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

Jansen, Steffy W.; Roelfsema, Ferdinand; Spoel, Evie van der; Akintola, Abimbola A.; Postmus, Iris; Ballieux, Bart E.; Slagboom, P. Eline; Cobbaert, Christa; Grond, Jeroen van der; Westendorp, Rudi G.J.; Pijl, Hanno; Heemst, Diana van

doi:10.1210/jc.2015-2624

Cited by 37 publications

(30 citation statements)

References 39 publications

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“…This study is underpowered to detect many small differences but adequately sampled to identify major differences in hormonal axes. Indeed, in the same study population, comprising men and women, offspring had a 59.9% higher total TSH secretion and a higher temporal correlation between TSH and fT3 compared to controls (13, 14). Furthermore, GH secretion was lower and tighter controlled in the offspring compared to controls (15).…”

Section: Discussionmentioning

confidence: 84%

“…To date, the 24-h profiles of three hypothalamic hormonal axes have been investigated in detail in the LLS. It was found that TSH secretion was higher and TSH–fT3 temporal relationship was stronger in the offspring compared to controls (13, 14). Furthermore, we found that GH secretion was diminished and tightly controlled in offspring compared to controls (15).…”

Section: Introductionmentioning

confidence: 93%

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

Spoel¹,

Roelfsema²,

Jansen³

et al. 2016

Front. Endocrinol.

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ContextA 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.ObjectiveTo study 24-h hormone concentration profiles of the HPG axis in men enriched for familial longevity and controls.DesignWe frequently sampled blood over 24 h in 10 healthy middle-aged male offspring of nonagenarian participants from the Leiden Longevity Study together with 10 male age-matched controls. Individual 24-h luteinizing hormone (LH) and testosterone concentration profiles were analyzed 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.ResultsMean [95% confidence interval (CI)] total LH secretion of the offspring was 212 (156–268) U/L/24 h, which did not differ significantly (p = 0.51) from the total LH secretion of controls [186 (130–242) U/L/24 h]. Likewise, mean (95% CI) total testosterone secretion of the offspring [806 (671–941) nmol/L/24 h] and controls [811 (676–947) nmol/L/24 h] 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.ConclusionThis 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 the results.

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Section: Discussionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 93%

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

Spoel¹,

Roelfsema²,

Jansen³

et al. 2016

Front. Endocrinol.

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“…Clinical studies support this view showing no adverse outcomes for mortality, cardiovascular events, fracture risk, or cognitive impairment in association with mildly elevated TSH levels (5–10 mIU/l) (70). In elderly patients with subclinical hypothyroidism, in contrast, life expectancy was found to be compromised with lower, not higher TSH values (9–13). …”

Section: Relational Stability Between Thyroid Parametersmentioning

confidence: 95%

“…Gaining control over energy expenditure independently of environmental short-term supply offers major systemic advantages (8). It is therefore unsurprising that the thyroid, within the broader biological complex, embodies these basic biological necessities, showing also associations with longevity in older populations (9–13). By nature, such systems tend to operate far away from their unstimulated resting point, and being metastable require considerable energy and systemic pressure in order to avoid collapse and to maintain a desired equilibrium point.…”

Section: Introductionmentioning

confidence: 99%

Relational Stability in the Expression of Normality, Variation, and Control of Thyroid Function

et al. 2016

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Thyroid hormone concentrations only become sufficient to maintain a euthyroid state through appropriate stimulation by pituitary thyroid-stimulating hormone (TSH). In such a dynamic system under constant high pressure, guarding against overstimulation becomes vital. Therefore, several defensive mechanisms protect against accidental overstimulation, such as plasma protein binding, conversion of T4 into the more active T3, active transmembrane transport, counter-regulatory activities of reverse T3 and thyronamines, and negative hypothalamic–pituitary–thyroid feedback control of TSH. TSH has gained a dominant but misguided role in interpreting thyroid function testing in assuming that its exceptional sensitivity thereby translates into superior diagnostic performance. However, TSH-dependent thyroid disease classification is heavily influenced by statistical analytic techniques such as uni- or multivariate-defined normality. This demands a separation of its conjoint roles as a sensitive screening test and accurate diagnostic tool. Homeostatic equilibria (set points) in healthy subjects are less variable and do not follow a pattern of random variation, rather indicating signs of early and progressive homeostatic control across the euthyroid range. In the event of imminent thyroid failure with a reduced FT4 output per unit TSH, conversion efficiency increases in order to maintain FT3 stability. In such situations, T3 stability takes priority over set point maintenance. This suggests a concept of relational stability. These findings have important implications for both TSH reference limits and treatment targets for patients on levothyroxine. The use of archival markers is proposed to facilitate the homeostatic interpretation of all parameters.

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“…It is known that motion regime leads to many positive effects. Motion and physical loading produce anti-stress action owing to activation of the nervous and hormonal mechanisms, improvement of tissue blood supply and cardiac heart activity [25]. Mental working ability increases and the mood improves; several kinds of metabolism, lipid in particular, are normalized: cholesterol level in the blood decreases and high-density lipoproteins level increases.…”

Section: Physical Activitymentioning

confidence: 99%

Mechanisms of Longevity Phenomenon in Azerbaijan

Sm¹

2016

GGM

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

Abstract: Familial longevity is associated with increased basal TSH secretion and a strong temporal relationship between TSH and free T3 but not with differences in ultradian or circadian TSH rhythmicity or feedback and forward interplay between TSH and TH.

Cited by 37 publications

References 39 publications

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

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

Relational Stability in the Expression of Normality, Variation, and Control of Thyroid Function

Mechanisms of Longevity Phenomenon in Azerbaijan

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