Do Histologically Aggressive Subtypes of Papillary Thyroid Microcarcinoma have Worse Clinical Outcome than Non-Aggressive Papillary Thyroid Microcarcinoma Subtypes? A Multicenter Cohort Study.

Histologically aggressive micropapillary thyroid carcinomas (PTMC) subtypes are thought to be associated with an aggressive clinical course. However, evidence for unfavorable clinical outcomes in patients with aggressive PTMC subtypes is not clear. In this study, we intended to determine the difference in clinical outcomes between patients with aggressive and non-aggressive PTMC subtypes. In this multicenter cohort study, the computer-recorded clinical and histopathological data of patients who underwent thyroid surgery between January 2000 - January 2021 in 9 referral centers and were diagnosed as PTMC were analyzed. A total of 1585 patients [female 1340 (84.5%), male 245 (15.5%), mean age 47.9±11.63 years), with a mean follow-up time of 66.55±37.16 months], were included in the study. Ninety-eight cases were diagnosed as aggressive and 1487 as non-aggressive subtypes. Persistent/recurrent disease was observed in 33 (33.7% )and 41 (2.8%) patients with aggressive and non-aggressive subtypes (p<0.001). Diseases-free survival rates were markedly lower in patients with aggressive than in those with non-aggressive PTMC subtypes (66.3 vs. 94.8%, log-rank p<0.001). Moreover, in multivariate analysis, aggressive histology was an independent predictor of persistent/recurrent disease, after controlling for other contributing factors (HR 5.78, 95% CI 3.32-10, p<0.001). Patients with aggressive PTMC subtypes had higher rates of incomplete biochemical and structural response than patients with non-aggressive subtypes as well (p<0.001). Aggressive PTMC subtypes share many characteristics with histologically identical tumors>1 cm in size. Therefore, the histopathological subtype of PTMC should be taken into consideration to tailor a personalized management plan.

The Detection of Preoperative Parathyroid Lesions: The Success of Ultrasonography, Technetium-99m Methoxyisobutylisonitrile Parathyroid Scintigraphy, and Single-Photon Emission Computed Tomography-Computed Tomography.

OBJECTIVE: We aimed to find and compare the efficacy of ultrasonography (US), technetium-99m methoxyisobutylisonitrile parathyroid scintigraphy (MIBI-S), and single-photon emission computed tomography-computed tomography (SPECT-CT) in detecting the localization of parathyroid adenomas in patients with primary hyperparathyroidism. METHODS: In total, 348 patients were included in this study. Preoperative parathyroid imaging with US, MIBI-S, and SPECT-CT was evaluated and compared with operative findings. The results of the imaging methods were compared with pathology and operation reports. RESULTS: In 318 patients (91.3%), one of the imaging methods was able to localize the lesion correctly. US detected the localization of the parathyroid lesions correctly in 268 patients (77%), whereas SPECT-CT and MIBI-S were correct in 254 (73%) and 209 (60%) patients, respectively. There was a statistically significant relationship between the parathyroid hormone (PTH) level and 3 imaging methods' success rates (P < .05). The PTH cut-off value, which best determined the correct localization, was 152.5 pg/mL for US, 143 pg/mL for MIBI-S, and 143 pg/mL for SPECT-CT. It was observed that the correct localization rate for parathyroid lesions increased with higher PTH levels. CONCLUSION: In our study population, US was more successful, in most cases, than other imaging methods in localizing parathyroid lesions but SPECT-CT was more accurate in localizing mediastinal lesions. In addition, it was found that preoperative PTH levels affect the accuracy of imaging methods.

The role of therapeutic plasmapheresis in patients with hyperthyroidism.

BACKGROUND: Hyperthyroidism is characterized by excess hormone secretion from the thyroid gland. Anti-thyroid drugs (ATDs), surgery, and radioactive iodine can be used in treatment. Plasmapheresis is a rapid and effective treatment option in cases where rapid euthyroidism is needed to be obtained due to complications of thyrotoxicosis and major adverse effects of ATDs. MATERIAL AND METHOD: We present patients receiving plasmapheresis to provide immediate euthyroidism due to severe hyperthyroidism, adverse effects of ATDs, or non-thyroid surgery from January 2012 to December 2016. RESULTS: This study included 18 patients. The etiology of hyperthyroidism was TDG in seven patients, TDMNG in two, TA in two, TMNG in four, and one patient had AIT. Plasmapheresis was performed to achieve euthyroidism before surgery in two patients. The mean plasmapheresis session was 5.35. The mean number of sessions needed for patients with TDG and TDMNG was 4, whereas it was 6.5 for patients with TA and TMNG (p = 0.07). The decrease of mean free thyroxine and free triiodothyronine were 57 % and 73 %, respectively (p < 0.001). After plasmapheresis, total thyroidectomy was performed in 14 patients. Euthyroidism was achieved with RAI in one patient and with medical therapy in three patients. CONCLUSIONS: Plasmapheresis therapy is a reliable and effective treatment option for patients who cannot use ATDs because of their adverse events and those with hyperthyroidism that does not resolve with these drugs, or to achieve euthyroidism before total thyroidectomy, RAI or non-thyroid emergency surgery. However, it cannot be used widely because it is expensive and invasive.

The role of serum osteoprotegerin level in diagnosis of disease and determining cardiovascular risk of polycystic ovary syndrome.

Objective: Although animal studies claim that osteoprotegerin (OPG) is preventive on this system, there are conflicting results in human studies. The aim of this study was to investigate the role of OPG in the diagnosis and determination of cardivovascular risk in patients with polycystic ovary syndrome (PCOS), which is a multisystem effective disease.Method: The study was performed on 28 premenopausal healthy female volunteers and 57 newly diagnosed PCOS patients in 2017. Anamnesis was obtained, body mass indexes were calculated, laboratory tests required for diagnosis and differential diagnosis of PCOS and suprapubic ovarian ultrasonography were performed, serum OPG level was studied by enzyme-linked immunosorbent assay.Results: OPG levels were similar in PCOS and control groups and there was no significant difference (49.392 ± 10.973 pg/ml vs 49.567 ± 13.57 pg/ml, p = .815). Correlation analysis showed a positive correlation between OPG and total testosterone levels in the PCOS group (r = 0.277, p = .045). No significant relationship with cardiovascular and metabolic parameters was detected.Conclusion: No difference was found between PCOS patients and control groups in terms of OPG levels. Therefore, it is thought that OPG level cannot be used in the diagnosis of the disease. There was no significant relationship between cardiometabolic parameters.

Serum zonulin level is not elevated in patients with polycystic ovary syndrome without metabolic syndrome.

AIM: Polycystic ovary syndrome (PCOS) is a complex disorder with gynecological, metabolic and carcinogenic effects. Increased intestinal permeability is related with obesity, insulin resistance, type 1 and 2 diabetes mellitus. The existence of such a relationship between PCOS and intestinal permeability has come to an end. Zonulin can change intestinal permeability, and this effect is reversible. We studied the relation between zonulin and the hormonal and metabolic parameters of PCOS. METHOD: A total of 45 women with PCOS and 17 healthy women were included in the study. Histories were taken from all the participants, body mass indexes were calculated, and biochemical tests and suprapubic over ultrasonography were made. Zonulin was studied with enzyme-linked immunosorbent assay. RESULTS: Serum zonulin levels were similar between PCOS and control groups (p = 0.893). In all participants, there were negative correlations between zonulin and the total cholesterol, LDL-cholesterol, triglycerides and non-HDL-cholesterol (respectively, p = 0.00, 0.018, 0.004, 0.002), there were boundary correlations with age and total cholesterol/HDL-cholesterol (respectively, p = 0.052 and 0.058). No statistically significant was detected in the PCOS group except negative correlation between zonulin and age (p = 0.046), boundary correlation between zonulin and total cholesterol/HDL-cholesterol (p = 0.064). CONCLUSION: PCOS patients did not have metabolic syndrome. Zonulin was not higher in PCOS then controls, and it had only negative relation with age. The negative relation between zonulin and some metabolic parameters in all participants was not detected in PCOS group. So zonulin is not a useful molecule for the diagnosis of PCOS without metabolic syndrome.

The impact of microscopic extrathyroidal extension on the clinical outcome of classic subtype papillary thyroid microcarcinoma: a multicenter study.

OBJECTIVES: Despite the presumed overdiagnosis of papillary thyroid microcarcinoma (PTMC) which has resulted in a new trend toward less-extensive surgery and a preference for active surveillance, the impact of microscopic extrathyroidal extension (mETE) on the clinical outcomes of PTMC is still controversial. This study assessed the impact of mETE on the clinical outcomes of patients with classic subtype PTMC. METHODS: The data of consecutive patients who underwent thyroidectomy and were histopathologically diagnosed as classic subtype PTMC were analyzed. Cox's proportional hazards model was used to assess the impact of contributing variables on persistent/recurrent disease. Disease-free survival was estimated using the Kaplan-Meier method. RESULTS: This study included 1013 patients (84% females), with a mean follow-up period of 62.5 ± 35.3 months. Patients with mETE had a significantly higher rate of locoregional persistent/recurrent disease than patients without mETE (9.8% vs 2.1%, p < 0.001). The disease-free survival rate was significantly lower in patients with mETE than in those without (90.2% vs 97%, Log-Rank p < 0.001). Furthermore, mETE and neck lymph node involvement were independent predictors of persistent/recurrent disease in multivariate analysis (HR: 2.43, 95% CI:1.02-5.81, p = 0.043; HR: 4.38, 95% CI: 1.7-11.2, p = 0.002, respectively). CONCLUSIONS: In patients with the classic subtype of PTMC, mETE is an independent predictor of persistent/recurrent disease and is associated with a lower DFS rate. However, neck lymph node involvement is the strongest predictor of persistent/recurrent disease. Therefore, PTMCs with mETE and neck lymph node involvement are at a higher risk of persistent/recurrent disease than individuals lacking both characteristics.

Disease-free survival and the prognostic factors affecting disease-free survival in patients with medullary thyroid carcinoma: a multicenter cohort study.

PURPOSE: Despite several factors that may have been associated with poor disease-free survival (DFS) in patients with medullary thyroid carcinoma (MTC), only a few studies have evaluated the prognostic factors affecting DFS in MTC patients. Therefore, this study evaluated the prognostic factors affecting DFS, in a large number of patients with MTC. METHODS: Patients treated for MTC were retrospectively analyzed. Patients were stratified as having persistent/recurrent disease and no evidence of disease (NOD) at the last follow-up. The factors affecting DFS after the initial therapy and during the follow-up period were investigated. RESULTS: This study comprised 257 patients [females 160 (62.3%), hereditary disease 48 (18.7%), with a mean follow-up time of 66.8 ± 48.5 months]. Persistent/recurrent disease and NOD were observed in 131 (51%) and 126 (49%) patients, respectively. In multivariate analysis, age > 55 (HR: 1.65, p = 0.033), distant metastasis (HR: 2.41, p = 0.035), CTN doubling time (HR: 2.7, p = 0.031), and stage III vs. stage II disease (HR 3.02, p = 0.048) were independent predictors of persistent/recurrent disease. Although 9 (8%) patients with an excellent response after the initial therapy experienced a structural recurrence, the absence of an excellent response was the strongest predictor of persistent/recurrent disease (HR: 5.74, p < 0.001). CONCLUSIONS: The absence of an excellent response after initial therapy is the strongest predictor of a worse DFS. However, a significant proportion of patients who achieve an excellent response could experience a structural recurrence. Therefore, careful follow-up of patients, including those achieving an excellent response is essential.

The effects of circulating MIR22-3p and MIR16-1-3p levels in different stages of subacute thyroiditis.

Subacute thyroiditis (SAT) is an inflammatory thyroid disease with a frequency is 5% among all thyroid diseases. miRNAs are endogenous, non-coding RNAs ranging in length from 19 to 25 nucleotides. They play an important role in the posttranscriptional regulation of gene expression. In this study, we aimed to investigate whether the expression levels of two circulating miRNAs, MIR22 and MIR16-1, can be used as a parameter in the diagnosis and follow-up of SAT disease. Fifty patients diagnosed with SAT and 41 healthy controls were included in this study. Expression levels of miRNAs were determined by real time-PCR method. Expression data of miRNAs were calculated by fold change (2-ΔΔCt) method. The statistical significance of miRNA expression was evaluated by t-test. The expression levels of MIR22-3p and MIR16-1-3p were not found to be statistically different between SAT patients and controls and also between the patients in different stages (hyperthyroid, euthyroid, and hypothyroid) of the disease. According to correlation analyses, we observed a positive strong correlation between erythrocyte sedimentation rate (ESR) and the expression levels of MIR22-3p and MIR16-1-3p (r = 0.960, p = 0.000 and r = 0.865, p = 0.006, respectively), and a positive strong correlation between fT4 and the expression levels of MIR22-3p in SAT patients in euthyroid stage (r = 0.712, p = 0.047). In this study, we showed that the expression levels of MIR22-3p and MIR16-1-3p have correlation with clinical characteristics of SAT disease. Our results suggest that MIR22 and MIR16-1 may be effective in the pathogenesis of SAT.

Benign cytology does not rule out malignancy in thyroid nodules larger than 4 cm.

BACKGROUND: For thyroid nodules ≥4 cm, the accuracy of fine-needle aspiration biopsy (FNAB) is controversial and the approach is unclear. We aimed to compare FNAB and operation of thyroid nodules and to determine the accuracy of FNAB. MATERIAL AND METHODS: All total thyroidectomies performed between January 2015 and December 2021 were evaluated. In the study, 301 patients were included. Euthyroid patients with preoperative thyroid ultrasound, FNAB results and operation results were recorded retrospectively. RESULTS: The nodule size was <4 cm in 79.1% of the patients, and ≥4 cm in 20.9%. In patients with nodule size ≥4 cm, 50.8% of FNAB results were reported as benign, and 43.7% of these patients were found to be malignant at the end of the operation. In nodules <4 cm, 36.8% of the patients whose FNAB results were found to be benign were malignant. False-negativity rate was found to be quite high in ≥4 cm nodules. CONCLUSIONS: For thyroid nodules, diagnostic lobectomy may be necessary because the false-negative rate of FNAB was high, especially in nodules ≥4 cm. In addition, intermediate results, such as AUS/FN, have a higher risk of malignancy in nodules of ≥4 cm compared to nodules of <4 cm.

The Relationship of Thyroid Functions with ADMA, IMA, and Metabolic Laboratory Parameters in Euthyroid Adults with and without Autoimmune Thyroiditis.

OBJECTIVE: To investigate the relationship between thyroid functions and asymmetric dimethylarginine (ADMA), ischemia-modified albumin (IMA), and other metabolic laboratory markers in euthyroid adults and whether narrower thyroidal targets are required for lower metabolic risk. MATERIALS AND METHODS: Thyroid functions, antithyroid autoantibodies, and metabolic parameters were measured for 115 patients. Forty-seven had autoimmune thyroiditis (AIT). Analyses were performed according to cutoff values of 1, 2, 2.5, and 3 mIU/L for thyrotropin, 0.84 ng/dL for free thyroxine (fT4), and 3.59 ng/dL for free tri-iodothyronine (fT3). RESULTS: There was no relationship between thyrotropin and fT3 cutoff values and metabolic parameters. Only C-reactive protein was lower in the group with thyrotropin ≤2.5 µIU/L. A weak positive correlation was found between fT4 with IMA and IMA corrected for albumin (r = 0.187, P = .05; r = 0.204, P = .034, respectively). There was no difference between AIT and the metabolic laboratory parameters examined in the study. CONCLUSION: This study is the first to evaluate ADMA in AIT. Narrower thyroid function targets are not required for better metabolic control in euthyroid adults.