Comparison of Preoperative Alpha-blockade for Resection of Paraganglioma and Pheochromocytoma.

OBJECTIVE: Phenoxybenzamine (nonselective, noncompetitive alpha-blocker) is the preferred drug for preoperative treatment of pheochromocytoma, but doxazosin (selective, competitive alpha-blocker) may be equally effective. We compared the efficacy of doxazosin vs phenoxybenzamine. METHODS: We conducted a prospective study of patients undergoing pheochromocytoma or paraganglioma resection by randomizing pretreatment with phenoxybenzamine or doxazosin at a single tertiary referral center. The high cost of phenoxybenzamine led to high crossover to doxazosin. Randomization was halted, and a consecutive historical cohort of phenoxybenzamine patients was included for a case-control study design. The efficacy of alpha-blockade was assessed with preinduction infusion of incremental doses of phenylephrine. The primary outcomes were mortality, cardiovascular complications, and intensive care unit admission. The secondary outcomes were hemodynamic instability index (proportion of operation outside of hemodynamic goals), adequacy of blockade by the phenylephrine titration test, and drug costs. RESULTS: Twenty-four patients were prospectively enrolled (doxazosin, n = 20; phenoxybenzamine, n = 4), and 15 historical patients treated with phenoxybenzamine were added (total phenoxybenzamine, n = 19). No major cardiovascular complications occurred in either group. The phenylephrine dose-response curves showed less blood pressure rise in the phenoxybenzamine than in the doxazosin group (linear regression coefficient = 0.008 vs 0.018, P = .01), suggesting better alpha-blockade in the phenoxybenzamine group. The median hemodynamic instability index was 14% vs 13% in the phenoxybenzamine and doxazosin groups, respectively (P = .56). The median highest daily cost of phenoxybenzamine was $442.20 compared to $5.06 for doxazosin. CONCLUSION: Phenoxybenzamine may blunt intraoperative hypertension better than doxazosin, but this difference did not translate to fewer cardiovascular complications and is offset by a considerably increased cost.

Surgery for Primary Hyperparathyroidism: Adherence to Consensus Guidelines in an Academic Health System.

OBJECTIVE: To determine the extent to which consensus guidelines for surgery in patients with primary hyperparathyroidism (PHPT) are followed within an academic health system. BACKGROUND: Previous studies have shown that adherence to consensus guidelines in community practice is low. METHODS: Adults with biochemically confirmed PHPT who received primary care within an academic health system were identified from 2005 to 2015. Multivariable logistic regression was used to analyze predictors of parathyroidectomy (PTx). RESULTS: In 617 patients, the overall PTx rate was 30.8%. When individual consensus criteria were examined, age <50 (P<0.01), serum calcium >11.3 mg/dL (P < 0.01), and hypercalciuria (P = 0.02) were associated with PTx; while nephrolithiasis (P = 0.07) and osteoporosis (P = 0.34) did not affect the PTx rate. The PTx rate increased with the number of consensus criteria satisfied (1 criterion, 33%; 2 criteria, 45%; 3 or more criteria, 82%, P < 0.01). Independent predictors of PTx included male sex [odds ratio (OR) 1.7, 95% confidence interval (CI) 1.1-2.8], increasing serum parathyroid hormone (OR 1.1 per 10 pg/mL 95% CI 1.05-1.13), and endocrinologist evaluation (OR 1.6, 95% CI 1.1-2.4); while Black race (OR 0.4, 95% CI 0.2-0.8), lack of 24-hour urine calcium measurement (OR 0.5, 95% CI 0.3-0.8), Charlson Comorbidity Index ≥ 2 (OR 0.6, 95% CI 0.4-0.9), and age ≥80 years (OR 0.2, 95% CI 0.1-0.4) predicted against PTx. CONCLUSION: Within an academic health system, consensus guidelines do appear to influence the decision for surgery in patients with PHPT. However, the level of compliance is generally low, and similar to that observed in community practice.

Biochemical and Skeletal Outcomes of Parathyroidectomy for Normocalcemic (Incipient) Primary Hyperparathyroidism.

BACKGROUND: Normocalcemic (incipient) primary hyperparathyroidism (PHPT) is characterized by inappropriately elevated parathyroid hormone (PTH) levels in the setting of normal serum calcium. The biochemical and skeletal outcomes after parathyroidectomy for normocalcemic PHPT are not well-described. METHODS: All patients who underwent parathyroidectomy for normocalcemic PHPT at a single institution were retrospectively reviewed (2006-2016). Pre- and postoperative calcium, PTH, and bone mineral density (BMD) were compared between patients with normalized versus persistently elevated PTH levels > 6 months after parathyroidectomy. Multivariable Cox regression was used to identify risk factors associated with persistently elevated PTH levels after parathyroidectomy. RESULT: Parathyroidectomy was performed in 71 patients with normocalcemic PHPT, of whom 38 (53.5%) had multi-gland disease. No patients became hypercalcemic, with a median follow-up of 23.1 months. Persistently elevated PTH levels were noted in 33 (46.5%) patients. In multivariable analysis, preoperative PTH > 100 pg/mL was associated with persistently elevated PTH levels after parathyroidectomy. In 38 patients with available pre- and postoperative BMD measurements, the mean preoperative BMD improved + 5.6% (p < 0.01) in patients with normalized PTH, while no significant change was observed in patients with persistently elevated PTH levels (- 2.2%, p = 0.47). CONCLUSIONS: Elevated PTH levels are common after parathyroidectomy for normocalcemic PHPT. Improvements in BMD may be predicated on long-term normalized PTH levels following surgery.

Risk Factors for Readmission After Parathyroidectomy for Renal Hyperparathyroidism.

BACKGROUND: Patients with renal hyperparathyroidism (RHPT) are susceptible to major electrolyte fluctuations following parathyroidectomy, which may predispose them to early readmission. The purpose of this study is to evaluate risk factors for readmission in patients undergoing parathyroidectomy for RHPT. METHODS: Patients with renal failure who underwent parathyroidectomy were abstracted from the California Office of Statewide Health Planning and Development (1999-2012). Multivariable logistic regression was used to identify risk factors for readmission within 30 days of discharge. RESULTS: The cohort included 4411 patients, of whom 17% were readmitted. Procedures included subtotal parathyroidectomy (74% of cases) and total parathyroidectomy with autotransplantation (26%). Median time to readmission was 9 days (interquartile range 4-16 days). Electrolyte disturbances including hypocalcemia were present in 36% of readmissions and were the most common cause for readmission. Independent risk factors for readmission included Black race [odds ratio (OR) 1.26, 95% confidence interval (CI) 1.00-1.57], Hispanic race (OR 1.38, 95% CI 1.12-1.71), disposition with home health (OR 1.94, 95% CI 1.35-2.77), disposition to a skilled nursing facility (OR 2.30, 95% CI 1.58-3.35), and total parathyroidectomy with autotransplantation (OR 1.27, 95% CI 1.06-1.52). Advancing age (OR 0.98, 95% CI 0.98-0.99) and surgery at a high-volume hospital (OR 0.53, 95% CI 0.36-0.77) were protective against readmission. CONCLUSIONS: Patients undergoing parathyroidectomy for RHPT have a high readmission rate, most frequently for metabolic complications. Increased postoperative vigilance, which may include outpatient laboratory monitoring, may be indicated in patients with risk factors for readmission.

BIOCHEMICAL DYNAMICS OF UNTREATED PRIMARY HYPERPARATHYROIDISM: AN OBSERVATIONAL STUDY.

Objective: The natural biochemical history of untreated primary hyperparathyroidism (PHPT) is poorly understood. The purpose of this study was to determine the extent of biochemical fluctuations in patients with PHPT. Methods: Retrospective cohort study from January 1, 1995, to December 31, 2014. Serum calcium and parathyroid hormone (PTH) levels in patients with classic (Ca >10.5 mg/dL, PTH >65 pg/mL) and nonclassic (Ca >10.5 mg/dL, PTH 40 to 65 pg/mL) PHPT were followed longitudinally at 1, 2, and 5 years. Biochemical profiles in follow-up were ranked in descending biochemical severity as classic PHPT, nonclassic PHPT, normal calcium with elevated PTH (Ca <10.5 mg/dL, PTH >65 pg/mL), possible PHPT (Ca >10.5 mg/dL, PTH 21 to 40 pg/mL), or absent PHPT (Ca >10.5 mg/dL, PTH <21 pg/mL or Ca <10.5 mg/dL, PTH <65 pg/mL). Results: Of 10,598 patients, 1,570 were treated with parathyroidectomy (n = 1,433) or medications (n = 137), and 4,367 were censored due to study closure, disenrollment, or death. In the remaining 4,661 untreated patients with 5 years of follow-up, 235 (5.0%) progressed to a state of increased biochemical severity, whereas 972 (20.8%) remained the same, and 3,454 (74.1%) regressed to milder biochemical states. In 2,522 untreated patients with classic PHPT, patients most frequently transitioned to the normal calcium with elevated PTH group (n = 1,257, 49.8%). In 2,139 untreated patients with nonclassic PHPT, patients most frequently transitioned to the absent PHPT group (n = 1,354, 63.3%). Conclusion: PHPT is a biochemically dynamic disease with significant numbers of patients exhibiting both increases and decreases in biochemical severity. Abbreviations: IQR = interquartile range; KPSC = Kaiser Permanente Southern California; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; PTx = parathyroidectomy.

NONOPERATIVE MANAGEMENT OF DIFFERENTIATED THYROID CANCER IN CALIFORNIA: A POPULATION-LEVEL ANALYSIS OF 29,978 PATIENTS.

OBJECTIVE: There has been increasing interest in active surveillance of papillary thyroid microcarcinoma. The objective of this study was to characterize the incidence and outcomes of nonoperatively managed differentiated thyroid cancers (DTCs) in California. METHODS: Biopsy-proven DTCs from the California Cancer Registry were linked to data from the California Office of Statewide Health Planning and Development (2004-2012). Low-risk tumors were defined as localized disease measuring <4 cm without extrathyroidal extension, nodal involvement, or distant metastasis. RESULTS: Of 29,978 patients with DTC, 318 (1.1%) were managed nonoperatively. Compared to operatively managed patients, patients managed nonoperatively were older with more comorbidities, larger tumors (mean size, 2.9 cm vs. 2.0 cm), and an increased rate of distant metastasis (20.4% vs. 3.4%). Independent predictors of nonoperative management included increasing age, larger tumor size, papillary histology, and distant metastases. Of 10,795 patients with low-risk tumors, 161 (1.5%) were managed nonoperatively, with tumor size as follows: <1 cm (15.5%), 1 to 2 cm (50.3%), >2 to 3 cm (24.3%), and >3 to 4 cm (9.9%). There were no disease-specific deaths in the low-risk, nonoperative group (median follow-up [interquar-tile range], 21.3 [5.7 to 51.1] months). The proportion of patients managed nonoperatively remained relatively stable over the study period (mean increase 0.1% per year, P = .09). All P values were <.05 unless otherwise stated. CONCLUSION: The vast majority of patients with DTCs are treated surgically, suggesting active surveillance is rarely practiced in California. Although follow-up was limited, no disease-specific mortality in nonoperatively managed, low-risk DTCs was observed. ABBREVIATIONS: CCI = Charlson Comorbidity Index; CCR = California Cancer Registry; CI = confidence interval; DTC = differentiated thyroid cancer; FTC = follicular thyroid carcinoma; HCC = Hürthle cell carcinoma; IQR = interquartile range; mPTC = papillary thyroid micro-carcinoma; OR = odds ratio; OSPHD = Office of Statewide Health Planning and Development; PTC = papillary thyroid carcinoma.

The impact of social determinants of health on thyroid cancer mortality and time to treatment.

BACKGROUND: Whereas racial disparities in thyroid cancer care are well established, the role of social determinants of health is less clear. We aimed to assess the individual and cumulative impact of social determinants of health on mortality and time to treatment among patients with thyroid cancer. METHODS: We collected social determinants of health data from thyroid cancer patients registered in the National Cancer Database from 2004 to 2017. We created a count variable for patients in the lowest quartile of each social determinant of health (ie, low income, low education, and no insurance). We assessed the association of social determinants of health with mortality and time to treatment and the association between cumulative social determinants of health count and time to treatment using Cox regression. RESULTS: Of the 142,024 patients we identified, patients with longer time to treatment had greater mortality compared to patients treated within 90 days (90-180 days, adjusted hazard ratio 1.21 (95% confidence interval 1.13-1.29, P < .001); >180 days, adjusted hazard ratio 1.57 (95% confidence interval 1.41-1.76, (P < .001). Compared to patients with no adverse social determinants of health, patients with 1, 2, or 3 adverse social determinants of health had a 10%, 12%, and 34%, respectively, higher likelihood of longer time to treatment (1 social determinant of health, hazard ratio 0.90, 95% confidence interval 0.89-0.92, P < .001; 2 social determinants of health, hazard ratio 0.88, 95% confidence interval 0.87-0.90, P < .001; 3 social determinants of health, hazard ratio 0.66, 95% confidence interval 0.62-0.71, P < .001 for all). On subgroup analysis by race, each adverse social determinant of health was associated with an increased likelihood of a longer time to treatment for Black and Hispanic patients (P < .05). CONCLUSION: A greater number of adverse social determinants of health leads to a higher likelihood of a longer time to treatment for patients with thyroid cancer, which, in turn, is associated with an increased risk for mortality.

Trends in thyroid function following radiofrequency ablation of benign, nonfunctioning thyroid nodules: A single institution review.

BACKGROUND: Radiofrequency ablation (RFA) effectively reduces volume and improves symptoms of benign, non-functioning thyroid nodules (NFTNs). Given RFA's unclear impact on thyroid function, we examined post-RFA trends in thyroid hormones and antibodies. METHODS: A retrospective cross-sectional analysis was conducted of patients treated at Columbia University with RFA for benign NFTNs between August 2019 and July 2023. Thyroid function tests were recorded pre-RFA and repeated 3, 6, and 12 months post-RFA. RESULTS: We analyzed 185 patients with 243 benign NFTNs who underwent RFA. Volume reduction ratio increased post-RFA. Mean TSH increased to 2.4 mlU/L (p â€‹= â€‹0.005) at 3 months post-RFA and decreased to 1.8 mlU/L (p â€‹= â€‹0.551) by 12 months post-RFA. Tg and TPO antibody levels peaked at 6 months post-RFA (103.1 IU/mL, p â€‹= â€‹0.868 and 66.6 IU/mL, p â€‹= â€‹0.523, respectively). CONCLUSIONS: With expected volume reduction post-RFA, we observed transient relative hypothyroidism as well as transient increases in thyroid antibodies, with normalization of these changes within 12 months.

Does the Adoption of Molecular Testing Cause Decreased Thyroidectomy Rates in a National Cohort? A Quasiexperimental Study of High- Versus Low-Adoption States.

Background: Over the last decade, the utilization of molecular testing (MT) for the evaluation of thyroid nodules has increased. Rates and patterns of adoption of MT and its effect on thyroidectomy rates nationally are unknown. Varying rates of MT adoption at the state level provide an opportunity to study the effects of MT on thyroidectomy rates using a quasiexperimental study design. Methods: We performed a retrospective analysis of American adult patients in the Merative™ MarketScan® Research Databases who underwent thyroid fine-needle aspiration (FNA) from 2011 to 2021. MT included commercially available DNA and RNA platforms and traditional targeted mutational analysis. Interrupted time series analysis was used to evaluate the inflection of MT adoption and thyroidectomy rates after 2015. Difference-in-differences (DID) analysis was used to causally analyze the effect of MT adoption on thyroidectomy rates in high-adoption (at least a 10% increase in MT utilization) versus low-adoption states (no more than 5% increase in MT utilization) from 2015 to 2021. Results: We identified 471,364 patients who underwent thyroid FNA. The utilization of MT increased over the study period from 0.01% [confidence interval, CI: 0.00% to 0.02%] to 10.1% [CI: 9.7% to 10.5%], in 2021, with an immediate (ß2 = 1.61, p = 0.002) and deeper (ß3 = 0.6, p < 0.001) increase in MT adoption after 2015. Utilization of MT was lower in black patients, the elderly, rural areas, and patients with Medicaid (p < 0.05). Thyroidectomy rates were inversely correlated with MT utilization (r = -0.98, p < 0.0001). From 2015 to 2021, the average MT utilization rate increased from 2.4% to 15.3% in high-adoption states and 1.6% to 5.6% in low-adoption states. In low-adoption states, thyroidectomy rates decreased more but to similar levels (18.5-13.2%) compared with high-adoption states (15.9-13.4%) with an adjusted DID rate of -3.3% [CI -5.6% to -0.8%]. Conclusions: The acceleration in adoption of MT after 2015 likely coincides with the publication of American Thyroid Association guidelines. Black, elderly, and rural patients are less likely to receive MT. Although thyroidectomy rates were inversely correlated with MT utilization, our study suggests that this correlation is not causal. The effect of MT on thyroidectomy rates may be overshadowed by decreasing aggressiveness of thyroid nodule evaluation.

Molecular Testing for Bethesda III Thyroid Nodules: Trends in Implementation, Cytopathology Call Rates, Surgery Rates, and Malignancy Yield at a Single Institution.

Background: Molecular testing (MT) has become standard practice to more accurately rule out malignancy in indeterminate Bethesda III (BIII) thyroid lesions. We sought to assess the adoption of this technology and its impact on cytology reporting, malignancy yield, and rates of surgery across community and academic sites affiliated with a tertiary medical center. Methods: We performed a retrospective cross-sectional study including all fine-needle aspirations (FNAs) analyzed at our institution from 2017 to 2021. We analyzed trends in MT utilization by platform and by community or academic site. We compared BIII call rates, MT utilization rates, rates of subsequent surgery, and malignancy yield on final pathology before and after MT became readily available using chi-square analysis and linear regression. Results: A total of 8960 FNAs were analyzed at our institution from 2017 to 2021. There was broad adoption of MT across both community and academic sites. There was a significant increase in both the BIII rate and the utilization of MT between the pre- and post-MT periods (p < 0.001 and p < 0.001). There was no significant change in the the malignancy yield on final pathology (57.1% vs. 50.0%, p = 0.347), while the positive predictive value of MT decreased from 85% to 50% (p = 0.008 [confidence interval 9.5-52.5% decrease]). Conclusions: The use of MT increased across the institution over the study period, with the largest increase seen after a dedicated pass for MT was routinely collected. This increased availability of MT may have led to an unintended increase in the rates of BIII lesions, MT utilization, and surgery for benign nodules. Physicians who use MT should be aware of potential consequences of its adoption to appropriately counsel patients.

A national study of postoperative thyroid hormone supplementation rates after thyroid lobectomy.

BACKGROUND: The American Thyroid Association updated guidelines in 2015 to allow lobectomy for low-risk thyroid cancers. The objectives of this study were (1) to determine thyroid hormone supplementation rates after lobectomy and (2) to evaluate the effect of the American Thyroid Association guideline change on lobectomy and hormone supplementation rates among thyroid cancer patients. METHODS: The Merative MarketScan Databases was used to identify adult (≥age 18) patients who underwent thyroidectomy for benign nodules or thyroid cancer. The association between indication for surgery and postoperative thyroid hormone supplementation was examined using χ2 analyses and multivariable logistic regression models. Among patients with thyroid cancer, lobectomy and hormone supplementation rates were compared in the periods before (2008-2015) and after the guideline change (2016-2019). RESULTS: Of the 81,926 patients identified, 33,756 (41.2%) underwent thyroid lobectomy, 45,104 (55.1%) underwent total thyroidectomy, and 3,066 (3.7%) underwent completion thyroidectomy. Patients who underwent lobectomy for malignancy were significantly more likely to require hormone supplementation (59.3% vs 39.4% [P < .001], adjusted odds ratio 2.34 [95% confidence interval 2.20-2.48]) compared to those with benign disease. Compared to the 2008 to 2015 period, the proportion of patients who underwent lobectomy for thyroid cancer was higher in the 2016 to 2019 period (34.3% vs 30.3%, P < .001), with fewer patients requiring completion thyroidectomy (25.6% vs 29.8%, P < .001) and thyroid hormone supplementation (56.9% vs 60.1%, P = .04). CONCLUSION: The postoperative thyroid hormone supplementation rate was significantly higher in patients who had thyroid cancers compared to benign diseases. After the American Thyroid Association guidelines changed, lobectomy rates increased significantly without a concomitant increase in the completion of thyroidectomy.

Population-level analysis of pancreatic neuroendocrine tumors 2 cm or less in size.

BACKGROUND: There is a paucity of evidence regarding incidence and predictors of survival in pancreatic neuroendocrine tumors (PNETs)≤2 cm in size. METHODS: Patients having undergone resection for nonfunctioning PNETs were selected from the SEER database (1988-2009) and an institutional pathology database (1996-2012). PNETs≤2 cm were compared with PNETs>2 cm. Data were analyzed with χ2 tests, ANOVA, the Kaplan-Meier method, log rank tests, and Cox proportional hazard, and binary logistic regression. RESULTS: The incidence of PNETs≤2 cm in the United States has increased by 710.4% over the last 22 years. Rates of extrapancreatic extension, nodal metastasis, and distant metastasis in PNETs≤2 cm in the SEER database were 17.9, 27.3, and 9.1%, respectively. The rate of nodal metastasis in our institutional series was 5.7%. Disease-specific survival at 5, 10, and 15 years for PNETs≤2 cm was 91.5, 84.0, and 76.8%. Decreased disease-specific survival was not associated with nodal metastasis, but rather with high grade [moderately differentiated, hazard ratio (HR) 37.2, 95% confidence interval (CI) 2.7-518.8; poorly differentiated, HR 94.2, 95% CI 4.9-1,794.4; reference, well differentiated], and minority race (Asian, HR 30.2, 95% CI 3.1-291.7; Black, HR 60.1, 95% CI 2.1-1,027.9; reference, White). CONCLUSIONS: Pancreatic neuroendocrine tumors≤2 cm are increasingly common, and the most significant predictors of disease-specific survival are grade and race. The SEER database excludes PNETs considered to be benign, and rates of extrapancreatic extension, nodal metastasis, and distant metastasis are overestimated. Small size, however, does not preclude malignant behavior.

If the price is right: Cost-effectiveness of radiofrequency ablation versus thyroidectomy in the treatment of benign thyroid nodules.

BACKGROUND: Radiofrequency ablation is an emerging technology in the United States to treat benign thyroid nodules. The cost-effectiveness of radiofrequency ablation in comparison with traditional thyroidectomy is unknown. METHODS: A patient-level state transition microsimulation decision model was constructed comparing radiofrequency ablation with lobectomy in the management of benign thyroid nodules. Our base case was a 45-year-old woman with a solitary 30-cm3 nodule. Estimates of health utilities, complications, and mortality were obtained from the literature, and costs were estimated using Medicare reimbursement data. The primary outcomes of interest included total cost, quality-adjusted life years, and incremental cost-effectiveness ratios. All model estimates were subjected to 1-way sensitivity analyses to identify factors that strongly influence cost-effectiveness. A probabilistic sensitivity analysis was run across 1 million simulations to gauge outcome confidence with a willingness-to-pay threshold set at $100,000/quality-adjusted life year. RESULTS: Radiofrequency ablation was assumed to cost $5,000, with an initial success rate of 78%. Patients with volume reduction ratio <50% underwent a second treatment of radiofrequency ablation. Radiofrequency ablation represented the dominant strategy, yielding 21.31 quality-adjusted life years for a total cost of $16,563 in comparison to lobectomy, which yielded 21.13 quality-adjusted life years for a total cost of $19,262. In a 1-way sensitivity analysis varying the cost of radiofrequency ablation across of range of values, the radiofrequency ablation strategy remained cost-effective until the cost of radiofrequency ablation exceeded $12,330 at willingness-to-pay $50,000 or $17,950 at willingness-to-pay $100,000. CONCLUSION: Radiofrequency ablation is a cost-effective strategy in the treatment of benign thyroid nodules but is most sensitive to the cost of radiofrequency ablation.

Older Adults With Newly Diagnosed AML: Hot Topics for the Practicing Clinician.

Over the past decade, our understanding of AML pathogenesis and pathophysiology has improved significantly with mutational profiling. This has led to translational advances in therapeutic options, as there have been 10 new US Food and Drug Administration (FDA) approvals for AML therapies since 2017, half of which target specific driver mutations in FLT3, IDH1, or IDH2. These new agents have expanded the therapeutic armamentarium for AML, particularly for patients who are considered ineligible for intensive chemotherapy with anthracycline- and cytarabine-containing regimens. These new treatment options are relevant because the median age at diagnosis is 68 years, and outcomes for patients older than 60 years have historically been dismal. However, the optimal approach to incorporating novel agents into frontline regimens remains a clinical challenge, particularly with regard to sequencing of therapies, considering the role of allogeneic hematopoietic stem cell transplantation and managing toxicities.

Phenoxybenzamine is no longer the standard agent used for alpha blockade before adrenalectomy for pheochromocytoma: A national study of 552 patients.

BACKGROUND: Phenoxybenzamine has been the standard agent for blockade before adrenalectomy for pheochromocytoma. However, high cost and limited availability have hampered its use. This study investigated whether other agents have supplanted the use of phenoxybenzamine as the first-line agent for alpha blockade in pheochromocytoma. METHODS: We performed a retrospective analysis of patients in the IBM MarketScan Database who underwent adrenalectomy for pheochromocytoma (2008-2019). Patients were categorized as having been blocked with phenoxybenzamine, selective alpha blockers, calcium channel blockers and/or beta blockers, or none of the above. The outcomes included prescription costs, perioperative costs, and length of stay. RESULTS: A total of 552 patients were identified; 58.7% were female, and the median age was 49 (interquartile range 40-57) years. In total, 291 (52.7%) patients were blocked with phenoxybenzamine, 114 (20.7%) with selective alpha blockers, 42 (7.6%) with only calcium channel blockers and/or beta blockers, and 76 (13.8%) with none. The proportion of patients blocked with phenoxybenzamine decreased from 71.0% in 2008 to 21.2% in 2019. The proportion of patients blocked with selective alpha blockers increased from 6.5% in 2008 to 42.4% and in 2019. The median cost of phenoxybenzamine increased from $722 (interquartile range $441-$1,514) in 2008 to $9,616 (interquartile range $5,049-$16,373) in 2019 (P < .001). Length of stay (2 [interquartile range 1-4] days vs 2 [interquartile range 0-3] days) and total perioperative costs ($24,250 [interquartile range $17,462-$33,849] vs $22,098 [interquartile range $16,341-$29,178] between phenoxybenzamine and selective alpha blocker groups were similar. CONCLUSION: There has been a significant shift away from phenoxybenzamine for preoperative blockade before resection of pheochromocytoma. Selective alpha blockers and calcium channel blockers are increasingly used, likely due to reduced costs, without compromised length of stay or intensive care unit admission.

Effectiveness of Molecular Testing Techniques for Diagnosis of Indeterminate Thyroid Nodules: A Randomized Clinical Trial.

IMPORTANCE: Approximately 20% of thyroid nodules display indeterminate cytology. Molecular testing can refine the risk of malignancy and reduce the need for diagnostic hemithyroidectomy. OBJECTIVE: To compare the diagnostic performance between an RNA test (Afirma genomic sequencing classifier) and DNA-RNA test (ThyroSeq v3 multigene genomic classifier). DESIGN, SETTING, AND PARTICIPANTS: This parallel randomized clinical trial of monthly block randomization included patients in the UCLA Health system who underwent thyroid biopsy from August 2017 to January 2020 with indeterminate cytology (Bethesda System for Reporting Thyroid Cytopathology category III or IV). INTERVENTIONS: Molecular testing with the RNA test or DNA-RNA test. MAIN OUTCOMES AND MEASURES: Diagnostic test performance of the RNA test compared with the DNA-RNA test. The secondary outcome was comparison of test performance with prior versions of the molecular tests. RESULTS: Of 2368 patients, 397 were eligible for inclusion based on indeterminate cytology, and 346 (median [interquartile range] age, 55 [44-67] years; 266 [76.9%] women) were randomized to 1 of the 2 tests. In the total cohort assessed for eligibility, 3140 thyroid nodules were assessed, and 427 (13.6%) nodules were cytologically indeterminate. The prevalence of malignancy was 20% among indeterminate nodules. The benign call rate was 53% (95% CI, 47%-61%) for the RNA test and 61% (95% CI, 53%-68%) for the DNA-RNA test. The specificities of the RNA test and DNA-RNA test were 80% (95% CI, 72%-86%) and 85% (95% CI, 77%-91%), respectively (P = .33); the positive predictive values (PPV) of the RNA test and DNA-RNA test were 53% (95% CI, 40%-67%) and 63% (95% CI, 48%-77%), respectively (P = .33). The RNA test exhibited a higher PPV compared with the prior test version (Afirma gene expression classifier) (54% [95% CI, 40%-67%] vs 38% [95% CI, 27%-48%]; P = .01). The DNA-RNA test had no statistically significant difference in PPV compared with its prior version (ThyroSeq v2 next-generation sequencing) (63% [95% CI, 48%-77%] vs 58% [95% CI, 43%-73%]; P = .75). Diagnostic thyroidectomy was avoided in 87 (51%) patients tested with the RNA test and 83 (49%) patients tested with the DNA-RNA test. Surveillance ultrasonography was available for 90 nodules, of which 85 (94%) remained stable over a median of 12 months follow-up. CONCLUSIONS AND RELEVANCE: Both the RNA test and DNA-RNA test displayed high specificity and allowed 49% of patients with indeterminate nodules to avoid diagnostic surgery. Although previous trials demonstrated that the prior version of the DNA-RNA test was more specific than the prior version of the RNA test, the current molecular test techniques have no statistically significant difference in performance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02681328.

End-organ effects of primary hyperparathyroidism: A population-based study.

BACKGROUND: Patients with primary hyperparathyroidism are at risk for skeletal and renal end-organ damage. METHODS: We studied patients with biochemically confirmed primary hyperparathyroidism from 1995-2014 and quantified the frequency of osteoporosis, nephrolithiasis, hypercalciuria, and decrease in renal function. RESULTS: The cohort comprised 9,485 patients. In total, 3,303 (35%) had preexisting end-organ effects (osteoporosis, 24%; nephrolithiasis, 10%; hypercalciuria, 5%). Of 6,182 remaining patients, 1,769 (29%) exhibited progression to 1 or more end-organ effects over a median 3.7 years. Among patients with classic primary hyperparathyroidism (calcium and parathyroid hormone increased), progression was unrelated to the degree of hypercalcemia (calcium >11.5 mg/dL, hazard ratio 1.03, 95% confidence interval 0.85-1.25; 11.1-11.5 mg/dL, HR 1.07, 95% confidence interval 0.93-1.23; 10.5-11.0 mg/dL = reference). Patients with nonclassic primary hyperparathyroidism (calcium increased, parathyroid hormone 40-65 pg/mL) had a lesser risk of progression (calcium >11.5 mg/dL, hazard ratio 0.68, 95% confidence interval 0.50-0.94; 11.1-11.5 mg/dL, hazard ratio 0.68, 95% confidence interval 0.56-0.82; 10.5-11.0 mg/dL, hazard ratio 0.66, 95% confidence interval 0.59-0.74). End-organ damage developed before or within 5 years of diagnosis for 62% of patients. CONCLUSION: End-organ manifestations of primary hyperparathyroidism develop before biochemical diagnosis or within 5 years in most patients. End-organ damage occurred more frequently in patients with classic primary hyperparathyroidism versus nonclassic primary hyperparathyroidism, regardless of severity of hypercalcemia.

Cost effectiveness of immediate biopsy versus surveillance of intermediate-suspicion thyroid nodules.

BACKGROUND: In an effort to reduce overdiagnosis of low-risk thyroid cancer, recent clinical guidelines increased the size-based biopsy thresholds for thyroid nodules. The cost-effectiveness of these guidelines is largely unknown. We hypothesized that ultrasound surveillance in lieu of immediate fine needle aspiration biopsy would be cost effective for a 1.0 cm thyroid nodule with American Thyroid Association Intermediate Suspicion sonographic features. METHODS: A Markov transition-state model was constructed to compare immediate fine needle aspiration versus ultrasound surveillance. Univariate and multivariate sensitivity analyses were used to examine the uncertainty of cost, probability, and utility estimates in the model. RESULTS: Ultrasound surveillance was $1,829 less costly and 0.016 quality-adjusted life years more effective than immediate fine needle aspiration. Immediate fine needle aspiration became cost effective when the probability of malignancy increased from 15% to 84% or the cost of ultrasound increased from $129 to $793. Immediate fine needle aspiration was cost-effective if the quality adjustment factor for observation following a benign fine needle aspiration result exceeded the quality adjustment factor for observation without a biopsy. CONCLUSION: Ultrasound surveillance is more cost-effective than immediate fine needle aspiration for 1.0 cm thyroid nodules with an intermediate-suspicion sonographic pattern. Additional investigation of health-related quality of life in patients undergoing fine needle aspiration or surveillance is necessary.

Risk Factors Associated With Reoperation and Disease-Specific Mortality in Patients With Medullary Thyroid Carcinoma.

Importance: The association of initial neck dissection with recurrence in medullary thyroid carcinoma (MTC) has not been evaluated on a population level to date. Objective: To elucidate risk factors associated with reoperation in MTC and disease-specific mortality. Design, Setting, and Participants: A retrospective analysis was performed of hospital data obtained from the California Cancer Registry and the Office of Statewide Health Planning and Development from January 1, 1999, through December 31, 2012. The dates of the analysis were January 1, 1999, to December 31, 2012. A population-based sample of 953 patients with MTC was identified. Patients who underwent thyroid surgery and had a minimum postoperative follow-up of 2 years (n = 609) were included in the analysis. Exposure: Initial neck dissection in MTC. Main Outcomes and Measures: Recurrent MTC leading to reoperation and disease-specific mortality. Results: Of the 609 patients with MTC who underwent thyroid surgery, the mean (SD) patient age at diagnosis was 52.6 (17.5) years, and 60.8% (n = 370) of the patients were female. The mean (SD) tumor size was 2.8 (2.0) cm. Although initial central neck dissection is recommended by published MTC guidelines, only 35.5% (216 of 609) of patients underwent central neck dissection at the time of the initial thyroidectomy. The rate of reoperation was 16.3% (99 of 609), and the median time to reoperation was 6.4 months. The presence of lymph node metastasis increased the risk of reoperation (hazard ratio [HR], 3.43; 95% CI, 2.00-5.90), while central and lateral neck dissection performed at the initial operation was protective (HR, 0.53; 95% CI, 0.30-0.93). In patients who underwent reoperation, 45.5% (45 of 99) were disease free at a median follow-up of 7.7 years. Five-year disease-specific mortality for the entire cohort was 13.5% (82 of 609). Independent risk factors for disease-specific mortality included older age (HR, 1.36 per decade; 95% CI, 1.17-1.59), tumor size greater than 2 cm (HR, 2.83; 95% CI, 1.08-7.44 for >2 to 4 cm and HR, 2.89; 95% CI, 1.09-7.71 for >4 cm), and regional (HR, 4.77; 95% CI, 2.29-9.94) and metastatic (HR, 21.08; 95% CI, 9.90-44.89) disease. Reoperation was not associated with increased mortality. Conclusions and Relevance: Lymph node dissection may decrease recurrence leading to reoperation for patients with MTC. Reoperation is a viable strategy to achieve long-term disease-free survival in appropriately selected patients. Central neck dissection remains underused.