ContextWith age, the prevalence of subclinical hypothyroidism rises. However, incidence and determinants of spontaneous normalization remain largely unknown.ObjectiveTo investigate incidence and... Show moreContextWith age, the prevalence of subclinical hypothyroidism rises. However, incidence and determinants of spontaneous normalization remain largely unknown.ObjectiveTo investigate incidence and determinants of spontaneous normalization of TSH levels in older adults with subclinical hypothyroidism.DesignPooled data were used from the (1) pretrial population and (2) in-trial placebo group from 2 randomized, double-blind, placebo-controlled trials (Thyroid Hormone Replacement for Untreated Older Adults With Subclinical Hypothyroidism Trial and Institute for Evidence-Based Medicine in Old Age thyroid 80-plus thyroid trial).SettingCommunity-dwelling 65+ adults with subclinical hypothyroidism from the Netherlands, Switzerland, Ireland, and the United Kingdom.ParticipantsThe pretrial population (N = 2335) consisted of older adults with biochemical subclinical hypothyroidism, defined as ≥1 elevated TSH measurement (≥4.60 mIU/L) and a free T4 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 MeasuresIncidence of spontaneous normalization of TSH levels and associations between participant characteristics and normalization.ResultsIn the pretrial phase, TSH levels normalized in 60.8% of participants in a median follow-up of 1 year. In the in-trial phase, levels normalized in 39.9% of participants after 1 year of follow-up. Younger age, female sex, lower initial TSH level, higher initial free T4 level, absence of thyroid peroxidase antibodies, and a follow-up measurement in summer were independent determinants for normalization.ConclusionBecause 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. Show less
Spoel, E. van der; Vliet, N.A. van; Heemst, D. van 2019
Specific hallmarks are thought to underlie the ageing process and age-related functional decline. In this viewpoint, we put forward the hypothesis that disturbances in the process of tissue... Show moreSpecific hallmarks are thought to underlie the ageing process and age-related functional decline. In this viewpoint, we put forward the hypothesis that disturbances in the process of tissue maintenance are an important common denominator that may lie in between specific hallmarks of ageing (i.e. damage and responses to damage) and their ultimate (patho)physiological consequences (i.e. functional decline and age-related disease). As a first step towards verifying or falsifying this hypothesis, it will be important to measure biomarkers of tissue maintenance in future studies in different study populations. The main aim of the current paper is to discuss potential biomarkers of tissue maintenance that could be used in such future studies. Among the many tissues that could have been chosen to explore our hypothesis, to keep the paper manageable, we chose to focus on a selected number of tissues, namely bone, cartilage, muscle, and the brain, which are important for mobility and cognition and affected in several common age-related diseases, including osteoporosis, osteoarthritis, sarcopenia, and neurodegenerative diseases. Furthermore, we discuss the advantages and limitations of potential biomarkers for use in (pre)clinical studies. The proposed biomarkers should be validated in future research, for example by measuring these in humans with different rates of ageing. Show less
Maintenance and repair is of key importance for the proper functioning of cells, tissues, and integrated physiology. We hypothesize that the balance between investments in growth, development, and... Show moreMaintenance and repair is of key importance for the proper functioning of cells, tissues, and integrated physiology. We hypothesize that the balance between investments in growth, development, and reproduction versus maintenance and repair is regulated by the brain. Specifically (the interplay of) hormones of the different hypothalamic-pituitary-target gland axes seem to be key regulators in constantly adjusting this balance to its optimal state. This thesis describes the associations between familial longevity and hormones of different hypothalamic-pituitary-target gland axes. In Chapter 2, the question is addressed whether circulating insulin-like growth factor 1 (IGF‐1) axis parameters associate with old age survival and functional status in nonagenarians from the LLS. In Chapter 3, we use growth hormone (GH) concentrations measured every 10 min over 24 h to derive and compare GH secretion parameters between offspring of long-lived families and their partners. In Chapter 4, we investigate the association between hypothalamic-pituitary-gonadal axis parameters and familial longevity. In Chapter 5, we use 24-h time series data of pituitary hormones to investigate how changes in the different hormonal axes are correlated with each other over time. In Chapter 6, we determine the circadian rhythm of bone turnover markers in healthy older subjects. Show less
Ogliari, G.; Smit, R.A.J.; Spoel, E. van der; Mari, D.; Torresani, E.; Felicetta, I.; ... ; Westendorp, R.G.J. 2017
