Context
Subacute thyroiditis (SAT) is a thyroid disease of viral or postviral origin. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that began in Wuhan, China, has spread rapidly worldwide and Italy has been severely affected by this outbreak.
Objectives
The objective of this work is to report the first case of SAT related to SARS-CoV-2 infection.
Methods
We describe the clinical, laboratory, and imaging features of an 18-year-old woman who came to our attention for fever, neck pain radiated to the jaw, and palpitations occurring 15 days after a SARS-CoV-2–positive oropharyngeal swab. Coronavirus disease 2019 (COVID-19) had been mild and the patient had completely recovered in a few days.
Results
At physical examination the patient presented with a slightly increased heart rate and a painful and enlarged thyroid on palpation. At laboratory exams free thyroxine and free triiodothyronine were high, thyrotropin undetectable, and inflammatory markers and white blood cell count elevated. Bilateral and diffuse hypoechoic areas were detected at neck ultrasound. One month earlier, thyroid function and imaging both were normal. We diagnosed SAT and the patient started prednisone. Neck pain and fever recovered within 2 days and the remaining symptoms within 1 week. Thyroid function and inflammatory markers normalized in 40 days.
Conclusions
We report the first case of SAT after a SARS-CoV-2 infection. We alert clinicians to additional and unreported clinical manifestations associated with COVID-19.
Context
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 18 million people worldwide and the pandemic is still spreading. After the first case we reported, we observed 4 additional cases of SAT related to SARS-CoV-2 infection.
Objectives
To describe additional cases of SAT associated with SARS-CoV-2 infection in order to alert physicians that SAT may be a manifestation of SARS-CoV-2 infection.
Methods
We describe clinical, biochemical and imaging features of the 4 patients with SAT related to SARS-CoV-2 infection.
Results
All patients were female (age 29-46 years). SAT developed 16 to 36 days after the resolution of coronavirus disease 2019 (COVID-19). Neck pain radiated to the jaw and palpitations were the main presenting symptoms and were associated with fever and asthenia. One patient was hospitalized because of atrial fibrillation. Thyroid function tests (available in three subjects) were suggestive of destructive thyroiditis and inflammatory markers were high. At neck ultrasound the thyroid was enlarged, with diffuse and bilateral hypoechoic areas and (in three patients) absent vascularization at color doppler. Symptoms disappeared a few days after commencement of treatment (prednisone in three patients and ibuprofen in one). Six weeks after the onset of SAT all patients were asymptomatic and inflammatory markers had turned back to the normal range. Two patients were euthyroid while two were diagnosed with subclinical hypothyroidism.
Conclusions
SAT may be an underestimated manifestation of COVID-19. Clinicians should keep in mind the possible occurrence of SAT during and after SARS-CoV-2 infection.
The sutureless repair group had proportionally more infracardiac total anomalous pulmonary venous connection and a higher rate of decline in postoperative right ventricular systolic pressure. Despite increased preoperative risk, no difference was observed in primary outcomes of death and reoperation in the conventional repair group.
Mortality and restenosis rates remained high despite the adoption of a sutureless technique. A preoperative pulmonary vein stenosis score of greater than 4 was a strong predictor of poor prognosis.
Summary
Programmed cell death protein 1/programmed cell death protein ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte antigen 4/B7 (CTLA-4/B7) pathways are key regulators in T-cell activation and tolerance. Nivolumab, pembrolizumab (PD-1 inhibitors), atezolizumab (PD-L1 inhibitor) and ipilimumab (CTLA-4 inhibitor) are monoclonal antibodies approved for treatment of several advanced cancers. Immune checkpoint inhibitors (ICIs)-related hypophysitis is described more frequently in patients treated with anti-CTLA-4; however, recent studies reported an increasing prevalence of anti-PD-1/PD-L1-induced hypophysitis which also exhibits slightly different clinical features. We report our experience on hypophysitis induced by anti-PD-1/anti-PD-L1 treatment. We present four cases, diagnosed in the past 12 months, of hypophysitis occurring in two patients receiving anti-PD-1, in one patient receiving anti-PD-1 and anti-CTLA-4 combined therapy and in one patient receiving anti-PD-L1. In this case series, timing, clinical presentation and association with other immune-related adverse events appeared to be extremely variable; central hypoadrenalism and hyponatremia were constantly detected although sellar magnetic resonance imaging did not reveal specific signs of pituitary inflammation. These differences highlight the complexity of ICI-related hypophysitis and the existence of different mechanisms of action leading to heterogeneity of clinical presentation in patients receiving immunotherapy.
Learning points:
PD-1/PD-L1 blockade can induce hypophysitis with a different clinical presentation when compared to CTLA-4 blockade.
Diagnosis of PD-1/PD-L1 induced hypophysitis is mainly made on clinical grounds and sellar MRI does not show radiological abnormalities.
Hyponatremia due to acute secondary adrenal insufficiency is often the principal sign of PD-1/PD-L1-induced hypophysitis and can be masked by other symptoms due to oncologic disease.
PD-1/PD-L1-induced hypophysitis can present as an isolated manifestation of irAEs or be in association with other autoimmune diseases
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