The aging thyroid

S. Mariotti, C. Franceschi, A. Cossarizza, A. Pinchera

Research output: Contribution to journalArticlepeer-review


The aging thyroid is associated with a number of morphological and functional changes. The question of whether and to what extent such changes are dependent on the aging process per se or on age-associated thyroidal or nonthyroidal diseases is a matter of debate. Most studies m experimental animals have been carried out in rodents, especially rats. There is morphological and biochemical evidence of decreased thyroid stimulation by TSH with a consequent decreased thyroid hormone secretion, and low serum T4 and T3 concentrations are in fact found in aged rats. The reduction is much more evident for T4, because of the concurrence of decreased thyroid secretion and increased peripheral degradation, which appears to be due to abnormalities of both the deiodinating and possibly nondeiodinating metabolic pathways. There are complex alterations of peripheral tissue responsiveness to thyroid hormones that may contribute in an age-dependent decline of metabolic activity. There is also evidence for a progressive age-dependent disturbance of hypothalamic-pituitary-thyroid function in rats that resembles central hypothyroidism. The relative contribution of suprahypothalamic and/or hypothalamic vs. pituitary dysfunction remains to be established. Several, but not all, of the above changes that occur in old rats also occur in elderly persons. The major discrepancy with respect to rodents is that there is decreased rather than increased peripheral degradation of T4 in man. The decreased degradation of T4 is mainly the consequence of reduced monodeiodination by 5'D and results in an age-dependent decline in serum T3 concentration. The question of whether and to what extent this and other changes are related to the coexistence of age-associated nonthyroidal illnesses is often difficult to establish, because marked impairment of 5'D activity is observed in nonthyroidal illnesses. Studies on healthy elderly subjects, selected by strict criteria to exclude coexistent diseases, suggest that several age-related changes in thyroid function are indeed independent of nonthyroid illnesses. These changes include a reduced thyroid hormone secretion, which results to a variable extent from impaired TSH stimulation, and decreased T4 degradation. The serum T4 concentration is unchanged because of the opposing effects of the changes in its secretion and degradation. Human aging is often associated with an increased prevalence of thyroid autoantibodies. Interestingly, this age-dependent increase is commonly observed in unselected elderly subjects, but not in healthy centenarians or in healthy 'younger' elderly populations selected on the basis of the absence of clinical or subclinical illnesses. These data suggest that thyroid autoimmune phenomena may not be the consequence of the aging process itself but, rather, an expression of age-associated disease. As in younger subjects, the entire spectrum of thyroid disease including clinical and subclinical hypo- and hyperthyroidism, nontoxic goiter, and thyroid cancer may be encountered in the elderly. Thyroid diseases in older patients differ to a variable extent from those observed in younger patients in their prevalence and/or in their clinical expression. Thus, autoimmune hypothyroidism is particularly prevalent in patients over age 60 yr; hyperthyroidism in the elderly is preferentially characterized by cardiovascular symptoms and is frequently due to toxic nodular variants that are often preceded by long-standing 'nontoxic' goiters with some degree of functional autonomy. Differentiated thyroid carcinoma is often more invasive in the elderly, and rare aggressive tumors such as anaplastic carcinoma and lymphoma are seen almost exclusively in subjects over 60 yr of age. The interpretation of thyroid function tests is also difficult in old individuals, because of the difficulty in differentiating age-associated changes and the more frequent alterations secondary to acute or chronic nonthyroidal illnesses and/or drugs from changes due to thyroid disease. Treatment of thyroid disease often deserves special attention in old patients because of the increased risk of complications. Several controversies are still unresolved on 'when' and 'how' to treat. A major, yet unresolved, problem is the question of whether and to what extent age-associated thyroid dysfunction contributes to the pathogenesis of age-associated disease such as atherosclerosis, CHD, and neurological disorders.

Original languageEnglish
Pages (from-to)686-715
Number of pages30
JournalEndocrine Reviews
Issue number6
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism


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