Use of thyroid hormones in hypothyroid and euthyroid patients: A survey of members of the Endocrine Society of Australia.

OBJECTIVE: Hypothyroidism is a common endocrine condition usually managed with levothyroxine (LT4). However, controversy remains around the use of liothyronine (LT3). We aimed to investigate the practices of Australian endocrinologists when managing patients with hypothyroidism, their use of LT3 + LT4 combination therapy and use of thyroid hormones in euthyroid patients. DESIGN AND PARTICIPANTS: Members of the Endocrine Society of Australia (ESA) were invited to participate in an online questionnaire. MEASUREMENTS: We analysed questionnaires that had complete demographic data. RESULTS: Eighty-seven questionnaires fulfilled the criteria. LT4 was used as first line treatment for hypothyroidism by all respondents. Only 45% reported that their patients were dispensed the brand of LT4 that they recommend. LT3 (alone or in combination) was prescribed by 44% in their clinical practice. Although 49% of respondents would consider LT3 + LT4 in patients with normal TSH who had ongoing symptoms of hypothyroidism, the inability of LT4 to restore normal physiology was ranked the least likely explanation for persistent symptoms and only 32% would consider it for themselves if they were diagnosed with hypothyroidism. The majority (55%), in accordance with evidence, would not prescribe thyroid hormone to euthyroid individuals but 39% would consider use in euthyroid female infertility with high levels of thyroid antibodies and 11% in euthyroid patients with a simple goitre growing over time. LT4 use in pregnancy was variable among members. CONCLUSIONS: Australian endocrinologists mostly follow international guidelines when prescribing thyroid hormone therapy and many prescribe combination LT3 and LT4 therapy, particularly for patients who remain symptomatic on LT4 monotherapy. Prescribing practices are largely similar to other countries who have completed similar questionnaires.

Use of levothyroxine for euthyroid, thyroid antibody positive women with infertility: Analyses of aggregate data from a survey of European thyroid specialists (Treatment of Hypothyroidism in Europe by Specialists: An International Survey).

OBJECTIVES: The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients. DESIGN: The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb. RESULTS: A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%-83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7-0.9) and respondents >60 years (OR: 0.7; 0.6-0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients ("weekly" [OR: 1.4; CI: 1.0-1.9], "daily" [OR: 1.8; CI: 1.3-2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3-1.9) were most likely to consider LT4. CONCLUSIONS: A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment.

International Expert Consensus on US Lexicon for Thyroid Nodules.

Multiple US-based systems for risk stratification of thyroid nodules are in use worldwide. Unfortunately, the malignancy probability assigned to a nodule varies, and terms and definitions are not consistent, leading to confusion and making it challenging to compare study results and craft revisions. Consistent application of these systems is further hampered by interobserver variability in identifying the sonographic features on which they are founded. In 2018, an international multidisciplinary group of 19 physicians with expertise in thyroid sonography (termed the International Thyroid Nodule Ultrasound Working Group) was convened with the goal of developing an international system, tentatively called the International Thyroid Imaging Reporting and Data System, or I-TIRADS, in two phases: (phase I) creation of a lexicon and atlas of US descriptors of thyroid nodules and (phase II) development of a system that estimates the malignancy risk of a thyroid nodule. This article presents the methods and results of phase I. The purpose herein is to show what has been accomplished thus far, as well as generate interest in and support for this effort in the global thyroid community.

The enigma of persistent symptoms in hypothyroid patients treated with levothyroxine: A narrative review.

A significant minority of patients with hypothyroidism report persistent symptoms despite achieving normal thyroid biochemistry after levothyroxine (L-T4) replacement. Four principal lines of thinking, which are not mutually exclusive, may explain this enigma. The 'low tissue liothyronine hypothesis' emphasizes the potential imperfections of L-T4 replacement therapy that may lead to hypothyroidism in some tissues such as the brain, while others (eg hypothalamus) are euthyroid. The 'Somatic Symptom and Related Disorders hypothesis' draws attention to an incidental coexistence of a diagnosis of Somatic Symptom and Related Disorders in patients with treated hypothyroidism. The 'autoimmune neuroinflammation hypothesis' highlights the potential consequences of inflammatory mediators due to thyroid autoimmunity (the commonest cause of hypothyroidism) on the brain. The 'comorbidities and psychosocial hypothesis' implicates a variety of physical and psychosocial factors that have been noted to be associated with a diagnosis of hypothyroidism, which may be primarily the cause of persistent complaints. Over the past twenty years, a great deal of time and effort has been expended pursuing the 'low tissue liothyronine hypothesis', which has failed to yield results that translate to patient benefits. This has skewed the balance in clinical practice, in favour of pursuing answers relating to L-T4 and liothyronine combination treatment, while the alternative explanations have been downplayed and potentially useful interventions have been given insufficient attention.

Use of thyroid hormones in hypothyroid and euthyroid patients: A THESIS questionnaire survey of UK endocrinologists.

OBJECTIVE: Management of hypothyroidism is controversial because of medication cost pressures and scientific uncertainty on how to address treatment dissatisfaction experienced by some patients. The objective was to investigate the experience and preferences of UK endocrinologists in use of thyroid hormones. DESIGN: Web-based survey. PATIENTS: UK endocrinologists were invited to participate. MEASUREMENTS: Responses to questionnaire. RESULTS: The response rate was 21% (272/1295). While levothyroxine monotherapy is regarded as the treatment of choice for hypothyroidism, 51% of respondents stated that combined treatment with levothyroxine and liothyronine could be considered for levothyroxine-treated patients whose symptoms persist despite normalisation of serum thyroid stimulating hormone (TSH) concentration. However, only 40% are currently prescribing such treatment, and just 23% would consider taking it themselves. A small minority prescribe desiccated thyroid extract, and those most likely to do so are aged over 60 years. Most respondents stated that they have no influence over brand or formulation of levothyroxine dispensed to their patients and expect no major differences in efficacy between different formulations. A total of 9% would prescribe levothyroxine for euthyroid enlarging goitre, and 29% for euthyroid female infertility with high titre thyroid peroxidase antibodies, despite recent trials finding no benefit. CONCLUSIONS: UK endocrine practice in management of hypothyroidism is broadly in line with international guidance. However, a minority of respondents would consider thyroid hormone supplementation in euthyroid individuals for female infertility, enlarging goitre, and other indications in which evidence of efficacy is lacking. Willingness to consider prescribing combined levothyroxine and liothyronine, for hypothyroid symptoms which persist despite normalised TSH, has increased in comparison to previous international surveys, despite inconsistent evidence of benefit.

Image-guided thermal ablation in autonomously functioning thyroid nodules. A retrospective multicenter three-year follow-up study from the Italian Minimally Invasive Treatment of the Thyroid (MITT) Group.

OBJECTIVES: To report the results of a multicenter retrospective evaluation of the clinical outcomes of thermal ablation (TA) in a large series of autonomously functioning thyroid nodules (AFTN) with a follow-up protracted up to 3 years. METHODS: Patients treated with single TA for an AFTN in Italy were included. Changes in nodule volume, TSH values, and ongoing anti-thyroid therapy were assessed at the 2-, 6-, 12-, 24-, and 36-month follow-up controls. Complications and need of any additional therapy after TA were also registered. RESULTS: A total of 361 patients (244 females, 117 males, median age 58 years, IQR 46-70 years) were included. Nodule volume was significantly reduced at all time points (p < 0.001) (median volume reduction 58% at 6-month and 60% at 12-month). Serum TSH values increased significantly at all time points. After TA, anti-thyroid therapy was withdrawn in 32.5% of patients at 2 months, in 38.9% at 6 months, and in 41.3% at 12 months. A significant difference in the rate of patients who withdrawn medical therapy at 12 months was registered between small (< 10 mL) (74%), medium (49%), or large (> 30 mL) nodules (19%). A single major complication occurred (0.25%). Additional treatments were needed in 34/361 (9.4%) of cases including 4 (1.1%) surgical treatment. CONCLUSIONS: Image-guided thermal ablation offers a further safe and effective therapeutic option in patients with AFTN. Clinical outcomes are significantly more favorable in small than in large size AFTN. KEY POINTS: • Thermal ablations (TA) can be safely and effectively used in patients with autonomously functioning thyroid nodules (AFTN). • TA results in a clinically significant nodule volume reduction that is paralleled by TSH level normalization and anti-thyroid drug therapy discontinuation (after TA anti-thyroid therapy was withdrawn in 41.3% at 12 months). • Clinical outcomes after TA are more favorable in small nodules, and when a large amount of thyroid nodule tissue is ablated.

Use of thyroid hormones in hypothyroid and euthyroid patients: a 2020 THESIS questionnaire survey of members of the Czech Society of Endocrinology.

BACKGROUND: Inconsistencies in the management of hypothyroidism have been reported among endocrinologists in different European countries. Aim of this study was to explore Czech endocrinologists' use of thyroid hormones in hypothyroid and euthyroid patients. METHODS: We used a web-based survey containing 32 questions regarding the use of thyroid hormones. Four-hundred thirty-two members of the Czech Society of Endocrinology received an e-mail invitation to participate in the survey. RESULTS: We received and analysed 157 responses (112 females and 45 males) from the 432 members (36.3%). According to 99.4% of the respondents, levothyroxine (LT4) is the primary drug of choice for the treatment of hypothyroidism. Liothyronine (LT3) was used in clinical practice by 29.9% of responders. According to 90.5% of respondents, thyroid hormones may be indicated in biochemically euthyroid patients. Female physicians prescribe thyroid hormones in euthyroid infertile women with high antibody levels more frequently than male physicians (P = 0.003). Most Czech endocrinologists (76.4%) consider combined therapy with LT4 and LT3 in various clinical scenarios, but only 1 of 29 hypothyroid physicians (3.5%) would recommend it to their patients, and only 4 out of 128 respondents (3.1%) would consider LT3 or desiccated thyroid for themselves, if diagnosed with hypothyroidism. CONCLUSION: LT4 is the primary thyroid hormone used in the Czech Republic for treatment of hypothyroidism. At variance with thyroid guideline recommendations, Czech endocrinologists are quite liberal when prescribing thyroid hormones to euthyroid patients and in the use of LT4/LT3 combination treatment for hypothyroid patients with persisting symptoms.

2022 Expert consensus on the use of laser ablation for papillary thyroid microcarcinoma.

OBJECTIVE: With the aim of standardizing and improving the use of ultrasound-guided PLA on PTMC, a panel of experts from China and Italy, jointly issued this expert consensus on the clinical use of PLA for low-risk PTMC. METHODS: This expert consensus was developed by Chinese and Italian experts who have specific competence and expertise in this area. An evidence-based approach combining the knowledge and practical experience of the panelists was utilized. RESULTS: Twenty-six expert consensus recommendations were developed, spanning topics including the indications and contraindications of PLA for PTMC, physician training, preoperative preparation of patients, intraoperative technical procedures, possible complications, efficacy assessment, follow-up strategy, the approach to new PTMC and metastatic lymph nodes after treatment, thyroid-stimulating hormone inhibition therapy, and quality control of the entire procedure. CONCLUSION: We summarized practical recommendations about standardized and improved PLA treatment for PTMC.

American Association of Clinical Endocrinology And Associazione Medici Endocrinologi Thyroid Nodule Algorithmic Tool.

OBJECTIVE: The first edition of the American Association of Clinical Endocrinology/American College of Endocrinology/Associazione Medici Endocrinologi Guidelines for the Diagnosis and Management of Thyroid Nodules was published in 2006 and updated in 2010 and 2016. The American Association of Clinical Endocrinology/American College of Endocrinology/Associazione Medici Endocrinologi multidisciplinary thyroid nodules task force was charged with developing a novel interactive electronic algorithmic tool to evaluate thyroid nodules. METHODS: The Thyroid Nodule App (termed TNAPP) was based on the updated 2016 clinical practice guideline recommendations while incorporating recent scientific evidence and avoiding unnecessary diagnostic procedures and surgical overtreatment. This manuscript describes the algorithmic tool development, its data requirements, and its basis for decision making. It provides links to the web-based algorithmic tool and a tutorial. RESULTS: TNAPP and TI-RADS were cross-checked on 95 thyroid nodules with histology-proven diagnoses. CONCLUSION: TNAPP is a novel interactive web-based tool that uses clinical, imaging, cytologic, and molecular marker data to guide clinical decision making to evaluate and manage thyroid nodules. It may be used as a heuristic tool for evaluating and managing patients with thyroid nodules. It can be adapted to create registries for solo practices, large multispecialty delivery systems, regional and national databases, and research consortiums. Prospective studies are underway to validate TNAPP to determine how it compares with other ultrasound-based classification systems and whether it can improve the care of patients with clinically significant thyroid nodules while reducing the substantial burden incurred by those who do not benefit from further evaluation and treatment.

Morphological and Molecular Assessment in Thyroid Cytology Using Cell-Capturing Scaffolds.

The increased frequency of thyroid nodules is paralleled by the rise of thyroid cancer diagnosis. To define the nature of most thyroid nodules, fine needle aspiration (FNA) followed by cytological evaluation is considered the method of choice. About 20% of FNA biopsies on thyroid nodules, however, show indeterminate cytological features and may require diagnostic surgery. Several immunocytochemical and molecular markers have been proposed to improve classification of thyroid nodules, but these tests require adequate cell amount and cytological paraffin inclusion. Polymeric matrices were recently proposed for the collection of cells for diagnostic purposes. In this study, we evaluated the diagnostic use of a new matrix (CytoMatrix). Morphological, molecular and immunohistochemical investigations were carried out on 23 FNA samples included in CytoMatrix and compared with data obtained from the definitive histology of surgical samples. Our results showed that CytoMatrix is suitable to capture and preserve the cellularity of the samples harvested by FNA and that its paraffin sections mimic the morphology of those obtained from real histological tissue. Immunohistochemistry on CytoMatrix samples was consistent with the immunophenotypical profile of the corresponding histological surgical specimens. Mutational analysis of the BRAF (V600E) gene performed on CytoMatrix inclusions and paired surgical tissue matched in all but one cases while matrix immunohistochemistry identified 91.6% of BRAF mutated samples. In conclusion, we suggest that CytoMatrix could be a reliable tool to overcome the current limits of traditional collection methods for the study of thyroid cytology, thereby improving their reliability for a conclusive diagnostic interpretation.

High-intensity focused ultrasound (HIFU) therapy for benign thyroid nodules: a 3-year retrospective multicenter follow-up study.

BACKGROUND: Outcomes of high-intensity focused ultrasound (HIFU), as a non-surgical treatment option for benign symptomatic thyroid nodules, has mainly been based on single-center studies and short-term follow-up. Therefore, we assessed the safety, and long-term efficacy of HIFU in benign thyroid nodules among four centers with expertise in thyroid mini-invasive procedures. PATIENTS AND METHODS: Retrospective three year follow-up study in four European centers, treating solid benign thyroid nodules causing pressure symptoms and/or cosmetic concerns. Nodule volume reduction was assessed at 1, 3, 6, 12, 24, and 36 months post-treatment. Technical efficacy, defined as a volume reduction rate (VVR) >50% was evaluated at 6, 12, 24 and 36 months. Predictive factors of efficacy were assessed using logistic models. Complications and side effects were classified according to the Interventional Radiology Guidelines and changes in local symptoms were scored on a visual-analog scale. RESULTS: Sixty-five patients (mean age 51.1 ± 14.0 years; 86.2% women) with a single thyroid nodule and a mean baseline nodule volume of 9.8 ± 10.3 mL were treated with a mean energy of 7.1 ± 3.1 kJ (range: 2.0 to 15.5 kJ). Median nodule volume reduction was 31.5% (IQR: -38.6% to -23.1%) at 12 months and 31.9% (IQR: -36.4% to -16.1%) at 36 months. Technical efficacy was obtained in 17.2% of cases at 6 months, 17.8% at 12 months, 3.4% at 24 months, and 7.4% at 36 months. The number of treated pixels and the mean energy delivered were positively correlated to VRR at 1, 6 and 12 months. The risk of treatment failure decreased by 4.3% for each additional unit of energy delivered. The procedure duration was inversely correlated with treatment failure (OR 1.043, 95% CI: 1.011-1.083; p = 0.014). Improvement of cervical pressure symptoms or cosmetic complaints were observed in less than 15% of the cases at 12, 24 and 36 months. Horner's syndrome occurred in one case (1.5%) and minor complications, not requiring treatment, in three (4.6%) patients. No change in thyroid function was registered. CONCLUSIONS: HIFU carried a low risk of complications. A single treatment resulted in a 30-35% thyroid nodule volume decrease within one year, reduction that remained stable for 2 years. Outcomes varied significantly between centers with different HIFU expertise. Focus on improved HIFU technology, adequate training, and appropriate selection of patients is needed to achieve efficacy comparable to other thermal ablation procedures.

Minimally-invasive treatments for benign thyroid nodules: a Delphi-based consensus statement from the Italian minimally-invasive treatments of the thyroid (MITT) group.

Benign thyroid nodules are a common clinical occurrence and usually do not require treatment unless symptomatic. During the last years, ultrasound-guided minimally invasive treatments (MIT) gained an increasing role in the management of nodules causing local symptoms. In February 2018, the Italian MIT Thyroid Group was founded to create a permanent cooperation between Italian and international physicians dedicated to clinical research and assistance on MIT for thyroid nodules. The group drafted this list of statements based on literature review and consensus opinion of interdisciplinary experts to facilitate the diffusion and the appropriate use of MIT of thyroid nodules in clinical practice. (#1) Predominantly cystic/cystic symptomatic nodules should first undergo US-guided aspiration; ethanol injection should be performed if relapsing (level of evidence [LoE]: ethanol is superior to simple aspiration = 2); (#2) In symptomatic cystic nodules, thermal ablation is an option when symptoms persist after ethanol ablation (LoE = 4); (#3) Double cytological benignity confirmation is needed before thermal ablation (LoE = 2); (#4) Single cytological sample is adequate in ultrasound low risk (EU-TIRADS ≤3) and in autonomously functioning nodules (LoE = 2); (#5) Thermal ablation may be proposed as first-line treatment for solid, symptomatic, nonfunctioning, benign nodules (LoE = 2); (#6) Thermal ablation may be used for dominant lesions in nonfunctioning multinodular goiter in patients refusing/not eligible for surgery (LoE = 5); (#7) Clinical and ultrasound follow-up is appropriate after thermal ablation (LoE = 2); (#8) Nodule re-treatment can be considered when symptoms relapse or partially resolve (LoE = 2); (#9) In case of nodule regrowth, a new cytological assessment is suggested before second ablation (LoE = 5); (#10) Thermal ablation is an option for autonomously functioning nodules in patients refusing/not eligible for radioiodine or surgery (LoE = 2); (#11) Small autonomously functioning nodules can be treated with thermal ablation when thyroid tissue sparing is a priority and ≥80% nodule volume ablation is expected (LoE = 3).

Ultrasound-guided laser ablation for local control of neck recurrences of medullary thyroid cancer. A feasibility study.

BACKGROUND: Surgery is the standard treatment for cervical metastases of medullary thyroid cancer (MTC) diagnosed after initial surgical treatment. Repeated neck dissections, however, carry an elevated risk of complications, have an adverse impact on the quality of life, and sometimes do not achieve cure of the disease Clinical case: In a patient who had undergone two cervical neck dissections complicated by accessory nerve injury, an US-guided laser ablation (LA) of a lymph node metastasis of MTC was performed. LA was performed with two treatments during a five month period. The procedure was carried out with one optical fiber and an energy delivery of 3300 and 360 Joules. Treatments were well tolerated and resulted in complete structural and biochemical cure during a 12 month follow-up. No major complication was registered. CONCLUSIONS: LA is a promising tool for the management of relapsing cervical metastases that are localized in non- critical areas and are characterized by low progression rate. Advantages of LA are the outpatient setting, the absence of general anesthesia, the tolerability and the safety of the procedure. Thus, LA may be considered as an alternative approach to surgery or active surveillance for the management of local recurrences of MTC in selected patients.

A comparison of laser with radiofrequency ablation for the treatment of benign thyroid nodules: a propensity score matching analysis.

PURPOSE: To compare technique efficacy and safety of laser ablation (LA) and radiofrequency ablation (RFA) in treatment of benign thyroid nodules. MATERIALS AND METHODS: Institutional review board approval was obtained, and patients' consent was waived. 601 nodules were treated from May 2009 to December 2014 at eight centres, 449 (309 females, age 57 ± 14 years) with LA and 152 (107 females, age 57 ± 14 years) with RFA. A matched cohort composed of 138 patients from each group was selected after adjustment with propensity score matching. Factors influencing volume reduction at 6 and 12 months and complications were evaluated. RESULTS: No significant differences were observed in the baseline characteristics between groups after propensity score matching adjustment. Mean nodule reduction at 6 and 12 months was -67 ± 19% vs. -57 ± 21% (p < 0.001) - 70 ± 19% vs. -62 ± 22% (p = 0.001) in LA group and in RFA group, respectively. Nodules with volume >30 mL had significantly higher percentage volume reduction at 6 and 12 months (-69 ± 19 vs. -50 ± 21, p = 0.001) and (-73 ± 18 vs. -54 ± 23 8, p = 0.001) in the LA group than in the RFA group, respectively. In both groups, operator's skills affected the results. Major complications occurred in 4 cases in each group (p = 0.116) Conclusions: LA and RFA showed nearly similar outcome but LA was slightly more effective than RFA in large nodules. Operator's skills could be crucial in determining the extent of nodule volume reduction regardless of the used technique.

ITALIAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS STATEMENT-REPLACEMENT THERAPY FOR PRIMARY HYPOTHYROIDISM: A BRIEF GUIDE FOR CLINICAL PRACTICE.

OBJECTIVE: Hypothyroidism requires life-long thyroid hormone replacement therapy in most patients. Oral levothyroxine (LT4) is an established safe and effective treatment for hypothyroidism, but some issues remain unsettled. METHODS: The Italian Association of Clinical Endocrinologists appointed a panel of experts to provide an updated statement for appropriate use of thyroid hormone formulations for hypothyroidism replacement therapy. The American Association of Clinical Endocrinologists' protocol for standardized production of clinical practice guidelines was followed. RESULTS: LT4 is the first choice in replacement therapy. Thyroid-stimulating hormone (TSH) should be maintained between 1.0 and 3.0 mIU/L in young subjects and at the upper normal limit in elderly or fragile patients. Achievement of biochemical targets, patient well-being, and adherence to treatment should be addressed. In patients with unstable serum TSH, a search for interfering factors and patient compliance is warranted. Liquid or gel formulations may be considered in subjects with hampered LT4 absorption or who do not allow sufficient time before or after meals and LT4 replacement. Replacement therapy with LT4 and L-triiodothyronine (LT3) combination is generally not recommended. A trial may be considered in patients with normal values of serum TSH who continue to complain of symptoms of hypothyroidism only after co-existent nonthyroid problems have been excluded or optimally managed. LT3 should be administered in small (LT4:LT3 ratio, 10:1 to 20:1) divided daily doses. Combined therapy should be avoided in elderly patients or those with cardiac risk factors and in pregnancy. CONCLUSION: LT4 therapy should be aimed at resolution of symptoms of hypothyroidism, normalization of serum TSH, and improvement of quality of life. In selected cases, the use of liquid LT4 formulations or combined LT4/LT3 treatment may be considered to improve adherence to treatment or patient well-being. ABBREVIATIONS: AACE = American Association of Clinical Endocrinologists FT3 = free triiodothyronine FT4 = free thyroxine LT3 = levotriiodothyronine LT4 = levothyroxine MeSH = medicine medical subject headings QoL = quality of life TSH = thyroid-stimulating hormone.

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).

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.

Hypothyroidism and Type D Personality: Results From E-MPATHY, a Cross-sectional International Online Patient Survey.

CONTEXT: Between 10% and 15% of people with hypothyroidism experience persistent symptoms, despite achieving biochemical euthyroidism. The underlying causes are unclear. Type D personality (a vulnerability factor for general psychological distress) is associated with poor health status and symptom burden but has not been studied in people with hypothyroidism. OBJECTIVE: To investigate type D personality in hypothyroidism and explore associations with other characteristics and patient-reported outcomes. DESIGN: Multinational, cross-sectional survey. SETTING: Online. PARTICIPANTS: Individuals with self-reported, treated hypothyroidism. INTERVENTION: Questionnaire. MAIN OUTCOME MEASURES: Type D personality and associations with baseline characteristics, control of the symptoms of hypothyroidism by medication, satisfaction with care and treatment of hypothyroidism, impact of hypothyroidism on everyday living. RESULTS: A total of 3915 responses were received, 3523 of which were valid. The prevalence of type D personality was 54.2%. Statistically significant associations were found between type D personality and several respondent characteristics (age, marital status, ethnicity, household income, comorbidities, type of treatment for hypothyroidism, most recent TSH level), anxiety, depression, somatization, poor control of the symptoms of hypothyroidism by medication, dissatisfaction with care and treatment of hypothyroidism, and a negative impact of hypothyroidism on everyday living). DISCUSSION: Our study found a high prevalence of type D personality among people with hypothyroidism who responded to the survey. Type D personality may be an important determinant of dissatisfaction with treatment and care among people with hypothyroidism. Our findings require independent confirmation. Close collaboration between the disciplines of thyroidology and psychology is likely to be key in progressing our understanding in this area.

Clinical Outcomes of Thermal Ablation Re-Treatment of Benign Thyroid Nodules: A Multicenter Study from the Italian Minimally Invasive Treatments of the Thyroid Group.

Background: Thermal ablation (TA) is an established therapeutic option alternative to surgery in patients with solid benign thyroid nodules causing local symptoms. However, a variable part of thyroid nodules remain viable after these nonsurgical treatments, and as many as 15% of nodules treated with TA may require a second treatment over time. This study aimed to evaluate the outcomes of TA re-treatment on symptomatic benign thyroid nodules where the volume decreased by <50% after the first procedure ( = technique inefficacy). Methods: We performed a multicenter retrospective cohort study including patients who underwent re-treatment with TA for benign thyroid nodules, whose volume decreased by <50% after initial treatment. The primary aim was to evaluate volume and volume reduction ratio (VRR) over time and compare the 6- and 12-month VRR after first versus second treatment. The secondary aim was to identify protective or risk factors for technique inefficacy, regrowth, and further treatments, expressed as adjusted hazard ratios (HRs) and confidence interval [CI], after adjustment for sex, age, nodule volume, structure and function, nodule regrowth or symptom relapse, technique used and if the same technique was used for the first and second TA and time between them. Results: We included 135 patients. Re-treatment led to VRR of 50% and 52.2% after 6 and 12 months. VRR after re-treatment was greater than after first treatment in small and medium size nodules (<30 mL), while there were no differences for large nodules (>30 mL). After re-treatment technique inefficacy rate was 51.9%, regrowth rate was 12.6%, and further treatment rate was 15.6%. Radiofrequency ablation (RFA) was protective toward technique inefficacy (HR = 0.40 [CI 0.24-0.65]) and need of further treatments (HR = 0.30 [CI 0.12-0.76]). Large nodule volume (>30 mL) was associated with increased risk of re-treatment (HR = 4.52 [CI 1.38-14.82]). Conclusions: This is the first study evaluating the outcomes of re-treatment on symptomatic benign thyroid nodules with a VRR <50% after the initial TA treatment. Best results were seen in small and medium nodules (<30 mL) and after RFA. Prospective confirmatory studies are needed.

A pharmacoeconomic analysis from Italian guidelines for the management of prolactinomas.

Background: Prolactinoma, the most common pituitary adenoma, is usually treated with dopamine agonist (DA) therapy like cabergoline. Surgery is second-line therapy, and radiotherapy is used if surgical treatment fails or in relapsing macroprolactinoma. Objective: This study aimed to provide economic evidence for the management of prolactinoma in Italy, using a cost-of-illness and cost-utility analysis that considered various treatment options, including cabergoline, bromocriptine, temozolomide, radiation therapy, and surgical strategies. Methods: The researchers conducted a systematic literature review for each research question on scientific databases and surveyed a panel of experts for each therapeutic procedure's specific drivers that contributed to its total cost. Results: The average cost of the first year of treatment was €2,558.91 and €3,287.40 for subjects with microprolactinoma and macroprolactinoma, respectively. Follow-up costs from the second to the fifth year after initial treatment were €798.13 and €1,084.59 per year in both groups. Cabergoline had an adequate cost-utility profile, with an incremental cost-effectiveness ratio (ICER) of €3,201.15 compared to bromocriptine, based on a willingness-to-pay of €40,000 per quality-adjusted life year (QALY) in the reference economy. Endoscopic surgery was more cost-effective than cabergoline, with an ICER of €44,846.64. Considering a willingness-to-pay of €40,000/QALY, the baseline findings show cabergoline to have high cost utility and endoscopic surgery just a tad above that. Conclusions: Due to the favorable cost-utility profile and safety of surgical treatment, pituitary surgery should be considered more frequently as the initial therapeutic approach. This management choice could lead to better outcomes and an appropriate allocation of healthcare resources.