The prevalence and associated risk factors of detectable renal morphological abnormalities in acromegaly.

PURPOSE: The aim of this study was to investigate the prevalence of simple renal cysts (SRCs) and kidney stone disease (KSD) together with laboratory data in patients with acromegaly through comparisons with healthy subjects, and to examine the possible risk factors associated with these abnormalities in acromegaly. METHODS: This retrospective, single-center study included 125 acromegaly patients (46.4 ± 11.6 years, 68 females/57 males) and 114 age-sex matched healthy individuals (45.3 ± 12.4 years, 59 females/55 males). Demographic data, clinical history, biochemical and abdominal/urinary system ultrasonographic data of the patients were reviewed. RESULTS: The SRC prevalence (28.8% vs. 8.8%, p < 0.001) and the longitudinal and transverse lengths of kidneys (p < 0.05) were significantly higher in patients with acromegaly compared to the control group. The presence of acromegaly was determined to increase the risk of SRC formation 12.8-fold. The prevalence of KSD was similar in both the patient and control groups (15.2% vs. 7.9%, p = 0.08). Patients with acromegaly with renal cysts (n = 36) compared to the group without cysts (n = 89) were older, had a higher male gender frequency, a longer pre-diagnosis symptom duration, and a higher incidence of hypertension and diabetes mellitus at the time of diagnosis. The multivariate logistic regression analysis showed that only advanced age and male gender were associated risk factors for SRCs in acromegaly patients. CONCLUSION: The results of this study showed that acromegaly disease significantly increased the prevalence of SRCs and kidney length compared to the age-sex matched healthy population, while the prevalence of KSD was similar. Advanced age and male gender were seen to be independent risk factors for SRC formation in patients with acromegaly.

Hypomagnesemia may be associated with symptomatic disease in patients with primary hyperparathyroidism.

AIM: Magnesium (Mg) homeostasis is closely related to calcium (Ca) metabolism. Hypercalcemia inhibits the reabsorption of Mg from the kidneys, leading to hypomagnesemia. Therefore, patients with primary hyperparathyroidism (PHPT) are predisposed to hypomagnesemia. However, there are few studies on the clinical significance of hypomagnesemia in PHPT. The aim of this study was to retrospectively evaluate the association of hypomagnesemia with the clinical outcomes of PHPT. MATERIALS AND METHODS: A retrospective evaluation was made of the data of 538 consecutive patients (478 females, 60 males) diagnosed with PHPT in our center. RESULTS: The mean age of the study population was 56.5 ± 11.66 years. The mean serum Mg level was 2 ± 0.26 mg/dl. Asymptomatic disease was present in 241 (44%) patients. Symptomatic patients with osteoporosis, Ca level ≥11.2 mg/dl, and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 had lower levels of Mg (p < 0.05). Hypomagnesemia was detected in 129 of 538 patients (23.9%). The patients with hypomagnesemia had a higher rate of symptomatic disease (80% vs. 48%, p < 0.0001). The serum parathormone (PTH) level was found to be higher in patients with hypomagnesemia and the lumbar and femur T-scores and serum vitamin D levels were lower (p < 0.05). Patients with hypomagnesemia had higher rates of kidney stones (34% vs. 21%, p = 0.003) and osteoporosis (74% vs. 32%, p < 0.001). Multivariate logistic regression analysis revealed that hypomagnesemia had a significant effect on the development of symptomatic disease (OR:6.88, CI 95%: 5.20-11.27, p < 0.001). CONCLUSIONS: The current study results demonstrate that hypomagnesemia may be associated with a higher risk of osteoporosis and kidney stones in PHPT patients. Routine evaluation of serum Mg may predict the clinical outcomes of PHPT.

Subacute THYROiditis Related to SARS-CoV-2 VAccine and Covid-19 (THYROVAC Study): A Multicenter Nationwide Study.

CONTEXT: The aims of the study are to compare characteristics of subacute thyroiditis (SAT) related to different etiologies, and to identify predictors of recurrence of SAT and incident hypothyroidism. METHODS: This nationwide, multicenter, retrospective cohort study included 53 endocrinology centers in Turkey. The study participants were divided into either COVID-19-related SAT (Cov-SAT), SARS-CoV-2 vaccine-related SAT (Vac-SAT), or control SAT (Cont-SAT) groups. RESULTS: Of the 811 patients, 258 (31.8%) were included in the Vac-SAT group, 98 (12.1%) in the Cov-SAT group, and 455 (56.1%) in the Cont-SAT group. No difference was found between the groups with regard to laboratory and imaging findings. SAT etiology was not an independent predictor of recurrence or hypothyroidism. In the entire cohort, steroid therapy requirement and younger age were statistically significant predictors for SAT recurrence. C-reactive protein measured during SAT onset, female sex, absence of antithyroid peroxidase (TPO) positivity, and absence of steroid therapy were statistically significant predictors of incident (early) hypothyroidism, irrespective of SAT etiology. On the other hand, probable predictors of established hypothyroidism differed from that of incident hypothyroidism. CONCLUSION: Since there is no difference in terms of follow-up parameters and outcomes, COVID-19- and SARS-CoV-2 vaccine-related SAT can be treated and followed up like classic SATs. Recurrence was determined by younger age and steroid therapy requirement. Steroid therapy independently predicts incident hypothyroidism that may sometimes be transient in overall SAT and is also associated with a lower risk of established hypothyroidism.

The role of elastography in the assessment of thyroid nodules in acromegaly.

BACKGROUND: Nodular thyroid disease is a frequent finding seen in patients with acromegaly. Ultrasound-elastography (US-E) appears to be a helpful tool for the diagnosis of thyroid cancer. The aims of this study were to evaluate thyroid nodules in acromegaly and to assess the diagnostic accuracy of US-E in detecting thyroid cancer in this population. METHODS: US-E was applied to 166 nodules detected in 102 acromegalic patients and to 105 nodules found in 95 nonacromegalic subjects. The lesions were classified according to the elasticity scores (ES) as soft (ES 1-2) or hard (ES 3-4). RESULTS: : Mean age was 55.1 ± 12.47 years [59 (58%) women]. The prevalence of hard nodules (ES 3 and 4) was significantly higher in the group of acromegalic patients than in control subjects (48% to 20%, p < 0.001). Mean ES was higher in patients with acromegaly (2.45 to 2.22, p: 0.001), however, the mean strain index (SI) was similar between groups (1.53 to 1.65, p: 0.204). DISCUSSION: Thyroid nodules in acromegaly patients have a higher elasto score and the prevalence of hard nodules is higher in active disease. However, increased stiffness of nodules by US-E in patients with acromegaly does not seem to estimate the malignancy of the nodules.

Real-time detection of acromegaly from facial images with artificial intelligence.

OBJECTIVE: Despite improvements in diagnostic methods, acromegaly is still a late-diagnosed disease. In this study, it was aimed to automatically recognize acromegaly disease from facial images by using deep learning methods and to facilitate the detection of the disease. DESIGN: Cross-sectional, single-centre study. METHODS: The study included 77 acromegaly (52.56 ± 11.74, 34 males/43 females) patients and 71 healthy controls (48.47 ± 8.91, 39 males/32 females), considering gender and age compatibility. At the time of the photography, 56/77 (73%) of the acromegaly patients were in remission. Normalized images were obtained by scaling, aligning, and cropping video frames. Three architectures named ResNet50, DenseNet121, and InceptionV3 were used for the transfer learning-based convolutional neural network (CNN) model developed to classify face images as "Healthy" or "Acromegaly". Additionally, we trained and integrated these CNN machine learning methods to create an Ensemble Method (EM) for facial detection of acromegaly. RESULTS: The positive predictive values obtained for acromegaly with the ResNet50, DenseNet121, InceptionV3, and EM were calculated as 0.958, 0.965, 0.962, and 0.997, respectively. The average sensitivity, specificity, precision, and correlation coefficient values calculated for each of the ResNet50, DenseNet121, and InceptionV3 models are quite close. On the other hand, EM outperformed these three CNN architectures and provided the best overall performance in terms of sensitivity, specificity, accuracy, and precision as 0.997, 0.997, 0.997, and 0.998, respectively. CONCLUSIONS: The present study provided evidence that the proposed AcroEnsemble Model might detect acromegaly from facial images with high performance. This highlights that artificial intelligence programs are promising methods for detecting acromegaly in the future.

Effect of thyroid nodule size on cytology reliability and incidence of malignancy: A large cohort of 1205 patients from a single center.

OBJECTIVE: There is controversy about whether the rates of malignancy and of false-negative malignancy are greater in large nodules. The aim of this study was to determine the reliability of cytology in ≥4cm nodules and to compare malignancy rates between ≥4cm and<4cm nodules. METHODS: The study included 1205 patients who underwent biopsy and subsequent thyroidectomy with the diagnosis of nodular thyroid disease between 2014 and 2019. The patients were separated into two groups, ≥4cm and<4cm, according to the size of the index nodule on ultrasonography. RESULTS: Two hundred and eleven index nodules (17.5%) were ≥4cm. Malignancy rate on definitive pathology was 51% in<4cm nodules and 30% in ≥4cm nodules. Malignancy risk was significantly lower in ≥4cm nodules than <4cm nodules (P<0.001). When<1cm nodules were excluded and 1-4cm and ≥4cm nodules were compared, malignancy risk was also significantly lower in ≥4cm nodules (P=0.001). On definitive pathology, there were 45 false-negative results among cytologically benign nodules. There was no difference in false-negative cytology rate between<4cm and ≥4cm nodules (P=0.209). CONCLUSION: The present study found no decrease in the reliability of cytology in ≥4cm nodules, and there may not be a linear relationship between nodule size and malignancy risk. Therefore, in asymptomatic cytologically benign ≥4cm nodules, surgery may not be recommended based on nodule size alone.

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.

Paradoxical GH increase during oral glucose load may predict overall remission in acromegalic patients.

BACKGROUND: The nadir growth hormone (nGH) during the oral glucose tolerance test (OGTT) is the gold standard method for diagnosing acromegaly. A paradoxical growth hormone (GH) response to oral glucose (OG) in acromegaly can be observed. The role of the paradoxical GH response on how the patients with acromegaly respond to the treatment has been addressed in few studies. The aim of this study was to investigate the association between glucose-dependent growth hormone results and and the responses of acromegalic patients to surgical and/or medical therapy following surgery. MATERIAL AND METHODS: This retrospective cohort study included patients with acromegaly who underwent surgery (n = 189) or received primary medical treatment (n = 9). The mean age was 50.44 ± 12.81 years (M/F: 84/114). The patients were grouped into paradoxical (GH-P) and non-paradoxical (GH-nP) according to GH response to OG and were compared in terms of clinical and pathological features, pituitary tumor size, invasiveness, biochemical profiles, and how they responded to the treatment. RESULTS: The mean age, gender distribution, and basal tumor diameter were all similar in both groups (p > 0.05). The GH-P group had a higher remission rate in response to medical therapy followed by surgery (83% vs. 55%; p = 0.026). Although a higher surgical remission rate in favor of GH-P was observed, it did not reach statistical significance (63% vs. 48%; p = 0.059). Overall treatment response rates were also higher in the GH-P group compared to the GH-nP group (89% vs. 71%; p = 0.005). CONCLUSION: A paradoxical GH response to OG load may help to predict the response to medical treatment in patients with acromegaly.

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.

Efficacy of cabergoline add-on therapy in patients with acromegaly resistance to somatostatin analogs treatment and the review of literature

ABSTRACT Objective: It is reported that adding cabergoline to somatostatin analog (SSA) normalizes IGF-1 levels approximately in one-third of patients with acromegaly. We investigated the effect of combination therapy and potential predictors of response in patients with acromegaly who do not respond to SSA therapy alone. Subjects and methods: Fifty acromegaly patients (M/F 23/27, mean age 50.88 ± 12.34 years) were divided into two groups as the active and control groups in this connection. Before and after treatment, we not only evaluated serum GH and IGF-1 levels and tumor size but also analyzed the factors relevant to the effect of the combined therapy. Results: Adding cabergoline to SSA treatment led to IGF-1 normalization in 42% (21/50) of patients. Mean GH levels decreased from 2.64 ± 1.79 to 1.34 ± 0.99 ng/mL (p < .0001) and IGF-1 levels decreased from 432.92 ± 155.61 to 292.52 ± 126.15 ng/mL (p < .0001). GH and IGF-1 reduction in percent (%) were significantly higher in the controlled group (63% to 40%, p = 0.023 and 45% to 19%, p = 0.0001). Moreover, tumor size decrease was significantly higher in controlled group (-3.6 cm to -1.66 cm, p = 0.005). Conclusions: According to the results of our study, the addition of cabergoline to SSA normalized IGF-1 levels in a considerable amount of acromegaly patients with a moderately elevated IGF-1 level, regardless of serum PRL levels. Besides, cabergoline treatment was also influential in patients with higher IGF-1 levels despite a lower remission rate.

Subacute thyroiditis paranchime heterogeneity may mask thyroid nodules and higher EU-TIRADS scores.

PURPOSE: Nonhomogenous and ill-defined hypoechoic areas are typical ultrasonographic features of subacute thyroiditis (SAT). Evaluating a thyroid nodule accurately in this heterogeneous paranchime may be troublesome. This study aims to compare thyroid nodules, their characteristics, and European Thyroid Imaging and Reporting Data System (EU-TIRADS) categories at the time of the diagnosis and in the remission of SAT. METHODS: Ultrasonographic features of SAT and characteristics and EU-TIRADS categories of thyroid nodules in the initial and control ultrasonography (US) of 350 patients with SAT have been evaluated in this retrospective observational study. Fine needle aspiration biopsy (FNAB) results and postsurgical data, if performed, have been estimated. RESULTS: A hundred patients (28.6%) with SAT had thyroid nodules at the time of the diagnosis, while 152 (43.4%) patients had a nodule in remission US (p < 0.001). The number of thyroid nodules was found to be higher in the control US as against the initial US (p = 0.001). EU-TIRADS scores of the nodules in the remission US were significantly higher than the scores at the time of the diagnosis (p < 0.001). FNAB was performed in 23% of nodules observed in the remission US, and the rate of thyroid carcinoma within them was 3.3%. CONCLUSION: Thyroid nodules, malignancy suspected features, and EU-TIRADS categories of them may not be appropriately evaluated due to heterogenous paranchime of SAT. Performing a control US examination after resolution of hypoechoic areas may be beneficial to avoid missing clinically significant nodules with high EU-TIRADS scores.

Efficacy of cabergoline add-on therapy in patients with acromegaly resistance to somatostatin analogs treatment and the review of literature.

Objective: It is reported that adding cabergoline to somatostatin analog (SSA) normalizes IGF-1 levels approximately in one-third of patients with acromegaly. We investigated the effect of combination therapy and potential predictors of response in patients with acromegaly who do not respond to SSA therapy alone. Methods: Fifty acromegaly patients (M/F 23/27, mean age 50.88 ± 12.34 years) were divided into two groups as the active and control groups in this connection. Before and after treatment, we not only evaluated serum GH and IGF-1 levels and tumor size but also analyzed the factors relevant to the effect of the combined therapy. Results: Adding cabergoline to SSA treatment led to IGF-1 normalization in 42% (21/50) of patients. Mean GH levels decreased from 2.64 ± 1.79 to 1.34 ± 0.99 ng/mL (p < .0001) and IGF-1 levels decreased from 432.92 ± 155.61 to 292.52 ± 126.15 ng/mL (p < .0001). GH and IGF-1 reduction in percent (%) were significantly higher in the controlled group (63% to 40%, p = 0.023 and 45% to 19%, p = 0.0001). Moreover, tumor size decrease was significantly higher in controlled group (-3.6 cm to -1.66 cm, p = 0.005). Conclusion: According to the results of our study, the addition of cabergoline to SSA normalized IGF-1 levels in a considerable amount of acromegaly patients with a moderately elevated IGF-1 level, regardless of serum PRL levels. Besides, cabergoline treatment was also influential in patients with higher IGF-1 levels despite a lower remission rate.

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.

Two cases of subacute thyroiditis after different types of SARS-CoV-2 vaccination

SUMMARY Although the development of subacute thyroiditis (SAT) following viral infections is well-documented, the actual mechanism has not been clearly elucidated. The occurrence of SAT after vaccination has been reported in several case series and possible mechanisms such as molecular mimicry due to the exposure to viral proteins and/or abnormal reactogenicity by adjuvants have been implicated. We describe two cases who developed SAT three days after the messenger RNA vaccine against COVID-19 (Pfizer-BioNTech®) and six days after the inactivated COVID-19 vaccine (CoronaVac®). SAT diagnosis of these patients was delayed for more than two weeks. When the current cases were evaluated together with 1 Pfizer-BioNTech® and 3 CoronaVac® related cases reported previously, the patients were female aged between 30-42, except for the male patient we presented, and the complaints of the patients initiated within the first 2-7 days. While two Pfizer-BioNTech® vaccine-related cases were severely symptomatic and thyrotoxic at presentation, there were cases with mild to moderate clinical manifestations in CoronaVac® vaccine-related group. Physicians should be aware of SAT that may occur within a few days following the COVID-19 vaccination.

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.

Two cases of subacute thyroiditis after different types of SARS-CoV-2 vaccination.

Although the development of subacute thyroiditis (SAT) following viral infections is well-documented, the actual mechanism has not been clearly elucidated. The occurrence of SAT after vaccination has been reported in several case series and possible mechanisms such as molecular mimicry due to the exposure to viral proteins and/or abnormal reactogenicity by adjuvants have been implicated. We describe two cases who developed SAT three days after the messenger RNA vaccine against COVID-19 (Pfizer-BioNTech®) and six days after the inactivated COVID-19 vaccine (CoronaVac®). SAT diagnosis of these patients was delayed for more than two weeks. When the current cases were evaluated together with 1 Pfizer-BioNTech® and 3 CoronaVac® related cases reported previously, the patients were female aged between 30-42, except for the male patient we presented, and the complaints of the patients initiated within the first 2-7 days. While two Pfizer-BioNTech® vaccine-related cases were severely symptomatic and thyrotoxic at presentation, there were cases with mild to moderate clinical manifestations in CoronaVac® vaccine-related group. Physicians should be aware of SAT that may occur within a few days following the COVID-19 vaccination.

Cushing's syndrome due to adrenocorticotropic hormone-secreting metastatic neuroendocrine tumor of unknown primary origin: a case report and literature review.

BACKGROUND: In this article, we present a case of neuroendocrine neoplasm of unknown primary origin (UPO NEN), which is a rare cause of ectopic Cushing's syndrome (ECS) presenting numerous challenges, together with a literature review. CASE REPORT: A 43-year-old male patient presented with clinical features consistent with Cushing's syndrome (CS) and adrenocorticotropic hormone (ACTH)-dependent hypercortisolemia. Despite a suspicious lesion on pituitary MRI, the high-dose dexamethasone suppression test and bilateral inferior petrosal sinus sampling results were not compatible with Cushing's disease. Bilateral non-homogeneous opacities were observed in the thorax CT of the patient, who also had a history of COVID-19 infection, but no tumoral lesion was detected. When 68Ga-SSTR PET/CT and 18FDG-PET/CT were performed, multiple metastatic foci were detected in mediastinal and hilar lymph nodes and the axial skeleton. Paratracheal-subcarinal lymph nodes were excised mediastinoscopically, and the diagnosis of NEN was made. Histopathological findings indicated that the possible origin was an atypical pulmonary carcinoid with a low Ki-67 labeling index. After controlling hypercortisolemia, a regimen of somatostatin analogs and capecitabine plus temozolomide was decided upon as treatment by a multidisciplinary council. CONCLUSION: This is a challenging case of UPO NEN presenting with ECS and confounding factors, such as previous infection and incidental lesions, during the diagnosis process. The case in question highlighted the fact that atypical pulmonary carcinoid with a low proliferation index may cause visible metastases even when radiologically undetectable.

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.