Since the emergence of the new coronavirus disease-2019 (COVID-19) pandemic, several vaccines have been approved. As vaccination progresses, several cases indicating a possible relationship between thyroid diseases and vaccination have been reported.
However, since the start of vaccination, several cases of thyroid dysfunction have been reported. Most of the reported cases occurred after Covid 19 mRNA vaccination although were also caused by adenoviral vector vaccine and inactivated whole virus vaccine. Two mechanisms have been suggested regarding post-vaccination thyroid dysfunction.
Autoimmune/inflammatory syndrome induced by vaccine adjuvants (ASIA) was first suggested in 2011. Adjuvants in vaccines are used as immunogenicity enhancing agents to induce the adaptive immune response and trigger adverse immune reactions causing ASIA syndrome.
Genetic predisposition may also play a role, as suggested by the association with Human Leukocyte Antigen–B35 (HLAB35) and the report of familial SAT cases. Notably, vaccines against influenza, hepatitis B, H1N1, HPV, have also been associated with SAT.
Previously, type 1 diabetes mellitus, primary ovarian failure, adrenal insufficiency, and thyroiditis (mostly SAT) have been reported to be related to ASIA syndrome after human papillomavirus, hepatitis B virus, and influenza vaccination.
Another mechanism is an autoimmune response after COVID-19 vaccination due to the spike glycoprotein of SARS-CoV-2 sharing a genetic similarity with a human protein. SAT is a well-known inflammatory disorder of the thyroid presenting with painful thyroid swelling and destructive thyrotoxicosis and is believed to be linked to upper respiratory viral infection or a post-viral inflammatory process. PT is suggested to be a part of the spectrum of autoimmune thyroid (AIT) diseases.
GD is one of the AIT diseases caused by autoantibodies binding to the thyroid stimulating hormone receptor antibody (TSHR-Ab), stimulating the thyroid, and overproducing thyroid hormones. Regardless of the similar symptoms and signs of thyrotoxicosis, a differential diagnosis is important because the clinical course and treatment differ depending on the cause. Except for neck pain observed in SAT, it is difficult to differentiate based on symptoms alone. In some patients, more than one causal disease may occur sequentially or simultaneously.
Here, we describe eight patients and all presenting with thyrotoxicosis after COVID-19 vaccination. The underlying etiologies were identified through diagnostic workup, with one case painless thyroiditis (PT), three cases of subacute painful thyroiditis (SAT), one case of hyperthyroidism (normal thyroid functions tests before vaccination), three cases of Graves’ disease (symptoms precipitated following the booster dose).
29 years old gentleman complaining of fatigue, myalgia, joint pain, parathesis in hand, stable weight.
Recently taken two doses of inactivated whole virus vaccine
On investigation found to have thyrotoxicosis
Sr TSH 0.0.106 mIU/ml (0.55-4.78), FT4 34.8 ng/dl (1.5-22.7)), FT3 6.7 pg/ml ( 2.05- 4.43), Anti TPO 234 (34), Anti Tg Ab 227
USG thyroid- Both lobes of thyroid gland show average size with heterogeneous echo pattern, normal vasculairy ? thyroiditis
It shows patchy and decreased. tracer uptakes.
Thyroid uptake 0.2% (0.4% to 3.0%)
In view of low tsh, there is possibility that this patient might have had thyroiditis and now in recovery phase.
99mTc Pertechnatate thyroid scan
29 years old gentleman with history of low-grade fever and pain in neck since last one week.
Received two doses of inactivated whole virus vaccine three weeks ago
On investigation found to have thyrotoxicosis? thyroiditis.
Sr TSH 0.0815mIU/ml (0.55-4.78), FT4 27.28 ng/dl (9.0-19.0)), FT3 8.08 pg/ml (2.63- 5.70),
USG thyroid- Asymmetrically enlarged thyroid with significant increase of the right lobe as compared to left lobe. Overall echogenicity is abnormal and heterogenous, sluggish blood flow. Swollen enlarged right lobe specially the upper middle part with bulging of the superior aspect. It demonstrated focal ill-defined upper pole hazy are with heterogenous echo pattern and normal flow- suggestive of focal right lobe thyroiditis on a background of diffuse thyroid disease like early Hashimoto’s/silent thyroiditis. MRI neck- thyroid gland shows heterogeneous MR signals possibly due to thyroiditis. The capsule is intact. No suspicious nodule could be seen.
Ill-defined thyroid gland with patchy and decreased tracer uptakes.
Thyroid uptake 0.1% (0.4% to 3.0%)
In view of low tsh, there is possibility that this patient might have had thyroiditis and now in early recovery phase.
99mTc Pertechnatate thyroid scan
42 years old gentleman complaining of neck pain along low grade fever, shivering, feeling cold, tiredness, sweating, palpitation since last one month Received Covid 19 mRNA vaccine three months ago.
On investigation found to have thyrotoxicosis
Sr TSH 0.01 mIU/ml (0.55-4.78), FT4 21.1 ng/dl (9.0-19.0)), FT3 6.08 pg/ml (2.63- 5.70), Anti TPO 8.75 (<34)
Ill-defined thyroid gland with patchy and decreased tracer uptakes.
Thyroid uptake 0.1% (0.4% to 3.0%)
In view of low tsh, there is possibility that this patient might have had thyroiditis and now in early recovery phase.
99mTc Pertechnatate thyroid scan
40 years old gentleman complaining of throat pain, swallowing difficulty along low grade fever since last two weeks.
Received:
a) Two doses of inactivated whole virus vaccine in Jan 2021. Becomes asymptomatic COVID positive in April 2021.
b) Two doses of Covid 19 mRNA vaccine in Nov 2021. Becomes symptomatic COVID positive in Feb 2022.
On investigation found to have thyrotoxicosis
Sr TSH 0.03 mIU/ml (0.27-4.2), FT3 6.97 pmo/L (3.1_6.8)), FT4 24.43 pmol/L (12.3-20.2), ESR 83 mm/hr (<= 15 mm/hr), CRP 37.22 mg/L(<5).
USG thyroid- Both the lobes are bulky and shows heterogeneous echotexture with ill-defined hypoechoic areas within- likely to represent thyroiditis.
Ill-defined thyroid gland with poor tracer uptakes.
Quantitative data
Thyroid uptake 0.0% (0.4% to 3.0%)
99mTc Pertechnatate thyroid scan
35 years old gentleman complaining of mild heat intolerance, tremors for two week following post inactivated whole virus vaccination (1st dose)
On investigation found to have thyrotoxicosis
Pre-vaccination thyroid functions tests were normal.
Sr TSH 0.009 mIU/ml (0.5-4.5), Sr. F T4 35.7 pmol/L (11.5-22.7), Tg 9.36 ng/ml, Anti thyro-peroxidase antibodies negative USG thyroid- Unremarkable.
The right lobe measures 5.4*2.8 cms and left lobe measures 5.2*2.2 cms in size approximately and shows uniform and increased tracer uptakes.
Tc-uptakes (0.4% to 3.0%) 4.6% (right lobe 2.4% & left lobe 2.3% uptakes).
99mTc Pertechnatate thyroid scan
22 years old lady complaining of palpitation, fatigue, headaches, blurred vision, joint pain since last 3 months. Received inactivated whole virus vaccine, 1st dose March 2nd dose, April and Booster dose in December 2021.
On investigation found to have thyrotoxicosis
Sr TSH 0.0083 mIU/ml (0.27-4.20), Sr. F T4 37.75 pmol/L (9.01-19.05), FT3 30.72 pmol/L (1.58-4.6) AntiTg 78.12 IU/ml (00-4.11), Anti thyroperoxidase antibodies (TPO) 45.61 IU/ml (00-5.61), ESR 40 mm/hr (00-20),
USG thyroid -Suggestive of thyroiditis (? graves’ disease)
99mTechnetium Pertechnetate Thyroid Scan
The right lobe measures 6.5*2.9 cms and left lobe measures 5.5*2.7 cms in size approximately.
Tracer uptake is uniform and increased
Tc-uptakes (0.4% to 3.0%) 14.0% (right lobe 7.7% and left lobe 6.4% uptakes).
MODERATE TO LARGE ASYMMETRICAL SIZED TOXIC DIFFUSGE GOITER.
99mTc Pertechnatate thyroid scan
31 years old gentleman following inactivated whole virus vaccine 2nd dose six months ago, started complaining of palpitation, weight loss and on combination of Neomercazole and Thyroxine medications.
On investigation found to have thyrotoxicosis.
Sr TSH <0.09 mIU/ml (0.4-4.00), Sr. F T4 0.66 ng/dl (0.93-1.7) FT3 2.57 pg.ml (2.56-5.01),), Vit D 25.4 ng/dl ( deficiency <10),
USG thyroid- hypoechoic nodule of variable size in both the lobes, largest one in right lobe 9.4*5.4 at the lower pole and in left lobe 7.5*5.5 mm at the upper pole. Color flow sonography shows diffusely increased vascularity in both the lobes. suggestive of graves’ disease (diffuse goiter).
The right lobe measures 5.9*2.6 cms and left lobe measures 6.0*2.7 cms in size approximately.
Small cold area/nodule seen in lower lateral portion of the right lobe. Rest of the gland shows relatively inhomogeneous but increased tracer uptakes.
Tc-uptakes (0.4% to 3.0%) 13.1% ( right lobe 6.7% and left lobe 6.4% uptakes).
LARGE SIZED TOXIC GOITRE WITH SMALL COLD AREA/NODULE IN LOWER LATERAL PORTION OF THE RIGHT LOBE.
99mTc Pertechnatate thyroid scan
38 years old lady following inactivated whole virus vaccine 2nd dose, started complaining of palpitation, shivering tiredness and weight loss since last 2 months and at present on tablet Neomercazole, Inderal and Magnesium medications.
On investigation found to have thyrotoxicosis.
Sr TSH <0.005 mIU/ml (0.270-4.2), Sr. F T4 63.20 pmol/L (7.84-14.41), FT3 40.01 pmol/L (3.80-6.0), Thyroid peroxidase Ab ( Anti TPO) 2537.00 IU/ml ( <9), Thyroglobulin Ab ( anti Tg) 1.2 IU/ml ( <4), Anti thyroid stimulating hormone ( TSH) receptor antibodies 7.90 IU/L ( <1.75), Sr calcium 9.60 mg/dl ( 8.60- 10.0),Sr Mg 1.74 mg/dl ( 1.90-2.50),
EKG sinus tachycardia
USG thyroid- (Right lobe three nodules a) 1*0.9 middle aspect, hyperechoic, round, smooth and no internal vascularity (TI rads 3, b) 4.7*4.7 mm, middle aspect solid, hypoechoic, ovoid, ill-defined and no internal vascularity- TI rads 4 c) 3.5*3.7 mm lower pole, solid, hyperechoic, ovoid, smooth and no internal vascularity- TI RADS 3..Left lobe 5.7*4.7 , solid hyperechoic, ovoid, ill-defined with no internal vascularity)
Bulky thyroid gland with micronodular pattern and lobulated outline suggestive of Hashimoto’s thyroiditis
The right lobe measures 5.5*3.1 cms and left lobe measures 6.1*3.0 cms in size approximately.
Tracer uptake is uniform and increased.
Tc-uptakes (0.4% to 3.0%) 26.2% ( right lobe 13.6% and left lobe 12.7% uptakes).
MODERATE TO LARGE SIZED TOXIC DIFFUSE GOITRE.
99mTc Pertechnatate thyroid scan
Based on the case reports, including present cases, COVID-19 vaccines can cause not only destructive thyroiditis but also AIT.
Clinicians should remain vigilant about the potential thyroid dysfunction after SARS-CoV-2 vaccination in the current pandemic.