It is still a matter of debate if subtle changes in selenium (Se) status affect thyroid function tests (TFTs) and bone mineral density (BMD). This is particularly relevant for the elderly, whose ...nutritional status is more vulnerable.
We investigated Se status in a cohort of 387 healthy elderly men (median age 77 yrs; inter quartile range 75-80 yrs) in relation to TFTs and BMD. Se status was determined by measuring both plasma selenoprotein P (SePP) and Se.
The overall Se status in our population was low normal with only 0.5% (2/387) of subjects meeting the criteria for Se deficiency. SePP and Se levels were not associated with thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroxine (T4), triiodothyronine (T3) or reverse triiodothyronine (rT3) levels. The T3/T4 and T3/rT3 ratios, reflecting peripheral metabolism of thyroid hormone, were not associated with Se status either. SePP and Se were positively associated with total BMD and femoral trochanter BMD. Se, but not SePP, was positively associated with femoral neck and ward's BMD. Multivariate linear analyses showed that these associations remain statistically significant in a model including TSH, FT4, body mass index, physical performance score, age, smoking, diabetes mellitus and number of medication use.
Our study demonstrates that Se status, within the normal European marginally supplied range, is positively associated with BMD in healthy aging men, independent of thyroid function. Thyroid function tests appear unaffected by Se status in this population.
The influence of hypercortisolism on phosphate homeostasis is relatively unknown. A few previous studies have reported on patients with Cushing's syndrome (CS) with hypophosphatemia in whom serum ...phosphate normalized after initiation of treatment for CS. We aimed to investigate the prevalence of hypophosphatemia in CS, the association between the degree of hypercortisolism and serum phosphate and the change in serum phosphate after remission of CS. We compared the prevalence of hypophosphatemia in CS with the prevalence in the population-based Rotterdam Study (RS).
Patients diagnosed with CS and treated at the Department of Endocrinology of Erasmus MC in the period of 2002-2020 were included and data was collected on age at diagnosis, sex, serum phosphate, calcium and potassium levels, kidney function and BMI. Using multivariate linear regression, we analyzed the association between 24h urinary free cortisol excretion (UFC) and serum phosphate. Changes in serum phosphate and covariates were tested with a repeated measurement ANOVA, using mean levels of laboratory values for the periods before remission, and 0-14 days and 15-180 days after remission.
Hypophosphatemia before treatment was present in 16% of the 99 CS patients with data on serum phosphate, 24h UFC and covariates. In comparison, the prevalence of hypophosphatemia in RS was 2.0-4.2%. Linear regression showed a negative association between the level of UFC and serum phosphate at diagnosis, which remained significant after adjusting for covariates β -0.002 (95%CI -0.004; -0.0004), p=0.021. A subset of 24 patients had additional phosphate measurements at 0-14 days and 15-180 days after remission. In this subgroup, serum phosphate significantly increased from 1.03 ± 0.17 mmol/L prior to remission to 1.22 ± 0.25 mmol/L 15-180 days after remission (
= 0.008). BMI decreased after remission -1.1 kg/m
, (95%CI -2.09 to -0.07), p=0.037. Other covariates did not show an equivalent change over time.
In this retrospective study, we found that 16% of patients with CS had hypophosphatemia. Moreover, serum phosphate was related to the level of cortisoluria and increased after remission of CS. Potential underlying mechanisms related to urinary phosphate excretion and possibly involving FGF23, BMI and parathyroid hormone levels should be further explored.
Objective Insulin-like growth factor-binding protein-2 (IGFBP-2) concentrations are low in subjects with metabolic syndrome and type 2 diabetes. Intriguingly, recent studies have demonstrated an ...association between high IGFBP-2 concentrations and increased mortality not only in populations with certain types of cancer, but also in relatively healthy populations. We evaluated the role of IGFBP-2 in relation to BMI and mortality. Design and Participants BMI, insulin sensitivity, insulin-like growth factor 1 (IGF-I) and IGFBP-2 were assessed repeatedly in 539 participants of the Baltimore Longitudinal Study of Aging around the ages of 55, 65 and 75 years. Results IGFBP-2 concentrations positively correlated with insulin sensitivity and inversely with BMI, both at baseline and follow-up. Independent of IGF-I, sex, BMI and insulin sensitivity, circulating IGFBP-2 levels positively correlated with age (P < 0.001). Changes over time in BMI were associated with an inverse correlation in IGFBP-2 concentrations. Furthermore, we found indications of a relationship between low baseline IGFBP-2 levels and mortality. Remarkably, after adjustment for insulin sensitivity, the opposite association was found, as a unit increase of log(IGFBP2) was associated with an increase in the log hazard by 1.43 (95% CI: 0.3-2.6). This accounted for both baseline (P = 0.02) as well as serial (P < 0.001) measurements of IGFBP2. Finally, in this longitudinal study, we found that IGF-I concentrations increased with age (0.82 ± 0.2 (µg/L)/year, P < 0.001). Conclusion This is the first study investigating the relationship between IGFBP-2 levels and age in a longitudinal setting. Serum IGFBP-2 levels increase with age after the age of 50 years and evolve in parallel with insulin sensitivity. IGFBP-2 may therefore be a potential marker for insulin sensitivity. We further show that IGFBP-2 levels can predict mortality in this aging population. However, its predictive value for mortality can only be interpreted in relation to insulin sensitivity. After adjustment for insulin sensitivity, high IGFBP-2 levels are predictive of increased mortality.
The Endocrinology of Aging Steven W. J. Lamberts; van den Beld, Annewieke W.; van der Lely, Aart-Jan
Science,
10/1997, Volume:
278, Issue:
5337
Journal Article
Peer reviewed
Open access
Most aging individuals die from atherosclerosis, cancer, or dementia; but in the oldest old, loss of muscle strength resulting in frailty is the limiting factor for an individual's chances of living ...an independent life until death. Three hormonal systems show decreasing circulating hormone concentrations during normal aging: (i) estrogen (in menopause) and testosterone (in andropause), (ii) dehydroepiandrosterone and its sulphate (in adrenopause), and (iii) the growth hormone/insulin-like growth factor I axis (in somatopause). Physical changes during aging have been considered physiologic, but there is evidence that some of these changes are related to this decline in hormonal activity. Hormone replacement strategies have been developed, but many of their aspects remain controversial, and increasing blood hormone levels in aging individuals to those found during mid-adult life has not been uniformly proven to be safe and of benefit.
The burden of atherosclerosis especially afflicts the increasing older segment of the population. Recent evidence has emphasized a protective role of endogenous sex hormones in the development of ...atherosclerosis in aging men.
We studied the association between endogenous sex hormones and progression of atherosclerosis in 195 independently living elderly men. Participants underwent measurements of carotid intima-media thickness (IMT) at baseline in 1996 and again in 2000. At baseline, serum concentrations of testosterone (total and free) and estradiol (total and free E2) were measured. Serum free testosterone concentrations were inversely related to the mean progression of IMT of the common carotid artery after adjustment for age (beta=-3.57; 95% CI, -6.34 to -0.80). Higher serum total and free E2 levels were related to progression of IMT of the common carotid artery after adjustment for age (beta=0.38; 95% CI, -0.11 to 0.86; and beta=0.018; 95% CI, -0.002 to 0.038, respectively). These associations were independent of body mass index, waist-to-hip ratio, presence of hypertension and diabetes, smoking, and serum cholesterol levels
Low free testosterone levels were related to IMT of the common carotid artery in elderly men independently of cardiovascular risk factors.
Context: Physiological changes in thyroid hormone concentrations might be related to changes in the overall physical function in the elderly.
Objective: We determined to what extent thyroid hormone ...concentrations are related to physical function and mortality in elderly men.
Design: A longitudinal population study (the Zoetermeer study) was conducted. Mortality was registered in the subsequent 4 yr.
Participants: Four hundred three independently and ambulatory living men (aged 73–94 yr) participated.
Main Outcome Measures: The study examined the association between serum thyroid hormones and parameters of physical function as well as the association with mortality.
Methods: TSH, free T4 (FT4) total T4, T3, rT3, and T4-binding globulin were measured. Physical function was estimated by the number of problems in activities of daily living, a measure of physical performance score (PPS), leg extensor strength and grip strength, bone density, and body composition.
Results: Serum rT3 increased significantly with age and the presence of disease. Sixty-three men met the biochemical criteria for the low T3 syndrome (decreased serum T3 and increased serum rT3). This was associated with a lower PPS, independent of disease. Furthermore, higher serum FT4 (within the normal range of healthy adults) and rT3 (above the normal range of healthy adults) were related with a lower grip strength and PPS, independent of age and disease. Isolated low T3 was associated with a better PPS and a higher lean body mass. Low FT4 was related to a decreased risk of 4-yr mortality.
Conclusions: In a population of independently living elderly men, higher FT4 and rT3 concentrations are associated with a lower physical function. High serum rT3 may result from a decreased peripheral metabolism of thyroid hormones due to the aging process itself and/or disease and may reflect a catabolic state. Low serum FT4 is associated with a better 4-yr survival; this may reflect an adaptive mechanism to prevent excessive catabolism.
Summary
objective Sensitivity to glucocorticoids differs between individuals, partially due to genetic variation in the glucocorticoid receptor (GR) gene. We studied the sequence alteration of a ...previously described intronic BclI polymorphism of the GR gene, and investigated whether there was an association with sensitivity to glucocorticoids and anthropometric parameters in a group of healthy elderly individuals.
design and measurements In study group 1, two overnight dexamethasone suppression tests (DSTs) were performed: with 1 mg dexamethasone, and 2·5 years later with 0·25 mg dexamethasone. Anthropometric parameters were measured in a larger population (study group 2), as well as in a third study group, in which we also measured body composition by dual‐energy X‐ray absorbtiometry (DEXA) scans.
subjects Groups 1 and 2, respectively, 191 and 1963 male and female participants of the Rotterdam study, a population‐based study in Dutch elderly. Study group 3: 370 elderly males (mean age 77·8 ± 0·2 years) from Zoetermeer, the Netherlands.
results We identified the BclI restriction site polymorphism as a C/G substitution in intron 2, 646 nucleotides downstream from exon 2. After both 1 mg and 0·25 mg DST, heterozygous (CG) and homozygous G‐allele carriers (GG) had lower cortisol levels than CC‐carriers (P = 0·01 and P = 0·02, respectively). In study group 2, we found a lower body mass index (BMI; P = 0·006) and waist–hip ratio (WHR; P = 0·02) in G‐allele carriers. In study group 3, again we found a lower BMI (P = 0·05) in G‐allele carriers. No differences were found in fat mass. However, lean mass tended to be lower in G‐allele carriers (P = 0·07).
conclusions We characterized a BclI‐RFLP (restriction fragment length polymorphism) of the GR gene as a C/G polymorphism in intron 2 of which the G‐allele was associated with hypersensitivity to glucocorticoids. This resulted in a lower BMI in older individuals in general, while our study in elderly males suggests that the lower BMI is probably due to a greater loss of lean mass during the ageing process.
Prediction of Mortality Risk in the Elderly Störk, Stefan; Feelders, Richard A.; van den Beld, Annewieke W. ...
The American journal of medicine,
06/2006, Volume:
119, Issue:
6
Journal Article
Peer reviewed
Ways to predict the risk of cardiovascular (CV) events or all-cause mortality have largely been derived from populations in which old and very old subjects were underrepresented. We set out to ...estimate the incremental prognostic utility of inflammation and atherosclerosis markers in the prediction of all-cause and CV mortality in elderly men.
In a prospective population-based cohort study, conventional CV risk factors were documented in 403 independently living elderly men. C-reactive protein (CRP) and interleukin (IL)-6 levels were measured. Carotid plaques were assessed by ultrasound. Analyses were performed with proportional hazards analyses, and bootstrapping was used for internal validation. Main outcome was CV and all-cause mortality occurring during 4 years of follow-up.
Increasing tertiles of CRP, IL-6, and number of plaques were independently associated with all-cause and CV mortality. With information on age, carotid plaques, IL-6, and CRP yielded good discriminatory power for all-cause and CV mortality: area under the receiver operating characteristic curve (95% confidence interval), 0.76 (0.70-0.82) and 0.74 (0.68-0.80), respectively. Combined use of only IL-6 and plaque burden allowed identification of subjects with low and high mortality risk. The Framingham PROCAM and a Dutch Risk Function poorly predicted mortality risk, similar or worse than a model using age alone.
In the old and very old, IL-6 and number of carotid plaques are powerful predictors of mortality risk in the years to come. Conventional risk scores seem to perform unsatisfactorily.
In the present cross-sectional study of 403 independently living elderly men, we tested the hypothesis that the decreases in bone mass, body composition, and muscle strength with age are related to ...the fall in circulating endogenous testosterone (T) and estrogen concentrations. We compared various measures of the level of bioactive androgen and estrogen to which tissues are exposed. After exclusion of subjects with severe mobility problems and signs of dementia, 403 healthy men (age, 73-94 yr) were randomly selected from a population-based sample. Total T (TT), free T (FT), estrone (E1), estradiol (E2), and sex hormone-binding globulin (SHBG) were determined by RIA. Levels of non-SHBG-bound T (non-SHBG-T), FT (calc-FT), the TT/SHBG ratio, non-SHBG-bound E2, and free E2 were calculated. Physical characteristics of aging included muscle strength measured using dynamometry, total body bone mineral density (BMD), hip BMD, and body composition, including lean mass and fat mass, measured by dual-energy x-ray absorptiometry. In this population of healthy elderly men, calc-FT, non-SHBG-T, E1, and E2 (total, free, and non-SHBG bound) decreased significantly with age. T (total and non-SHBG-T) was positively related with muscle strength and total body BMD (for non-SHBG-T, respectively, beta = 1.93 +/- 0.52, P < 0.001 and beta = 0.011 +/- 0.002, P < 0.001). An inverse association existed between T and fat mass (beta = -0.53 +/- 0.15, P < 0.001). Non-SHBG-T and calc-FT were more strongly related to muscle strength, BMD, and fat mass than TT and were also significantly related to hip BMD. E1 and E2 were both positively, independently associated with BMD (for E2, beta = 0.21 +/- 0.08, P < 0.01). Non-SHBG-bound E2 was slightly strongly related to BMD than total E2. The positive relation between T and BMD was independent of E2. E1 and E2 were not related with muscle strength or body composition. In summary, bioavailable T, E1, total E2, and bioavailable E2 all decrease with age in healthy old men. In this cross-sectional study in healthy elderly men, non-SHBG-bound T seems to be the best parameter for serum levels of bioactive T, which seems to play a direct role in the various physiological changes that occur during aging. A positive relation with muscle strength and BMD and a negative relation with fat mass was found. In addition, both serum E1 and E2 seem to play a role in the age-related bone loss in elderly men, although the cross-sectional nature of the study precludes a definitive conclusion. Non-SHBG-bound E2 seems to be the best parameter of serum bioactive E2 in describing its positive relation with BMD.
PDF
