MANAGEMENT OF ENDOCRINE DISEASE: l-Thyroxine replacement therapy in the frail elderly: a challenge in clinical practice

Abstract

The number of elderly people, mostly aged over 85 years (the 'oldest old'), is increasing worldwide. As a consequence, accompanying morbidity and disability have been increasing, and frailty, defined as an age-related condition of decline of physiological reserves and vulnerability, represents an emerging problem. Caring for older frail people may represent a challenge, since the elderly differ significantly from younger adults in terms of comorbidity, polypharmacy, pharmacokinetics and greater vulnerability to adverse drug reactions. Specific criteria of therapeutic appropriateness and modified goals of care are needed in such patients, also in endocrine care settings. Indeed, thyroid dysfunctions are among the most common conditions in older, multimorbid populations. The prevalence of overt and subclinical hypothyroidism is as high as 20% and thyroid hormone prescription is common in the elderly, with a trend toward levothyroxine treatment of more marginal degrees of hypothyroidism. In addition, older patients have the highest rate of overtreatment during replacement therapy and are more susceptible to developing adverse effects from thyroid hormone excess. Recently, results of a multicentric randomized controlled trial, the TRUST-IEMO collaboration trial, added further insights to the debated question of whether and when levothyroxine treatment is required and if it is beneficial in the elderly. With this in mind, we revised the relevant literature on the impact of thyroid dysfunction and replacement therapy among older people, with the aim to better define indications, benefits and risks of l-T4 replacement therapy in the frail elderly.

Effect of Levothyroxine on Blood Pressure in Patients With Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis

“…Although many trials have been published to evaluate the possible benefits of LT4 therapy in SCH patients ( 5 , 65 , 66 ), the impact of LT4 therapy on blood pressure in SCH patients has not been defined yet. To our best knowledge, this meta-analysis is unique and it is the first systematic review and meta-analysis aiming to study the effect of LT4 therapy on blood pressure in SCH patients.…”

“…Because SCH has an obviously adverse impact on cardiovascular function, it has been proposed that restoring TSH level to the normal range through LT4 therapy may reverse its negative impact on cardiovascular function ( 5 , 9 , 66 ). Some studies have shown that certain risk factors of cardiovascular disease can be reversed by LT4 therapy among SCH patients ( 65 , 67 ). Though a meta-analysis published in 2007 concluded that LT4 therapy was not effective in decreasing cardiovascular morbidity in SCH patients ( 68 ), several recent studies found that LT4 therapy could reverse some detrimental impacts caused by SCH ( 21 , 22 , 69 , 70 ).…”

Aging Is Associated with Low Thyroid State and Organ-Specific Sensitivity to Thyroxine

“…hypothyroidism in older adults is still ongoing (8,23,24). In addition, recent studies have emphasized the risk of potential adverse effects of overtreatment in older adults, who may be prone to an increased likelihood of T 4 -induced side effects and even increased mortality (25).…”

Impaired breathing, sleeping, vitality, and depression, and negative impact of L-T4 treatment characterize health-related quality of life in older people with stable CVD

“…Even when hypertension is excluded, the prevalence of CVD in men and women aged 60-79 increases from 18-25 to 34-43% in individuals over 80 years [1]. Mild thyroid dysfunction is found in over 10% of older people, and the prevalence of subclinical hypothyroidism, i.e., mildly elevated thyroid-stimulating hormone (TSH) concentrations is even higher, i.e., 21% in women and 16% in men aged 74 years or older [2,3]. In a recent meta-analysis, in nonpregnant adults with subclinical hypothyroidism, levothyroxine (LT-4) substitution did not improve general quality of life or possible thyroid-related symptoms [4].…”