Kebebew, Electron

Importance Primary hyperparathyroidism (PHPT) is common and contributes to skeletal and kidney end-organ damage. Although parathyroidectomy can mitigate these complications, many patients are managed with observation, and real-world data on the population-based frequency and timing of end-organ damage under usual care are limited. Objective To evaluate the frequency and timing of end-organ damage associated with PHPT. Design, Setting, and Participants This cohort study included a population-based cohort identified from national electronic health record (EHR) and claims data (2010-2023) with follow-up through 2023. Participants were adults with a new biochemical diagnosis of PHPT. Data analysis was performed from August 2025 to April 2026. Exposure A new biochemical diagnosis of PHPT was defined as an elevated PTH (>65 pg/mL) within 1 month after a second elevated calcium level (serum calcium >10.2 mg/dL or ionized calcium >1.3 mmol/L or >5.3 mg/dL). Main Outcomes and Measures PHPT-associated end-organ damage (osteoporosis, atraumatic fractures, kidney stones, stage 3 or worse chronic kidney disease) at or after PHPT diagnosis using EHR or claim codes and laboratory data, in addition to the frequency and timing of parathyroidectomy. Results A total of 43 399 patients with PHPT were identified (mean [SD] age, 67.9 [12.5] years; 33 854 [78%] female and 9545 [22%] male), of whom 22 279 (51.3%) had end-organ damage at diagnosis. Among 21 120 patients without end-organ damage at diagnosis, 6762 (32.0%) progressed to end-organ damage after a median (IQR) 516 (166-1125) days. Only 4442 patients (19.9%) with end-organ damage at diagnosis were treated with parathyroidectomy. Among those who progressed to end-organ damage, 1348 (19.9%) underwent subsequent parathyroidectomy, which occurred a median (IQR) 154 (41-439) days later. Conclusions and Relevance In this national cohort of adults with a biochemical diagnosis of PHPT, 67% had PHPT-associated end-organ damage at diagnosis or on follow-up. Despite this, parathyroidectomy was uncommon. These findings may inform strategies to optimize utilization of parathyroidectomy and mitigate PHPT-associated morbidity.

Background: Anaplastic thyroid cancer (ATC) is a rare but highly lethal form of thyroid cancer. Since the guidelines for the management of ATC by the American Thyroid Association were first published in 2012, significant clinical and scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, and researchers on published evidence relating to the diagnosis and management of ATC. Methods: The specific clinical questions and topics addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of the Task Force members (authors of the guideline). Relevant literature was reviewed, including serial PubMed searches supplemented with additional articles. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations. Results: The guidelines include the diagnosis, initial evaluation, establishment of treatment goals, approaches to locoregional disease (surgery, radiotherapy, targeted/systemic therapy, supportive care during active therapy), approaches to advanced/metastatic disease, palliative care options, surveillance and long-term monitoring, and ethical issues, including end of life. The guidelines include 31 recommendations and 16 good practice statements. Conclusions: We have developed evidence-based recommendations to inform clinical decision-making in the management of ATC. While all care must be individualized, such recommendations provide, in our opinion, optimal care paradigms for patients with ATC.

Background: Recent advances in research on thyroid carcinogenesis have yielded applications of diagnostic molecular biomarkers and profiling panels in the management of thyroid nodules. The specific utility of these novel, clinically available molecular tests is becoming widely appreciated, especially in perioperative decision making by the surgeon regarding the need for surgery and the extent of initial resection. Methods: A task force was convened by the Surgical Affairs Committee of the American Thyroid Association and was charged with writing this article. Results/Conclusions: This review covers the clinical scenarios by cytologic category for which the thyroid surgeon may find molecular profiling results useful, particularly for cases with indeterminate fine-needle aspiration cytology. Distinct strengths of each ancillary test are highlighted to convey the current status of this evolving field, which has already demonstrated the potential to streamline decision making and reduce unnecessary surgery, with the accompanying benefits. However, the performance of any diagnostic test, that is, its positive predictive value and negative predictive value, are exquisitely influenced by the prevalence of cancer in that cytologic category, which is known to vary widely at different medical centers. Thus, it is crucial for the clinician to know the prevalence of malignancy within each indeterminate cytologic category, at one's own institution . Without this information, the performance of the diagnostic tests discussed below may vary substantially.

Abstract Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies, but its genetic drivers remain little understood. In this study, we report losses in expression of the miRNA miR30a, which is downregulated in ATC compared with differentiated thyroid cancer and normal tissue. miR30a downregulation was associated with advanced differentiated thyroid cancer and higher mortality. Mechanistically, we found miR30a decreased cellular invasion and migration, epithelial–mesenchymal transition marker levels, lysyl oxidase (LOX) expression, and metastatic capacity. LOX was identified as a direct target of miR30a that was overexpressed in ATC and associated with advanced differentiated thyroid cancer and higher mortality rate. Consistent with its role in other cancers, we found that LOX inhibited cell proliferation, cellular invasion, and migration and metastasis in vitro and in vivo. Together, our findings establish a critical functional role for miR30a downregulation in mediating LOX upregulation and thyroid cancer progression, with implications for LOX targeting as a rational therapeutic strategy in ATC. Cancer Res; 75(2); 367–77. ©2014 AACR.