Thyroid Gland Dysfunction and Keratoconus

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To the Editor:
I read with interest the article by Thanos et al1 regarding the potential role of thyroxine in the development of keratoconus and commend the authors for their epidemiologic and laboratory investigations into this possible association. There are, however, some limitations in the interpretation of their epidemiologic data regarding the prevalence of thyroid gland dysfunction (TGD) among their subjects with keratoconus. They report a rate of TGD of 13.6% (21/154) on the basis of free T4 levels beyond the reference range. The authors do not report whether any of these patients had previously diagnosed TGD or whether any of these patients had signs/symptoms of TGD. They report that this rate of (presumably clinical/overt and subclinical) TGD is significantly higher than the rate of TGD in the general population, referencing the Whickham survey from a population in the United Kingdom in the 1970s that identified a rate of clinical/overt TGD of ∼2%.2 Many more recent epidemiologic studies have been performed, and subclinical hypothyroidism has been reported to affect 3% to 15% of the general population.3 In Germany alone, marked geographic variation in the rates of undiagnosed TGD has been identified, with abnormal thyroid-stimulating hormone (TSH) values ranging from 7.8% to 15.8% and an overall prevalence of thyroid disorders of up to 81.5%.4 Many factors may influence the measured prevalence rates of TGD, including age and sex ratio of the sampled population, dietary intake of iodine, testing methodology, and normal test reference ranges. Without a control group from the same population, it is difficult to make any definitive conclusion regarding whether the rate of TGD is elevated in the studied population.
I studied the rate of TGD in a population of patients with keratoconus who underwent corneal transplantation between 2000 and 2014 (University of Auckland ethics #013907). I reviewed the medical histories taken by the ophthalmologist and anesthetist at the time of transplantation and any available laboratory and pharmacy records to identify individuals with diagnosed or treated TGD at the time of, or since, transplantation. The records of 429 patients were reviewed (251 men and 178 women), with a current mean age of 40.7 ± 12.7 years and 31.7 ± 11.5 years at the time of transplantation. Of the study patients, 53% (228/429) had undergone laboratory testing for TGD with TSH levels on at least 1 occasion and free thyroxine/T4 levels measured reflexively when TSH was outside normal limits. The TSH normal reference range was 0.30 to 4.00 mIU/L, and the free T4 normal reference range varied slightly depending on the year of testing, with a lower limit ranging from 9.0 to 12.0 pmol/L and upper limit from 19.0 to 24.0 pmol/L. Overall, the rate of diagnosed or treated TGD was 3.0% (13/429), with hypothyroidism representing 2.3% (10/429). TGD was present in 5.6% of women (10/178) and 1.2% of men (3/251). These prevalence rates are very similar to those from a survey of 12,488 adults in New Zealand that reported TGD in 5.9% of women and 1.2% of men.5 Based on this preliminary study, the rate of TGD in our population of patients with severe keratoconus does not appear elevated, although further study, using a matched control group, is warranted to investigate any potential association.
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