg Hospital. Subjects. Twenty hospitalised patients who were diagnosed with TB. Outcome measures. Respiratory rate, pulse rate and blood pressure were recorded, and urinary sodium and osmolality were measured. Serum ACTH, cortisol, dehydroepiandrosterone- sulphate (DHEA-S) and aldosterone were assayed. Results. None of the patients demonstrated biochemical evidence of overt adrenal insufficiency. There were no significant differences between the two groups before or during therapy for any biochemical indices, electrolytes, hormones or calculated osmolality. Mean basal cortisol concentrations were substantially elevated and DHEA-S levels were consistently subnormal, resulting in a high cortisol / DHEA-S ratio. In the ciprofloxacin group, cortisol responses to ACTH stimulation on day 1 were not significantly lower than on day 5. In the rifampicin group, cortisol concentrations decreased at each time point on day 5 compared with day 1 (p = 0.001). However, a significantly higher mean incremental rise from the basal cortisol concentration was measured on day 5 at 60 minutes (p = 0.04). In the entire cohort of 20 patients, 40% demonstrated an incremental cortisol rise of Conclusions. Rifampicin did not additionally impair adrenocortical function during the initial period of therapy. The high cortisol / DHEA-S ratio might be of clinical relevance.
Insulin-receptor activity in nondiabetic and diabetic urbanized South African black women.
V R Panz ,
B I Joffe ,
J R Wing ,
F J Raal and
H C Seftel
Carbohydrate and Lipid Metabolism Research Group, ...University of the Witwatersrand Medical School, Johannesburg, South Africa.
Abstract
OBJECTIVE--To evaluate insulin receptor binding characteristics of urbanized South African black women with normal glucose
tolerance and of patients with newly diagnosed untreated non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN
AND METHODS--Four groups of 10 subjects each were selected by the following criteria: group A, young (20-39 yr) nonobese (body
mass index BMI 19.0-24.9 kg/m2) nondiabetic women; group B, middle-aged (40-60 yr) nonobese nondiabetic women; group C,
middle-aged obese (BMI greater than 30.0 kg/m2) nondiabetic women; and group D, middle-aged obese newly diagnosed but untreated
female patients with NIDDM. Insulin binding to monocyte receptors was determined by radioreceptor assay. Fasting plasma samples
were analyzed for glucose, insulin, C-peptide, and nonesterified fatty acids. RESULTS--In the four groups studied, maximum
specific binding and receptor concentration were highest in group A, with a progressive and significant decrease in values
through groups B and C to group D. Significant inverse correlations were obtained between maximum specific binding, 50% inhibition
dose, and total receptor concentration on the one hand and glucose, insulin, and NEFA on the other. CONCLUSIONS--Our study
of urban South African black women showed decreasing insulin-receptor activity with obesity and glucose intolerance. In patients
with NIDDM, hyperglycemia and beta-cell dysfunction were associated with a reduction in receptor concentration. In this regard,
our findings in South African blacks are consistent with results of similar studies of NIDDM in other communities.
Relationship between plasma insulin and blood pressure in South African black women in Johannesburg.
B I Joffe ,
V R Panz ,
J R Wing ,
F J Raal and
H C Seftel
Department of Medicine, University of ...Witwatersrand Medical School, Johannesburg, South Africa.
Abstract
OBJECTIVE--To examine the relationship between fasting plasma insulin and blood pressure (BP) in 40 urbanized normotensive
South African black women aged 24-60 yr, and to assess the effects of body mass index (BMI) and fasting plasma glucose on
BP. RESEARCH DESIGN AND METHODS--The women comprised equal numbers of young nonobese nondiabetic subjects, middle-aged nonobese
nondiabetic subjects, middle-aged obese nondiabetic subjects, and middle-aged obese newly diagnosed non-insulin-dependent
diabetic subjects. Systolic and diastolic BPs were recorded (in duplicate) after 15 min of recumbency, and fasting plasma
glucose and insulin levels were determined thereafter. The data were analyzed by simple and multivariate regression. RESULTS--There
was a wide distribution of individual physical and biochemical features. With simple correlations, systolic BP correlated
significantly with age, BMI, and fasting glucose but not with insulin. Diastolic BP correlated significantly with all four
variables (r = 0.37, P less than 0.05). When adjusted for age, BMI, and glucose, however, the significant correlation between
diastolic BP and insulin diminished (r = -0.04). CONCLUSIONS--As in other nonwhite communities, plasma insulin does not appear
to play a major role in regulating the BP of South African black women.
The prevalence of hyperthyroidism owing to Graves' disease is increasing among urban black South Africans. Thyroid-associated ophthalmopathy is often observed in this context, but its pathogenesis ...remains unclear. No close relationship has been noted between antiflavoprotein (Fp) antibodies or thyrotropin receptor antibodies and ocular involvement in black patients. We measured serum antibodies against eye muscle and orbital connective tissue antigens in black patients with Graves' disease, correlating them with eye signs. Of 11 patients with clinical ophthalmopathy, 2 (18%) had antibodies against collagen type XIII, 3 (27%) against flavine adenine dinucleotide (FAD), 1 (9%) against Fp, and 4 (35%) against G2s. Antibody prevalences in eight patients without clinical ophthalmopathy were 12.5% for collagen XIII, 12.5% for FAD, 25% for Fp and 0% for G2s. These differences were not statistically significant. None of the individual mean antibody levels were significantly different between the two subgroups of thyrotoxic patients. Serum antibody levels were negative in 10 black South African controls. In summary, eye muscle and orbital connective tissue antibodies were found in small proportions of patients with Graves' disease with no close relationship of any antibody to eye signs. Thus, a substantial proportion of black South Africans with overt clinical ophthalmopathy remains in whom currently availabe serologic tests are unhelpful for screening and laboratory confirmation.
Elevated serum concentrations of endothelium-associated adhesion molecules occur in Graves' disease. However, no data exist in African subjects, among whom the incidence is rising. Therefore, 20 ...black South Africans with Graves' hyperthyroidism were evaluated and 10 healthy controls were also studied. Quantitative determinations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble E-Selectin (sE-Selectin) were performed in serum samples by an enzyme-linked immunosorbent assay. Mean levels of sVCAM-1 were significantly increased in the thyrotoxic patients compared to controls, but this did not apply to the other adhesion molecules. The presence of ophthalmopathy in 12 patients did not further increase the mean sVCAM-1 concentration, and the administration of antithyroid medication in 5 patients had no measurable effect. In conclusion, sVCAM-1 appears to be a useful marker of active Graves' disease in black South Africans although it does not seem to reflect the occurrence of eye involvement in such patients.
The frequency of DNA polymorphisms in the tyrosine kinase domain (exons 17-21) of the insulin receptor gene was assessed in 30 black and 30 white South Africans, using single-stranded conformation ...polymorphism and direct sequencing analysis. A comparison of the frequencies of the normal versus the combined polymorphic alleles, found only in exon 17, showed a significant difference between black and white groups (P = 0.037).
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