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.

Effects of successful parathyroidectomy on neuropsychological and cognitive status in patients with asymptomatic primary hyperparathyroidism.

PURPOSE: Besides typical clinical symptoms, primary hyperparathyroidism (pHPT) is associated with impaired quality of life and cognitive status. The aim of this study was to evaluate the quality of life and cognitive impairment in patients with pHPT, before and after parathyroidectomy. METHODS: We conducted a panel study, which included asymptomatic pHPT patients scheduled for parathyroidectomy. Besides demographic and clinical data, patients' quality of life and cognitive capacity were recorded before, 1 month, and 6 months following parathyroidectomy using the Short Form 36 questionnaire (RAND-36), Beck Depression Inventory (BDI), Depression Anxiety Stress Scales (DASS), Mini-Mental State Examination (MMSE), and Symptom Check List 90-revised version (SCL90R). RESULTS: During a 2-year follow-up, 101 patients entered the study (88 women), with an average age of 60.7 years. The Global score of RAND-36 test ameliorated by almost 50% 6 months after parathyroidectomy. The most sustained subscores of the RAND-36 test were role functioning/physical and health change, with an improvement of more than 125%. According to the BDI, DASS depression subscore, and SCL90R depression subscore, the extent of depressive symptoms reduction was approximately 60% 6 months postoperatively. The level of anxiety was reduced by 62.4%, measured by both the DASS and SCL90R anxiety subscores. The stress level was almost halved according to the DASS stress subscore (from 10.7 to 5.6 points). The results of the MMSE test showed a significant improvement postoperatively, for 1.2 points (4.4%). A worse preoperative score of each tool was related to the higher magnitude of improvement 6 months after parathyroidectomy. CONCLUSION: A considerable number of pHPT patients, even without other typical symptoms, show signs of impaired quality of life and neurocognitive status preoperatively. After a successful parathyroidectomy, there is an improvement in quality of life, declined levels of depression, anxiety, and stress, as well as amelioration of cognitive status. Patients with more impaired quality of life and pronounced neurocognitive symptoms may expect more benefits from the surgery.

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.

Case-control study of primary hyperparathyroidism in juvenile vs. adult patients.

OBJECTIVES: Primary hyperparathyroidism in juveniles is extremely rare condition, but in the last few decades the incidence is increasing. The aim of this study was to compare biochemical and clinical characteristics of juvenile and adult primary hyperparathyroidism patients. METHODS: A retrospective case-control study was conducted from 2004 until 2017 in high volume endocrine surgery center. Juvenile group consisted of all primary hyperparathyroidism patients younger than 20 who have undergone parathyroidectomy, and two-fold more patients older than 20 were classified in control (adult) group. RESULTS: A total of 14 patients with the age ≤20 years were included in the juvenile group, while 28 patients older than 20 were selected for the control group. Female-to-male ratio in juveniles was 1:1, and in adults 8:1 (p = 0.005). The most common form of the disease in juveniles was bone disease (42.9%) and most of adults were asymptomatic (39.3%). Mean preoperative serum calcium level was significantly higher in juveniles than in adults, 3.47 ± 0.74 mmol/L vs. 2.96 ± 0.25 mmol/L, p = 0.025. Mean preoperative PTH level was higher in juveniles than in control group, 572.6 ± 533.3 ng/L vs. 331.8 ± 347.5 ng/L, p = 0.089. CONCLUSION: Clinical manifestations of primary hyperparathyroidism significantly differ in juvenile and adult patients. Juvenile primary hyperparathyroidism represents more severe form of the disease, often with end-organ damages, and it should be considered in patients with unspecific symptoms.

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.

Validation and cross-cultural adaptation of the questionnaire ThyPRO in thyroid patients in Serbia.

UNLABELLED: BACKGRAUND/AIM: The Thyroid Specific Patient Reported Outcome Measure (ThyPRO) questionnaire is self-administered and intended to measure quality of life of thyroid patients. The aim of this study was to investigate the validity and reliability of the translated new, ThyPRO questionnaire in Serbian patients with thyroid disease. METHODS: The translation process followed an internationally accepted methodology. The questionnaire was validated in 100 consecutive thyroid patients hospitalized in a tertiary level hospital, between April and August 2012. Internal reliabilities of ThyPRO scales were assesessed using Cronbach's α coefficient. Association between age, gender, education, marital and employment status, place of living, diagnosis, current treatment, hormonal status and patient quality of life were determined using Pearson's (r) and Spearman's (q) correlation coefficients. RESULTS: Internal consistency and reliability for ThyPRO scales were satisfactory. Cronbach's α coefficients of 13 multi-item scales of the ThyPRO were > 0.83 (range 0.83-0.95). The scores, obtained by this questionnaire, correlated significantly with patients gender, employment status, diagnosis, current treatment and place of living. A highly significant inverse relationship was found between scores and hormonal status as well as between scores and disease duration. Patients' age, marital status and thyroid-stimulating hormone level did not influence any scale score. CONCLUSION: The ThyPRO may be useful in measuring health-related quality of life in patients with thyroid disease in Serbia.

The relationship between proliferation activity and parathyroid hormone levels in parathyroid tumors.

PURPOSE: This article examines as to whether the Ki-67 index may be useful as a marker for cell proliferation, as well as to whether Ki-67 immunohistochemical expression and parathyroid hormone (PTH) levels are useful in distinguishing between parathyroid carcinoma (PC) and adenoma. METHODS: A retrospective analysis of 50 patients (10 with PC and 40 with adenoma) who had been previously diagnosed with primary hyperparathyroidism (PHPT) was conducted. Normal parathyroid glands served as the control group. Immunostaining of Ki-67 was estimated through image analysis and the results were statistically analyzed. RESULTS: Ki-67 was higher in PC patients (median 785.15) compared to adenoma patients (median 297.41; Mann-Whitney U-test p<0.001). ROC analysis confirmed that Ki-67 has a positive predictive marker in diagnosing cancer. Mann-Whitney U-test confirmed a highly statistically significant difference in the preoperative PTH levels between the PC and adenoma group (p <0.001). The PTH serum preoperative level was higher in PC patients (median 1721) than in those with adenoma (median 189.5). A highly significant correlation was also found between Ki-67 and preoperative PTH levels (p <0.001). CONCLUSION: A higher rate of cellular proliferation was noted in malignant tumors as compared to benign tumors. Moreover, the expression profile of Ki-67 and high PTH levels in this study indicates a role for them as potential markers of malignancy.

Total thyroidectomy as a method of choice in the treatment of Graves' disease - analysis of 1432 patients.

BACKGROUND: Graves' disease represents an autoimmune disease of the thyroid gland where surgery has an important role in its treatment. The aim of our paper was to analyze the results of surgical treatment, the frequency of microcarcinoma and carcinoma, as well as to compare surgical complications in relation to the various types of operations performed for Graves' disease. METHODS: We analysed 1432 patients (221 male and 1211 female) who underwent surgery for Graves' disease at the Centre for Endocrine Surgery in Belgrade during 15 years (1996-2010). Average age was 34.8 years. Frequency of surgical complications within the groups was analyzed with nonparametric Fisher's test. RESULTS: Total thyroidectomy (TT) was performed in 974 (68%) patients, and Dunhill operation (D) in 221 (15.4). Carcinoma of thyroid gland was found in 146 patients (10.2%), of which 129 (9%) were a microcarcinoma. Complication rates were higher in the TT group, where there were 31 (3.2%) patients with permanent hypoparathyroidism, 9 (0.9%) patients with unilateral recurrent nerve paralysis and 10 (1.0%) patients with postoperative bleeding. Combined complications, such as permanent hypoparathyroidism with bleeding were more common in the D group where there were 2 patients (0,9%), while unilateral recurrent nerve paralysis with bleeding was more common in the TT group where there were 3 cases (0,3%). CONCLUSIONS: Frequency of complications were not significantly statistically different in relation to the type of surgical procedure. Total thyroidectomy represents a safe and efficient method for treating patients with Graves' disease, and it is not followed by a greater frequency of complications in relation to less extensive procedures.

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.

Age as a prognostic factor in anaplastic thyroid cancer.

Background. Anaplastic thyroid cancer (ATC) is one of the tumors with the shortest survival in human medicine. Aim. The aim was to determine the importance of age in survival of patients with ATC. Material and Methods. We analyzed the data on 150 patients diagnosed with ATC in the period from 1995 to 2006. The Kaplan-Meier method and log-rank test were used to determine overall survival. Prognostic factors were identified by univariate and multivariate Cox regression analysis. Results. The youngest patient was 35 years old and the oldest was 89 years old. According to univariate regression analysis, age was significantly associated with longer survival in patients with ATC. In multivariate regression analysis, patients age, presence of longstanding goiter, whether surgical treatment is carried out or not, type of surgery, tumor multicentricity, presence of distant metastases, histologically proven preexistent papillary carcinoma, radioiodine therapy, and postoperative radiotherapy were included. According to multivariate analysis, besides surgery (P = 0.000, OR = 0.43, 95% CI = 0.29-0.63), only patients age (P = 0.023, OR = 0.68, 95% CI = 0.49-0.95) was independent prognostic factor of favorable survival in patients with ATC. Conclusion. Age is a factor that was independently associated with survival time in ATC. Anaplastic thyroid cancer has the best prognosis in patients younger than 50 years.

Improvement of quality of life in patients with benign goiter after surgical treatment.

PURPOSE: A quality of life (QoL) assessment is considered an important outcome measure in the treatment of benign thyroid diseases. The aims of this study were to analyze the impact of different surgical treatments on QoL in patients with benign thyroid diseases and to evaluate factors correlating with the QoL outcomes. METHODS: A prospective longitudinal study was conducted. One hundred thirty-two patients met the inclusion/exclusion criteria and completed the disease-specific questionnaire, thyroid patient-reported outcome (ThyPRO), before surgery and after 6 months. Preoperative and postoperative QoL outcomes were compared and correlating factors were analyzed. RESULTS: Indication for surgery was euthyroid goiter, toxic goiter, and suspicious malignant thyroid disease in 58.3, 29.5, and 12.1 % of the patients, respectively. None of the patients had overtly toxic goiter. There were 65.2 % of the patients who underwent total thyroidectomy, while 34.8 % underwent hemithyroidectomy. The total postoperative complication rate was 5.3 %. QoL improved significantly after surgical treatment, independent of the extent of performed surgery. The most affected domain, pre- and postoperative, was for tiredness. QoL improvement was significant for women in all domains, while for men, it was significant in only three domains (goiter symptoms, emotional susceptibility, and cosmetic complaints) and in overall QoL. Younger patients had significantly better cognitive functioning and daily life, while elderly patients had significantly less cosmetic complaints. The factors that significantly correlated with improvement of QoL in different domains were lower education level, duration of disease, and microcarcinoma at final histology. CONCLUSION: QoL in patients with benign thyroid diseases improves significantly after operative treatment, independent of the extent of the operation.

A case-control study of papillary thyroid cancer in children and adolescents.

Thyroid carcinomas in children and adolescents are rare tumors and the most common among them is papillary thyroid cancer (PTC). Its etiology is still under research and has not been clearly defined thus far, especially in young individuals. The aim of this case-control study was to determine potential risk factors for the development of PTC in children and adolescents. This type of study has not been carried out previously in this age group. A case-control study was carried out during a 15-year period, between 1995 and 2009. The case group included 75 patients with PTC younger than 20 years of age, with the youngest patient being 6.5 years old; 45 patients were female and 30 were male. The control group included the same number of participants, and the cases were individually matched by sex, age, and place of residence. Conditional univariate and multivariate logistic regression methods were applied in data analysis. According to univariate logistic regression analysis, PTC in children and adolescents was significantly related to the following factors: family history of thyroid cancer, family history of residence in an endemic-goiter area, family history of benign thyroid disease, and family history of nonthyroid malignant tumors. According to the multivariate logistic regression method, PTC in children and adolescents was independently related to a family history of thyroid cancer (odds ratio=4.5, 95% confidence interval=1.2-19.8) and a family history of nonthyroid malignant tumors (odds ratio=3.8, 95% confidence interval=1.4-8.7). In conclusion, all of the factors associated with the development of PTC in children and adolescents were related to their family history.