SARS-CoV-2 (anti-Covid-19) vaccination is currently reducing the Covid-19 pandemic. Much has been discussed in scientific circles and also in the press about the possible side effects of vaccines. In a very recent article published in Thyroid, the official journal ATA (American Thyroid Association), Mexican researchers report for the first time Graves Basedow’s hyperthyroidism suddenly onset in two young and healthy subjects 2-3 days after the first dose of Pfizer BioNTech vaccine [ 1].
GRAVES BASEDOW DISEASE
Graves Basedow’s disease is the most frequent cause of hyperthyroidism with an incidence of between 1.5 and 3% of the population. Graves Basedow disease primarily affects females, with a male / female ratio of 1: 5-1: 10. It can occur at any age, but is more frequent between the ages of 30 and 40 and over sixty.
Symptoms at the onset of the disease have faded. Psychic disorders are often interpreted with difficulty. The patient can thus complain of excessive emotional reactions, anxiety, difficulty sleeping, irritability, worry for negligible reasons, cognitive disturbances, easy mental fatigue, to the point of developing real depressive pictures.
Full-blown Graves Basedow disease presents the typical symptoms of hyperthyroidism: fine distal tremors, tachycardia, arrhythmias (up to atrial fibrillation), weakness, heat intolerance with profuse sweating, redness of the face and neck, menstrual disorders up to amenorrhea , decreased libido and fertility, disorders of the hive with frequent episodes of diarrhea, enlarged thyroid gland (goiter), shortness of breath, brittle nails, weight loss despite increased appetite. Hyperphagia can in some cases cause weight gain, dispelling the common belief that hyperthyroid people necessarily lose weight.
Protrusion of the eyes (exophthalmos) and paralysis of the extrinsic eye muscles with diplopia (double vision) and strabismus fortunately affect a small percentage (5-10%) of patients with Graves Basedow’s disease. In most patients, ocular symptoms are limited to eyelid retraction (reversible), lacrimation, photophobia (light intolerance), a feeling of sand in the eyes and mild periorbital edema.
OBJECTIVE SIGNS OF GRAVES BASEDOW DISEASE
The neck of a patient with Graves Basedow’s disease may be swollen due to goiter due to an increase in the volume of the thyroid gland. Thyroid ultrasound confirms the presence of diffuse goiter and hypoechoic gland (darker than normal) due to lymphocyte infiltrate (Fig. 2). A characteristic ultrasound aspect is thyroid hypervascularization detectable with color Doppler or with a microV study that detects fast and slow vascular flows. This ultrasound picture is called “thyroid hell” (Fig. 3). Graves Basedow’s disease is a manifestation of chronic autoimmune thyroiditis and in some ways the ultrasound aspects of Graves Basedow’s disease resemble this (Il pane quotidiano dell’Endocrinologo: LA TIROIDE)
Many symptoms may remain vague in the elderly patient, except for asthenia, cardiovascular and myopathic symptoms (muscle pain), which tend to be accentuated. The natural history of Graves Basedow’s disease generally does not have a uniform course, the alternation of remissions and relapses is characteristic. In 30-40% of cases the disease goes into stable remission or evolves into hypothyroidism. Probably this type of evolution occurs in a higher percentage of cases because the few patients who do more than 2 years of antithyroid therapy may have a tendency to switch off their hyperthyroidism.
The origin of Graves’ disease is on an autoimmune basis and is influenced by an important genetic and hereditary component. In patient serum it is possible to find abnormal autoantibodies directed against enzymatic components (antibodies to thyroperoxidase) or against thyroglobulin (antibodies to thyroglobulin), a protein that contains preformed thyroid hormones. Characteristic of Graves Basedow’s disease are antibodies directed against the TSH receptor. TSH is the pituitary hormone that stimulates the synthesis of thyroid hormones; the binding of these antibodies to the TSH receptor reproduces the stimulatory effects of TSH on thyroid activity. Hyperthyroidism therefore derives from functional hyperactivation of the thyroid gland, with an increase in the circulation of both thyroid hormones (FT4 and FT3) and blockage of TSH, almost always wearable given the known negative feedback effect exerted by thyroid hormones on TSH (elevated thyroid hormones reduce TSH levels). Still rather obscure remains the reason for this self-antibody attack.
To make the diagnosis of Graves’ disease, in addition to the clinical examination of the patient (search for the symptoms and risk factors listed above), the dosage of thyroid hormones, TSH and antithyroid and antireceptor TSH antibodies, associated with ultrasound images of the thyroid with echocolordoppler to investigate its vascularization or, more modernly, with microV. The microV doppler displays slow flows and capillary flows, and the thyroid typically lights up in color with the picture of “thyroid hell”. Thyroid scintigraphy is no longer needed to make a diagnosis.
Basedow’s disease therapy aims to reduce the amount of circulating thyroid hormones and to this end makes use of thyrostatic drugs, thionamides, with immunosuppressive action. These medicines are represented by methimazole, propylthiouracil (preferred in pregnancy). The beta blocker propranolol is used in the early stages to dominate cardiovascular symptoms.
Drug therapy of Graves’ disease must be continued at gradually decreasing doses and – with a dosage calibrated on the individual patient based on the aggressiveness of the disease – continued until clinical hormonal remission of the hyperthyroid syndrome. Destructive treatment of the thyroid with radioactive iodine or (only in extreme situations) with thyroidectomy is reserved for forms that cannot be managed with drug therapy. Treatment of severe ocular symptoms of basedowian orbitobathy is with local or systemic cortisone. In the early stages, biological drugs such as rituximab or infliximab have shown promising results. Corrective surgeries are reserved for the most severe cases.
CLINICAL CASES OF GRAVES BASEDOW DISEASE ARISING AFTER VACCINATION SARS-CoV-2 PFIZER BIONTECH
CLINICAL CASE 1
40-year-old woman, hospital worker, hypertensive, with a history of Covid-19 infection which resolved 8 months earlier. Two days after vaccination Pfizer BioNTech presented with nausea, vomiting, asthenia, insomnia and palpitations.
Physical examination: fine distal tremors, hyperreflexia, cardiac arrhythmia.
Thyroid function tests revealed suppressed TSH, elevated fT3, fT4; positive antibodies antiTPO, antiTg and TSH antireceptor. The TSI was positive (Table 1).
The thyroid Doppler ultrasound showed an increase in size and hypervascularization of the thyroid gland.
ECG monitoring according to Holter revealed sinus tachycardia and episodes of paroxysmal atrial fibrillation. The patient was treated with propranolol 60 mg / day, diltiazem 120 mg / day, ivabradine 5 mg / day and methimazole 10 mg / day with good response.
CLINICAL CASE 2
28-year-old female, previously healthy, trainee, with no history of AIED (Auto Immune Endocrine Disease). Three days after the SARS-CoV-2 vaccination (Pfizer BioNTech) she was experiencing anxiety, insomnia, palpitations, distal tremor. Blood tests were normal, except for the thyroid function tests. TSH was suppressed and fT3 and fT4 were increased. Antithyroid antibodies were elevated (Table 1). Holter ECG monitoring was normal.
The patient was treated with propranolol 40 / mg day and methimazole 10 mg / day with adequate response.
Neither patient presented any signs of dermopathy, orbitopathy or other signs of undifferentiated connective tissue disease.
These are the first cases described in the literature of Graves Basedow’s disease onset after SARS-Cov-2 vaccination, in this case Pfizer BioNTech. Information regarding autoimmune endocrine diseases following SARS-Cov-2 vaccination is limited.
The authors attribute the onset of hyperthyroidism to Adjuvant-Induced Autoimmune / Inflammatory Syndrome (ASIA). One of the conditions recognized as ASIA is post-vaccination syndromes.
Vaccines contain adjuvant substances, which increase the antigen-specific immune response. Vaccines can trigger an immune response that leads to a broad spectrum of autoimmune diseases, including autoimmune thyroid disease .
In the two cases presented in the article by Olga Vera-Lastra et al, the clinical manifestations of hyperthyroidism, the appearance of antithyroid antibodies including TSH antireceptor antibodies, of TSI (Thyroid Stimulating Immunoglobulin) and ultrasound imaging made it possible to diagnose the disease. by Graves Basedow. It is unusual that the time of onset of the manifestations of hyperthyroidism was extremely short (2-3 days). A possible mechanism for the rapid onset of symptoms is that the concentration of the viral protein contained in the vaccine reaches a peak in 24-48 hours, triggering an autoimmune response (3). Pfizer BioNTech vaccine is composed of lipid nanoparticles formulated with a nucleoside RNA that encodes a modified SARS-Cov-2 virus spike protein. The vaccine has been shown to be safe and 94.6% effective .
The cases presented by Mexican scholars represent an example of the different clinical manifestations of vaccine-induced autoimmune reactions. The authors strongly recommend monitoring the thyroid effects of recently introduced SARS-CoV-2 vaccines.
- Olga Vera-Lastra, Alberto Ordinola Navarro, Maria Pilar Cruz Domiguez, Gabriela Medina, Tania Ivonne Sánchez Valadez, Luis J Jara. Two Cases of Graves’ Disease Following SARS-CoV-2 Vaccination: An Autoimmune/Inflammatory Syndrome Induced by Adjuvants. Thyroid 2021 May 3. doi: 10.1089/thy.2021.0142. Online ahead of print. PMID: 33858208 DOI: 10.1089/thy.2021.0142
- Ruiz JT, et al. Adjuvants- and vaccines-induced autoimmunity: animal models. Immunol Res. 2017. PMID: 27417999
- Skowronski DM, De Serres G. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2021 Apr 22;384(16):1576-1577. doi: 10.1056/NEJMc2036242. Epub 2021 Feb 17. PMID: 33596348