Incidence and determinants of spontaneous normalization of subclinical hypothyroidism in older adults.

CONTEXT

With age, the prevalence of subclinical hypothyroidism rises. However, incidence and determinants of spontaneous normalization remain largely unknown.

OBJECTIVE

To investigate incidence and determinants of spontaneous normalization of thyroid-stimulating hormone (TSH) levels in older adults with subclinical hypothyroidism.

DESIGN

Pooled data were used from the (i) pre-trial population, and (ii) in-trial placebo group from two randomized, double-blind, placebo-controlled trials (TRUST and IEMO thyroid 80-plus thyroid trial).

SETTING

Community-dwelling 65 + adults with subclinical hypothyroidism from the Netherlands, Switzerland, Ireland, and the United Kingdom.

PARTICIPANTS

The pre-trial population (N = 2335) consisted of older adults with biochemical subclinical hypothyroidism, defined as ≥1 elevated TSH measurement (≥4.60 mIU/L) and a free thyroxine (fT4) within the laboratory-specific reference range. Individuals with persistent subclinical hypothyroidism, defined as ≥2 elevated TSH measurements ≥3 months apart, were randomized to levothyroxine/placebo, of which the in-trial placebo group (N = 361) was included.

MAIN OUTCOME MEASURES

Incidence of spontaneous normalization of TSH levels and associations between participant characteristics and normalization.

RESULTS

In the pre-trial phase, TSH levels normalized in 60.8% of participants in a median follow-up of one year. In the in-trial phase, levels normalized in 39.9% of participants after one year follow-up. Younger age, female sex, lower initial TSH level, higher initial fT4 level, absence of thyroid peroxidase antibodies, and a follow-up measurement in summer were independent determinants for normalization.

CONCLUSIONS

Since TSH levels spontaneously normalized in a large proportion of older adults with subclinical hypothyroidism (also after confirmation by repeat measurement), a third measurement may be recommended before considering treatment.