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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.

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.

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, In this study, the prevalence of cancer and noninvasive follicular thyroid neoplasm with papillary‐like nuclear features in PET positive cytologically indeterminate thyroid nodules was 28.6–36.4% depending on the method of calculation. The benign call rate of Afirma GSC in these nodules was 64%. When combining Afirma GEC/GSC tested PET positive cytologically indeterminate thyroid nodules, the benign call rate was higher in nodules with a lower risk sonographic pattern.

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.

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

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 BRAF(V600E), NRAS(Q61R), and HRAS(Q61R) 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 BRAF(V600E) appears lower in papillary thyroid carcinomas from AA patients of >80% African ancestry (3/14; 21%) than in AA patients of

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.

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.

Introduction: Somatic mutations of RAS- and BRAFV600E- are the most common driver mutation in thyroid cancer (TC) and in the majority of cases, these are mutually exclusive1,2. Clinical characteristics of TC with either RAS or BRAFV600E mutation is not systemically studied. Methods: This is a retrospective study at the Ohio State University (OSU) from 1/2000 to 12/2018. Data were extracted from OSU Endocrine Neoplasia Repository (ENR). Medullary thyroid cancer was excluded. The treating physician determined patient management. Statistical analysis was performed with the chi-square test for categorical values and Mann-Whitney U test for continuous unpaired values. Two-sided P values of less than 0.05 were considered statistically significant. Results: Out of 320 patients, 152 patients had a positive mutational profile. Of these, 128 patients had a BRAFV600E mutation and 14 had a RAS mutation. Details of RAS mutation were as follows; NRASQ61K (n=2), NRASQ61R (n=1), HRASQ61R (n=1), HRASQ61K (n=1), NRAS without further details (n=9). Local lymph node metastasis was significantly less in RAS mutated cancer (58% vs 16%, p Conclusion: Thyroid cancer associated with a RAS-mutation has less tendency to metastasize locally and has a higher incidence of bone metastasis compared to thyroid cancer with BRAFV600E-mutation. Individualized clinical follow up may be indicated depends on their mutational profile. References: 1. Cancer Genome Atlas Research N. Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014;159(3):676-690. 2. Nikiforova MN, Lynch RA, Biddinger PW, et al. RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma. J Clin Endocrinol Metab. 2003;88(5):2318-2326.

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 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.

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.

RAS mutations are common in the available mutational analysis of cytologically indeterminate (Cyto-I) thyroid nodules. However, their reported positive predictive value (PPV) for cancer is widely variable. The reason for this variability is unknown, and it causes clinical management uncertainty. A systematic review was performed, evaluating the PPV for cancer in RAS mutation positive Cyto-I nodules, and variables that might affect residual heterogeneity across the different studies were considered.PubMed was searched through February 22, 2017, including studies that evaluated at least one type of RAS mutation in Cyto-I nodules, including any (or all) of the Bethesda III/IV/V categories or their equivalents and where the histological diagnosis was available. The PPV residual heterogeneity was investigated after accounting for Bethesda classification, blindedness of the histopathologist to the RAS mutational status, Bethesda category-specific cancer prevalence for each study, and which RAS genes and codons were tested. This was studied using five meta-regression models fit to different sets of Bethesda classification categories: Bethesda III, IV, or V (III/IV/V); Bethesda III or IV (III/IV); Bethesda III only; Bethesda IV only; and Bethesda V only.Of 1831 studies, 23 were eligible for data inclusion. Wide ranges of PPV were found at 0-100%, 28-100%, and 0-100% in Bethesda III, IV, and V, respectively. Residual heterogeneity remained moderately high for PPV after accounting for the above moderators for Bethesda III/IV/V (21 studies; IThe PPV of RAS mutations in Bethesda III and IV categories is quite heterogeneous across different studies, creating low confidence in the accuracy of a single estimate of PPV. Clinicians must appreciate this wide variability when managing a RAS-mutated Cyto-I nodule. Future studies should seek to resolve this unexplained variability.

OBJECTIVE: Post-operative thyroglobulin (Tg) levels can predict the likelihood of residual cancer, including distant metastases, thereby influencing postsurgical treatment strategies even in patients with low-risk disease. Circulating anti-thyroglobulin antibodies (anti-Tg Abs) interfere with Tg measurement preventing this clinical use. It is not known if the presence of anti-Tg Abs predicts metastatic disease on post-therapy scan in patients with low-risk disease or if they should influence the use or dose of I-131 therapy. In the present study, we compare post-therapy scans in low-risk patients with and without anti-Tg Abs. METHODS: This is a single-institution retrospective study. The study population (Group A) included all patients with low-risk differentiated thyroid cancer (DTC) who underwent total thyroidectomy and RAI between 1/1/2006 to 9/11/2015 with intrathyroidal T1–T2, Nx, N0 or N1a (≤5 nodes all measuring, when reported

Thyroglobulin (Tg) measurement in patients with positive antithyroglobulin antibodies (anti-TgAbs) is not reliable. Tg measurement using liquid chromatography-tandem mass spectrometry (LC/MS) may be useful in this setting.This is a retrospective study with the objective of determining the accuracy of Tg-LC/MS in patients with thyroid cancer with anti-TgAbs. All patients with follicular cell-derived thyroid cancer (TC) who had thyroglobulin measured using LC/MS assay from November 1, 2013, to November 7, 2014, were evaluated. The frequency of detectable Tg-LC/MS was evaluated, with a functional sensitivity (FS) of 0.5 ng/mL in patients with structural disease. Then performance of Tg-LC/MS versus Tg immunometric assay (IMA) was compared using either Immulite assay (Tg-1) with a FS of 0.9 ng/mL or Beckman assay (Tg-B) with a FS of 0.1 ng/mL in detecting structural disease in patients with positive anti-TgAbs.A total of 154 consecutive patients were included in this evaluation. Of these, 116 (75%) patients were positive for anti-TgAbs. In patients with structural disease and positive anti-TgAbs, Tg-LC/MS was undetectable in 43.7% of patients. Then the diagnostic accuracy for structural disease of Tg-LC/MS was compared with each Tg-IMA assay separately. In the 26 patients with positive anti-TgAbs where a Tg-I assay was used, the sensitivity and specificity for detecting structural disease were 33.3% and 88.2%, respectively, for the Tg-I assay, and 44.4% and 94.1%, respectively, for the Tg-LC/MS assay. In the 74 patients with positive anti-TgAbs where Tg-B was used, the sensitivity and specificity for detection of structural disease were 72.7% and 71.4%, respectively, for the Tg-B assay, and 62.6% and 93.7%, respectively, for the Tg-LC/MS assay.In patients with thyroid cancer with positive anti-TgAbs, Tg-LC/MS was frequently undetectable and was less sensitive for detecting disease than a Tg assay was with a functional sensitivity of 0.1 ng/mL. For patients with detectable Tg-LC/MS and anti-TgAbs, use of the assay for monitoring requires further prospective studies.

A 60-year-old man who was recently diagnosed with lung adenocarcinoma underwent 18F-FDG positron emission tomography/computed tomography (FDG PET/CT) scan for staging. The FDG PET/CT scan showed incidental hypermetabolic uptake in the pituitary gland and focal hypermetabolic activity in the left thyroid lobe. Histopathologic evaluation revealed these to be a non-functioning pituitary adenoma and papillary thyroid cancer, respectively. Incidental hypermetabolic uptake in the pituitary and thyroid glands on FDG PET/CT scan are uncommon. It is important to determine their etiologies as this may lead in some cases to incorrect staging of the primary cancer and, therefore, inappropriate clinical management. In this case report we will discuss the clinical presentation and the imaging findings of this patient and review the related literature.

Objective. Thyroid disease has been reported among the endocrinopathies that can occur after treatment with ipilimumab. Graves’ disease, however, has been rarely reported with this medication. Here we report a case of Graves’ disease diagnosed after initiation of ipilimumab in a patient with melanoma.Methods. We present the clinical presentation and management course of this patient followed by a related literature review.Results. A 67-year-old male with metastatic melanoma was started on ipilimumab. He developed hyperthyroidism after two doses of ipilimumab. The cause of hyperthyroidism was determined to be Graves’ disease. Ipilimumab was held and the patient was started on methimazole with return to euthyroid status. Ipilimumab was resumed and the patient continued methimazole during the course of ipilimumab therapy, with controlled hyperthyroidism. Restaging studies following four cycles of ipilimumab showed complete response in the lungs, with residual melanoma in the neck. The patient then underwent total thyroidectomy and left neck dissection as a definitive treatment for both hyperthyroidism and residual melanoma.Conclusion. Graves’ disease can develop after starting ipilimumab and methimazole can be an effective treatment. For patients whose hyperthyroidism is well-controlled on methimazole, ipilimumab may be resumed with close monitoring.

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.

Immune checkpoint inhibitors (ICI) represent an important milestone in the modern era of antineoplastic therapy and have ushered optimism amongst oncologists and patients alike. These agents, however, are associated with significant potential toxicities, the importance of which cannot be overstated. The clinical presentation, diagnosis, and management strategies of immune-related endocrinopathies associated with ICI use are described in this case-based review.An increasing number of ICI have shown promise in the management of various malignancies in the recent years. These include cytotoxic T lymphocyte antigen-4 inhibitors, programmed cell death 1 (PD-1) antibodies, and PD-ligand 1 (PD-L1) antibodies. Several endocrinopathies, including hypophysitis, thyroid dysfunction, hyperglycemia, and primary adrenal insufficiency, have been associated with the use of these agents. Toxicities may range from mild transient laboratory abnormalities to potentially life-threatening ones, warranting immediate therapeutic intervention. Combination ICI therapies may be associated with a greater risk of endocrine dysfunction when compared with monotherapy. The clinical presentation and laboratory assessment of these patients often pose a diagnostic challenge as they may be confused by the symptoms related to their underlying malignancy or potential associated acute illnesses.ICI use is associated with serious endocrinopathies that may have a nonspecific initial presentation. A constant eye for these symptoms and a systematic approach to diagnosis are essential for prompt initiation of therapy and prevention of significant complications.

Increasingly, patients with thyroid nodule cytology labeled atypical (or follicular lesion) of undetermined significance (AUS/FLUS) or follicular neoplasm (FN) undergo diagnostic analysis with the Afirma gene expression classifier (GEC). No long-term, multisite analysis of Afirma GEC performance has yet been performed.We analyzed all patients who had received Afirma GEC testing at five academic medical centers between 2010 and 2013. Nodule and patient characteristics, fine needle aspiration cytology, Afirma GEC results, and subsequent clinical or surgical follow-up were obtained for 339 patients. Results were analyzed for pooled test performance, impact on clinical care, and site-to-site variation.Three hundred thirty-nine patients underwent Afirma GEC testing of cytologically indeterminate nodules (165 AUS/FLUS; 161 FN; 13 suspicious for malignancy) and 174 of 339 (51%) indeterminate nodules were GEC benign, whereas 148 GEC were suspicious (44%). GEC results significantly altered care recommendations, as 4 of 175 GEC benign were recommended for surgery in comparison to 141 of 149 GEC suspicious (P.01). Of 121 Cyto Indeterminate/GEC Suspicious nodules surgically removed, 53 (44%) were malignant. Variability in site-to-site GEC performance was confirmed, as the proportion of GEC benign varied up to 29% (P=.58), whereas the malignancy rate in nodules cytologically indeterminate/GEC suspicious varied up to 47% (P=.11). Seventy-one of 174 GEC benign nodules had documented clinical follow-up for an average of 8.5 months, in which 1 of 71 nodules proved cancerous.These multicenter, clinical experience data confirm originally published Afirma GEC test performance and demonstrate its substantial impact on clinical care recommendations. Although nonsignificant site-to-site variation exists, such differences should be anticipated by the practicing clinician. Follow-up of GEC benign nodules thus far confirm the clinical utility of this diagnostic test.

Thyroid cancer is an increasingly prevalent malignancy throughout the world. Management guidelines for both thyroid nodules and thyroid cancer have been published and updated by a number of societies internationally. All of these guidelines recognize this increasing incidence, particularly of small papillary thyroid cancers, due in part to improved technology enabling early or even ‘over’ diagnosis. Recent advances in molecular imaging and molecular methods have been developed to better characterize thyroid nodules, and a number of studies that have clarified risk stratification systems that can be modified over time allow for individualization of diagnosis, initial treatment, and subsequent follow-up strategies. Advances in surgical approaches and new treatments for patients with the most aggressive forms of thyroid cancer have all influenced management guidelines. Despite substantial similarities, there also are important differences between recent guidelines for some of the common clinical scenarios encountered by physicians in clinical practice. In the present manuscript, we will highlight similarities and differences between several of the most recently published guidelines focused on key areas of importance to clinical care and controversy. These are key areas for future research to strengthen the data to support future guideline recommendations.

Purpose To determine the prevalence of secondary causes of bone loss among patients with breast cancer with osteopenia and osteoporosis. Patients and Methods All women referred to a bone health clinic over a 6-year period for bone evaluation were included in this retrospective study and stratified based on presence or absence of a breast cancer history. The prevalence of secondary causes of bone loss in the two groups was compared. Results Of the 238 women identified, 64 women had breast cancer. The non–breast cancer group (n = 174) was significantly older (P = .015), had a lower mean weight (P = .019), lower 25 hydroxy-vitamin D level (P = .019), and greater degree of bone loss in both the spine and hip (P < .001 and 0.004, respectively). The presence of at least one secondary cause of bone loss, excluding cancer-related therapies, was seen in 78% of the breast cancer patient group and in 77% of the non–breast cancer group (P = not significant). Newly diagnosed metabolic bone disorders were seen in 58% of the breast cancer population. The most common was vitamin D deficiency, seen in 38% of patients in the breast cancer group and 51% of patients in the non–breast cancer group. Idiopathic hypercalciuria was diagnosed in 15.6%, primary hyperparathyroidism in 1.6%, and normocalcemic hyperparathyroidism in 3.1% of the breast cancer population. Conclusion A high prevalence of secondary causes of bone loss among patients with breast cancer supports a comprehensive evaluation in these patients, particularly those considering therapy with an aromatase inhibitor.

K.D., a 20-year-old white female college student was brought by her parents for evaluation of hypoglycemia. She had experienced multiple episodes of palpitations, blurred vision, and left facial paresthesias for a year, progressively worsening and occurring more frequently in the 2 months just before her appointment. Usually the episodes occurred between 3:00 and 7:30 p.m. The symptoms occurred without regard to meals and were relieved with food or juice. Her most severe witnessed episode, which occurred while she was at college, happened a few days before the consultation, while K.D. was working, 2 hours postprandially. Observers reported that she appeared confused, agitated, and diaphoretic. Her glucose via fingerstick by paramedics was 35 mg/dl. She received intravenous dextrose, and subsequently her glucose rose to 217 mg/dl with resolution of her symptoms. She had several episodes with neuroglycopenic symptoms and glucose levels of 35-45 mg/dl. There was no history indicating diabetic medications in her home. She also complained of a 25-lb weight gain during the past year. A year before her visit, K.D. was diagnosed with diabetes by oral glucose tolerance test (OGTT). The results were: View this table: At that time, she had a normal hemoglobin A1c, and she was instructed in diet and exercise. No antidiabetic medications had been prescribed. K.D. had a psychiatric evaluation, was diagnosed with depression, and was started on sertraline. In the month before the consultation, she also had a neurological work-up with negative computed tomography scans of the head and normal electroencephalogram. Her family history was significant only for diabetes of a maternal aunt. She denied allergies or use of cigarettes, alcohol, or illicit drugs. She was taking sertraline, 50 mg daily for the past year; ethinyl estradiol/norgestimate, one daily for the past 2 years; and oxcarbazepine, 175 mg twice daily for the …

A number of patients with poor glycemic control receive the diagnosis of type 2 diabetes despite the fact that they do not exhibit some of the traditional characteristics of the disease, such as obesity. A more accurate diagnosis for many of these patients is latent autoimmune diabetes of adulthood (LADA). In this article, Dr Nabhan and coauthors describe features that LADA has in common with type 1 and type 2 diabetes, as well as those that distinguish LADA from these more widely recognized forms of diabetes. The authors also describe the pathogenesis of the disease, potential complications, and treatment options.

Lingual thyroid and thyroid hemiagenesis are rare thyroid developmental abnormalities. These conditions can be present with other thyroid diseases, whether functional ones involving abnormal thyroid hormone levels, or structural ones such as presence of thyroid nodules, however the association with thyroid cancer and lingual thyroid or thyroid hemiagenesis is rare. In addition to that, when thyroid hemiagenesis is present, it is usually in the left lobe. We describe here a pregnant patient who presented with metastatic cervical nodes from thyroid cancer who was found on imaging to have right thyroid hemiagenesis. After she underwent an initial surgery for thyroid cancer and metastatic nodal disease, she was then later discovered to have a lingual thyroid. In this case we report this extremely rare combination and also discuss the potential implications of this association on the diagnosis and management of these patients particularly initial surgery and imaging studies needed for the thyroid cancer.

To control rain ingress, the Exterior Insulation and Finish Systems (EIFS) can be constructed with one of two design principles • a drain screen (rain screen, pressure equalized rain screen-PER) approach • a face sealed (barrier) approach While the barrier approach has an inherently higher risk for moisture damage, it offers econormc advantages and may be successfully used under a multitude of cli matic and service conditions. Its performance evaluation is carried out in three steps: 1. Examine whether this system can be used for a specific set of climatic and use con ditions 2. Formulate necessary measures for material and field quality control in the design specifications 3. Examine the system for integrity under cycling environmental conditions and long-term performance Step 1 of this evaluation is based on the moisture control strategy of the whole wall assembly. Step 2 requires the addition of several small-scale material tests, and Step 3 involves full-scale system testing. The full scale testing is necessary to incor porate several parameters that act on the system simultaneously (thermal stress, thermal and moisture originated expansion and contraction, structural movements, material changes caused by weathering and aging, presence of moisture, etc.). The in teraction among these factors may provide conditions with severity significantly in excess of those achieved when these parameters are tested separately. This discussion paper consists of three parts: Part 1: Deals with the assessment of constituent materials of the EIFS with a view to ensuring (characterizing) hygrothermal performance of the system (by testing and characterization of the constituent materials, one may limit the range of variation in the hygrothermal performance of the whole system). Part 2: Postulates a new test for evaluation of EIFS integrity under simulated expo sure to climatic cycling. Part 3: Recommends EIFS design solutions and construction details for both new and retrofit construction. These details are discussed in the context of specific environmental/climatic conditions. This will be published in a later issue of JTIBE. Testing EIFS cladding systems for integrity under simulated exposure to climatic cycling involves preconditioning under simultaneous exposure to a water vapor gra dient and temperature gradient followed by exposure to severe conditions of one- sided, uni-directional climatic cycling. The testing and characterization of the con stituent materials (Step 1) coupled with the full-scale test for EIFS integrity under exposure to climatic cycling (Step 2) will increase the reliability of the EIFS systems in North America. Part 3 fills the gap between the current understanding of moisture control princi ples and construction practices. Many small changes in materials and technology create a compound effect that increases the frequency of inadequate field perform ance. Though most inherent EIFS flaws may be minor, those, when coupled with a number of failures of wall systems involving EIFS, caused an adverse attitude toward EIFS, perhaps more prevalent in some regions of North America. This paper pro vides a fundamental framework to cement many of the previously postulated correc tive measures into a coherent package aiming at the improvement of the EIFS reli ability in North America.

Anti-thyroglobulin antibodies are commonly identified in patients with differentiated follicular cell-derived thyroid cancer. When present, they interfere with the measurement of thyroglobulin (Tg), which is the primary biochemical marker used for disease surveillance, creating challenges in monitoring patients for residual or recurrent disease. Moreover, there is variability in measuring anti-Tg antibodies according to the different assays, such that not all patients with anti-Tg antibodies are identifiable on a single assay system. The persistence of anti-Tg antibodies, especially if levels are rising, may indicate persistent, recurrent, or progressive thyroid cancer. In contrast, declining anti-Tg antibody levels may indicate reduced tumor burden or the absence of disease. In this review, we will explore in a case-based manner the data supporting monitoring and treatment paradigms for patients with anti-Tg antibodies and will stress areas where more evidence is needed to better inform clinicians regarding the management of patients with this challenging situation.

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.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 glucose180 mg/dL. Median inpatient glucose levels in patients with diabetes were assessed using statistical process control methodology.Between January 2004 and September 2007, median glucose for all inpatients with diabetes decreased 15% from 159 mg/dL to135 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.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.