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.

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.

Significance of arsenic and lead in Hashimoto's thyroiditis demonstrated on thyroid tissue, blood, and urine samples.

Our previous investigation showed significantly increased arsenic (As) content in thyroid tissue samples of patients with Hashimoto's thyroiditis (HT). This research aimed to extend previous findings and provide reliable insight into the close relationship between As and other trace elements with HT by considering a greater number of thyroid tissue samples, accompanied by blood and urine samples. The essential trace elements for thyroid homeostasis (Mn, Cu, Zn, Se) and the main threatening toxic trace elements (Ni, As, Pb, Cd, U) was analyzed by inductively coupled plasma-mass spectrometry (ICP-MS). Relevant parameters that could affect the concentration of trace elements were considered. This research showed that there was a difference in the elemental profile between HT and control samples. The most important findings were related to the elevated As and Pb content in the thyroid tissue and HT blood samples. The obtained negative correlations between As and Pb with Se may explain the antagonistic effect of As and Pb on the extrusion of essential Se from the HT tissue. The reduced Se content in the blood and its increased content in urine samples may further confirm this hypothesis and explain the lack of Se in HT. Furthermore, the reported results may highlight the unresolved molecular basis of HT and could indicate the role of trace element effects on thyroid homeostasis.

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.

Evaluation of trace metals in thyroid tissues: Comparative analysis with benign and malignant thyroid diseases.

Evaluation of trace metals at level of solid tissue can provide better information than blood or urine and, therefore, could highlight the role of metals in the etiology of organ-specific disease. The current study aimed to establish the baseline content of four essential (Mn, Cu, Zn, Se) and four toxic metals (As, Cd, Pb, U) in the healthy thyroid tissues (HTTs) by considering sex, age and smoking habits. A further aim was to examine whether differences in the content of metals exist in regard to the thyroid diseases, such as benign tumor (BT), Hashimoto's thyroiditis (HT), multinodular goiter (MNG) and thyroid cancer (TC). A total number of investigated tissue samples were 423. All metals were quantified by inductively coupled plasma-mass spectrometry (ICP-MS). It was found that the content of Cu and U was higher in HTTs of women, while the content of Zn was higher in HTTs of men. Increased content of Zn and decreased content of U was found in the group of HTTs above 50 years compared to a younger group (<50 years). Increased content of Cd, Pb and U distinguish smokers from the non-smokers. In comparison with other population groups worldwide, investigated Serbian population had up to 15 times reduced content of Se. Despite the difference in metal's profile according to biological variables, this study also demonstrated, for the first time, that each thyroid disease has its unique metal's profile. The most altered metal's content was found in tissues with HT. Contrarily, the greatest similarity in metal's content with HTTs was found in BT tissues. Based on the increased content, metal's that dominantly discriminated HTTs from the HT, MNG and TC was As, Pb and Cd, respectively. Reported results could highlight the role of toxic and essential trace metals in the not very well clarified etiology of thyroid diseases and, moreover, could provide a molecular basis for pathophysiological changes of metal's hazardous effects on thyroid health at the tissue level.

Differences in Chromatin Texture and Nuclear Fractal Dimension Between Hashimoto's and Lymphocytic Thyroiditis Lymphocytes.

Previous evidence suggested that lymphocytic thyroiditis (LT) was a variant of Hashimoto's thyroiditis (HT), thus the aim of the current study is to quantify structural changes in histological specimens taken from HT and LT patients. A total of 600 images containing a single lymphocyte nucleus (300 nuclei per group) were obtained from 20 patients with HT and LT. In order to quantify changes in the nuclear architecture of investigated lymphocytes, the fractal dimension (FD) and some gray-level co-occurrence matrix texture parameters (angular second moment, inverse difference moment, contrast, entropy, and correlation) were calculated for each nucleus. A statistically significant difference in the FD of the "binary-outlined" nucleus and that of the corresponding "black-and-white" nucleus was detected between HT and LT lymphocyte nuclei. In addition, there was also a statistically significant difference in contrast and correlation between HT and LT lymphocyte nuclei. In conclusion, the results of this study suggested that there was a difference in structural complexity between investigated lymphocyte nuclei; additionally, LT lymphocytes possessed probably more complex texture and larger variations as well as more asymmetrical nuclei compared with HT lymphocytes. Accordingly, these findings indicate that LT is probably not a variant of HT; however, more complex studies are necessary to estimate differences between these types of thyroiditis.

Overexpression of epidermal growth factor receptor and its downstream effector, focal adhesion kinase, correlates with papillary thyroid carcinoma progression.

Epidermal growth factor receptor (EGFR) and its downstream effector, focal adhesion kinase (FAK), have been shown to be overexpressed frequently in human malignancies and implicated in tumour aggressiveness. We aimed to investigate the relationship between EGFR and FAK expression and their possible correlation with the clinical phenotype of patients with papillary thyroid carcinoma (PTC). Expression profiles of EGFR and FAK were analysed in PTC tissue samples (n = 104) by immunohistochemistry and Western blotting. Additionally, EGFR and FAK were immunohistochemically analysed in 20 primary tumours paired with their metastatic tissue in lymph nodes. High expression of EGFR and FAK was found in 55.77% and 57.69% cases, respectively, with a strong positive association between them (P < 0.0001, Spearman's correlation coefficient = 0.844). Expression of each molecule and their coexpression correlated significantly with the presence of lymph node metastasis (LNM), degree of tumour infiltration, extrathyroid invasion and pT status of the patients. Western blot analysis confirmed that coexpression of high levels of EGFR and FAK correlated with adverse clinicopathological features. When compared to the corresponding primary tumour, increased or maintained high levels of EGFR and FAK were found in LNM, indicating their concordant expression during lymphatic spread. In conclusion, high levels of EGFR and its downstream effector, FAK, in association with lymphatic spread and tumour infiltration indicate their involvement in PTC progression and suggest that both molecules may predict its aggressive behaviour. Furthermore, FAK could be a potential target for anticancer therapy in patients with advanced thyroid cancer.

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.

Giant Posttraumatic Cervical Hematoma: Acute Presentation of Papillary Thyroid Carcinoma in an Adolescent.

OBJECTIVE: To describe a rare case of acute presentation of papillary thyroid carcinoma (PTC). CLINICAL PRESENTATION AND INTERVENTION: A 19-year-old male presented with an expanding cervical mass following blunt trauma. A computed tomography scan revealed a mass suspected to be hematoma that was compressing the vessels and thereby deviating the trachea. Immediate surgery was performed. Neither vascular injury nor active bleeding was seen; instead, a solid, hematoma-like tumefaction in the right thyroid lobe was revealed. A total thyroid lobectomy was performed. A histologic paraffin section confirmed a PTC that was permeated by hematoma. CONCLUSION: This was a unique case of an acute, life-threatening presentation of previously asymptomatic PTC in an adolescent.

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.