Assessing thyroid cancer risk using polygenic risk scores.

Genome-wide association studies (GWASs) have identified at least 10 single-nucleotide polymorphisms (SNPs) associated with papillary thyroid cancer (PTC) risk. Most of these SNPs are common variants with small to moderate effect sizes. Here we assessed the combined genetic effects of these variants on PTC risk by using summarized GWAS results to build polygenic risk score (PRS) models in three PTC study groups from Ohio (1,544 patients and 1,593 controls), Iceland (723 patients and 129,556 controls), and the United Kingdom (534 patients and 407,945 controls). A PRS based on the 10 established PTC SNPs showed a stronger predictive power compared with the clinical factors model, with a minimum increase of area under the receiver-operating curve of 5.4 percentage points (P ≤ 1.0 × 10-9). Adding an extended PRS based on 592,475 common variants did not significantly improve the prediction power compared with the 10-SNP model, suggesting that most of the remaining undiscovered genetic risk in thyroid cancer is due to rare, moderate- to high-penetrance variants rather than to common low-penetrance variants. Based on the 10-SNP PRS, individuals in the top decile group of PRSs have a close to sevenfold greater risk (95% CI, 5.4-8.8) compared with the bottom decile group. In conclusion, PRSs based on a small number of common germline variants emphasize the importance of heritable low-penetrance markers in PTC.

Thyroid cancer, recent advances in diagnosis and therapy.

Over the past several decades, the approach to the diagnosis and management of patients with follicular cell-derived thyroid cancer has evolved based on improved classification of patients better matching clinical outcomes, as well as advances in imaging, laboratory, molecular technologies and knowledge. While thyroid surgery, radioactive iodine therapy and TSH suppression remain the mainstays of treatment, this expansion of knowledge has enabled de-escalation of therapy for individuals diagnosed with low-risk well-differentiated thyroid cancer; better definition of treatment choices for patients with more aggressive disease; and improved ability to optimize treatments for patients with persistent and/or progressive disease. Most recently, the advancement of knowledge regarding the molecular aspects of thyroid cancer has improved thyroid cancer diagnosis and has enabled individualized therapeutic options for selected patients with the most aggressive forms of the disease. Guidelines from multiple societies across the world reflect these changes, which focus on taking a more individualized approach to clinical management. In this review, we discuss the current more personalized approach to patients with follicular cell-derived thyroid cancer and point toward areas of future research still needed in the field.

Long-Term Efficacy of Lymph Node Reoperation for Persistent Papillary Thyroid Cancer: 13-Year Follow-Up.

BACKGROUND: Current recommendations for persistent or recurrent locoregional papillary thyroid cancer (PTC) include consideration of surgical resection versus active surveillance. The purpose of this study is to determine long-term outcomes after surgical resection of recurrent or persistent metastatic PTC in cervical lymph nodes after failure of initial surgery and radioactive iodine therapy using newer validated clinical outcomes measures. METHODS: Outcomes of 70 patients who underwent cervical lymphadenectomy (n = 110) from 1999 to 2013 for recurrent or persistent locoregional PTC metastases were reviewed. Measures included biochemical remission (BCR) based on Tg levels, American Thyroid Association classifications for response to treatment [biochemical incomplete response (BIR), structural incomplete response (SIR), indeterminate response (IR), and excellent response (ER)], need for reoperation, surgical complications, disease progression, and death. RESULTS: The median follow-up was 13.1 years, with only two additional reoperations since 2010, one of which had no metastasis on pathology with the other developing anaplastic thyroid cancer in background PTC. ER was achieved in 31 (44%) patients, all of whom remained in ER at time of last follow-up (median 14.1 years). There were no structural recurrences in patients with persistent BIR or IR after reoperation. Patients with SIR had stable disease, except for one who died due to anaplastic thyroid cancer. CONCLUSIONS: Patients who achieved ER after reoperation had no need for further treatment. Patients with persistent detectable Tg levels after reoperation rarely developed structural recurrence. ATA outcomes can be safely used to guide treatment decisions over a decade after reoperation for PTC.

Ultrasound Features and Performance of Afirma Gene Sequencing Classifier in Cytologically Indeterminate Thyroid Nodules.

Background: Cytologically indeterminate thyroid nodules (ITN) pose a management challenge. Here we analyze if adding ultrasound characteristics to Afirma Genome Sequence Classifier (GSC) results increases GSC diagnostic performance. Methods: We retrospectively analyzed 237 GSC-tested Bethesda III/IV ITNs between July 2017 and December 2019 and classified them by American Thyroid Association (ATA) and the Thyroid Imaging Reporting and Data System (TIRADS) of the American College of Radiology. Results: The benign call rate was higher in Bethesda III ITNs with TIRADS <5 vs TIRADS 5 (89% vs 68%. P = .015). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of GSC in ATA high-risk Bethesda III ITNs vs lower were 100% vs 80% (P = 1), 89.5% vs 91.5% (P = .67), 66.7% vs 25% (P = .13), and 100% vs 99.2% (P = 1), respectively, and for TIRADS 5 vs <5 were 100% vs 80% (P = 1), 88.2% vs 91.4% (P = .65), 71.4% vs 23.5% (P = .06), and 100% vs 99.3% (P = 1). The sensitivity, specificity, PPV, and NPV of GSC in high-risk ATA Bethesda IV ITNs vs lower were 66.7% vs 100% (P = .42), 83.3% vs 85.7% (P = 1), 66.7% vs 64.3% (P = 1), and 83.3% vs 100% (P = .3), respectively, and for TIRADS 5 vs <5 were 66.7% vs 90% (P = .42), 88.9% vs 83.8% (P = 1), 66.7% vs 60% (P = 1), and 88.9% vs 96.9% (P = .39). Conclusion: Sensitivity, specificity, NPV, and PPV of GSC were not significantly different in ATA high-risk and TIRADS 5 ITNs compared to ATA < high-risk and TIRADS 1-4 ITNs.

Presumed Pathogenic Germ Line and Somatic Variants in African American Thyroid Cancer.

Background: African American (AA) thyroid cancer patients have worse prognoses than European Americans (EA), which has been attributed to both health care disparities and possible genetic differences. We investigated the impact of both germ line and somatic variants on clinical outcome in a cohort of AA nonmedullary thyroid cancer (NMTC) patients who had received therapeutic intervention from cancer centers. Methods: Whole-exome sequencing was performed on DNA from available blood/normal tissues (N = 37) and paired tumor samples (N = 32) collected from 37 and 29 AA NMTC patients, respectively. Variants with Combined Annotation Depletion Dependent (CADD) score of ≥20 and VarSome Clinical classification of likely pathogenic or pathogenic were classified as presumed pathogenic germ line or somatic variants (PPGVs/PPSVs). PPGVs/PPSVs in cancer-related genes and PPGVs in cardiovascular risk genes were further investigated, and PPGVs/PPSVs associated with African (AFR) ancestry were identified. Results: Among 17 PPGVs identified in 16 cancer predisposition or known cancer-related genes, only WRN was previously known to associate with NMTC predisposition. Among PPSVs, BRAFV600E was most the prevalent and detected in 12 of the 29 (41%) tumors. Examining PPGVs/PPSVs among three patients who died from NMTC, one patient who died from papillary thyroid carcinoma/anaplastic thyroid carcinoma (PTC/ATC) led us to speculate that the PPGV ERCC4R799W may have increased the risk of PPSV TP53R273H acquisition. Among PPGVs identified in 18 cardiovascular risk genes, PPGVs in SC5NA, GYG1, CBS, CFTR, and SI are known to have causal and pathogenic implications in cardiovascular disease. Conclusion: In this cohort, most AA-NMTC patients exhibit favorable outcomes after therapeutic intervention given at cancer centers, suggesting that health care disparity is the major contributor for worse prognoses among AA-NMTC patients. Nevertheless, the clinical impact of PPGVs that might facilitate the acquisition of TP53 tumor mutations, and/or PPGVs that predispose individuals to adverse cardiovascular events, which could be exacerbated by therapy-induced cardiotoxicity, needs to be further explored. Integrated analysis of PPGV/PPSV profiles among NMTC patients with different stages of disease may help to identify NMTC patients who require close monitoring or proactive intervention.

Indolent behavior of malignant Bethesda III nodules compared to Bethesda V/VI nodules.

BACKGROUND: The Bethesda System classifies all fine needle aspiration specimens into one of six categories. We speculated that cancers within each Bethesda category would have distinct clinical behavior. METHODS: This is a retrospective analysis of patients from a single academic medical center with a histologic diagnosis of thyroid cancer who had an initial diagnosis of Bethesda III, IV, V, or VI cytology. RESULTS: A total of 556 cases were included, with 87 cases of Bethesda III, 109 cases of IV, 120 cases of V, and 240 cases of VI. Bethesda III showed similarities with V/VI compared to IV with predominance of papillary thyroid cancer. The interval from diagnosis to surgery was longer in Bethesda III compared to Bethesda V/VI (median 78 vs. 41 days, p<0.001) (Figure 1). Yet, patients with Bethesda III had a higher probability of achieving remission (62 vs.46 %, p<0.03), a lower possibility of recurrence (8 vs. 24%, p<0.001) and a shorter interval to achieve remission (median 1218 vs.1682 days p = 0.02) compared to Bethesda V/VI which did not change after adjusting for age, gender, radioactive iodine therapy, mode of surgery and tumor size. More than 70% of Bethesda III that later presented with recurrence had T3/T4 disease or distant metastasis. CONCLUSIONS: Cancers with Bethesda III cytology had a less aggressive clinical phenotype with better prognosis compared to V/VI despite histological similarities. The time to remission was shorter in Bethesda III despite a longer interval between diagnosis and surgery. The initial cytological diagnosis may guide management.

Personalized radioiodine therapy for thyroid cancer patients with known disease.

Radioactive iodine (RAI) 131I is a targeted therapy for patients with RAI-avid follicular cell-derived thyroid cancer. However, the responsiveness to 131I therapy varies among thyroid cancer patients mainly owing to differential RAI uptake and RAI radiosensitivity among patients' lesions. A personalized approach to maximize 131I therapeutic efficacy is proposed based on recent scientific advances and future opportunities.

Pembrolizumab in a Patient with Treatment-Naïve Unresectable BRAF-Mutation Negative Anaplastic Thyroid Cancer.

Immune check point inhibitor (ICI) therapy can be a potentially effective salvage treatment for anaplastic thyroid cancer (ATC) with progression despite standard of care therapies. We report a case of unresectable treatment-naïve ATC showing a dramatic and durable response to first-line pembrolizumab therapy. A 69-year-old male presented with a large, right-sided neck mass associated with compressive symptoms. A neck ultrasound showed a large, right-sided, and highly suspicious thyroid nodule. A fine needle aspiration (FNA) biopsy revealed tumor cells consistent with ATC that were positive for PD-L1, with an expression score of >95% and negative for the BRAF V600E mutation. Imaging studies were negative for distant metastases. The disease was declared surgically inoperable, and the patient declined chemotherapy/radiation therapy (XRT), but agreed to ICI therapy with intravenous pembrolizumab 200 mg every three weeks. The patient has received 25 doses of pembrolizumab to date, with rapid resolution of symptoms and a significant reduction in tumor size. He remains alive without disease progression 18 months since initial diagnosis.

Prevalence of cancer and the benign call rate of afirma gene classifier in 18 F-Fluorodeoxyglucose positron emission tomography positive cytologically indeterminate thyroid nodules.

BACKGROUND: 18 F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) positive (PET+) cytologically indeterminate thyroid nodules (ITNs) have variable cancer risk in the literature. The benign call rate (BCR) of Afirma Gene Classifier (Gene Expression Classifier, GEC, or Genome Sequence Classifier, GSC) in (PET +) ITNs is unknown. METHODS: This is a retrospective study at our institution of all patients with (PET+) ITNs (Bethesda III/IV) from 1 January 2010 to 21 May 2019 who underwent Afirma testing and/or surgery or repeat FNA with benign cytology. RESULTS: Forty-five (PET+) ITNs were identified: 31 Afirma-tested (GEC = 20, GSC = 11) and 14 either underwent surgery (n = 13) or repeat FNA (Benign cytology) (n = 1) without Afirma. The prevalence of cancer and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) including only resected nodules and ITN with repeat benign FNA (n = 33) was 36.4% (12/33). Excluding all Afirma "suspicious" non-resected ITNs and assuming all Afirma "benign" ITNs were truly benign, that prevalence was 28.6% (12/42). The BCR with GSC was 64% compared to 25% with GEC (p = 0.056). Combining GSC/GEC-tested ITNs, the BCR was higher in ITNs demonstrating low/very low-risk sonographic pattern by the American Thyroid Association (ATA) classification and ITNs scoring <4 by the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR-TI-RADS) than ITNs with higher sonographic pattern/score (p = 0.025). CONCLUSIONS: The prevalence of cancer/NIFTP in (PET+) ITNs was 28.6-36.4% depending on the method of calculation. The BCR of Afirma GSC was 64%. Combining Afirma GEC/GSC-tested ITNs, BCR was higher in ITNs with a lower risk sonographic pattern.

Features of Cytologically Indeterminate Molecularly Benign Nodules Treated With Surgery.

BACKGROUND: Most cytologically indeterminate thyroid nodules (ITNs) with benign molecular testing are not surgically removed. The data on clinical outcomes of these nodules are limited. METHODS: We retrospectively analyzed all ITNs where molecular testing was performed either with the Afirma gene expression classifier or Afirma gene sequencing classifier between 2011 and 2018 at a single institution. RESULTS: Thirty-eight out of 289 molecularly benign ITNs were ultimately resected. The most common reason for surgery was compressive symptoms (39%). In multivariable modeling, patients aged <40 years, nodules ≥3 cm, presence of an Afirma suspicious nodule other than the index nodule, and compressive symptoms were associated with higher surgery rates with hazard ratios for surgery of 3.5 (P < 0.001), 3.2 (P < 0.001), 16.8 (P < 0.001), and 7.31 (P < 0.001), respectively. Of resected nodules, 5 were malignant. False-negative rate (FNR) was 1.7%, presuming all unresected nodules were truly benign and 13.2% restricting analysis to resected cases. The FNR was significantly higher in nodules with a high-risk sonographic appearance for cancer (American Thyroid Association high-risk classification and American College of Radiology Thyroid Imaging Reporting and Data Systems score of 5) compared with nodules with all other sonographic categories (11.8% vs 1.1%; P = 0.03 and 11.1% vs 1.1%; P = 0.02, respectively). CONCLUSIONS: Younger age, larger nodule size, presence of an Afirma suspicious nodule other than the index nodule, and compressive symptoms were associated with a higher rate of surgery. The FNR of benign Afirma was significantly higher in nodules with high-risk sonographic features.

Reducing hyperglycemia hospitalwide: the basal-bolus concept.

BACKGROUND: Hyperglycemia has been identified as potent and independent risk factor for adverse outcomes for patients. An initiative was undertaken to reduce hyperglycemia hospitalwide in adults. METHODS: In a multistep process, insulin protocols were implemented hospitalwide via an electronic provider order entry system. Education regarding basal bolus insulin delivery preceded implementation. Protocols were modified in an ongoing manner on the basis of clinical staff feedback and blood glucose monitoring. Key practice changes included intravenous insulin for initial management in ICU patients, insulin replacement based on the basal bolus approach, elimination of sliding-scale insulin, standardization of blood glucose monitoring before meals, adjustment of prandial dose insulin based on food consumed, administration of prandial dose after the meal, evening snacks ordered based on insulin type, and a glycosolated hemoglobin (A1C) determination for patients with admission glucose > 180 mg/dL. Median inpatient glucose levels in patients with diabetes were assessed using statistical process control methodology. RESULTS: Between January 2004 and September 2007, median glucose for all inpatients with diabetes decreased 15% from 159 mg/dL to < 135 mg/dL. The percentage of inpatients with diabetes who experienced a day with a glucose measurement above 180 mg/dl decreased from 66% to 53%. Frequency of hypoglycemia (< 60 mg/dL) did not change following protocol implementation. DISCUSSION: Major improvements in hospitalwide blood glucose control are feasible and safe, employing standard protocols based on the basal-bolus concept. Improvement was sustained during a four-year period with ongoing institutional support, multidisciplinary education, collaboration between clinical services, and monitoring of clinical outcomes on a quarterly basis.

Vandetanib-induced Phototoxic Drug Eruption Treated with Polypodium Leucotomos Extract: A Case Report and Review of the Literature.

Vandetanib is a tyrosine kinase inhibitor approved by the United States Food and Drug Administration for the treatment of metastatic medullary thyroid cancer. It has been linked to a variety of dermatologic reactions, including photosensitivity. We describe the case of a 55-year-old man who developed a severe, painful, erythematous, bullous eruption in sun-exposed areas one month after the initiation of vandetanib. The eruption was initially refractory to treatment with steroids and did not resolve with strict sun avoidance, but finally cleared after a few weeks of oral supplementation with Polypodium leucotomos (P. leucotomos) extract. P. leucotomos is an extract derived from a tropical fern, with antioxidant effects that mitigate ultraviolet-induced cutaneous erythema via inflammatory interference and the promotion of other cytotoxic responses. This case illustrates the potential for P. leucotomos to be used as a safe and effective photoprotective agent for refractory phototoxic reactions. Further randomized, controlled trials are needed to better understand the mechanism of action and photoprotective properties of P. leucotomos in the treatment of tyrosine kinase-induced phototoxicity and other dermatoses.

Molecular Variants and Their Risks for Malignancy in Cytologically Indeterminate Thyroid Nodules.

Background: Gene panels are routinely used to assess predisposition to hereditary cancers by simultaneously testing multiple susceptibility genes and/or variants. More recently, genetic panels have been implemented as part of solid tumor malignancy testing assessing somatic alterations. One example is targeted variant panels for thyroid nodules that are not conclusively malignant or benign upon fine-needle aspiration (FNA). We systematically reviewed published studies from 2009 to 2018 that contained genetic data from preoperative FNA specimens on cytologically indeterminate thyroid nodules (ITNs) that subsequently underwent surgical resection. Pooled prevalence estimates per gene and variant, along with their respective positive predictive values (PPVs) for malignancy, were calculated. Summary: Our systematic search identified 540 studies that were supplemented by 18 studies from bibliographies or personal files. Sixty-one studies met all inclusion criteria and included >4600 ITNs. Overall, 26% of nodules contained at least 1 variant or fusion. However, half of them did not include details on the specific gene, variant, and/or complete fusion pair reported for inclusion toward PPV calculations. The PPVs of genomic alterations reported at least 10 times were limited to BRAFV600E (98%, 95% confidence interval [CI 96-99%]), PAX8/PPARG (55% [CI 34-78%]), HRASQ61R (45% [CI 22-72%]), BRAFK601E (42% [CI 19-68%]), and NRASQ61R (38% [CI 23-55%]). Excluding BRAFV600E, the pooled PPV for all other specified variants and fusions was 47%. Multiple variants within the same nodule were identified in ∼1% of ITN and carried a cumulative PPV of 77%. Conclusions: The chance that a genomic alteration predicts malignancy depends on the individual variant or fusion detected. Only five alterations were reported at least 10 times; BRAFV600E had a PPV of 98%, while the remaining four had individual PPVs ranging from 38% to 55%. The small sample size of most variants and fusion pairs found among ITNs, however, limits confidence in their individual PPV point estimates. Better specific reporting of genomic alterations with cytological category, histological subtype, and cancer staging would facilitate better understanding of cancer prediction, and the independent contribution of the genomic profile to prognosis.

Afirma Gene Sequencing Classifier Compared with Gene Expression Classifier in Indeterminate Thyroid Nodules.

Background: The Afirma Gene Expression Classifier (GEC) has been used to further characterize cytologically indeterminate (cyto-I) thyroid nodules into either benign or suspicious categories. However, its relatively low positive predictive value (PPV) limited its use as a classifier for patients with suspicious results. The Afirma Gene Sequencing Classifier (GSC) was developed to improve PPV while maintaining a high negative predictive value (NPV), yet real-world assessment of its performance is lacking. Methods: We analyzed all patients who had cyto-I nodules and molecular testing with either GEC or GSC between 2011 and 2018 at a single academic medical center. Clinical information was obtained for 343 GEC-tested nodules and 164 GSC-tested nodules. Results: The GSC had a statistically significant higher benign call rate (76.2% vs. 48.1%, p < 0.001), PPV (60.0% vs. 33.3%, p = 0.01), and specificity (94.3% vs. 61.4%, p < 0.001) than the GEC. Improvement was statistically significant in both Bethesda III and Bethesda IV nodules. In particular, the benign call rate of GSC was significantly higher in nodules with Hürthle cell changes (88.8% vs. 25.7%, p < 0.01). The rate of surgical intervention in the indeterminate nodule cohort has decreased by 66.4% since switching to the GSC; 52.5% of indeterminate nodules went to surgery while using the GEC compared with 17.6% with the GSC (p < 0.001). This reduction was statistically significant in nodules with Bethesda III diagnoses, demonstrating a 70.9% decrease (GEC 51.3% vs. GSC 14.9%, p < 0.001), and in nodules with Bethesda IV cytology, a 39.2% decrease was noted (GEC 54.8% vs. GSC 33.3%, p = 0.003). Conclusions: Data from a single academic tertiary center show an improved specificity and PPV while maintaining high sensitivity and NPV for GSC compared with GEC. A statistically significant increase in benign call rates was observed in GSC compared with GEC, likely indicating fewer false positive results. After implementation of GSC, surgical interventions have been reduced by 68%.

Risk Haplotypes Uniquely Associated with Radioiodine-Refractory Thyroid Cancer Patients of High African Ancestry.

BACKGROUND: Thyroid cancer patients with radioiodine-refractory (RAI-R) disease, resulting from insufficient RAI delivery and/or RAI resistance, have increased mortality and limited treatment options. To date, studies have largely focused on tumor mutations associated with different stages of disease, which could provide prognostic value for RAI-R disease. It was hypothesized that germline variants contributing to intrinsic differences in iodine metabolism, tumor microenvironment, and/or immune surveillance are associated with RAI-R disease. METHODS: Whole-genome genotyping data analysis was performed on 1145 Caucasian (CAU) patients, 244 of whom were RAI-R, and 55 African American (AA) patients, nine of whom were RAI-R. Germline-variant association studies were conducted using candidate genes involved in iodine metabolism or DNA-damage repair, as well as genome-wide association analysis. Initial data indicated several notable variants in a small number of patients (n = 7), who were later determined to be AA patients of >80% African ancestry (n = 37). This led to the study focusing on germline single nucleotide polymorphisms uniquely associated with RAI-R AA patients. Sanger sequencing was performed to validate risk alleles and identify the incidence of the common somatic mutations BRAFV600E, NRASQ61R, and HRASQ61R in AA patients whose primary tumor samples were available (28/55). RESULTS: TG, BRCA1, and NSMCE2 haplotypes were identified as being uniquely associated with RAI-R AA patients of >80% African ancestry. All patients with the TG haplotype (n = 4) had a biochemical incomplete response to RAI therapy. Patients with the NSMCE2 haplotype (n = 4) were diagnosed at a young age (13, 17, 17, and 26 years old) with distant metastatic disease at initial diagnosis. The BRCA1 haplotype co-occurred in three out of four patients with the NSMCE2 haplotype. The incidence of BRAFV600E appears lower in papillary thyroid carcinomas from AA patients of >80% African ancestry (3/14; 21%) than in AA patients of <80% African ancestry (6/9; 67%), albeit only just approaching statistical significance (p = 0.077). The tumors available from three RAI-R AA patients were negative for BRAFV600E, NRASQ61R, and HRASQ61R. CONCLUSIONS: The identification of candidate RAI-R risk haplotypes may allow early stratification of clinical manifestations of RAI-R disease followed by early intervention and personalized treatment strategies. Functional annotation of candidate RAI-R risk haplotypes may provide insights into the mechanisms underlying RAI-R disease.

Analytic bias among certified methods for the measurement of hemoglobin A1c: a cause for concern?

We studied the magnitude, significance, and origin of an analytic bias that emerged between our point-of-care (POC) and our central laboratory (CL) methods for the measurement of hemoglobin A1c (HbA1c) and evaluated the analytic accuracy of 7 commonly used HbA1c methods relative to the National Glycohemoglobin Standardization Program (NGSP) reference method. The POC and CL methods were compared by split-sample analysis of clinical specimens and time series analyses of the HbA1c results reported for a 33-month period. The relative accuracies of 7 HbA1c methods were evaluated using College of American Pathologists proficiency survey results. Long-term drifts in the CL- and POC-analyzed test results caused the median intermethod bias [(POC result)-(CL result)] to increase from -0.4% to -0.9% HbA1c. Systematic biases, drifts in analytic performance over time, and intermethod variability were frequently observed among the 7 NGSP-certified HbA1c methods. Intermethod variability is a potential source of inaccuracy whenever HbA1c results are interpreted relative to universal, fixed, clinical decision thresholds.

Neck Ultrasound in Patients with Follicular Thyroid Carcinoma.

There are limited data on the role of neck ultrasound (US) in the surveillance of patients with follicular thyroid cancer (FTC). Here, we analyze the likelihood of US to find structural disease in patients with FTC and evaluate if initial American Thyroid Association (ATA) risk stratification and the response to therapy categories [the latter based on thyroglobulin (Tg) levels] modify that likelihood. We conducted a retrospective cohort study of 32 patients with FTC in our institution. We included all patients with well-differentiated FTC who underwent total thyroidectomy and radioactive iodine (RAI) treatment without neck structural disease at the time of RAI and with Tg and US at least 6 months after RAI. After a median follow-up of 4.3 years, two patients (6.3%) had structural disease by US. None of the 18 patients with initial ATA low-risk disease had structural disease by US in contrast to higher, but not significant, frequency of 18.2% (2/11) in patients with initial ATA high-risk disease (p = 0.14). Based on Tg levels, 24/32 patients had excellent response to therapy and 8/32 had biochemical incomplete/indeterminate response. None of the patients with excellent response had structural disease by US versus 2/8 (25%) patients with biochemical incomplete/indeterminate response all of whom had other sites of structural disease (p = 0.054). Our findings suggest that neck US in FTC is unlikely to find structural disease with initial low-risk ATA or excellent response to therapy but can detect structural disease in some patients with initial ATA high-risk or incomplete/indeterminate responses to therapy.