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. 2023 Mar 10;12(2):e220200.
doi: 10.1530/ETJ-22-0200. Print 2023 Apr 1.

Long-term outcome of thyroid abnormalities in patients with severe Covid-19

Ilaria Muller  1   2 , Anita Daturi  2 , Matteo Varallo  2 , Tiziana E Re  3 , Davide Dazzi  4 , Sara Maioli  2 , Erica Crivicich  2 , Francesco Di Marco  2 , Virgilio Longari  5 , Beatrice Dazzi  1 , Massimo Castellani  5 , Giovanna Mantovani  1   2 , Maura Arosio  1   2 , Mario Salvi  1
Affiliations

Long-term outcome of thyroid abnormalities in patients with severe Covid-19

Ilaria Muller et al. Eur Thyroid J. .

Abstract

Objective: We have previously observed thyroid dysfunction, i.e. atypical thyroiditis (painless thyrotoxicosis associated with non-thyroidal illness syndrome), in patients with severe acute respiratory syndrome coronavirus 2 disease (Covid-19). This study aimed to analyse the evolution of thyroid dysfunction over time.

Methods: One hundred eighty-three consecutive patients hospitalised for severe Covid-19 without known thyroid history were studied at hospital admission (baseline). Survivors were offered 12-month longitudinal follow-up including assessment of thyroid function, autoantibodies and ultrasound scan (US). Patients showing US focal hypoechoic areas suggestive of thyroiditis (focal hypoechogenicity) also underwent thyroid 99mTc or 123I uptake scan.

Results: At baseline, after excluding from TSH analysis, 63 out of 183 (34%) Covid-19 patients commenced on steroids before hospitalisation, and 12 (10%) showed atypical thyroiditis. Follow-up of 75 patients showed normalisation of thyroid function and inflammatory markers and no increased prevalence of detectable thyroid autoantibodies. Baseline US (available in 65 patients) showed focal hypoechogenicity in 28% of patients, of whom 82% had reduced thyroid 99mTc/123I uptake. The presence of focal hypoechogenicity was associated with baseline low TSH (P = 0.034), high free-thyroxine (FT4) (P = 0.018) and high interleukin-6 (IL6) (P = 0.016). Focal hypoechogenicity persisted after 6 and 12 months in 87% and 50% patients, respectively, but reduced in size. After 9 months, thyroid 99mTc/123I uptake partially recovered from baseline (+28%) but was still reduced in 67% patients.

Conclusions: Severe Covid-19 induces mild transient thyroid dysfunction correlating with disease severity. Focal hypoechogenicity, associated with baseline high FT4, IL6 and low TSH, does not seem to be related to thyroid autoimmunity and may persist after 1 year although decreasing in size. Long-term consequences seem unlikely.

Keywords: Covid-19; SARS-CoV-2; thyroid; thyroiditis.

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Conflict of interest statement

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Figures

Figure 1
Figure 1
Study design. (A) Thyroid assessments were planned at different time points following the hospitalisation for Covid-19 (time 0). (B) Numbers of patients evaluated at the time of hospital admission for Covid-19, included in the study at baseline and attending at least one follow-up time point. TSH, thyroid-stimulating hormone.
Figure 2
Figure 2
Correlation between thyroid-stimulating hormone (TSH) assessed at hospital admission and Covid-19 disease severity. Scatter plots of correlations between serum concentrations of TSH and albumin (A) and lymphocyte count (B). Bar graphs of median TSH serum concentrations measured in patients grouped according to the different type of oxygen support required (C). CPAP/HFNC, continuous positive airway pressure or high-flow nasal cannula.
Figure 3
Figure 3
Thyroiditis-like areas (focal hypoechogenicity). Representative images in transverse (A) and longitudinal (B) planes at thyroid ultrasound (US) showing focal hypoechoic areas (white arrows). (C) Bar graphs showing the prevalence of focal hypoechoic areas at thyroid US (black if present, grey if absent) in patients with serum concentrations at hospital admission of thyroid-stimulating hormone (TSH) < 0.45 mIU/L, the lower cut-off for automated reflex TSH assay (low TSH), or above 0.45 mIU/L and within the normal reference range (normal TSH). Box plots of the association between the presence or absence of focal areas of hypoechogenicity at US (F. Hypoechoic US) and serum concentrations at hospital admission of free-thyroxine (FT4; D) and interleukin-6 (IL-6; E).
Figure 4
Figure 4
Evolution of thyroiditis-like features at thyroid ultrasound and scintigraphy scans during follow-up. Representative images of thyroid ultrasound scan (A and B) and SPECT tomographic acquisitions of thyroid scintigraphy scan with iodine-123 (C and D) at baseline and follow-up. Yellow arrows indicate hypoechoic areas suggestive of thyroiditis at ultrasound, reduced in size at the 6-month follow-up (B) compared with baseline (A). Thyroid scintigraphy images at 9-month follow-up (D) show an overall increased iodine-123 uptake and disappeared areas of focally reduced uptake (white arrows) in the middle region of the right lobe and middle/polar region of the left lobe, compared with baseline (C).
Figure 5
Figure 5
Longitudinal evolution of biochemical parameters. Kernel density plot of thyroid-stimulating hormone (TSH, A) and box plots of free-thyroxine (FT4, B), free-triiodothyronine (FT3, C), C-reactive protein (CRP, D), lymphocyte count (E) and neutrophil count (F) measured at the time of hospital admission (Hospital.: day 0), after 3 months (days +84), 6 months (days +194) and 12 months (days +443). P values refer to the comparison between Hospital. and 3 months time point (t test).
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