Degree of Peripheral Thyroxin Deiodination, Frailty, and Long-Term Survival in Hospitalized Older Patients

Pasqualetti, Giuseppe; Calsolaro, Valeria; Bernardini, Sara; Linsalata, Giuseppe; Bigazzi, Renato; Caraccio, N; Monzani, Fabio

doi:10.1210/jc.2017-02149

Cited by 70 publications

(74 citation statements)

References 24 publications

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“…Those with higher FT 4 values at baseline presented a worse prognosis in term of frailty index (31). Consistently, other experiences in the elderly showed the importance of thyroid hormones peripheral values in term of clinical outcomes (32) reinforcing the hypothesis that, apart from TSH level in very old population, the peripheral pattern of FT 4 and FT 3 may also play a central role in the lifespan regulation at least in older population at risk of frailty (32).…”

Section: Modification Of the Hypothalamus-pituitary-thyroid Axis In Tsupporting

confidence: 70%

“…On that note, the evaluation of TSH levels and the trend over time is crucial; the international guidelines have set the cut-off level to 10 mUI/L, double checked and confirmed over 3 and 6 months before commencing the treatment (48, 49). Other than the TSH levels, the clinician should check the clinical presentation with signs and symptoms before deciding for any therapeutic approach (48), bearing in mind that many symptoms are unspecific (i.e., fatigue, constipation, sleeping pattern alteration, and fatigue), especially in the elderly with comorbidities (32). A well-structured approach, including a multidimensional geriatric assessment (67), comprehends a wide evaluation, which includes laboratory tests (FT 3 , FT 4 , TgAb, TPOAb) and US scan, to identify potential causes of thyroid failure (gland atrophy or autoimmune thyroiditis), responsible for permanently increased TSH levels.…”

Section: Hypothyroidism In the Elderly: When To Treat?mentioning

confidence: 99%

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

et al. 2019

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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 LT 4 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 LT 4 , particularly when poly-therapy is in place, and the importance of a tailored therapeutic approach and follow-up, to avoid overtreatment.

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Section: Modification Of the Hypothalamus-pituitary-thyroid Axis In Tsupporting

confidence: 70%

Section: Hypothyroidism In the Elderly: When To Treat?mentioning

confidence: 99%

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

et al. 2019

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“…In this study FT3/FT4 ratio was inversely related to multi prognostic index (MPI), a reliable marker of frailty, even in subjects with normal FT3. In addition, Cox regression analysis documented a significantly, independent increase of long-term mortality moving from the highest through the lowest quartile of FT3/FT4 ratio (42).…”

Section: Discussionmentioning

confidence: 93%

Heterogeneity of Thyroid Function and Impact of Peripheral Thyroxine Deiodination in Centenarians and Semi-Supercentenarians: Association With Functional Status and Mortality

Ostan

Monti

Mari

et al. 2018

The Journals of Gerontology: Series A

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Thyroid hormones (FT3, FT4) and TSH were evaluated in a population of 672 well-characterized Italian subjects (age range: 52-113 years), including an unprecedented number of centenarians, semi-supercentenarians, as well as centenarian's offspring and age-matched elderly (CENT, 105+, CENTOFF and CTRL, respectively). The results show that FT3 level and FT3/FT4 ratio decrease while FT4 and TSH increase in an age-dependent manner. In CENT/105+, higher FT4 level and lower FT3/FT4 ratio are associated with an impaired functional status and an increased mortality. A cluster analysis identified three clusters of CENT/105+ based on their FT3, FT4 and TSH levels. Cluster3, characterized by lower FT3 and TSH and higher FT4, shows the worst health status and the shortest survival. Thus, the age-related changes of thyroid hormones extend to the most advanced age and CENT/105+ are highly heterogeneous regarding thyroid function. This heterogeneity is related to different health, functional and cognitive status, as well as with survival/mortality in CENT/105+. Finally, we investigated a remarkable number of CENT/105+ showing a thyroid profile suggestive of non-thyroidal illness syndrome (NTIS) (excluded from the previous analysis). NTIS CENT/105+ are characterized by a worse functional and cognitive status and an increased mortality with respect to CENT/105+ without NTIS.

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“…, fatigue, cognitive alterations, sleep disturbances, constipations, etc. ), especially in frail older patients with comorbidity [57]. According to these considerations, a comprehensive, multidimensional geriatric assessment [58] may be helpful in the clinical approach to older patients with increased serum TSH values [44].…”

Section: Treatment Of Hypothyroidism and Shtmentioning

confidence: 99%

“…Nonetheless, in our opinion, in the clinical management of older people with sHT, physicians should take into account not only the TSH cutoff value but also the presence of positive antithyroid autoantibody titers, as well as chronic comorbidities, especially if potentially impaired by hypothyroidism, such as HF [48]. Moreover, particular attention should be given to the presence of frailty, a well-described clinical entity affecting the prognosis of older patients and their QoL [57, 61]. Indeed, frail patients are more vulnerable to drug side effects for several reasons, and the prescription of l -T4 should be carefully balanced with the risk of overtreatment ( e.g.…”

Section: Treatment Of Hypothyroidism and Shtmentioning

confidence: 99%

Hypothyroidism in the Elderly: Who Should Be Treated and How?

Calsolaro

Niccolai

Pasqualetti

et al. 2018

Journal of the Endocrine Society

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Hypothyroidism is among the most frequent chronic diseases in the elderly, and levothyroxine (l-T4) is worldwide within the 10 drugs more prescribed in the general population. Hypothyroidism is defined by increased serum thyroid-stimulating hormone (TSH) values and reduced circulating free thyroid hormones, whereas subclinical hypothyroidism (sHT) is characterized by free hormone fractions within the normal ranges and has been divided into two classes, depending on circulating TSH levels (above or below 10 mIU/L). Given that during aging, a natural trend toward higher values of circulating TSH has been reported, it is necessary to verify carefully the diagnosis of sHT to tailor an appropriate follow-up and ad hoc therapy, avoiding unnecessary or excessive treatment. In the current review, we evaluate the state of the art on hypothyroidism in the elderly with special focus on the effect of sHT on cognition and the cardiovascular system function. We also summarize the recommendations for a correct diagnostic workup and therapeutic approach to older people with an elevated TSH value, with special attention to the presence of frailty, comorbidities, and poly therapy. In conclusion, personalized therapy is crucial in good clinical practice, and in the management of older patients with sHT, multiple factors must be considered, including age-dependent TSH cutoffs, thyroid autoimmunity, the burden of comorbidities, and the possible presence of frailty. l-T4 is the drug of choice for the treatment of hypothyroid older people, but the risk of overtreatment, potential adverse drug reactions, and patient compliance should always be considered and thyroid status periodically reassessed.

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Degree of Peripheral Thyroxin Deiodination, Frailty, and Long-Term Survival in Hospitalized Older Patients

Abstract: Overall, our study documented a strong association between FT3/FT4 ratio reduction, a surrogate marker of peripheral thyroxin deiodination, and frailty. Moreover, FT3/FT4 ratio value emerged as independent marker of survival, even in patients with normal FT3 values.

Cited by 70 publications

References 24 publications

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

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

Heterogeneity of Thyroid Function and Impact of Peripheral Thyroxine Deiodination in Centenarians and Semi-Supercentenarians: Association With Functional Status and Mortality

Hypothyroidism in the Elderly: Who Should Be Treated and How?

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