Maternal Health, Pregnancy and Offspring Factors, and Maternal Thyroid Cancer Risk: A Nordic Population-Based Registry Study.

Thyroid cancer incidence is higher in women than men, especially during the reproductive years, for reasons that remain poorly understood. Using population-based registry data from 4 Nordic countries through 2015, we examined associations of perinatal characteristics with risk of maternal thyroid cancer. Cases were women diagnosed with thyroid cancer ≥2 years after last birth (n = 7,425, 83% papillary). Cases were matched to controls (n = 67,903) by mother's birth year, country, and county of residence. Odds ratios (ORs) were estimated using conditional logistic regression models adjusting for parity. Older age at first pregnancy, postpartum hemorrhage (OR = 1.18, 95% (confidence interval) CI: 1.08, 1.29), and benign thyroid conditions (ORs ranging from 1.64 for hypothyroidism to 10.35 for thyroid neoplasms) were associated with increased thyroid cancer risk, as were higher offspring birth weight (per 1-kg increase, OR = 1.17, 95% CI: 1.12, 1.22) and higher likelihood of offspring being large for gestational age (OR = 1.26, 95% CI: 1.11, 1.43). Unmarried/noncohabiting status (OR = 0.91, 95% CI: 0.84, 0.98), maternal smoking (OR = 0.75, 95% CI: 0.67, 0.84), and preterm birth (OR = 0.90, 95% CI: 0.83, 0.98) were associated with reduced risk. Several factors (e.g., older age at first pregnancy, maternal smoking, goiter, benign neoplasms, postpartum hemorrhage, hyperemesis gravidarum, and neonatal jaundice) were associated with advanced thyroid cancer. These findings suggest that some perinatal exposures may influence maternal thyroid cancer risk.

Symptomatic aseptic necrosis of benign thyroid lesions after microwave ablation: risk factors and clinical significance.

BACKGROUND: Symptomatic aseptic necrosis (SAN) followed by nodule rupture is a kind of severe complications after thermal ablation for benign thyroid nodules (BTN). No studies are available to evaluate its pathologic process, clinical manifestations, risk factors and effectiveness of therapies after microwave ablation (MWA). METHODS: From 2012 to 2019, 398 patients who received MWA for BTN were retrospectively reviewed. Clinical data included baseline patient characteristics, imaging features (internal vascularity and the proportion of the solid component), ablation power and time, complications and prognosis were collected and documented. RESULTS: Ten patients (2.51%) experienced post-MWA SAN, eight patients with nodule rupture and the other two without. The mean time from MWA to SAN symptom was 8.6 days and to rupture was 16.3 days. The initial symptoms of SAN patients were neck bulging, swelling and discomfort. Patients would go through nodule rupture once the nodule contents extended into the extrathyroidal area with the discontinuity of the anterior thyroid capsule, and fistula formed unavoidably in this condition. Incision drainage was effective for rupture and early treatment of non-steroidal anti-inflammatory drug might cure the early-stage SAN. Multivariate analysis showed sex (OR = 0.13; 95% CI: 0.03, 0.61; p=.03) was the risk factor leading to SAN and males were more vulnerable to SAN. CONCLUSION: SAN after MWA came earlier and initially illustrated as neck bulging, swelling and discomfort. Early detection and early treatment might prevent the rupture of nodules. Once the breakdown of thyroid capsule occurred, rupture of ablated nodules out of skin was unavoidable and invasive procedures might be the most effective treatment.

Association between thyroid gland diseases and breast cancer: a case-control study.

BACKGROUND: At the present time, there is no consensus on the association between benign thyroid diseases and breast cancer (BC). Therefore, the aim of this study is to help shed some light on the association between hyperthyroidism, hypothyroidism, and thyroiditis and breast cancer risk. METHODS: Use of the Disease Analyzer database (IQVIA) enabled us to perform a retrospective case-control study of 7408 women aged between 18 and 80, who were treated for an initial breast cancer diagnosis in a general practice in the United Kingdom between 2006 and 2015 (index date). Patients with a previous cancer diagnosis and an observation time of less than 12 months prior to the index date were excluded. The control group consisted of 7408 healthy women, who were matched to cases 1:1 by age, body mass index, hormone replacement therapy, and physician. The main outcome parameters of this study were the presence of thyroid disease (hypothyroidism, hyperthyroidism, struma, and thyroiditis) and the TSH values in the two groups. A univariate logistic regression model was used to investigate the association between benign thyroid diseases, TSH values, and BC. RESULTS: The mean age was 58.4 years in both groups. We found a significant association between thyroiditis and BC (OR: 1.91, p = 0.01) and were able to refute the association between hyperthyroidism/hypothyroidism and BC. We also found that thyroid-stimulating hormone (TSH) had no significant effect on breast cancer risk. CONCLUSION: Many experimental studies suggest a link between hyperthyroidism/hypothyroidism and BC. We were able to demonstrate an epidemiological association between thyroiditis and an increased BC risk. This shows the need for close monitoring for BC in women with thyroiditis.

Association between benign thyroid disease and breast cancer: a single center experience.

BACKGROUND: The relationship between breast cancer (BC) and thyroid disease (TD) is still controversial. The aim of the study was to investigate the possible coexistence of TD in patients with newly diagnosed BC and its correlation with BC clinical presentation with regard to menopausal status and stage of disease. METHODS: This is a retrospective cohort study of all patients treated for primary BC between 2014 and 2016 at the Breast Unit of Trieste University Hospital. Clinical charts and reports were reviewed for coexisting thyroid disorders (i.e. hyperthyroidism, hypothyroidism, benign TD, thyroid cancer, thyroid autoimmunity) and menopausal status at the time of BC diagnosis. Biomolecular profile, stage, and grading of BC were also evaluated. RESULTS: A total of 786 women and 7 men were included in the study. Co-presence of TD was found in 161(20.3%) cases: of these, 151(19.4%) patients presented benign TD and 10(1.3%) patients presented thyroid carcinoma. Thyroid autoimmunity was found in 51(32%) patients. Regarding thyroid function, 88(55%) patients had hypothyroidism, 19(12%) hyperthyroidism, and 54(33%) normal thyroid function. No statistically significant correlation was found between age and TD (p = 0.16), although TD was more common in women aged ≥60 years. Women with BC diagnosed at pre-menopausal age were more likely to have thyroid autoimmune diseases (45% vs. 29%, p = 0.05). No association was detected among BC molecular profiles with either thyroid autoimmunity (p = 0.26) or altered thyroid function (p = 0.63). High-grade BC was more frequent in women with hyperthyroidism (52.9%, p = 0.04), but the grading was independent from the presence of thyroid autoimmune disease (p = 0.87). BC stage was related to both thyroid autoimmunity (p = 0.04) and thyroid function (p < 0.001), with 55.2% of women affected by benign TD presenting with stage I BC and more aggressive BCs found in hypothyroid patients. CONCLUSIONS: According our study results, patients with primary BC present a greater incidence of autoimmunity disorders, especially when diagnosed in the pre-menopausal setting. However, further prospective studies are required to definitively prove causality.

Association of benign thyroid diseases with thyroid cancer risk: a meta-analysis of prospective observational studies.

PURPOSE: Evidence showed that benign thyroid disease was one of the risk factors for thyroid cancer. However, the results of some studies were inconsistent and were previously meta-analyses of case-control studies. Therefore, we performed a meta-analysis of prospective studies to investigate the relationship between benign thyroid diseases and thyroid cancer risk. METHODS: All eligible studies were identified via systematic searches of multiple literature databases. The combined RR (relative risk)/HR (hazard ratio) or SIR (standardized incidence ratio) with 95% confidence interval was calculated. Heterogeneity was assessed with the I2 test. Publication bias and subgroup analyses were also performed. RESULTS: Twelve studies were eligible for inclusion in the meta-analysis. The pooled RR/HR of thyroid carcinoma in benign thyroid diseases was 4.39 (95% CI 3.22-5.55). The pooled SIR of thyroid carcinoma in benign thyroid diseases was 5.98 (95% CI 4.09-7.86). Subgroup analysis was performed using the type of benign thyroid diseases. Effect value was RR/HR: hyperthyroidism (RR/HR = 3.89, 95% CI = 1.69-6.08), hypothyroidism (RR/HR = 2.72, 95% CI = 1.04-4.41), and goiter (RR/HR = 22.18, 95% CI = 12.09-32.28). Effect value was SIR: hyperthyroidism (RR/HR = 5.96, 95% CI = 1.88-10.03), goiter (RR/HR = 7.65, 95% CI = 6.94-8.37), and thyroiditis (RR/HR = 3.25, 95% CI = 1.62-4.89). CONCLUSIONS: Our study has shown that benign thyroid diseases might be associated with increased risk of thyroid cancer, especially in hyperthyroidism, hypothyroidism, and goiter. However, further investigation is needed to better understand the underlying biological mechanisms.

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.

THE ROMANIAN VERSION OF THE THYROID-RELATED PATIENT-REPORTED OUTCOMES THYPRO AND THYPRO-39. TRANSLATION AND ASSESSMENT OF RELIABILITY AND CROSS-CULTURAL VALIDITY.

BACKGROUND: ThyPRO is a recently developed thyroid-specific quality of life (QoL) questionnaire applicable to patients with benign thyroid disorders(BTD). The aim of the present study was to translate ThyPRO and ThyPRO-39 into Romanian, and to evaluate reliability and cross-cultural validity. METHODS: Standard methodology for translation and linguistic validation of patient-reported outcomes (PRO) was applied. The questionnaire was completed by 130 patients with benign thyroid diseases seen at Department of Endocrinology in the Emergency County Hospital, Tîrgu Mures, Romania, between October 2015 and March 2016. Internal reliability of the Romanian version of the ThyPRO (ThyPROro) scales was assessed for multi-item scales using Cronbach's alpha coefficient. An efficient method for testing cross-cultural validity is analysis of differential item functioning (DIF). Uniform DIF between the Romanian and the original Danish sample was investigated using ordinal logistic regression. The translation process proceeded without difficulties, and any disagreements were revised by one of the developers and the language coordinator. RESULTS: Internal reliability for ThyPRO was satisfactory. Cronbach`s alpha coefficients for the 13 scales ranged from 0.78 to 0.93 for the ThyPROro and 0.78 to 0.87 for the ThyPROro-39. In the 85-item ThyPRO, nine instances of DIF were found. Most were minor, explaining <3% of the variation in scale score, but DIF in positively worded items were larger, with explained variance (R2's) around 10-15%. CONCLUSION: The ThyPROro questionnaire is ready for assessment of health-related quality of life in Romanian patients with benign thyroid diseases.

Possible Impact of RET Polymorphism and Its Haplotypic Association Modulates the Susceptibility to Thyroid Cancer.

Rearranged during Transfection (RET) gene polymorphisms act to influence thyroid cancer in a polygenic and low-penetrance manner and no study regarding RET alterations in thyroid cancer has undergone from this part of the world (North India). We evaluated RET G691S (rs1799939), L769L (rs1800861), and S904S (rs1800863) polymorphisms to elucidate their possible role as risk factors in papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). Polymorphic analysis of RET gene was performed by polymerase chain reaction (PCR), followed by restriction fragment length polymorphism (RFLP). In RET G691S polymorphism, the overall distribution of variant alleles (GA + AA) in cases was 62.9% as against 44.5% in controls (P < 0.05) whereas frequency of RET L769L variant alleles (TG + GG) in cases was 70% versus 88% in controls (P < 0.05). In RET S904S, frequency of variant alleles (CG + GG) in cases was 56% versus 44% in controls (P < 0.05). Interestingly, G691S/L769L variant showed increased risk for the non-smokers (P < 0.05). RET S904S variant showed association with benign thyroid disease as against those with no history. The over-representation of homozygotes in G691S and L769L polymorphic variants was not observed, which suggest a "Dominant mode of inheritance." The S904S polymorphism heterozygote lies almost in the middle of the two homozygotes confirming an "Additive mode of inheritance." In conclusion, RET gene G691S/S904S polymorphisms were over-represented and L769L polymorphism was under-represented in PTC and FTC patients. RET polymorphic variants could act synergistically in the development or progression of PTC and FTC.

Benign thyroid disease and the risk of breast cancer: An updated systematic review and meta-analysis.

Background: The correlation between benign thyroid disease (BTD) and breast cancer (BC) has long been discussed. However, the definite relationship and potential mechanism between them are still disputed. The current meta-analysis aimed at performing a comprehensive assessment of the relationship between different types of benign thyroid disease and the risk of breast cancer, furthermore, assessing whether benign thyroid disease exerts an influence on the aggressiveness of breast cancer. Method: A systematic literature search (PubMed, Web of Science, MEDLINE, and Embase databases) identified studies to evaluate the correlation between BTD and BC risk. Data were analyzed using version 16.0 STATA software, including the odds ratio (OR) and its corresponding 95% confidence intervals (CIs). Publication bias and quality assessment were conducted for the included studies. Result: Overall, 18 studies involving 422,384 patients with BTD were incorporated. The outcome showed that autoimmune thyroiditis (OR: 2.56, 95%CI: 1.95-3.37, I2 = 0.0%, p=0.460), goiter (OR: 2.13, 95%CI: 1.19-3.79, I2 = 80.6%, p=0.000), and Graves' disease (OR: 5.01, 95%CI: 1.49-16.82, I2 = 0.0%, p=0.358) was connected with a higher risk of BC. Both hypothyroidism (OR: 0.82, 95%CI: 0.64-1.04, I2 = 85.0%, p=0.000) and hyperthyroidism (OR: 1.07, 95%CI: 0.93-1.24, I2 = 24.9%, p=0.206) had no significant association with the risk of BC. Additionally, the pooled analysis showed no apparent correlation between BTD and aggressiveness of BC. However, subgroup analysis indicated a positive relationship between BTD and aggressiveness of BC in the Europe subgroup (HR: 2.05, 95%CI: 1.32-3.17, I2 = 86.4%, p=0.000). Conclusion: Autoimmune thyroiditis, goiter, and Graves' disease are connected with an increased risk of BC. Furthermore, subgroup analysis suggested that BTD increases the aggressiveness of BC in the European population geographically. Nevertheless, further research is needed to prove these discoveries.

Thyroid disease-specific quality of life questionnaires - A systematic review.

INTRODUCTION: Thyroid diseases are very common and rarely life-threatening. One of the main therapeutic goals is an improvement in quality of life, making it important to measure in clinical and research settings. The aim of this systematic review is to provide an overview of the currently available thyroid-specific quality of life questionnaires with regard to their validation quality in order to make recommendations for clinical use with a special focus on German questionnaires. METHODS: A systematic literature search was performed in Pubmed, Google Scholar and the Cochrane Library. A total of 904 studies were identified. After excluding duplicates, non-English- or German-language texts, full texts that were not freely available and studies with irrelevant content, 64 studies reporting on 16 different questionnaires were included in the analysis. RESULTS: Four questionnaires concerned benign thyroid diseases (ThyPRO, ThyPRO-39, Thy-R-HRQoL and Thy-D-QOL), six malignant thyroid diseases (THYCA-QoL, ThyCa-HRLQOL, EORTC-Thy34, MADSI-Thy, QOL-Thyroid and ThyCAT), and six endocrine orbitopathy (GO-QOL, GO-QLS, TED-QOL, STED-QOL, TAO-QoL and Ox-TED). Only five questionnaires were at least developed, if not validated, in German, and five were developed in more than two languages. CONCLUSIONS: ThyPRO and the ThyPRO-39 are the best-evaluated questionnaires for benign thyroid diseases. Alternatively, in hypothyroid patients, the adequately validated Thy-D-QoL can be used. For malignant thyroid diseases, the choice should be made individually, as all six questionnaires (THYCA-QoL, ThyCA-HRQOL, EORTC-Thy34, MDASI-Thy, QOL-Thyroid and ThyCAT) have different strengths and weaknesses. The GO-QOL is the best-validated questionnaire in endocrine orbitopathy. However, the TED-QOL is also suitable as a short-screening questionnaire for these patients.

Incidentally discovered papillary thyroid microcarcinoma in patients undergoing thyroid surgery for benign disease.

INTRODUCTION: The incidence of thyroid carcinoma has grown significantly over the last few decades. A possible explanation is the increased diagnosis of small thyroid microcarcinoma (TMc). TMc reach a maximum diameter of ≤1 cm, identified during histopathology examination following a thyroidectomy performed for reasons not pertaining to malignancy. This study aims to investigate the prevalence of papillary thyroid microcarcinoma (PTMc) according to the benign pathology that refers patients to surgery and its trend evolution. METHODS: Retrospective cohort analysis of 1815 patients who underwent total thyroidectomy for non-malignant diseases in the 2005-2020 period. RESULTS: The mean age of the subjects was 53.5 years, with a higher proportion of women (1481, 82.1%). A total of 167 PTMc (9.3%) were incidentally discovered. A multivariate logistic regression analysis was performed, showing no differences in prevalence according to sex or age in patients with PTMc compared to final benign histology. Multinodular goiter increases the risk of PTMc with an odds ratio of 2.2 (p = 0.001) compared to Hashimoto's thyroiditis and Graves' disease (GD). There is a statistically significant increase in the incidence of PTMc in the group operated in the 2017-2020 vs. 2005-2008 period (p = 0.005). CONCLUSION: The overall prevalence of PTMc in patients who underwent thyroid surgery for the benign disease was 9.3%. Thyroid nodular hyperplasia was the most frequent benign pathology associated with PTMc compared to Hashimoto's or GD. Gender and age were not correlated with the prevalence of TMc. Over the years, surgical findings of PTMc have grown, particularly in the 2017-2020 period.

Quality of life in obese patients after thyroidectomy for goiter.

BACKGROUND: Compressive symptoms are common in thyroid disease. Many studies have focused on the size of the gland and its effects on patients. However, few have taken into account the body mass of the patient. The aim of our study was to examine whether or not a patient's body mass index (BMI) influences symptomatic outcomes following thyroid surgery for benign disease. METHODS: We conducted a prospective analysis evaluating 60 patients that underwent thyroidectomy for benign goiter (single or multinodular) disease. Patients were classified as obese, overweight, or normal based on BMI. Pre- and post-operative surveys were administered including the MRC breathlessness scale, M.D. Anderson Dysphagia Inventory (MDADI), and the ThyPRO quality of life questionnaire to evaluate dysphagia, dyspnea, and quality of life respectively. RESULTS: Patients classified as obese (n=37) scored significantly worse pre-operatively on MRC, MDADI, and ThyPRO surveys when compared to overweight (n=13) or normal weight (n=10) counterparts. Subjects in the obese group, but not the other groups, showed post-surgical improvement on both the MRC and MDADI surveys (P<0.0001). Similarly, obese subjects showed significant improvement on all 11 domains of the ThyPRO survey following surgery (P<0.0001), and overall degree of improvement was highly correlated with BMI among all subjects (r=0.60; P=0.0005). CONCLUSIONS: Obesity, as determined by BMI, is a critical factor to consider in the alleviation of compressive symptoms before and after thyroidectomy for goiter. Our analysis of survey data indicates obese subjects have increased benefit of surgery compared to their lighter counterparts.

Validity and reliability of the German version of the shortened thyroid-specific quality of life questionnaire (ThyPRO-39de).

OBJECTIVES: Validation of a German version of the ThyPRO-39 questionnaire for quality of life (QoL) in patients with benign thyroid diseases. DESIGN: Internal consistency, retest reliability, and validity were to be assessed in a test-retest study. METHODS: The ThyPRO-39 was translated based on standard methodology. A sample of 98 patients with benign thyroid diseases was tested with the ThyPRO-39de and the generic EuroQol 5D-5L. Forty-four patients with stable symptoms after 2 weeks formed the repeated measures sample. Cronbach's alpha was calculated for the ThyPRO-39de composite score and for each disease-specific scale. Intraclass correlations between the original and the repeated measures sample were calculated for each scale as well as Pearson correlations between various ThyPRO scales and the EuroQol. T-tests were used to test for differences in the goiter and hyperthyroid symptom scales between relevant patient groups and other patients. RESULTS: Internal consistency was between satisfactory and good, except for two scales (tiredness and cosmetic complaints/appearance). The test-retest correlation was between 0.62 and 0.8 for most scales, but below 0.5 for two scales (tiredness and impaired social life). There were significant correlations between the EuroQol index score and most aspects of the ThyPRO-39de. Only the hyperthyroid symptoms scale was specific for the relevant patient group (Graves' disease). CONCLUSION: The ThyPRO-39de may be recommended for use in clinical and research settings, especially with regards to the composite score. However, the underlying thyroid disease should always be kept in mind when interpreting the test results. A larger sample would be needed to implement further improvements.

Benign Thyroid Diseases: Are There Gender-Specific Differences for Diagnosis and Treatment of Nontoxic Thyroid Nodules? Results from a 4-Year Retrospective Analysis of an Endocrine Tumor Board.

INTRODUCTION: Benign nodular goiters are endemic in Germany and diagnostic thyroidectomy is one of the most frequent surgical procedures. Less than 10% result in a malignant finding which is a poor ratio in comparison to other European countries. There is a female preponderance in almost all thyroid pathologies according to the current literature but not much is known concerning gender-specific differences in thyroid nodules. OBJECTIVE: We aimed at finding gender-specific differences in diagnosis and treatment of nontoxic thyroid nodules and focused on preoperative workup as well as cytological and histological findings of patients with solitary and multinodular nontoxic goiters. METHODS: We retrospectively analyzed 392 cases out of 693 thyroid cases managed interdisciplinarily by the endocrine board of a university center between January 2015 and December 2018 (4 years). RESULTS: The combination of fine needle biopsy and interdisciplinary case discussion resulted in a rate of malignancy of 28.9% in patients undergoing surgery for solitary and multinodular nontoxic goiter. Although there was no significant gender-specific difference in the distributions and malignancy rates of Bethesda categories, male patients had a significantly higher malignancy rate of 40% in our collective (p = 0.04). CONCLUSIONS: Surgical treatment for male patients with suspicious hypofunctioning thyroid nodules should be favored. However, well-designed prospective studies are required to investigate gender-specific recommendations for the treatment of benign thyroid diseases in the future.

Correction for hyperfunctioning radiation-induced stunning (CHRIS) in benign thyroid diseases.

PURPOSE: Radioiodine-131 treatment has been a well-established therapy for benign thyroid diseases for more than 75 years. However, the physiological reasons of the so-called stunning phenomenon, defined as a reduced radioiodine uptake after previous diagnostic radioiodine administration, are still discussed controversially. In a recent study, a significant dependence of thyroid stunning on the pre-therapeutically administered radiation dose could be demonstrated in patients with goiter and multifocal autonomous nodules. A release of thyroid hormones to the blood due to radiation-induced destruction of thyroid follicles leading to a temporarily reduced cell metabolism was postulated as possible reason for this indication-specific stunning effect. Therefore, the aim of this study was to develop dose-dependent correction factors to account for stunning and thereby improve precision of radioiodine treatment in these indications. METHODS: A retrospective analysis of 313 patients (135 with goiter and 178 with multifocal autonomous nodules), who underwent radioiodine uptake testing and radioiodine treatment, was performed. The previously determined indication-specific values for stunning of 8.2% per Gray in patients with multifocal autonomous nodules and 21% per Gray in patients with goiter were used to modify the Marinelli equation by the calculation of correction factors for hyperfunctioning radiation-induced stunning (CHRIS). Subsequently, the calculation of the required activity of radioiodine-131 to obtain an intra-therapeutic target dose of 150 Gy was re-evaluated in all patients. Furthermore, a calculation of the hypothetically received target dose by using the CHRIS-calculated values was performed and compared with the received target doses. RESULTS: After integrating the previously obtained results for stunning, CHRIS-modified Marinelli equations could be developed for goiter and multifocal autonomous nodules. For patients with goiter, the mean value of administered doses calculated with CHRIS was 149 Gy and did not differ from the calculation with the conventional Marinelli equation of 152 Gy with statistical significance (p = 0.60). However, the statistical comparison revealed a highly significant improvement (p < 0.000001) of the fluctuation range of the results received with CHRIS. Similar results were obtained in the subgroup of patients with multifocal autonomous nodules. The mean value of the administered dose calculated with the conventional Marinelli equation was 131 Gy and therefore significantly below the CHRIS-calculated radiation dose of 150 Gy (p < 0.05). Again, the fluctuation range of the CHRIS-calculated radiation dose in the target volume was significantly improved compared with the conventional Marinelli equation (p < 0.000001). CONCLUSIONS: With the presented CHRIS equation it is possible to calculate a required individual stunning-independent radioiodine activity for the first time by only using data from the radioiodine uptake testing. The results of this study deepen our understanding of thyroid stunning in benign thyroid diseases and improve precision of dosimetry in radioiodine-131 therapy of goiter and multifocal autonomous nodules.

Racial disparities in surgical outcomes for benign thyroid disease.

INTRODUCTION: Previous studies have shown racial disparities in surgical outcomes in malignant thyroid disease. We hypothesize that minority groups have a higher incidence of postoperative complications following surgery for benign thyroid disease. METHODS: Using NSQIP (2016-2017), patients (>17 years) undergoing thyroid surgery for benign disease were identified. Outcomes included neck hematoma, recurrent laryngeal nerve (RLN) injury, and hypocalcemia. Multivariate analysis was performed controlling for patient factors. RESULTS: 6817 patients were identified. Postoperative outcomes were neck hematoma (2.0%), RLN injury (5.2%), and significant hypocalcemia (4.9%). Compared to White patients, Black patients had higher chance of neck hematoma (OR 2.32, 95% CI 1.51-3.55) and RLN injury (OR 1.97, 95% CI 1.53-2.55) while Asian patients had significantly greater odds of RLN injury (OR 1.88, 95% CI 1.15-3.06). CONCLUSION: Minority compared to White patients are more likely to have significant postoperative complications which indicates racial disparities in the surgical treatment for benign thyroid disease.

Hemithyroidectomy for benign euthyroid asymmetric nodular goitre.

BACKGROUND: There is no consensus on the optimal surgery extent for patients with benign euthyroid asymmetric nodular goitre (AMNG). METHODS: We reviewed medical literature using the PubMed engine to address the following issues: definition and prevalence, rationale for hemithyroidectomy, long-term outcomes, follow-up, revision surgery and image-guided thermal ablation of contralateral benign thyroid nodules following hemithyroidectomy for AMNG. RESULTS: In total, 102 articles were found in MEDLINE using a keyword search strategy; subsequently, we selected 36 articles with clinical pertinence. CONCLUSIONS: AMNG is a common clinical and surgical problem. Depending on the extent of the disease and individual surgeon preferences, either unilateral or bilateral thyroidectomy can be performed. Hemithyroidecomy can be considered for some patients with AMNG and the low risk of recurrent disease as a safer alternative to total thyroidectomy but it requires life-long follow-up, is associated with a higher recurrence risk and a need for revision thyroidectomy in selected subjects.

Thyroid stunning in radioiodine-131 therapy of benign thyroid diseases.

PURPOSE: Existence and cause of thyroid stunning was controversially discussed for decades but the underlying mechanism remains unclear. Numerous studies describe thyroid stunning in radioiodine-131 therapy (RIT) of differentiated thyroid carcinoma. However, there are no studies evaluating thyroid stunning in benign thyroid diseases caused by the radioiodine uptake test (RIUT). Therefore, the influence of pre-therapeutic tracer radiation dose on therapeutic iodine-131 uptake was evaluated retrospectively. METHODS: A total of 914 RIT patients were included. Exclusion criteria were anti-thyroid drugs, pre- and/or intra-therapeutic effective half-lives (EHL) beyond 8.04 days and externally performed RIUT or 24 h RIUT. All patients received RIUT 1 week before RIT. Thyroid volume was estimated via ultrasound. Tracer radiation dose to the thyroid was calculated retrospectively. The dependence of changes in the pre-therapeutic to the therapeutic extrapolated-maximum-131I-uptake (EMU) from the dose in RIUT was evaluated statistically. RESULTS: EMU in RIUT ranged from 0.10 to 0.82 (median: 0.35) and EMU in RIT ranged from 0.10 to 0.74 (median: 0.33). Averaged over the whole cohort the therapeutic EMU decreased significantly (2.3% per Gray intra-thyroidal tracer radiation dose). A disease-specific evaluation showed dose-dependent thyroid stunning from 1.2% per Gray in solitary toxic nodules (n = 327) to 21% per Gray in goiters (n = 135) which was significant for the subgroups of disseminated autonomies (n = 114), multifocal autonomies (n = 178) and goiters (p < 0.05) but not for Graves' diseases (n = 160) and solitary toxic nodules (p > 0.05). CONCLUSIONS: The presented data indicate for the first time a significant dependence of pre-therapeutic radiation dose on thyroid stunning in goiter and disseminated and multifocal autonomy. To achieve the desired intra-thyroidal radiation dose, RIT activity should be adapted depending on the dose in RIUT.

Impact of different approaches to calculation of treatment activities on achieved doses in radioiodine therapy of benign thyroid diseases.

PURPOSE: Radioiodine has been used for the treatment of benign thyroid diseases for over 70 years. However, internationally, there is no common standard for pretherapeutic dosimetry to optimally define the individual therapy activity. Here, we analyze how absorbed tissue doses are influenced by different approaches to pretherapeutic activity calculation of varying complexity. METHODS: Pretherapeutic determination of treatment activity was retrospectively recalculated in 666 patients who had undergone radioiodine therapy for benign thyroid diseases (Graves' disease, non-toxic goiter, and uni- and multinodular goiter). Approaches considering none, some, or all of a set of individual factors, including target volume, maximum radioiodine uptake, and effective half-life, were applied. Assuming individually stable radioiodine kinetics, which had been monitored twice a day under therapy, hypothetically achieved tissue doses based on hypothetically administered activities resulting from the different methods of activity calculation were compared to intended target doses. RESULTS: The Marinelli formula yields the smallest deviations of hypothetically achieved doses from intended target doses. Approaches taking individual target volume into consideration perform better than fixed therapy activities, which lead to high variances in achieved doses and high deviations of hypothetically achieved doses from intended target doses. CONCLUSION: Elaborate pretherapeutic dose planning, taking individual radioiodine uptake, half-life, and target volume into consideration, should be used whenever possible. The use of disease-specific fixed activities cannot be recommended. Deviations of achieved tissue doses from target doses can already be significantly lowered by application of volume-adapted treatment activities if more elaborate means are not available.

Penetrance of a rare familial mutation predisposing to papillary thyroid cancer.

Familial non-medullary thyroid cancer (FNMTC) is clinically defined as two or more first-degree relatives with NMTC and appears to follow an autosomal dominant inheritance pattern. Approximately 5-7% of NMTC is hereditary and affects multiple generations with a young age of onset. The primary aim of this study was to determine the age-specific penetrance of NMTC in individuals from a large family with FNMTC with a previously identified private mutation at 4q32, with a secondary aim to determine the penetrance for benign thyroid disease in this family. We present a large family with NMTC in which we had previously described a culpable mutation. Participants provided their personal medical history and family history. The germline 4q32 A > C mutation was detected in 34 of 68 tested individuals. Age-specific penetrance of thyroid cancer and benign thyroid disease was determined using the inverted Kaplan-Meier method of segregation analysis. Individuals who tested positive for the 4q32 mutation have a 68.9% (95% CI 46.5-88.7) risk of developing thyroid cancer by age 70 and a 65.3% (95% CI 46.0-83.8) risk of developing benign thyroid disease by age 70. The 4q32 A > C mutation significantly increases the risk to develop thyroid cancer but not benign thyroid disease in members of this family. The female:male sex ratio of 1.33 that we observed in affected mutation carriers differs greatly from the ratio of approximately 3:1 observed in PTC, supporting a central role of the mutation. Early thyroid surveillance with annual ultrasound is recommended to individuals testing positive for this private familial mutation.