Computer-interpretable guidelines: electronic tools to enhance the utility of thyroid nodule clinical practice guidelines and risk stratification tools.

Clinicians seeking guidance for evaluating and managing thyroid nodules currently have several resources. The principal ones are narrative clinical guidelines and clinical risk calculators. This paper will review the strengths and weaknesses of both. The paper will introduce a concept of computer interpretable guideline, a novel way of transforming narrative guidelines in to a clinical decision support tool that can provide patient specific recommendations at the point of care. The paper then describes an experience of developing an interactive web based computer interpretable guideline for thyroid nodule management, called Thyroid Nodule Management App (TNAPP). The advantages of this approach and the potential barriers for widespread adaptation are discussed.

The TNAPP web-based algorithm improves thyroid nodule management in clinical practice: A retrospective validation study.

Background: The detection of thyroid nodules has been increasing over time, resulting in an extensive use of fine-needle aspiration (FNA) and cytology. Tailored methods are required to improve the management of thyroid nodules, including algorithms and web-based tools. Study aims: To assess the performance of the Thyroid Nodule App (TNAPP), a web-based, readily modifiable, interactive algorithmic tool, in improving the management of thyroid nodules. Methods: One hundred twelve consecutive patients with 188 thyroid nodules who underwent FNA from January to December 2016 and thyroid surgery were retrospectively evaluated. Neck ultrasound images were collected from a thyroid nodule registry and re-examined to extract data to run TNAPP. Each nodule was evaluated for ultrasonographic risk and suitability for FNA. The sensitivity, specificity, positive and negative predictive values, and overall accuracy of TNAPP were calculated and compared to the diagnostic performance of the other two algorithms by the American Association of Clinical Endocrinology/American College of Endocrinology/Associazione Medici Endocrinologi (AACE/ACE/AME), which it was derived from the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS). Results: TNAPP performed better in terms of sensitivity (>80%) and negative predictive value (68%) with an overall accuracy of 50.5%, which was similar to that found with the AACE/ACE/AME algorithm. TNAPP displayed a slightly better performance than AACE/ACE/AME and ACR TI-RADS algorithms in selectively discriminating unnecessary FNA for nodules with benign cytology (TIR 2 - Bethesda class II: TNAPP 32% vs. AACE/ACE/AME 31% vs. ACR TI-RADS 29%). The TNAPP reduced the number of missed diagnoses of thyroid nodules with suspicious and highly suspicious cytology (TIR 4 + TIR 5 - Bethesda classes V + VI: TNAPP 18% vs. AACE/ACE/AME 26% vs. ACR TI-RADS 20.5%). A total of 14 nodules that would not have been aspirated were malignant, 13 of which were microcarcinomas (92.8%). Discussion: The TNAPP algorithm is a reliable, easy-to-learn tool that can be readily employed to improve the selection of thyroid nodules requiring cytological characterization. The rate of malignant nodules missed because of inaccurate characterization at baseline by TNAPP was lower compared to the other two algorithms and, in almost all the cases, the tumors were microcarcinomas. TNAPP's use of size >20 mm as an independent determinant for considering or recommending FNA reduced its specificity. Conclusion: TNAPP performs well compared to AACE/ACE/AME and ACR-TIRADS algorithms. Additional retrospective and, ultimately, prospective studies are needed to confirm and guide the development of future iterations that incorporate different risk stratification systems and targets for diagnosing malignancy while reducing unnecessary FNA procedures.

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.

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.

In-Practice Endocrine Surgery Fellowship: A Novel Training Model.

OBJECTIVE: Endocrine surgery is an expanding field within otolaryngology. We hypothesized that a novel endocrine surgery fellowship model for in-practice otolaryngologists could result in expert-level training. STUDY DESIGN: Qualitative clinical study with chart review. SETTING: Urban community practice and academic medical center. METHODS: Two board-certified general otolaryngologists collaborated with a senior endocrine surgeon to increase their endocrine surgery expertise between March 2015 and December 2017. The senior surgeon provided intensive surgical training to both surgeons for all of their endocrine surgeries. Both parties collaborated with endocrinology to coordinate medical care and receive referrals. All patients undergoing endocrine surgery during this time frame were reviewed retrospectively. RESULTS: A total of 235 endocrine surgeries were performed. Of these, 198 thyroid surgeries were performed, including 98 total thyroidectomies (48%), 90 lobectomies (45%), and 10 completion thyroidectomies (5%). Sixty cases demonstrated papillary thyroid carcinoma, 11 follicular thyroid carcinoma, and 4 medullary thyroid carcinoma. Neck dissections were performed in 14 of the cases. Thirty-seven parathyroid explorations were performed. There were no reports of permanent hypoparathyroidism. Thirteen patients (5.5%) developed temporary hypoparathyroidism. Six patients (2.5%) developed postoperative seroma. Three patients (1.3%) developed postoperative hematomas requiring reoperation. One patient (0.4%) developed permanent vocal fold paralysis, and 3 patients (1.3%) had temporary dysphonia. Thirty-five of 37 (94.5%) parathyroid explorations resulted in biochemical resolution of the patient's primary hyperparathyroidism. CONCLUSION: This is the first description of a new fellowship paradigm where a senior surgeon provides fellowship training to attending surgeons already in practice.

The impact of an adrenal incidentaloma algorithm on the evaluation of adrenal nodules.

OBJECTIVE: To determine the impact of the use of an electronic medical record tool on the evaluation of adrenal incidentalomas. METHODS: Retrospective chart review was used to compare rates of hormone testing and follow up imaging for adrenal incidentalomas. Patients whose radiology reports contained an algorithm with recommendations, based on our 2013 clinical guideline for the workup of these nodules, were compared to those whose imaging reports did not contain the algorithm. RESULTS: For patients whose Radiology reports contained the algorithm, 69% had hormonal testing versus 43% of controls (p < 0.0001). By contrast, 57% of study group patients had a follow up imaging study, compared to 51% of controls (p = 0.1000). However, when the 18% of controls that were given guidance by the radiologist to perform follow-up imaging were excluded from those who received no guidance, there was a statistically significant difference in the rate of follow up imaging (57% vs 48%, p < 0.0001). CONCLUSION: Implementation of a clinical algorithm for the evaluation of adrenal incidentalomas in radiology reports and on the intranet site of a major clinical center led to improved rates of hormone testing. There was also a significant increase in the rate of follow up imaging, compared to when no guidance was given. Additional efforts to further improve performance are needed to increase the detection of clinically significant lesions, particularly hormone secreting tumors that should be removed.

Palladium-catalysed electrophilic aromatic C-H fluorination.

Aryl fluorides are widely used in the pharmaceutical and agrochemical industries, and recent advances have enabled their synthesis through the conversion of various functional groups. However, there is a lack of general methods for direct aromatic carbon-hydrogen (C-H) fluorination. Conventional methods require the use of either strong fluorinating reagents, which are often unselective and difficult to handle, such as elemental fluorine, or less reactive reagents that attack only the most activated arenes, which reduces the substrate scope. A method for the direct fluorination of aromatic C-H bonds could facilitate access to fluorinated derivatives of functional molecules that would otherwise be difficult to produce. For example, drug candidates with improved properties, such as increased metabolic stability or better blood-brain-barrier penetration, may become available. Here we describe an approach to catalysis and the resulting development of an undirected, palladium-catalysed method for aromatic C-H fluorination using mild electrophilic fluorinating reagents. The reaction involves a mode of catalysis that is unusual in aromatic C-H functionalization because no organometallic intermediate is formed; instead, a reactive transition-metal-fluoride electrophile is generated catalytically for the fluorination of arenes that do not otherwise react with mild fluorinating reagents. The scope and functional-group tolerance of this reaction could provide access to functional fluorinated molecules in pharmaceutical and agrochemical development that would otherwise not be readily accessible.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY DISEASE STATE COMMENTARY: MANAGING THYROID TUMORS DIAGNOSED AS NONINVASIVE FOLLICULAR THYROID NEOPLASM WITH PAPILLARY-LIKE NUCLEAR FEATURES.

This commentary summarizes the history and reclassification of noninvasive follicular thyroid neoplasm with papillary-like nuclei (NIFTP). It reviews the salient histopathologic features that are based on immunohistochemical and molecular profiles and serve as inclusion and exclusion criteria. The authors also provide their own point of view regarding the practical issues and possible concerns that may be raised by both clinicians and patients based on the diagnosis of NIFTP. ABBREVIATIONS: AACE = American Association of Clinical Endocrinologists EFVPTC = encapsulated FVPTC FNA = fine-needle aspiration FVPTC = follicular variant of papillary thyroid carcinoma NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features PTC = papillary thyroid carcinoma.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY PROTOCOL FOR STANDARDIZED PRODUCTION OF CLINICAL PRACTICE GUIDELINES, ALGORITHMS, AND CHECKLISTS - 2017 UPDATE.

Clinical practice guideline (CPG), clinical practice algorithm (CPA), and clinical checklist (CC, collectively CPGAC) development is a high priority of the American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE). This 2017 update in CPG development consists of (1) a paradigm change wherein first, environmental scans identify important clinical issues and needs, second, CPA construction focuses on these clinical issues and needs, and third, CPG provide CPA node/edge-specific scientific substantiation and appended CC; (2) inclusion of new technical semantic and numerical descriptors for evidence types, subjective factors, and qualifiers; and (3) incorporation of patient-centered care components such as economics and transcultural adaptations, as well as implementation, validation, and evaluation strategies. This third point highlights the dominating factors of personal finances, governmental influences, and third-party payer dictates on CPGAC implementation, which ultimately impact CPGAC development. The AACE/ACE guidelines for the CPGAC program is a successful and ongoing iterative exercise to optimize endocrine care in a changing and challenging healthcare environment. ABBREVIATIONS: AACE = American Association of Clinical Endocrinologists ACC = American College of Cardiology ACE = American College of Endocrinology ASeRT = ACE Scientific Referencing Team BEL = best evidence level CC = clinical checklist CPA = clinical practice algorithm CPG = clinical practice guideline CPGAC = clinical practice guideline, algorithm, and checklist EBM = evidence-based medicine EHR = electronic health record EL = evidence level G4GAC = Guidelines for Guidelines, Algorithms, and Checklists GAC = guidelines, algorithms, and checklists HCP = healthcare professional(s) POEMS = patient-oriented evidence that matters PRCT = prospective randomized controlled trial.

MANAGING THYROID TUMORS DIAGNOSED AS NON-INVASIVE FOLLICULAR TUMOR WITH PAPILLARY LIKE NUCLEAR FEATURES (NIFTP).

This commentary summarizes the history and reclassification of noninvasive follicular thyroid tumor with papillary like nuclei (NIFTP). The salient histopathologic features, which are based on immunohistochemical and molecular profiles and serve as inclusion and exclusion criteria are reviewed. The authors also provide their own point of view regarding the practical issues and possible concerns that may be raised by both clinicians and patients based on the diagnosis of NIFTP.

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).

TRANSCULTURALIZATION RECOMMENDATIONS FOR DEVELOPING LATIN AMERICAN CLINICAL PRACTICE ALGORITHMS IN ENDOCRINOLOGY--PROCEEDINGS OF THE 2015 PAN-AMERICAN WORKSHOP BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY.

The American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) convened their first Workshop for recommendations to optimize Clinical Practice Algorithm (CPA) development for Latin America (LA) in diabetes (focusing on glycemic control), obesity (focusing on weight loss), thyroid (focusing on thyroid nodule diagnostics), and bone (focusing on postmenopausal osteoporosis) on February 28, 2015, in San Jose, Costa Rica. A standardized methodology is presented incorporating various transculturalization factors: resource availability (including imaging equipment and approved pharmaceuticals), health care professional and patient preferences, lifestyle variables, socio-economic parameters, web-based global accessibility, electronic implementation, and need for validation protocols. A standardized CPA template with node-specific recommendations to assist the local transculturalization process is provided. Participants unanimously agreed on the following five overarching principles for LA: (1) there is only one level of optimal endocrine care, (2) hemoglobin A1C should be utilized at every level of diabetes care, (3) nutrition education and increased pharmaceutical options are necessary to optimize the obesity care model, (4) quality neck ultrasound must be part of an optimal thyroid nodule care model, and (5) more scientific evidence is needed on osteoporosis prevalence and cost to justify intervention by governmental health care authorities. This 2015 AACE/ACE Workshop marks the beginning of a structured activity that assists local experts in creating culturally sensitive, evidence-based, and easy-to-implement tools for optimizing endocrine care on a global scale.