Abstract
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I agree with Dr. Christiaan F Mooij and Prof. A. S. Paul van Trotsenburg that a potential correlation exists between quality of life (QoL)/depression and thyroid autoimmunity. However, I am still not convinced of a simple correlation that is reflected by thyroid peroxidase antibody (TPO-Ab) positivity.
In the correspondence from Drs Mooij and van Trotsenberg, 1 they do not agree with my statement in the accompanying commentary discussing the role of thyroid autoantibodies “… population-based studies do not demonstrate a correlation between TPO-Abs, and QoL or depression” referring to the systemic review by Groenewegen et al. 4 They summarize the study “… the relationship between the presence of TPO-Abs (as proxy for thyroid autoimmunity), and persisting symptoms and impaired QoL and included 30 observational studies (seven disease-based and 23 population-based). The majority of these 30 studies (five of seven disease-based, 16 of 23 population-based) reported an association between the presence of TPO-Abs, and persisting symptoms or impaired QoL. Of these, seven were comparing patients with hypothyroidism to controls and 23 were populations-based.” 1
There are many possible explanations for the conflicting findings in the studies listed in the systemic review, including sample size, instruments used to measure the outcome, study design, exclusion criteria, geographical population, statistical analysis adjustments, and TPO-Ab-positivity definitions. In the clinical studies comparing patients with controls, a high risk of bias is present, as the patient is treated and is aware of having Hashimoto's disease. Although thyroid function is comparable on levothyroxine (LT4) treatment, we still know that QoL is lower in LT4-treated patients and that there are different potential explanations for that. The data from patient studies are, therefore, tricky to interpret.
If focusing concentrating on the population-based studies, the systemic review reported that 16 of the 23 studies found a significant correlation effect. 4 The limitation section of the systematic review states that a meta-analysis could not be performed made due to the disparate instruments used to evaluate QoL.
The number of patients assessed in the studies showing a positive correlation was 8015, compared with 20,837 in studies showing no significant correlation. 4 Therefore, only comparing the number of studies, not to the number of patient included in the studies, is not a correct interpretation.
In the systematic review, 4 the authors stated that the population-based study from Ittermann et al. 5 supported their hypothesis, although the authors of the original study concluded that they did not find an overall correlation between TPO-Ab positivity and depression. In the systematic review, the positive results selected to support the hypothesis were based on a subgroup analysis of patients diagnosed with hypothyroidism, but not taking medication. Furthermore, they focus on data showed a significant association when TPO-Ab are in a gray zone 60/100–200 IU/mL but not in individuals with positive TPO-Ab >200 IU/mL. By this, I would argue that the study from Ittermann et al. 5 does not support the hypothesis.
We recently published a follow-up of the Danish Gesus study, 6 including 10,541 individuals having a baseline TPO-Ab measurement, and we followed them for a median of 7.8 years and found that during this period, 783 individuals (7.4% of 10,541 individuals) had incident antidepressant use. LT4 treatment (odds ratio [OR] 1.3 confidence interval [CI] 1.10–1.62), but not the presence of TPO-Ab (OR 0.90 CI 0.78–1.03), were associated with the prescription of antidepressive medication. 7
My point is still that I do not believe that we have sufficient evidence to conclude that there is a simple correlation between TPO-Ab positivity and depression/decreased QoL.
The explanation for the increased risk of decreased QoL and depression in LT4 treated hypothyroid patients is still lacking and, in my opinion, more complicated than the presence of TPO-Abs or not.
Thyroid autoimmunity in Hashimoto is often thought to be the same as the presence of TPO-Abs. If this was the truth, a logical conclusion could be that if we could remove the TPO-Abs, we would remove the autoimmunity and improve QoL. We need to explore thyroid autoimmunity more extensively and look for other explanations than “just” the presence of TPO-Ab.
Footnotes
Author's Contributions
B.N. was responsible for conceptualization, writing, editing, and approving this final article.
Author Disclosure Statement
No competing financial interests exist.
Funding Information
No funding was received for this article.