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Background:Thyroid nodule image reporting and data systems (TIRADS) provide the indications for fine-needle aspiration (FNA) based on a combination of nodule sonographic features and size. We compared the TIRADS-based recommendations for FNA with those based on the personal expertise of qualified US investigators in the diagnosis of thyroid malignancy. Methods:Seven highly experienced ultrasound (US) investigators from 4 countries evaluated, online, the US video recordings of 123 histologically verified thyroid nodules. Technical resources provided the operators with a diagnostic approach close to the real-world practice. Altogether, 4,305 TIRADS scores were computed. The combined diagnostic potential of TIRADS (TIRSYS) and the personal recommendations of the investigators (PERS) were compared against 3 possible goals: to recognize all malignant lesions (allCA), nonpapillary plus non-pT1 papillary cancers (nPnT1PCA), or stage II-IV cancers (st2-4CA). Results:For allCA and nPnT1PCA, TIRSYS had lower sensitivity than PERS (69.8 vs. 87.2 and 83.5 vs. 92.6%, respectively, p <0.01), while in st2-4CA the sensitivities were the same (99.1 vs. 98.6% and TIRSYS vs. PERS, respectively). TIRSYS had a higher specificity than PERS in all 3 types of cancers (p< 0.001). PERS recommended FNA in a similar proportion of lesions smaller or larger than 1 cm (76.9 vs. 82.7%; ns). Conclusions:Recommendations for FNA based on the investigators’ US expertise demonstrated a better sensitivity for thyroid cancer in the 2 best prognostic groups, while TIRADS methodology showed superior specificity over the full prognostic range of cancers. Thus, personal experience provided more accurate diagnoses of malignancy, missing a lower number of small thyroid cancers, but the TIRADS approach resulted in a similar accuracy for the diagnosis of potentially aggressive lesions while sparing a relevant number of FNAs. Until it is not clearly stated what the goal of the US evaluation is, that is to diagnose all or only clinically relevant thyroid cancers, it cannot be determined whether one diagnostic approach is superior to the other for recommending FNA.

Background:Thyroid nodule image reporting and data systems (TIRADS) provide the indications for fine-needle aspiration (FNA) based on a combination of nodule sonographic features and size. We compared the TIRADS-based recommendations for FNA with those based on the personal expertise of qualified US investigators in the diagnosis of thyroid malignancy. Methods:Seven highly experienced ultrasound (US) investigators from 4 countries evaluated, online, the US video recordings of 123 histologically verified thyroid nodules. Technical resources provided the operators with a diagnostic approach close to the real-world practice. Altogether, 4,305 TIRADS scores were computed. The combined diagnostic potential of TIRADS (TIRSYS) and the personal recommendations of the investigators (PERS) were compared against 3 possible goals: to recognize all malignant lesions (allCA), nonpapillary plus non-pT1 papillary cancers (nPnT1PCA), or stage II-IV cancers (st2-4CA). Results:For allCA and nPnT1PCA, TIRSYS had lower sensitivity than PERS (69.8 vs. 87.2 and 83.5 vs. 92.6%, respectively, p <0.01), while in st2-4CA the sensitivities were the same (99.1 vs. 98.6% and TIRSYS vs. PERS, respectively). TIRSYS had a higher specificity than PERS in all 3 types of cancers (p< 0.001). PERS recommended FNA in a similar proportion of lesions smaller or larger than 1 cm (76.9 vs. 82.7%; ns). Conclusions:Recommendations for FNA based on the investigators’ US expertise demonstrated a better sensitivity for thyroid cancer in the 2 best prognostic groups, while TIRADS methodology showed superior specificity over the full prognostic range of cancers. Thus, personal experience provided more accurate diagnoses of malignancy, missing a lower number of small thyroid cancers, but the TIRADS approach resulted in a similar accuracy for the diagnosis of potentially aggressive lesions while sparing a relevant number of FNAs. Until it is not clearly stated what the goal of the US evaluation is, that is to diagnose all or only clinically relevant thyroid cancers, it cannot be determined whether one diagnostic approach is superior to the other for recommending FNA.

Standard therapeutic approaches for benign thyroid lesions that warrant intervention are surgery for cold and either surgery or radioiodine for autonomously functioning thyroid nodules (AFTN). Image-guided thermal ablation (TA) procedures are increasingly proposed as therapy options for selected clinical conditions. Due to mounting scientific evidence and widening availability, ETA considered it appropriate to develop guidelines for the use of TA in adult patients. TA procedures are well tolerated, but a dedicated training of the operators is required and information on possible complications needs to be shared with the patients. The following factors should be considered when weighing between observation, surgery, and TA for benign thyroid nodules. In solid non-hyperfunctioning nodules, TA induces a decrease in thyroid nodule volume, paralleled by improvement in symptoms. Nodule re-growth is possible over time and may necessitate repeat treatment, or surgery, in a dialogue with the patient. In AFTN, radioactive iodine is the first-line treatment, but TA may be considered in young patients with small AFTN due to higher probability of restoring normal thyroid function and avoidance of irradiation. In cystic nodules, ethanol ablation (EA) is the most effective and least expensive treatment. TA may be considered for cystic lesions that relapse after EA or have a significant residual solid component following drainage and EA. TA should be restricted to benign lesions that cause symptoms or cosmetic concern. Presently, laser and radiofrequency ablation are the most thoroughly assessed techniques, with similar satisfactory clinical results. Microwaves and high-intensity focused ultrasound therapy options remain to be fully evaluated.

Objective:Image-guided interventional ultrasound (US) techniques represent diagnostic and therapeutic tools for non-surgical management of thyroid nodular disease. We sought to investigate the attitude of European Thyroid Association (ETA) members towards the use of minimally invasive techniques (MIT) in diagnosis/therapy of symptomatic nodular goitre. Methods:ETA members were invited to participate in an online survey investigating the use of MIT in benign and malignant thyroid nodular disease. Of 865 invited members, 221 (25.5%) completed the survey. The respondents were from 40 countries; 139 (74.7%) were from European countries. Results:Respondents personally performed thyroid US (91.6%), Fine needle aspiration (FNA; 75.3%), ethanol ablation (EA; 22.1%), core needle biopsy (CNB; 11%) and thermal treatments (4.8%). When skills and/or technology were unavailable, only 13.4% referred patients “often” or “always” to other centres with specific expertise in this field. Surgery was the preferred first option in patients with recurrent cysts, 4.0 cm benign nodules, local (radioiodine-avid or non-avid) lymph node metastases, or papillary cancers <1.0 cm. For autonomously functioning nodules radioactive iodine treatment was the preferred choice, followed by surgery. Thermal ablation (TA) was the preferred option only for a 4 cm benign nodule in old patients with comorbidities. Conclusions:US, US-guided FNA and surgery were available to nearly all respondents, while MIT was not. CNB and EA were employed only by about 1/3 of the respondents and TA procedures were available and personally performed only by a minority. For most thyroid lesions, surgery was the preferred option versus thermal therapies. The ETA needs to develop guidelines and establish teaching to overcome geographic inequality and promote the use of MIT as a valid therapy option in appropriate cases.

Standard therapeutic approaches for benign thyroid lesions that warrant intervention are surgery for cold and either surgery or radioiodine for autonomously functioning thyroid nodules (AFTN). Image-guided thermal ablation (TA) procedures are increasingly proposed as therapy options for selected clinical conditions. Due to mounting scientific evidence and widening availability, ETA considered it appropriate to develop guidelines for the use of TA in adult patients. TA procedures are well tolerated, but a dedicated training of the operators is required and information on possible complications needs to be shared with the patients. The following factors should be considered when weighing between observation, surgery, and TA for benign thyroid nodules. In solid non-hyperfunctioning nodules, TA induces a decrease in thyroid nodule volume, paralleled by improvement in symptoms. Nodule re-growth is possible over time and may necessitate repeat treatment, or surgery, in a dialogue with the patient. In AFTN, radioactive iodine is the first-line treatment, but TA may be considered in young patients with small AFTN due to higher probability of restoring normal thyroid function and avoidance of irradiation. In cystic nodules, ethanol ablation (EA) is the most effective and least expensive treatment. TA may be considered for cystic lesions that relapse after EA or have a significant residual solid component following drainage and EA. TA should be restricted to benign lesions that cause symptoms or cosmetic concern. Presently, laser and radiofrequency ablation are the most thoroughly assessed techniques, with similar satisfactory clinical results. Microwaves and high-intensity focused ultrasound therapy options remain to be fully evaluated.

Objective:Image-guided interventional ultrasound (US) techniques represent diagnostic and therapeutic tools for non-surgical management of thyroid nodular disease. We sought to investigate the attitude of European Thyroid Association (ETA) members towards the use of minimally invasive techniques (MIT) in diagnosis/therapy of symptomatic nodular goitre. Methods:ETA members were invited to participate in an online survey investigating the use of MIT in benign and malignant thyroid nodular disease. Of 865 invited members, 221 (25.5%) completed the survey. The respondents were from 40 countries; 139 (74.7%) were from European countries. Results:Respondents personally performed thyroid US (91.6%), Fine needle aspiration (FNA; 75.3%), ethanol ablation (EA; 22.1%), core needle biopsy (CNB; 11%) and thermal treatments (4.8%). When skills and/or technology were unavailable, only 13.4% referred patients “often” or “always” to other centres with specific expertise in this field. Surgery was the preferred first option in patients with recurrent cysts, 4.0 cm benign nodules, local (radioiodine-avid or non-avid) lymph node metastases, or papillary cancers <1.0 cm. For autonomously functioning nodules radioactive iodine treatment was the preferred choice, followed by surgery. Thermal ablation (TA) was the preferred option only for a 4 cm benign nodule in old patients with comorbidities. Conclusions:US, US-guided FNA and surgery were available to nearly all respondents, while MIT was not. CNB and EA were employed only by about 1/3 of the respondents and TA procedures were available and personally performed only by a minority. For most thyroid lesions, surgery was the preferred option versus thermal therapies. The ETA needs to develop guidelines and establish teaching to overcome geographic inequality and promote the use of MIT as a valid therapy option in appropriate cases.

Alazami syndrome (MIM#615071) is a rare developmental disorder caused by biallelic variants in the LARP7gene. Hallmark features include short stature, global developmental delay, and distinctive facial features. To date, 23 patients from 11 families have been reported in the literature. Here we describe a 19-year-old man who, in association with the typical features of Alazami syndrome, was diagnosed at the age of 14 years with papillary thyroid carcinoma, harboring the somatic BRAFV600E mutation. Whole exome sequencing revealed two novel LARP7variants in compound heterozygosity, whereas only common variants were detected in genes associated with familial nonmedullary thyroid cancer (MIM#188550). LARP7acts as a tumor suppressor in breast and gastric cancer, and possibly, according to recent studies, in thyroid tumors. Since thyroid cancer is rare among children and adolescents, we hypothesize that the LARP7variants identified in our patient are responsible for both Alazami syndrome and tumor susceptibility. We also provide an overview of the clinical findings in all Alazami syndrome patients reported to date and discuss the possible pathogenetic mechanism that may underlie this condition, including the role of LARP7in tumor susceptibility.

Thyroid ultrasonography (US) is the gold standard for thyroid imaging and its widespread use is due to an optimal spatial resolution for superficial anatomic structures, a low cost and the lack of health risks. Thyroid US is a pivotal tool for the diagnosis and follow-up of autoimmune thyroid diseases, for assessing nodule size and echostructure and defining the risk of malignancy in thyroid nodules. The main limitation of US is the poor reproducibility, due to the variable experience of the operators and the different performance and settings of the equipments. Aim of this consensus statement is to standardize the report of thyroid US through the definition of common minimum requirements and a correct terminology. US patterns of autoimmune thyroid diseases are defined. US signs of malignancy in thyroid nodules are classified and scored in each nodule. We also propose a simplified nodule risk stratification, based on the predictive value of each US sign, classified and scored according to the strength of association with malignancy, but also to the estimated reproducibility among different operators.

Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Six scientific Italian societies entitled to cure thyroid cancer patients (the Italian Thyroid Association, the Medical Endocrinology Association, the Italian Society of Endocrinology, the Italian Association of Nuclear Medicine and Molecular Imaging, the Italian Society of Unified Endocrine Surgery and the Italian Society of Anatomic Pathology and Diagnostic Cytology) felt the need to develop a consensus report based on significant scientific advances occurred in the field. The document includes recommendations regarding initial evaluation of thyroid nodules, clinical and ultrasound criteria for fine-needle aspiration biopsy, initial management of thyroid cancer including staging and risk assessment, surgical management, radioiodine remnant ablation, and levothyroxine therapy, short-term and long-term follow-up strategies, and management of recurrent and metastatic disease. The objective of this consensus is to inform clinicians, patients, researchers, and health policy makers about the best strategies (and their limitations) relating to the diagnosis and treatment of differentiated thyroid cancer.

A consensus lexicon for describing thyroid nodules at US will anchor the development of an international risk stratification system, encourage consistent worldwide reporting, and facilitate international efficacy studies.

Background:While thyroid nodules are frequent in endocrine clinical practice, patients are often asymptomatic and euthyroid, and death is rare in cases of malignancy. Objectives:To evaluate the perception of current international guidelines regarding thyroid nodule management among Italian endocrinologists, and to compare daily clinical practice with suggested recommendations. Methods:Italian Association of Clinical Endocrinologists (AME) members were invited to participate in a Web-based survey. Results:A total of 566 physicians responded. About 50% had read the full text of the guidelines. Over half appreciated the suggested ultrasound (US) risk categories. Fine-needle aspiration (FNA) was obtained more frequently than recommended. Follow-up of a cytologically benign nodule was largely performed according to the guidelines. Molecular testing would be most commonly requested when cytology reports showed atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) (TIR3A for Italian System). Iodine and/or levothyroxine were largely prescribed for cytologically benign asymptomatic nodules. Laser/radiofrequency ablation and percutaneous ethanol injection were commonly considered as alternatives to surgery (46.2 and 71.4%, respectively). Conclusions:Efforts are needed to make the guidelines more user-friendly and to encourage the use of codified risk categories in thyroid US reports. FNA indications remain a matter of debate as FNA is obtained in clinical practice more often than is recommended. Current US follow-up modalities for a benign nodule are correct, but probably could be performed less frequently without any harm. Molecular testing, if accessible, would be helpful in guiding clinicians' strategies in cases of AUS/FLUS-TIR3A cytologic results. Nonsurgical procedures are favorably embraced.

Background:While thyroid nodules are frequent in endocrine clinical practice, patients are often asymptomatic and euthyroid, and death is rare in cases of malignancy. Objectives:To evaluate the perception of current international guidelines regarding thyroid nodule management among Italian endocrinologists, and to compare daily clinical practice with suggested recommendations. Methods:Italian Association of Clinical Endocrinologists (AME) members were invited to participate in a Web-based survey. Results:A total of 566 physicians responded. About 50% had read the full text of the guidelines. Over half appreciated the suggested ultrasound (US) risk categories. Fine-needle aspiration (FNA) was obtained more frequently than recommended. Follow-up of a cytologically benign nodule was largely performed according to the guidelines. Molecular testing would be most commonly requested when cytology reports showed atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) (TIR3A for Italian System). Iodine and/or levothyroxine were largely prescribed for cytologically benign asymptomatic nodules. Laser/radiofrequency ablation and percutaneous ethanol injection were commonly considered as alternatives to surgery (46.2 and 71.4%, respectively). Conclusions:Efforts are needed to make the guidelines more user-friendly and to encourage the use of codified risk categories in thyroid US reports. FNA indications remain a matter of debate as FNA is obtained in clinical practice more often than is recommended. Current US follow-up modalities for a benign nodule are correct, but probably could be performed less frequently without any harm. Molecular testing, if accessible, would be helpful in guiding clinicians' strategies in cases of AUS/FLUS-TIR3A cytologic results. Nonsurgical procedures are favorably embraced.

The transdifferentiation of epithelial cells toward a mesenchymal condition (EMT) is a complex process that allows tumor cells to migrate to ectopic sites. Cadherins are not just structural proteins, but they act as sensors of the surrounding microenvironment and as signaling centers for cellular pathways. However, the molecular mechanisms underlying these signaling functions remain poorly characterized. Cadherin-6 (CDH6) is a type 2 cadherin, which drives EMT during embryonic development and it is aberrantly re-activated in cancer. We recently showed that CDH6 is a TGFβ target and an EMT marker in thyroid cancer, suggesting a role for this protein in the progression of this type of tumor. Papillary thyroid carcinomas (PTCs) are usually indolent lesions. However, metastatic spreading occurs in about 5% of the cases. The identification of molecular markers that could early predict the metastatic potential of these lesions would be strategic to design more tailored approaches and reduce patients overtreatment. In this work, we assessed the role of CDH6 in the metastatic progression of thyroid cancer. We showed that loss of CDH6 expression profoundly changes cellular architecture, alters the inter-cellular interaction modalities and attenuates EMT features in thyroid cancer cells. Using a yeast two-hybrid screening approach, based on a thyroid cancer patients library, we showed that CDH6 directly interacts with GABARAP, BNIP3 and BNIP3L, and that through these interactions CDH6 restrains autophagy and promotes re-organization of mitochondrial network through a DRP1-mediated mechanism. Analysis of the LIR domains suggests that the interaction with the autophagic machinery may be a common feature of many cadherin family members. Finally, the analysis of CDH6 expression in a unique cohort of human PTCs showed that CDH6 expression marks specifically EMT cells. and it is strongly associated with metastatic behavior and worse outcome of PTCs.

With the intent to address the lack of a standardized tool for risk-based stratification, the International Medullary Carcinoma Grading System (IMTCGS), based on necrosis, mitosis and Ki67, has been proposed for medullary thyroid carcinomas (MTCs). With the same purpose, a risk stratification study based on the SEER database highlighted significant differences in MTCs in terms of clinical-pathological variables. We aimed to validate both the IMTCGS and the SEER-based risk table on 66 cases of MTC, with special attention to angioinvasion and the genetic profile.

Idati epidemiologici indicano che l’ipoparatiroidismo post-chirurgico è la più frequente tra le complicanze della chirurgia tiroidea. Si manifesta in percentuale variabile a seconda della casistiche, e può essere transitorio o permanente. Il rischio di sviluppare ipocalcemia post-operatoria dipende principalmente dalla indicazione chirurgica (rischio superiore per malattia di Graves, inferiore in caso di carcinoma e di gozzo nodulare) e dalla estensione chirurgica (inferiore per tiroidectomia totale, superiore per svuotamento linfatico del compartimento centrale e del compartimento laterale). Non sono disponibili indicatori affidabili in grado di prevedere quali pazienti ipoparatiroidei lo rimarranno in modo stabile e quali invece recupereranno una normale funzione paratiroidea. Il trattamento si basa essenzialmente sulla somministrazione in dosi adeguate di calcitriolo e di calcio per via orale. La somministrazione endovenosa di calcio è riservata ai casi di ipocalcemia severa sintomatica. Normalmente si inizia il trattamento se la calcemia scende sotto i 7,8-8 mg/dl. I valori di calcemia vengono monitorati ogni 3–7 giorni, modificando la posologia dei farmaci in accordo con l’andamento della calcemia. Nella maggior parte dei casi l’ipoparatiroidismo è transitorio, ed è possibile ridurre progressivamente l’apporto esogeno di calcio e vitamina D fino a sospensione completa (strategia “reattiva”). Questo è l’atteggiamento più diffuso, e comporta un certo numero di ipocalcemie sintomatiche. è stato riportato che un dosaggio di PTH eseguito 6 ore dopo la tiroidectomia è un indicatore affidabile dello sviluppo di successiva ipocalcemia. Qualora l’organizzazione locale consenta di disporre di questo dato, pertanto, è possibile iniziare trattamento precoce con calcitriolo/calcio in caso di riduzione del PTH di più del 90% rispetto al valore basale (strategia “predittiva”). In alcuni Centri si procede a iniziare la somministrazione di calcitriolo/calcio a tutti i pazienti operati, a prescindere dai valori e dall’andamento della calcemia (strategia “preventiva”), evitando così l’insorgenza di ipocalcemia ma trattando anche pazienti che non ne avrebbero avuto necessità. Una scelta operativa pratica può essere di adottare la strategia reattiva, riservando la strategia preventiva ai casi ad alto rischio di sviluppo di successiva ipocalcemia.

Objective: To provide an overview of ultrasound (US)-guided percutaneous ethanol injection (PEI) therapy for thyroid cystic nodules and discuss the practical and technical details. Methods: We present preliminary data of a controlled randomized study involving 281 patients (221 women and 60 men; 18 to 85 years old) with benign thyroid cystic nodules. Study inclusion criteria were local discomfort or cosmetic damage, cystic volume more than 2 mL, 50% or more fluid component, benignity as confirmed by cytologic specimen obtained by US-guided fine-needle aspiration biopsy (FNAB), and euthyroidism. Exclusion criteria were inadequate, suspicious, or positive FNAB cytology, high serum calcitonin, and contralateral laryngeal cord palsy. By random assignment, 138 patients underwent simple cyst evacuation, and 143 underwent cyst evacuation plus PEI by a skilled operator using a US-guided technique. The amount of ethanol injected was 50 to 70% of the cystic fluid extracted. Results: Before treatment, the mean (±SD) nodule volume was 19.0 ± 19.0 mL versus 20.0 ± 13.4 mL in the PEI versus the simple evacuation group (no significant difference). After 1 year, volumes were 5.5 ± 11.7 mL versus 16.4 ± 13.7 mL (P<0.001), with a median 85.6% versus 7.3% reduction, respectively (P<0.001), of the initial volume. The median nodule volume reduction after PEI was 88.8% and 65.8% in empty body and mixed thyroid cysts, respectively. Compressive and cosmetic symptoms disappeared in 74.8% and 80.0% of patients treated with PEI versus 24.4% and 37.4% of patients treated with simple evacuation, respectively (P<0.001). Side effects were minor. Conclusion: These data provide definitive evidence that PEI is a safe and effective treatment for thyroid cystic nodules. Unicameral thyroid cysts are the most suitable candidate nodules for PEI. (Endocr Pract. 2004;10:269-275)

Objective: To assess the performance of neck ultrasonography (US) in the detection of lymph node lesions metastatic from differentiated thyroid carcinoma (DTC) and the detection of parathyroid adenomas. Methods: Neck US was performed in 667 patients with DTC (173 men and 494 women; mean age, 47.7 years). In cases of suspicious neck nodes, US-guided fine-needle aspiration biopsy (US-FNAB) plus measurement of thyroglobulin in the needle washouts (FNAB-Tg) was done. In addition, 75 patients with primary hyperparathyroidism (pHPT) (15 men and 60 women; mean age, 56 years) underwent neck US and sestamibi scintiscanning for localization of parathyroid adenoma. For confirmation of US findings, US-FNAB plus measurement of parathyroid hormone in the needle washouts (FNAB-PTH) was performed. FNAB-PTH was also measured in 129 suspected parathyroid adenomas incidentally detected in a series of 4,129 patients undergoing neck US examination for thyroid disease. Results: The presence of DTC metastatic lesions was confirmed in 46 of 95 patients with suspicious neck nodes. US sensitivity and specificity were 82.1% and 91.2%, respectively. The positive predictive value (PPV) of US-FNAB + FNAB-Tg was 94.7%. In the 75 patients with pHPT, US followed by US-FNAB + FNAB-PTH showed a higher PPV (97.5%) in comparison with sestamibi scintiscanning (83.7%) in the detection of parathyroid adenoma. A parathyroid adenoma was also incidentally detected in 0.62% of the 4,129 patients undergoing neck US for thyroid disease. Conclusion: US accurately detects DTC neck metastatic lesions and localizes parathyroid adenomas. Moreover, neck US may lead to discovery of parathyroid incidentalomas. (Endocr Pract. 2004;10:261-268)

L’iperparatiroidismo primitivo consiste in un’alterazione del metabolismo fosfo-calcico caratterizzata da una relativa e parzialmente incontrollata secrezione di paratormone (PTH) da parte di una o più paratiroidi iperfunzionanti. La malattia si presenta in forma asintomatica in oltre l’ 80% dei casi; nefrolitiasi (15–20%) e osteopenia (20–25%) sono le manifestazioni cliniche più frequenti. La storia naturale dell’iperparatiroidismo, in particolare nel paziente asintomatico, non è a tutt’oggi completamente delineata. Nel caso vi sia un’indicazione all’intervento chirurgico, la diagnosi biochimica di iperparatiroidismo viene seguita da indagini volte a localizzare la lesione responsabile. L’ecografia cervicale è in grado di identificare la patologia paratiroidea nel 70–85% dei casi. La scintigrafia mostra analoga sensibilità ed è particolarmente utile nell’identificare le lesioni paratiroidee a sede ectopica. L’agoaspirato paratiroideo, completato dal dosaggio di PTH sul liquido di lavaggio, permette di confermare l’origine paratiroidea di una lesione dimostrata in ecografia. Tutti i pazienti con iperparatiroidismo primitivo sintomatico sono candidati alla paratiroidectomia. Le indicazioni chirurgiche individuate dalla NIH Consensus Conferencedel 1990 sono state recentemente modificate in un workshoporganizzato sulla gestione dell’iperparatiroidismo primitivo asintomatico, per quanto riguarda i valori soglia di incremento della calcemia e gli indici di riferimento nella valutazione della densità minerale ossea. Nei pazienti non sottoposti a intervento chirurgico, è necessario controllare, con la terapia medica, gli effetti sistemici della malattia, quali l’ipercalcemia e l’osteopenia.

The follow-up of patients with differentiated thyroid carcinoma (DTC) is traditionally carried out with ¹³¹I whole body scan (¹³¹I WBS) and serum thyroglobulin (Tg) measurement. Neck ultrasonography (US) is also used. We compared the roles of Tg measurement (IRMA assay) after l-thyroxine (T4) withdrawal, ¹³¹I WBS, and US in the diagnosis of DTC neck recurrences. Diagnosis of DTC neck recurrences was based on fine-needle aspiration biopsy (FNAB) or on histologic results. Four hundred ninety-four DTC patients (120 males, 374 females; mean age, 49.3 years), submitted to total thyroidectomy and subsequent radioablative ¹³¹I treatment, underwent serum Tg measurement off T4 therapy, ¹³¹I WBS, and neck US at our institution. Mean (± SD) follow-up time was 55.1 ± 37.7 months. Neck DTC recurrences were detected in 51 (10.3%) patients (34 females, 17 males; mean age, 49.5 years). Neck recurrences occurred after 44.6 ± 21.4 months from initial treatment. Serum Tg levels increased (≥ 2 ng/mL) off T4 therapy in 29 patients (sensitivity 56.8%), ¹³¹I WBS showed neck uptake in 23 patients (sensitivity 45.1%) and coexisting distant metastases were detected in 9 of 23 patients, and US identified neck recurrence in 48 patients (sensitivity 94.1%). Of these 48 neck recurrences, 19 were found in the laterocervical compartment and 29 in the central neck compartment. Traditional techniques for the surveillance of DTC patients are not as sensitive as US in the detection of neck recurrences. Neck US detects recurrences in patients with undetectable serum Tg levels and negative IWBS and should be performed as the first-line test in the follow-up of all DTC patients. Cancer 2003;97:90–6. © 2003 American Cancer Society. DOI 10.1002/cncr.11031

Conventional cytology cannot discriminate between benign and malignant follicular neoplasms. Our study evaluated the diagnostic role of computer-assisted image analysis in the presurgical assessment of thyroid follicular neoplasms. Fifty-eight patients (14 males, 44 females, age range, 45-75 years) who underwent surgery for cytologic diagnosis of thyroid follicular neoplasm were studied. All patients were first evaluated on clinical grounds and assigned a high/low suspicion of malignancy on the basis of gender, age, and nodule size. Cell image analysis was subsequently performed using a Cytometrica BYK Gulden microscope image processor on Feulgen-stained thyroid cytologic smears. A different population of 50 benign and 50 malignant, histologically evaluated nodules was studied in order to establish image analysis criteria suggestive of thyroid malignancy. Ploidy histogram, proliferation index (PI), nuclear area coefficient of variation (NACV), and anisocariosis ratio (AR) were studied. Thyroid cancer was diagnosed in 16 of 58 follicular neoplasms. Only 7 of these lesions were clinically suspicious (43.7%), whereas 14 of 16 (87.5%) malignant tumors were identified by image analysis. Positive and negative predictive values of image analysis versus clinical evaluation were 46.6% versus 30.4% and 92.8% versus 74.3%, respectively. The distribution of ploidy pattern was different in benign versus malignant follicular neoplasms (χ28.25, p= 0.016), malignant lesions showing an increased frequency of heteroclonal aneuploid DNA content (37.5% vs. 7.1%). Increased PI (mean ± standard deviation (SD) = 11.3 ± 5.7 vs. 7.1 ± 6.1; p< 0.01) and NACV (mean ± SD = 25.28 ± 1.89 vs. 20.14 ± 0.91; p< 0.01) levels were also observed in malignant follicular neoplasms. In conclusion, computer-assisted image analysis may profitably support clinical evaluation in the assessment of thyroid follicular neoplasms.

The aim of our study was to evaluate the incidence of incidentally found parathyroid adenomas (incidentalomas) in patients undergoing sonography of the neck for thyroid disease. A total of 1,686 patients (305 men and 1,381 women) underwent sonography of the neck; the mean age was 49.6 ± 21.7 years. In 38 patients (2.3%; 7 men and 31 women) with a mean age of 48.7 ± 14.7 years, hypoechoic, homogeneous, oval nodules (mean volume, 1.0 ± 0.9 cm³) adjacent to the thyroid parenchyma were observed. All these lesions, compatible with the shape of an enlarged parathyroid gland, underwent ultrasound-guided fine-needle aspiration biopsy (FNAB), with measurement of parathyroid hormone (PTH) and thyroglobulin (Tg) levels in the needle washings (FNAB-PTH and FNAB-Tg). Biochemical screening for hyperparathyroidism was also performed. Cytologic examination plus FNAB-PTH/FNAB-Tg measurements revealed the presence of cellular material consistent with parathyroid tissue in 9 patients (24%), thyroid tissue in 22 patients (58%), and lymphoid tissue in 4 patients (11%). A tissue diagnosis was not established in 3 patients (8%). Five of 9 patients with parathyroid enlargement had high serum PTH and calcium levels. Enlarged parathyroid glands may be incidentally discovered during sonography of the thyroid. In patients with thyroid disease, the positive-predictive value of sonography in the identification of parathyroid tissue was low. Ultrasound-guided FNAB-PTH determination should be carried out when parathyroid adenoma is suspected. The incidental finding of an enlarged parathyroid may or may not be associated with yet undiagnosed hyperparathyroidism. © 1999 John Wiley & Sons, Inc. J Clin Ultrasound 27:492–498, 1999.

We report two patients with incidentally discovered enlarged parathyroid glands while performing neck ultrasonography (US) for thyroid nodules. The parathyroid masses were seen as hy-poechoic, homogeneous, oval nodules, separated from the thyroid gland. Both patients were completely asymptomatic, although subclinical evidence of hyperparathyroidism (serum PTH and calcium levels in the upper limit of the normal range, increased ionized serum calcium, osteocalcin, urinary calcium and hydroxyproline) was subsequently found in one patient. An enhanced uptake on ses-ta-MIBI scinti scan was concordant with the US finding in the two cases. PTH levels in the wash-out from the US-guided fine needle aspiration biopsy, confirmed the parathyroid origin of the lesions. Cytology and immunocitochemistry were, in our cases, unreliable diagnostic procedures. The extensive use of US imaging in thyroid pathology may increase the finding of US incidentally discovered parathyroid adenomas. The early detection of silent parathyroid pathologic findings may extend the natural history of these masses to a preclinical stage. Further investigations are necessary to evaluate the evolution of parathyroid incidentalomas and therefore their clinical significance.

The distribution of glucocorticoid receptor (GR) in the rat testis was investigated by means of immunocytochemistry (IR) and computer-assisted image analysis. A monoclonal antibody against rat liver GR showed the presence of GR IR selectively in the nuclei of interstitial and tubular cells. The semiquantitative microdensitometry of GR IR revealed that 77% of the specific staining was localized in the tubular compartment of rat testis. After adrenalectomy, GR IR was greatly reduced both in interstitial and tubular cells, roughly at the same degree. Corticosterone treatment (50 mg/kg, for 5 d) of adrenalectomized animals yielded a recovery of nuclear immunopositivity without changing the cellular distribution of GR, as observed in control rats. Nevertheless, the high dose of corticosterone administered produced a significant (p<0.01) decrease of GR IR with respect to control rats. These results provide evidence for a prevalent nuclear binding of GR in the tubular compartment in basal conditions. On the other hand, adrenalectomy or repeated corticosterone treatment seem to affect GR similarly in all positive cells without changing significantly the proportion of GR IR in the different testicular compartments. This uneven distribution of GR IR suggests that tubular cells can be a major target of corticosterone when affecting directly testicular functions in the rat.

The seminiferous epithelium is a highly proliferating tissue in which germ cell "degeneration" is a constant feature. Recent data based on morphological analysis have shown that spontaneously dying germ cells display some characteristics of apoptosis. In order to evaluate the molecular signals controlling the phenomenon, adult male rats were studied after in vivotreatment with ethane dimethane sulphonate, an agent which leads to testosterone withdrawal by a selective destruction of Leydig cells. DNA fragmentation by agarose gel electrophoresis and cell DNA content by flow cytometry after propidium iodide staining were used to evaluate and quantify apoptosis in the testis. Despite the simultaneous presence of cells with different ploidies, the present data suggest that testosterone withdrawal induces death by apoptosis and that this phenomenon is particularly evident in aploid germ cells. Thus, this study support the involvement of testosterone in regulating programmed cell death, beside cell proliferation and differentiation,during spermatogenesis.

By means of semiquantitative immunocytochemistry, possible age-related changes in dopamine and cyclic AMP-regulated phosphoprotein mr 32 (DARPP-32) and glial fibrillary acidic protein (GFAP) immunoreactivities (IR) were investigated in tanycytes of the arcuate nucleus. These two markers showed opposite changes during aging. DARPP-32 IR decreased by around 70%, whereas GFAP IR increased by around 300% in 24-month-old vs. 3-month-old rats. These changes were accompanied by a progressive loss in the number of tanycytes, measured by counting of their long processes in the arcuate nucleus. No significant age-related change was observed either in GFAP IR in astrocytic populations of the mediobasal hypothalamus or in tyrosine hydroxylase IR in dopaminergic neurons of the dorsal arcuate nucleus. These observations indicate that the tanycytic population of the arcuate nucleus undergoes important modifications during aging, which include cell loss, impairment in the intracellular signalling cascade linked to DARPP-32, and hypertrophy. These changes may be related to the alterations in the neuroendocrine systems known to occur during aging.

Dans la majorité des pays Européens, la diffusion des techniques mini-invasives dans le traitement des nodules thyroïdiens bénins reste confidentielle, seuls quelques centres spécialisés les proposant aux patients. Une enquête de L’European Thyroid Association (ETA) auprès de tous ses membres a permis de déterminer que la raison principale de cette faible diffusion était l’absence de recommandations officielles dictées par les Sociétés Savantes, pour les indications et l’utilisation de ces techniques. Le comité exécutif de l’ETA a mandaté l’un de ses membres pour constituer une « Task-force » ayant pour mission de produire des Guidelines. Le projet une fois rédigé, a été soumis au « Guidelines Board » puis à l’attention de tous les membres de l’ETA pour une évaluation critique. Les commentaires furent analysés par les auteurs et des modifications furent incorporées dans le document final avant publication [1]. Le score GRADE fut adopté pour coter les recommandations. Elles sont au nombre de 17 réparties dans 5 groupes : Généralités, Eligibilité et préparation, Procédure et suivi, Nodules solides, Nodules liquidiens, Nodules autonomes. Associées à des publications Européennes relatives à des cohortes robustes, elles devraient faciliter le processus de reconnaissance des techniques mini-invasives appliquées aux nodules thyroïdiens bénins.