Abstract:Ambulatory hypercalcemia is a proxy for primary hyperparathyroidism. Reports of an increased incidence of hypercalcemia and undiagnosed primary hyperparathyroidism in several electronic medical record studies have prompted a population-based trend analysis of serum calcium. Data from the 2000-2020 U.S. National Health and Nutritional Examination Survey were used to study the trend of serum calcium and related factors. The NHANES has contemporary insight into the ambulatory state of health in the large and diverse U.S. population. Joinpoint regression estimated yearly changes of serum calcium and related factors using annual percentage changes. Serum calcium levels increased by an average of 0.65 mg/dL/y from 2000 to 2004 and then decreased on average by 0.12 mg/dL annually from 2004 to 2020. Among women, serum calcium levels increased by an average of 0.69 mg/dL/y from 2000 to 2004 but then decreased on average by 0.13 mg/dL annually from 2004 to 2020. Among men, serum calcium levels increased by an average of 0.61 mg/dL/y from 2000 to 2004 and then remained stable. Trends of body mass index increased by an average of 0.49/y from 2014 to 2020. Ambulatory hypercalcemia is a proxy for primary hyperparathyroidism. Over 20 years in the U.S. National Health and Nutritional Examination Survey (2000-2020), calcium levels have been decreasing slightly since 2004 after an increase while body mass index has been increasing since 2014. These data conflict with reported observations of the undiagnosed and increased incidence of primary hyperparathyroidism. These data may ultimately serve to refine primary hyperparathyroidism data phenotype for machine learning deployed within an electronic medical record.

Importance Preoperative parathyroid localization has been a great advance in the success of surgery for patients with primary hyperparathyroidism (pHPT) over the past 40 years. Objective To highlight the amount of radiation exposure from contemporary parathyroid imaging options and to suggest intentional imaging use in planning for parathyroidectomy. Evidence Review Contemporary parathyroid imaging modalities and their respective radiation exposure were reviewed. The analysis focused on patients undergoing preoperative parathyroid imaging related to pHPT and persistent/recurrent pHPT. Exposure of patients to ionizing radiation from devices and radiotracers measured in mSv was reported. Findings The parathyroid imaging recommendations include ultrasonography (0 mSv), technetium Tc 99m sestamibi single-photon emission computed tomography (SPECT) with or without computed tomography (CT) (8.6-12.1 mSv), and second-line/complex imaging for patients undergoing revision parathyroid surgery: 4-dimensional CT (9.3-20.2 mSv) or choline-based positron emission tomography (PET) with or without CT (6.7-11.8 mSv). Conclusions and Relevance Imaging should be conducted only when the diagnosis is confirmed. When making decisions about imaging, consider radiation exposure, sensitivity/specificity for adenoma detection, local expertise in the imaging modality, and cost.

Evidence for obesity and vitamin D deficiency as components of a data phenotype for primary hyperparathyroidism (pHPT) is critical to understanding primary hyperparathyroidism. This study examined the association between vitamin D, body mass index (BMI), albumin total calcium, parathyroid hormone (PTH) and data from National Health and Nutrition Examination Survey (NHANES). Associations of 25-hydroxyvitamin D, albumin adjusted calcium, and BMI with elevated PTH were evaluated, with elevated PTH being defined as>9.02 pmol/l. Outcomes were PTH (pmol/l), 25-hydroxyvitamin D (nmol/l), albumin adjusted calcium (mmol/l), and BMI. A weighted multivariable logistic regression model estimated the associations. A total of 9740 survey respondents were included in the study, 3.5% had elevated PTH. Mean vitamin D level was 57.7 (SD=22.6) nmol/l and BMI was 28.6 (SD=6.5) kg/m2. A one unit increase in BMI was associated with higher odds of elevated PTH [adjusted odds ratio (aOR)=1.04; 95% confidence interval (CI): 1.02, 1.06] whereas a one unit increase in vitamin D (aOR=0.97; 95% CI: 0.96, 0.98) or calcium (aOR=0.51; 95% CI: 0.29, 0.89) had decreased odds of elevated PTH. Higher BMI and lower levels of 25-hydroxyvitamin D are components of the primary hyperparathyroidism data phenotype. A refined data phenotype may improve detection/management of pHPT.

IMPORTANCE:Predicting primary hyperparathyroidism in data may facilitate earlier diagnosis and treatment. OBJECTIVE:Primary Hyperparathyroidism (pHPT) is the leading cause of hypercalcemia and up to 75% of hypercalcemic patients go undiagnosed. The purpose of this study was to examine the use of predictive modeling using a large clinical database to predict pHPT in patients with benign thyroid nodules. DESIGN:Retrospective analysis and predictive modeling of pHPT using a large discharge database. A predictive model of pHPT was created using logistic regression and compared to three machine learning algorithms: a Gaussian naive Bayes classifier, a stochastic gradient descent classifier, and a histogram-based gradient boosting classifier. SETTING:Vizient hospital discharge database from over 1000 hospitals including academic health centers. PARTICIPANTS:Data from the Vizient Clinical Database (CDB), 2 541 901 patients with benign thyroid nodules were identified between 2020 and 2023, of whom 83 555 (3.29%) had pHPT. INTERVENTION(S) (FOR CLINICAL TRIALS) OR EXPOSURE(S) (FOR OBSERVATIONAL STUDIES): Analyses controlled for demographics (age, sex, race), comorbidities (body mass index (BMI), diabetes, hypertension, smoking status, renal disease) and use of proton pump inhibitors and bisphosphonates. MAIN OUTCOME(S) AND MEASURE(S):The primary outcome measure was the presence of pHPT, which was identified using ICD-10 codes. Model performance was compared using the area under the receiver operating characteristics (ROC) curve. RESULTS:In the baseline predictive model, several demographic characteristics were significant predictors of pHPT. The logistic regression model had an area under the ROC curve of 68.1%, which was lower than that of the histogram gradient boosting model (68.7%) but equivalent to the gradient descent classifier (68.1%). Furthermore, the logistic regression model correctly classified 80.4% of pHPT cases, compared to 80.5% for both the histogram gradient boosting classifier and the gradient descent classifier. A threshold of 5% yielded a sensitivity of 38.5% and specificity of 81.8% for logistic regression. CONCLUSIONS AND RELEVANCE:Predictive modeling of pHPT among patients with benign thyroid nodules is possible using a large clinical database. The predictive equation could be built into decision support systems to alert clinicians to potentially undiagnosed pHPT and aid in timely diagnosis and treatment of pHPT.

Background:Pre-operative imaging is a well-established practice for managing hyperparathyroidism with the plan for excision; however, there is a paucity of information regarding the success rate of concordant imaging studies. Our goal was to compare the accuracy (sensitivity) of four-dimensional computed tomography (4DCT) and ultrasound (US) when predicting the side and quadrant of parathyroid lesions, confirmed with surgical location (from a single surgeon). Methods:A retrospective review of 437 patients from a single surgeon undergoing parathyroidectomy from December 2013 to January 2020 at an academic medical center was performed. Masses >5 mm in dimension in eutopic parathyroid locations were identified as possible parathyroid lesions on 4DCT. A unique codified system was utilized to accurately record imaging results for each modality and compared to surgical findings. Results:Four hundred and thirty-seven patients underwent parathyroid surgery, of those 431 underwent 4DCT, 413 underwent US, and 408 underwent both. 4DCT accurately lateralized lesions in 319 (74.0%; N=431). US lateralized lesions in 265 (64.2%; N=413). The sensitivity for lateralization was 81.2% and 69.9% for 4DCT and US, respectively. Conclusions:4DCT and US identify the majority of parathyroid lesions. 4DCT outperformed US in lateralization yet both modalities remain useful and are complimentary in planning for successful parathyroidectomy. Newer imaging approaches such as 18F-choline positron emission tomography/computed tomography (PET/CT) and artificial intelligence as an augmentation to imaging review may play in role to identify parathyroid adenomas/hyperplasia, but their roles have yet to be clearly defined.

BACKGROUND:This study examined the trajectory of health-related quality of life (HRQoL) for patients with clinical stage N0 HNSCC enrolled in ACRIN 6685 who underwent elective neck dissection(s). METHODS:HRQoL of 230 patients in the ACRIN 6685 trial was measured prospectively up to 2 years following surgery using the University of Washington Quality of Life instrument. RESULTS:General Health Within the Last 7 Days did not differ significantly from baseline at any follow-up. General Health Relative to Before Cancer fell significantly by 5.8 points following surgery (p = 0.048), and then returned to 3.0 points above baseline at 1 year (p = 0.65). For Overall Quality of Life, HRQoL fell significantly by 4.3 points following surgery (p = 0.031) and then returned to levels not significantly different from baseline. CONCLUSIONS:Patients with stage N0 HNSCC experience significant declines in HRQoL immediately following surgery, including neck dissection, which recovers to near or better than baseline within 1-2 years.

Postoperative hypoparathyroidism may cause significant patient morbidity and even mortality. Emerging technologies centered on autofluorescent properties of parathyroid glands when exposed to near-infrared light hold promise to improve surgical parathyroid gland identification and preservation. Two systems (probe-based and camera-based) are commercially available currently; however, neither system alone provides indication of vascular viability or postoperative parathyroid gland function. The administration of indocyanine green, when combined with near-infrared fluorescence imaging, enables subjective assessment of parathyroid gland perfusion. Additional technologies to assess parathyroid gland perfusion are being developed. The impact of these nascent technologies on relevant clinical outcomes is an area of active investigation.

ImportanceOncocytic (Hürthle cell) thyroid carcinoma is a follicular cell-derived neoplasm that accounts for approximately 5% of all thyroid cancers. Until recently, it was categorized as a follicular thyroid carcinoma, and its management was standardized with that of other differentiated thyroid carcinomas. In 2022, given an improved understanding of the unique molecular profile and clinical behavior of oncocytic thyroid carcinoma, the World Health Organization reclassified oncocytic thyroid carcinoma as distinct from follicular thyroid carcinoma. The International Thyroid Oncology Group and the American Head and Neck Society then collaborated to review the existing evidence on oncocytic thyroid carcinoma, from diagnosis through clinical management and follow-up surveillance.ObservationsGiven that oncocytic thyroid carcinoma was previously classified as a subtype of follicular thyroid carcinoma, it was clinically studied in that context. However, due to its low prevalence and previous classification schema, there are few studies that have specifically evaluated oncocytic thyroid carcinoma. Recent data indicate that oncocytic thyroid carcinoma is a distinct class of malignant thyroid tumor with a group of distinct genetic alterations and clinicopathologic features. Oncocytic thyroid carcinoma displays higher rates of somatic gene variants and genomic chromosomal loss of heterozygosity than do other thyroid cancers, and it harbors unique mitochondrial DNA variations. Clinically, oncocytic thyroid carcinoma is more likely to have locoregional (lymph node) metastases than is follicular thyroid carcinoma—with which it was formerly classified—and it develops distant metastases more frequently than papillary thyroid carcinoma. In addition, oncocytic thyroid carcinoma rarely absorbs radioiodine.Conclusions and RelevanceThe findings of this review suggest that the distinct clinical presentation of oncocytic thyroid carcinoma, including its metastatic behavior and its reduced avidity to radioiodine therapy, warrants a tailored disease management approach. The reclassification of oncocytic thyroid carcinoma by the World Health Organization is an important milestone toward developing a specific and comprehensive clinical management for oncocytic thyroid carcinoma that considers its distinct characteristics.

Importance:Oncocytic (Hürthle cell) thyroid carcinoma is a follicular cell-derived neoplasm that accounts for approximately 5% of all thyroid cancers. Until recently, it was categorized as a follicular thyroid carcinoma, and its management was standardized with that of other differentiated thyroid carcinomas. In 2022, given an improved understanding of the unique molecular profile and clinical behavior of oncocytic thyroid carcinoma, the World Health Organization reclassified oncocytic thyroid carcinoma as distinct from follicular thyroid carcinoma. The International Thyroid Oncology Group and the American Head and Neck Society then collaborated to review the existing evidence on oncocytic thyroid carcinoma, from diagnosis through clinical management and follow-up surveillance. Observations:Given that oncocytic thyroid carcinoma was previously classified as a subtype of follicular thyroid carcinoma, it was clinically studied in that context. However, due to its low prevalence and previous classification schema, there are few studies that have specifically evaluated oncocytic thyroid carcinoma. Recent data indicate that oncocytic thyroid carcinoma is a distinct class of malignant thyroid tumor with a group of distinct genetic alterations and clinicopathologic features. Oncocytic thyroid carcinoma displays higher rates of somatic gene variants and genomic chromosomal loss of heterozygosity than do other thyroid cancers, and it harbors unique mitochondrial DNA variations. Clinically, oncocytic thyroid carcinoma is more likely to have locoregional (lymph node) metastases than is follicular thyroid carcinoma-with which it was formerly classified-and it develops distant metastases more frequently than papillary thyroid carcinoma. In addition, oncocytic thyroid carcinoma rarely absorbs radioiodine. Conclusions and Relevance:The findings of this review suggest that the distinct clinical presentation of oncocytic thyroid carcinoma, including its metastatic behavior and its reduced avidity to radioiodine therapy, warrants a tailored disease management approach. The reclassification of oncocytic thyroid carcinoma by the World Health Organization is an important milestone toward developing a specific and comprehensive clinical management for oncocytic thyroid carcinoma that considers its distinct characteristics.

Secondary hyperparathyroidism (SHPT) does not initiate as a primary dysfunction of parathyroid glands resulting from an intrinsic defect or disease but is the physiologic response of parathyroids to metabolic changes elsewhere in the body occurring over time. SHPT is a manifestation of a chronic condition that classically occurs from chronic kidney disease. In fact, given the relatively recent transition of populations from outside (agrarian) to indoor (industrial, information technology, and so forth) employment and a consequent reduction in sun exposure, combined with diets of highly processed food, vitamin D and calcium deficiencies are now the leading causes of SHPT.

Supplementary Figure S4. JQ1 suppresses MCC-2 cell proliferation; successful knockdown of p21, p27 and p57 expression in MCC cells; JQ1 increases Notch1 and NFï«B gene expressions in MCC-3 and MCC-5 cells.

Background: With recent efforts to decrease opioid use following surgery, this study aims to answer: what pain regimen do patients follow at home? Is it controlling pain? Methods: This is a prospective, pilot study of thyroid and parathyroid surgery patients. Patients were prescribed acetaminophen, ibuprofen, and tramadol dispensed in smart pill (Pillsy) bottles that record "events" corresponding to medication use. Patients received messages querying their current pain level. Patients were compared to historical controls. Results: 26 patients were in the Pillsy group and 30 in the control group. In the Pillsy group, pain scores averaged 3.67 out of 10 in the first 24 h after surgery and decreased each day. Patients took an average of 6.45 doses of acetaminophen, 6.64 doses of ibuprofen, and 1.82 doses of tramadol in the first week. Conclusions: Pain scores are highest in the first 24 h after surgery and decrease thereafter. This acceptable level of pain can be achieved with non-opioid medications.

Supplementary Figure S3. JQ1 exerts no effect on mTOR pathway and MCC cells express characteristic MCC makers, including a Merkel cell specific transcription factor Math1.