Among hospitalized patients with COVID-19, elevated serum reverse triiodothyronine (rT3) was the most frequently observed change (∼63%), followed by elevated serum free thyroxine (fT4) (∼21%) and low serum thyrotropin (TSH) levels (∼7.3%), researchers reported in Thyroid.
The observational, longitudinal, prospective cohort study assessed thyroid hormone levels and their association with serum pro-inflammatory biomarkers and severity and mortality associated with COVID-19. A total of 245 patients hospitalized with confirmed COVID-19 infection at a tertiary referral hospital in Brazil from June 2020 to August 2020 were enrolled.
The patients included were on average 62 years old (range: 49-74.5) and 145 patients (59.1%) were men. The average hospital stay was 8.3 days. During this period, 58 patients (23.6%) were admitted to the intensive care unit, of whom 41 (16.7%) later died. Patients were classified as not critically ill (n = 181) and critically ill (n = 64) within 48 hours of admission to hospital.
Of the full cohort of 245 patients, 16 (∼6.5%) had nonthyroidal disease syndrome (NTIS) with isolated low levels of free triiodothyronine (fT3). Critically ill patients had lower fT3 levels than noncritical patients (2.82 [2.46-3.29] pg/mL versus 3.09 [2.67-3.63] pg/mL, respectively, P = 0.007). Serum reverse triiodothyronine (rT3) was somewhat elevated but to a lesser degree in critically ill patients compared to the level in non-critically ill patients (0.36 [0.28-0.56] ng/mL versus 0.51 [0.31-0.67] ng/mL, respectively, P = 0.001).
A univariate logistic regression analysis demonstrated a correlation between hospital mortality and serum fT3 levels (odds ratio [OR] 0.47; 95% CI, 0.29-0.74; P= 0.0019), rT3 levels (OR 0.09; CI, 0.01-0.49; P= 0.006), and the product fT3 × rT3 (OR 0.47; CI, 0.28-0.74; P= 0.0026). Serum thyrotropin, free thyroxine, and fT3/rT3 levels were not significantly associated with mortality or disease severity.
Analysis with the score of the area under the receiver operating characteristic (ROC) and the area under the curve (AUC) showed 3 predictors of COVID-19 mortality: serum fT3 (AUC = 0.66) , rT3 (AUC = 0.64) and the product of serum fT3 × rT3 (AUC = 0.70). Non-thyroid disease syndrome (fT3 < 2.0 pg/mL) was associated with an OR of 7.05 for mortality (CI, 1.78-28.3, P= 0.005), and the product rT3 × fT3 ≤1.29 was associated with an OR of 8.08 for mortality (CI, 3.14-24.2; P< .0001).
The investigators acknowledged that their analysis was limited to patients hospitalized with moderate to severe COVID-19 disease, and it was unclear whether decreased calorie intake, weight loss, or a combination of these factors led to a decreased fT3 levels in people who were critically ill with COVID-19.
“Unexpectedly, NTIS was observed in only about 6.5% of patients,” the investigators said. “The data revealed the importance of early assessment of thyroid function in hospitalized patients with COVID-19, given the good prognostic value of fT3, rT3 and fT3×rT3 serum products.”
In a related comment (Moretti et al), the researchers wrote: “This study was unique: the novel observation that the product fT3 × rT3 had the highest prognostic value of all parameters, including biomarkers stereotyped inflammatory diseases, with a sensitivity and specificity of 80% and 57%, respectively.
Disclosure: One of the study’s lead authors has declared affiliations with biotechnology, pharmaceutical, and/or device companies. Please see the original citation for a full list of author disclosures.
- Beltrão FEDL, Beltrão DCDA, Carvalhal G, et al. Thyroid hormone levels on hospital admission inform disease severity and mortality in patients with COVID-19. Thyroid.2021;31(11):1639-1649. doi:10.1089/thy.2021.0225
2. Moretti B, Papaleontiou M. Prognostic value of thyroid hormone levels in hospitalized patients with moderate to severe COVID-19 infection. Wink Thyroidol.2021;33(12):511-515. http://doi.org/10.1089/ct.2021;33.511-515