Publications by authors named "Jennifer A Sipos"

26 Publications

  • Page 1 of 1

Personalized radioiodine therapy for thyroid cancer patients with known disease.

Fac Rev 2021 7;10:36. Epub 2021 Apr 7.

Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, OH 43210, USA.

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

Download full-text PDF

Source
http://dx.doi.org/10.12703/r/10-36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103907PMC
April 2021

NIS in non-thyroidal tissues and impact on thyroid cancer therapy.

Endocr Relat Cancer 2021 May 1. Epub 2021 May 1.

J Sipos, Endocrinology, The Ohio State University, Columbus, 43210, United States.

Radioiodine (131I) has been used to ablate thyroid tissue not removed by surgery or to treat differentiated thyroid cancer that has metastasized to other parts of the body for the past 80 years. However, the Na+/I- symporter (NIS), which mediates active iodide uptake into thyroid follicular cells, is also expressed in several non-thyroidal tissues. This NIS expression permits 131I accumulation and radiation damage in these non-target tissues, which accounts for the adverse effects of radioiodine therapy. We will review the data regarding the expression, function, and regulation of NIS in non-thyroidal tissues. We will explain the seemingly paradoxical adverse effects induced by 131I: the self-limited gastrointestinal adverse effects in contrast to the permanent salivary dysfunction that is seen after 131I therapy. We propose that prospective studies are needed to uncover the time-course of pathological processes underlying development and progression or ultimate resolution of 131I-induced salivary ductal obstruction and nasolacrimal duct obstruction. Finally, preventive measures and early therapeutic interventions that can be applied potentially to eliminate or alleviate long-term radioiodine adverse effects will be discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/ERC-21-0035DOI Listing
May 2021

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

Cancer Med 2021 02 15;10(3):1084-1090. Epub 2021 Jan 15.

Division of Endocrinology, Diabetes, and Metabolism, The Ohio State University Wexner Medical Center and Arthur G. James Cancer Center, Columbus, Ohio, USA.

Background: 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.3704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897903PMC
February 2021

Physician Confidence in Neck Ultrasonography for Surveillance of Differentiated Thyroid Cancer Recurrence.

JAMA Otolaryngol Head Neck Surg 2020 Dec 23. Epub 2020 Dec 23.

Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor.

Importance: Neck ultrasonography, a mainstay of long-term surveillance for recurrence of differentiated thyroid cancer (DTC), is routinely used by endocrinologists, general surgeons, and otolaryngologists; however, physician confidence in their ability to use ultrasonography to identify lymph nodes suggestive of cancer recurrence remains unknown.

Objective: To evaluate physicians' posttreatment surveillance practices for DTC recurrence, specifically their use of and confidence in ultrasonography.

Design, Setting, And Participants: Cross-sectional study of 448 physicians in private and academic hospitals who completed a survey on DTC posttreatment practices from October 2018 to August 2019 (response rate, 69%) and self-reported involvement in long-term surveillance for thyroid cancer recurrence. Physicians were identified by patients affiliated with the Surveillance, Epidemiology, and End Results Program registries in Georgia State and Los Angeles County. Of the respondents, 320 physicians who reported involvement with DTC surveillance were included in the analysis.

Main Outcomes And Measures: Physician-reported long-term surveillance practices for DTC, including frequency of use and level of confidence in ultrasonography for detecting lymph nodes suggestive of cancer recurrence.

Results: In the cohort of 320 physicians who reported involvement with DTC surveillance, 186 (60%) had been in practice for 10 years to less than 30 years; 209 (68%) were White; and 212 (66%) were men. The physicians included 170 (56%) endocrinologists, 67 (21%) general surgeons, and 75 (23%) otolaryngologists. Just 84 (27%) physicians reported personally performing bedside ultrasonography. Only 57 (20%) had high confidence (rated quite or extremely confident) in their ability to use bedside ultrasonography to identify lymph nodes suggestive of recurrence; 94 (33%) did not report high confidence in either their ability or a radiologist's ability to use ultrasonography to detect recurrence. Higher confidence in ultrasonography was associated with the general surgery subspecialty (odds ratio [OR], 5.7; 95% CI, 2.2-14.4; reference endocrinology) and with treating a higher number of patients per year (>50 patients: OR, 14.4; 95% CI, 4.4-47.4; 31-50 patients: OR, 8.4; 95% CI, 2.6-26.7; 11-30 patients: OR, 4.3; 95% CI, 1.5-12.1; reference 0-10 patients).

Conclusions And Relevance: Given the importance of neck ultrasonography in long-term surveillance for thyroid cancer, these findings of physicians' low confidence in their own ability and that of radiologists to use ultrasonography to detect recurrence point to a major obstacle to standardizing long-term DTC surveillance practices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoto.2020.4471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758830PMC
December 2020

Features of Cytologically Indeterminate Molecularly Benign Nodules Treated With Surgery.

J Clin Endocrinol Metab 2020 11;105(11)

Division of Endocrinology, Diabetes, and Metabolism, The Ohio State University and Arthur G. James Cancer Center, Columbus, Ohio.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgaa506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497819PMC
November 2020

Use of Molecular Diagnostic Tests in Thyroid Nodules with Hürthle Cell-Dominant Cytology.

Thyroid 2020 09 4;30(9):1390-1392. Epub 2020 May 4.

Division of Endocrinology, Diabetes, and Metabolism, The Ohio State University and Arthur G. James Cancer Center, Columbus, Ohio, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/thy.2020.0021DOI Listing
September 2020

Prospects for Redifferentiating Agents in the Use of Radioactive Iodine Therapy for Thyroid Cancer.

Thyroid 2020 04 26;30(4):471-473. Epub 2020 Mar 26.

Division of Endocrinology and Metabolism, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/thy.2020.0143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187962PMC
April 2020

The American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Thyroid Disease in Adults.

Ann Surg 2020 03;271(3):e21-e93

Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Objective: To develop evidence-based recommendations for safe, effective, and appropriate thyroidectomy.

Background: Surgical management of thyroid disease has evolved considerably over several decades leading to variability in rendered care. Over 100,000 thyroid operations are performed annually in the US.

Methods: The medical literature from 1/1/1985 to 11/9/2018 was reviewed by a panel of 19 experts in thyroid disorders representing multiple disciplines. The authors used the best available evidence to construct surgical management recommendations. Levels of evidence were determined using the American College of Physicians grading system, and management recommendations were discussed to consensus. Members of the American Association of Endocrine Surgeons reviewed and commented on preliminary drafts of the content.

Results: These clinical guidelines analyze the indications for thyroidectomy as well as its definitions, technique, morbidity, and outcomes. Specific topics include Pathogenesis and Epidemiology, Initial Evaluation, Imaging, Fine Needle Aspiration Biopsy Diagnosis, Molecular Testing, Indications, Extent and Outcomes of Surgery, Preoperative Care, Initial Thyroidectomy, Perioperative Tissue Diagnosis, Nodal Dissection, Concurrent Parathyroidectomy, Hyperthyroid Conditions, Goiter, Adjuncts and Approaches to Thyroidectomy, Laryngology, Familial Thyroid Cancer, Postoperative Care and Complications, Cancer Management, and Reoperation.

Conclusions: Evidence-based guidelines were created to assist clinicians in the optimal surgical management of thyroid disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000003580DOI Listing
March 2020

Executive Summary of the American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Thyroid Disease in Adults.

Ann Surg 2020 03;271(3):399-410

Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Objective: The aim of this study was to develop evidence-based recommendations for safe, effective and appropriate thyroidectomy.

Background: Surgical management of thyroid disease has evolved considerably over several decades leading to variability in rendered care. Over 100,000 thyroid operations are performed annually in the United States.

Methods: The medical literature from January 1, 1985 to November 9, 2018 was reviewed by a panel of 19 experts in thyroid disorders representing multiple disciplines. The authors used the best available evidence to construct surgical management recommendations. Levels of evidence were determined using the American College of Physicians grading system, and management recommendations were discussed to consensus. Members of the American Association of Endocrine Surgeons reviewed and commented on preliminary drafts of the content.

Results: These clinical guidelines analyze the indications for thyroidectomy as well as its definitions, technique, morbidity, and outcomes. Specific topics include Pathogenesis and Epidemiology, Initial Evaluation, Imaging, Fine Needle Aspiration Biopsy Diagnosis, Molecular Testing, Indications, Extent and Outcomes of Surgery, Preoperative Care, Initial Thyroidectomy, Perioperative Tissue Diagnosis, Nodal Dissection, Concurrent Parathyroidectomy, Hyperthyroid Conditions, Goiter, Adjuncts and Approaches Laryngology Familial Thyroid Cancer, Postoperative Care and Complications, Cancer Management, and Reoperation.

Conclusion: Evidence-based guidelines were created to assist clinicians in the optimal surgical management of thyroid disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000003735DOI Listing
March 2020

The Thyroid Nodule Conundrum: Evaluate or Leave it Alone?

Authors:
Jennifer A Sipos

J Clin Endocrinol Metab 2020 03;105(3)

Division of Endocrinology, The Ohio State University Wexner Medical Center, Columbus, Ohio.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgz124DOI Listing
March 2020

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

Thyroid 2019 08 17;29(8):1115-1124. Epub 2019 Jul 17.

1Division of Endocrinology, Diabetes, and Metabolism; The Ohio State University and Arthur G. James Cancer Center, Columbus, Ohio.

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. 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. The GSC had a statistically significant higher benign call rate (76.2% vs. 48.1%,  < 0.001), PPV (60.0% vs. 33.3%,  = 0.01), and specificity (94.3% vs. 61.4%,  < 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%,  < 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 ( < 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%,  < 0.001), and in nodules with Bethesda IV cytology, a 39.2% decrease was noted (GEC 54.8% vs. GSC 33.3%,  = 0.003). 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%.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/thy.2018.0733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141558PMC
August 2019

Clinical Diagnostic Evaluation of Thyroid Nodules.

Endocrinol Metab Clin North Am 2019 03;48(1):61-84

Division of Endocrinology and Metabolism, The Ohio State University Wexner Medical Center, 1581 Dodd Drive, 5th Floor McCampbell Hall, South, Columbus, OH 43210, USA. Electronic address:

The presence of a thyroid nodule may be recognized by the patient or the clinician on palpation of the neck or it may be an incidental finding during an imaging study for some other indication. The method of detection is less important, however, than distinguishing benign lesions from more aggressive neoplasms. This article outlines the diagnostic algorithm for the evaluation of thyroid nodules including biochemical testing, imaging, and, when appropriate, fine-needle aspiration. In addition, the authors review the natural history of benign nodules, follow-up strategies, and indications for repeat aspiration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecl.2018.11.001DOI Listing
March 2019

Performance of a Multigene Genomic Classifier in Thyroid Nodules With Indeterminate Cytology: A Prospective Blinded Multicenter Study.

JAMA Oncol 2019 02;5(2):204-212

Department Pathology, University of Cincinnati Medical Center, Cincinnati, Ohio.

Importance: Approximately 20% of fine-needle aspirations (FNA) of thyroid nodules have indeterminate cytology, most frequently Bethesda category III or IV. Diagnostic surgeries can be avoided for these patients if the nodules are reliably diagnosed as benign without surgery.

Objective: To determine the diagnostic accuracy of a multigene classifier (GC) test (ThyroSeq v3) for cytologically indeterminate thyroid nodules.

Design, Setting, And Participants: Prospective, blinded cohort study conducted at 10 medical centers, with 782 patients with 1013 nodules enrolled. Eligibility criteria were met in 256 patients with 286 nodules; central pathology review was performed on 274 nodules.

Interventions: A total of 286 FNA samples from thyroid nodules underwent molecular analysis using the multigene GC (ThyroSeq v3).

Main Outcomes And Measures: The primary outcome was diagnostic accuracy of the test for thyroid nodules with Bethesda III and IV cytology. The secondary outcome was prediction of cancer by specific genetic alterations in Bethesda III to V nodules.

Results: Of the 286 cytologically indeterminate nodules, 206 (72%) were benign, 69 (24%) malignant, and 11 (4%) noninvasive follicular thyroid neoplasms with papillary-like nuclei (NIFTP). A total of 257 (90%) nodules (154 Bethesda III, 93 Bethesda IV, and 10 Bethesda V) had informative GC analysis, with 61% classified as negative and 39% as positive. In Bethesda III and IV nodules combined, the test demonstrated a 94% (95% CI, 86%-98%) sensitivity and 82% (95% CI, 75%-87%) specificity. With a cancer/NIFTP prevalence of 28%, the negative predictive value (NPV) was 97% (95% CI, 93%-99%) and the positive predictive value (PPV) was 66% (95% CI, 56%-75%). The observed 3% false-negative rate was similar to that of benign cytology, and the missed cancers were all low-risk tumors. Among nodules testing positive, specific groups of genetic alterations had cancer probabilities varying from 59% to 100%.

Conclusions And Relevance: In this prospective, blinded, multicenter study, the multigene GC test demonstrated a high sensitivity/NPV and reasonably high specificity/PPV, which may obviate diagnostic surgery in up to 61% of patients with Bethesda III to IV indeterminate nodules, and up to 82% of all benign nodules with indeterminate cytology. Information on specific genetic alterations obtained from FNA may help inform individualized treatment of patients with a positive test result.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoncol.2018.4616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439562PMC
February 2019

Combination therapy with capecitabine and temozolomide in patients with low and high grade neuroendocrine tumors, with an exploratory analysis of O-methylguanine DNA methyltransferase as a biomarker for response.

Oncotarget 2017 Nov 24;8(61):104046-104056. Epub 2017 Oct 24.

Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.

Recent advances in the treatment of neuroendocrine tumors (NET), including the combination regimen of capecitabine and temozolomide (CAPTEM), have mostly focused on grade 1 and 2 pancreatic neuroendocrine tumors (pNET). We undertook a retrospective review of 38 patients with advanced NET treated with CAPTEM, including patients with non-pancreatic tumors as well as grade 2 and 3 tumors. O-methylguanine DNA methyltransferase (MGMT) expression was assessed as a predictive biomarker. We found that CAPTEM demonstrated activity in patients with all grades and in pNET and non-pNET. Median progression free survival (mPFS) was 13.0 months (95% CI: 5.6-17.0) and median overall survival (mOS) 29.3 months (95% CI 17.7 - 45.3). Among evaluable patients, there were 11 (38%) partial responses, 15 (52%) stable disease, and 3 (10%) progressive disease for a disease control rate of 90%. A higher rate of partial responses occurred in patients whose tumors had low levels of MGMT expression (63%) compared to intermediate-high (17%) (p=0.19). Our results show that CAPTEM therapy is active in patients with NET including in previously treated patients and in those with poorly-differentiated histology. We observed a trend towards increased response rate, median PFS, and median OS in patients whose tumors had low MGMT protein expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.22001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732786PMC
November 2017

United States and European Multicenter Prospective Study for the Analytical Performance and Clinical Validation of a Novel Sensitive Fully Automated Immunoassay for Calcitonin.

Clin Chem 2017 Sep 7;63(9):1489-1496. Epub 2017 Jul 7.

Institute for Clinical Chemistry, Leipzig University, Germany.

Background: The objective of this study is the validation and proof of clinical relevance of a novel electrochemiluminescence immunoassay (ECLIA) for the determination of serum calcitonin (CT) in patients with medullary thyroid carcinoma (MTC) and in different diseases of the thyroid and of calcium homeostasis.

Methods: This was a multicenter prospective study on basal serum CT concentrations performed in 9 US and European referral institutions. In addition, stimulated CT concentrations were measured in 50 healthy volunteers after intravenous calcium administration (2.5 mg/kg bodyweight).

Results: In total, 1929 patients and healthy controls were included. Limits of blank, detection, and quantification for the ECLIA were 0.3, 0.5, and 1 ng/L, respectively. Highest intra- and interassay coefficients of variation were 7.4% (CT concentration, 0.8 ng/L) and 7.0% (1.1 ng/L), respectively. Medians (interval) of serum CT concentrations in 783 healthy controls were 0.8 ng/L (<0.5-12.7) and 3 ng/L (<0.5-18) for females and males, respectively (97.5th percentile, 6.8 and 11.6 ng/L, respectively). Diagnostic sensitivity and specificity were 100%/97.1% and 96.2%/96.4%, for female/males, respectively. Patients (male/female) with primary hyperparathyroidism, renal failure, and neuroendocrine tumors showed CT concentrations >97.5th percentile in 33%/4.7%, 18.5%/10%, and 8.3%/12%, females/males, respectively. Peak serum CT concentrations were reached 2 min after calcium administration (161.7 and 111.8 ng/L in males and females, respectively; < 0.001).

Conclusions: Excellent analytical performance, low interindividual variability, and low impact of confounders for increased CT concentrations in non-MTC patients indicate that the investigated assay has appropriate clinical utility. Calcium-stimulated CT results suggest good test applicability owing to low interindividual variability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1373/clinchem.2016.270009DOI Listing
September 2017

Correlative study of dose to thyroid and incidence of subsequent dysfunction after head and neck radiation.

Head Neck 2017 03 1;39(3):548-554. Epub 2016 Dec 1.

Department of Radiation Oncology, The Ohio State University, Columbus, Ohio.

Background: Thyroid dysfunction is common after radiotherapy (RT) for patients with head and neck cancers. We attempted to discover RT dose parameters that correspond with RT-induced thyroid dysfunction.

Methods: Records of 102 patients who received RT from 2008 to 2010 were reviewed with respect to thyroid function. Abnormalities were grouped in 2 ways: (1) none, transient, or permanent; and (2) overt or subclinical.

Results: At median follow-up of 33.5 months, incidence of any thyroid abnormality was 39.2% (women vs men - 50% vs 35%). Permanent dysfunction was seen in 24.5% with higher incidence in women versus men (42.9% vs 17.6%; p = .0081). Permanent abnormalities most strongly correlated with D (p = .0275). V also correlated with thyroid dysfunction post-RT (p = .0316). Concurrent chemotherapy increased permanent dysfunction (p = .0008).

Conclusion: Achieving D <50 Gy, V <50%, and mean dose <54.58 Gy during RT planning may decrease the incidence; whereas female sex and concurrent chemotherapy seem to increase the risk of RT-induced hypothyroidism. © 2016 Wiley Periodicals, Inc. Head Neck 39: 548-554, 2017.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.24643DOI Listing
March 2017

LONG-TERM NONOPERATIVE RATE OF THYROID NODULES WITH BENIGN RESULTS ON THE AFIRMA GENE EXPRESSION CLASSIFIER.

Endocr Pract 2016 Jun 20;22(6):666-72. Epub 2016 Jan 20.

Objective: The primary objective was to assess the operative rate in patients with a benign result from the Afirma gene expression classifier (GEC) during long-term follow-up at nonacademic medical facilities. The secondary endpoint of this study was the treating physician's opinion regarding the safety of GEC use compared to the hypothetical situation of providing thyroid nodule management without the GEC.

Methods: This was a retrospective study of nonacademic medical practices utilizing the GEC. Those clinicians utilizing the GEC testing who had three or more 'benign' results during the data collection period (September 2010 through June 2014) were invited to participate. Operative status and patient demographics were documented for patients with GEC testing at least 36 months (± 3 months) prior to the date of data collection. A survey also was administered to the treating physicians to assess their perceived safety of using the GEC in patient care.

Results: During 36 months (± 3 months) of follow-up, 17 of 98 patients (17.3%) with a 'benign' GEC result underwent surgery. Within the first 2 years after a 'benign' GEC, 88% of surgeries were performed. Regarding safety of the GEC, the treating physicians reported that patient safety was improved by using the GEC compared to not using the GEC in 78 of 91 cases (86%).

Conclusion: It appears that a 'benign' result on the GEC is associated with a reduction in the rate of thyroid surgeries compared to published data when patients are followed for 36 months after testing. A nonoperative approach to follow-up was felt to be a safe alternative to diagnostic surgery by the majority of responsible physicians in the study.

Abbreviations: AUS = atypia of undetermined significance FLUS = follicular lesion of undetermined significance FN = follicular neoplasm FNA = fine-needle aspiration GEC = gene expression classifier.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4158/EP151006.ORDOI Listing
June 2016

Ernest L. Mazzaferri, MD, MACP (1936-2013).

Thyroid 2013 Aug;23(8):917-23

Department of Endocrinology, Veracyte, Inc., South San Francisco, California, USA.

Professor and physician Dr. Ernest L. Mazzaferri Sr. passed away on May 14, 2013, at 76 years of age ( 1 , 2 ). Ernie is remembered as a caring and talented physician, an accomplished scholar and educator, as well as a loving husband, father, and grandfather. He was a luminary figure, and few people have had a greater impact in thyroidology in recent decades. Here we include reflections from a few of us that knew him, as well as commentaries from people who did not. Ernie's passion was caring for patients and how to improve their care. Our goal is to pay tribute and memorialize the person we knew and the impact that he had on patients around the world through his dedication to research, lecturing, and writing that achieved remarkable global influence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/thy.2013.2308.obDOI Listing
August 2013

In thyroidectomized patients with thyroid cancer, a serum thyrotropin of 30 μU/mL after thyroxine withdrawal is not always adequate for detecting an elevated stimulated serum thyroglobulin.

Thyroid 2013 Feb;23(2):185-93

Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA.

Background: The thyrotropin (TSH) level or duration of thyroid hormone withdrawal (THW) required to detect stimulated thyroglobulin (Tg) in differentiated thyroid cancer (DTC) monitoring is unknown. The objective of this study was to evaluate the TSH cutoff of >30 μU/mL as a means to detect stimulated Tg ≥2 ng/mL after THW (THW-Tg≥2), and sensitivity of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire for detecting hypothyroid symptoms.

Methods: This was a prospective longitudinal cohort study done at a tertiary academic medical center. Forty-seven patients with DTC undergoing their first Tg stimulation or after previously abnormal Tg stimulation had weekly measurements of TSH and Tg during the 4 weeks THW, and repeated questionnaire assessments.

Results: TSH did not reach a plateau in any patient, and in those whose Tg did not remain undetectable, Tg continued to rise. Seventy-five percent of patients had an undetectable Tg <0.2 ng/mL at baseline (95% were <0.5 mg/mL) with 16% remaining undetectable throughout THW. The majority of patients (72.7% and 97.8%) achieved TSH >30 μU/mL by 3 and 4 weeks THW, respectively. Of the 15 patients with maximum stimulated THW-Tg≥2, 38% were detected before the minimal TSH >30 μU/mL cutoff. At 2 weeks THW, 3 had a TSH>30 μU/mL, and none of them had Tg ≥2 ng/mL. At 3 weeks THW, 11 had a TSH >30 μU/mL, and 64% of them had Tg ≥2 ng/mL. Only 60% were detected at 3-week THW regardless of their TSH level. Eighty-six percent were detected by TSH 60-<80 μU/mL. Conversely, all patients whose serum Tg was <0.2 ng/mL when their serum TSH was >20 μU/mL did not achieve a THW-Tg≥2.

Conclusion: The minimal TSH cutoff of >30 μU/mL was inadequate to detect many patients with final stimulated THW-Tg≥2 during complete THW. TSH >80-100 μU/mL was a better cutoff, achieved in only 53% after 4-week THW. Conversely, we propose a preliminary THW-stopping rule for ending THW early in selected patients. In patients with a Tg <0.2 ng/mL when TSH >20 μU/mL, all had a final stimulated Tg ≤2 ng/mL, potentially saving qualifying patients 40% of THW duration compared to 4-week THW. FACIT-F correlated with TSH, but was not sensitive to detect mild hypothyroidism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/thy.2012.0327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919477PMC
February 2013

Imaging of thyrotoxicosis.

Am J Med 2012 Sep;125(9):S1-2

Division of Endocrinology, The Ohio State University, Columbus, USA.

The diagnostic algorithm for patients with Graves' disease frequently involves the use of thyroid autoantibody testing and radioisotope scanning (full text available online: http://education.amjmed.com/pp1/248). However, ultrasound has myriad uses in the evaluation of patients with hyperthyroidism. The purpose of this paper is to review the medical literature outlining the important role that ultrasonography (US) can play in the diagnosis and management of patients with hyperthyroidism. We will make a case for the use of ultrasonography in the initial evaluation of all patients with thyrotoxicosis. This review will delineate the advantages of ultrasonography compared to nuclear medicine imaging in determining the etiology of the hyperthyroidism. The role of sonography in predicting remission and relapse of Graves' disease will also be examined. Finally, this paper will detail the importance of ultrasonography in the workup of hyperthyroidism during pregnancy. We will also outline its utility for predicting fetal thyroid dysfunction in maternal Graves' disease without the need for cordocentesis and its attendant complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjmed.2012.05.012DOI Listing
September 2012

Graves' disease: diagnostic and therapeutic challenges (multimedia activity).

Am J Med 2011 Jun;124(6):S2-3

Department of Medicine, Gutenberg University Medical Center, Mainz, Germany.

Graves' disease is the most common cause of hyperthyroidism in the United States. Graves' disease occurs more often in women with a female:male ratio of 5:1 and a population prevalence of 1% to 2%. A genetic determinant to the susceptibility to Graves' disease is suspected because of familial clustering of the disease, a high sibling recurrence risk, the familial occurrence of thyroid autoantibodies, and the 30% concordance in disease status between identical twins. Graves' disease is an autoimmune thyroid disorder characterized by the infiltration of immune effector cells and thyroid antigen-specific T cells into the thyroid and thyroid-stimulating hormone receptor expressing tissues, with the production of autoantibodies to well-defined thyroidal antigens, such as thyroid peroxidase, thyroglobulin, and the thyroid-stimulating hormone receptor. The thyroid-stimulating hormone receptor is central to the regulation of thyroid growth and function. Stimulatory autoantibodies in Graves' disease activate the thyroid-stimulating hormone receptor leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Below-normal levels of baseline serum thyroid-stimulating hormone receptor, normal to elevated serum levels of T4, elevated serum levels of T3 and thyroid-stimulating hormone receptor autoantibodies, and a diffusely enlarged, heterogeneous, hypervascular (increased Doppler flow) thyroid gland confirm diagnosis of Graves' disease (available at: http://supplements.amjmed.com/2010/hyperthyroid/faculty.php). This Resource Center is also available through the website of The American Journal of Medicine (www.amjmed.com). Click on the “Thyroid/Graves' Disease” link in the “Resource Centers” section, found on the right side of the Journal homepage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjmed.2011.03.001DOI Listing
June 2011

Thyroid cancer: emerging role for targeted therapies.

Ther Adv Med Oncol 2010 Jan;2(1):3-16

Division of Endocrinology, The Ohio State University, Columbus, OH, USA.

The histology and clinical behavior of thyroid cancer are highly diverse. Although most are indolent tumors with a very favorable outcome with the current standard of care therapy, a small subset of tumors may be among the most lethal malignancies known to man. While surgery and radioactive iodine are the standard of care for differentiated thyroid cancers (DTC) and are effective in curing a majority of such patients, those with iodine-resistant cancers pose a great challenge for clinicians, as these patients have limited treatment options and poor prognoses. Medullary thyroid carcinoma (MTC) has no effective systemic therapy despite the genetic and signaling defects that have been well characterized for the last two decades. Anaplastic thyroid cancer (ATC) is one of the most aggressive solid tumors that remains fatal despite conventional multimodality therapy. Increased understanding of the pathogenesis of papillary thyroid carcinoma, the most common type of DTC, as well as ATC, has led to the development of targeted therapies aimed at signaling pathways and angiogenesis that are critical to the development and/or progression of such tumors. Development of tyrosine kinase inhibitors targeting known pathogenetic defects in MTC has led to testing of such agents in the clinic. Numerous clinical trials have been conducted over the last 5 years to examine the effects of these targeted molecular therapies on the outcomes of patients with iodine-refractory DTC, MTC and ATC. Conduction of such trials in the last few years represents a major breakthrough in the field of thyroid cancer. Several trials testing targeted therapies offer promise for setting new standards for the future of patients with progressive thyroid cancer. The purpose of this paper is to outline the recent advances in understanding of the pathogenesis of thyroid cancer and to summarize the results of the clinical trials with these targeted therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1758834009352667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126004PMC
January 2010

Advances in ultrasound for the diagnosis and management of thyroid cancer.

Authors:
Jennifer A Sipos

Thyroid 2009 Dec;19(12):1363-72

Division of Endocrinology and Metabolism, The Ohio State University , Columbus, Ohio, USA.

Background: Ultrasonography (US) is increasingly being employed by endocrinologists and surgeons in the diagnosis and management of patients with thyroid nodules and thyroid cancer. Recent consensus guidelines from the American Thyroid Association highlight the importance of this modality by recommending that patients with thyroid nodules should undergo further evaluation with cervical US to stratify the risk of malignancy. Likewise, ultrasound is advocated for the preoperative and postoperative diagnosis of cervical lymph node metastases.

Summary: This article will summarize the US characteristics that impart a suspicious appearance on thyroid nodules and cervical lymph nodes as well as those findings that are reassuring. Likewise, the indications for thyroid nodule and lymph node fine-needle aspiration will be reviewed. Finally, this article will briefly discuss adjunctive tools in US such as elastography, percutaneous ethanol ablation, and radiofrequency ablation.

Conclusions: US may be used to help stratify the risk of malignancy in thyroid nodules and cervical lymph nodes. This tool further aids in the diagnosis of malignancy when used in conjunction with fine-needle aspiration. US plays an important role as both a diagnostic and therapeutic tool in the evaluation of patients with neck masses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/thy.2009.1608DOI Listing
December 2009

Do tumor characteristics predict risk of malignancy in thyroid nodules with indeterminate cytology?

Nat Clin Pract Endocrinol Metab 2009 Mar 3;5(3):140-1. Epub 2009 Feb 3.

Division of Endocrinology, Diabetes and Metabolism, Ohio State University College of Medicine, Columbus, OH 43210, USA.

The use of ultrasonography-guided, fine-needle aspiration cytology (FNAC) has enhanced the preoperative characterization of thyroid nodules and reduced the need for diagnostic surgeries. However, complete preoperative characterization is not yet possible for patients with an indeterminate FNAC result. Here, results are discussed from a retrospective study by Banks et al. that aimed to refine preoperative risk assessment of thyroid cancer in patients with indeterminate FNAC results. The authors found that patients' age, nodule size and specific cytological diagnoses were all associated with thyroid malignancy. These variables were used to construct a diagnostic predictor model. The study by Banks et al. provides general guidance for clinicians who need to estimate thyroid cancer risk for patients with indeterminate FNAC results. Refinements in risk assessment for thyroid malignancy might help to individualize care of these patients; however, the results also underscore the need for enhanced diagnostic methods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ncpendmet1078DOI Listing
March 2009

Iodine-refractory differentiated thyroid cancer: an ominous diagnosis with the potential for a brighter future.

Clin Adv Hematol Oncol 2008 Oct;6(10):767-9

The Ohio State University Medical Center, Columbus, OH 43210, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
October 2008

The therapeutic management of differentiated thyroid cancer.

Expert Opin Pharmacother 2008 Oct;9(15):2627-37

University of Florida, 1600 Archer Road, PO Box 100226, Gainesville, FL 32610, USA.

Background: The management of thyroid cancer is difficult because the tumors comprise a wide range of biologic behaviors, from small papillary thyroid microcarcinomas that pose little or no threat to survival for the patient, to anaplastic thyroid cancers that are arguably the most lethal tumor. Although it may be difficult initially to determine at which end of the prognostic spectrum a patient resides, one can ordinarily estimate a patient's risk for tumor recurrence and mortality based on a triad of features as simple as the patient's age at the time of diagnosis, the tumor stage at presentation, and its initial response to therapy. While staging systems are available to assist in the management process, all are inexact and leave wide gaps in the treatment plan for a given patient. This is largely because randomized controlled trials are lacking as a result of the low incidence and generally favorable prognosis of the disease. As a practical matter, it may sometimes be difficult to reassure a patient, given the generally favorable prognosis of this group of tumors, knowing that without adequate therapy some become unexpectedly aggressive and recur years after initial management. The treatment of these tumors rests on a fine balance of providing care that reflects the anticipated course of the disease without overtreating the patient or providing reassurance that is unfounded.

Objective: To outline the treatment strategy for patients with differentiated thyroid cancer based on the available literature and to guide clinicians through a management algorithm utilizing patient and tumor characteristics.

Methods: This review is limited to the treatment of patients with differentiated thyroid cancer - papillary and follicular thyroid cancer - and the standard therapy required for the majority of patients.

Results/conclusion: The treatment of differentiated thyroid cancer requires a multidisciplinary approach, involving an experienced surgeon, radiologists and an endocrinologist. There are many unanswered questions in the management algorithm and ongoing research is needed to further define the best treatment strategy for patients with differentiated thyroid cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1517/14656566.9.15.2627DOI Listing
October 2008