Elevated Thyrotropin Levels Associated With Depression

Thyroid dysfunction is related with increased risk for depression, according to results of a study published in Thyroid.

Thyroid hormone levels in the normal range are essential for normal brain function, Previous study findings suggest an association between depression and abnormal hypothalamic-pituitary-thyroid axis function.

To better assess the relationship between thyrotropin (TSH) levels and depression, investigators from the Mayo Clinic and University of Utah School of Medicine in the United States conducted a retrospective, cross-sectional study. Patients (N=33,138) who attended University of Utah Health between 2016 and 2021 and completed a Patient Health Questionnaire (PHQ-9) assessment and had TSH levels measured were evaluated for clinically relevant depression (PHQ-9 score ≥10).

Among the study population, 69.10% were women, 80.67% were White, and 91.79% had TSH within the normal range. The patients had a mean (SD) age of 42.41 (16.10) years and BMI of 29.85 (7.88) kg/m²,

The overall mean (SD) PHQ-9 score was 10.11 (6.94), and 49.70% of patients had clinically relevant depression. In addition, 23.02% and 15.90% of patients were diagnosed with single-episode and recurrent major depressive disorder, respectively. The rates of bipolar disorder, persistent mood disorder, and unspecified mood disorder diagnoses were 4.95%, 0.85%, and 0.52%, respectively.

Overall, TSH levels were associated with risk for clinically relevant depression (adjusted odds ratio [aOR], 1.01; 95% CI, 1.01-1.02; P <.009).

The relationship between TSH and depression was observed among:

• Female patients (aOR, 1.02; 95% CI, 1.01-1.02; P <.0001);
• Patients with hypothyroidism (aOR, 1.02; 95% CI, 1.01-1.03; P <.0001);
• Patients using thyroid hormone replacement (aOR, 1.02; 95% CI, 1.01-1.03; P <.0001);
• Patients with a mood disorder diagnosis (aOR, 1.01; 95% CI, 1.00-1.02; P =.02);
• Patients without a mood disorder diagnosis (aOR, 1.01; 95% CI, 1.01-1.02; P =.0007);
• Patients who did not use antidepressants (aOR, 1.01; 95% CI, 1.01-1.02; P =.0002); and,
•  Patients with increasing age (aOR, 1.01; 95% CI, 1.00-1.02; P =.002).

Stratified by thyroid disorder subtype, TSH levels were also associated with depression among individuals with subclinical hypothyroidism (aOR, 1.02; 95% CI, 1.00-1.03; P =.02). After further stratification by mood disorder, the relationship between TSH levels and depression among individuals with subclinical hypothyroidism was only observed among those with a mood disorder (aOR, 1.03; 95% CI, 1.00-1.05; P =.03).

In addition to depression, TSH levels were negatively correlated with fatigue (r, -0.013; P =.014) and impaired concentration (r, -0.046; P <.001). Overall, TSH levels were associated with fatigue (odds ratio [OR], 1.01; 95% CI, 1.00-1.01; P =.0004) but not with impaired concentration (OR, 1.00; 95% CI, 1.00-1.01; P .59).

Free thyroxine levels were correlated with PHQ-9 scores (r, -0.053; P <.001). However, the researchers observed no relationship between free thyroxine levels and clinically relevant depression (aOR, 0.90; 95% CI, 0.80-1.01; P =.08).

Study limitations include the high rate of clinically relevant depression among the study population, making it unclear whether these findings may be generalizable.

The study authors concluded, “[T]hyroid dysfunction was associated with depression. Increasing TSH levels were associated with a small increase in the odds of [clinically relevant depression], especially among women, and patients who were not prescribed [antidepressants] or were on [thyroid hormone replacement].”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Endocrinology Advisor