Ethanol ablation of papillary thyroid carcinoma nodal metastases: Long-term outcomes.

BACKGROUND: Percutaneous ethanol ablation has emerged as a treatment for recurrent papillary thyroid carcinoma in the lateral neck after compartment-oriented therapeutic lymphadenectomy. However, the safety and utility of percutaneous ethanol ablation as a primary treatment modality for lateral neck metastases remains undefined. We aimed to investigate long-term outcomes of percutaneous ethanol ablation of lateral neck papillary thyroid carcinoma recurrence both with and without prior lymphadenectomy. METHODS: We conducted a retrospective study of patients with lateral neck papillary thyroid carcinoma treated with percutaneous ethanol ablation from 2013 to 2018. Patient characteristics, disease volume, morbidity, and recurrence (development of new lymphadenopathy within a percutaneous ethanol ablation-treated nodal compartment) were assessed. RESULTS: We identified 117 patients who underwent percutaneous ethanol ablation for papillary thyroid carcinoma lateral neck metastases-67 (57%) had a prior lateral neck dissection. Median follow-up after percutaneous ethanol ablation was 5.5 years (interquartile range 3.1-7.5). On average, 1.4 lymph nodes (range: 1-6) were treated. Three patients (3%) developed transient nerve-related complications after percutaneous ethanol ablation. Of 15 patients who underwent lateral neck dissection after percutaneous ethanol ablation (including patients undergoing repeat lateral neck dissection), dissection was "difficult" in 8 (53%) (7 of whom had previously undergone lateral neck dissection), and 4 (27%) developed complications (transient nerve dysfunction = 3, lymphatic leak = 1). Thirty-three patients (28%) developed recurrent papillary thyroid carcinoma. No difference in recurrence was seen between patients who did or did not undergo pre-percutaneous ethanol ablation lateral neck dissection (no pre-percutaneous ethanol ablation lateral neck dissection: 24%, pre-percutaneous ethanol ablation lateral neck dissection, 31%; hazard ratio = 1.27, 95% confidence interval 0.62-2.58; P = .514). CONCLUSION: Percutaneous ethanol ablation may be a safe primary treatment modality for papillary thyroid carcinoma lateral neck nodal recurrence in selected patients with low-volume nodal disease.

Clinician feedback using a shared decision-making tool for the evaluation of patients with thyroid nodules-an observational study.

BACKGROUND: We pilot-tested an encounter conversation aid to support shared decision making (SDM) between patients with thyroid nodules and their clinicians. OBJECTIVE: Characterize the clinician feedback after providing care to patients with thyroid nodules using a tool to promote SDM conversations during the clinical encounter, and evaluate how clinicians used the tool during the visit. METHODS: Mixed method study in two academic centers in the U.S., including adult patients presenting for evaluation of thyroid nodules and their clinicians. We thematically analyzed interviews with clinicians after they used the SDM tool in at least three visits to characterize their feedback. Additionally, investigators evaluated visits recordings to determine the extent to which clinicians engaged patients in the decision-making process (OPTION score, scale 0 to 100, higher levels indicating higher involvement), the tool's components used (fidelity), and encounter duration. Using a post-visit survey, we evaluated the extent to which clinicians felt the tool was easy to use, helpful, and supportive of the patient-clinician collaboration. RESULTS: Thirteen clinicians participated in the study and used the SDM tool in the care of 53 patients. Clinicians thought the tool was well-organized and beneficial to patients and clinicians. Clinicians noticed a change in their routine with the use of the conversation aid and suggested it needed to be more flexible to better support varying conversations. The median OPTION score was 34, the fidelity of use 75%, and the median visit duration 17 min. In most encounters, clinicians agreed or strongly agreed the tool was easy to use (86%), helpful (65%), and supported collaboration (62%). CONCLUSION: Clinicians were able to use a SDM tool in the care of patients with thyroid nodules. Although they wished it were more flexible, they found on the whole that its use in the clinical encounter was beneficial to patients and clinicians.

Patient feedback receiving care using a shared decision making tool for thyroid nodule evaluation-an observational study.

PURPOSE: To characterize the feedback of patients with thyroid nodules receiving care using a shared decision making (SDM) tool designed to improve conversations with their clinicians related to diagnostic options (e.g. thyroid biopsy, ultrasound surveillance). METHODS: Investigators qualitatively analyzed post-encounter interviews with patients to characterize their feedback of a SDM tool used during their clinical visits. Additionally, investigators counted instances of diagnostic choice awareness and of patients' expression of a diagnostic management preference in recordings of clinical encounters of adult patients presenting for evaluation of thyroid nodules in which the SDM tool was used. RESULTS: In total, 53 patients (42 (79%) women); median age 62 years were enrolled and had consultations supported by the SDM tool. Patients were favorable about the design of the SDM tool and its ability to convey information about options and support patient-clinician interactions. Patients identified opportunities to improve the tool through adding more content and improve its use in practice through training of clinicians in its use. There was evidence of diagnostic choice awareness in 52 (98%) of these visits and patients expressed a diagnostic management preference in 40 (76%). CONCLUSION: User centered design including feedback from patients and real life observation supports the use of the SDM tool to facilitate collaboration between patients and clinicians.

Radiofrequency Ablation of Benign and Malignant Thyroid Nodules.

Thyroid nodule treatment has significantly evolved over recent years with attempts to individualize treatment on the basis of the cause of the nodule and patient performance status. The risks and complications associated with surgery and radioactive iodine have promoted interest in additional therapies such as radiofrequency ablation (RFA). RFA creates an electrical current through a target tissue (thyroid nodule) with resultant tissue heating causing coagulative necrosis. National and international groups are beginning to recognize the role of RFA as a viable therapeutic option in the treatment of thyroid nodules. Based on numerous guidelines, RFA is indicated in the treatment of symptomatic benign nodules and autonomously functioning nodules when surgery is refused or when the patient would not tolerate surgery. The treatment of thyroid malignancy with RFA is controversial, with some groups advocating for its use in the treatment of small papillary thyroid cancers in specific scenarios. The most important aspect of RFA is the preprocedural workup and adequate patient selection. Procedural technique varies among centers. However, RFA is typically performed as a single-day-admission outpatient procedure. Methods such as hydrodissection and a moving shot technique are employed to ensure adequate coverage of the nodule without overtreating the peripheries and damaging sensitive structures. As a result, the procedure is well tolerated, and major complications such as recurrent laryngeal nerve injury and nodule rupture are very rare. In the proper patient cohort, thyroid RFA offers an efficacious and safe option in the management of thyroid nodules. An invited commentary by Filippiadis and Vrachliotis is available online. ©RSNA, 2022.

Clinician Agreement on the Classification of Thyroid Nodules Ultrasound Features: A Survey of 2 Endocrine Societies.

CONTEXT: Thyroid nodule risk stratification allows clinicians to standardize the evaluation of thyroid cancer risk according to ultrasound features. OBJECTIVE: To evaluate interrater agreement among clinicians assessing thyroid nodules ultrasound features and thyroid cancer risk categories. DESIGN, SETTING, AND PARTICIPANTS: We surveyed Endocrine Society and Latin American Thyroid Society members to assess their interpretation of composition, echogenicity, shape, margins, and presence of echogenic foci of 10 thyroid nodule cases. The risk category for thyroid cancer was calculated following the American College of Radiology-Thyroid Imaging Reporting & Data System (ACR-TIRADS) framework from individual responses. MAIN OUTCOMES AND MEASURES: We used descriptive statistics and Gwet's agreement coefficient (AC1) to assess the primary outcome of interrater agreement for ACR-TIRADS risk category. As secondary outcomes, the interrater agreement for individual features and a subgroup analysis of interrater agreement for the ACR-TIRADS category were performed (ultrasound reporting system, type of practice, and number of monthly appraisals). RESULTS: A total of 144 participants were included, mostly endocrinologists. There was moderate level of agreement for the absence of echogenic foci (AC1 0.53, 95% CI 0.24-0.81) and composition (AC1 0.54, 95% CI 0.36-0.71). The agreement for margins (AC1 0.24, 95% CI 0.15-0.33), echogenicity (AC1 0.34, 95% CI 0.22-0.46), and shape assessment (AC1 0.42, 95% CI 0.13-0.70) was lower. The overall agreement for ACR-TIRADS assessment was AC1 0.29, (95% CI 0.13-0.45). The AC1 of ACR-TIRADS among subgroups was similar. CONCLUSIONS: This study found high variation of judgments about ACR-TIRADS risk category and individual features, which poses a potential challenge for the widescale implementation of thyroid nodule risk stratification.

Nonsurgical Management of Thyroid Nodules: The Role of Ablative Therapies.

CONTEXT: After a thorough evaluation most thyroid nodules are deemed of no clinical consequence and can be observed. However, when they are compressive, toxic, or involved by papillary thyroid carcinoma surgery or radioactive iodine (RAI) (if toxic) are the treatments of choice. Both interventions can lead to hypothyroidism and other adverse outcomes (eg, scar, dysphonia, logistical limitation with RAI). Active surveillance might be used for papillary thyroid microcarcinoma (PTMC) initially, but anxiety leads many cases to surgery later. Several ablative therapies have thus evolved over the last few years aimed at treating these nodules while avoiding described risks. CASES: We present 4 cases of thyroid lesions causing concern (compressive symptoms, thyrotoxicosis, anxiety with active surveillance of PTMC). The common denominator is patients' attempt to preserve thyroid function, bringing into focus percutaneous ethanol injection (PEI) and thermal ablation techniques (radiofrequency ablation [RFA] being the most common). We discuss the evidence supporting these approaches and compare them with standard therapy, where evidence exists. We discuss additional considerations for the utilization of these therapies, their side-effects, and conclude with a simplified description of how these procedures are performed. CONCLUSION: Thermal ablation, particularly RFA, is becoming an attractive option for managing a subgroup of solid thyroid nodules, while PEI has a role in managing thyroid cysts and a select group of PTMC. Their role in the algorithm of thyroid nodule management is still being refined and technical expertise will be essential to reproduce the reported results into everyday practice.

A novel method for causal structure discovery from EHR data and its application to type-2 diabetes mellitus.

Modern AI-based clinical decision support models owe their success in part to the very large number of predictors they use. Safe and robust decision support, especially for intervention planning, requires causal, not associative, relationships. Traditional methods of causal discovery, clinical trials and extracting biochemical pathways, are resource intensive and may not scale up to the number and complexity of relationships sufficient for precision treatment planning. Computational causal structure discovery (CSD) from electronic health records (EHR) data can represent a solution, however, current CSD methods fall short on EHR data. This paper presents a CSD method tailored to the EHR data. The application of the proposed methodology was demonstrated on type-2 diabetes mellitus. A large EHR dataset from Mayo Clinic was used as development cohort, and another large dataset from an independent health system, M Health Fairview, as external validation cohort. The proposed method achieved very high recall (.95) and substantially higher precision than the general-purpose methods (.84 versus .29, and .55). The causal relationships extracted from the development and external validation cohorts had a high (81%) overlap. Due to the adaptations to EHR data, the proposed method is more suitable for use in clinical decision support than the general-purpose methods.

Thyroid Nodule Size as a Predictor of Malignancy in Follicular and Hurthle Neoplasms.

INTRODUCTION: The management of follicular (FN) and Hurthle cell neoplasms (HCN) is often difficult because of the uncertainty of malignancy risk. We aimed to assess characteristics of benign and malignant follicular and Hurthle neoplasms based on their shape and size. MATERIALS AND METHODS: Patients with Follicular adenoma (FA) or carcinoma (FC) and Hurthle Cell adenoma (HCA) or carcinoma (HCC) who had preoperative ultrasonography were included. Demographic data were retrieved. Size and shape of the nodules were measured. Logistic regression analyses and odds ratios were performed. RESULTS: A total of 115 nodules with 57 carcinomas and 58 adenomas were included. Logistic regression analysis shows that the nodule height and the patient age are predictors of malignancy (p-values = 0.001 and 0.042). A cutoff value of nodule height ≥ 4 cm. produces an odds ratio of 4.5 (p-value = 0.006). An age ≥ 55 year-old demonstrates an odds ratio of 2.4-3.6 (p-value = 0.03). Taller-than-wide shape was not statistically significant (p-value = 0.613). CONCLUSION: FC and HCC are larger than FA and HCA in size, with a cutoff at 4 cm. Increasing age increases the odds of malignancy with a cutoff at 55 year-old. Taller-than-wide shape is not a predictor of malignancy.

Association of BMI, comorbidities and all-cause mortality by using a baseline mortality risk model.

OBJECTIVE: The association of body mass index (BMI) and all-cause mortality is controversial, frequently referred to as a paradox. Whether the cause is metabolic factors or statistical biases is still controversial. We assessed the association of BMI and all-cause mortality considering a wide range of comorbidities and baseline mortality risk. METHODS: Retrospective cohort study of Olmsted County residents with at least one BMI measurement between 2000-2005, clinical data in the electronic health record and minimum 8 year follow-up or death within this time. The cohort was categorized based on baseline mortality risk: Low, Medium, Medium-high, High and Very-high. All-cause mortality was assessed for BMI intervals of 5 and 0.5 Kg/m2. RESULTS: Of 39,739 subjects (average age 52.6, range 18-89; 38.1% male) 11.86% died during 8-year follow-up. The 8-year all-cause mortality risk had a "U" shape with a flat nadir in all the risk groups. Extreme BMI showed higher risk (BMI <15 = 36.4%, 15 to <20 = 15.4% and ≥45 = 13.7%), while intermediate BMI categories showed a plateau between 10.6 and 12.5%. The increased risk attributed to baseline risk and comorbidities was more obvious than the risk based on BMI increase within the same risk groups. CONCLUSIONS: There is a complex association between BMI and all-cause mortality when evaluated including comorbidities and baseline mortality risk. In general, comorbidities are better predictors of mortality risk except at extreme BMIs. In patients with no or few comorbidities, BMI seems to better define mortality risk. Aggressive management of comorbidities may provide better survival outcome for patients with body mass between normal and moderate obesity.

A Computational Method for Learning Disease Trajectories From Partially Observable EHR Data.

Diseases can show different courses of progression even when patients share the same risk factors. Recent studies have revealed that the use of trajectories, the order in which diseases manifest throughout life, can be predictive of the course of progression. In this study, we propose a novel computational method for learning disease trajectories from EHR data. The proposed method consists of three parts: first, we propose an algorithm for extracting trajectories from EHR data; second, three criteria for filtering trajectories; and third, a likelihood function for assessing the risk of developing a set of outcomes given a trajectory set. We applied our methods to extract a set of disease trajectories from Mayo Clinic EHR data and evaluated it internally based on log-likelihood, which can be interpreted as the trajectories' ability to explain the observed (partial) disease progressions. We then externally evaluated the trajectories on EHR data from an independent health system, M Health Fairview. The proposed algorithm extracted a comprehensive set of disease trajectories that can explain the observed outcomes substantially better than competing methods and the proposed filtering criteria selected a small subset of disease trajectories that are highly interpretable and suffered only a minimal (relative 5%) loss of the ability to explain disease progression in both the internal and external validation.

Radiologic and clinicopathologic characteristics of thyroid nodules with focal 68Ga-DOTATATE PET activity.

OBJECTIVE: Our aim was to determine the radiologic and clinicopathologic characteristics of thyroid nodules with focal 68Ga-DOTATATE activity. METHODS: In this retrospective study of 1927 consecutive 68Ga-DOTATATE PET scans, 85 patients with incidental and nonincidental focal 68Ga-DOTATATE avid thyroid nodules were identified, of which 31 patients with 33 thyroid nodules underwent fine-needle aspiration (FNA) or surgery. These 33 nodules were reviewed for Krenning score and SUVmax of the thyroid nodule, contralateral thyroid lobe and left atrium. RESULTS: Cytology/histopathology included 58% (19/33) with benign findings, 18% (6/33) medullary thyroid carcinoma (MTC), 9% (3/33) atypia or follicular lesion of undetermined significance (AUS/FLUS), 9% (3/33) suspicious for follicular neoplasm and Hurthle cell adenoma (SFN/HCA) and 6% (2/33) nondiagnostic cytology. Median serum calcitonin was 1156 pg/mL (range, 460-1828) in MTC and was <5.0 pg/mL (<5.0-12.5) in patients with benign nodules. Nodules had Krenning score of 1, 2 and 3 in 46% (15/33), 27% (9/33) and 27% (9/33). The majority of MTC and AUS/FLUS nodules had a Krenning score of 3, and there was substantial intragroup variation in Krenning score among the benign nodules. The mean SUVmax for the entire cohort was 5.5 ± 2.9 (mean ± SD), and the range was 2.0-13.0. There was overlap in the nodule/contralateral thyroid SUVmax ratios between groups. The MTC and AUS/FLUS nodules tended to have a higher nodule/blood pool SUVmax ratio than the other pathologic groups. CONCLUSION: There was considerable variation in radiologic characteristics among benign thyroid nodules. The ratio of thyroid nodule SUVmax/blood pool SUVmax may be useful to differentiate pathologic groups, but larger studies are needed to investigate this further. Given the potential for malignancy in thyroid nodules with focal 68Ga-DOTATATE activity, further evaluation with serum calcitonin and FNA may be considered.Video Abstract: http://links.lww.com/NMC/A186.

Predicting Outcomes in Sporadic and Hereditary Medullary Thyroid Carcinoma over Two Decades.

Background: Medullary thyroid cancer (MTC) can be associated with significant morbidity and mortality in advanced cases. Hence, we aimed to identify factors at the time of MTC surgery that predict overall survival (OS), disease-specific survival (DSS), locoregional recurrence/persistence (LR), and distant metastases (DM). Methods: We performed a retrospective study of clinicopathologic, radiological, and laboratory data in MTC patients who underwent thyroidectomy at Mayo Clinic from January 1995 to December 2015. Results: We identified 163 patients (mean age 48.4 years, 48% males), 102 with sporadic MTC and 61 with hereditary disease (n = 46 multiple endocrine neoplasia [MEN] 2A, n = 3 MEN 2B, n = 12 familial MTC) with a median follow-up time of 5.5 years. On univariate analysis, age >55 years, male sex, DM at the time of surgery (M1), lateral neck lymph node (LN) involvement (N1b), gross extrathyroidal extension (ETE), American Joint Committee on Cancer (AJCC) stage 3/4, tumor size (T) 3/4, tumor size, and postoperative calcitonin (Ctn) and carcinoembryonic antigen (CEA) were significant predictors of worse OS and DSS. On multivariable analysis, both gross ETE (hazard ratio [HR] 4.62, 6.58) and M1 (HR 5.11, 10.45) remained significant predictors of worse OS as well as DSS, while age >55 years (HR 3.21), male sex (HR 2.42), and postoperative Ctn (HR 1.002 for every 100 pg/mL increase) were significant only for worse OS. On univariate analysis, male sex, M1, N1b, gross ETE, stage 3/4, T 3/4, tumor size, number of LNs involved, and postoperative Ctn were significant predictors of LR and DM; age >55 years was additionally significant for DM. On multivariable analysis, gross ETE (HR 3.16, 5.93) and N1b (HR 4.31, 4.64) remained significant predictors of LR and DM; ratio of resected/involved LN (HR 10.91) was additionally predictive for LR and postoperative Ctn (HR 1.003 for every 100 pg/mL increase) for DM. Conclusions: Disease burden at initial surgery, especially gross ETE, lateral neck LN involvement, and DM, as well as the biochemical response to surgery appear to be more important than demographic factors in terms of MTC prognosis. These findings highlight the importance of rigorous perioperative assessment to better predict MTC outcomes.

PANCYTOPENIA SECONDARY TO AUTOIMMUNE VITAMIN B12 DEFICIENCY IN GRAVES DISEASE.

OBJECTIVE: To describe a case of Graves disease (GD) and coexistent pancytopenia associated with autoimmune vitamin B12 deficiency. While thyrotoxicosis and antithyroid drugs can cause pancytopenia, other autoimmune conditions such as vitamin B12 deficiency can occur, leading to severe anemia and pancytopenia. METHODS: A 19-year-old female with GD treated with methimazole presented with thyrotoxicosis and evidence of pancytopenia. Diagnostic studies included a complete blood cell count, peripheral blood smears, thyroid function tests, and a bone marrow biopsy. RESULTS: White blood cells were 2.4 × 109 cells/L (reference range [RR] is 3.4 to 9.6 × 109 cells/L), hemoglobin was 7.9 g/dL (RR is 11.6 to 15.0 g/dL), neutrophil count was 1.2 × 109 cells/L, and platelets were 84 × 109 cells/L (RR is 157 to 371 × 109 cells/L). Thyroid-stimulating hormone was <0.01 mIU/L (RR is 0.50 to 4.30 mIU/L), free thyroxine was 3.7 ng/dL (RR is 1.0 to 1.6 ng/dL), and total triiodothyronine was 221 ng/dL (RR is 91 to 218 ng/dL). Due to suspicion for drug-induced pancytopenia, methimazole was discontinued. Three days later, she was hospitalized for a syncopal episode with a further decline in hemoglobin to 6.7 g/dL, neutrophils to 0.68 × 109 cells/L, and platelets to 69 × 109 cells/L. Bone marrow biopsy findings showing marrow hypercellularity and hypersegmented neutrophils suggested vitamin B12 deficiency. Vitamin B12 was <70 ng/L (RR is 180 to 914 ng/L). Intramuscular vitamin B12 injections were initiated, and pancytopenia resolved within 1 month. CONCLUSION: Although rarely described in the literature, autoimmune vitamin B12 deficiency can be missed as an underlying etiology for pancytopenia in patients with GD. The clinical picture can be further confounded when these patients are treated with antithyroid drugs known to cause bone marrow suppression.

Long-Term Results of Treating With Ethanol Ablation 15 Adult Patients With cT1aN0 Papillary Thyroid Microcarcinoma.

BACKGROUND: Currently acceptable management options for patients with adult papillary thyroid microcarcinoma (APTM) range from immediate surgery, either unilateral lobectomy or bilateral lobar resection, to active surveillance (AS). An alternative minimally invasive approach, originally employed for eliminating neck nodal metastases, may be ultrasound-guided percutaneous ethanol ablation (EA). Here we present our experience of definitively treating with EA 15 patients with APTM. PATIENTS AND METHODS: During 2010 through 2017, the 15 cT1aN0M0 patients selected for EA were aged 36 to 86 years (median, 45 years). Tumor volumes (n = 17), assessed by sonography, ranged from 25 to 375 mm3 (median, 109 mm3). Fourteen of 15 patients had 2 ethanol injections on successive days; total volume injected ranged from 0.45 to 1.80 cc (median, 1.1 cc). All ablated patients were followed with sonography and underwent recalculation of tumor volume and reassessment of tumor perfusion at each follow-up visit. RESULTS: The ablated patients have now been followed for 10 to 100 months (median, 64 months). There were no complications and no ablated patient developed postprocedure recurrent laryngeal nerve dysfunction. All 17 ablated tumors shrank (median 93%) and Doppler flow eliminated. Median tumor volume reduction in 9 identifiable avascular foci was 82% (range, 26%-93%). After EA, 8 tumors (47%) disappeared on sonography after a median of 10 months. During follow-up no new PTM foci and no nodal metastases have been identified. CONCLUSIONS: Definitive treatment of APTM by EA is effective, safe, and inexpensive. Our results suggest that, for APTM patients who do not wish neck surgery and are uncomfortable with AS, EA represents a well-tolerated and minimally invasive outpatient management option.

Thyroid nodules: diagnostic evaluation based on thyroid cancer risk assessment.

Thyroid nodules are extremely common and can be detected by sensitive imaging in more than 60% of the general population. They are often identified in patients without symptoms who are undergoing evaluation for other medical complaints. Indiscriminate evaluation of thyroid nodules with thyroid biopsy could cause a harmful epidemic of diagnoses of thyroid cancer, but inadequate selection of thyroid nodules for biopsy can lead to missed diagnoses of clinically relevant thyroid cancer. Recent clinical guidelines advocate a more conservative approach in the evaluation of thyroid nodules based on risk assessment for thyroid cancer, as determined by clinical and ultrasound features to guide the need for biopsy. Moreover, newer evidence suggests that for patients with indeterminate thyroid biopsy results, a combined assessment including the initial ultrasound risk stratification or other ancillary testing (molecular markers, second opinion on thyroid cytology) can further clarify the risk of thyroid cancer and the management strategies. This review summarizes the clinical importance of adequate evaluation of thyroid nodules, focuses on the clinical evidence for diagnostic tests that can clarify the risk of thyroid cancer, and highlights the importance of considering the patient's values and preferences when deciding on management strategies in the setting of uncertainty about the risk of thyroid cancer.

Predicting diabetes clinical outcomes using longitudinal risk factor trajectories.

BACKGROUND: The ubiquity of electronic health records (EHR) offers an opportunity to observe trajectories of laboratory results and vital signs over long periods of time. This study assessed the value of risk factor trajectories available in the electronic health record to predict incident type 2 diabetes. STUDY DESIGN AND METHODS: Analysis was based on a large 13-year retrospective cohort of 71,545 adult, non-diabetic patients with baseline in 2005 and median follow-up time of 8 years. The trajectories of fasting plasma glucose, lipids, BMI and blood pressure were computed over three time frames (2000-2001, 2002-2003, 2004) before baseline. A novel method, Cumulative Exposure (CE), was developed and evaluated using Cox proportional hazards regression to assess risk of incident type 2 diabetes. We used the Framingham Diabetes Risk Scoring (FDRS) Model as control. RESULTS: The new model outperformed the FDRS Model (.802 vs .660; p-values <2e-16). Cumulative exposure measured over different periods showed that even short episodes of hyperglycemia increase the risk of developing diabetes. Returning to normoglycemia moderates the risk, but does not fully eliminate it. The longer an individual maintains glycemic control after a hyperglycemic episode, the lower the subsequent risk of diabetes. CONCLUSION: Incorporating risk factor trajectories substantially increases the ability of clinical decision support risk models to predict onset of type 2 diabetes and provides information about how risk changes over time.

The Levothyroxine Absorption Test: A Four-Year Experience (2015-2018) at The Mayo Clinic.

Background: Levothyroxine (LT4) is the mainstay of therapy for hypothyroidism. Yet, despite physician efforts at dose titration, some patients remain hypothyroid on LT4 doses in excess of weight-based calculations, a condition known as refractory hypothyroidism. The LT4 absorption test (LT4AT) has been proposed to have utility in these patients by enabling distinction of LT4 malabsorption from pseudomalabsorption, a condition of intentional nonadherence. Given its rare use in clinical practice, we reviewed our institution's experience with the LT4AT to assess its impact on management of refractory hypothyroidism. Methods: We reviewed the charts of 16 patients diagnosed with refractory hypothyroidism and who had completed the LT4AT between January 2015 to January 2019. The primary aim was to determine the utility of this test in distinguishing LT4 malabsorption from pseudomalabsorption. Secondary aims were to determine whether the results of this test impacted physicians' management decisions, as well as to report on clinical outcomes at follow-up. Our LT4AT is a six-hour test wherein patients receive a weight-based dose of LT4 followed by serial measurements of total thyroxine (TT4) and thyrotropin (TSH). Percentage absorption is calculated using the following formula, with normal absorption being ≥60%: [Formula: see text] Results: Percentage absorption was calculated in 13 of 16 patients due to lack of TT4 data for 3 patients. Absorption was impaired in one patient (% absorbed = 0), who had known causes of malabsorption. The remaining 12 patients had normal absorption by hour 4 of the test (% absorption 60-158) in conjunction with upward TT4 trends. Clinical follow-up ranged from 1 to 32 months (median 6.5 months), with 11 patients having follow-up data. Six of these had normal or suppressed TSH values at most recent follow-up, and four had improved but persistent TSH elevations. The one said patient with malabsorption improved with intravenous LT4. Conclusions: The LT4AT can provide valuable information for distinguishing malabsorption from pseudomalabsorption. Our findings support the combined use of calculated percentage absorptions with TT4 trends for at least a four-hour time frame when making determinations regarding absorption.