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.

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.

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.

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.

Cell Type-Specific Whole-Genome Landscape of ΔFOSB Binding in the Nucleus Accumbens After Chronic Cocaine Exposure.

BACKGROUND: The ability of neurons to respond to external stimuli involves adaptations of gene expression. Induction of the transcription factor ΔFOSB in the nucleus accumbens, a key brain reward region, is important for the development of drug addiction. However, a comprehensive map of ΔFOSB's gene targets has not yet been generated. METHODS: We used CUT&RUN (cleavage under targets and release using nuclease) to map the genome-wide changes in ΔFOSB binding in the 2 main types of nucleus accumbens neurons-D1 or D2 medium spiny neurons-after chronic cocaine exposure. To annotate genomic regions of ΔFOSB binding sites, we also examined the distributions of several histone modifications. Resulting datasets were leveraged for multiple bioinformatic analyses. RESULTS: The majority of ΔFOSB peaks occur outside promoter regions, including intergenic regions, and are surrounded by epigenetic marks indicative of active enhancers. BRG1, the core subunit of the SWI/SNF chromatin remodeling complex, overlaps with ΔFOSB peaks, a finding consistent with earlier studies of ΔFOSB's interacting proteins. Chronic cocaine use induces broad changes in ΔFOSB binding in both D1 and D2 nucleus accumbens medium spiny neurons of male and female mice. In addition, in silico analyses predict that ΔFOSB cooperatively regulates gene expression with homeobox and T-box transcription factors. CONCLUSIONS: These novel findings uncover key elements of ΔFOSB's molecular mechanisms in transcriptional regulation at baseline and in response to chronic cocaine exposure. Further characterization of ΔFOSB's collaborative transcriptional and chromatin partners specifically in D1 and D2 medium spiny neurons will reveal a broader picture of the function of ΔFOSB and the molecular basis of drug addiction.

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.

Limited disease progression in endocrine surgery patients with treatment delays due to COVID-19.

BACKGROUND: The COVID-19 pandemic profoundly impacted the delivery of care and timing of elective surgical procedures. Most endocrine-related operations were considered elective and safe to postpone, providing a unique opportunity to assess clinical outcomes under protracted treatment plans. METHODS: American Association of Endocrine Surgeon members were surveyed for participation. A Research Electronic Data Capture survey was developed and distributed to 27 institutions to assess the impact of COVID-19-related delays. The information collected included patient demographics, primary diagnosis, resumption of care, and assessment of disease progression by the surgeon. RESULTS: Twelve out of 27 institutions completed the survey (44.4%). Of 850 patients, 74.8% (636) were female; median age was 56 (interquartile range, 44-66) years. Forty percent (34) of patients had not been seen since their original surgical appointment was delayed; 86.2% (733) of patients had a delay in care with women more likely to have a delay (87.6% vs 82.2% of men, χ2 = 3.84, P = .05). Median duration of delay was 70 (interquartile range, 42-118) days. Among patients with a delay in care, primary disease site included thyroid (54.2%), parathyroid (37.2%), adrenal (6.5%), and pancreatic/gastrointestinal neuroendocrine tumors (1.3%). In addition, 4.0% (26) of patients experienced disease progression and 4.1% (24) had a change from the initial operative plan. The duration of delay was not associated with disease progression (P = .96) or a change in operative plan (P = .66). CONCLUSION: Although some patients experienced disease progression during COVID-19 delays to endocrine disease-related care, most patients with follow-up did not. Our analysis indicated that temporary delay may be an acceptable course of action in extreme circumstances for most endocrine-related surgical disease.

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.

Intraoperative Neuromonitoring: Evaluating the Role of Continuous IONM and IONM Techniques for Emerging Surgical and Percutaneous Procedures.

Intraoperative nerve monitoring (IONM) is a tool used during thyroid surgery to assist in the identification of the recurrent laryngeal nerve (RLN). Multiple IONM systems that exist for thyroidectomy require intubation with an endotracheal tube. Given that one of the advantages of thermal ablation procedures, such as radiofrequency ablation, is that they can be done safely without the use of general anesthesia, nerve monitoring systems that utilize cutaneous surface electrodes have been developed, though are not widely available in the United States. This article will review the use of IONM for RFA including the cutaneous surface electrode system.

Ethanol ablation for the treatment of benign thyroid nodules.

BACKGROUND: Ethanol ablation (EA) is a non-surgical option for the treatment of benign cystic thyroid nodules. This study summarizes our preliminary experience with the efficacy and safety of EA. METHODS: A retrospective analysis was performed of patients undergoing EA for symptomatic, benign, cystic and predominantly cystic (≥75%) thyroid nodules. Baseline nodule volume, cosmetic scores, and symptom scores were assessed, as well as volume reduction ratio (VRR), cosmetic and symptom scores at post-procedure months 1, 3, 6, and 12. RESULTS: 31 patients underwent an uncomplicated EA for a single cyst with an average volume of 21.3 cc (range: 1.7-101.4 cc). Follow-up was limited by the COVID-19 pandemic. Mean nodule VRRs were 66 ± 20% (1 m, n = 17), 87 ± 15% (3 m, n = 9), 72 ± 20% (6 m, n = 7), and 78% (12 m, n = 3). Mean symptom and cosmetic scores decreased concurrently post-procedure. CONCLUSION: EA is a safe, effective option for benign cystic and predominantly cystic thyroid nodules.

Analyzing the adoption of radiofrequency ablation of thyroid nodules using the diffusion of innovations theory: understanding where we are in the United States?

Thyroid nodules are very common and found in up to 68% of the general U.S. population on ultrasound. Although thyroidectomy has long been the mainstay of treatment for malignant and symptomatic benign thyroid nodules, various interventional ablative techniques have emerged in the last couple of decades as alternative non-surgical treatment options. Globally, the most widely adopted technique has been ultrasound-guided radiofrequency ablation (RFA). RFA of thyroid nodules was first performed in 2002, and there has been an expanding body of evidence since 2006 showing that RFA and other interventional ablative techniques are effective treatments for benign solid thyroid nodules, toxic adenomas, and thyroid cysts. More recently, evidence has emerged that these techniques may be effective treatment for low-risk thyroid cancer and recurrent disease. Despite these findings, the United States has been slow to adopt these techniques, with only a single publication on RFA more than a decade after the first series was published. EM Rogers' Diffusion of Innovation Theory provides us the appropriate lens to carefully analyze the process of adoption of RFA for thyroid nodules-to understand where we are currently, as well as, the important next steps that must be accomplished in order for RFA and other ablative techniques to be successfully adopted into the management algorithm of thyroid nodules in the United States.

Optimal surgeon-volume threshold for neck dissections in the setting of primary thyroid malignancies.

BACKGROUND: Although the surgeon-volume relationship is well documented for thyroidectomy, less is known about central neck and lateral neck dissections. The aim of this study was to evaluate and determine the surgeon-volume threshold for central neck and lateral neck dissections for thyroid cancer. METHODS: A retrospective analysis of patients with thyroid malignancies who received a central or lateral neck dissection in the New York Statewide Planning and Research Cooperative System was performed (2007-2017). Demographic variables included age, sex, race, and a Charlson Comorbidity Score. Thirty-day complications were identified using International Classification of Diseases (ICD) codes for central neck, lateral neck, and other surgical complications. Optimal surgeon-volume threshold was estimated using a change-point logistic regression. Using the identified threshold, surgeons were then classified to low versus high volume surgeons. Logistic regression analysis was conducted to examine the effect of high-volume status on outcomes. RESULTS: In total, 3,808 patients who underwent neck dissections (3,485 central neck dissections and 977 lateral neck dissections) were analyzed. Surgeon-volume threshold to distinguish high volume surgeons for central neck dissections and lateral neck dissections was 7.0 (95% bootstrap confidence interval 1.3-7.5) and 3.3 (1.2-4.8) neck dissections/year, respectively. For central neck dissection, high volume surgeons were associated with a lower rate of vocal cord paralysis (odds ratio 0.45 [0.24-0.82]), hypocalcemia (0.31 [0.14-0.65]), and all-cause complications (0.42 [0.29-0.59]). For lateral neck dissection, high volume surgeons were associated with a lower odds all-cause complications (0.42 [0.23-0.74]) but not lateral neck specific complications (0.18 [0.01-1.07]). CONCLUSION: A threshold of 7.0 central neck dissections and 3.3 lateral neck dissections for thyroid cancer per year improves outcomes. Guidelines for training and centralization of care can be guided by these results to reduce complications.

Primary Hyperparathyroidism Is Associated With Shorter QTc Intervals, but Not Arrhythmia.

CONTEXT: Primary hyperparathyroidism (PHPT) is associated with subclinical cardiovascular disease, but data regarding cardiac conduction abnormalities are limited. OBJECTIVE AND DESIGN: Retrospective cross-sectional comparison of cardiac conduction in patients with PHPT or thyroid disease (TD). PARTICIPANTS AND SETTING: Patients ≥40 years old who underwent parathyroidectomy or thyroidectomy at a single tertiary institution from 2013 to 2018. METHODS AND OUTCOMES: Demographics and preoperative electrocardiogram (EKG) parameters were compared using the Mann-Whitney U, chi-square test, and linear regression. RESULTS: A total of 1242 patients were included: 49.8% PHPT (n = 619) and 50.2% TD (n = 623). Median age was 60.5 years [interquartile range (IQR) 53.6-67.9]. Compared to controls, PHPT patients had higher median serum calcium [10.7 mg/dL (IQR 10.4-11.1) vs 9.5 mg/dL (IQR 9.3-9.8), P < 0.001] as expected, as well as, a higher prevalence of hyperlipidemia (49% vs 36%, P < 0.001) and hypertension (50.1% vs 42.2%, P < 0.01). Based on EKG, there was no difference in PR interval or the prevalence of arrhythmia, atrioventricular block, ST segment/T wave changes, premature ventricular complexes, right bundle branch block, or left bundle branch block after adjusting for covariates. The PHPT group had a lower mean corrected QT interval (414 ± 24) ms vs 422 ± 24 ms, P < 0.01), adjusted for covariates. Serum calcium predicted QTc independently of age, sex, and other covariates. CONCLUSIONS: In the largest study to date, PHPT patients had shorter QTc intervals compared to TD controls but no increased prevalence of arrhythmia based on preoperative EKG.

Temporal inhibition of chromatin looping and enhancer accessibility during neuronal remodeling.

During development, looping of an enhancer to a promoter is frequently observed in conjunction with temporal and tissue-specific transcriptional activation. The chromatin insulator-associated protein Alan Shepard (Shep) promotes Drosophila post-mitotic neuronal remodeling by repressing transcription of master developmental regulators, such as brain tumor (brat), specifically in maturing neurons. Since insulator proteins can promote looping, we hypothesized that Shep antagonizes brat promoter interaction with an as yet unidentified enhancer. Using chromatin conformation capture and reporter assays, we identified two enhancer regions that increase in looping frequency with the brat promoter specifically in pupal brains after Shep depletion. The brat promoters and enhancers function independently of Shep, ruling out direct repression of these elements. Moreover, ATAC-seq in isolated neurons demonstrates that Shep restricts chromatin accessibility of a key brat enhancer as well as other enhancers genome-wide in remodeling pupal but not larval neurons. These enhancers are enriched for chromatin targets of Shep and are located at Shep-inhibited genes, suggesting direct Shep inhibition of enhancer accessibility and gene expression during neuronal remodeling. Our results provide evidence for temporal regulation of chromatin looping and enhancer accessibility during neuronal maturation.

The zinc-finger protein OEF-1 stabilizes histone modification patterns and promotes efficient splicing in the Caenorhabditis elegans germline.

To ensure stable transmission of genetic information to the next generation, germ cells frequently silence sex chromosomes, as well as autosomal loci that promote inappropriate differentiation programs. In Caenorhabditis elegans, silenced and active genomic domains are established in germ cells by the histone modification complexes MES-2/3/6 and MES-4, which promote silent and active chromatin states, respectively. These states are generally mutually exclusive and modulation of one state influences the pattern of the other. Here, we identify the zinc-finger protein OEF-1 as a novel modifier of this epigenetic balance in the C. elegans germline. Loss of oef-1 genetically enhances mes mutant phenotypes. Moreover, OEF-1 binding correlates with the active modification H3K36me3 and sustains H3K36me3 levels in the absence of MES-4 activity. OEF-1 also promotes efficient mRNA splicing activity, a process that is influenced by H3K36me3 levels. Finally, OEF-1 limits deposition of the silencing modification H3K27me3 on the X chromosome and at repressed autosomal loci. We propose that OEF-1 might act as an intermediary to mediate the downstream effects of H3K36me3 that promote transcript integrity, and indirectly affect gene silencing as a consequence.

Preoperative imaging predicts change in bone mineral density after parathyroidectomy for primary hyperparathyroidism.

BACKGROUND: Bone Mineral Density (BMD) improves after parathyroidectomy (PTX), but data on factors that predict bone recovery are limited. No studies have evaluated if preoperative imaging findings are associated with postoperative change in BMD. We hypothesized that larger, metabolically active glands would be associated with greater increase in BMD after PTX. METHODS: Patients with primary hyperparathyroidism (PHPT) who underwent combined Tc-99m sestamibi and 4D-CT imaging prior to PTX and had pre- and post-operative dual-energy X-ray absorptiometry (DXA) at our institution were considered for inclusion. Retrospectively, data were collected from imaging studies on each parathyroid gland, including estimated weight (using the ellipsoid formula) and contrast enhancement on 4D-CT as well as sestamibi avidity. Total estimated parathyroid weight was calculated. The main outcome measure was the percent change in BMD at the lumbar spine (LS) from pre- to post-operative DXA. Predictors of change in BMD at the LS were assessed. RESULTS: Complete DXA data was available in 25 patients. Median total parathyroid weight on 4D-CT was 270 mg, and mean change in BMD at the LS was 2.4 ± 4.3%. The increase in BMD was best predicted by higher preoperative serum calcium (p = 0.01), greater estimated parathyroid weight (p = 0.001), sestamibi avidity (p = 0.03), and increased time between DXA scans (p = 0.03) in the multivariable model (R2 = 0.79, p < 0.0001). CONCLUSION: In PHPT, higher preoperative serum calcium, parathyroid gland weight on imaging, and sestamibi avidity are associated with greater increases in BMD after curative PTX. These findings suggest that larger, metabolically active adenomas may mobilize more calcium from bone.

The effect of chronic kidney disease on intraoperative parathyroid hormone: A linear mixed model analysis.

BACKGROUND: Reduced creatinine clearance is an indication for surgery in asymptomatic primary hyperparathyroidism, and a significant proportion of patients undergoing parathyroidectomy have chronic kidney disease. The purpose of this study was to evaluate the kinetics of intraoperative parathyroid hormone decline during parathyroidectomy in patients who have chronic kidney disease compared with those with who have normal renal function. METHODS: This is a single-center, retrospective study of patients with primary hyperparathyroidism undergoing parathyroidectomy (n = 646). Patients were grouped based on estimated glomerular filtration rate greater than (normal renal function) or less than (chronic kidney disease) 60 mL/min/1.73m2. All patients had intraoperative parathyroid hormone monitoring and ≥6-month postoperative serum studies to confirm surgical cure. Intraoperative parathyroid hormone kinetic curves were analyzed using a linear mixed model. RESULTS: Despite similar pre-excision values, patients with chronic kidney disease had significantly higher intraoperative parathyroid hormone values at 5 minutes (76 vs 58 pg/mL, P = .02) and 10 minutes (54 vs 37 pg/mL, P = .004) postexcision. No significant difference was observed in whether patients met Miami criterion by 5 minutes (chronic kidney disease 71%, normal renal function 78%, P = .255) or by 10 minutes (chronic kidney disease 95%, normal renal function 96%, P = .751) postexcision. Using a linear mixed model, glomerular filtration rate did not have a significant effect on the change in intraoperative parathyroid hormone over time. CONCLUSION: Patients with chronic kidney disease had significantly higher postexcision intraoperative parathyroid hormone levels. However, renal function did not affect the change in intraoperative parathyroid hormone over time, nor did renal function ultimately affect the likelihood of meeting the Miami criterion. Intraoperative parathyroid hormone monitoring remains useful in this population, although additional time points may be needed to observe normalization of values.