Fifteen-Year History of Virilization in a 17th-Century Woman.

The Spanish artist, Jusepe de Ribera, painted a portrait of a virilized woman in 1631. He provided a brief clinical history on stone tablets, which indicates that the woman most likely harbored a benign, androgen-secreting ovarian tumor for 15 years.

Are Prepubertal Gynaecomastia and Premature Thelarche Linked to Topical Lavender and Tea Tree Oil Use?

Various studies, conducted since 2007, have reported a total of eight boys with prepubertal gynaecomastia and four girls with premature thelarche following exposure to lavender and/or tree tea oil. All patients experienced regression of the breast tissue after they stopped using these oils. Both of these essential oils, and several of their constituents, have oestrogenic and antiandrogenic activity in vitro. However, limited dermal penetration of some of the components means that the in vitro findings cannot be extrapolated to the in vivo situation. There are unanswered questions as to how much lavender or tea tree oil was actually present in the skincare products used by the children and a lack of information about exposure to other agents. Furthermore, since both prepubertal gynaecomastia and premature thelarche often spontaneously regress, it cannot be concluded that the use of lavender and/or tree tea oil is the cause of the gynaecomastia and thelarche in these children.

Expanded Parameters in Active Surveillance for Low-risk Papillary Thyroid Carcinoma: A Nonrandomized Controlled Trial.

Importance: Unlike for prostate cancer, active surveillance for thyroid cancer has not achieved wide adoption. The parameters by which this approach is feasible are also not well defined, nor is the effect of patient anxiety. Objective: To determine if expanded size/growth parameters for patients with low-risk thyroid cancer are viable, as well as to assess for cohort differences in anxiety. Design, Setting, and Participants: This prospective nonrandomized controlled trial was conducted at a US academic medical center from 2014 to 2021, with mean [SD] 37.1 [23.3]-month follow-up. Of 257 patients with 20-mm or smaller Bethesda 5 to 6 thyroid nodules, 222 (86.3%) enrolled and selected treatment with either active surveillance or immediate surgery. Delayed surgery was recommended for size growth larger than 5 mm or more than 100% volume growth. Patients completed the 18-item Thyroid Cancer Modified Anxiety Scale over time. Interventions: Active surveillance. Main Outcomes and Measures: Cumulative incidence and rate of size/volume growth. Results: Of the 222 patients enrolled, the median (IQR) age for the study population was 46.8 (36.6-58) years, and 76.1% were female. Overall, 112 patients (50.5%) underwent treatment with active surveillance. Median tumor size was 11.0 mm (IQR, 9-15), and larger tumors (10.1-20.0 mm) comprised 67 cases (59.8%). One hundred one (90.1%) continued to receive treatment with active surveillance, 46 (41.0%) had their tumors shrink, and 0 developed regional/distant metastases. Size growth of more than 5 mm was observed in 3.6% of cases, with cumulative incidence of 1.2% at 2 years and 10.8% at 5 years. Volumetric growth of more than 100% was observed in 7.1% of cases, with cumulative incidence of 2.2% at 2 years and 13.7% at 5 years. Of 110 patients who elected to undergo immediate surgery, 21 (19.1%) had equivocal-risk features discovered on final pathology. Disease severity for all such patients remained classified as stage I. Disease-specific and overall survival rates in both cohorts were 100%. On multivariable analysis, immediate surgery patients exhibited significantly higher baseline anxiety levels compared with active surveillance patients (estimated difference in anxiety scores between groups at baseline, 0.39; 95% CI, 0.22-0.55; P < .001). This difference endured over time, even after intervention (estimated difference at 4-year follow-up, 0.50; 95% CI, 0.21-0.79; P = .001). Conclusions and Relevance: The results of this nonrandomized controlled trial suggest that a more permissive active surveillance strategy encompassing most diagnosed thyroid cancers appears viable. Equivocal-risk pathologic features exist in a subset of cases that can be safely treated, but suggest the need for more granular risk stratification. Surgery and surveillance cohorts possess oppositional levels of worry, elevating the importance of shared decision-making when patients face treatment equivalence. Trial Registration: ClinicalTrials.gov Identifier: NCT02609685.

Spurious Serum Hormone Immunoassay Results: Causes, Recognition, Management.

For over 50 years, immunoassays have been extensively used to quantitate hormones in blood, other fluids and tissues. Each assay has its own sensitivity, specificity and other analytical components. Despite the differences between commercial products, these assays provide important clinical information about hormone levels in patients. However, inaccurate results can occur because of technical issues, as well as patient-specific factors that can interfere with immunoassay hormone measurements. The latter include excessive normal blood or serum components, the presence of cross-reacting substances, extremely high levels of hormones leading to the high-dose hook effect, and interference from a variety of endogenous factors such as human antibodies that interact with the assay components or high levels of biotin in the serum from exogenous ingestion. This article briefly reviews the sources and recognition of endogenous interference, and describes methods to determine the correct serum hormone concentration.

Predictive Impact of Metastatic Lymph Node Burden on Distant Metastasis Across Papillary Thyroid Cancer Variants.

Background: While numerous factors determine prognosis in papillary thyroid carcinoma (PTC), distant metastasis (M1) represents one of the most dire. Escalating nodal burden and aggressive histology may contribute to higher metastatic risk, but this relationship is poorly defined and challenging to anticipate. We evaluate the predictive impact of these histological features on predicting distant metastases at initial presentation. Methods: Univariate and multivariable logistic regression models of conventional and aggressive thyroid cancer variants (well-differentiated papillary thyroid carcinoma [WDPTC], diffuse sclerosing variant [DSV], tall cell variant [TCV], poorly differentiated thyroid cancer [PDTC], and anaplastic thyroid carcinoma [ATC]) identified via U.S. cancer registry data were constructed to determine associations between M1 status and quantitative nodal burden. Associations between metastatic lymph node (LN) number and M1 disease were modeled using univariate and multivariable logistic regression with interaction terms, as well as a linear continuous probability model. Results: Overall, M1 prevalence at disease presentation was 3.6% (n = 1717). When stratified by subtype, M1 prevalence varied significantly by histology (WDPTC [1.0%], DSV [2.3%], TCV [4.1%], PDTC [17.4%], ATC [38.4%] [p < 0.001]). For WDPTC, M1 prevalence escalated with metastatic LN number (0 LN+ [0.5%], 1-5 LN+ [2.0%], 6-10 LN+ [3.4%], >10 LN+ [5.5%] [p < 0.001]) and LN ratio (p < 0.001). A statistically significant interaction was observed between histology and increasing nodal burden for M1 risk. On multivariable analysis, each successive metastatic LN conferred increased M1 risk for WDPTC (odds ratio [OR] 1.06 [1.05-1.08], p < 0.001) and TCVs (OR 1.04 [1.02-1.07], p < 0.001). In contrast, other aggressive variants had a higher baseline M1 risk, but this did not vary based on the number of positive LN (DSV, OR 1.02 [0.95-1.10], p = 0.52; PDTC, OR 1.00 [0.98-1.02], p = 0.66; ATC, 1.00 [0.98-1.02], p = 0.97). Conclusions: Progressive nodal burden independently escalates the risk of distant metastasis in WDPTC and TCVs of PTC. Conversely, aggressive variants such as PDTC and ATC have substantial M1 risk at baseline and appear to be minimally affected by metastatic nodal burden. Consideration of these factors after surgery may help tailor clinical decision-making for treatment and surveillance. Further studies are warranted to calibrate the ideal management approach for these higher risk patient groups.

Incidental parathyroidectomy in thyroidectomy and central neck dissection.

BACKGROUND: Although higher thyroidectomy volume has been linked with lower complication rates, its association with incidental parathyroidectomy remains less studied. The volume relationship is even less clear for central neck dissection, where individual parathyroid glands are at greater risk. METHODS: Patients undergoing thyroidectomy with or without central neck dissection were evaluated for incidental parathyroidectomy, hypoparathyroidism, and hypocalcemia. Univariate and multivariable analyses were performed using binary logistic regression. RESULTS: Overall, 1,114 thyroidectomies and 396 concurrent central neck dissections were performed across 7 surgeons. Incidental parathyroidectomy occurred in 22.4% of surgeries (range, 16.9%-43.6%), affecting 7.1% of parathyroids at risk (range, 5.8%-14.5%). When stratified by surgeon, lower incidental parathyroidectomy rates were associated with higher thyroidectomy volumes (R2 = 0.77, P = .008) and higher central neck dissection volumes (R2 = 0.93, P < .001). On multivariable analysis, low-volume surgeon (odds ratio 2.94, 95% confidence interval 2.06-4.19, P < .001), extrathyroidal extension (odds ratio 3.13, 95% confidence interval 1.24-7.87, P = .016), prophylactic central neck dissection (odds ratio 2.68, 95% confidence interval 1.65-4.35, P <.001), and therapeutic central neck dissection (odds ratio 4.44, 95% confidence interval 1.98-9.96, P < .001) were the most significant factors associated with incidental parathyroidectomy. In addition, incidental parathyroidectomy was associated with a higher likelihood of temporary hypoparathyroidism (odds ratio 2.79, 95% confidence interval 1.45-5.38, P = .002) and permanent hypoparathyroidism (odds ratio 4.62, 95% confidence interval 1.41-5.96, P = .025), but not permanent hypocalcemia (odds ratio 1.27, 95% confidence interval 0.48-3.35, P = .63). Higher lymph node yield in central neck dissection was not associated with higher incidental parathyroidectomy rates (odds ratio 1.13, 95% confidence interval 0.85-8.81, P = .82). CONCLUSION: Higher surgical volume conferred a lower rate of incidental parathyroidectomy. Nonetheless, greater lymph node yield in central neck dissections did not result in greater parathyroid-related morbidity. Such findings support the value of leveraging surgical volume to both optimize oncologic resection and minimize complication rates.

Prognostic Impact of Histologic Grade for Papillary Thyroid Carcinoma.

BACKGROUND: While numerous factors affect prognosis in papillary thyroid carcinoma (PTC), the comparative impact of histologic grade has not been well described. Moreover, indications for external beam radiation therapy (EBRT) remain imprecise. We evaluate clinicopathologic characteristics and outcomes for PTC stratified by grade. METHODS: We profiled histologic grade for PTC (well differentiated, moderately differentiated, poorly differentiated) via hospital (National Cancer Database) and population-based (Surveillance, Epidemiology, and End Results) registries. Cox regression was used to adjust for clinicopathologic covariates. Statistical interactions between subtypes and the effect of EBRT on survival were assessed. RESULTS: Collectively, worsening clinicopathologic factors (age, tumor size, extrathyroidal extension, nodal spread, M1 disease) and outcomes (disease-free survival, overall survival) correlated with less differentiated state, across all histologic grades (p < 0.001). Multivariable analysis showed escalating hazard with loss of differentiation relative to well-differentiated PTC (moderately differentiated hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.04-1.41, p = 0.02; poorly differentiated HR 2.62, 95% CI 2.23-3.08, p < 0.001). Correspondingly, greater survival benefit was associated with EBRT for poorly differentiated cases (HR 0.36, 95% CI 0.18-0.72, p = 0.004). This finding was upheld after landmark analysis to address potential immortal time bias (HR 0.37, 95% CI 0.17-0.80, p = 0.01). CONCLUSIONS: Worsening histologic grade in PTC is independently associated with parallel escalation in mortality risk, on a scale approximating or surpassing established thyroid cancer risk factors. On preliminary analysis, EBRT was associated with improved survival in the most aggressive or least differentiated subvariants. Further investigation is warranted to examine the efficacy of EBRT for select poorly differentiated thyroid carcinomas.

Incidence and Mortality Risk Spectrum Across Aggressive Variants of Papillary Thyroid Carcinoma.

Importance: While well-differentiated papillary thyroid carcinoma (WDPTC) outcomes have been well characterized, the prognostic implications of more aggressive variants are far less defined. The rarity of these subtypes has led to their consolidation as intermediate risk for what are in fact likely heterogeneous diseases. Objective: To analyze incidence, clinicopathologic characteristics, and outcomes for aggressive variants of papillary thyroid carcinoma (PTC). Design, Setting, and Participants: This cohort study used data from 2000 to 2016 from hospital-based and population-based US cancer registries to analyze aggressive PTC variants, including diffuse sclerosing (DSV), tall-cell (TCV), insular, and poorly differentiated (PDTC) subtypes. These variants were compared against WDPTC and anaplastic cases. Data analysis was conducted from January 2019 to October 2019. Main Outcomes and Measures: Age-adjusted incidence was calculated via annual percentage change (APC) using the weighted least-squares method. Overall survival and disease-specific survival were analyzed via Cox regression. Propensity-score matching was used to adjust survival analyses for clinical and demographic covariates. Results: Collectively, 5447 aggressive PTC variants were identified (including 415 DSV, 3339 TCV, 362 insular, and 1331 PDTC cases), as well as 35 812 WDPTC and 2249 anaplastic cases. Over the study period, a substantial increase in aggressive variant incidence was observed (APC, 9.1 [95% CI, 7.33-10.89]; P < .001), surpassing the relative increases observed in WDPTC (APC, 5.1 [95% CI, 3.98-6.12]; P < .001) and anaplastic cases (APC, 1.9 [95% CI, 0.75-3.05]; P = .003; parallelism P < .007). Survival varied markedly based on histologic subtype, with a wide spectrum of mortality risk noted; 10-year overall survival was 85.4% (95% CI, 84.6%-86.3%) in WDPTC, 79.2% (95% CI, 73.6%-85.3%) in DSV, 71.9% (95% CI, 68.4%-75.6%) in TCV, 45.1% (95% CI, 40.2%-50.6%) in PDTC, 27.9% (95% CI, 20.0%-38.9%) in the insular variant, and 8.9% (95% CI, 7.5%-10.6%) in anaplastic cases (P < .001). These differences largely persisted even after adjusting for inherent differences in baseline characteristics by multivariable Cox regression and propensity-score matching. Conclusions and Relevance: An upsurge in aggressive PTC incidence was observed at a rate beyond that seen in WDPTC or anaplastic thyroid carcinoma. Moreover, long-term survival outcomes for aggressive PTC subgroups exhibit heterogeneous clinical behavior and a wide range of mortality risk, suggesting that treatment should be tailored to specific histologic subtypes. Given increasing prevalence and disparate outcomes, further investigation to identify optimal therapeutic strategies is needed in these diverse, understudied populations.

Mortality Risk of Nonoperative Papillary Thyroid Carcinoma: A Corollary for Active Surveillance.

Background: Active surveillance is established as an alternative to surgery for papillary thyroid microcarcinomas, but inclusion criteria and mortality risk for pursuing a nonsurgical approach have not been clearly defined. To gauge the feasibility of expanding active surveillance thresholds, we investigated the effects of increasing size and age on disease-specific survival (DSS) in a large nonoperative thyroid cancer cohort, compared against a matched group of surgical patients. Methods: Papillary thyroid carcinoma patients staged T1-4N0M0 were identified in the Surveillance, Epidemiology, and End Results (SEER) database between 1975 and 2015, stratified by nonsurgical and surgical management. Propensity score matching was performed to adjust for imbalances in covariates. Multivariable models were constructed using restricted cubic splines to model nonlinear relationships of age and tumor size with DSS. Results: Overall, 1453 nonoperative patients and 54,718 surgical patients met the inclusion criteria. Collectively, increasing age and size after certain thresholds independently led to greater differences in DSS between nonsurgical and surgical patients. For younger ages (14-55 years), surgical approach compared with nonsurgical approach was not associated with any difference in the 10-year DSS among 0-4 cm cancers (99.8% vs. 100%, p = 0.470), 4.1-6 cm cancers (98.8% vs. 100%, p = 0.599), or >6 cm cancers (97.3% vs. 100%, p = 0.718). Older patients with larger tumors (>75 years, >6 cm) demonstrated the greatest difference in DSS (48.1% vs. 91.3%, p < 0.001). Similar results were found when applying propensity score matching. For age, restricted cubic spline plots showed minimal relative survival hazard in nonoperative cases beginning after age 60 years, with a change point illustrating acceleration in relative hazard beyond age 72 years. For size, relative survival hazard was observed after 2.0 cm and increased slowly with nodule growth up to an inflection point of 4.5 cm. Beyond this, mortality risk escalated with each additional year without plateau. Conclusions: Increasing age and size lead to progressively greater mortality risk without surgery, but only beyond certain thresholds. We define escalating gradients at which a nonsurgical approach may be deemed appropriate, and beyond which survival benefits from surgery become apparent. Such findings reconcile controversial observations regarding age and size in active surveillance and further reshape evolving treatment paradigms in thyroid cancer.

Age at Menarche and Risk of Cardiovascular Disease Outcomes: Findings From the National Heart Lung and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation.

Background Previous studies have reported an association between the timing of menarche and cardiovascular disease ( CVD ). However, emerging studies have not examined the timing of menarche in relation to role of estrogen over a lifetime and major adverse cardiac events ( MACE ). Methods and Results A total of 648 women without surgical menopause undergoing coronary angiography for suspected ischemia in the WISE (Women's Ischemia Syndrome Evaluation) study were evaluated at baseline and followed for 6 years (median) to assess major adverse CVD outcomes. MACE was defined as the first occurrence of all-cause death, nonfatal myocardial infarction, nonfatal stroke, or heart failure hospitalization. Age at menarche was self-reported and categorized (≤10, 11, 12, 13, 14, ≥15 years) with age 12 as reference. Total estrogen time and supra-total estrogen time were calculated. Cox regression analysis was performed adjusting for CVD risk factors. Baseline age was 57.9 ± 12 years (mean ± SD ), body mass index was 29.5 ± 6.5 kg/m2, total estrogen time was 32.2 ± 8.9 years, and supra-total estrogen time was 41.4 ± 8.8 years. MACE occurred in 172 (27%), and its adjusted regression model was J-shaped. Compared with women with menarche at age 12 years, the adjusted MACE hazard ratio for menarche at ≤10 years was 4.53 (95% CI 2.13-9.63); and at ≥15 years risk for MACE was 2.58 (95% CI , 1.28-5.21). Conclusions History of early or late menarche was associated with a higher risk for adverse CVD outcomes. These findings highlight age at menarche as a potential screening tool for women at risk of adverse CVD events. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT00000554.

Pharmacogenetic profile and major depressive and/or bipolar disorder treatment: a retrospective, cross-sectional study.

AIM: To compare pharmacogenetic test predictions with self-reported treatment experience and side effect tolerability among patients with depression taking psychotherapeutic medications. METHODS: Subjects completed a survey recalling medication effectiveness and side effects and then underwent pharmacogenetic testing. RESULTS: Our 15 gene pharmacogenetic panel predicted efficacy (p < 0.001) but did not predict side effect tolerability (p = 0.70) in a group of 352 patients. The pharmacogenetic panel and reported efficacy corresponded 60% of the time and medication tolerability agreed 71% of the time. CONCLUSION: Pharmacogenetic testing may be a useful adjunct to predict efficacy of medications used to treat depression.

Mutation detection using plasma circulating tumor DNA (ctDNA) in a cohort of asymptomatic adults at increased risk for cancer.

PURPOSE: The primary purpose of this study was to clinically evaluate circulating tumor DNA (ctDNA) with a nine gene, 96 mutation panel among subjects at increased risk for cancer with no previous cancer diagnosis. SUBJECTS AND METHODS: DNA from 1059 asymptomatic subjects was analyzed for detection of low levels ctDNA using a blood plasma liquid biopsy assay. Subjects with detectable copies of ctDNA were asked to provide additional blood samples and relevant medical records throughout their one-year of participation. Subjects with a negative result were followed-up at one-year with a questionnaire. RESULTS: Mutations were detected in 58 subjects and not detected in 1001 subjects. Among the subjects who tested positive for one or more mutations, four were diagnosed with cancer, two of which through study-triggered clinical follow-up. Two subjects who tested negative on the screen received an early cancer diagnosis over the course of the year. The sensitivity of the assay at a threshold of ≥2 copies in this population was 66.67% and specificity was 94.87%. While the negative predictive value was 99.8%, the positive predictive value was only 6.9% in this cohort. Analysis of buffy coat DNA from eight positive subjects, including one who was diagnosed with cancer, revealed matching mutations suggesting that the ctDNA could have been derived from clonal hematopoiesis. CONCLUSION: The observed false positive rate of ctDNA on a 96-mutation assay in an asymptomatic high-risk population is much greater than the true positive rate, limiting its usefulness as a cancer screening tool in its current form.

IS MEASUREMENT OF CIRCULATING TUMOR DNA OF DIAGNOSTIC USE IN PATIENTS WITH THYROID NODULES?

OBJECTIVE: Circulating tumor DNA (ctDNA), a subset of cell-free DNA (cfDNA), is a potential biomarker for thyroid cancer. We determined the performance of a ctDNA panel for detecting thyroid malignancy in patients with thyroid nodules. METHODS: Sixty-six patients with thyroid nodules without a prior history of cancer enrolled in a prospective, 1-year study in which blood was drawn for ctDNA analysis prior to undergoing fine-needle aspiration biopsy (FNAB) of thyroid nodules. The ctDNA panel consisted of 96-mutations in 9 cancer driver genes. The primary outcome measures were the sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of our ctDNA panel for the diagnosis of thyroid malignancy as determined by pathologic and/or molecular tissue examination. RESULTS: Results from 10 subjects could not be determined due to inadequate volume or technical issues. The final classifications of the thyroid nodules were 13 malignant and 43 benign lesions. A KRAS G12V mutation was detected in the plasma of 1 patient with stage IVA papillary carcinoma whose tissue contained the same mutation. Two of the 43 patients with benign lesions also had ctDNA detected, giving a sensitivity of 7.7%, specificity of 95.35%, PPV of 33.33%, and NPV of 77.35%. There were no significant differences between benign or malignant lesions in cfDNA levels. CONCLUSION: Neither cfDNA measurements nor our panel of ctDNA mutations are sensitive or specific enough to provide valuable information over FNAB. An expanded panel and the inclusion of proteomics may improve sensitivity and specificity for thyroid cancer detection. ABBREVIATIONS: cfDNA = cell-free DNA; ctDNA = circulating tumor DNA; FNAB = fine-needle aspiration biopsy; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features.

Tumor-associated DNA mutation detection in individuals undergoing colonoscopy.

The majority of colorectal cancers (CRC) harbor somatic mutations and epigenetic modifications in the tumor tissue, and some of these mutations can be detected in plasma as circulating tumor DNA (ctDNA). Precancerous colorectal lesions also contain many of these same mutations. This study examined plasma for ctDNA from patients undergoing a screening or diagnostic colonoscopy to determine the sensitivity and specificity of the ctDNA panel for detecting CRC and precancerous lesions. Two hundred patients without a history of nonskin cancer had blood drawn before a colonoscopy. Plasma ctDNA was measured with a 96 mutation panel for nine cancer driver genes. The ctDNA results were correlated with the findings at colonoscopy. Of the 200 patients, 176 (88%) had wild-type DNA, 12 (6%) had mutations detected, and 12 (6%) had indeterminate results. Colonoscopy was normal in 80% of the patients and 20% were found to have polyps. No CRC was found in this study, precluding a determination of true-positive rate for CRC detection. Our ctDNA panel was positive in 13.2% of patients with colonic polyps found at colonoscopy, while 4.7% of patients with normal colonoscopy also had ctDNA detected, which may represent ctDNA released from a benign process, an occult tumor, or an acquired somatic mutation from clonal hematopoiesis.

Pharmacoeconomics of genotyping-based treatment decisions in patients with chronic pain.

INTRODUCTION: Genotyping-based treatment decisions may optimize treatment response and minimize adverse drug events (ADEs) in patients with chronic pain. OBJECTIVES: To estimate the financial impact of genotyping-based treatment decisions in patients with moderate to severe chronic pain in a managed care setting. METHODS: A budget impact model was built with a 1-year time horizon to estimate costs of genotyping-based treatment decisions in a 1000-patient cohort. The model includes drug costs, type and cost of ADEs, distribution of treatments used, and genotyping costs. Event rates and health care costs were derived from primary literature. Three patient cohorts were assessed with and without genotyping-based treatment decisions: no genetic testing; 50% genetic testing; and 100% genetic testing. Sensitivity analysis was performed varying costs, adherence, and the percentage of patients treated according to genotyping results. RESULTS: Medical and ADE costs varied by patient severity and genotyping rates. Without genotyping, drug and ADE costs ranged from $1,544,377 to $24,313,844. With genotyping-based treatment, total costs ranged from $1,780,922 to $18,868,032. Sensitivity analysis, varying costs, adherence, and genotyping rates suggested genotyping improves outcomes and is cost saving in patients with chronic pain. CONCLUSION: Genotyping-based treatment costs are offset by reduced medication utilization and adverse event costs. Genotyping should be considered for patients with chronic pain in clinical practice and within clinical trials.

Menopausal symptoms and cardiovascular disease mortality in the Women's Ischemia Syndrome Evaluation (WISE).

OBJECTIVE: Studies have linked vasomotor symptoms (VMS) to markers of cardiovascular disease (CVD) risk, yet few have considered clinical cardiovascular events. Data suggest that associations may depend upon the age that symptoms occur. We examined associations between VMS and cardiovascular events and endothelial function, considering age of symptom onset. METHODS: The Women's Ischemia Syndrome Evaluation enrolled women referred for coronary angiography for suspected myocardial ischemia. A total of 254 women aged more than 50 years, postmenopausal, with both ovaries, not taking hormone therapy underwent a baseline evaluation, were followed annually (median = 6.0 y), and the National Death Index was searched to ascertain CVD mortality (median = 9.3 y). A subset of participants underwent brachial artery ultrasound for flow-mediated dilation (FMD). Receiver-operating curve analysis was used to determine vasomotor symptom groups (symptoms beginning < age 42 [early onset], beginning ≥42 [later onset], never) which were examined in relation to cardiovascular events and FMD in Cox proportional hazard and linear regression models. RESULTS: Women reporting early onset VMS (HR = 3.35, 95% CI = 1.23-7.86, P = 0.005) and women who never had VMS (HR = 2.17, 95% CI = 1.02-4.62, P = 0.05) had higher CVD mortality than women with later onset symptoms (multivariable models). Women with early onset VMS had lower FMD than women with later onset symptoms (b = -4.31, SE = 2.10, P = 0.04, multivariable). CONCLUSIONS: Women with signs and symptoms of ischemia who had VMS beginning early in midlife had higher CVD mortality and reduced endothelial function relative to women with later onset symptoms. Future research should evaluate the vascular phenotype of women with early midlife VMS.

LYMPHOCYTIC THYROIDITIS IS ASSOCIATED WITH INCREASED NUMBER OF BENIGN CERVICAL NODES AND FEWER CENTRAL NECK COMPARTMENT METASTATIC LYMPH NODES IN PATIENTS WITH DIFFERENTIATED THYROID CANCER.

OBJECTIVE: Whether or not autoimmune thyroid disease influences the progression of differentiated thyroid cancer (DTC) remains controversial. Findings of previous studies are influenced by lead time bias and/or procedure bias selection. These biases can be reduced by studying a single-institution patient population that underwent a similar extent of surgical resection. METHODS: From a cohort of 660 patients with DTC who underwent thyroidectomy, we retrospectively studied 357 patients who underwent total thyroidectomy and central compartment node dissection (CCND) for DTC between 2003 and 2013. RESULTS: Forty-one percent (140/345) of study patients had lymphocytic thyroiditis (LT), and 30% (91/301) had serum positive for thyroglobulin antibody (TgAb). LT was reported in 78% of the TgAb-positive cases. Sixty percent (213/357) of cases had metastatic thyroid carcinoma in 1 or more neck lymph nodes (55% [198/357] central compartment, and 22% [77/356] lateral compartment). Patients with LT had fewer metastatic cervical lymph nodes than those with no LT (2.7 ± 4.7 vs 3.5 ± 4.8, respectively, P = .0285). Patients with positive TgAb and thyroiditis had a larger number of benign cervical lymph nodes removed than those with negative TgAb or no LT. No significant difference was observed in age, tumor size, multifocality, extrathyroidal extension, vascular invasion, or frequency of cervical lymph node metastasis between TgAb-negative and -positive cases or between cases with and without LT. CONCLUSION: Lymphocytic thyroiditis is associated with fewer central neck compartment metastatic lymph nodes and a larger number of excised reactive benign cervical lymph nodes. Whether this association indicates a protective role of thyroid autoimmunity in lymph node spreading remains unclear. ABBREVIATIONS: CCND = central compartment node dissection DTC = differentiated thyroid cancer HT = Hashimoto thyroiditis LT = lymphocytic thyroiditis TgAb = thyroglobulin antibody TPO = thyroid peroxidase.