Tissue effects
	No physician in his/her right mind is happy to treat laboratory values only. Hence, before considering treatment, we want to know whether minimal thyroid failure is accompanied by tissue effects, i.e. mild clinical and/or metabolic abnormalities. All the evidence suggests that this is indeed the case. Although by definition subclinical hypothyroidism is asymptomatic, a careful evaluation may reveal some clinical abnormalities (2) as well as abnormal laboratory findings in addition to the increased TSH. Even before the advent of TSH measurements, cases of presumed subclinical hypothyroidism were shown to present metabolic abnormalities. In 1965 our group from Glasgow reported that persons with positive AAB but no clinical evidence of thyroid disease had on average an iodine metabolism pattern similar to that of Hashimoto’s thyroiditis, but milder (14). Later Bastenie and his co-workers from Brussels propagated the idea that persons with positive AAB have on average an increased serum cholesterol and a tendency to develop coronary artery disease (15). Now abnormalities of lipid metabolism are well established (13,15–21). Total serum cholesterol may not be always increased, but low-density cholesterol is19, whereas high-density is decreased, and apoprotein A may be increased (19,20). In a review of the literature, Tanis et al. (21) found a slightly elevated total serum cholesterol. These lipid abnormalities are not the only ones found in subclinical hypothyroidism. Our group has shown that flow–mediated, endothelium-dependent vasodilatation is impaired in subclinical hypothyroidism (22). This is shown in Fig. 1. Such a defect is considered an early event in the development of atherosclerosis. Some cardiac parameters also may be abnormal, depending on the degree of hypothyroidism. Subclinical hypothyroidism may cause alterations in systolic time intervals and myocardial contractility, and may increase the risk of atherosclerotic cardiovascular disease when it is superimposed on another underlying cardiac or metabolic disorder (1,23). Figure 1: Moreover, in patients with subtle changes of thyroid function, as in subclinical hypothyroidism, we could detect an increased prevalence (29.8%) of sideropenia and of manifest sideropenic anemia (15.7%), suggesting that sideropenia is a common finding in patients with subclinical hypothyroidism. Therefore, the control of iron metabolism must be considered in patients in early stages of dysfunction of thyroid gland (Duntas et al.24). Furthermore, in subclinical hypothyroidism muscle dysfunction is present25, and the stapedial reflex (acoustic or middle-ear muscular reflex) is abnormal (26). Both these abnormalities revert to normal with thyroxine treatment. Finally, a relation between subclinical hypothyroidism and depression has been suggested (27–30). Monzani et al. (29) observed anxiety, depression, hysteria and other somatic complaints, which improved with thyroxine treatment. Recently Pop et al. (30) found depression to be significantly related to increased TPOAb levels, but not to subclinical or overt hyper- or hypothyroidism. Nevertheless, the high Odds Ratios (2.9 to 7.9) found by Pop et al. (30) in all these thyroid disorders, even if not statistically significant, are very suggestive. It seems likely that if the authors had studied more cases they would reach statistical significance.