The effect of COVID-19 pandemic restrictions on the management of differentiated thyroid cancer in Turkey: a single tertiary centre experience.

PURPOSE: Many countries have implemented unprecedented health measures since the World Health Organisation declared the novel coronavirus disease 2019 (COVID-19) a global pandemic. These measures have resulted in delays in the diagnosis of differentiated thyroid cancer (DTC). However, there is limited data on the impact of restrictions imposed during the pandemic on DTC management. Thus, the aim of this study is to analyse the clinicopathological and follow-up data of DTC patients diagnosed before and during the COVID-19 outbreak. METHODS: This retrospective study included 191 DTC patients that were diagnosed between December 2018 and June 2021. The patients were divided into two groups: patients diagnosed before (December 2018 to February 2020) and during (March 2020 to June 2021) the COVID-19 pandemic. The clinicopathological and follow-up data between the two groups were compared. RESULTS: Similar preoperative cytology results were obtained from the two groups. No difference with regard to tumour size, lymphovascular invasion and extrathyroidal invasion was observed between the two groups. While the American Thyroid Association risk stratification was similar between the two groups, radioactive iodine (RAI) therapy was applied less during the COVID-19 period. Although RAI therapy was administered at a lower rate during the COVID-19 period, the recurrence rates among patients after two years of follow-up were similar to those during the pre-COVID-19 period. CONCLUSION: Although the COVID-19 pandemic restrictions during the pandemic period caused difficulties in the management of DTC patients, this did not negatively affect their prognosis. These findings can confirm the applicability of active surveillance in DTC patients and may help change the real-life treatment practices in selected low-risk DTC patients.

Relapsed and newly diagnosed Graves' disease due to immunization against COVID-19: A case series and review of the literature.

In addition to genetic factors, environmental factors such as viruses are thought to be triggers in the development of autoimmune thyroid diseases (AITD) such as Graves' disease (GD). In this context, AITD cases that may be associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or immunization have begun to be reported in increasing numbers. Although it is not clear by which pathogenetic mechanisms immunization against coronavirus disease 2019 (COVID-19) triggers the development of AITD, both the potential effect of the adjuvants in the vaccines and the cross-reactivity that can be generated by the molecular similarity of viral particles with mammalian proteins seem to be possible mechanisms. In this article, 7 GD patients consisting of relapsed and newly diagnosed cases following the COVID-19 vaccination were presented. Of these 7 cases, 5 (71.4%) were female, and the median age of the patients was 47 years (range, 31-53). One of the patients was associated with the inactivated COVID-19 vaccine, while the others were associated with the mRNA COVID-19 vaccine. The median post-vaccination symptom onset was 7 days (range, 4-30). Three of the patients had a history of GD and one had a history of Hashimoto's thyroiditis. Rapidly developing Graves' ophthalmopathy was detected in one patient. These cases are cautionary that GD and its extrathyroidal manifestations may develop in a short period after COVID-19 vaccination. When considered together with the literature review, the history of AITD in approximately half of the patients suggests that more attention should be paid to these patients in the post-vaccination period. Nevertheless, multicenter, prospective studies are needed to better understand this possible causal relationship.

The predictive value of hematologic parameters in the risk of thyroid malignancy in cases with atypia/follicular lesion of undetermined significance.

BACKGROUND: Atypia/follicular lesion of undetermined significance (AUS/FLUS) is still the most challenging category in the Bethesda System for Reporting Thyroid Cytopathology. Therefore, the aim of the current study was to investigate the value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV) in predicting malignancy in cases with AUS/FLUS nodules. METHODS: A total of 200 patients with AUS/FLUS nodules who underwent thyroidectomy were included in this study. Preoperative hemogram parameters, ultrasonographic findings, fine-needle aspiration results, and postoperative final histopathological diagnoses of the patients were recorded retrospectively. RESULTS: Thyroid malignancies were detected in 122 of the patients (61.0%). Patients in the benign group (BG) were older than those in the malignancy group (MG) (52.0 ± 11.3 vs. 45.9 ± 12.3 years, p < 0.001). The median TSH values of the two groups were comparable. Statistically significant differences were obtained between the two groups in respect of mean WBC of 7.53 ± 1.44 in MG and 6.87 ± 1.35 (103/mm3) in BG, mean neutrophil of 4.65 ± 1.12 in MG and 3.95 ± 0.99 (103/mm3) in BG, and median NLR of 2.18 (0.71-4.57) in MG and 1.75 (0.80-3.42) in BG (p < 0.001). The median PLR and MPV values of the two groups were similar. When NLR cut-off point was designated as 2.24, the accuracy of NLR in distinguishing malignancy from the benign condition was 0.65 in ROC analysis (area under the curve, 0.665; specificity, 0.808; sensitivity, 0.492). CONCLUSION: High NLR values may provide limited help in predicting thyroid malignancy in the AUS/FLUS nodule population, while PLR and MPV are not reliable parameters.

The Effects of Chronic Lymphocytic Thyroiditis on Clinicopathologic Factors in Papillary Thyroid Cancer.

OBJECTIVE: This study evaluated the impact of chronic lymphocytic thyroiditis (CLT) on clinicopathologic parameters, prognostic outcome, and initial treatment responses in patients with papillary thyroid cancer (PTC). METHODS: A retrospective review was conducted of 1409 patients with PTC, comprising 443 patients with pathology-proven PTC with CLT and 447 patients with PTC without CLT. RESULTS: The median follow-up time was 58 months (range, 8-380 months), and the median age at the time of diagnosis was 43 years. The age at diagnosis was significantly lower in patients with CLT than in those without CLT (42 years vs 45 years, respectively; P = .001). The preoperative thyroid-stimulating hormone level was found to be significantly higher in patients with CLT than in those without CLT (1.71 mIU/L vs 1.28 mIU/L, respectively; P < .001). Multifocality and capsular, lymphovascular, and perineural invasion were detected at a higher rate in the group with CLT than in the group without CLT (P = .015, P = .024, P = .004, and P = .039, respectively). No difference was found between the 2 groups in terms of tumor size, bilaterality, extrathyroidal invasion, lymph node metastasis, disease stage, or response to treatment (P > .05). CONCLUSION: The results of the present study demonstrated that the coexistence of PTC and CLT is very frequent. Patients with the coexistence of PTC and CLT were diagnosed at a younger age, and the thyroid-stimulating hormone level was higher in these patients. Contrary to previous studies, no positive effect of the CLT and PTC combination was detected on any clinicopathologic factor. In addition, lymphovascular and perineural invasions, which had negative effects on prognosis, were more common in the group with CLT.

The Evaluation of Low- and High-Dose Steroid Treatments in Subacute Thyroiditis: A Retrospective Observational Study.

OBJECTIVE: The optimal steroid regimen in the treatment of subacute thyroiditis (SAT) is controversial. This study aims to compare low- and high-dose steroid regimens in the treatment of SAT. METHODS: A single-center, retrospective observational cohort study with up to 1 year of follow-up was conducted. A total of 44 patients in the 16-mg methylprednisolone (MPS) group and 47 patients in the 48-mg MPS group were enrolled. Clinical and laboratory findings from the time of diagnosis to 1-year of the follow-up were assessed. Treatment response, recurrence, and hypothyroidism (HPT) rates were evaluated. RESULTS: Clinical symptoms, sedimentation rates, C-reactive protein, and thyroid hormone levels of the patients were similar in the 2 groups. Recovery was achieved in all patients at the end of the treatments; however, treatment duration needed to be extended for 6 (13.6%) and 1 (2.1%) of the patients in the 16-mg and 48-mg MPS groups, respectively. The 48-mg MPS group had a higher SAT recurrence rate than the 16-mg MPS group (P = .04). Logistic regression analysis suggested that a lower thyroid-stimulating hormone level at the end of the treatment was a predictor of recurrence (ß = -0.544, P = .014, 95% CI: 0.376-0.895). While the transient HPT rate was 10 (21.3%) and 10 (22.7%) in the 48-mg and 16-mg MPS groups, respectively, a permanent HPT developed in 5 (10.6%) of patients in the 48-mg MPS and 3 (6.8%) in the 16-mg MPS group. The permanent and transient HPT rates were determined to be similar in the low- and high-dose groups (P > .05). CONCLUSION: Low-dose steroid therapy may be sufficient to achieve a complete recovery and better outcomes in SAT.

The visceral adiposity index, lipid accumulation product, and plasma atherogenic index are associated with subclinical atherosclerosis in patients with newly diagnosed acromegaly.

BACKGROUND: Acromegaly is a rare chronic endocrine disorder, the active form of which is associated with an increased risk of cardiovascular and metabolic disease. Therefore, early diagnosis and treatment of cardiovascular diseases in acromegaly patients are important in terms of morbidity and mortality. The aim of this study was to determine whether the visceral adiposity index (VAI), lipid accumulation product (LAP), and plasma atherogenic index (PAI) are early cardiovascular risk markers in patients with active acromegaly. METHODS: The study included 45 patients newly diagnosed with acromegaly and 45 age-sex matched healthy control subjects. The VAI, LAP, and PAI values were calculated, and carotid artery intima media thickness (CIMT) was measured in both the patients and control groups. RESULTS: The PAI, VAI, LAP, and CIMT values were significantly higher in patients with acromegaly compared with the control subjects (p < 0.004, p < 0.027, p <0.012, and p <0.001, respectively). In the patient group, a significant positive correlation was found between the growth hormone (GH) and insulin-like growth factor I (IGF-I) levels, and between the VAI, LAP and PAI values. A significant positive correlation was determined between CIMT and LAP values in the patient group. DISCUSSION: CIMT is a noninvasive method used to show early atherosclerosis. However, it is operator dependent. Therefore, VAI, LAP and PAI can be used as noninvasive, simple measurement methods to evaluate early atherosclerosis in patients with acromegaly.

Evaluation of serum anti-Müllerian hormone levels in women with Hashimoto thyroiditis in the reproductive age

Background/aim: Autoimmune thyroid disease in women is associated with subfertility and early pregnancy loss, and patients with primary ovarian insufficiency have a high prevalence of thyroid autoimmune disorders. The aim of this study was to investigate the association between Hashimoto thyroiditis (HT) and ovarian reserve. Materials and methods: Levels of serum thyroid stimulating hormones, thyroid autoantibodies, and anti-Müllerian hormone (AMH) were measured in women with HT and a healthy control group between 2018 and 2019. Results: Evaluation was made of 108 premenopausal women with HT, and a control group of 172 healthy females with normal antithyroid antibody levels and thyroid function. Serum AMH levels were determined to be significantly lower in the HT group compared to the control group. Conclusion: Ovarian reserve evaluated by serum AMH concentration is affected by thyroid autoimmunity independently of antithyroid antibodies type or titers.

The diagnostic value of elastography score and strain index for the evaluation of thyroid micronodules

Background/aim: In the general population, the frequency of thyroid micronodules is increasing, and the prevalence of malignancy is higher for such nodules. Ultrasonography findings of these nodules are neither specific nor sensitive. The aim of this study was to investigate the diagnostic value of elastography in patients with thyroid micronodules. Materials and methods: A total of 224 patients with thyroid micronodules were recruited in this prospective study. All patients underwent a thyroid fine-needle aspiration biopsy. Elastography scores (ESs) and strain indexes (SIs) were measured with real-time ultrasound elastography. Results: Malignant micronodules had higher ES and SI values than those of benign micronodules (P < 0.001). When ES was used to diagnose malignancy, scores of >3 showed sensitivity of 79.4% and specificity of 98.1%. The area under the curve (AUC) for ES was 0.888 (P < 0.001). The optimal SI cutoff value that differentiated benign from malignant micronodules was 3.06 (98% sensitivity; 91% specificity). The AUC for SI was 0.970 (P < 0.001). Conclusions: ES and SI are beneficial markers for detecting malignant thyroid micronodules. We showed that SI is better than ES when assessing the malignancy of thyroid micronodules.

Evaluation of psoriasis patients with long-term topical corticosteroids for their risk of developing adrenal insufficiency, Cushing's syndrome and osteoporosis.

PURPOSE: In this study, we will investigate the possible side effects of psoriasis patients using long-term topical corticosteroids (TCS) such as adrenal insufficiency, Cushing's Syndrome (CS) and osteoporosis and determine how these side effects develop. MATERIAL AND METHODS: Forty-nine patients were included in the study. The patients were divided into two groups based on the potency of the topical steroid they took and the patients' ACTH, cortisol and bone densitometer values were evaluated. RESULTS: There was no significant difference between the two groups regarding the development of surrenal insufficiency, CS and osteoporosis. One patient in group 1 and 4 patients in group 2 were evaluated as iatrogenic CS. ACTH stimulation tests of these patients in group 2 showed consistent results with adrenal insufficiency, while no adrenal insufficiency was detected in the patient in Group 1. Patients who used more than 50g of superpotent topical steroids per week compared to patients who used 50g of superpotent topical steroids per week. It was identified that patients who used more than 50g of superpotent topical steroids had significantly lower cortisol levels, with a negatively significant correlation between cortisol level and the amount of topical steroid use (p < .01).Osteoporosis was detected in 3 patients in group 1 and 8 patients in Group 2. Because of the low number of patients between two groups, statistical analysis could not be performed to determine the risk factors. CONCLUSIONS: Our study is the first study that we know of that investigated these three side effects. We have shown that the development of CS, adrenal insufficiency and osteoporosis in patients who use topical steroids for a long time depends on the weekly TCS dosage and the risk increases when it exceeds the threshold of 50 grams per week. therefore, our recommendation would be to avoid long-term use of superpotent steroids and to choose from the medium-potent group if it is to be used.

Impact of the COVID-19 pandemic on the incidence, seasonal distribution, and characteristics of subacute thyroiditis.

PURPOSE: An increasing number of cases of subacute thyroiditis (SAT) related to the coronavirus disease 2019 (COVID-19) and its vaccines continue to be published. The aim of this study was to investigate any change in the incidence and characteristics of SAT by comparing the pre-pandemic and pandemic periods. METHODS: This retrospective, single-center study included 432 newly-diagnosed SAT patients between January 2018 and December 2021. The annual frequency of SAT was calculated as the number of newly-diagnosed SAT cases divided by the total number of outpatients that year. RESULTS: The frequencies of newly-diagnosed SAT were 0.136% in 2018, 0.127% in 2019, 0.157% in 2020, and 0.114% in 2021 (p = 0.19). While SAT patients were clustered in the autumn (35.1%) in 2018 and 2019, it was found that this cluster shifted to the winter (33.0%) in 2020 and 2021, in parallel with COVID-19 case peaks (p = 0.017). The patients were separated into two groups as pre-COVID-19 pandemic SAT (n = 272) and COVID-19 pandemic SAT (n = 160). The mean ages of the groups were similar. There were more male patients in the COVID-19 pandemic SAT group than in the pre-pandemic group (30.6% vs. 18.7%, p = 0.005). Frequencies of overt hyperthyroidism and median free-thyroxine levels were significantly higher in the COVID-19 pandemic SAT group (p = 0.029, p = 0.001). Treatment modalities, recurrence rates, and permanent hypothyroidism were similar in both groups. CONCLUSION: With the COVID-19 pandemic, although there was a change in seasonal variation of SAT and an increase in the number of male patients, there was no change in the incidence and clinical course of SAT.

Evaluation of the diagnostic features and clinical course of COVID-19 vaccine-associated subacute thyroiditis.

OBJECTIVE: This study aimed to identify cases of coronavirus disease 2019 (COVID-19) vaccine-associated subacute thyroiditis (SAT) during the active vaccination period of the pandemic, analyze the characteristics of these cases, and compare them with cases of non-vaccine associated SAT diagnosed in the same period. METHODS: A total of 55 patients diagnosed with SAT in our outpatient clinic between February and October, 2021, were included in this retrospective single-center study. RESULTS: Of the study population, 16 (29.1%) were diagnosed with COVID-19 vaccine-associated SAT (10 with CoronaVac® and six with Pfizer-BioNTech® vaccine), with a median time to onset of symptoms after vaccination of 6.5 (range, 2-20) days. There was no statistically significant difference between the vaccine-associated (VA) and non-vaccine associated (NVA) groups in terms of age, gender, time to diagnosis, thyroid volumes, thyroid function tests, and acute phase reactants. Seven (43.8%) and 25 (64.1%) patients were treated with methylprednisolone in the VA group and NVA group, respectively (p = 0.16). Follow-up data of 45 patients (16/16 for VA and 29/39 for NVA) were available. The mean follow-up of these patients was 47.4 ± 19.4 days, and the follow-up periods of the VA group and NVA group were comparable (p = 0.24). There was no difference between the two groups in terms of the frequency of euthyroidism at the follow-up visit (12/16 vs.14/29, p = 0.08). CONCLUSION: With the increase in COVID-19 vaccination rates during the current pandemic, VA SAT cases are seen more frequently. The present study demonstrated that these cases have similar diagnostic features and clinical course to that of classic forms of SAT. In addition, most patients with VA SAT had a mild clinical course that improved with non-steroidal anti-inflammatory drugs.

The value of routine measurement of serum calcitonin on insufficient, indeterminate, and suspicious thyroid nodule cytology.

Routine calcitonin measurement in patients with nodular thyroid disease is rather controversial. The aim of this study was to evaluate the contribution of serum calcitonin measurement in the diagnostic evaluation of thyroid nodules with insufficient, indeterminate, or suspicious cytology. Out of 1668 patients who underwent thyroidectomy with the diagnosis of nodular thyroid disease and were screened, 873 patients with insufficient, indeterminate, or suspicious fine needle aspiration biopsy results were included in the study. From the total number of patients in this study, 10 (1.1%) were diagnosed as medullary thyroid cancer (MTC) using histopathology. The calcitonin level was detected to be above the assay-specific cut-off in 23 (2.6%) patients ranging between 6.5 - 4450 pg/mL. While hypercalcitoninemia was detected in all 10 MTC patients, a false positive elevation of serum calcitonin was detected in 13 patients (1.5%). Of the MTC group, 7 patients had cytology results that were suspicious for malignancy (Bethesda V), one patient's cytology showed atypia of undetermined significance (Bethesda III) and two patient's cytology results were suspicious for follicular neoplasm (Bethesda IV). Among the cases with non-diagnostic cytology (Bethesda I), none of the patients were diagnosed with MTC. In conclusion, routine serum calcitonin measurement can be performed in selected cases rather than in all nodular thyroid patients. While it is reasonable to perform routine calcitonin measurement in patients with Bethesda IV and Bethesda V, this measurement was not useful in Bethesda I patients. In Bethesda III patients, patient-based decisions can be made according to their calcitonin measurement.

Two Important Issues in Subacute Thyroiditis Management: Delayed Diagnosis and Inappropriate Use of Antibiotics.

BACKGROUND: Subacute thyroiditis (SAT) is a rare inflammatory disease of the thyroid gland. It has been noticed that patients with a diagnosis of SAT visit more other clinics and receive antibiotics unnecessarily. Therefore, the aim of this study was to reveal the degree of delay in the diagnosis of SAT, prediagnosis antibiotic use rates, and the awareness of clinics for the diagnosis of SAT. METHODS: A total of 121 patients with SAT were enrolled in the study. A retrospective analysis was made of the history of patient symptoms during the diagnosis, which physicians they visited, antibiotic use, laboratory test results, and ultrasonographic findings. RESULTS: The median age of the patients was 41 years. Neck pain radiating to the jaw/ear was seen in most patients (71.1%). The median time from symptom onset to a diagnosis of SAT was 23 days (range, 6-70 days). Antibiotics were erroneously prescribed to 71 patients (58.7%) before the diagnosis. The median time to diagnosis was 28 days in patients using antibiotics and 20 days in the group not using antibiotics (p < 0.001). Two or more physicians had been visited before SAT diagnosis by 89 (73.6%) patients, and more antibiotics were prescribed to these patients than the group who visited fewer physicians (p < 0.05). The frequency of prescribing antibiotics by physicians was 73.7% by emergency physicians, 53.1% by family doctors, 51.1% by ENT specialists, and 35.4% by internal medicine specialists. CONCLUSION: The diagnosis of SAT is often delayed, and misdiagnosis leads to erroneous antibiotic overuse. Physicians should increase their awareness of the diagnosis of SAT in patients with neck pain.

The prognostic and diagnostic use of hematological parameters in subacute thyroiditis patients.

BACKGROUND: Subacute thyroiditis (SAT) is an acute inflammatory disease of the thyroid. Mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) values determined from peripheral blood, are accepted as available and practical indicators of systemic inflammation. The purpose of this study was to evaluate the value of hematological parameters in the diagnosis and prognosis of subacute thyroiditis patients. METHODS: This retrospective study included 306 SAT patients and 102 healthy control subjects. Retrospective analyses were made of age, gender, complete blood counts, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), thyroid function tests, NLR, PLR, and thyroid volume of the patients and the results were compared with the control group. RESULTS: The mean follow-up time of patients was 29.5 ± 14 months. The ESR, CRP, white blood cell (WBC) count, neutrophil count, hemoglobin, platelet counts, NLR, and PLR were significantly higher in the SAT patients. MPV and lymphocyte count were significantly lower in the SAT patients. The rates of recurrence and permanent hypothyroidism were 15.4% and 9.8%, respectively. The values of ESR, CRP, NLR, PLR, and MPV at the time of diagnosis were not determined to have any effect on recurrence or the development of permanent hypothyroidism. CONCLUSIONS: The results of this study showed higher PLR and NLR values in SAT patients compared with healthy control subjects, and a lower MPV value. These findings demonstrate that the assessment of hematological parameters in conjunction with radiological and clinical findings will assist in establishing an accurate diagnosis, especially in complicated SAT cases.

Insulin-like growth factor 1, liver enzymes, and insulin resistance in patients with PCOS and hirsutism.

AIM: Hyperinsulinemia and insulin resistance are commonly seen in patients with hirsutism and polycystic ovary syndrome (PCOS), and are associated with cardiovascular disease risk. However, it is not yet known whether insulin-like growth factor I (IGF-I) and alanine transaminase (ALT) produced by the liver play roles in hyperinsulinemia and subclinical atherosclerotic process in patients with PCOS and idiopathic hirsutism (IH). MATERIALS AND METHODS: This was a prospective case-controlled study. The study population consisted of 25 reproductive-age PCOS women, 33 women with IH, and 25 control subjects. RESULTS: Mean IGF-I levels and median ALT levels were higher in patients with IH and PCOS than controls, but these differences were not statistically significant. The participants who had a homeostasis model assessment insulin resistance index (HOMA-IR) greater than 2.7 had significantly higher IGF-1 and ALT levels. ALT levels were positively correlated with body mass index, FG, insulin and HOMA-IR. CONCLUSION: The study illustrated that IGF-1 and ALT levels were significantly higher in patients with increased insulin resistance. Due to short disease duration in younger participants, we did not observe any correlation between IGF-1 and hyperinsulinemia. These findings suggest that increased hepatic production of IGF-I and ALT might be an early indicator of insulin resistance in hirsutism.