Overt and Subclinical Hypothyroidism in the Elderly: When to Treat?

Hypothyroidism is characterized by increased thyrotropin (TSH) levels and reduced free thyroid hormone fractions while, subclinical hypothyroidism (sHT) by elevated serum TSH in the face of normal thyroid hormones. The high frequency of hypothyroidism among the general population in Western Countries made levothyroxine (LT4) one of the 10 most prescribed drugs. However, circulating TSH has been demonstrated to increase with aging, regardless the existence of an actual thyroid disease. Thus, when confronting an increase in circulating TSH levels in the elderly, especially in the oldest old, it is important to carry an appropriate diagnostic path, comprehensive of clinical picture as well as laboratory and imaging techniques. In the current review, we summarize the recommendations for a correct diagnostic workup and therapeutic approach to older people with elevated TSH value, with special attention to the presence of frailty, comorbidities, and poly-therapy. The treatment of choice for hypothyroid patients is hormone replacement with LT4 but, it is important to consider multiple factors before commencing the therapy, from the age dependent TSH increase to the presence of an actual thyroid disease and comorbidities. When treatment is necessary, a tailored therapy should be chosen, considering poly-pharmacy and frailty. A careful follow-up and treatment re-assessment should be always considered to avoid the risk of over-treatment. It is important to stress the need of educating the patient for a correct administration of LT4, particularly when poly-therapy is in place, and the importance of a tailored therapeutic approach and follow-up, to avoid overtreatment

Is subclinical hypothyroidism a cardiovascular risk factor in the elderly?

The negative impact of subclinical hypothyroidism (sHT) on cardiovascular risk, widely recognized in young adults (aged 65 y), especially in the oldest olds (>80 y). EVIDENCE ACQUISITION: We searched Medline for reports published with the following search terms: "hypothyroidism," "subclinical hypothyroidism," "ageing," "elderly," "L-thyroxin," "thyroid," "guidelines," "treatment," "quality of life," "cardiovascular risk," "heart failure," "coronary heart disease" (CHD), "atherosclerosis," and "endothelial dysfunction." We limited our search to reports in English published after 1980, although we incorporated some reports published before 1980. We supplemented the search with records from personal files, textbooks, and relevant articles. Analyzed parameters included the epidemiology of thyroid failure, the effect of thyroid hormone on the aging process, cardiovascular function, and CHD risk factors. We also included the potential benefits of L-T4 therapy on the quality of life, cardiovascular events, and survival. EVIDENCE SYNTHESIS: TSH levels increase with age, even in older people without thyroid disease. Most longitudinal studies show an increased risk for CHD events and mortality in sHT participants. This increase is less evident in the elderly, mainly in cases of serum TSH values above 10 mIU/L. Lower mortality rate in a cohort of the oldest olds (>85 y) has been reported. CONCLUSIONS: sHT in older people should be not regarded as a unique condition, and moderately old patients (aged <70-75 y) could be considered clinically similar to the adult population, albeit with a higher optimal TSH target value. Conversely, the oldest old subjects should be carefully followed with a wait-and-see strategy, generally avoiding hormonal treatment. The decision to treat elderly people is still an unresolved clinical challenge--first, due to a lack of appropriately powered randomized controlled trials of L-T4 in sHT patients, examining cardiovascular hard endpoints in various classes of age; and second, because of the negative effects of possible overtreatment

Clinical and biochemical features of muscle dysfunction in subclinical hypothyroidism

Alterations in muscle structure and function have been reported in overt hypothyroidism, with decreased activity of enzymes involved in anaerobic and oxidative glucose metabolism. To test whether similar changes in muscle energy metabolism are present in subclinical hypothyroidism (sHT), we studied 12 patients with sHT who complained of mild neuromuscular symptoms. The control group included 10 sex- and age-matched healthy volunteers. Skeletal muscle lactate and pyruvate production were determined in the resting state and during dynamic arm exercise. During exercise, blood lactate was significantly higher in sHT patients than in controls from the third exercise step onward (P = 0.02 at 30%, p = 0.008 at 40%, and P = 0.002 at 50% of maximal voluntary contraction). Moreover, the mean increment in blood lactate during exercise was positively related (r2 = 0.44; P = 0.02) to the duration of sHT, but not to serum levels of TSH, free T3, or free T4. No significant difference was found in blood pyruvate concentrations between the two groups at baseline or during exercise. Thus, the lactate/pyruvate ratio curve paralleled the lactate curve in patients as well as controls. We conclude that muscle energy metabolism is impaired in sHT in rough proportion to the known duration of the disease. Early L-T4 therapy may be useful not only to provide specific treatment for such metabolic changes, but also to avoid progression to frank hypothyroidism

Cardiovascular risk and quality of life in elderly people with mild thyroid hormone deficiency

Subclinical hypothyroidism (sHT) is a common condition in the general population, the prevalence increases with age, especially in women. An association between sHT and increased coronary heart disease (CHD) and heart failure (HF) risk and mortality has been described. However, this association is far to be established in older people (>65 years), especially in the oldest old (>85 years). Individuals with sHT may experience symptoms that resemble those observed in the overt form of the disease, leading to an impaired quality of life (QoL). Although very old people are frequently frail and potentially more susceptible to the effects of a disease, few studies were designed to assess the effect of sHT on QoL in this subset of population. Interestingly, the serum TSH concentration curve of general population has a skewed distribution with a "tail" toward higher values, which is amplified with aging. Thus, the diagnosis of sHT and the interpretation of its potential effects on CV function and QoL in older people may be a challenge for the clinician. Giving these premises, we reviewed the English scientific literature available on National Library of Medicine (www.pubmed.com) since 1980 regarding hypothyroidism, sHT, elderly, cardiovascular risk, CHD or HF events and mortality, health-related QoL, and LT4 therapy. Consistent results among large prospective cohort studies suggest an age-independent relationship between sHT and HF progression, while an impact of sHT on CHD events and mortality is essentially reported in young adults (aged below 65-70 years) with long-lasting disease. Scanty data are available on QoL of older people with sHT (>65 years) and, generally, no significant alterations are described

Optimal Type 2 Diabetes Mellitus Management and Active Ageing

Type two diabetes mellitus (T2DM) represents a chronic condition with increasing prevalence worldwide among the older population. The T2DM condition increases the risk of micro and macrovascular complications as well as the risk of geriatric syndromes such as falls, fractures and cognitive impairment. The management of T2DM in the older population represents a challenge for the clinician, and a Comprehensive Geriatric Assessment should always be prioritized, in order to tailor the glycated hemoglobin target according to functional and cognitive status comorbidities, life expectancy and type of therapy. According to the most recent guidelines, older adults with T2DM should be categorized into three groups: healthy patients with good functional status, patients with complications and reduced functionality and patients at the end of life; for each group the target for glycemic control is different, also according to the type of treatment drug. The therapeutic approach should always begin with lifestyle changes; after that, several lines of therapy are available, with different mechanisms of action and potential effects other than glucose level reduction. Particular interest is growing in sodium-glucose cotransporter-2 inhibitors, due to their effect on the cardiovascular system. In this review, we evaluate the therapeutic options available for the treatment of older diabetic patients, to ensure a correct treatment approach