AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ASSOCIAZIONE MEDICI ENDOCRINOLOGI MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR THE DIAGNOSIS AND MANAGEMENT OF THYROID NODULES--2016 UPDATE.

Thyroid nodules are detected in up to 50 to 60% of healthy subjects. Most nodules do not cause clinically significant symptoms, and as a result, the main challenge in their management is to rule out malignancy, with ultrasonography (US) and fine-needle aspiration (FNA) biopsy serving as diagnostic cornerstones. The key issues discussed in these guidelines are as follows: (1) US-based categorization of the malignancy risk and indications for US-guided FNA (henceforth, FNA), (2) cytologic classification of FNA samples, (3) the roles of immunocytochemistry and molecular testing applied to thyroid FNA, (4) therapeutic options, and (5) follow-up strategy. Thyroid nodule management during pregnancy and in children are also addressed. On the basis of US features, thyroid nodules may be categorized into 3 groups: low-, intermediate-and high-malignancy risk. FNA should be considered for nodules ≤10 mm diameter only when suspicious US signs are present, while nodules ≤5 mm should be monitored rather than biopsied. A classification scheme of 5 categories (nondiagnostic, benign, indeterminate, suspicious for malignancy, or malignant) is recommended for the cytologic report. Indeterminate lesions are further subdivided into 2 subclasses to more accurately stratify the risk of malignancy. At present, no single cytochemical or genetic marker can definitely rule out malignancy in indeterminate nodules. Nevertheless, these tools should be considered together with clinical data, US signs, elastographic pattern, or results of other imaging techniques to improve the management of these lesions. Most thyroid nodules do not require any treatment, and levothyroxine (LT4) suppressive therapy is not recommended. Percutaneous ethanol injection (PEI) should be the first-line treatment option for relapsing, benign cystic lesions, while US-guided thermal ablation treatments may be considered for solid or mixed symptomatic benign thyroid nodules. Surgery remains the treatment of choice for malignant or suspicious nodules. The present document updates previous guidelines released in 2006 and 2010 by the American Association of Clinical Endocrinologists (AACE), American College of Endocrinology (ACE) and Associazione Medici Endocrinologi (AME).

HEALTH-RELATED QUALITY OF LIFE AFTER PERCUTANEOUS RADIOFREQUENCY ABLATION OF COLD, SOLID, BENIGN THYROID NODULES: A 2-YEAR FOLLOW-UP STUDY IN 40 PATIENTS.

OBJECTIVE: We studied the impact of radiofrequency ablation (RFA) on health-related quality of life (HRQL) in patients with benign thyroid nodules (TN) in a 2-year follow-up. METHODS: Forty patients (35 women and 5 men; age, 54.9 ± 14.3 years) with cold thyroid solitary nodules or a dominant nodule within a normofunctioning multi-nodular goiter (volume range, 6.5 to 90.0 mL) underwent RFA of thyroid nodular tissue under ultrasound real-time assistance. RESULTS: Data are mean and standard deviation. Energy delivered was 37,154 ± 18,092 joules, with an output power of 37.4 ± 8.8 watts. Two years after RFA, nodule volume decreased from 30.0 ± 18.2 mL to 7.9 ± 9.8 mL (-80.1 ± 16.1% of initial volume; P<.0001). Thyroid-stimulating hormone, free triiodothyronine, and free thyroxine levels remained stable. Symptom score measured on a 0- to 10-cm visual analogue scale (VAS) declined from 5.6 ± 3.1 cm to 1.9 ± 1.3 cm (P<.0001). Cosmetic score (VAS 0-10 cm) declined from 5.7 ± 3.2 cm to 1.9 ± 1.5 cm (P<.0001). Two patients became anti-thyroglobulin antibody-positive. Physical Component Summary (PCS)-12 improved from 50.4 ± 8.9 to 54.5 ± 5.3, and the Mental Component Summary (MCS)-12 improved from 36.0 ± 13.3 to 50.3 ± 6.3 (P<.0001 for both score changes). CONCLUSION: Our 2-year follow-up study confirms that RFA of benign TNs is effective in reducing nodular volume and compressive and cosmetic symptoms, without causing thyroid dysfunction or life-threatening complications. Our data indicate that the achievement of these secondary endpoints is associated with HRQL improvement, measured both as PCS and MCS.

Levothyroxine liquid solution versus tablet for replacement treatment in hypothyroid patients.

BACKGROUND: Although replacement treatment with L-thyroxine (LT4) seems easy to manage, about one-third of hypothyroid patients show thyroid-stimulating hormone (TSH) values outside the normal range. OBJECTIVES: To explore whether LT4 liquid formulation (monodose vials or drops) affects TSH stability values and to assess its ability to maintain TSH within the normal range compared to tablets. METHODS: A total of 100 hypothyroid patients on replacement treatment with LT4 liquid solution were enrolled (Liquid Group) at a follow-up visit (revisit). The inclusion criteria were 1) treatment for surgical hypothyroidism for at least 2 years or autoimmune hypothyroidism for at least 5 years, 2) normal TSH at the previous visit 12 months before enrollment (baseline visit), and 3) maintenance of the same LT4 dosage during the time interval between the baseline and the follow-up visit. Using the same selection process, we also enrolled 100 hypothyroid patients on replacement treatment with LT4 tablets (Tablet Group). RESULTS: At the follow-up visit, 19 patients of the Tablet Group and 8 patients of the Liquid Group had abnormal TSH values (P = .023). Weekly and daily LT4 dosage per kilogram were higher in Tablet Group (P = .016 and .006, respectively). The magnitude of TSH change from baseline to follow-up visit was greater in the Tablet Group (P<.001). CONCLUSION: The use of LT4 liquid formulation compared to tablet resulted in a significantly higher number of hypothyroid patients who maintained the euthyroid state in a 12-month follow-up period and a reduced variability in TSH values.

A Computer-Interpretable Version of the AACE, AME, ETA Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules.

OBJECTIVE: Clinical practice guidelines (CPGs) could have a more consistent and meaningful impact on clinician behavior if they were delivered as electronic algorithms that provide patient-specific advice during patient-physician encounters. We developed a computer-interpretable algorithm for U.S. and European users for the purpose of diagnosis and management of thyroid nodules that is based on the "AACE, AME, ETA Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules," a narrative, evidence-based CPG. METHODS: We initially employed the guideline-modeling language GuideLine Interchange Format, version 3, known as GLIF3, which emphasizes the organization of a care algorithm into a flowchart. The flowchart specified the sequence of tasks required to evaluate a patient with a thyroid nodule. PROforma, a second guideline-modeling language, was then employed to work with data that are not necessarily obtained in a rigid flowchart sequence. Tallis-a user-friendly web-based "enactment tool"- was then used as the "execution engine" (computer program). This tool records and displays tasks that are done and prompts users to perform the next indicated steps. The development process was iteratively performed by clinical experts and knowledge engineers. RESULTS: We developed an interactive web-based electronic algorithm that is based on a narrative CPG. This algorithm can be used in a variety of regions, countries, and resource-specific settings. CONCLUSION: Electronic guidelines provide patient-specific decision support that could standardize care and potentially improve the quality of care. The "demonstrator" electronic thyroid nodule guideline that we describe in this report is available at http://demos.deontics.com/trace-review-app (username: reviewer; password: tnodule1). The demonstrator must be more extensively "trialed" before it is recommended for routine use.

The Influence of Impedance on the Efficacy of Radiofrequency Ablation for Benign Thyroid Nodules.

OBJECTIVE: Radiofrequency ablation (RFA) uses the heat generated by a high-frequency alternating electric current, and according to Ohm's and Joule's law, the delivered current is inversely proportional to the circuit impedance. The primary objective of this study was to investigate whether tissue impedance during radiofrequency ablation (RFA) for benign thyroid nodules is related to the degree of volume reduction. METHODS: This observational study included consecutive patients treated with RFA for benign thyroid nodules from February 2020 to August 2023. Technical effectiveness was defined as a volume reduction percentage (VRP) >75% at 6 months after the treatment. Multivariate logistic regression analyses were performed to identify the potential role of clinical factors and changes in tissue impedance on technique effectiveness. RESULTS: Totally 72 patients were included with 73 benign thyroid nodules. Maximal impedance peaks reached <18 times, and mean procedural impedance ≤300 Ω were significantly associated with a volume decrease of >75% at bivariate analysis. These cutoff points were exploratory, as no existing literature suggests these variables are related to the degree of volume reduction. After adjusting for age, volume, and composition, significant associations were found for mean electrical impedance in the multivariate analysis (OR = 4.86 [confidence interval [CI] 1.29-18.26], p = 0.019). The energy adjusted by volume (delivered energy) was not associated with a VRP >75% (p = 0.7746). CONCLUSIONS: This study suggests that a mean procedural impedance

Vocal Cord Monitoring by Flexible Fiberoptic Laryngoscopy During Thyroid Radiofrequency Ablation.

Introduction: Thermal injury to recurrent laryngeal nerve (RLN) during radiofrequency ablation (RFA) can produce temporary or permanent vocal cord paralysis.1 Hydrodissection with cold 5% glucose of "danger triangle" protects RLN during RFA.2 When RFA is performed under local anesthesia, RLN function is monitored by patients producing vocal sounds.3 Large lesions requiring longer RFAs warrant general sedation where voice cannot be assessed, therefore, an additional technique for RLN protection is advisable. Observation of passive symmetrical vocal cord movements during breathing by laryngeal ultrasonography is useful in assessing vocal cord function4; however, flexible-fiberoptic fibrolaringoscopy (FFL) is gold standard for assessing vocal cord movements,5 anticipating potential RLN damage. We report FFL monitoring during RFA under general sedation on a large thyroid nodule. FFL during RFA may detect RLN irritation and dysfunction if asymmetry in passive vocal cord movements is noted. Should asymmetry appear, RFA operator stops delivering energy and repositions electrode needle. Materials and Methods: Thyroid function tests, blood glucose, creatinine, transaminase, International-Normalized-Ratio, and electrocardiogram were performed. Operating room (OR) layout created sufficient space for ear-nose-throat (ENT) and RFA operators. An examination with a fiberscope camera demonstrated normal vocal cord adduction during phonation and abduction during breathing. The procedure was assisted by an anesthetist administering fentanyl 50 mcg, midazolam 1.5 to 5.0 mg, and propofol infusion 2 mg/(kg·h). General sedation was conducted so that reflexes were attenuated but still observable. Incorporating in OR by an anesthetist who performs general sedation reduces side effects and complications.6 Ultrasonography showed a 34-mL right lobe nodule abutting on the RLN area. After sedation with propofol, the ENT specialist inserted an endoscope until the glottic plane. During calm breathing, vocal cords moved symmetrically. After obtaining anterior nodule hydrodissection from strap and sternocleidomastoid muscles with 10 mL of 2% lidocaine, posterior hydrodissection was achieved by ultrasound-guided administration of 30 mL of 5% cold glucose. Anterior and posterior hydrodissections merged, separating nodule from neck structures. The radiofrequency electrode needle was then inserted into the nodule, initially positioned in inferior nodule portion adjacent to danger triangle previously isolated by hydrodissection. Initial power was 30 watts. Moving-shot technique was used. Results: FFL was performed throughout thyroid RFA. Symmetric vocal cord movements during breathing demonstrated no RLN irritation. FFL monitoring allowed observation of natural reflexive phenomena, including swallowing. Complete nodule ablation was achieved. FFL performed post-RFA confirmed normal vocal cord motility. Conclusions: We report the first-time use of FFL for vocal cord monitoring during RFA. FFL was easily performed by the ENT specialist and well tolerated by the patient. Avoiding danger triangle and precise RFA needle positioning is key in preventing RLN injury. Benign nodules regrow if total ablation is not achieved7 and some authors propose additional procedures to complete ablation8 that obviously incurs costs. Total RFA nodule ablation-assisted FFL monitoring eliminates the need for repetitive RFAs, thus reducing overall treatment costs. Finally, FFL monitoring does not prolong procedure, as it is performed simultaneously with RFA. FFL is a valid technique when used in conjunction with hydrodissection to further prevent RLN thermal injury during RFA, especially indicated for large thyroid nodule ablation and professional voice users. Patient Consent and Permission: The patient provided written consent for FFL monitoring and permission to use his portrayals and ultrasonographic images during RFA. The study was completed in accordance with the Declaration of Helsinki as revised in 2013. Adherence to institutional review board protocols was granted. Disclaimer: Representation of any instrumentation within the video does not indicate any endorsement of the product and/or company by the publisher, the American Thyroid Association, or the authors. No competing financial interests exist. Runtime of video: 9 mins 39 secs.

Long-term effectiveness of ultrasound-guided laser ablation of hyperfunctioning parathyroid adenomas: present and future perspectives.

OBJECTIVE: Although surgery is the first-choice treatment of primary hyperparathyroidism (pHPT), some patients present with contraindications or refuse surgery. Data from alternative nonsurgical therapies are inconclusive. To study the long-term efficacy of laser ablation in the treatment of pHPT, we retrospectively reviewed six cases of laser-treated patients. MATERIALS AND METHODS: Six patients with pHPT were treated with laser ablation using a flat-tip technique. Energy was administered by means of one optic fiber placed into the parathyroid adenoma through a 21-gauge Chiba needle connected to a neodymium:yttrium-aluminum-garnet laser. The mean (± SD) delivered energy for all patients was 2.067 ± 1440 J (range, 1000-4200 J). Treatment was fractionated in two (n = 2 patients) or in three (n = 1 patient) ultrasound-guided sessions. Patients' serum parathyroid hormone (PTH) and calcium levels were checked periodically, with neck ultrasound performed. The mean duration of follow-up was 54 ± 34 months (range, 12-84 months). RESULTS: Two months after laser ablation, serum PTH and calcium levels decreased in six and five patients, respectively. At the last follow-up examination, serum PTH and calcium levels were above the normal range in six and three patients, respectively. Three patients underwent surgery for persistent pHPT. Laser ablation therapy was safe and without permanent side effects. One patient reported transient dysphonia. CONCLUSION: Laser ablation produces a transient reduction of serum PTH and calcium levels but not a lasting resolution of hyperparathyroidism. Laser cannot be proposed as the definitive therapy of pHPT. Thus, studies aiming to identify therapeutic algorithms specific for parathyroid glands are needed to verify the utility of laser ablation in pHPT.

Radiofrequency ablation and related ultrasound-guided ablation technologies for treatment of benign and malignant thyroid disease: An international multidisciplinary consensus statement of the American Head and Neck Society Endocrine Surgery Section with the Asia Pacific Society of Thyroid Surgery, Associazione Medici Endocrinologi, British Association of Endocrine and Thyroid Surgeons, European Thyroid Association, Italian Society of Endocrine Surgery Units, Korean Society of Thyroid Radiology, Latin American Thyroid Society, and Thyroid Nodules Therapies Association.

BACKGROUND: The use of ultrasound-guided ablation procedures to treat both benign and malignant thyroid conditions is gaining increasing interest. This document has been developed as an international interdisciplinary evidence-based statement with a primary focus on radiofrequency ablation and is intended to serve as a manual for best practice application of ablation technologies. METHODS: A comprehensive literature review was conducted to guide statement development and generation of best practice recommendations. Modified Delphi method was applied to assess whether statements met consensus among the entire author panel. RESULTS: A review of the current state of ultrasound-guided ablation procedures for the treatment of benign and malignant thyroid conditions is presented. Eighteen best practice recommendations in topic areas of preprocedural evaluation, technique, postprocedural management, efficacy, potential complications, and implementation are provided. CONCLUSIONS: As ultrasound-guided ablation procedures are increasingly utilized in benign and malignant thyroid disease, evidence-based and thoughtful application of best practices is warranted.

Effect of estrogen therapy for 1 year on thyroid volume and thyroid nodules in postmenopausal women.

OBJECTIVE: Estrogen receptors are present in thyroid follicular cells in normal and neoplastic tissue. We evaluated changes in total thyroid volume and volume of thyroid nodules in postmenopausal women given either hormone therapy (HT) or no treatment in a 1-year observational follow-up. DESIGN: We studied 33 women receiving HT and 76 women receiving no treatment, comparing total thyroid volume, thyroid nodule volume, and serum concentrations of thyroid-stimulating hormone and estradiol at baseline and 1 year of follow-up. RESULTS: Serum thyroid-stimulating hormone concentrations were not different between groups either at baseline or at 1 year. Estradiol rose significantly in the HT group. The final percent changes in total thyroid volume were comparable between groups (HT, 1.59 +/- 2.56%; no treatment, 1.20 +/- 2.28%). At baseline, nodules were detected in 17 (51.5%) and 33 (43.4%) of women in the HT and no treatment groups, respectively, with no statistically significant difference between groups. The final number of nodules was unchanged or reduced in 88.2% and 81.1% and increased in 11.8% and 18.9% of women in the HT and no treatment groups, respectively, with no differences between groups. Baseline volumes of thyroid nodules were 0.8 +/- 0.4 and 1.4 +/- 0.4 mL in women in the HT and no treatment groups, respectively (P = 0.4). After 1 year the volume of thyroid nodules was unchanged or reduced in 47.1% and 52.8% and increased in 52.9% and 47.2% of women in the HT and no treatment groups, respectively, with no differences between groups. CONCLUSIONS: Estrogen administration for 1 year did not affect thyroid volume or the number and volume of thyroid nodules in postmenopausal women.

American Association of Clinical Endocrinologists and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules.

Thyroid nodules are common and are frequently benign. Current data suggest that the prevalence of palpable thyroid nodules is 3% to 7% in North America; the prevalence is as high as 50% based on ultrasonography (US) or autopsy data. The introduction of sensitive thyrotropin (thyroid-stimulating hormone or TSH) assays, the widespread application of fine-needle aspiration (FNA) biopsy, and the availability of high-resolution US have substantially improved the management of thyroid nodules. This document was prepared as a collaborative effort between the American Association of Clinical Endocrinologists (AACE) and the Associazione Medici Endocrinologi (AME). Most Task Force members are members of AACE. We have used the AACE protocol for clinical practice guidelines, with rating of available evidence, linking the guidelines to the strength of recommendations. Key observations include the following. Although most patients with thyroid nodules are asymptomatic, occasionally patients complain of dysphagia, dysphonia, pressure, pain, or symptoms of hyperthyroidism or hypothyroidism. Absence of symptoms does not rule out a malignant lesion; thus, it is important to review risk factors for malignant disease. Thyroid US should not be performed as a screening test. All patients with a palpable thyroid nodule, however, should undergo US examination. US-guided FNA (US-FNA) is recommended for nodules > or = 10 mm; US-FNA is suggested for nodules < 10 mm only if clinical information or US features are suspicious. Thyroid FNA is reliable and safe, and smears should be interpreted by an experienced pathologist. Patients with benign thyroid nodules should undergo follow-up, and malignant or suspicious nodules should be treated surgically. A radioisotope scan of the thyroid is useful if the TSH level is low or suppressed. Measurement of serum TSH is the best initial laboratory test of thyroid function and should be followed by measurement of free thyroxine if the TSH value is low and of thyroid peroxidase antibody if the TSH value is high. Percutaneous ethanol injection is useful in the treatment of cystic thyroid lesions; large,symptomatic goiters may be treated surgically or with radioiodine. Routine measurement of serum calcitonin is not recommended. Suggestions for thyroid nodule management during pregnancy are presented. We believe that these guidelines will be useful to clinical endocrinologists, endocrine surgeons, pediatricians, and internists whose practices include management of patients with thyroid disorders. These guidelines are thorough and practical, and they offer reasoned and balanced recommendations based on the best available evidence.

Sonography of Normal and Abnormal Thyroid and Parathyroid Glands.

Ultrasonography (US) represents the most sensitive and efficient method for the evaluation of the thyroid and parathyroid glands. Infectious and autoimmune thyroiditis are common diseases, usually diagnosed and followed up by clinical examination and laboratory analyses. Nevertheless, US plays an important role in confirming diagnoses, predicting outcomes and, in autoimmune hyperthyroidism, in titrating therapy. Conversely, in nodular thyroid disease US is the imaging method of choice for the characterization and surveillance of lesions. It provides consistent clues in predicting the risk of malignancy, thus directing patient referral for fine-needle aspiration (FNA) biopsy. Suspicious US features generally include marked hypoechogenicity, a shape taller than it is wide, ill-defined or irregular borders, microcalcifications and hardness at elastographic evaluation. Finally, the role of US in thyroid cancer is to evaluate extension beyond the thyroid capsule and to assess nodal metastases or tumor recurrence. The main application of US in parathyroid diseases is represented by primary hyperparathyroidism. In this condition, US plays a role after biochemical diagnosis, and it should always be strictly performed for localization purposes. In both thyroidal and parathyroid diseases, US is recommended as a guide in FNA biopsies.

Ultrasound B-flow imaging in the evaluation of thermal ablation of thyroid nodules.

The aim of percutaneous thermal ablation is to reduce the volume of benign thyroid nodules. B-flow imaging, a non-Doppler technology for blood flow imaging, provides a real-time visualization of vascularity, and gives accurate information on the vessel lumen in high spatial and temporal resolution. Little is known about the possible application of this new technique on thyroid nodules after thermal treatments. Color power Doppler and contrast-enhanced ultrasound are the methods currently used in this context, but they present some limitations. Conversely, during the thermal procedures, B-flow imaging--suppressing unwanted signals (e.g., noise and tissue) and boosting weak signals (e.g., blood echoes)--permits an accurate spatial analysis of the intranodular flow. B-flow imaging may clearly show a complete ablation during the treatment. Moreover, it can also be useful during the follow-up in highlighting the possible intranodular flow regrowth. In conclusion, B-flow imaging--overcoming the limitations of color power Doppler and contrast-enhanced ultrasound-is useful to evaluate, in real time, the necrotic area of thyroid nodules during and after thermal ablative procedures.

Challenges in neck ultrasonography: lymphadenopathy and parathyroid glands.

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.

Ultrasound-guided percutaneous ethanol injection therapy in thyroid cystic nodules.

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.

Ultrasound thyroid nodule measurements: the "gold standard" and its limitations in clinical decision making.

OBJECTIVE: To highlight the limitations associated with use of ultrasonography for the evaluation of thyroid nodule or gland volume for clinical decision making. METHODS: We review the equipment (scanners and probes) used for ultrasonography and the appropriate measurements for assessment of thyroid nodules. The limitations of ultrasound thyroid measurements are summarized, particularly in reference to repeated measurements over time. RESULTS: Thyroid ultrasonography is the recognized "gold standard" for an accurate and reliable assessment of gland volume and thyroid nodules. Many endocrinologists refer patients for surgical treatment because of detection of growth of thyroid nodules. In daily practice, they often make this decision by comparing ultrasound thyroid measurements determined over time. Although reliable, evaluation of thyroid nodule volume by ultrasonography has technologic, biologic, and examination technique limitations. These are particularly important in routine clinical practice, where ultrasound measurements are performed in less standardized settings than in experimental trials. CONCLUSION: In daily medical office applications, ultrasound measurements of thyroid nodules should be used with caution in decision making.

The peculiar ultrasonographic and elastographic features of thyroid nodules after treatment with laser or radiofrequency: similarities and differences.

The aim of percutaneous thermal ablation with laser (LA) or radiofrequency (RFA) is to reduce the volume of benign thyroid nodules. Little is known about ultrasonographic and elastographic appearances of thyroid lesions after treatment. For the first time, we report in detail the main ultrasonographic and elastographic characteristics of thermally ablated nodules and their underlying similarities and differences. Both thermal treatments usually produce a marked hypoechoic area of coagulative necrosis. LA-treated lesions usually become highly heterogeneous due to the presence of cavitations and charring; they then evolve into hyperechoic scars. In RFA-treated nodules, instead, the necrotic area is more homogeneous but presents more irregular margins compared to those observed in LA-treated lesions. Regardless of the thermal method used, vascularity is typically reduced in all treated nodules and stiffness, evaluated with qualitative elastography, increases. In conclusion, ultrasonographic and elastographic appearances of the thermally ablated thyroid lesions differ slightly according to the adopted procedure. Furthermore, they are peculiar, changeable over time, and potentially misleading.

Incidental thyroid cancer in toxic and nontoxic goiter: Is TSH associated with malignanCy rate? Results of a meta-analysis.

OBJECTIVE: In the last 6 years, several studies reported a positive association between thyrotropin (TSH) and papillary cancer risk. The rationale is based on stimulatory action exerted by TSH on thyroid cell proliferation and/or progression of a pre-existing papillary carcinoma. To validate this hypothesis, we performed a meta-analysis comparing the incidence of thyroid cancer in 2 groups of patients who underwent surgery for toxic or nontoxic nodular goiter. METHODS: Using data from 2,150 patients with toxic multinodular goiter (TMNG) and 873 patients with toxic adenoma (TA), the overall incidence of thyroid cancer (and 95% confidence interval [CIs]) was estimated to be 5.9% (3.9 to 8.3) for patients with TMNG and 4.8% (2.5 to 7.9) for patients with TA. Four studies were included in the meta-analysis with a total of 1,964 subjects undergoing thyroidectomy for allegedly benign thyroid disease (520 patients with TMNG or TA and 1,444 for multinodular goiter [MNG] or uninodular goiter [UNG]). RESULTS: We did not find any significant differences in the risk of incidental thyroid cancer (ITC) in patients with TMNG versus MNG (odds ratio [OR]: 0.91, 95% CI: 0.47 to 1.77, I²: 62.6%), TA versus uninodular goiter (UNG) (OR: 0.46, 95% CI: 0.12 to 1.79, I²: 12%), and TMNG or TA versus MNG or UNG (pooled analysis) (OR: 0.86, 95% CI: 0.46 to 1.60, I²: 51.5%). CONCLUSIONS: The results of this meta-analysis did not confirm an association between low TSH values and lower thyroid cancer rate, at least in patients with nodular disease.

A longitudinal study of thyroidectomized patients in a region of northern Italy: benign versus malignant disease.

OBJECTIVE: Thyroid disease is very common, particularly nodular goiter. Total thyroidectomy is a therapeutic option for both malignant and benign disease. The aim of the study was to evaluate the number of total thyroidectomy surgeries and the rate of benign and malignant histologic exams over the last decade. METHODS: Hospital discharge records in the Emilia Romagna region (Italy) that reported total thyroidectomy as the principal surgical procedure and included the relative histologic diagnosis were reviewed for the period 2000 to 2010. Mean increment and geometric mean of increments per year were calculated to evaluate differences over the years. RESULTS: More than 25,000 patients underwent total thyroidectomy between 2000 and 2010. The total number of thyroidectomies increased over this period, with a mean increment of 7.16% per year. The percentage of malignancies among the total number of thyroidectomies increased from 26.1% (2000) to 39.9% (2010) (mean increment, 1.38% per year). Nontoxic multinodular goiter was the most frequent diagnosis, accounting for 36% of all thyroidectomies. CONCLUSIONS: Between 2000 and 2010, the proportion of patients thyroidectomized for benign disease progressively decreased, as documented by a lower thyroidectomy/malignancy ratio. Currently, about 60% of thyroid interventions are performed for benign pathology. Improved preoperative diagnostic accuracy and the availability of nonsurgical procedures will presumably further reduce the number of thyroidectomies with benign histologic diagnoses.

Ultrasound-guided percutaneous laser ablation of papillary thyroid microcarcinoma: a feasibility study on three cases with pathological and immunohistochemical evaluation.

BACKGROUND: Ultrasound-guided thermal laser ablation (LA) is a nonsurgical technique that has been proposed, but not fully assessed, for papillary thyroid microcarcinoma (PTMC) treatment. The objectives of this study were to evaluate the clinical feasibility of LA on PTMC as a primary treatment and to prove histologically the absence of residual viable tumor after LA procedure. METHODS: Three patients with a Thy 6 diagnosis at fine-needle aspiration cytology with a single PTMC smaller than 10 mm volunteered after full explanation of the protocol. At ultrasound examination, patients had no extrathyroid extension and no evidence of lymph node metastasis. Patients underwent percutaneous ultrasound-assisted LA of the PTMC in the operating room under general anesthesia. One 300 µm plane-cut optic fiber was inserted through the sheath of 21G Chiba needle, exposing 5 mm of the nude fiber in direct contact with tumor tissue, and connected with a laser source operating at 1.064 µm with 3 W output power. Total energy delivery was 1800 J. The surgeon directly started a standard total thyroidectomy. During surgical inspection, no remarkable laser sign was observed in the muscles, the perithyroidal tissues, or the recurrent laryngeal nerves. RESULTS: Conventional histology showed destructured and carbonized tissue. Lack of vitality was demonstrated by complete loss of TTF1 and antimitochondria antibody expression in the whole ablated area and in the rim of normal tissue surrounding the tumor. BRAF V600E mutation was detected in cases 1 and 2. Furthermore, in cases 2 and 3, incidental papillary microfoci were found. A lymph node micrometastasis (200 µm) was observed in case 2. CONCLUSIONS: This study demonstrates that percutaneous LA is technically feasible for complete PTMC destruction. Now, LA may be useful in selected patients with PTMC, either when the surgeon or a patient refuses surgery, or when the patient is at high risk for an operation. LA may become a primary choice of treatment for PTMC only if future new knowledge would permit preoperative recognition of multifocality and lymph node metastasis.

Thyrotropin values in patients with micropapillary thyroid cancer versus benign nodular disease.

OBJECTIVE: Studies published in the last few years suggest that increased thyroid-stimulating hormone (TSH) values are associated with increased risk of thyroid cancer and/or a more advanced stage of malignancy. The aim of this study was to explore the hypothesis that TSH may be a risk factor for thyroid cancer initiation, which was tested by comparing TSH concentrations in patients with incidental micro papillary cancer (mPTC) and controls with a negative histologic exam. METHODS: Patients were retrospectively selected from medical records from 3 district hospitals. Patients with biochemical/histologic evidence of autoimmunity, thyroid function-interfering drugs, and autonomously functioning areas, were excluded. TSH values of 41 patients with an incidental mPTC were then compared with a sex- and age-matched group of patients who had a negative histologic exam at a 4:1 ratio (164 patients). RESULTS: TSH was not significantly different in the mPTC group compared to the controls (1.1 ± 0.7 vs. 1.3 ± 1.0 mIU/L). After adjustment for age and gender, TSH levels were still not found to be significantly different between groups. In the mPTC group, TSH levels were not found to be a significant predictor of tumor size after adjusting for age and gender (ß = 0.035, SE = 0.73, P = .844). CONCLUSIONS: On the basis of these results, the hypothesis that TSH is involved in de novo oncogenesis of PTC is not supported.