Clinico-pathological factors associated with radioiodine refractory differentiated thyroid carcinoma status.

PURPOSE: Risk factors for developing radioiodine refractory thyroid cancer (RAIR-TC) have rarely been analyzed. The purpose of the present study was to find clinical and pathological features associated with the occurrence of RAIR-disease in differentiated thyroid cancers (DTC) and to establish an effective predictive risk score. METHODS: All cases of RAIR-DTC treated in our center from 1990 to 2020 were retrospectively reviewed. Each case was matched randomly with at least four RAI-avid DTC control patients based on histological and clinical criteria. Conditional logistic regression was used to examine the association between RAIR-disease and variables with univariate and multivariate analyses. A risk score was then developed from the multivariate conditional logistic regression model to predict the risk of refractory disease occurrence. The optimal cut-off value for predicting the occurrence of RAIR-TC was assessed by receiver operating characteristic (ROC) curves and Youden's statistic. RESULTS: We analyzed 159 RAIR-TC cases for a total of 759 controls and found 7 independent risk factors for predicting RAIR-TC occurrence: age at diagnosis ≥ 55, vascular invasion, synchronous cervical, pulmonary and bone metastases at initial work-up, cervical and pulmonary recurrence during follow-up. The predictive score of RAIR-disease showed a high discrimination power with a cut-off value of 8.9 out of 10 providing 86% sensitivity and 92% specificity with an area under the curve (AUC) of 0.95. CONCLUSION: Predicting the occurrence of RAIR-disease in DTC patients may allow clinicians to focus on systemic redifferentiating strategies and/or local treatments for metastatic lesions rather than pursuing with ineffective RAI-therapies.

Treatment of Obesity with Thyroid hormones in Europe. Data from the THESIS* Collaboration.

PURPOSE: The use of thyroid hormones (TH) to treat obesity is unsupported by evidence as reflected in international guidelines. We explored views about this practice, and associations with respondent characteristics among European thyroid specialists. METHODS: Specialists from 28 countries were invited to a survey via professional organisations. The relevant question was whether "Thyroid hormones may be indicated in biochemically euthyroid patients with obesity resistant to lifestyle interventions". RESULTS: Of 17,232 invitations 5695 responses were received (33% valid response rate; 65% women; 90% endocrinologists). Of these, 290 (5.1%) stated that TH may be indicated as treatment for obesity in euthyroid patients. This view was commoner among non-endocrinologists (8.7% vs. 4.7%, p < 0.01), private practice (6.5% vs. 4.5%, p < 0.01), and varied geographically (Eastern Europe, 7.3%; Southern Europe, 4.8%; Western Europe, 2.7%; and Northern Europe, 2.5%). Respondents from Northern and Western Europe were less likely to use TH than those from Eastern Europe (p < 0.01). Gross national income (GNI) correlated inversely with this view (OR 0.97, CI: 0.96-0.97; p < 0.001). Having national guidelines on hypothyroidism correlated negatively with treating obesity with TH (OR 0.71, CI: 0.55-0.91). CONCLUSIONS: Despite the lack of evidence, and contrary to guidelines' recommendations, about 5% of respondents stated that TH may be indicated as a treatment for obesity in euthyroid patients resistant to life-style interventions. This opinion was associated with (i) respondent characteristics: being non-endocrinologist, working in private practice, treating a small number of hypothyroid patients annually and (ii) national characteristics: prevalence of obesity, Eastern Europe, low GNI and lack of national hypothyroidism guidelines.

Impact on testicular function of a single ablative activity of 3.7 GBq radioactive iodine for differentiated thyroid carcinoma.

STUDY QUESTION: What are the consequences of radioactive iodine (RAI) therapy for testicular function? SUMMARY ANSWER: A single activity of 3.7 GBq RAI for differentiated thyroid carcinoma (DTC) treatment in young men transiently altered Sertoli cell function and induced sperm chromosomal abnormalities. WHAT IS KNOWN ALREADY: Few studies, mainly retrospective, have reported the potential impacts of RAI on endocrine and exocrine testicular function. STUDY DESIGN, SIZE, DURATION: A longitudinal prospective multi-center study on testicular function performed in DTC patients before a single 131I ablative activity of 3.7 GBq (V0) and at 3 months (V3) and 13 months (V13) after treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS: Forty male patients, aged 18-55 years, with DTC participated. Hormonal analysis included FSH, LH, testosterone and inhibin B serum levels at V0, V3 and V13. Furthermore, sperm parameters, DNA fragmentation and sperm chromosomal abnormalities were evaluated at each time points. The differences in all parameters, between V0-V3, V0-V13 and V3-V13, were analyzed, using a Wilcoxon test. MAIN RESULTS AND THE ROLE OF CHANCE: Prior to RAI administration, all patients had normal gonadal function. At V3, a statistically significant increase in FSH levels and a decrease in inhibin B levels were observed and sperm concentration, as well as the percentage of morphologically normal spermatozoa, were significantly decreased (P < 0.0001). These modifications were transient as both sperm concentration and normal morphology rate returned to baseline values at V13. However, at this later time point, FSH and inhibin B levels were still impacted by RAI administration but remained in the normal range. Although no DNA fragmentation was observed at V3 nor V13, our study revealed a statistically significant increase in the number of sperm chromosomal abnormalities both at V3 (P < 0.001) and V13 (P = 0.01). LIMITATIONS, REASONS FOR CAUTION: Among the 40 patients included in the study, only 24 had all the parameters available at all visits. WIDER IMPLICATIONS OF THE FINDINGS: Prospective studies with longer term follow up would be helpful to determine whether the chromosome abnormalities persist. These studies would be required before sperm banking should be suggested for all patients. However, sperm preservation for DTC patients who require cumulative radioiodine activities higher than 3.7 GBq should be proposed. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Programme Hospitalier de Recherche Clinique, AP-HP (No. P040419). The authors report no conflict of interest in this work. TRIAL REGISTRATION NUMBER: NCT01150318.

[Efficacy and tolerance of salvage curative radiotherapy for patients with cervical relapse of differentiated thyroid carcinoma]. / Efficacité et tolérance de la radiothérapie externe pour les patients atteints d'une récidive d'un carcinome différencié de la thyroïde.

PURPOSE: Radiation therapy is often the last resource treatment for cervical relapse in iodine refractory differentiated thyroid cancer. We present locoregional control data in patients with cervical relapse treated with curative intent radiation therapy with or without concomitant carboplatin. MATERIAL AND METHODS: This monocentric retrospective study gathered data on patients with differentiated thyroid carcinoma - vesicular or papillary - in relapse after thyroidectomy who received a curative intent cervical radiation therapy. Locoregional progression free survival (LRPFS), progression free survival (PFS), overall survival (OS) were gathered as well as acute and chronic adverse events assessed with the CTCAE v4. RESULTS: Thirty-nine patients were consecutively included between 2005 and 2019. The median follow-up was 36.6months. Fifteen patients (38%) had a locoregional relapse, locoregional control at 2years was 66.7%. The median LRPFS was 48months [32.9-not reached] and the median overall survival 49months [38.8-not reached]. In multivariate analysis, initial incomplete resection was associated with poorer OS (HR: 24.39 [3.57-166.78], P=0.00113) and LRPFS (HR: 33.91 [4.46-257.61], P=0.00066), extra nodal spread was associated with poorer LRPFS (HR: 13.45 [1.81-99,76], P=0.011). ECOG performance status was associated with OS (HR: 5.11 [1.57-16.66], P=0.00688). Carboplatin association with radiation therapy was not associated with improved survivals (OS: P=0.34, LRPFS: P=0.84). The rate of acute grade 3 toxicities was 14%. CONCLUSION: Salvage cervical radiation therapy was associated with a locoregional control of 66.7% at 2years with a reasonable toxicity rate. Carboplatin association with radiation therapy did not improve locoregional control nor overall survival in comparison with radiotherapy alone.

SFE-AFCE-SFMN 2022 consensus on the management of thyroid nodules: Synthesis and algorithms.

The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid with benign and non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians and surgeons but also involves other specialists. Therefore, this consensus statement was established jointly by 3 societies, the French Society of Endocrinology (SFE), the French Association of Endocrine Surgery (AFCE) and the French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This specific text is a summary chapter taking up the recommendations from specific sections and presenting algorithms for the exploration and management of thyroid nodules.

Outcomes of active surveillance of EU-TIRADS 5 thyroid nodules.

OBJECTIVE: Active surveillance of cytologically proven microcarcinomas has been shown as a safe procedure. However, fine needle aspiration biopsy (FNAB) is not recommended by European Thyroid Association (ETA) and American Thyroid Association (ATA) guidelines for highly suspicious nodules ≤ 10 mm. The aim of the study was to assess the outcomes of active surveillance of EU-TIRADS 5 nodules ≤ 10 mm not initially submitted to FNAB. PATIENTS AND METHODS: 80 patients with at least one EU-TIRADS 5 nodule ≤ 10 mm and no suspicious lymph nodes, accepting active surveillance, were included. RESULTS: Mean baseline diameter and volume were 5.4 mm (±2.0) and 64.4 mm3 (±33.5), respectively. After a median follow-up of 36.1 months, a volumetric increase ≥ 50% occurred in 28 patients (35.0%) and a suspicious lymph node in 3 patients (3.8%). Twenty-four patients underwent an FNAB (30.0%) after at least a 1 year follow-up of which 45.8% were malignant, 8.3% benign, 33.3% undetermined and 8.3% nondiagnostic. Sixteen patients (20.0%) underwent conversion surgery after a median follow-up of 57.2 months, confirming the diagnosis of papillary carcinoma in 15/16 cases (not described in 1 histology report), all in remission at 6-12 months postoperative follow-up. CONCLUSION: Applying ETA and ATA guidelines to avoid FNA of EU-TIRADS 5 sub-centimeter nodules and proceeding to active surveillance of such nodules in selected patients is a safe procedure. Thus, US-FNAB could be postponed until the nodule shows signs of progression or a suspicious lymph node appears, with no added risk for the patient.

Impact of age on survival in radioiodine refractory differentiated thyroid cancer patients.

OBJECTIVE: The objectives of our study were to analyze the influence of age on the survival of patients with RAIR-DTC and to determine their prognostic factors according to age. METHODS: This single-center, retrospective study enrolled 155 patients diagnosed with RAIR-DTC. The primary end point was overall survival (OS) according to different cutoff (45, 55, 65, 75 years). Secondary endpoints were progression free survival (PFS) and prognostic factors in patients under and over 65 years. RESULTS: Median OS after RAIR diagnosis was 8.2 years (95% IC: 5.3-9.6). There was no difference according to age with a 65 (P = 0.47) and 55 years old cutoff (P = 0.28). Median OS improved significantly before 45 years old (P = 0.0043). After 75 years old, median OS significantly decreased (P = 0.0008). Median PFS was 2.1 years (95% CI: 0.8-3) in patients < 65 years old, and 1 year in patients ≥ 65 years old (95% CI: 0.8-1.55) with no statistical difference (P = 0.22). There was no impact of age on PFS with any cutoff. In both groups, progressive disease despite 131I treatment reduced OS. In patients < 65 years old, an interval of less than 3 years between the initial diagnosis and the diagnosis of RAIR metastatic disease was predictive of poor survival. In patients > 65 years old, the presence of a mediastinum metastasis was a significant factor for mortality (HR: 4.55, 95% CI: 2.27-9.09). CONCLUSION: In RAIR-DTC patients, a cut-off age of 65 years old was not a significant predictive factor of survival. Forty-five and 75-years-old cutoff were predictive for OS but not PFS.

[Management of thyroid nodule]. / Conduite à tenir devant un nodule thyroïdien.

The widespread use of imaging (ultrasonography, doppler, CT) has led to an "epidemic" of thyroid nodules. More often observed in women, the management of thyroid nodules is a recurring problem in routine clinical practice. Fine needle aspiration cytology (FNAC) of suspicious nodule on ultrasound is the most reliable tool to select patients requiring surgery. Scintigraphy is not accurate enough to predict malignancy, the small size of a nodule is not a reassuring factor for the clinician and the prevalence of cancer is as frequent for isolated nodules or multinodular goiter. Thyroid cancer corresponds to 9 to13% of nodules undergoing FNAC and prognosis is good for differentiated carcinomas.

TIRADS score is of limited clinical value for risk stratification of indeterminate cytological results.

CONTEXT: Thyroid nodules with cytological indeterminate results represent a daily and recurrent issue for patient management. OBJECTIVE: The primary aim of our study was to determine if TIRADS (Thyroid Imaging Reporting and Data System) could be used to stratify the malignancy risk of these nodules and to help in their clinical management. Secondary objective was to estimate if this risk stratification would change after reclassification of encapsulated non-invasive follicular variant of papillary carcinomas (FVPTC) as non-invasive follicular thyroid neoplasm (NIFTP). PATIENTS AND METHODS: Single-center retrospective study of a cohort of 602 patients who were referred for ultrasound-guided fine-needle aspiration from January 2010 to December 2016 with an indeterminate cytological result and in whom histological results after surgery were available. TIRADS score was prospectively determined for all patients included. Nodules that had been classified as FVPTC were submitted to a rereading of histological report and reclassified as NIFTP when judged relevant. A table of malignancy risk crossing Bethesda and TIRADS results was built before and after this reclassification. RESULTS: The study included 602 cytologically indeterminate nodules. TIRADS score was positively correlated with the malignancy rate (P < 0.0001). Risk stratification with TIRADS was significant only in Bethesda V nodules (P = 0.0004). However, the risk of malignancy in this Bethesda V category was always above 45%, whatever the TIRADS score. CONCLUSION: For a clinician facing an indeterminate cytological result for a thyroid nodule, return to TIRADS score is of limited value in most conditions to rule in or rule out malignancy and to guide subsequent management of patients.

Comparison of seven serum thyroglobulin assays in the follow-up of papillary and follicular thyroid cancer patients.

BACKGROUND: Serum thyroglobulin (Tg) is the marker of differentiated thyroid cancer after initial treatment and TSH stimulation increases its sensitivity for the diagnosis of recurrent disease. AIM: The goal of the study is to compare the diagnostic values of seven methods for serum Tg measurement for detecting recurrent disease both during L-T4 treatment and after TSH stimulation. METHODS: Thyroid cancer patients who had no evidence of persistent disease after initial treatment (total thyroidectomy and radioiodine ablation) were studied at 3 months on L-T4 treatment (Tg1) and then at 9-12 months after withdrawal or recombinant human TSH stimulation (Tg2). Sera with anti-Tg antibodies or with an abnormal recovery test result were excluded from Tg analysis with the corresponding assay. The results of serum Tg determination were compared to the clinical status of the patient at the end of follow-up. RESULTS: Thirty recurrences were detected among 944 patients. A control 131I total body scan had a low sensitivity, a low specificity, and a low clinical impact. Assuming a common cutoff for all Tg assays at 0.9 ng/ml, sensitivity ranged from 19-40% and 68-76% and specificity ranged from 92-97% and 81-91% for Tg 1 and Tg2, respectively. Using assays with a functional sensitivity at 0.2-0.3 ng/ml, sensitivity was 54-63% and specificity was 89% for Tg1. Using the two methods with a lowest functional sensitivity at 0.02 and 0.11 ng/ml resulted in a higher sensitivity for Tg1 (81% and 78%), but at the expense of a loss of specificity (42% and 63%); finally, for these two methods, using an optimized functional sensitivity according to receiver operating characteristic curves at 0.22 and 0.27 ng/ml resulted in a sensitivity at 65% and specificity at 85-87% for Tg1. CONCLUSION: Using an assay with a lower functional sensitivity may give an earlier indication of the presence of Tg in the serum on L-T4 treatment and may be used to study the trend in serum Tg without performing any TSH stimulation. Serum Tg determination obtained after TSH stimulation still permits a more reliable assessment of cure and patient's reassurance.

Usefulness of fine needle aspiration cytology in the diagnosis of loco-regional recurrence of differentiated thyroid carcinoma.

AIM: The aim of our study was to define the usefulness of fine needle aspiration cytology (FNAC) in the assessment of loco-regional recurrence of differentiated thyroid carcinoma (DTC). METHODS: Among 1182 consecutive patients treated and followed for DTC from 1992 to 2001, we retrospectively analysed 65 FNAC results of patients presenting a suspicion of loco-regional recurrence. Recurrences were proved at histology in 35 cases and by cervical radioiodine uptake on post-therapeutic WBS (whole body scan) in nine cases. RESULTS: Among the 44 recurrences, FNAC results were malignant, benign and unsatisfactory in 33, two and nine cases, respectively. For the diagnosis of malignancy, FNAC sensitivity was 94%, specificity 100%, positive predictive value 100% and negative predictive value 87%. In the 35 cases where divergent results between diagnostic WBS (37-111MBq (131)I) and Tg level were observed, FNAC assessed the final status in 22 cases (malignant and benign in 17 and five cases, respectively). Of the 12 non-functioning and non-secreting lesions, FNAC diagnosed malignancy in four of the five malignant cases and ruled out malignancy in all seven benign lesions. CONCLUSION: These results outline the interest of FNAC in the assessment of loco-regional recurrences of DTC, especially when classical follow-up tools such as WBS and/or Tg level are unable to detect the recurrences.

Indications for radioiodine administration in follicular-derived thyroid cancer.

Indications for radioiodine administration after thyroid cancer surgery have shifted in recent years toward personalized management, adapted to the individual risk of tumor progression. The most recent guidelines and studies favor de-escalation in indications for administration, dosage and means of preparation with exogenous recombinant TSH stimulation as treatment of choice. Radioiodine administration has 3 possible objectives: • ablation of normal thyroid tissue remnants in patients with low risk of progression, using low radioiodine activity levels, with the advantage of completing disease staging on whole-body scintigraphy performed after administration of the radioiodine capsule, and of facilitating follow-up by thyroglobulin assay; • adjuvant treatment for suspected microscopic metastases in patients with intermediate or high risk of progression, using higher activity levels, with the theoretic aim of limiting recurrence and mortality; • curative treatment in high-risk patients with proven metastases, using exclusively high activity levels, with a view to improving specific survival. In future, indications for ablation and/or activity prescription may be governed by an algorithm incorporating individual baseline progression risk (essentially founded of pTNM staging) and postoperative data such as thyroglobulin level and neck ultrasound results.

Components of the fibrinolytic system are differently altered in moderate and severe hypothyroidism.

T(4) levels are determinant of several components of the fibrinolytic system. However, relationships between hypothyroidism and alteration of fibrinolytic capacity are not well established, and published data remain conflicting. As the impact of hypothyroidism on both degradation and synthesis of proteins may vary according to the severity of the disease, we measured fibrinolytic activity across varying states of hypothyroidism. We measured fibrinogen, D-dimers (DDI), alpha(2)-antiplasmin activity, tissue plasminogen activator antigen (t-PA Ag), plasminogen, plasminogen activator inhibitor antigen (PAI-1 Ag), and factor XII (FXII) of the coagulation. We prospectively included 76 middle-aged female subjects: 25 controls, 24 patients displaying moderate hypothyroidism (TSH, 10--50 mU/L), and 27 patients with severe hypothyroidism (TSH, >50 mU/L). Blood pressure, body mass index, smoking habits, total cholesterol as well as high and low density lipoprotein subfractions, triglyceride, fasting glycemia, and insulinemia were recorded. We found a different pattern of fibrinolytic abnormalities according to the severity of hypothyroidism. Compared with controls, patients with moderate hypothyroidism displayed a decreased fibrinolytic activity, as reflected by lower DDI levels, higher alpha(2)-antiplasmin activities, and higher levels of t-PA and PAI-1 Ag. In sharp contrast, patients with severe hypothyroidism exhibited higher DDI levels, lower alpha(2)-antiplasmin activities, and lower t-PA and PAI-1 Ag levels. These results were not accounted for by confounding factors such as age, smoking, and components of the insulin resistance syndrome. Free T(4) was significantly associated with fibrinogen, alpha(2)-antiplasmin, PAI-1 Ag, total cholesterol, and triglyceride and was negatively associated with DDI. The main hypotheses underlying the mechanisms by which thyroid status may affect the fibrinolytic system remain to be established. In conclusion, patients with moderate hypothyroidism, who were consistently shown to be at high risk for cardiovascular disease, have decreased fibrinolytic activity. Subjects with severe hypothyroidism have a tendency toward increased fibrinolytic activity, and these modifications may participate to the bleeding tendency observed in such patients.

Survival and therapeutic modalities in patients with bone metastases of differentiated thyroid carcinomas.

Data for patients with bone metastases (BMs) of differentiated thyroid carcinoma (DTC) were retrospectively studied to identify factors associated with survival. We especially studied the impact of therapies. Among the 1977 patients followed for DTC in our department from 1958 to 1999, 109 (77 females and 32 males; age range, 20--87 yr) presented BMS: All patients except 1 underwent total thyroidectomy, followed by radioiodine therapy (> or =3.7 gigabecquerels) in 95 cases. Survival rates at 5 and 10 yr were 41% and 15%, respectively. Univariate analyses indicated that a young age at BM discovery (P < 0.005) and the discovery of BM as a revealing symptom of DTC (P < 0.05) were features significantly associated with improved survival as well as radioiodine therapy (P < 10(-4)) and BM complete surgery (P < 0.02). Using multivariate analysis, the detection of BMs as a revealing symptom of thyroid carcinoma (P < 0.0005), the absence of metastasis appearance in other organs than bones during the follow-up (P < 0.03), the cumulative dose of radioiodine therapy (P < 0.0001), and complete BM surgery in young patients (P < 0.04) appeared as independent prognostic features associated with an improved survival.

Indications and limits of ultrasound-guided cytology in the management of nonpalpable thyroid nodules.

Although ultrasound (US)-guided fine needle aspiration biopsy (FNAB) is widely prescribed in nonpalpable thyroid nodules, the goal of this study was to define precisely the indications and limits of US-FNAB in a series of 450 nonpalpable nodules. Among 94 surgically controlled cases, 20 (8 infracentimetric and 12 centimetric or supracentimetric) carcinomas were diagnosed. The diagnosis of malignancy was successfully made by US-FNAB in 16 of 20 carcinomas, 3 were missed because of insufficient cytological material, and 1 was misdiagnosed. US-FNAB sensitivity and specificity were 94% and 63%, respectively. A logistic model indicated that nodule size (P < 0.6) was not associated with histological diagnosis, but that solid hypoechoic features were more likely to be malignant (P < 0.0003), with US sensitivity and specificity for malignancy of 80% and 70%, respectively. Logistic regression indicated that adequate cytological material significantly increased with nodule size (P < 0.0001). This result outlined the limits of US-FNAB in small nodules. Hence, indication of US-FNAB appears judicious in centimetric or supracentimetric nodules or in solid and hypoechoic ones. Such a management would allow the discovery of 15 of 20 carcinomas and would avoid 16% of unnecessary biopsies.

Relationship of circulating C-reactive protein levels to thyroid status and cardiovascular risk in hyperlipidemic euthyroid subjects: low free thyroxine is associated with elevated hsCRP.

The mechanism(s) by which low circulating levels of thyroid hormones may lead to development of premature atherosclerosis remain to be established. These mechanisms include indirect effects of thyroid hormones on cardiovascular risk factors such as plasma lipoproteins, homocysteine and fibrinogen. High-sensitivity C-reactive protein (hsCRP) has been identified as an independent predictor of cardiovascular events. We presently investigated the relationship between hsCRP and free thyroxine (FT4) levels in a large population of euthyroid hyperlipidemic patients (n=429, mean age: 47.1 years, 28% of current smokers). None of these subjects presented a recent history of infection or inflammatory disease and those taking drugs known to influence thyroid or hsCRP were excluded. Serum FT4 levels were measured by radioimmunoassay and CRP, by a high-sensitivity immunoassay. In the population of non-smokers, plasma FT4 levels were negatively and significantly correlated with those of hsCRP (r=-0.13, P=0.02). Significant correlations between FT4 levels and age (r=-0.16, P=0.003), glycemia (r=-0.14, P=0.01), and fibrinogen (r=-0.18, P=0.001) were equally observed. Upon division of the population on the basis of FT4 tertiles, the mean level of hsCRP was significantly higher in non-smoker patients with the lowest FT4 tertile as compared to those displaying the highest FT4 level (3.04mg/l versus 1.77mg/l, respectively, P<0.05). No correlation between FT4 levels and CRP was found in smokers.In conclusion, we demonstrate that hsC-reactive protein is significantly negatively correlated with free thyroxine levels in non-smoker hyperlipidemic patients, suggesting that low thyroxine levels in euthyroid hyperlipidemic subjects constitute a new biomarker of elevated cardiovascular risk.

Advances in diagnostic practices affect thyroid cancer incidence in France.

OBJECTIVE: To analyse trends in diagnostic practices of thyroid diseases and to relate them to the increase in thyroid cancer incidence in France over time. DESIGN: From 1980 to 2000, a French retrospective multicentric (three endocrinology and three nuclear medicine centres) study of thyroid diseases was conducted on 20 consecutive unselected patients' records, sampled every 5 years in each centre. METHODS: Characteristics of the population and diagnosis procedures (thyroid ultrasonography (US), radionuclide scan, cytology and hormonal measurements) were described over time. Changing trends in operated patients and in cancer prevalence were analysed as well as the impact of practices on cancer incidence. RESULTS: The study included 471 patients (82% female, mean age 46.7, range 9-84 years), referred for nodular thyroid diseases (66.7%) or thyroid dysfunctions (33.3%). A significant increase in US (3 to 84.8%) and cytological practices (4.5 to 23%), and a decrease (89.4 to 49.6%) in radionuclide scan procedures were observed over time. Although the proportion of patients undergoing surgery remained constant (24.8%), the prevalence of cancer increased among operated patients from 12.5 to 37% (P=0.006). In a Cox's proportional hazard model stratified on the clinical characteristics of patients, only the cytological practice, regardless of its results, was significantly associated with the occurrence of cancer: relative risk (RR)=4.4 (95% confidence interval (CI): 1.1-16; P=0.04). CONCLUSIONS: From 1980 to 2000, a major evolution in clinical practices has led to the increase in thyroid cancer reported in France. Such changes in medical, as well as in surgical and pathological, practices must be taken into account in incidence measurement.

Secondary thyroidectomy in patients with prior thyroid surgery for benign disease: a study of 203 cases.

BACKGROUND: The goal of this study was to evaluate the complication rate of secondary thyroidectomy in patients with prior thyroid surgery for benign disease. METHODS: Over an 8-year period, 203 thyroid reoperations were performed on 202 patients. All information relating to operative procedures, pathology, and complications was recorded prospectively. RESULTS: There were 24 men and 178 women with a mean age of 52 years. Prior surgery was unilateral in 136 cases (67%) and bilateral in 67 cases (33%), and 14 patients (6.9%) had more than 1 previous thyroid operation. For euthyroid or pretoxic recurrent nodular goiter, 190 reoperations were performed and 13 reoperations were performed for recurrent thyrotoxicosis. Twenty-three cancers were found in a specimen (11.4%). Completion thyroidectomy was done in 143 patients. Postoperative complications occurred in 21 patients (10.4%): recurrent laryngeal nerve palsy (7 patients), hypocalcemia (8 patients), hematoma requiring surgical evacuation (5 patients), and wound infection (1 patient). Complications remained permanent in 4 patients (2%). CONCLUSIONS: The permanent complication rate is higher in thyroid reoperations than in primary thyroid operations. However, we believe that this 2% rate is low enough to allow reoperation whenever it is necessary, provided precise operative rules are respected.

Amyloid goiter as the initial manifestation of systemic amyloidosis due to familial mediterranean fever with homozygous MEFV mutation.

We describe a case of amyloid goiter revealing a systemic amyloidosis secondary to familial Mediterranean fever (FMF) with homozygous MEFV mutation, and we review the literature. A 45-year-old euthyroid Sephardic man, known to suffer from FMF, developed a goiter with cold nodule, after which a subtotal thyroidectomy was performed. Histologic evaluation revealed diffuse AA amyloid deposition without any associated thyroid neoplasia. At that time, no other organ was found to be affected by amyloidosis. Colchicine and levothyroxine were prescribed. Eight years later, the patient presented with a rapidly growing neck enlargement. He reported that he had discontinued colchicine therapy 2 years earlier. The serum thyrotropin (TSH) and calcitonin levels were normal. Renal, digestive, and salivary gland biopsies confirmed the presence of systemic AA amyloidosis. Despite the reintroduction of colchicine, the onset of compressive symptoms led to the completion of the total thyroidectomy. The histopathology again demonstrated amyloid deposition, and excluded a malignant neoplasm. Nine cases of amyloid goiter associated with FMF have been reported in the literature; none of them had an amyloid goiter as the first manifestation of systemic amyloidosis. To our knowledge, this is the first case of FMF in which an amyloid goiter preceded the development of secondary systemic amyloidosis. The cessation of colchicine therapy may have played a role in local relapse and the secondary spread of amyloid deposits.

[What is the contribution of imaging?]. / Que faut-il attendre de l'imagerie?

Thyroid imaging has an essentially diagnostic value, but is also plays a role in definition of indications and operative techniques. Ultrasound is the most useful examination. Scintigraphy has become less useful, but remains indicated in hyperthyroidism and in certain retrosternal goitres inaccessible to ultrasound. The other examinations only have a limited value.