Posthemithyroidectomy Hypothyroidism: Updated Meta-Analysis of Risk Factors and Rates of Remission.

INTRODUCTION: The aim of this study was to determine the incidence and risk factors for hypothyroidism, both clinical and subclinical, following hemithyroidectomy in preoperatively euthyroid patients, as well as hypothyroidism remission and its time of remission. MATERIALS AND METHODS: A search was performed in Medline (via PubMed), Web of Science, and the Cochrane Library using the keywords "hemithyroidectomy + postoperative + hypothyroidism" and "hemithyroidectomy + hormone supplementation". RESULTS: Fifty-four studies with a total of 9,999 patients were included. After a mean follow-up interval of 48.2 mo, the pooled hypothyroidism rate was 29%. The subclinical hypothyroidism rate was 79% of patients with hypothyroidism (18 studies). Moreover, a meta-analysis of 12 studies indicated a pooled hypothyroidism remission rate after hemithyroidectomy of 42% (95% CI: 24%-60%). Older patient age (MD = -2.54, 95% CI = -3.99, -1.10, P = 0.0006), female gender (OR = 0.69, 95% CI = 0.58, 0.82, P < 0.0001), higher preoperative thyroid-stimulating hormone levels (MD = -0,81, 95% CI = -0.96, -0.66, P < 0.00001), pathological preoperative anti-thyroid peroxidase antibodies (OR = 0.37, 95% CI = 0.24, 0.57, P < 0.00001) and anti-thyroglobulin antibodies (OR = 0.52, 95% CI = 0.36, 0.75, P = 00,005), and right-sided hemithyroidectomy (OR = 0.54, 95% CI = 0.43, 0.68, P < 0.00001) were associated with postoperative hypothyroidism development. In metaregression analysis, Asia presented a significantly higher hypothyroidism rate after hemithyroidectomy (34.6%, 95% CI = 29.3%-9.9%), compared to Europe (22.9%, 95% CI = 16.2%-29.5%, P = 0.037) and Canada (1.8%, 95% CI = -22.6%-26.2%, P = 0.013). CONCLUSIONS: Hypothyroidism is a frequent and significant postoperative sequela of hemithyroidectomy, necessitating individualization of treatment strategy based on the underlying disease as well as the estimated risk of hypothyroidism and its risk factors.

Parathyroid carcinoma in chronic renal disease - a case series of three patients and review of literature.

BACKGROUND: Apart from being a rare endocrine tumor, parathyroid carcinoma is also one of the rarest malignancies in human beings. Parathyroid carcinoma is even more uncommon in haemodialysis patients with end-stage renal disease. The pathogenesis of parathyroid hyperplasia in haemodialysis patients is well known, but the mechanism of development of parathyroid carcinoma in these patients remains unclear. METHODS: Three cases of parathyroid carcinoma in haemodialysis patients are presented in this study: a 69-year-old male patient and two female patients (67 and 61 years old). In all cases parathyroid carcinoma infiltrated the ipsilateral thyroid lobe and in one patient the right laryngeal nerve was involved as well. One patient underwent three surgical procedures. RESULTS: After surgical treatment, all patients were normocalcaemic and showed a significant reduction in PTH levels. CONCLUSION: In patients with secondary hyperparathyroidism, who develop parathyroid carcinoma, surgical resection is the only viable treatment option.

Case Control Study of Risk Factors for Occurrence of Postoperative Hematoma After Thyroid Surgery: Ten Year Analysis of 6938 Operations in a Tertiary Center in Serbia.

BACKGROUND: Post-thyroidectomy bleeding is rare, but potentially life-threatening complication. Early recognition with immediate intervention is crucial for the management of this complication. Therefore, it is very important to identify possible risk factors of postoperative hemorrhage as well as timing of postoperative hematoma occurrence. METHODS: Retrospective review of 6938 patients undergoing thyroidectomy in a tertiary center in a ten year period (2009-2019) revealed 72 patients with postoperative hemorrhage requiring reoperation. Each patient who developed postoperative hematoma was matched with four control patients that did not develop postoperative hematoma after thyroidectomy. The patients and controls were matched by the date of operation and surgeon performing thyroidectomy. RESULTS: The incidence of postoperative bleeding was 1.04%. On univariate analysis older age, male sex, higher BMI, higher ASA score, preoperative use of anticoagulant therapy, thyroidectomy for retrosternal goiter, larger thyroid specimens, larger dominant nodules, longer operative time, higher postoperative blood pressure and the use of postoperative subcutaneous heparin were identified as risk factors for postoperative bleeding. Sixty-nine patients (95.8%) bled within first 24 h after surgery. CONCLUSION: The rate of postoperative bleeding in our study is consistent with recent literature. Male sex, the use of preoperative anticoagulant therapy, thyroidectomy for retrosternal goiter and the use of postoperative subcutaneous heparin remained statistically significant on multivariate analysis (p < 0.001). When identified, these risk factors may be an obstacle to the outpatient thyroidectomy in our settings.

Preoperative Anxiety is Associated With Postoperative Complications in Vascular Surgery: A Cross-Sectional Study.

BACKGROUND: Preoperative anxiety is associated with increased morbidity and/or mortality in surgical patients. This study investigated the incidence, predictors, and association of preoperative anxiety with postoperative complications in vascular surgery. METHODS: Consecutive patients undergoing aortic, carotid, and peripheral artery surgery, under general and regional anesthesia, from February until October 2019 were included in a cross-sectional study. Anesthesiologists assessed preoperative anxiety using a validated Serbian version of the Amsterdam Preoperative Anxiety and Information Scale. Patients were divided into groups with low/high anxiety, both anesthesia- and surgery-related. Statistical analysis included multivariate linear logistic regression and point-biserial correlation. RESULTS: Of 402 patients interviewed, 16 were excluded and one patient refused to participate (response rate 99.7%). Out of 385 patients included (age range 39-86 years), 62.3% had previous surgery. High-level anesthesia- and surgery-related anxieties were present in 31.2 and 43.4% of patients, respectively. Independent predictors of high-level anesthesia-related anxiety were having no children (OR = 0.443, 95% CI: 0.239-0.821, p = 0.01), personal bad experiences with anesthesia (OR = 2.294, 95% CI: 1.043-5.045, p = 0.039), and time since diagnosis for ≥ 4 months (OR = 1.634, 95% CI: 1.023-5.983, p = 0.04). The female sex independently predicted high-level surgery-related preoperative anxiety (OR = 2.387, 95% CI: 1.432-3.979, p = 0.001). High-level anesthesia-related anxiety correlated with postoperative mental disorders (rpb = 0.193, p = 0.001) and pulmonary complications (rpb = 0.104, p = 0.042). Postoperative nausea (rpb = 0.111, p = 0.03) and postoperative mental disorders (rpb = 0.160, p = 0.002) correlated with high-level surgery-related preoperative anxiety. CONCLUSIONS: Since preoperative anxiety affects the postoperative course and almost every third patient experiences anxiety preoperatively, routine screening might be recommended in vascular surgery.

Risk Factors for New Onset Atrial Fibrillation during Thyroid Gland Surgery.

OBJECTIVE: Thyroid dysfunction is a common cause of atrial fibrillation (AF). Incidence of AF is high in patients with both expressed and subclinical hyperthyroidism. The aim of our study was to determine the incidence and predictors of new onset atrial fibrillation (NOAF) in euthyroid patients undergoing thyroid surgery. SUBJECT AND METHODS: The study included 1,252 euthyroid patients with American Society of Anesthesiologists (ASA) physical status ASA 2 and ASA 3, who were 18 years and older and were in sinus rhythm. Patients without comorbidity and patients with persistent AF were excluded. We investigated the influence of the following preoperative characteristics on the occurrence of NOAF: age, sex, body mass index, ASA score, admission diagnoses, and comorbidity. We noted the influence of difficult intubation of trachea, type and duration of surgery, and time under general anaesthesia. Univariate and multivariate logistic regression were used to determine predictors of occurrence of NOAF. RESULTS: NOAF was noted in 0.72% of patients. Patients with NOAF were older (63.11 vs. 56.81 years) than patients without NOAF, but this was not statistically significant. Significantly more patients from the NOAF group had preoperative heart rhythm disturbance and a history of angina pectoris, in contrast to patients without registered NOAF (p = 0.001; p = 0.017). Multivariate analysis showed that a history of heart rhythm disturbance was an independent predictor of NOAF. CONCLUSIONS: Incidence of NOAF during thyroid surgery is similar to the other type of surgery, if the values of thyroid hormones are normal.

Patients' Fears and Perceptions Associated with Anesthesia.

Background and Objectives: It has been suggested that intense feelings of fear/anxiety and significant patient concerns may affect the perioperative course. Those findings emphasize the importance of surgical patients' preoperative feelings. Still, current knowledge in this area is based on a limited number of studies. Thus, we think that there is a need to further explore patients' preoperative fears, better characterize risk factors and reasons for their occurrence, and evaluate patients' perspectives associated with anesthesia. Materials and Methods: A total of 385 patients undergoing vascular surgery were preoperatively interviewed using a questionnaire that included demographics and questions related to patients' fears and perceptions of anesthesia. Statistical analyses included descriptive statistics, Pearson's χ2 and McNemar tests, and multivariate ordinal logistic regression. Results: The main causes of patients' preoperative fear were surgery (53.2%), potential complications (46.5%), and anesthesia (40%). Female sex was a predictor of surgery and anesthesia-related fear (OR = 3.07, p = 0.001; OR = 2.4, p = 0.001, respectively). Previous experience lowered the fear of current surgery (OR = 0.65, p = 0.031) and anesthesia (OR = 0.6, p = 0.017). Type of surgery, type of anesthesia, educational and socioeconomic status, and personal knowledge of an anesthesiologist affected specific anesthesia-related fears. Over 25% of patients did not know that an anesthesiologist is a physician, and only 17.7% knew where anesthesiologists work. Level of education and place of residence influenced patients' perceptions of anesthesia. Conclusions: Anesthesia-related fears are affected by the type of surgery/anesthesia, experience with previous surgery, and personal knowledge of an anesthesiologist. Women, patients with lower education levels, and patients with poorer socioeconomic status are at higher risk of developing those fears. The perception of anesthesiologists is inadequate, and knowledge of anesthesia is poor. Promotion of patient education regarding anesthesia is needed to alleviate those fears and increase understanding of anesthesia.

Predictive Value of Calcium Test for Preoperative Diagnosis of Medullary Thyroid Carcinoma in Patients With Moderately Elevated Basal Calcitonin.

OBJECTIVE: Medullary thyroid carcinoma (MTC) can be very aggressive, and early diagnosis is based on routine measurement of serum calcitonin (CT) and RET genetic testing for hereditary forms. Basal serum CT (bCT) concentrations are useful in the early detection of MTC, although it is still unclear whether they can also be used for the differential diagnosis between MTC and C-cell hyperplasia (CCH). Since false-positive results can be obtained with the basal measurement of CT, a provocative test to evaluate stimulated CT (sCT) is often needed. The objective of this study was to investigate the utility of a calcium gluconate test for CT in distinguishing MTC from CCH, a precancerous condition in hereditary forms of MTCs but with unclear significance in sporadic MTCs. METHODS: A total of 74 patients underwent the calcium loading test before thyroidectomy, and bCT and sCT levels were compared with histologic results by receiver operating characteristic plot analyses. RESULTS: A peak CT level of 388.4 pg/mL after stimulation with calcium gluconate was able to significantly distinguish patients with MTC from those with CCH and those without C-cell pathology, with 81.8% sensitivity and 36.5% specificity. A bCT level of 16.1 pg/mL was able to distinguish between these 2 groups of patients with a sensitivity of 90%. CONCLUSION: High-dose calcium test is an effective procedure that can be applied for differential diagnosis of MTC and CCH. Reference ranges for calcium sCT levels and CT thresholds in different groups of patients have been identified.

Prognostic significance of immunohistochemical markers in adrenocortical carcinoma.

Background: To present basic demographic and clinical characteristics of patients with adrenocortical carcinoma (ACC), to determine the overall survival rate and to analyze the results of immunohistochemical staining and its correlation with the length of survival.Material and methods: The study was conducted during the period between 1996 and 2010 and included 30 patients with ACC. Immunohistochemical staining (MMP9, melan A, inhibin, caltretinin, D2-40, synaptophysin and Ki-67) was performed.Results: ACC was diagnosed in 19 females and 11 men (1.7:1). The average age was 50.1 years. The median tumor size was 10 cm, the median weight 400 g. Majority of subjects had positive immunohistochemical staining for the markers of interest. Patients with any negative staining had shorter cancer-specific survival than ones with positive staining. According to the log-rank test results as well as according to the results of the univariate Cox analysis, negative staining for inhibin, D2-40 and synaptophysin and Ki-67 expression ≥7% were associated with poorer prognosis.Conclusions: The results of our study suggest that the absence of staining for some immunohistochemical markers and increased expression of Ki-67 are associated with a poorer prognosis and shorter survival of patients with ACC. Immunohistochemical markers may serve as a prognostic factor for ACC.

High expression and localization of ß-catenin and epidermal growth factor receptor identify high risk papillary thyroid carcinoma patients.

We have evaluated the clinical significance of deregulated expression of ß-catenin and epidermal growth factor receptor (EGFR) during papillary thyroid carcinoma (PTC) progression. Immunohistochemical expression of ß-catenin and EGFR was analyzed in 104 archival tissues of PTC and 19 matched lymph node metastases (LNMs). ß-catenin (39/104, 37.5%) and EGFR (58/104, 55.7%) were co-expressed and co-localized in primary PTCs (p < .0001), which was confirmed by double immunofluorescent staining. The high expression of each molecule, as well as their high cytosolic co-expression, correlated with adverse clinicopathological features of the patients (p < .05). High expression of the proteins did not associate with the presence of BRAFV600E mutation (p > .05), tested by mutant allele-specific PCR amplification. Although nuclear localization of ß-catenin was found in a subset of PTC patients (16/104, 15.4%), no ß-catenin mutations were found in exon 3 of the CTNNB1 gene (screened by PCR in combination with denaturing gradient gel electrophoresis and confirmed by next generation sequencing). Cases with additional nuclear ß-catenin staining showed strong association with high EGFR expression (15/16, 93.7%), the presence of capsule invasion (12/16, 81.25%) and regional LNM (9/16, 52.3%). In corresponding LNMs, ß-catenin and EGFR expressions were maintained at high levels or further increased. Co-expression of high levels of ß-catenin and EGFR in association with clinicopathological features implicates their clinical utility in risk stratification of PTC patients, and supports the possibility of crosstalk between Wnt/ß-catenin and EGFR signaling during PTC progression.

Risk factors associated with intrathyroid extension of thyroid microcarcinomas.

PURPOSE: The aims of this study were to investigate the rate of intrathyroid extension of papillary thyroid microcarcinoma (PTMC) in patients operated for benign thyroid disease and to identify independent risk factors associated with it. METHODS: A retrospective study of 301 patients operated for benign thyroid diseases (hyperthyroid diseases, multinodular goitre, Hashimoto thyroiditis and benign thyroid tumours) was performed at a high-volume endocrine surgery unit of a tertiary referral academic hospital, in a 5-year period. These patients had a PTMC incidentally discovered on definite histopathological findings following total or near-total thyroidectomy. Since distinguishing between intrathyroid extension of PTMC as the result of intrathyroid dissemination or as the result of multicentricity is challenging, we observed them together as multifocality. In statistical analysis, we used standard descriptive statistics and univariate and multivariate logistic regression analysis to determine independent risk factors associated with multifocality. RESULTS: In our study, there were 85.4% females and 14.6% males with a median age of 54 years. A multinodular goitre (32.5%) was the most common indication for an operation. Most patients (68.4%) had a PTMC that was 5 mm or smaller. The most frequent histological variants of PTMC were the follicular variant (52.8%), followed by the papillary variant (22.6%) and the mixed follicular-papillary variant (18.6%). A multifocal PTMC was present in 26.6% of cases. An independent protective factor for multifocality of PTMC was a thyroid gland that weighed more than 38 g (OR 0.55, 95% CI 0.31-0.97, p = 0.039). Size of PTMC greater than 5 mm was an independent risk factor for a multifocal PTMC (OR 3.26, 95% CI 1.85-5.75, p = 0.000). Finally, the mixed follicular-papillary variant of PTMC represents an independent risk factor for a multifocal PTMC (OR 2.42, 95% CI 1.09-5.36, p = 0.030). CONCLUSIONS: Intrathyroid extension is present in more than a quarter of PTMCs found in patients operated for benign thyroid disease. Independent risk factors for intrathyroid extension are size of PTMC greater than 5 mm and the mixed follicular-papillary variant of PTMC, while a large thyroid gland is an independent protective factor.

Survival and prognostic factors for survival, cancer specific survival and disease free interval in 239 patients with Hurthle cell carcinoma: a single center experience.

BACKGROUND: Hurthle cell carcinoma makes up 3 to 5% of all thyroid cancers and is considered to be a true rarity. The aim of our study was to analyze clinical characteristics and survival rates of patients with Hurthle cell carcinoma. METHODS: Clinical data regarding basic demographic characteristics, tumor grade, type of surgical treatment and vital status were collected. Methods of descriptive statistics and Kaplan-Meier survival curves were used for statistical analysis. Cox proportional hazards regression was used to identify independent predictors. RESULTS: During the period from 1995 to 2014, 239 patients with Hurthle cell carcinoma were treated at our Institution. The average age of the patients was 54.3, with female to male ratio of 3.6:1 and average tumor size was 41.8 mm. The overall recurrence rate was 12.1%, with average time for relapse of 90.74 months and average time without any signs of the disease of 222.4 months. Overall 5-year, 10-year and 20-year survival rates were 89.4%, 77.2%, 61.9% respectively. The 5-year, 10-year and 20-year cancer specific survival rates were 94.6%, 92.5%, 87.4%, respectively. When disease free interval was observed, 5-year, 10-year and 20-year rates were 91.1%, 86.2%, 68.5%, respectively. The affection of both thyroid lobes and the need for reoperation due to local relapse were unfavorable independent prognostic factors, while total thyroidectomy as primary procedure was favorable predictive factor for cancer specific survival. CONCLUSION: Hurthle cell carcinoma is a rare tumor with an encouraging prognosis and after adequate surgical treatment recurrences are rare.

Surgical treatment of concomitant thyroid and parathyroid disorders: analysis of 4882 cases.

The thyroid gland disease incidence in hyperparathyroidism (HPT) is higher than the incidence of thyroid disease in general population. Likewise, HPT is more frequent in patients primary admitted due to thyroid disease, than in general population. The aim of this study was to determine the incidence and clinical characteristics of concomitant HPT and thyroid disease, based on a single center experience. From 2009 to 2014, a total of 4882 patients underwent thyroidectomy and/or parathyroidectomy at the Center for Endocrine Surgery, Belgrade. We reviewed the database to find out indications for surgery, clinical characteristics, operative and histopathological findings. Out of 4033 patients, who underwent thyroidectomy, in 114 cases (2.8 %) parathyroidectomy was simultaneously performed. Out of these 114 patients, 42 patients (37 %) had normocalcemic HPT. Among 849 patients primary operated due to HPT, thyroid gland disease that required surgery was found in 224 (26.4 %). In patients primary seen for HPT, thyroid cancer was found in 22 (9.8 %), Hashimoto's thyroiditis in 41 (18.3 %) and micropapillary carcinoma in 36 cases (16.1 %). Due to residual or recidivant HPT, 16 patients (15 who primary underwent parathyroidectomy and 1 primary seen for thyroid disease) needed a reoperation. There are a considerable number of patients with concomitant thyroid and parathyroid disease; this justifies the routine analyses of calcemia and PTH level in patients preparing for thyroidectomy, and sets up the ground for the thyroid investigations in HPT.

Risk Factors for Intraoperative Hypertension during Surgery for Primary Hyperparathyroidism.

OBJECTIVE: To investigate the incidence and identify risk factors for the occurrence of intraoperative hypertension (IOH) during surgery for primary hyperparathyroidism (pHPT). SUBJECTS AND METHODS: The study included 269 patients surgically treated between January 2008 and January 2012 for pHPT. IOH was defined as an increase in systolic blood pressure ≥20% compared to baseline values which lasted for 15 min. The investigated influence were demographic characteristics, surgical risk score related to physical status (based on the American Society of Anesthesiologists [ASA] classification), comorbidities, type and duration of surgery, and duration of anesthesia on IOH occurrence. The investigated factors were obtained from the patients' medical history, anesthesia charts, and the daily practice database. Logistic regression analysis was done to determine the predictors of IOH. RESULTS: Of the 269 patients, 153 (56.9%) had IOH. Based on the univariate analysis, age, body mass index, ASA status, duration of anesthesia, and preoperative hypertension were risk factors for the occurrence of IOH. Multivariate analysis showed that independent predictors of IOH were a history of hypertension (OR = 2.080, 95% CI: 1.102-3.925, p = 0.024) and age (OR = 0.569, 95% CI: 0.360-0.901, p = 0.016). CONCLUSION: In this study, a high percentage (56%) of the patients developed IOH during surgery for pHPT, which indicates that special attention should be paid to these patients, especially to the high-risk groups: older patients and those with a history of hypertension. Further, this study showed that advanced age and hypertension as a coexisting disease prior to parathyroid surgery were independent risk factors for the occurrence of IOH.

Papillary Thyroid Carcinoma: A Malignant Tumor with Increased Antioxidant Defense Capacity.

Papillary thyroid carcinoma (PTC) is the commonest thyroid malignancy worldwide for which the radiation exposure is the most influential risk factor. The levels of oxidative stress in PTC are not well characterized on the tissue level. The objective of this study was to evaluate total oxidant status (TOS) and total antioxidant status (TAS) in PTC and benign goiter (BG) tissues and to examine their association with clinicopathological characteristics. Tumor and normal thyroid tissue samples were collected from 59 PTC patients, and goiter tissues were collected from 50 BG patients. TOS and TAS were quantified in the tissue homogenates by spectrophotometric assays. TOS values in tumor tissues did not differ significantly from normal and goiter tissues; however, PTC tissues have significantly higher TAS values than normal and goiter tissues. TOS values correlated with retrosternal growth in BG patients. The significant correlations were found between TOS and TAS values and thyroid function parameters. In 17 PTC patients with multiple tumor foci (multicentric phenotype), TAS values were significantly lower, compared to 42 patients with unicentric PTC. TAS and TOS are the most useful predictors of thyroid capsular invasion by PTC. The age, sex, body mass index, smoking, familial history of thyroid disease and nodule size did not influence TOS and TAS in PTC or BG patients. In conclusion, we show the profiles of TOS and TAS in PTC and BG tissues. Importantly, PTC tissues possess increased antioxidant capacity. The redox status influences the parameters of the thyroid function and tumor's biological behavior.

Analysis of malignancy predictors for oxyphile thyroid tumors.

PURPOSE: In contrast to other thyroid carcinomas it is difficult to establish a correct preoperative diagnosis for oxyphile carcinoma of the thyroid. In this study we looked for predictive malignancy factors in order to enable surgeons to choose operative treatment and to perform an adequate operation for each patient with an oxyphile neoplasm of the thyroid. METHODS: In this retrospective study we have analyzed the medical files of all patients with oxyphile tumors of the thyroid operated between 1999 and 2008 in our institution. A total of 256 patients were included and divided into oxyphile adenomas (142) and carcinomas (114) on the basis of their definite histopathological diagnosis. The most important demographic and clinical characteristics were analyzed by univariate and multivariate logistic regression analysis. RESULTS: Univariate analysis showed that male gender, thyroglobulin concentrations ≥300 ng/ml and tumor diameter >30 mm were significantly more frequent in patients with oxyphile carcinoma compared to patients with oxyphile adenoma, while coexisting Hashimoto thyreoiditis and positive AntiTPO antibodies appeared significantly less frequent in the carcinoma group. All variables with a p value <0.1 in the univariate test were subjected to multivariate regression analysis in which elevated preoperative thyroglobulin concentrations (≥300 ng/ml) was shown as the only independent predictive factor for oxyphile thyroid carcinomas (OR=5.88, 95% CI 2.78-12.05, p=0.001). CONCLUSIONS: Preoperative thyroglobulin concentration is an independent predictor of malignancy for oxyphile thyroid carcinomas.

Retrospective evaluation of the incidental finding of 403 papillary thyroid microcarcinomas in 2466 patients undergoing thyroid surgery for presumed benign thyroid disease.

BACKGROUND: The aim of our study was to investigate the incidence of papillary thyroid microcarcinoma (PTMC) in patients operated for benign thyroid diseases (BTD) and its relation to age, sex, extent of surgery and type of BTD. METHODS: Retrospective study of 2466 patients who underwent thyroid surgery for BTD from 2008 to 2013. To determine independent predictors for PTMC we used three separate multivariate logistic regression models (MLR). RESULTS: There were 2128 (86.3%) females and 338 (13.7%) males. PTMC was diagnosed in 345 (16.2%) females and 58 (17.2%) males. Age ranged from 14 to 85 years (mean 54 years). Sex and age were not related to the incidence of PTMC. The overall incidence of PTMC was 16.3%. The highest incidence was in Hashimoto thyroiditis (22.7%, χ(2) = 10.80, p < 0.001); and in patients with total/near-total thyroidectomy (17.7%, χ(2) = 7.05, p < 0.008). The lowest incidence (6.6%, χ(2) = 9.96, p < 0.001) was in a solitary hyperfunctional thyroid nodule (SHTN). According to MLR, Hashimoto thyroiditis (OR 1.54, 95% CI 1.15-2.05, p < 0.003) and SHTN (OR 0.43, 95% CI 0.21-0.87, p < 0.019) are independent predictors. Since the extent of surgery was an independent predictor (OR 1.45, 95% CI 1.10-1.92, p = 0.009) for all BTD, and sex and age were not; when the MLR model was adjusted for them, Graves disease (OR 0.72, 95% CI 0.53-0.99, p < 0.041) also proved to be an independent predictor. CONCLUSIONS: Sex and age are not statistically related to the incidence of PTMC in BTD. The incidence of PTMC is higher in Hashimoto thyroiditis and patients with total/near-total thyroidectomy; and lower in patients with a SHTN and Graves disease.

Improved quality of life in hyperthyroidism patients after surgery.

BACKGROUND: The most common causes of hyperthyroidism are Graves disease (GD) and toxic nodular goiter (TNG). GD and TNG might influence patients' quality of life (QoL). The aim of our study was to analyze and compare the QoL of patients with GD with that of TNG patients and to evaluate the influence of surgical treatment on their QoL. MATERIALS AND METHODS: A prospective case-control study was conducted at the Center for Endocrine surgery in Belgrade, Serbia. The ThyPRO questionnaire was used in the QoL assessment of the GD and TNG patients (31 and 28, respectively) pre- and post-operatively. RESULTS: All patients were receiving antithyroid drugs, and none of the patients were overtly hyperthyroid at the time of completing the preoperative questionnaire. The QoL of the GD patients was worse than that of the TNG patients, with significant differences in eye symptoms, anxiety, and sex life domains (P < 0.001, P = 0.005, and P = 0.004, respectively), preoperatively, and in eye symptoms, anxiety, emotional susceptibility, and overall QoL (P = 0.001, P = 0.027, P = 0.005 and P = 0.013, respectively), postoperatively. The improvement in QoL in the GD patients was significant after surgical treatment in all ThyPRO domains. In the TNG patients, the improvement was significant in all but one ThyPRO domain, sex life (P = 0.066). CONCLUSIONS: The QoL of GD patients is worse than those of TNG patients. Surgery may improve QoL in patients with GD and TNG even if they have achieved satisfying thyroid status with medication treatment, preoperatively.

SMAD4 gene promoter mutations in patients with thyroid tumors.

As a key component of the transforming growth factor beta (TGFB) pathway, which regulates the expression of thyroid-specific genes, tumor suppressor SMAD4 is crucial for thyroid development and function. Aberrant expression of SMAD4 in thyroid tumor tissue was reported and mutations affecting the coding region have been detected, but a potential role of mutations in SMAD4 gene regulatory regions remains unexplored. The aim of this study was to analyze SMAD4 gene promoters in thyroid tumors. A total of 76 thyroidectomy specimens were studied, including 42 malignant and 34 benign tumors. The presence of mutations in four SMAD4 gene promoters was analyzed in thyroid tumor tissue and peripheral blood by PCR and DNA sequencing. The expression and intracellular localization of endogenous SMAD4 protein in selected tumor samples was studied by immunostaining and confocal microscopy. Of three novel variants detected, two were within promoter A (-204T/C and -5C/T) and one in promoter D (-180delA). Unlike somatic mutations previously detected in the nearby region, germline mutation -180delA in promoter D doesn't appear to affect SMAD4 expression in the thyroid tumor tissue. However, all newly detected SMAD4 promoter variants affect predicted binding sites of transcription factors involved in cell cycle regulation and should be further characterized functionally. Although not directly involved in carcinogenesis, detected variants may alter SMAD4 transcriptional regulation to some extent. Considering that dosage dependence is of great importance for the role of SMAD4 protein as a tumor suppressor, potential clinical significance of SMAD4 gene promoter mutations is worth further investigation.

Cross-cultural validity of the thyroid-specific quality-of-life patient-reported outcome measure, ThyPRO.

BACKGROUND AND PURPOSE: Thyroid diseases are common and often affect quality of life (QoL). No cross-culturally validated patient-reported outcome measuring thyroid-related QoL is available. The purpose of the present study was to test the cross-cultural validity of the newly developed thyroid-related patient-reported outcome ThyPRO, using tests for differential item functioning (DIF) according to language version. METHODS: The ThyPRO consists of 85 items summarized in 13 multi-item scales and one single item. Scales cover physical and mental symptoms, well-being and function as well as social and daily function and cosmetic concerns. Translation applied standard forward-backward methodology with subsequent cognitive interviews and reviews. Responses (N = 1,810) to the ThyPRO were collected in seven countries: UK (n = 166), The Netherlands (n = 147), Serbia (n = 150), Italy (n = 110), India (n = 148), Denmark (n = 902) and Sweden (n = 187). Translated versions were compared pairwise to the English version by examining uniform and nonuniform DIF, i.e., whether patients from different countries respond differently to a particular item, although they have identical level of the concept measured by the item. Analyses were controlled for thyroid diagnosis. DIF was investigated by ordinal logistic regression, testing for both statistical significance and magnitude (ΔR (2) > 0.02). Scale level was estimated by the sum score, after purification. RESULTS: For twelve of the 84 tested items, DIF was identified in more than one language. Eight of these were small, but four were indicative of possible low translatability. Twenty-one instances of DIF in single languages were identified, indicating potential problems with the particular translation. However, only seven were of a magnitude which could affect scale scores, most of which could be explained by sample differences not controlled for. CONCLUSION: The ThyPRO has good cross-cultural validity with only minor cross-cultural invariance and is recommended for use in international multicenter studies.

Survival and prognostic factors for adrenocortical carcinoma: a single institution experience.

BACKGROUND: Adrenocortical carcinoma (ACC) is aggressive, but rare tumours that have not been sufficiently studied. The aim of our study was to present the demographic and clinical characteristics of patients with ACC, to determine the overall survival rates, analyse the effect of prognostic factors on survival, as well as to identify favorable and unfavourable predictors of survival. METHOD: The study included 72 patients (42 women and 30 men) with ACC. We analysed the prognostic value of the demographic and clinical characteristics of the patients, tumour characteristics, therapy administered and survival rates. Kaplan-Meier survival curves and the log-rank test were used to estimate the overall and specific survival probabilities and the Cox regression model was used to identify independent prognostic factors for survival. RESULTS: The patients had mean age of 50 years. The 1-, 5-, and 10-year probabilities of survival in patients with ACC were 52.5 %, 41.1 %, and 16.4 %, respectively. The median survival time was 36 months. The results of multivariate Cox regression analysis showed that the presence of lymphatic metastases (HR = 7.37, 95 % CI = 2.31-23.48, p = 0.001) and therapy with mitotane (HR = 0.11, 95 % CI = 0.04-0.27, p = 0.001) were independent prognostic factors for survival. CONCLUSION: The presence of lymphatic metastasis is an unfavourable prognostic factor, while postoperative therapy with mitotane is a favorable prognostic factor for survival in patients with ACC.