Thyroid status and mortality in nonagenarians from long-lived families and the general population

Pathophysiology, epidemiology and therapy of agein

Interrelationships Between Pituitary Hormones as Assessed From 24-hour Serum Concentrations in Healthy Older Subjects

Context: Hormones of the hypothalamic-pituitary-target gland axes are mostly investigated separately, whereas the interplay between hormones might be as important as each separate hormonal axis.Objective: Our aim is to determine the interrelationships between GH, TSH, ACTH, and cortisol in healthy older individuals.Design: We made use of 24-hour hormone serum concentrations assessed with intervals of 10 minutes from 38 healthy older individuals with a mean age (SD) of 65.1 (5.1) years from the Leiden Longevity Study. Cross-correlation analyses were performed to assess the relative strength between 2 24-hour hormone serum concentration series for all possible time shifts. Cross-approximate entropy was used to assess pattern synchronicity between 2 24-hour hormone serum concentration series.Results: Within an interlinked hormonal axis, ACTH and cortisol were positively correlated with a mean (95% confidence interval) correlation coefficient of 0.78 (0.74-0.81) with cortisol following ACTH concentrations with a delay of 10 minutes. Between different hormonal axes, we observed a negative correlation coefficient between cortisol and TSH of -0.30 (-0.36 to -0.25) with TSH following cortisol concentrations with a delay of 170 minutes. Furthermore, a positive mean (95% confidence interval) correlation coefficient of 0.29 (0.22-0.37) was found between TSH and GH concentrations without any delay. Moreover, cross-approximate entropy analyses showed that GH and cortisol exhibit synchronous serum concentration patterns.Conclusions: This study demonstrates that interrelations between hormones from interlinked as well as different hypothalamic-pituitary-target gland axes are observed in healthy older individuals. More research is needed to determine the biological meaning and clinical consequences of these observations.Pathophysiology, epidemiology and therapy of agein

Incidence and determinants of spontaneous normalization of subclinical hypothyroidism in older adults.

CONTEXT With age, the prevalence of subclinical hypothyroidism rises. However, incidence and determinants of spontaneous normalization remain largely unknown. OBJECTIVE To investigate incidence and determinants of spontaneous normalization of thyroid-stimulating hormone (TSH) levels in older adults with subclinical hypothyroidism. DESIGN Pooled data were used from the (i) pre-trial population, and (ii) in-trial placebo group from two randomized, double-blind, placebo-controlled trials (TRUST and IEMO thyroid 80-plus thyroid trial). SETTING Community-dwelling 65 + adults with subclinical hypothyroidism from the Netherlands, Switzerland, Ireland, and the United Kingdom. PARTICIPANTS The pre-trial population (N = 2335) consisted of older adults with biochemical subclinical hypothyroidism, defined as ≥1 elevated TSH measurement (≥4.60 mIU/L) and a free thyroxine (fT4) within the laboratory-specific reference range. Individuals with persistent subclinical hypothyroidism, defined as ≥2 elevated TSH measurements ≥3 months apart, were randomized to levothyroxine/placebo, of which the in-trial placebo group (N = 361) was included. MAIN OUTCOME MEASURES Incidence of spontaneous normalization of TSH levels and associations between participant characteristics and normalization. RESULTS In the pre-trial phase, TSH levels normalized in 60.8% of participants in a median follow-up of one year. In the in-trial phase, levels normalized in 39.9% of participants after one year follow-up. Younger age, female sex, lower initial TSH level, higher initial fT4 level, absence of thyroid peroxidase antibodies, and a follow-up measurement in summer were independent determinants for normalization. CONCLUSIONS Since TSH levels spontaneously normalized in a large proportion of older adults with subclinical hypothyroidism (also after confirmation by repeat measurement), a third measurement may be recommended before considering treatment

Familial Longevity Is Associated With Higher TSH Secretion and Strong TSH-fT3 Relationship

Pathophysiology, epidemiology and therapy of agein

Growth hormone secretion is diminished and tightly controlled in humans enriched for familial longevity

Pathophysiology, epidemiology and therapy of agein

Familial Longevity Is Not Associated with Major Differences in the Hypothalamic–Pituitary–Gonadal Axis in Healthy Middle-Aged Men

Context: A trade-off between fertility and longevity possibly exists. The association of the male hypothalamic-pituitary-gonadal (HPG) axis with familial longevity has not yet been investigated.Objective: To study 24h hormone concentration profiles of the HPG axis in men enriched for familial longevity and controls. Design: We frequently sampled blood over 24 hours in 10 healthy middle-aged male offspring of nonagenarian participants from the Leiden Longevity Study together with 10 male age-matched controls. Individual 24h luteinizing hormone (LH) and testosterone concentration profiles were analysed by deconvolution analyses to estimate secretion parameters. Furthermore, the temporal relationship between LH and testosterone was assessed by cross-correlation analysis. We used (cross-) approximate entropy to quantify the strength of feedback and/or feedforward control of LH and testosterone secretion.Results: Mean (95% confidence interval (CI)) total LH secretion of the offspring was 212 (156–268) U/L/24h, which did not differ significantly (p=0.51) from the total LH secretion of controls (186 (130–242) U/L/24h). Likewise, mean (95% CI) total testosterone secretion of the offspring (806 (671–941) nmol/L/24h) and controls (811 (676–947) nmol/L/24h) were similar (p=0.95). Other parameters of LH and testosterone secretion were also not significantly different between offspring and controls. The temporal relationship between LH and testosterone and the strength of feedforward/feedback regulation within the HPG axis were similar between offspring of long-lived families and controls. Conclusions: This relatively small study suggests that in healthy male middle-aged participants, familial longevity is not associated with major differences in the HPG axis. Selection on both fertility and health may in part explain for the results