Is thyroid hormone level linked to macular degeneration?
Older adults with higher levels of free thyroid hormone, even within the normal range, were more likely to develop age-related macular degeneration over the following years.
Source
Thyroid function and age-related macular degeneration: a prospective population-based cohort study--the Rotterdam Study
Study at a glance
- Design
- Cohort — Prospective population-based cohort (Rotterdam Study cohorts I and II); baseline TSH and free T4 related to incident AMD graded from repeated fundus photographs using Cox models, plus a bidirectional GWAS look-up for shared genetic variants.
- N
- N=5573 · 5,573 participants aged 55 and over without AMD at baseline who had thyroid measurements and follow-up eye exams; 805 developed AMD. The genetic sub-analysis used 4,646 participants with genotype data.
- Population
- Mainly Caucasian adults aged 55 years and older living in Ommoord, a suburb of Rotterdam, the Netherlands.
- Outcome
- Incident early or late age-related macular degeneration (AMD) and specific AMD lesions (retinal pigment alterations, large drusen).
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What they did
The researchers used a long-running Dutch population cohort of people aged 55 and over. They measured thyroid-stimulating hormone (TSH) and free thyroxine (FT4) in blood at baseline, excluded anyone who already had macular degeneration, and then graded retinal photographs at repeated follow-up visits. They estimated the risk of developing AMD across levels of each hormone, adjusting for age, sex, smoking, blood pressure, cholesterol, diabetes and BMI, and checked whether genetic variants for thyroid function and AMD overlapped.
What they found
Of 5,573 participants followed for a median of 6.9 years, 805 developed AMD. TSH was not related to AMD risk (HR 0.99), but higher FT4 was: people in the highest normal-range FT4 quintile had a higher risk than those in the middle quintile (HR 1.34). This held after adjusting for vascular risk factors, when restricted to people with fully normal thyroid function, and after excluding thyroid medication users. Higher FT4 was also linked to retinal pigment changes, an early AMD lesion, and the only shared genetic variant (in VEGF-A) did not explain the association.
The limits
What it doesn't show
Thyroid hormones were measured only once at baseline, so the study cannot tell whether changes over time matter, and residual confounding is possible despite adjustment. It shows an association rather than proof that thyroid hormone damages the retina; the proposed mechanisms come mainly from mouse studies. The cohort was mostly white Europeans aged 55 and over, so results may not generalise, and the p-value for the overall quintile trend was not significant, making the size of the effect uncertain.
Key terms
- Age-related macular degeneration (AMD)
- A disease of the central retina in older people, marked by drusen and pigment changes, that can progress to irreversible vision loss.
- Free thyroxine (FT4)
- The unbound, biologically active fraction of the main hormone produced by the thyroid gland.
- Thyroid-stimulating hormone (TSH)
- A pituitary hormone that rises when thyroid hormone is low and falls when it is high; the usual screening test for thyroid function.
- Cox proportional hazards model
- A regression method for time-to-event data that estimates hazard ratios while adjusting for other variables.
- Hazard ratio (HR)
- How much faster an event occurs in one group than in a reference group over follow-up; a value above one means a higher rate.
- Euthyroid
- Having thyroid hormone and TSH levels within the normal reference range.
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Quiz yourself
Which thyroid measure was associated with higher AMD risk?
Common questions
Why would FT4 be associated with AMD but TSH not?
The authors suggest the individual set point of the pituitary-thyroid axis changes with ageing, so in older people FT4 may better reflect actual tissue exposure to thyroid hormone than TSH.
Could thyroid medication explain the link?
Probably not: excluding people taking thyroid medication or with known thyroid disease did not change the result, which points to the body's own hormone levels.
Does this mean older people should lower their thyroid hormone?
No. It is an observational association in people with mostly normal levels; the authors call for functional and clinical studies before any causal or treatment conclusions.
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