Subclinical Hypothyroidism: is it Really Subclinical with Aging?

Abstract

No recent study has focused on clinical features of subclinical hypothyroidism (SCH), especially in older patients. TSH measurement has remarkably evolved these last 20 years and thus reconsideration is needed. In our prospective multicenter study (2012-2014) including 807 subjects aged <60 years (<60y) and 531 subjects ≥60 years (≥60y), we have monitored 11 hypothyroidism-related clinical signs (hCS) together with TSH, FT4, FT3 and anti-thyroperoxidase antibodies values. hCS expression has been compared in patients with SCH vs euthyroidism in each age group. The number of hCS above 60y of age were found to be more elevated in the euthyroid population (1.9 vs 1.6, p<0.01) than in the SCH population (2.3 vs 2.6, p=0.41) while increase in hCS is limited to SCH subjects in the <60y group (p<0.01). The percentage of subjects with at least 3 signs increased with SCH in the <60y group (42.6% vs 25.0%, p<0.01) but not ≥60y (34.4% vs 33.9%, p=0.96). In older individuals, only three hCS could be related to both SCH and a decreased T3/T4-ratio (0.26 vs 0.27, p<0.01), suggesting either a reduced activity of TSH, or an adaptive response with aging. While hCS are clearly associated with SCH in patients <60y, they are not so informative in older subjects. TSH measurements carried out on the basis of hCS need to be interpreted with caution in aged patients. A reassessment of the TSH reference range in older patients is clearly needed and should be associated to more appropriate monitoring of thyroid dysfunction.

Keywords: TSH; aging; symptoms; thyroid deficiency.

Figure 1.

Flowchart of the recruitment, selection and exclusion process of the cohort.

Figure 2.. Mean TSH (A), FT3 (B), FT4 (C) levels and FT3/FT4 ratios (D) as a function of TSH levels

Asterisks indicate significant differences between age groups (**, p<0.01) and crosses indicate significant differences between normal (0.17-4.05 mIU/L) and elevated (>4.05 mIU/L) TSH groups or difference between the absence/presence of TPOAbs when TSH is in the 4.1-10.0mIU/L range (†, p<0.05; ††, p<0.01).

Figure 3.. Percentage of subjects with 0, 1, 2, or 3 or more clinical signs by TSH groups

Data from all subjects (A), subjects <60y (B) and ≥60y (C) are presented.

Figure 4.. Prevalence of individual hypothyroidism-related clinical signs according to age

Age groups are <60y (white bars) and ≥60y (black bars). A) euthyroid subjects (TSH, 0.17-4.05mIU/L); B) subclinical hypothyroid subjects (TSH, >4.05mIU/L). Bars with an asterisk are significantly different between <60y and ≥60y groups (*p<0.05; **p<0.01).