Research Updates
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Latest Research
UCLA Endocrine Surgery is committed to ongoing research in a quest to develop new treatments and cures for all for patients with conditions of the thyroid, parathyroid, and adrenal glands.
1. Fatigue, Constipation, and Depressed Mood
Surgery: A Case-Based Clinical Review, May 2026
Fatigue, constipation, and low mood are among the most commonly dismissed symptoms in clinical practice. This case-based review demonstrates how these presentations can be the first signal of an underlying, treatable endocrine disorder. Working through real patient cases, it gives clinicians and trainees a structured framework for recognizing when nonspecific symptoms warrant hormonal investigation, reducing the diagnostic delays that too often precede conditions like hypothyroidism, hypercalcemia, or adrenal insufficiency.
Journal of Clinical Endocrinology & Metabolism, February 2026
Oncocytic thyroid nodules are a particularly challenging diagnostic problem: their cytologic features frequently fall into indeterminate categories, and histopathology after surgery often reveals benign disease. This study evaluates how genomic sequencing classifiers perform in this specific nodule type, quantifying how often molecular testing can correctly stratify malignancy risk and spare patients from diagnostic surgery that carries real costs and complications. The findings directly inform whether current genomic tools are reliable enough to guide observation over the operating room.
3. Chinese Language Patients' Perceptions on Thyroid Disease and Treatment: A Qualitative Study
American Journal of Surgery, April 2026
Surgical decision-making in thyroid disease depends on shared understanding between patient and clinician. Language barriers and culturally shaped illness beliefs can fundamentally alter how patients interpret a diagnosis and weigh their options. Through qualitative interviews with Chinese-speaking patients, this study maps specific gaps in comprehension and trust, identifying where standardized communication falls short. The findings offer a concrete basis for developing culturally adapted counseling that supports genuine informed consent rather than assumed agreement.
Thyroid, January 2026
Radioactive iodine has been a default component of papillary thyroid cancer treatment for decades, but accumulating evidence questions its benefit in lower-risk disease. This commentary examines whether patients who have already undergone therapeutic lateral neck dissection represent a population in whom iodine ablation can be safely omitted, shifting the conversation from routine adjuvant treatment toward individualized, evidence-based de-escalation that reduces toxicity without compromising oncologic control.
Clinical Endocrinology, January 2025
For patients who achieve an excellent response to initial thyroid cancer therapy, defined by undetectable thyroglobulin, routine neck ultrasound adds surveillance burden without meaningfully changing management or detecting clinically significant recurrence. This work reinforces that risk-stratified follow-up protocols, rather than uniform imaging schedules, are the appropriate standard, with direct implications for reducing patient anxiety, healthcare resource use, and the costs of low-yield surveillance.
6. Genetic Testing Referral Rates for Pheochromocytoma and Paraganglioma in an Academic Tertiary Centre
Clinical Endocrinology, 2025
Pheochromocytomas and paragangliomas are hereditary in a substantial proportion of cases, with germline mutations carrying implications not only for the index patient but for at-risk family members. Despite clear guideline recommendations for genetic testing, this study audits real-world referral rates at a specialized centre and finds meaningful gaps in uptake. Identifying where the pathway breaks down, at diagnosis, surgical follow-up, or long-term surveillance, is the first step toward ensuring hereditary disease is not missed.
7. Association of BRAF V600E Allele Frequency With Outcomes in Papillary Thyroid Cancer
JCEM, November 2025
BRAF V600E is the most common somatic mutation in papillary thyroid cancer, but its presence alone has shown inconsistent prognostic value across studies. This work examines whether the proportion of tumor cells harboring the mutation, allele frequency, correlates with clinically meaningful outcomes including recurrence and disease-free survival. If allele burden proves independently prognostic, it would add a quantitative dimension to mutation-based risk stratification and inform decisions about adjuvant therapy intensity.
8. NCCN Guidelines Updates: Thyroid Carcinoma (Version 1.2025)
JNCCN, July 2025
NCCN guidelines represent the most widely referenced framework for thyroid cancer management in North America, directly shaping institutional protocols and individual clinical decisions across surgical oncology, endocrinology, and nuclear medicine. Version 1.2025 incorporates the latest trial data and expert consensus to update recommendations on surgery extent, radioactive iodine use, molecular testing, and surveillance. Clinicians across specialties need to understand what has changed and why, as these updates will set the standard of care applied to thousands of patients annually.
Thyroid, May 2025
Indeterminate thyroid nodules occupy a diagnostic gray zone that currently sends many patients to surgery for what turns out to be benign disease. Ultrasound imaging and molecular testing each provide complementary information, but are typically interpreted in isolation. This study tests whether a deep learning model integrating both data streams can outperform either alone in predicting malignancy, a clinically meaningful advance if it can reduce diagnostic uncertainty and concentrate surgery on patients who genuinely need it.
Surgery, May 2025
When papillary thyroid cancer has spread to lateral neck lymph nodes, surgeons face a recurring decision: whether to also dissect the central neck prophylactically in the absence of clinically evident disease there. This study measures how frequently occult central disease is actually present in this setting and whether its removal translates into better oncologic outcomes, directly informing a surgical choice with real implications for operative time, recurrent laryngeal nerve risk, and hypoparathyroidism.
JCEM, May 2025
Primary hyperparathyroidism is increasingly diagnosed in younger, reproductive-age patients, yet its effects on fertility and pregnancy remain poorly characterized in large populations. Persistent hypercalcemia carries potential risks for both mother and fetus, but the magnitude of those risks at the population level, and how they are modified by treatment, has not been well established. This population-based analysis quantifies those outcomes, providing the evidence base that clinicians need when counseling patients on the timing of parathyroidectomy relative to pregnancy planning.
American Surgeon, April 2025
Rural patients with thyroid cancer face compounding disadvantages: longer travel to specialized centers, limited access to multidisciplinary care, and greater economic burden from time away from work. Rather than simply documenting these disparities, this qualitative study engages rural patients and providers directly to identify innovations they consider feasible and acceptable. The result is an equity-focused agenda grounded in the perspectives of those most affected, moving the conversation from problem description to actionable solutions.
JCEM Case Reports, March 2025
Risk-stratified management of hereditary medullary thyroid carcinoma depends on knowing how aggressively a specific RET variant behaves: when to recommend prophylactic thyroidectomy, how intensively to surveil, and what prognosis to convey to carriers and their families. The RET K666N variant is rare enough that outcomes data are sparse. This case series characterizes the clinical course in a defined cohort of heterozygous carriers, filling an evidence gap that directly affects counseling and the timing of surgical intervention.
14. Histopathologic and Clinical Features of Bethesda III-VI Nodules Harboring Isolated RAS Mutations
Endocrine Practice, March 2025
RAS mutations are among the most commonly detected alterations on thyroid molecular testing, but their clinical significance varies considerably depending on the cytologic and histopathologic context. Isolated RAS, without co-occurring high-risk mutations, has been associated with predominantly benign or low-risk disease, but the actual distribution of pathology in molecularly screened nodules across Bethesda categories is not uniformly established. This study characterizes the histopathologic outcomes in this molecularly defined group, helping clinicians calibrate surgical recommendations when RAS is the only detected alteration.
Thyroid, January 2025
Surgeon volume is consistently associated with better thyroid surgery outcomes, but it may not fully account for the institutional environment in which surgery is performed. Safety-net hospitals serve disproportionately high proportions of low-income and uninsured patients, and face resource constraints that can influence perioperative care regardless of individual surgeon skill. This study isolates the contribution of safety-net burden to outcomes among high-volume surgeons, asking whether where a surgeon practices modifies the volume-outcome relationship, with implications for both health policy and how surgical quality metrics are reported.
16. Primary Hyperparathyroidism -- 'Overtones' May Be Overblown
JAMA Surgery, September 2024
Observational data have long suggested that patients with primary hyperparathyroidism carry a burden of nonspecific symptoms, including fatigue, cognitive fog, and mood changes, that improve after parathyroidectomy. This commentary critically examines the strength of that evidence, questioning whether symptom improvement in unblinded studies reflects a specific biochemical effect of normalized calcium or a placebo response to surgical intervention. The distinction matters because vague, self-reported symptoms have become a significant driver of surgical referrals, and the operative indication should rest on more solid footing.
JAMA Otolaryngology, May 2024
Active surveillance of low-risk papillary thyroid microcarcinoma is supported by high-quality prospective data demonstrating safety equivalent to immediate surgery, yet uptake in clinical practice remains low across North America. This paper examines the structural, psychological, and systems-level factors that drive that disconnect, from patient anxiety to surgeon discomfort with watchful waiting, and considers what would be required to align real-world management with what the evidence supports. Narrowing this gap has direct implications for reducing overtreatment at scale.
18. Outcomes of Cytologically Indeterminate Thyroid Nodules Managed with Genomic Sequencing Classifier
JCEM, February 2024
Genomic sequencing classifiers for indeterminate thyroid nodules were validated in controlled research settings; this study examines how they perform when deployed in routine clinical practice across a real patient population. Measuring rates of malignancy among patients who underwent surgery after genomic testing, and rates among those who were observed based on a benign classifier result, directly quantifies how well the test translates from trial conditions to clinical decision-making, and whether the promise of reducing unnecessary surgery is being realized.
Nano Today, October 2024
Monitoring differentiated thyroid cancer after treatment currently relies on thyroglobulin levels and neck ultrasound, tools with meaningful limitations in patients with thyroglobulin antibodies or structurally inaccessible disease. Liquid biopsy, which detects circulating tumor-derived material in blood, offers a potentially more sensitive and accessible surveillance tool. This study applies a click chemistry enrichment strategy to simultaneously capture both circulating tumor cells and extracellular vesicles, characterizing the technique's feasibility and signal in thyroid cancer patients and laying groundwork for a blood-based monitoring approach.
JCEM, April 2024
The use of AI in thyroid nodule evaluation has expanded rapidly, with dozens of models now published for ultrasound interpretation, cytology classification, and molecular data analysis. This systematic review synthesizes that literature to assess where AI genuinely improves on standard diagnostic approaches, where evidence remains insufficient, and what technical and regulatory barriers stand between current research prototypes and clinical deployment. For clinicians navigating an increasingly crowded landscape of diagnostic tools, this overview provides a grounded and critical assessment of what AI currently can and cannot do.
21. Malignant Pheochromocytoma Presenting as a Large Adrenal Mass with Cavoatrial Tumor Thrombus
AACE Endocrinology and Diabetes, June 2024
Pheochromocytoma with intravascular extension to the inferior vena cava and right heart is an exceptionally rare presentation that demands coordinated management across endocrinology, surgery, and cardiac surgery. This case documents the clinical course, preoperative endocrine preparation, and surgical approach in a patient with cavoatrial tumor thrombus, a scenario where delay or incomplete preoperative alpha blockade carries life-threatening consequences. Detailed case reports of this presentation serve as an important reference for multidisciplinary teams encountering a condition too rare to study prospectively.
22. Rural-Urban Disparities in the Continuum of Thyroid Cancer Care: Analysis of 92,794 Cases
Thyroid, May 2024
Prior disparities research in thyroid cancer has largely focused on single stages of care, access to surgery or receipt of radioactive iodine, but gaps may exist across the entire treatment continuum, from time to diagnosis through long-term surveillance. Analyzing nearly 93,000 cases, this study provides population-level evidence on how rural-urban location shapes each step of that journey. The scale of the dataset allows meaningful subgroup analysis and moves the conversation beyond whether disparities exist to where along the care pathway they are most pronounced and therefore most addressable.
23. Extent of Surgery for Medullary Thyroid Cancer and Prevalence of Occult Contralateral Foci
JAMA Otolaryngology, January 2024
In hereditary medullary thyroid carcinoma, total thyroidectomy is standard because of the bilateral and multicentric nature of the disease, but in sporadic cases, the necessity of contralateral thyroid resection is less clear. This study measures how often occult disease is found in the contralateral lobe of patients undergoing surgery for apparently unilateral sporadic medullary thyroid cancer, providing direct evidence to inform the extent-of-surgery decision and the tradeoffs between completeness of oncologic resection and the risks of bilateral dissection.
Journal of Clinical & Translational Endocrinology, March 2024
TERT promoter mutations are among the most clinically significant alterations in thyroid cancer, consistently associated with aggressive disease behavior, dedifferentiation, and worse survival. When detected in a cytologically indeterminate nodule, a TERT mutation fundamentally changes the risk picture, yet the histopathologic spectrum of TERT-mutated indeterminate nodules has not been well characterized. This study defines what surgeons and pathologists actually find at resection in this molecularly high-risk group, establishing the histologic correlates of TERT positivity and supporting its role as a marker that should prompt definitive surgery.
Surgery, January 2024
Hurthle cell-predominant thyroid nodules are a well-recognized challenge for both cytologic and molecular diagnosis: they generate high rates of indeterminate cytology and contain molecular alterations that can overlap between benign oxyphilic adenomas and malignant Hurthle cell carcinomas. This study specifically evaluates the diagnostic performance of genomic classifiers in this cytologic subtype, determining sensitivity, specificity, and malignancy rates in classifier-positive versus classifier-negative nodules. The findings establish how much confidence clinicians can place in molecular test results when Hurthle cell features are present.
JCEM, January 2024
As genomic sequencing of thyroid nodules becomes routine practice, understanding the full distribution and co-occurrence of molecular alterations across a large, real-world population is essential for interpreting individual test results. Drawing on a multicenter cohort, this study maps the molecular landscape of thyroid nodules, characterizing mutation frequencies, co-mutation patterns, and their associations with histopathologic outcomes. The dataset provides a reference framework that clarifies not just which mutations matter, but how they interact to shape malignancy risk and disease behavior.
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