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198 Thyroid Hormone

LT4 replacement therapy should be considered for three main reasons: i) to prevent progression of sHT to overt hypothyroidism which, however, is much more important in young patients; ii) to reduce the symptoms associated with mild thyroid failure, which are especially scarce in the elderly; iii) to improve the lipid profile and other risk factors that

Subclinical thyroid failure causes changes in cardiac function similar to, but less marked than, those occurring in patients with overt hypothyroidism. Diastolic dysfunction both at rest and upon effort is the most consistent cardiac abnormality in patients with sHT, even in those with slightly elevated TSH levels (>6 mIU/L) (Arem et al., 1996; Biondi & Cooper, 2012;). Mild thyroid failure may also increase diastolic blood pressure as a result of increased systemic vascular resistances (Faber et al., 2002; Kahaly, 2000; Luboshitzky et al., 2002). Interestingly, restoration of euthyroidism by LT4 replacement is able to reduce systemic hypertension as well as improve left ventricular myocardial function (Brenta et al., 2003). Moreover, sHT has been claimed to be a risk factor for atherosclerosis and ischemic CVD, therefore, it is appropriate to consider whether treatment confers some protection from such a risk. Although a consensus is still lacking, the strongest evidence for a beneficial effect of levothyroxine replacement therapy is the substantial demonstration that restoration of euthyroidism can lower TC and LDLc levels in most patients with sHT. Besides hypercholesterolemia several emerging risk factors for CHD have been claimed to be associated with sHT. Among them, altered coagulation parameters, endothelial dysfunction, and elevated CRP levels are consistently regarded to combine with the raised LDLc levels of

As a whole, these findings suggest that the decision to treat patients with sHT should depend on the presence of risk factors, rather than on a TSH threshold. International organizations and guidelines suggest starting replacement therapy in patients who have TSH concentrations greater than 10 mIU/liter and in those with evidence of autoimmunity, and in symptomatic patients with TSH levels between 4.5 and 10 mIU/L (Gharib et al., 2005a,b; Surks et al., 2004). However, the treatment of sHT patients, especially the elderly, must be individualized once any underlying coexisting morbidity or pharmacologic interference has been excluded. Generally LT4 replacement results effective and safe in young patients, providing that excessive dosing is avoided by monitoring serum TSH level. Indeed, LT4 replacement therapy can always be discontinued if there is no apparent benefit. It is noteworthy that, once a stable, elevated TSH value is detected, the costs of annual follow-up with clinical assessment and laboratory testing are relatively similar whether or not a patient is treated with LT4 (Cooper et al., 2001). On the other hand, the possibility that restoring euthyroidism may be harmful in the older population has been raised, and should be taken into account in making the decision of treating such patients, especially those older than 85 years. In this setting, hormonal replacement might be considered in old patients on the base of a specific evaluation of the possible thyroid dysfunction causes, pre-existent cardiovascular risk including cholesterol level, hearth failure as well as the presence of comorbidities or frailty and the level of TSH. However, until adequate data are accumulated, clinicians should consider each patient a unique situation, and best clinical practice continues to be a combination of clinical judgment and the patient's preference.

may contribute to atherosclerosis progression and CV events.

untreated patients with sHT to enhance the cardiovascular risk.

Giuseppe Pasqualetti, Angela Dardano, Sara Tognini, Antonio Polini and Fabio Monzani *Geriatrics Unit, Department of Internal Medicine, University of Pisa, Italy* 
