Thyroid surgery in children and adolescents: results from a multi-institutional German and Austrian database.

BACKGROUND: Outcomes of paediatric thyroid surgery have only been reported in smaller series or over long intervals. The aim of this multicentre study was to describe the recent outcomes of paediatric thyroid surgery in Germany and Austria. METHODS: Patients aged less than or equal to 18 years who underwent thyroid surgery and were prospectively documented in the StuDoQ|Thyroid registry between March 2017 and August 2022 were studied. RESULTS: In total, 604 patients from 90 institutions were included. The mean age was 15.4 years and 75 per cent of patients were female. The most frequent benign pathologies were nodular goitre (35.6 per cent), follicular adenoma (30.1 per cent), and Graves' disease (28.5 per cent). Among 126 thyroid malignancies, papillary thyroid carcinoma was diagnosed in 77.8 per cent of patients, follicular thyroid carcinoma was diagnosed in 10.3 per cent of patients, and medullary thyroid carcinoma was diagnosed in 8.7 per cent of patients. Lymph node metastases were found in 45.9 per cent of patients with papillary thyroid carcinoma and in 36.4 per cent of patients with medullary thyroid carcinoma. Vascular invasion was found in 62.9 per cent of patients with follicular thyroid carcinoma. The mean tumour diameters were 18, 42, and 13 mm in patients with papillary thyroid carcinoma, follicular thyroid carcinoma, and medullary thyroid carcinoma respectively. Early postoperative recurrent laryngeal nerve injury was seen in 27 of 556 patients (4.9 per cent) (22 of 617 (3.6 per cent) nerves at risk with intermittent intraoperative nerve monitoring and 5 of 237 (2.1 per cent) nerves at risk with continuous intraoperative nerve monitoring). Persistent recurrent laryngeal nerve injury was documented in 4 of 556 patients (0.7 per cent). Early postoperative hypoparathyroidism correlated with Graves' disease, thyroid carcinoma, and lymph node dissection. CONCLUSION: Papillary thyroid carcinoma and follicular thyroid carcinoma in children were often advanced at presentation. Persistent or recurrent lymph node metastases were mainly seen in papillary thyroid carcinoma. Overall survival was excellent, but longer follow-up is needed.

Preoperative calcitonin testing improves the diagnosis of medullary thyroid carcinoma in female and male patients.

AIM: Calcitonin (Ctn) measurement in patients with thyroid disease could potentially increase the detection rates of medullary thyroid carcinoma (MTC) but remains a controversial issue. The aim of this study was to evaluate routine preoperative Ctn measurements. METHODS: All patients with thyroid surgery documented in the prospective StuDoQ|Thyroid registry between March 2017 and September 2020 were included. Cutoff levels for Ctn were determined with receiver-operating characteristic analyses to assess the preoperative diagnosis of MTC in subgroups for females and males. FINDINGS: In 29 590 of 39 679 patients (75%) participating in the registry, routine preoperative Ctn testing was performed. In 357 patients (227 females and 130 males), histopathology confirmed MTC with a mean tumor size of 14.7 mm (±12.43). Biochemical cure was achieved in 71.4% of the patients. Ctn levels between 11 and 20 pg/mL were seen in 2.6% of the patients, and only 0.7% of the patients had Ctn levels above 21 pg/mL. Cutoff levels for the diagnosis of MTC were 7.9 pg/mL for females and 15 pg/mL for males (P < 0.001). The sensitivity and specificity for females were 95 and 98%, and 96 and 97% for males, respectively. CONCLUSION: Routine Ctn testing is a reliable predictor for MTC and provides the opportunity for earlier thyroidectomy before lymph node metastases occur, resulting in a better prognosis. Females with Ctn levels >7.9 pg/mL and males >15 pg/mL without any other extrathyroidal sources for an elevated Ctn should be monitored. Thyroid surgery should be considered if Ctn levels are increasing or ultrasound detects suspicious thyroid lesions.

The EANM practice guidelines for parathyroid imaging.

INTRODUCTION: Nuclear medicine parathyroid imaging is important in the identification of hyperfunctioning parathyroid glands in primary hyperparathyroidism (pHPT), but it may be also valuable before surgical treatment in secondary hyperparathyroidism (sHPT). Parathyroid radionuclide imaging with scintigraphy or positron emission tomography (PET) is a highly sensitive procedure for the assessment of the presence and number of hyperfunctioning parathyroid glands, located either at typical sites or ectopically. The treatment of pHPT is mostly directed toward minimally invasive parathyroidectomy, especially in cases with a single adenoma. In experienced hands, successful surgery depends mainly on the exact preoperative localization of one or more hyperfunctioning parathyroid adenomas. Failure to preoperatively identify the hyperfunctioning parathyroid gland challenges minimally invasive parathyroidectomy and might require bilateral open neck exploration. METHODS: Over a decade has now passed since the European Association of Nuclear Medicine (EANM) issued the first edition of the guideline on parathyroid imaging, and a number of new insights and techniques have been developed since. The aim of the present document is to provide state-of-the-art guidelines for nuclear medicine physicians performing parathyroid scintigraphy, single-photon emission computed tomography/computed tomography (SPECT/CT), positron emission tomography/computed tomography (PET/CT), and positron emission tomography/magnetic resonance imaging (PET/MRI) in patients with pHPT, as well as in those with sHPT. CONCLUSION: These guidelines are written and authorized by the EANM to promote optimal parathyroid imaging. They will assist nuclear medicine physicians in the detection and correct localization of hyperfunctioning parathyroid lesions.

Short-Term Outcomes of Surgery for Graves' Disease in Germany.

BACKGROUND: Surgical treatment of Graves' disease (GD) has a potentially increased incidence of postoperative hypoparathyroidism, recurrent laryngeal nerve palsy (RLNP) and bleeding. The aim of this study was to evaluate the current extent of surgery for the treatment of GD and its safety as a short-term outcome. METHODS: Patients who underwent thyroid resection for GD were identified from the prospective StuDoQ/Thyroid registry. Patient data were retrospectively analyzed regarding demographics, surgical procedures and perioperative outcomes. Statistics were performed with Student's t-test or Fisher's exact test and multivariate Cox regression analysis. The level of statistical significance was set at p < 0.05. RESULTS: A total of 1808 patients with GD with a median age of 44 (range 14-85) years were enrolled in a 25-month period by 78 departments, of which 35.7% (n = 645) had an endocrine orbitopathy and 0.1% (n = 6) had thyrotoxic crisis. Conventional open surgery was used in 98.6% of cases and minimally invasive or remote-access approaches were used in 1.4%. Total thyroidectomy was performed in 93.4% of cases (n = 1688). Intraoperative neuromonitoring (IONM) was used in 98.9% (n = 1789) of procedures. In 98.3% (n = 1777) at least one parathyroid gland was visualized and in 20.7% (n = 375) parathyroids were autografted. The rates of unilateral and bilateral transient RLNP were 3.9% (n = 134/3429 nerves at risk) and 0.1% (n = 4/3429 NAR). The rates of transient RLNP tended to be higher when intermittent IONM was used compared to continuous IONM (4.1% vs. 3.4%, p < 0.059). The rate of transient postoperative hypoparathyroidism was overall 29% (n = 525/1808). Multivariate analysis revealed fewer than 300 thyroid resections and fewer than 15 thyroid resections for GD per year, male sex, BMI > 30, autotransplantation of parathyroid glands and previous bilateral thyroid surgery as independent risk factors for postoperative temporary hypoparathyroidism. Reoperations for bleeding (1.3%) were rare. CONCLUSION: Total thyroidectomy with IONM is safe and currently the most common surgical therapy for GD in Germany. Postoperative hypoparathyroidism is the major complication which should be focused on.

[Current treatment strategies for papillary thyroid microcarcinoma]. / Aktuelle Therapiestrategien beim papillären Mikrokarzinom der Schilddrüse.

Surgical treatment of papillary thyroid microcarcinoma (PTMC) is evolving more and more into a controversial issue. As in Japan more than 50% of PTMCs are only observed, an increasing number of physicians in the western world are calling for active surveillance instead of lobectomy or total thyroidectomy. Unifocal carcinomas of older patients without extrathyroidal growth or lymph node involvement seem to be candidates for active surveillance. First estimations for a lifelong observation show that patients <30 years old will have a probability of tumor progression of more than 60%. A decision for surgery versus active surveillance has to weigh up all the arguments for and against, which have to be discussed and planned in detail together with the patient.

Symptoms of Primary Hyperparathyroidism in Men and Women: The Same but Different?

INTRODUCTION AND OBJECTIVE: Typical symptoms for primary hyperparathyroidism (pHPT) include osteoporosis, bone or joint pain, and nephrolithiasis, as well as fatigue, depression, gastritis, and cardiovascular disease. The female:male ratio was 3:1. The aim of this retrospective study was to evaluate the possible influence of gender-specific aspects of these symptoms. METHODS: From February 2018 to November 2019, parathyroid surgery was performed in 125 patients with pHPT (age: 23-83 years); 95 (76%) were female, and 30 (24%) were male. Preoperatively, a standardized medical history including 7 typical symptoms of pHPT was used for routine clinical documentation according to the StuDoQ Thyroid and Parathyroid Registry. RESULTS: For both groups (mean age: 60.4 years for females and 60.2 years for males), no sex differences were found in serum calcium or parathyroid hormone levels. For females, there was a tendency towards smaller hyperfunctioning parathyroid glands (16.8 vs. 20.5 mm) with less weight (1.14 vs. 1.52 g) and multiglandular disease. Nephrolithiasis was significantly more frequent in men than in women (36.7 vs. 16.8%, respectively; p = 0.036), but the difference in hypertension was not significant (60% in men vs. 47.4% in women, p = 0.230). Women reported significantly more often bone and joint pain (44.2% in women vs. 20% in men, p = 0.053) and depressive episodes (32.6% in women vs. 10% in men, p = 0.016). CONCLUSION: 91.2% of patients transferred for parathyroidectomy described typical symptoms of pHPT. However, an unexpected high gender difference was found following the analysis of symptoms documented in the StuDoQ Registry.

Current Practice of Surgery for Benign Goitre-An Analysis of the Prospective DGAV StuDoQ|Thyroid Registry.

BACKGROUND: To evaluate the current indications, resection strategies and short-term outcomes of surgery for benign goitre in a country with endemic goitre. METHODS: Data of patients who underwent surgery for benign goitre were retrieved from the prospective StuDoQ/Thyroid registry and retrospectively analysed regarding the patient's demographics, indications for surgery, surgical procedures, histology, and perioperative outcomes. RESULTS: In a 15-month period, 12,888 patients from 83 departments underwent thyroid resections for benign conditions. Main indications for surgery were exclusion of malignancy (68%), compression symptoms (20.7%) and hyperthyroidism (9.7%). Preoperative fine needle aspiration cytology was performed in only 12.2% of patients with the indication "exclusion of malignancy". Thyroidectomy (49.8%) or hemithyroidectomy (36.9%) were performed in 86.7% of patients. Minimally invasive or alternative surgical techniques were applied in only 2.2%. Intraoperative neuromonitoring was used in 98.4% of procedures, in 97.5% of patients at least one parathyroid gland was visualized, and in 15.3% of patients parathyroid tissue was autografted, respectively. The rates of unilateral and bilateral transient recurrent nerve palsy were 3.6% and 0.07% of nerves at risk, the rate of transitory hypoparathyroidism was 15.3%. The rates of postoperative bleeding and wound infections requiring reoperation were 1.4% and 0.07%, respectively. CONCLUSIONS: The indication "exclusion of malignancy" is made too liberally, and there is a strong attitude to perform complete thyroid resections. Postoperative hypoparathyroidism is the major complication after surgery for benign thyroid disease, thus requiring more awareness.

Can preoperative vitamin D deficiency predict postoperative hypoparathyroidism following thyroid surgery?

IMPORTANCE: Postoperative hypoparathyroidism remains a relevant problem after thyroid surgery. Although the roles of vitamin D deficiency and other risk factors have been discussed in previous studies, variable results have been reported. OBJECTIVE: Predicting the risk of postoperative hypocalcemia could be helpful for individual prognoses and medical treatment. PATIENTS AND METHODS: Documentation and analysis of bilateral thyroid operations performed between July 2011 and May 2014 were studied. Results involving age, gender, diagnosis, surgical techniques, pre- and postoperative calcium and parathyroid hormone (PTH) levels, and especially, the role of preoperative vitamin D levels were assessed in uni- and multivariate analyses. RESULTS: Bilateral thyroid surgery was performed in 361 patients with multinodular goiters (n = 224), Graves' disease (n = 40), or thyroid carcinoma (n = 97). In total, 124 patients (34%) with postoperative hypoparathyroidism, defined as having a PTH level ≤ 10 pg/mL, were treated with calcium and vitamin D regardless of their symptoms. The rate of permanent hypoparathyroidism was 3.6% and correlated with the extent of surgery; the highest risks were shown for total thyroidectomy and central lymph node dissection. In univariate analysis, the extent of surgery, parathyroid autotransplantation, and histopathology were the strongest predictors of hypoparathyroidism. Even severe vitamin D deficiency (< 10 ng/mL) showed a trend only towards a higher transient hypoparathyroidism risk (p = 0.0514) but failed to predict permanent hypoparathyroidism. CONCLUSION: Postoperative PTH levels accurately identified patients at risk for hypoparathyroidism. Decreased preoperative vitamin D levels could not predict hypocalcemia, and high vitamin D levels could not prevent permanent hypoparathyroidism.

Prediction of Postoperative Vocal Fold Function After Intraoperative Recovery of Loss of Signal.

OBJECTIVES/HYPOTHESIS: This multicenter study aimed to 1) evaluate early postoperative vocal fold function in relation to intraoperative amplitude recovery, and 2) determine optimal absolute and relative thresholds of intraoperative amplitude recovery heralding normal early postoperative vocal fold function, both after segmental type 1 and after global type 2 loss of signal (LOS). STUDY DESIGN: Prospective outcome study. METHODS: This study, encompassing nine surgical centers from four countries, correlated intraoperative amplitude recovery with early postoperative vocal fold function using receiver operating characteristic analysis. RESULTS: Included in this study were 68 patients, 48 women and 20 men, who sustained transient recurrent laryngeal nerve injury during thyroid surgery under continuous intraoperative nerve monitoring. Early transient vocal fold palsy was seen in 18 (64%) of 28 patients with ipsilateral segmental LOS type 1, and in 10 (25%) of 40 patients with ipsilateral global LOS type 2. On receiver operating characteristic analysis, relative amplitude thresholds were superior to absolute amplitude thresholds in predicting vocal fold function after LOS type 2 (area under the curve [AUC]: 0.83 vs. 0.65; P = .01 vs. P = .15; Youden index 44% and 253 µV) and LOS type 1 (AUC: 0.96 vs. 0.97; P < .001 each; Youden index 49% and 455 µV). Amplitude recovery ≥50% of baseline after LOS always indicated intact vocal fold function. CONCLUSIONS: When the nerve amplitude recovers ≥50% of baseline after segmental LOS type 1 or global LOS type 2, it is appropriate to extend completion thyroidectomy to the other side during the same session. LEVEL OF EVIDENCE: 2b Laryngoscope, 129:525-531, 2019.

Medullary Thyroid Carcinoma: Why Is Specialization Mandatory?

Medullary thyroid carcinoma (MTC) represents a distinct form of thyroid cancer with a potentially aggressive behavior, early lymph node metastases, and sporadic as well as hereditary forms. Only surgery with total thyroidectomy and lymph node dissection is able to achieve biochemical cure. Due to the uncommon nature of MTC, a specialization in endocrine surgery for diagnosis as well as therapy of MTC seem to be mandatory for a successful treatment. Knowledge of genotype-phenotype correlations for hereditary forms or routine calcitonin screening for sporadic forms is important to analyze preoperative findings and plan surgical procedures. Postoperative follow-up depends on biochemical cure or monitoring for patients with elevated calcitonin levels.

Is C-11 Methionine PET/CT Able to Localise Sestamibi-Negative Parathyroid Adenomas?

BACKGROUND: Patients with primary hyperparathyroidism (pHPT) and a negative preoperative Tc-99 sestamibi (MIBI) scintigraphy are considered to have a higher risk of persistent disease. The aim of this study was to assess whether additional imaging with C-11 methionine positron emission tomography/computed tomography (Met-PET/CT) is able to localise sestamibi-negative hyperfunctioning parathyroid glands. METHODS: In 50 patients (38 females, 12 males, age 13-81 years) with pHPT and negative localisation procedures such as ultrasound and sestamibi, a Met-PET/CT was performed before parathyroid surgery. The results of Met-PET/CT were analysed prospectively and compared with intraoperative and histopathological findings. 22% of the patients underwent previous parathyroid and/or thyroid surgery. RESULTS: Met-PET/CT correctly located a single-gland adenoma in 33 of 45 (73%) patients with pHPT. In 5 patients with multiglandular disease, Met-PET/CT detected at least one hyperfunctional parathyroid gland in 4 patients (80%). In 3 patients with double adenomas, 5 of 6 parathyroids were correctly located. Overall, 40 of 57 (70%) hyperfunctioning glands were identified with Met-PET/CT. Met-PET/CT was false-negative in 12 of 50 (24%) patients and false-positive in only one case (2%). Postoperatively, 48 of 50 patients (96%) were cured. CONCLUSIONS: Additional pre-interventional imaging with Met-PET/CT was able to identify hyperfunctioning parathyroid glands in 74% of patients with pHPT and negative sestamibi scans, thus enabling successful parathyroid surgery.

Local recurrence in the neck and survival after thyroidectomy for metastatic renal cell carcinoma.

BACKGROUND: Most investigations of thyroidectomy for metastatic renal cell carcinoma (RCC) are case studies or small series. This study was conducted to determine the contribution of clinical and histopathologic variables to local recurrence in the neck and overall survival after thyroidectomy for RCC metastases. METHODS: The medical records of 140 patients with thyroidectomy for metastatic RCC performed between 1979 and 2012 at 25 institutions in Germany and Austria were analyzed. RESULTS: The median interval between nephrectomy and thyroidectomy was 120 months. Concurrence of thyroid and pancreatic metastases was present in 23 % of the patients and concurrence of thyroid and adrenal metastases in 13 % of the patients. Clinical outcome data were available for 130 patients with a median follow-up period of 34 months. The 5-year overall survival rate was 46 %, and 28 % of patients developed a local neck recurrence at a median of 12 months after thyroidectomy. Multivariate analysis showed that invasion of adjacent cervical structures (hazard ratio [HR] 3.2; p = 0.001), patient age exceeding 70 years (HR 2.5; p = 0.004), and current or past evidence of metastases to nonendocrine organs (HR 2.4; p = 0.003) were independent determinants of inferior overall survival. Conversely, invasion of adjacent cervical structures (HR 12.1; p < 0.0001) and year of thyroidectomy (HR 5.7 before 2000; p < 0.0001) were shown to be independently associated with local recurrence in the neck by multivariate analysis. CONCLUSIONS: Although significant improvement of local disease control in patients with thyroid metastases of RCC has been achieved during the last decade, overall outcome continues to be poor for patients with locally invasive thyroid metastases.

Differentiated thyroid cancer-personalized therapies to prevent overtreatment.

The concept of individualized therapy is rapidly gaining recognition in the management of patients with differentiated thyroid cancer (DTC). This Review provides an overview of the most important elements of this paradigm shift in DTC management and discusses the implications for clinical practice. In the majority of patients with DTC who have an inherently good prognosis, the extent of surgery, the dosage of (131)I therapy and the use of levothyroxine therapy are all aspects suitable for individualization, on the basis of both the stage of disease and the response to treatment. In individuals with advanced disease, newer imaging techniques, advances in (131)I therapy and the use of targeted molecular therapies (such as multitargeted kinase inhibitors) have provided new options for the personalized care of patients, for whom until recently no effective therapies were available. Individualized therapies could reduce adverse effects, including the sometimes debilitating hypothyroidism that used to be required before initiation of (131)I treatment, and major salivary gland damage, a common and unpleasant side effect of (131)I therapy. Highly individualized interdisciplinary treatment of patients with DTC might lead to improved outcomes with reduced severity and frequency of complications and adverse effects. However, in spite of ongoing research, personalized therapies remain in their infancy.

Parathyroidectomy, elevated depression scores, and suicidal ideation in patients with primary hyperparathyroidism: results of a prospective multicenter study.

OBJECTIVE: To assess anxiety and depression symptoms, suicidal ideation, and health-related quality of life (HRQOL) in a large series of consecutive patients with primary hyperparathyroidism (pHPT) before and after parathyroidectomy. DESIGN: This prospective multicenter study investigated preoperative and postoperative depression, anxiety, suicidal ideation, and HRQOL in patients with pHPT and compared these variables with a control group with nontoxic thyroid nodules. PATIENTS: The study included 194 patients with pHPT and 186 control subjects. MAIN OUTCOME MEASURES: Depression was evaluated with the Hospital Anxiety and Depression Scale (HADS) and the Patient Health Questionnaire-9, which also assessed suicidal ideation. Anxiety was evaluated with the HADS. Health-related quality of life was measured with the 36-Item Short Form survey. RESULTS: Parathyroidectomy achieved a 98% cure rate. Preoperatively, severe depression (HADS score ≥ 11) was seen in 20% of the pHPT group and 9% of the control group. The Patient Health Questionnaire-9 detected moderate to severe depression in 17% of the patients with pHPT and 7% of the control subjects. Patients with pHPT had higher HADS anxiety scores (mean, 7.7) than control subjects (P < .01) or the German normative sample (P < .001). Compared with control subjects, patients with pHPT had significantly lower 36-Item Short Form survey preoperative physical and mental health summary scores (42.7 vs 49.5 and 41.2 vs 46.8, respectively; P = .001 for both comparisons). At 12 months follow-up, depression and anxiety decreased significantly in patients with pHPT; the prevalence of suicidal ideation was more than halved from the baseline (10.7% vs 22%; P = .008). Both physical and mental health scores (45.7 and 47.7, respectively) improved in patients with pHPT (P < .001 each) but not in control subjects. CONCLUSIONS: Depression, anxiety, and decreased HRQOL appear to be related to pHPT. Successful parathyroidectomy seems to reduce psychopathologic symptoms and improve HRQOL in this setting.

Accurate preoperative localization of parathyroid adenomas with C-11 methionine PET/CT.

BACKGROUND: Focused unilateral or minimally invasive parathyroidectomy for primary hyperparathyroidism (pHPT) depends on the successful preoperative localization of parathyroid adenomas. The aim of this prospective study was to determine the accuracy of C-11 methionine positron emission tomography/computed tomography (Met-PET/CT), a novel localization procedure for hyperfunctional parathyroid tissue. METHODS: Preoperative Met-PET/CT scans of the neck and mediastinum of 102 patients undergoing parathyroidectomy for pHPT were preoperatively evaluated by a radiologist and a nuclear medicine physician and prospectively documented. The results of Met-PET/CT were compared with intraoperative and histopathological findings. RESULTS: pHPT was caused by a single-gland adenoma in 97 patients, whereas 5 patients had multiglandular disease. Met-PET/CT correctly located a single-gland adenoma in 83 of 97 (86%) patients with pHPT (sensitivity 91%). The positive predictive value of Met-PET/CT in localizing a single-gland adenoma was 93%. Of the 5 patients with multiglandular disease, Met-PET/CT identified 2 hyperfunctioning parathyroid glands in 1 patient, 1 gland in 3 individuals, and was negative in the fifth patient (sensitivity 80%). A highly significant correlation was observed between true-positive findings and the size (mean = 1.81 ± 0.84 cm) and weight (mean = 1.50 ± 2.56 g) of parathyroid adenoma, whereas patients with false-negative findings had significantly smaller (mean = 1.09 ± 0.41 cm) and lighter (mean = 0.37 ± 0.29 g) glands (P < 0.001 and P = 0.001, respectively). CONCLUSIONS: This study demonstrates the high accuracy of Met-PET/CT in the preoperative localization of parathyroid adenomas in a large series of patients with pHPT.

Familial nonmedullary thyroid carcinoma-clinical relevance and prognosis. A European multicenter study. ESES Vienna presentation.

PURPOSE: Approximately 5% of differentiated thyroid carcinomas are of familial origin. These familial nonmedullary thyroid carcinomas (FNMTC) have an increased risk of multifocal disease and lymph node involvement. Consequently, higher recurrence rates and decreased disease-specific survival rates are described. The best surgical approach is discussed controversially. PATIENTS AND METHODS: A survey among the international members of the German Society of Endocrine Surgeons revealed 20 families with two or more first-degree relatives with FNMTC. The mean age of the 41 patients (30 female, 11 male) with FNMTC was 40.6 years (18-73 years). RESULTS: Total thyroidectomy was performed in 31 of 41 patients (76%). Ninety-five percent of the tumors were papillary carcinomas. Two of 41 patients had follicular carcinomas. Ten patients (24%) with papillary carcinomas were diagnosed with Hashimoto's thyroiditis. The mean tumor size was 1.45 cm. FNMTC was multifocal in 12 patients (29%). A systematic lymph node dissection was performed in 21 of 41 patients (51%). Lymph nodes metastases were found in seven of these 21 patients. Twenty-eight of the patients (68%) underwent postoperative radioiodine ablation. After a mean follow-up of 7.2 years, 39 patients (95%) were disease free. One patient developed local recurrence and lung metastases, 10 and 25 years, respectively, after initial diagnosis. Another patient died 2 years postoperatively from advanced metastatic disease. CONCLUSIONS: FNMTC is associated with an early onset of small, mostly papillary thyroid carcinomas and an increased risk of multifocality and lymph node involvement. Total thyroidectomy and systematic neck dissection are recommended together with radioiodine ablation. Screening for first-degree relatives should start at age 18 years.

Urokinase receptor, MMP-1 and MMP-9 are markers to differentiate prognosis, adenoma and carcinoma in thyroid malignancies.

The identification of high-risk patients with thyroid cancer and the preoperative differentiation between follicular adenoma and carcinoma remain clinically challenging. Our study was conducted to analyze whether the quantification of matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator receptor (u-PAR) and transcription factor binding to the u-PAR promoter improve prognostic predictability and differential diagnosis of thyroid tumors. Tumor/normal tissue was collected from 69 prospectively followed patients with thyroid carcinomas (papillary, medullary, follicular and anaplastic, PTC, MTC, FTC and ATC) or follicular adenomas. U-PAR, MMP-1, MMP-7 and MMP-9 amounts were determined by ELISA, and transcription factor binding was determined by electrophoretic mobility shift assay. Binding of transcription factors to the u-PAR promoter was observed, but not associated with u-PAR expression. Carcinomas except MTC expressed significantly more u-PAR/MMPs than adenomas/normal tissues, this being associated with advanced pT- or M-stages. MMP-1 and MMP-9 were significantly higher in follicular carcinomas than in adenomas. In carcinomas, high u-PAR-gene expression correlated significantly with high MMP-9, the latter being associated with MMP-7 in normal tissues. Poor survival in differentiated tumors was associated in trend (p = 0.07); poor survival of all patients (p = 0.043) and especially of patients with carcinomas of follicular origin (including ATC), but not medullary carcinomas, were significantly associated with high u-PAR-protein (p = 0.015). Quantification of u-PAR is of prognostic relevance in thyroid carcinomas of non-c-cell origin, and u-PAR in part may be regulated nontranscriptionally in thyroid cancers. This is the first study to suggest MMP-1/-9 as significant differentiation markers between follicular adenoma and follicular carcinoma.