American Association of Clinical Endocrinology Disease State Clinical Review: The Clinical Utility of Minimally Invasive Interventional Procedures in the Management of Benign and Malignant Thyroid Lesions

ObjectiveThe objective of this disease state clinical review is to provide clinicians with a summary of the nonsurgical, minimally invasive approaches to managing thyroid nodules/malignancy, including their indications, efficacy, side effects, and outcomes.MethodsA literature search was conducted using PubMed and appropriate key words. Relevant publications on minimally invasive thyroid techniques were used to create this clinical review.ResultsMinimally invasive thyroid techniques are effective and safe when performed by experienced centers. To date, percutaneous ethanol injection therapy is recommended for recurrent benign thyroid cysts. Both ultrasound-guided laser and radiofrequency ablation can be safely used for symptomatic solid nodules, both toxic and nontoxic. Microwave ablation and high-intensity focused ultrasound are newer approaches that need further clinical evaluation. Despite limited data, encouraging results suggest that minimally invasive techniques can also be used in small-size primary and locally recurrent thyroid cancer.ConclusionSurgery and radioiodine treatment remain the conventional and established treatments for nodular goiters. However, the new image-guided minimally invasive approaches appear safe and effective alternatives when used appropriately and by trained professionals to treat symptomatic or enlarging thyroid masses.     

Consensus Statement by the American Association of Clinical Endocrinology (AACE) and the American Head and Neck Society Endocrine Surgery Section (AHNS) on Pediatric Benign and Malignant Thyroid Surgery

ObjectivesTo provide a clinical disease state review of recent relevant literature and to generate expert consensus statements regarding the breadth of pediatric thyroid cancer diagnosis and care, with an emphasis on thyroid surgery. To generate expert statements to educate pediatric practitioners on the state-of-the-art practices and the value of surgical experience in the management of this unusual and challenging disease in children.MethodsA literature search was conducted and statements were constructed and subjected to a modified Delphi process to measure the consensus of the expert author panel. The wording of statements, voting tabulation, and statistical analysis were overseen by a Delphi expert (J.J.S.).ResultsTwenty-five consensus statements were created and subjected to a modified Delphi analysis to measure the strength of consensus of the expert author panel. All statements reached a level of consensus, and the majority of statements reached the highest level of consensus.ConclusionPediatric thyroid cancer has many unique nuances, such as bulky cervical adenopathy on presentation, an increased incidence of diffuse sclerosing variant, and a longer potential lifespan to endure potential complications from treatment. Complications can be a burden to parents and patients alike. We suggest that optimal outcomes and decreased morbidity will come from the use of advanced imaging, diagnostic testing, and neural monitoring of patients treated at high-volume centers by high-volume surgeons.     

Thyroid Nodule Evaluation and Management in Older Adults: A Review of Practical Considerations for Clinical Endocrinologists

ObjectiveContextualizing the evaluation of older adults with thyroid nodules is necessary to fully understand which management strategy is the most appropriate. Our goal was to summarize available clinical evidence to provide guidance in the care of older adults with thyroid nodules and highlight special considerations for thyroid nodule evaluation and management in this population.MethodsWe conducted a literature search of PubMed and Ovid MEDLINE from January 2000 to November 2020 to identify relevant peer-reviewed articles published in English. References from the included articles as well as articles identified by the authors were also reviewed.ResultsThe prevalence of thyroid nodules increases with age. Although thyroid nodules in older adults have a lower risk of malignancy, identified cancers are more likely to be of high-risk histology. The goals of thyroid nodule evaluation and the tools used for diagnosis are similar for older and younger patients with thyroid nodules. However, limited evidence exists regarding thyroid nodule evaluation and management to guide personalized decision making in the geriatric population.ConclusionConsidering patient context is significant in the diagnosis and management of thyroid nodules in older adults. When making management decisions in this population, it is essential to carefully weigh the risks and benefits of thyroid nodule diagnosis and treatment, in view of older adults’ higher prevalence of high-risk thyroid cancer as well as increased risk for multimorbidity, functional and cognitive decline, and treatment complications.     

Comparison of the Efficacy and Safety of the American Thyroid Association Guidelines and American College of Radiology TI-RADS

ObjectiveTo evaluate the 2015 American Thyroid Association (ATA) guidelines and 2017 American College of Radiology (ACR) Thyroid Imaging, Reporting and Data System (TI-RADS) for their efficacy in predicting malignant thyroid nodules and safety in recommending fine needle aspiration (FNA).MethodsWe reviewed data of 970 thyroid nodules from 908 patients with core needle biopsy pathology. We calculated the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for each guideline to predict malignancies. We compared the areas under the curve and FNA recommendations between the 2 guidelines.ResultsAccording to the core needle biopsy pathology, 59.9% (581/970) of the thyroid nodules were malignant. Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value was 68%, 91%, 33%, 67%, and 70%, respectively, for the ATA guidelines and 70%, 84%, 49%, 71%, and 68%, respectively, for the ACR TI-RADS. Areas under the curve (ATA: 0.71 vs ACR TI-RADS: 0.74; P = .054) were similar when predicting malignancies. For the 545 nodules with maximum diameter ≥1.0 cm, the ACR TI-RADS recommended FNA less often than the ATA guidelines (83.3% [454/545] vs 87.7% [478/545]; P = .01). For the 321 malignant nodules with maximum diameter ≥1.0 cm, the proportions of FNA recommendations were not significantly different (ACR TI-RADS: 90.7% [291/321] vs ATA: 92.5% [297/321]; P = .06).ConclusionThe 2015 ATA guidelines and 2017 ACR TI-RADS showed a similar ability in predicting malignancies. Reducing FNA recommendations by the ACR TI-RADS would not lead to a significant decrease in the FNA recommendations given for malignancies with maximum diameter ≥1.0 cm.     

American Association of Clinical Endocrinology Disease State Clinical Review: Evaluation and Management of Immune Checkpoint Inhibitor-Mediated Endocrinopathies: A Practical Case-Based Clinical Approach

ObjectiveThe aim of this case-based clinical review was to provide a practical approach for clinicians regarding the management of patients with immune checkpoint inhibitor (ICI)-mediated endocrinopathies.MethodsA literature search of PubMed, Embase, and Scopus was conducted using appropriate keywords. The discussions and strategies for the diagnosis and management of ICI-mediated endocrinopathies are based on evidence available from prospective, randomized clinical studies; cohort studies; cross-sectional studies; case-based studies; and an expert consensus.ResultsImmunotherapy with ICIs has transformed the treatment landscape of diverse types of cancers but frequently results in immune-mediated endocrinopathies that can cause acute and persistent morbidity and, rarely, death. The patterns of endocrinopathies differ between the inhibitors of the cytotoxic T-lymphocyte antigen 4 and programmed cell death protein 1 or programmed cell death protein 1 ligand pathways but most often involve the thyroid and pituitary glands. The less common but important presentations include insulin-deficient diabetes mellitus, primary adrenal insufficiency, primary hypoparathyroidism, central diabetes insipidus, primary hypogonadism, and pancreatitis, with or without subsequent progression to diabetes mellitus or exocrine insufficiency.ConclusionIn recent years, with increasing numbers of patients with cancer being treated with ICIs, more clinicians in a variety of specialties have been called upon to diagnose and treat ICI-mediated endocrinopathies. Herein, we reviewed case scenarios of various clinical manifestations and emphasized the need for a high index of clinical suspicion by all clinicians caring for these patients, including endocrinologists, oncologists, primary care providers, and emergency department physicians. We also provided diagnostic and therapeutic approaches for ICI-induced endocrinopathies and proposed that patients on ICI therapy be evaluated and treated by a multidisciplinary team in collaboration with endocrinologists.     

Impact of Electronic Consultation on Timeliness and Guideline Concordance of Workups Leading to Thyroid Nodule Fine-Needle Aspiration Biopsy

ObjectiveElectronic consultations (e-consults) are commonly used to obtain endocrinology input on clinical questions without a face-to-face visit, but sparse data exist on the resultant quality of care for specific conditions. We examined workups resulting in a thyroid nodule fine-needle aspiration (FNA) biopsy to investigate whether endocrinology e-consults were more timely and similarly guideline-concordant compared with endocrinology face-to-face visits and whether endocrinology e-consults were more guideline-concordant compared with workups without endocrinology input.MethodsWe retrospectively reviewed charts of 302 thyroid FNA biopsies conducted in the Veterans Affairs health system between May 1, 2017, and February 4, 2020 (e-consult, n = 99; face-to-face visit, n = 100; no endocrinology input, n = 103). We used t tests to compare timeliness, χ² tests to compare the proportion of guideline-concordant workups, and multivariable linear and logistic models to control for demographic factors.ResultsFNAs preceded by an endocrinology e-consult had more timely workups compared with those preceded by endocrinology face-to-face visits in terms of days elapsed between referral and FNA biopsy (geometric mean 44.7 days vs 61.7 days, P = .01). The difference in the summary measure of guideline concordance across groups was not statistically significant (P =.38).ConclusionE-consults were faster than face-to-face consults and similarly guideline-concordant compared with both face-to-face consults and no endocrinology input for workups resulting in FNA. Decisions about the appropriate use of e-consults for thyroid nodules should take into account these data while also considering the potential benefits of direct patient-endocrinologist interaction for complex situations.     

American Association of Clinical Endocrinology Consensus Statement: Addressing Stigma and Bias in the Diagnosis and Management of Patients with Obesity/Adiposity-Based Chronic Disease and Assessing Bias and Stigmatization as Determinants of Disease Severity

ObjectiveTo focus on the intersection of perception, diagnosis, stigma, and weight bias in the management of obesity and obtain consensus on actionable steps to improve care provided for persons with obesity.MethodsThe American Association of Clinical Endocrinology (AACE) convened a consensus conference of interdisciplinary health care professionals to discuss the interplay between the diagnosis of obesity using adiposity-based chronic disease (ABCD) nomenclature and staging, weight stigma, and internalized weight bias (IWB) with development of actionable guidance to aid clinicians in mitigating IWB and stigma in that context.ResultsThe following affirmed and emergent concepts were proposed: (1) obesity is ABCD, and these terms can be used in differing ways to communicate; (2) classification categories of obesity should have improved nomenclature across the spectrum of body mass index (BMI) using ethnic-specific BMI ranges and waist circumference (WC); (3) staging the clinical severity of obesity based on the presence and severity of ABCD complications may reduce weight-centric contribution to weight stigma and IWB; (4) weight stigma and internalized bias are both drivers and complications of ABCD and can impair quality of life, predispose to psychological disorders, and compromise the effectiveness of therapeutic interventions; (5) the presence and of stigmatization and IWB should be assessed in all patients and be incorporated into the staging of ABCD severity; and (6) optimal care will necessitate increased awareness and the development of educational and interventional tools for health care professionals that address IWB and stigma.ConclusionsThe consensus panel has proposed an approach for integrating bias and stigmatization, psychological health, and social determinants of health in a staging system for ABCD severity as an aid to patient management. To effectively address stigma and IWB within a chronic care model for patients with obesity, there is a need for health care systems that are prepared to provide evidence-based, person-centered treatments; patients who understand that obesity is a chronic disease and are empowered to seek care and participate in behavioral therapy; and societies that promote policies and infrastructure for bias-free compassionate care, access to evidence-based interventions, and disease prevention.     

Can Age at Diagnosis and Sex Improve the Performance of the American Thyroid Association Risk Stratification System for Prediction of Structural Persistent and Recurrent Disease in Patients With Differentiated Thyroid Carcinoma? A Multicenter Study

ObjectiveAlthough the age at diagnosis has been suggested as a major determinant of disease-specific survival in the recent TNM staging system, it is not included in the recent American Thyroid Association (ATA) guidelines to estimate the risk of recurrence. Nevertheless, the effect of sex on differentiated thyroid carcinoma (DTC) recurrence is controversial. Therefore, this multicenter study was conducted to assess whether age at diagnosis and sex can improve the performance of the ATA 3-tiered risk stratification system in patients with DTC with at least 5 years of follow-up.MethodsIn this study, the computer-recorded data of the patients diagnosed with DTC between January 1985 and January 2016 were analyzed. Only patients with proven structural persistent/recurrent disease were selected for comparisons.ResultsThis study consisted of 1691 patients (female, 1367) with DTC. In Kaplan-Meier analysis, disease-free survival (DFS) was markedly longer in females only in the ATA low-risk category (P = .045). Nevertheless, a markedly longer DFS was observed in patients aged <45 years in the ATA low- and intermediate-risk categories (P = .004 and P = .009, respectively), whereas in patients aged <55 years, DFS was markedly longer only in the ATA low-risk category (P < .001). In the Cox proportional hazards model, ages of ≥45 and ≥55 years at diagnosis and the ATA risk stratification system were all independent predictors of persistent/recurrent disease.ConclusionApplying the age cutoff of 45 years in the ATA intermediate- and low-risk categories may identify patients at a higher risk of persistence/recurrence and may improve the performance of the ATA risk stratification system, whereas sex may improve the performance of only the ATA low-risk category.     

Transverse and Longitudinal Ultrasound Location of Thyroid Nodules and Risk of Thyroid Cancer

BackgroundThe high prevalence of thyroid nodules demands accurate assessment tools to avoid unnecessary biopsies. Prior studies demonstrated a correlation between the longitudinal location of thyroid nodules and the likelihood of malignancy. No study has evaluated the predictive value of transverse location on ultrasonography with malignancy.MethodsWe retrospectively reviewed the records of thyroid nodules that underwent fine-needle aspiration over 13 years, including demographics, risk factors, nodule sonographic features, location, and surgical pathology. Univariate and multivariable logistic regression models were used to evaluate the risk of malignancy.ResultsOf the 668 thyroid nodules, 604 were analyzed with a definitive diagnosis. Thirty-seven nodules were malignant, representing a prevalence of 6.1%. In the longitudinal plane, the upper pole nodules carried the highest incidence of malignancy (14.9%). In the transverse plane, the highest incidence of malignancy occurred in nodules located laterally (12.5%) and anterior-laterally (11.8%). Compared with the upper pole, the odds of malignancy were significantly lower for lower pole (odds ratio [OR] = 0.26, 95% confidence interval [CI]: 0.09-0.70) and midlobe nodules (OR = 0.31, 95% CI: 0.12-0.83). In the transverse plane, posteriorly situated nodules carried a significantly lower risk of malignancy (OR = 0.07, 95% CI: 0.01-0.69). Multiple logistic regression confirmed these associations after adjusting for age, sex, family history, radiation exposure, nodule size, and sonographic characteristics.ConclusionBoth the transverse and longitudinal planes were independent predictors of cancer in thyroid nodules. Lateral, anterior-lateral, and upper pole nodules carried the highest risk and posterior nodules had the lowest risk of malignancy.     

Association of Thyroid Function During Pregnancy With the Risk of Pre-eclampsia and Gestational Diabetes Mellitus

ObjectiveTo estimate the association of maternal thyroid dysfunction with the risk of gestational hypertension and diabetes. Whether the association was affected by gestational age at diagnosis and thyroid autoimmunity was further explored.MethodsA cohort study of 41 647 participants was conducted. Thyroid function (ie, thyroid-stimulating hormone [TSH] and free thyroxine [FT4]) was measured by electrochemiluminescence immunoassay. Thyroid antibody positivity (eg, thyroperoxidase, thyroglobulin, and TSH receptor antibody) was indicated if the values of these antibodies exceeded the upper targets of the reference range. The relationship between maternal thyroid dysfunction and the risk of pre-eclampsia (PE) and gestational diabetes mellitus (GDM) was assessed by multivariate logistic regression.ResultsIsolated hypothyroxinemia (defined as 5th ≤ TSH ≤ 95th percentile, FT4 < 5th percentile) was associated with the risk of PE (odds ratio [OR], 1.32; 95% CI, 1.10-1.58). Overt hypothyroidism (TSH > 95th percentile; FT4 < 5th percentile) was related to the risk of severe PE (OR, 2.59; 95% CI, 1.05-6.37). Being positive for TSH receptor antibody was associated with a decreased risk of GDM (OR, 0.49; 95% CI, 0.35-0.70). A marginally significant association between overt hypothyroidism detected at the first trimester and the risk of GDM was found (OR, 1.60; 95% CI, 1.00-2.83). The association of thyroid dysfunction with the risk of PE and GDM was stronger among pregnant women who were negative for autoantibodies.ConclusionSome types of thyroid dysfunction during pregnancy were associated with the risk of PE and GDM. The associations varied by gestational age at diagnosis and by thyroid autoantibody status.     

A Retrospective Study of Clinicopathologic Outcomes of Nodules With Hürthle Cell Cytology and the Thyroid Nodule App (TNAPP) Ultrasound Recommendations

ObjectivesHürthle cells are a common finding on thyroid fine-needle aspiration, but when they are the predominant cytology, they represent a difficult diagnostic challenge. The Thyroid Nodule App (TNAPP) is a new, publicly available web application utilizing ultrasound (US) features based on the updated 2016 American Association of Clinical Endocrinologists clinical practice guidelines for thyroid nodule management. This pilot study was performed to assess the TNAPP recommendations and surgical pathology outcomes of Hürthle cell-predominant thyroid nodules.MethodsA retrospective review of nodules with Bethesda III (atypia of undetermined significance with Hürthle cells) or Bethesda IV (suspicious for Hürthle cell neoplasm) cytology, for which surgery was performed between 2017 and 2021, was conducted. TNAPP US categories 1, 2, and 3 (low, intermediate, and high risk, respectively) were assigned based on nodule characteristics, and clinical management recommendations were recorded. Results were compared with histology-proven diagnoses.ResultsFifty-nine nodules in 57 patients where surgical pathology was available were analyzed with the TNAPP algorithm. Of the 59 nodules, 4 were US category 1 (low risk/suspicion), 40 were US category 2 (intermediate risk/suspicion), and 15 were US category 3 (high risk/suspicion). All US category 1 nodules were benign, while 30% of the US category 2 and 40% of the US category 3 nodules were malignant. Of the patients who had molecular marker testing with ThyroSeq, 22 out of 29 (76%) were positive, indicating either an intermediate or high risk of malignancy, 7 of which were malignant.ConclusionThis preliminary study suggests that TNAPP is a useful clinical tool for sonographic assessment of thyroid nodules with Hürthle cell cytology.     

Agreement Between American and European Thyroid Imaging,Reporting, and Data System (TIRADS) in the Diagnosis of 473 Thyroid Nodules From a Single Center in Brazil

ObjectiveTo compare 2 ultrasound-based risk stratification systems in malignancy risk assessment of thyroid nodules and the clinical applicability of these guidelines in Brazil.MethodsWe retrospectively reviewed the ultrasound findings of 314 patients (473 thyroid nodules) who underwent fine-needle aspiration (FNA) biopsy and/or surgery between February 2018 and March 2019. All nodules were classified using 2 systems: the Thyroid Imaging, Reporting, and Data System (TIRADS) of the American College of Radiology (ACR-TIRADS) and the TIRADS of the European Thyroid Association (EU-TIRADS). Both risk stratification systems were analyzed. We identified the diagnostic predictive values that yielded optimal sensitivity, specificity, positive predictive value, negative predictive value, and accuracy.ResultsOf the 473 nodules, all underwent FNA, and histopathology was performed for 332 nodules. The agreement between the ACR-TIRADS and EU-TIRADS results and that between cytology and histopathology findings was 92.6% (kappa = 0.84) and 86.7% (kappa = 0.73), respectively. The area under the curve for the ACR-TIRADS and EU-TIRADS was 0.871 and 0.828, respectively (P < .001). The EU-TIRADS had the best sensitivity and negative predictive value, whereas the ACR-TIRADS had the best specificity, positive predictive value, and accuracy. Of the 473 nodules studied, only 158 (33.4%) followed the FNA size criteria suggested by the ACR-TIRADS.ConclusionACR-TIRADS and EU-TIRADS had good diagnostic performances. However, most aspirated nodules did not follow the TIRADS indication; thus, the overuse of FNA as a diagnostic tool was observed.     

Frequency of Thyroid Hormone Replacement After Lobectomy for Differentiated Thyroid Cancer

ObjectiveTo determine the frequency of levothyroxine (LT4) supplementation after therapeutic lobectomy for low-risk differentiated thyroid cancer (DTC).MethodsThis retrospective cohort study enrolled adult patients with low-risk DTC confirmed using surgical pathology who underwent therapeutic lobectomy at a single institution from January 2016 through May 2020. The outcome measures were postoperative serum thyroid-stimulating hormone (TSH) levels and the initiation of LT4. The predictors of a postoperative TSH level of >2 mU/L and initiation of LT4 were evaluated using Cox proportional hazards models.ResultsPostoperative TSH levels were available for 115 patients (91%), of whom 97 (84%) had TSH levels >2 mU/L after thyroid lobectomy. Over a median follow-up of 2.6 years, a postoperative TSH level of >2 mU/L was associated with older age (median 52 vs 37 years; P = .01), higher preoperative TSH level (1.7 vs 0.85 mU/L; P < .001), and primary tumor size of <1 cm (38% vs 11%, P = .03). Multivariate analysis revealed that only preoperative TSH level was an independent predictor of a postoperative TSH level of >2 mU/L (hazard ratio [HR] 1.53, P = .003). Among patients with a postoperative TSH level of >2 mU/L, 66 (68%) were started on LT4 at a median of 74 days (interquartile range 41-126) after lobectomy, with 51 (77%) undergoing at least 1 subsequent dose adjustment to maintain compliance with current guidelines.ConclusionMore than 80% of the patients who underwent therapeutic lobectomy for DTC developed TSH levels that were elevated beyond the recommended range, and most of these patients were prescribed LT4 soon after the surgery.     

Nomogram to Assess the Risk of Central Cervical Lymph Node Metastasis in Patients With Clinical N0 Papillary Thyroid Carcinoma

ObjectiveTo develop and validate an individualized risk prediction model for the need for central cervical lymph node dissection in patients with clinical N0 papillary thyroid carcinoma (PTC) diagnosed using ultrasound.MethodsUpon retrospective review, derivation and internal validation cohorts comprised 1585 consecutive patients with PTC treated from January 2017 to December 2019 at hospital A. The external validation cohort consisted of 406 consecutive patients treated at hospital B from January 2016 to June 2020. Independent risk factors for central cervical lymph node metastasis (CLNM) were determined through univariable and multivariable logistic regression analysis. An individualized risk prediction model was constructed and illustrated as a nomogram, which was internally and externally validated.ResultsThe following risk factors of CLNM were established: a solitary primary thyroid nodule’s diameter, shape, calcification, and capsular abutment-to-lesion perimeter ratio. The areas under the receiver operating characteristic curves of the risk prediction model for the internal and external validation cohorts were 0.921 and 0.923, respectively. The calibration curve showed good agreement between the nomogram-estimated probability of CLNM and the actual CLNM rates in the 3 cohorts. The decision curve analysis confirmed the clinical usefulness of the nomogram.ConclusionThis study developed and validated a model for predicting the risk of CLNM in individual patients with clinical N0 PTC, which should be an efficient tool for guiding clinical treatment.     

Telehealth for Endocrinology: Experience and Effect on Utilization in the Prepandemic Era

ObjectiveTelehealth (TH) use in endocrinology was limited before the COVID-19 pandemic but will remain a major modality of care postpandemic. Reimbursement policies have been limited historically due to concerns of overutilization of visits and testing. Additionally, there is limited literature on endocrinology care delivered via TH for conditions other than diabetes. We assess real-world TH use for endocrinology in a prepandemic environment with the hypothesis that TH would not increase the utilization of total visits or related ancillary testing services compared with conventional (CVL) face-to-face office visits.MethodsA single-institution retrospective cohort study assessing the prepandemic use of TH in endocrinology, consisting of 75 patients seen via TH and 225 patients seen in CVL visits. For most patients, TH was conducted via a clinic-to-clinic model. Outcomes measured were total endocrine visit frequency and frequency of related laboratory and radiology testing per patient, hemoglobin A1C, microalbumin, low-density lipoprotein, thyroid-stimulating hormone, thyroglobulin, and thyroid ultrasounds.ResultsFor all endocrine visits, TH patients had a median of 0.24 (interquartile range, 0.015-0.36) visits per month. CVL patients had a median of 0.20 visits per month (interquartile range, 0.11-0.37). Total visits per month did not vary significantly between groups (P = .051). Hemoglobin A1C outcomes were equivalent and there was no increase in ancillary laboratory testing for the TH group.ConclusionOur observations demonstrate that, in a prepandemic health care setting, TH visits can provide equivalent care for endocrinology patients, without increasing utilization of total visits or ancillary services.     

Use of Structured Templates to Improve Completeness of Endocrinology Referrals

ObjectiveEndocrinology referrals frequently lack important clinical information, which may increase the risk of inefficiency and adverse outcomes. This quality improvement project aimed to improve the completeness of new referrals by utilizing structured referral templates for common endocrine conditions at a large Veterans Health Administration medical center. Our target was of at least a 30% improvement in referral completeness for each condition after the intervention.MethodsElectronic structured referral templates were designed utilizing existing resources and input from primary care providers and endocrinologists. Essential elements were identified and included in the templates. We conducted a retrospective chart review to compare referrals for 125 patients referred between January 1, 2021 and September 1, 2021 (preintervention) and 125 patients referred between October 1, 2021 and September 30, 2022 (postintervention). Each referral was rated using a scoring system derived from the criteria in the data abstraction tool formulated by the investigators.ResultsOn average, preintervention referrals included 52% of the essential elements and postintervention referrals included 93%. Improvements in referral scores for each condition all met the prespecified 30% improvement target. The greatest improvement was for the element “type of visit preference.” A separate analysis excluding that element showed an average improvement from 64% of essential elements preintervention to 92% postintervention.ConclusionStructured referral templates, designed with the input of primary care providers and endocrinologists and embedded into an electronic referral system, can improve the availability of essential information and increase the quality of referrals. Future work should examine the effect of structured referral templates on efficiency, specialist experience, patient experience of care, and clinical outcomes.     

Thyroid Immune-Related Adverse Events in Patients with Cancer Treated with anti-PD1/anti-CTLA4 Immune Checkpoint Inhibitor Combination: Clinical Course and Outcomes

ObjectiveThyroid immune-related adverse events (irAEs) have been reported to have prognostic significance among patients with cancer treated with anti-programmed cell death-1 (PD1) and anti-programmed death-ligand 1 monotherapies. We evaluated the clinical course and predictors of thyroid irAEs in relation to outcomes of patients with advanced cancer treated with combination anti-PD1/anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4).MethodsWe conducted a regional study and identified patients with advanced cancer who received ≥1 cycle of combination anti-PD1/anti-CTLA4 between 2015 and 2019 in Hong Kong. Thyroid function tests (TFTs) were monitored every 3 weeks. Thyroid irAE was defined by ≥2 abnormal TFTs after initiation of combination anti-PD1/anti-CTLA4 in the absence of other causes.ResultsOne hundred and three patients were included (median age: 59 years; 71.8% men). About 45% had prior anti-PD1 exposure. Upon median follow-up of 6.8 months, 17 patients (16.5%) developed thyroid irAEs, where 6 initially presented with thyrotoxicosis (overt, n = 4; subclinical, n = 2) and 11 with hypothyroidism (overt, n = 2; subclinical, n = 9). Eventually, 10 patients (58.8%) required continuous thyroxine replacement. Systemic steroid was not required in all cases. Prior anti-PD1 exposure (odds ratio, 3.67; 95% CI, 1.19–11.4; P = .024) independently predicted thyroid irAEs. Multivariable Cox regression analysis revealed that occurrence of thyroid irAEs was independently associated with better overall survival (adjusted hazard ratio, 0.34; 95% CI, 0.17–0.71; P = .004).ConclusionThyroid irAEs are common in routine clinical practice among patients with advanced cancer treated with anti-PD1/anti-CTLA4 combination and might have potential prognostic significance. Regular TFT monitoring is advised for timely treatment of thyroid irAEs to prevent potential morbidities.     

Updated Review of Nuclear Molecular Imaging of Thyroid Cancers

ObjectivesWe initiate this comprehensive review to update the advances in this field by objectively elucidating the efficacies of promising radiopharmaceuticals.MethodsWe performed a comprehensive PUBMED search using the combined terms of “thyroid cancer” and “radiopharmaceuticals” or “nuclear medicine”, yielding 3273 and 11026 articles prior to December 31, 2020, respectively.ResultsBased on the mechanism of molecular metabolism, the evaluation of differentiated thyroid cancer and dedifferentiated thyroid cancer is largely centered around radioiodine and fluorine 18 (¹⁸F)-fludeoxyglucose, respectively. Further, ¹⁸F-L-dihydroxyphenylalanine and gallium 68 DOTATATE are the preferred tracers for medullary thyroid cancer. In dedifferentiated medullary thyroid cancer and anaplastic thyroid cancer, ¹⁸F-fludeoxyglucose is superior.ConclusionsThe future lies in advances in molecular biology, novel radiopharmaceuticals and imaging devices, paving ways to the development of personalized medication for thyroid cancer patients.