The Clinical Characteristics and Outcomes of COVID-19 Patients with Pre-Existing Thyroid Dysfunction: A Nationwide Study.

To which extent the pre-existing hypothyroidism or hyperthyroidism has an impact on coronavirus infection 2019 (COVID-19) outcomes remains unclear. The objective of this study was to evaluate COVID-19 morbidity and mortality in patients with pre-existing thyroid dysfunction. A retrospective cohort of patients with a polymerase chain reaction (PCR)-confirmed COVID-19 infection (n=14 966) from March 11 to May 30, 2020, was established using the database of the Turkish Ministry of Health. We compared the morbidity and mortality rates of COVID-19 patients with pre-existing hypothyroidism (n=8813) and hyperthyroidism (n=1822) to those patients with normal thyroid function (n=4331). Univariate and multivariate regression analyses were performed to identify the factors associated with mortality. Mortality rates were higher in patients with hyperthyroidism (7.7%) and hypothyroidism (4.4%) than those with normal thyroid function (3.4%) (p<0.001 and p=0.008, respectively). Pre-existing hyperthyroidism was significantly associated with an increased risk of mortality (OR 1.54; 95% CI, 1.02-2.33; p=0.042) along with advanced age, male gender, lymphopenia and chronic kidney disease (p<0.001 for all). Although a potential trend was noted, the association between pre-existing hypothyroidism and mortality was not significant (OR 1.36; 95% CI, 0.99-1.86; p=0.055). In conclusion, this study showed an association between pre-existing hyperthyroidism with higher COVID-19 mortality. A potential trend towards increased mortality was also observed for hypothyroidism. The risk was more pronounced in patients with hyperthyroidism.

No association of Gaucher disease with COVID-19-related outcomes: a nationwide cohort study.

BACKGROUND: It is well documented that patients with chronic metabolic diseases, such as diabetes and obesity, are adversely affected by the COVID-19 pandemic. However, when the subject is rare metabolic diseases, there are not enough data in the literature. AIM: To investigate the course of COVID-19 among patients with Gaucher disease (GD), the most common lysosomal storage disease. METHODS: Based on the National Health System data, a retrospective cohort of patients with confirmed (polymerase chain reactionpositive) COVID-19 infection (n = 149 618) was investigated. The adverse outcomes between patients with GD (n = 39) and those without GD (n = 149 579) were compared with crude and propensity score-matched (PSM) groups. The outcomes were hospitalisation, the composite of intensive care unit (ICU) admission and/or mechanical ventilation and mortality. RESULTS: The patients with GD were significantly older and had a higher frequency of hypertension (HT), Type 2 diabetes mellitus (T2DM), dyslipidaemia, asthma or chronic obstructive pulmonary disease, chronic kidney disease, coronary artery disease, heart failure and cancer. Although hospitalisation rates in Gaucher patients were found to be higher in crude analyses, the PSM models (model 1, age and gender matched; model 2, matched for age, gender, HT, T2DM and cancer) revealed no difference for the outcomes between patients with GD and the general population. According to multivariate regression analyses, having a diagnosis of GD was not a significant predictor for hospitalisation (P = 0.241), ICU admission/mechanical ventilation (P = 0.403) or mortality (P = 0.231). CONCLUSION: According to our national data, SARS-CoV-2 infection in patients with GD does not have a more severe course than the normal population.

The clinical outcomes of COVID-19 infection in patients with a history of thyroid cancer: A nationwide study.

BACKGROUND: There are scarce published data in differentiated thyroid cancer patients about new coronavirus disease 2019 (COVID-19) disease outcomes and mortality. Here, we evaluated COVID-19 infection outcomes and mortality in thyroid cancer patients with COVID-19 infection. DESIGN AND METHODS: We included a cohort of patients with thyroid cancer with PCR-confirmed COVID-19 disease from 11 March to 30 May 2020 from the Turkish Ministry of Health database in our nationwide, retrospective study. We compared the mortality and morbidity of COVID patients with or without thyroid cancer. Univariate and multivariate analyses were used to assess the independent factors for mortality, length of hospital stay and intensive care unit (ICU) admission and mechanical ventilation. We also analysed the effect of radioiodine treatment on severity and death rate of COVID-19 disease. RESULTS: We evaluated 388 COVID-19 patients with thyroid cancer [median age: 54 years, interquartile range (IQR) 18 years, males: 23%] and age and gender-matched 388 COVID-19 patients without thyroid cancer. Patients with thyroid cancer had a similar mortality ratio compared with the non-cancer group. Among patients with thyroid cancer, age, presence of diabetes mellitus, asthma/COPD, heart failure, chronic kidney disease, prior coronary artery disease, RAS blocker usage and low lymphocyte count were associated with mortality. Radioactive iodine (RAI) treatment and cumulative radioactive iodine dosage did not negatively affect the severity and mortality of COVID-19 disease in our patient group. CONCLUSIONS: Our study indicated that history of thyroid cancer did not have an increased risk of mortality or morbidity in COVID-19 disease. Besides, RAI therapy history and doses of radioactive iodine did not affect mortality or outcome.

SONOGRAPHIC FOLLOW-UP OF PATIENTS WITH DIFFERENTIATED THYROID CARCINOMA: A COMPARISON OF THE ULTRASOUND ELASTOGRAPHY, POWER DOPPLER ULTRASOUND, AND B-MODE ULTRASOUND FEATURES IN DETECTING MALIGNANT LYMPH NODES.

Objective: The aim of this study was to assess and compare the diagnostic power of B-mode ultrasonography (US), power Doppler US (PD), and ultrasound elastography (USE) in detecting malignant lymph nodes (LNs) during follow-up of patients who were operated on for differentiated thyroid cancer (DTC). Methods: In this prospective study, a total of 103 cervical LNs having suspicious malignant features from 72 patients with DTC were examined using US, PD, and USE. USE scores were classified from 1 to 3 according to the presence of elasticity (1, soft; 2, intermediate; 3, hard). The strain ratios (SRs) of all LNs were calculated according to adjacent muscle tissue. Results: The most-sensitive ultrasonographic features were hilum loss and hypoechogenicity, with 94.4% and 80.6% sensitivity and 93.5% and 84.4% negative predictive value, respectively. The most-specific feature was the presence of cystic component, with 98.5% specificity and 85.7% positive predictive value. Presence of diffuse/chaotic or irregular vascularity in PD had 47.2% sensitivity and 83.6% specificity in predicting metastasis. In USE, the sensitivity and specificity of score 3 were 56.7% and 74.2%, respectively. The median SR of metastatic LNs was higher than that of benign LNs (median SR [min-max], 3.0 [0.16 and 29] vs. 1.89 [0.26 and 37.9]), but the difference was not significant (P = .07). Multivariate logistic regression analyses revealed 4.9-, 6.6-, and 10-fold increases in metastasis risk for short/long axis ratio ≥0.5, nodal vascularity, and score 3 USE, respectively (P<.05). Conclusion: While USE had higher sensitivity, PD had higher specificity in detecting malignant LNs, but none of these techniques was as sensitive and specific as gray-scale US features. Abbreviations: CI = confidence interval; DTC = differentiated thyroid cancer; LN = lymph node; LN-Tg = lymph node-thyroglobulin; NPV = negative predictive value; PD = power Doppler; PPV = positive predictive value; ROI = region of interest; SR = strain ratio; US = ultrasonography; USE = ultrasound elastography.

Acute suppurative thyroiditis following fine-needle aspiration biopsy in an immunocompetent patient.

The thyroid gland is remarkably resistant to infectious agents owing to several protective mechanisms. Acute suppurative thyroiditis after fine-needle aspiration (FNA) in an immunocompetent patient is very rare. We report the case of a 50-year-old immunocompetent male patient who presented with painful cervical swelling, fever, and chills after an FNA of the thyroid. His physical and laboratory examination suggested an acute suppurative thyroiditis. Repeat FNA results were consistent with thyroid abscess. Physicians should be aware of the probability of acute bacterial thyroiditis after FNA.

Effect of post-transplant diabetes mellitus on cardiovascular events and mortality: a single-center retrospective cohort study.

PURPOSE: This study aims to investigate the impact of post-transplant diabetes mellitus (PTDM) on cardiovascular events, graft survival, and mortality and to determine the risk factors involved in developing PTDM. METHODS: A total of 703 patients who underwent kidney transplantation were included in the study. The total sample was subdivided into three groups: (i) patients with PTDM; (ii) patients who had diabetes before the transplantation (DM); and (iii) patients without diabetes (NoDM). The data on graft failure, cardiovascular events, all-cause mortality, and the potential risk factors that play a role in developing PTDM were recorded and analyzed. RESULTS: The patients were followed for a median of 80 (6-300) months after transplantation. Out of all patients, 41 (5.8%) had DM before transplantation, and 101 (14.4%) developed PTDM. Recipient BMI, post-transplant fasting plasma glucose, and hepatitis C seropositivity were independent risk factors for PTDM development. The incidence of cardiovascular events was 6.1% in the NoDM group, 14.9% in the PTDM group, and 29.3% in the DM group (p < 0.001). In PTDM patients, hepatitis C seropositivity and the recipient's age at transplant were independent predictors of a cardiovascular event. There were no significant differences between the groups regarding the risk of graft loss. PTDM had no significant effect on all-cause mortality. However, the survival rates of DM patients were significantly reduced compared to those with NoDM or PTDM. CONCLUSIONS: PTDM had no impact on patient survival. Hepatitis C seropositivity and recipient age at transplant predicted cardiovascular events in PTDM patients.

Evaluation of Microvascular Complications in Kidney Recipients With Posttransplant Diabetes Mellitus.

CONTEXT: The paucity of data on microvascular complications in patients with posttransplant diabetes (PTDM) is an obstacle to developing follow-up algorithms. OBJECTIVE: To evaluate diabetic microvascular complications in patients with long-standing PTDM. METHODS: In patients with ≥5-year history of PTDM and age-matched renal transplant recipients without PTDM (NDM), diabetic peripheral neuropathy was evaluated using the Michigan Neuropathy Screening Instrument, the CASE IV device, and in vivo corneal confocal microscopy (CCM). Cardiac autonomic neuropathy tests were performed using heart rate variability. Nephropathy screening was assessed using spot urine albumin/creatinine ratio and eGFR calculation. Diabetic retinopathy was evaluated by fundus examination and photography, and optical coherence tomography. RESULTS: This study included 41 patients with PTDM and 45 NDM patients. The median follow-up was 107.5 months in the PTDM group. Peripheral neuropathy was significantly higher in the PTDM group than in the NDM group (P = .02). In the PTDM patients with peripheral neuropathy, corneal nerve fiber density examined by CCM was significantly lower than in PTDM patients without neuropathy (P = .001). Parasympathetic involvement was observed in 58.5% of the PTDM group and 22% of the NDM group (P = .001). Sympathetic involvement was present in 65.9% of the PTDM group and 29.3% of the NDM group (P = .001). Retinopathy was observed in 19.5% of patients in the PTDM group and in none of the NDM patients (P < .001). Renal functions were similar between the study groups. CONCLUSION: Cardiac autonomic neuropathy and diabetic retinopathy can affect patients with PTDM at a high rate. Diabetic retinopathy is a threat to the vision of PTDM patients. Diabetic peripheral neuropathy can be detected early in PTDM patients by CCM.

COVID-19 vaccination and thyroiditis.

At the end of 2019, the world began to fight the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus-2. Many vaccines have quickly been developed to control the epidemic, and with the widespread use of vaccines globally, several vaccine-related adverse events have been reported. This review mainly focused on COVID-19 vaccination-associated thyroiditis and summarized the current evidence regarding vaccine-induced subacute thyroiditis, silent thyroiditis, Graves' disease, and Graves' orbitopathy. The main clinical characteristics of each specific disease were outlined, and possible pathophysiological mechanisms were discussed. Finally, areas lacking evidence were specified, and a research agenda was proposed.

The role of ultrasound elastography in preoperative localization of parathyroid lesions: a new assisting method to preoperative parathyroid ultrasonography.

BACKGROUND: After the definition of minimally invasive procedures, preoperative localization of parathyroid lesions is now crucial. False-positive results up to 30% were reported by B-mode grayscale ultrasonography (US) in localization of parathyroid lesions. Parathyroid adenomas are relatively stiff lesions. Ultrasound elastography (USE) can accurately evaluate tissue stiffness and might detect the stiff parathyroid lesions. OBJECTIVE: The aim of this study is to demonstrate whether USE can detect the level of the stiffness and help the preoperative localization of parathyroid lesions during parathyroid ultrasonography examination. PATIENTS: The patients who were candidates for parathyroidectomy were prospectively enrolled to this study and were evaluated by USE. RESULTS: Seventy-two patients with 93 parathyroid lesions underwent parathyroidectomy. Sixty-three patients including three multiple endocrine neoplasia type-1 patients had primary hyperparathyroidism, three patients with chronic renal disease (CRD) had tertiary hyperparathyroidism, three patients with CRD and two renal transplanted patients had persistent secondary hyperparathyroidism. One patient was excluded. While all parathyroid adenomas exhibited high levels of stiffness (score 3 and 4), 17 (63%) out of 27 parathyroid hyperplasia lesions were shown to have significantly higher elasticity. The evaluation of median strain ratios of parathyroid lesions revealed that parathyroid adenomas demonstrated significantly higher levels of stiffness than hyperplasias (P ≤ 0·001). CONCLUSIONS: This is the first study that evaluates the ultrasound elastographic features of parathyroid lesions. Parathyroid adenomas were shown to appear as stiff lesions, and half of the hyperplasias showed high elasticity. Parathyroid elastography is a novel technique to evaluate parathyroid lesions and might be a guide for surgeons to determine the type of operation to apply.

Type 1 diabetes mellitus following SARS-CoV-2 mRNA vaccination.

PURPOSE: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines have been reported to trigger immune side effects. Type 1 diabetes as a manifestation of autoimmune/inflammatory syndrome induced by adjuvants has been reported in a limited number of cases after vaccinations. A few type 1 diabetes cases after SARS-CoV-2 vaccination have been reported. This study aims to report type 1 diabetes cases associated with the mRNA-based SARS-CoV-2 vaccination. METHODS: We report four cases of type 1 diabetes mellitus after mRNA-based SARS-CoV-2 vaccine, BNT162b2 (Pfizer-BioNTech). In the medical history, one subject had autoimmune thyroid disease. All patients had autoantibodies against glutamate decarboxylase. RESULTS: In the presented case series, type 1 diabetes developed a few weeks after BNT162b2 vaccination. After developing type 1 diabetes, the insulin dose requirements of all patients decreased rapidly, and the need for insulin therapy in three patients disappeared during follow-up. Acute deterioration of glucose regulation in a patient followed by BNT162b2 administration may be due to vaccine-induced autoimmune diabetes. CONCLUSION: Vaccination with BNT162b2 may trigger type 1 diabetes.

SARS-CoV-2 Vaccine-induced Thyroiditis: Safety of Revaccinations and Clinical Follow-up.

CONTEXT: The number of reported cases with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine-induced subacute thyroiditis (SAT) and Graves' disease (GD) is growing. However, active debate continues about managing such side effects and the safety of repeat or booster doses of the vaccines in such cases. OBJECTIVES: This study aims to present long-term clinical follow-up of SARS-CoV-2 vaccine-induced SAT or GD cases and provide data regarding the safety of revaccinations. METHODS: Patients diagnosed with SARS-CoV-2 vaccine-induced SAT or GD were included. Data regarding the long-term clinical follow-up of SARS-CoV-2 vaccine-induced SAT and GD cases and outcomes of repeat or booster SARS-CoV-2 vaccinations were documented. The literature, including cases of SARS-CoV-2 vaccine-induced SAT or GD, was reviewed. RESULTS: Fifteen patients with SARS-CoV-2 vaccine-induced SAT and 4 with GD were included. Pfizer/BioNTech COVID-19 vaccine (BNT162b2) was associated with symptoms in a majority of cases with SAT and all with GD. Median time from vaccination to symptom onset was 7 and 11.5 days, respectively, while 7 and 2 patients required medical treatment in SAT and GD groups, respectively. Remission was documented in 10 SAT patients, with a median time to remission of 11.5 weeks. No exacerbation/recurrence of SAT occurred in 7 of 9 patients who received a repeat vaccination dose, while symptoms of SAT worsened following the second vaccination in 2 cases. None of the patients experienced severe side effects that could be associated with revaccinations. CONCLUSIONS: Revaccinations appear to be safe in patients with SARS-CoV-2 vaccine-induced SAT cases, while more evidence is needed regarding SARS-CoV-2 vaccine-induced GD.

Association of Human Leukocyte Antigen Genotypes with Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine-Induced Subacute Thyroiditis.

Background: Despite mass vaccination, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced subacute thyroiditis (SAT) is rarely seen as a complication. The reason why some individuals are susceptible to developing vaccine-induced SAT is not known. SAT develops in genetically predisposed individuals who carry specific human leukocyte antigen (HLA) haplotypes. It is unknown whether specific HLA alleles are associated with SARS-CoV-2 vaccine-induced SAT. Objective: This study compared the HLA profiles of patients with SARS-CoV-2 vaccine-induced SAT to controls, to assess whether there is an association between specific HLA genotypes and development of SAT. The relationship between HLA genotypes and the clinical course of SARS-CoV-2 vaccine-induced SAT was also evaluated. Methods: A case-control study was conducted in a Turkish tertiary care center. Fourteen patients with SARS-CoV-2 vaccine-induced SAT and 100 healthy controls were included. HLA-A, HLA-B, HLA-C, HLA-DQB1, and HLA-DRB1 frequencies were analyzed by next-generation sequencing. Results: The frequencies of HLA-B*35 and HLA-C*04 alleles were significantly higher in SARS-CoV-2 vaccine-induced SAT cohort when compared with controls (HLA-B*35: 13 [93%] vs. 40 [40%], p < 0.001; HLA-C*04: 13 [93%] vs. 43 [43%], p < 0.001, respectively). More severe thyrotoxicosis was seen in patients having HLA-B*35 and HLA-C*04 homozygous alleles (free thyroxine: 4.47 ng/dL [3.77-5.18] vs. 1.41 ng/dL [1.22-2.63], p = 0.048). Inflammation tended to be more severe in homozygous patients (C-reactive protein: 28.2 mg/dL [13.6-42.9] vs. 4.8 [1.2-10.5], p = 0.07). Conclusions: The frequencies of HLA-B*35 and HLA-C*04 alleles were higher in SARS-CoV-2 vaccine-induced SAT compared with controls. Homozygosity for HLA-B*35 and HLA-C*04 was associated with thyrotoxicosis and a greater inflammatory reaction. Our findings should be confirmed in studies of other populations.

Assessment of 4DCT imaging findings of parathyroid adenomas in correlation with biochemical and histopathological findings.

PURPOSE: To assess polar vessel presence and enhancement 4DCT imaging and their relation with biochemical and histopathological features. METHODS: Patients with primary hyperparathyroidism and preoperative 4DCT imaging were screened retrospectively and those with histopathologically proven diagnosis of PA were included. Biochemical findings, densitometric measurements (HUprecontrast, HUarterial, HUvenous, HUwash-in, HUwash-out, HUretained) and CTvolume of PA on 4DCT, presence of a polar vessel (PV), and histopathological features were recorded. Correlations between serum PTH, calcium levels and densitometric measurements of PA on 4DCT were investigated. Differences between subgroups created according to PV presence were also evaluated. RESULTS: Thirty-nine patients were enrolled (F/M = 32/7, median age = 57, interquartile range = 50-62 years). In all patients, serum PTH levels positively correlated with CTvolume (r = 0.398, p = 0.012) but negatively correlated with HUarterial (r = - 0.366; p = 0.022), HUvenous (r = - 0.452; p = 0.004) and HUretained (r = - 0.421; p = 0.008). In PV (-) PAs, PTH levels were positively correlated with CTvolume (r = 0.608, p ≤ 0.002) and negatively with HUarterial (r = - 0.449, p ≤ 0.028), HUvenous (r = - 0.560, p = 0.004), HUwash-in (r = - 0.460, p = 0.024), and HUretained (r = - 0.539, p = 0.007). No correlation between PTH levels and densitometric measurements was found in PV (+) PAs. HUwash-in and HUwash-out were significantly higher in PV (+) PAs compared to PV (-) PAs (p = 0.021 and p = 0.033, respectively). Histopathologic features revealed no difference according to the presence of PV. CONCLUSION: PTH levels might have an association with imaging findings of PAs, especially when categorized with respect to PV presence. PTH levels were negatively correlated with degree of enhancement in PV (-) PAs. Therefore, radiologists should be aware that in patients with high serum PTH levels and without a discernible PV, PA might be difficult to localize.

Clinical Characteristics and Outcomes of COVID-19 Patients with Overweight and Obesity: Turkish Nationwide Cohort Study (TurCObesity).

PURPOSE: While obesity is related to more severe outcomes of coronavirus disease 2019 (COVID-19), factors leading to poor prognosis still remain unclear. The present study evaluated the outcomes of COVID-19 patients who were overweight or obese and variables associated with severe disease in a large group of consecutive cases. METHODS: A nationwide retrospective cohort study was performed using the Turkish National Healthcare Database. Demographic characteristics, laboratory tests, comorbidities, and medications of patients registered between March 11 and May 30, 2020, were recorded. RESULTS: A total of 14, 625 patients (median age:42, IQR:26 years; female 57.4%) with normal weight (34.7%), overweight (35.6%), and obesity (29.7%) were included. Hospitalization, ICU admission, intubation/mechanical ventilation, pulmonary involvement, and mortality were significantly higher in patients who were overweight or obese. In adjusted analyses, both overweight (OR, 95% CI: 1.82, 1.04-3.21; p=0.037) and obesity (OR, 95% CI: 2.69, 1.02-1.05; p<0.001) were associated with a higher intubation/mechanical ventilation rate but only obesity was associated with increased mortality (OR, 95% CI: 2.56, 1.40-4.67; p=0.002). Old age, male gender, chronic kidney disease, and high C reactive protein levels were independently associated with COVID-19 mortality in overweight or obese patients. CONCLUSIONS: COVID-19 patients who were overweight or obese were more likely to have adverse outcomes but only obesity was a predictor of mortality. Such patients should receive urgent medical attention and active management, especially the elderly, men, and people with chronic kidney disease.

Higher rate of COVID-19 mortality in patients with type 1 than type 2 diabetes: a nationwide study.

INTRODUCTION: COVID-19 disease has a worse prognosis in patients with diabetes, but comparative data about the course of COVID-19 in patients with type 1 (T1DM) and type 2 diabetes (T2DM) are lacking. The purpose of this study was to find out the relative clinical severity and mortality of COVID-19 patients with T1DM and T2DM. MATERIAL AND METHODS: A nationwide retrospective cohort of patients with confirmed (PCR positive) COVID-19 infection (n = 149,671) was investigated. After exclusion of individuals with unspecified diabetes status, the adverse outcomes between patients with T1DM (n = 163), T2DM (n = 33,478) and those without diabetes (n = 115,108) were compared by using the propensity score matching method. The outcomes were hospitalization, the composite of intensive care unit (ICU) admission and/or mechanical ventilation, and mortality. RESULTS: The patients with T1DM had higher mortality than the age- and gender-matched patients with T2DM (n = 489) and those without diabetes (n = 489) (p < 0.001). After further adjustment for the HbA1c, and microvascular and macrovascular complications, the odds of mortality (OR: 3.35, 95% CI: 1.41-7.96, p = 0.006) and ICU admission and/or mechanical ventilation (OR: 2.95, 95% CI: 1.28-6.77, p = 0.011) were significantly higher in patients with T1DM compared to those with T2DM. Older age (OR: 1.06, 95% CI: 1.01-1.12, p = 0.028) and lymphopaenia (OR: 5.13, 95% CI: 1.04-25.5, p = 0.045) were independently associated with mortality in patients with T1DM. CONCLUSIONS: Patients with T1DM had worse prognosis of COVID-19 compared to T2DM patients or those without diabetes. These cases should be cared for diligently until more data become available about the causes of increased COVID-19 mortality in T1DM.

Three Cases of Subacute Thyroiditis Following SARS-CoV-2 Vaccine: Postvaccination ASIA Syndrome.

CONTEXT: Autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome) can be seen as a postvaccination phenomenon that occurs after exposure to adjuvants in vaccines that increase the immune responses. There are very limited data regarding ASIA syndrome following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. OBJECTIVES: This work aims to report cases of subacute thyroiditis related to the SARS-CoV-2 vaccine. METHODS: We describe the clinical, laboratory, and imaging features of 3 cases of subacute thyroiditis after inactivated SARS-CoV-2 vaccine (CoronaVac®). Three female healthcare workers have applied to our clinic with anterior neck pain and fatigue 4 to 7 days after SARS-CoV-2 vaccination. Two of them were in the breastfeeding period. They were negative for thyroid antibodies, and there was no previous history of thyroid disease, upper respiratory tract infection, or COVID-19. Laboratory test results and imaging findings were consistent with subacute thyroiditis. RESULTS: SARS-CoV-2 vaccination can lead to subacute thyroiditis as a phenomenon of ASIA syndrome. Subacute thyroiditis may develop within a few days after the SARS-CoV-2 vaccination. Being in the postpartum period may be a facilitating factor for the development of ASIA syndrome after the SARS-CoV-2 vaccination. CONCLUSIONS: This is the first report of subacute thyroiditis as a phenomenon of ASIA syndrome after inactivated COVID-19 vaccination. Clinicians should be aware that subacute thyroiditis may develop as a manifestation of ASIA syndrome after the inactive SARS-CoV-2 vaccine.

Clinical course and management of pembrolizumab-associated isolated adrenocorticotrophic hormone deficiency: a new case and literature review.

Hypophysitis is rarely reported in patients receiving pembrolizumab-only immunotherapies. Since the clinical presentation is usually as isolated adrenocorticotrophic hormone (ACTH) deficiency, patients may be misjudged as having clinical symptoms due to cancer or chemotherapy. A 49-year-old male with laryngeal cancer applied to our clinic just after the tenth cycle of his pembrolizumab treatment, with weakness and nausea/vomiting. Serum morning cortisol and ACTH were 0.47 mcg/dl and 10.1 pg/ml, respectively; the remaining anterior pituitary hormone levels were normal. Pituitary MRI revealed mild glandular enlargement and loss of posterior pituitary bright-spot. All symptoms and signs improved with low-dose prednisolone. This is the second reported case of pembolizumab-associated isolated ACTH deficiency having abnormal pituitary MRI findings as we have reviewed all reported cases in the literature.

Lay abstract Immune check point inhibitors (ICIs) are used in order to enhance antitumoral immune mechanisms in certain cancers. As a result, immune-related side effects have commonly been reported in patients taking ICIs, one of which is hypophysitis. Pembrolizumab is a type of ICI which has rarely been associated with hypophysitis. Since the clinical presentation of pembrolizumab-associated hypophysitis is usually as isolated adrenocorticotrophic hormone deficiency and related cortisol insufficiency, patients may be misjudged as having clinical symptoms due to cancer or chemotherapy, due to shared symptoms such as fatigue, loss of appetite and nausea. Here we have reported a case with pembrolizumab-associated isolated adrenocorticotrophic hormone deficiency and reviewed all other cases available in the literature to improve our understanding of such patients.

Oxysterol species generated by auto-oxidation in subclinical hypothyroidism.

BACKGROUND: Auto-oxidized oxysterols are implicated in the pathogenesis of various chronic diseases. Their concentrations are indicators of oxidative stress in vivo and associated with atherosclerosis. Subclinical hypothyroidism is related with cardiac diseases and oxidative stress, but the exact mechanisms underlying these associations are not clear yet. OBJECTIVE: To investigate the auto-oxidized oxysterols, 7-ketocholesterol (7-KC) and cholestane-3ß,5α,6ß-triol (chol-triol), in patients with subclinical hypothyroidism, as well as to evaluate the impact of restoring euthyroidism on oxysterol concentrations. METHODS: In this prospective observational study, 64 patients with newly diagnosed autoimmune thyroiditis (41 with subclinical hypothyroidism and 23 euthyroidism), and 45 healthy controls were enrolled. Age, gender, and body mass index were matched among patient groups and healthy controls. Anthropometric measurements were obtained and fasting plasma 7-ketocholesterol and cholestane-3ß,5α,6ß-triol concentrations were measured by using liquid chromatography coupled with tandem mass spectrometry. Levothyroxine was then administered to all patients with subclinical-hypothyroidism. After three months, measurements of the oxysterols and serum cholesterols from the patients who have become euthyroid were repeated. RESULTS: Concentrations of 7-ketocholesterol and cholestane-3ß,5α,6ß-triol were significantly higher in patients with subclinical-hypothyroidism when compared to both euthyroid patients and healthy controls (p < 0.001 for both oxysterols). After restoration of euthyroidism, concentrations of 7-ketocholesterol and cholestane-3ß,5α,6ß-triol decreased significantly and reached similar concentrations observed in healthy controls (p < 0.001 for both oxysterols). CONCLUSIONS: Auto-oxidized oxysterol species are higher in patients with mild thyroid dysfunction, and supported the rationale for treating subclinical-hypothyroidism.

Salivary and serum oxidative stress biomarkers and advanced glycation end products in periodontitis patients with or without diabetes: A cross-sectional study.

BACKGROUND: Non-invasive methods for periodontitis diagnosis would be a clinically important tool. This cross-sectional study aimed to investigate the association between oxidative stress, glycation, and inflammation markers and periodontal clinical parameters in periodontitis and periodontally healthy patients with type 2 diabetes and corresponding systemically healthy controls. METHODS: Sixty-seven periodontally healthy (DM-H, n = 32) and periodontitis (DM-P, n = 35) patients with type 2 diabetes, and 54 systemically healthy periodontitis (H-P, n = 26) and periodontally healthy (H-H, n = 28) controls were included. Clinical periodontal parameters, body mass index, fasting glucose, hemoglobin A1c (HbA1c), along with saliva and serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA), 4-hydroxy-2-nonenal (4-HNE), advanced glycation end products (AGE), AGE receptor (RAGE) and high sensitivity C-reactive protein (hsCRP) levels were recorded and analyzed. RESULTS: Salivary 8-OHdG levels were significantly higher in periodontitis compared to periodontally healthy patients, regardless of systemic status (P < 0.001). Salivary MDA levels were significantly higher in all disease groups compared to H-H group (P ≤ 0.004). Serum AGE levels were significantly higher in diabetic groups than systemically healthy groups (P < 0.001) and in H-P compared to H-H (P < 0.001). Bleeding on probing (BOP) and clinical attachment level (CAL) strongly correlated with salivary 8-OHdG and serum hsCRP (P < 0.001). In systemically healthy patients, salivary 8-OHdG was the most accurate marker to differentiate periodontitis from controls (AUC = 0.84). In diabetics salivary 4-HNE and RAGE were the most accurate (AUC = 0.85 for both). CONCLUSION: Salivary 8-OHdG alone or in combination with 4-HNE, AGE and RAGE for diabetics, and salivary 8-OHdG alone or in combination with MDA and hsCRP for systemically healthy persons, could potentially serve as non-invasive screening marker(s) of periodontitis.

Clinical outcomes of non-diabetic COVID-19 patients with different blood glucose levels: a nationwide Turkish study (TurCoGlycemia).

PURPOSE: New coronavirus disease 2019 (COVID-19) has a worse prognosis in patients with diabetes. However, there are insufficient data about the effect of hyperglycemia on COVID-19 prognosis in non-diabetic patients. This study aimed to investigate the relationship between random blood glucose levels measured at the time of diagnosis and prognosis of COVID-19 disease in non-diabetic patients. METHODS: A nationwide retrospective cohort of non-diabetic patients with confirmed COVID-19 infection from 11 March to 30 May 2020 in the Turkish Ministry of Health database was investigated. The patients were stratified into three groups according to blood glucose levels which were <100 mg/dL in group-1, in the range of 100-139 mg/dl in group-2, and the range of 140-199 mg/dl in group-3. Clinical characteristics and outcomes were compared among the groups. The primary outcome was mortality. RESULTS: A total of 12,817 non-diabetic patients (median age [IQR]: 44 [25] years, females: 50.9%) were included. Patients in group-2 (5%) and group-3 (14%) had higher mortality rates than patients in group-1 (2.1%). The rates of hospitalization, hospital stays longer than 8 days, intensive care unit (ICU) admission, ICU stay more than 6 days, and mechanical ventilation were also significantly higher in group-3 patients. Likewise, glucose levels in the range of 140-199 mg/dL were an independent associate of mortality and composite of ICU admission and/or mechanical ventilation. CONCLUSION: Hyperglycemia at the time of COVID-19 diagnosis is associated with poor prognosis in non-diabetic patients. Clinicians should be more careful in the treatment of non-diabetic COVID-19 patients with hyperglycemia.