Faculty Bibliography

BACKGROUND:Adrenal venous sampling is routinely used to lateralize aldosterone hypersecretion but has an unclear role in adrenocorticotropic hormone-independent autonomous hypercortisolism. We define clinical scenarios where adrenal venous sampling provides value for surgical decision-making. METHODS:We performed a single-center retrospective review of patients undergoing adrenal venous sampling for hypercortisolism (January 2012-April 2025). Lateralization was defined by a lateralization ratio >2 using aldosterone as a reference hormone. We also conducted a scoping review of studies describing adrenal venous sampling use in hypercortisolism identified through a comprehensive literature search. RESULTS:Nine patients with isolated hypercortisolism were included, of which 88.9% were female, with a median age of 60 years (range, 41-76). Seven patients presented with mild autonomous cortisol secretion and 2 with overt Cushing's syndrome. Six patients had bilateral adrenal nodules. Mean nodule size was 2.71 ± 0.85 cm. Eight patients underwent a 1-mg dexamethasone suppression test, with all patients meeting the >1.8 μg/dL threshold for elevated serum cortisol (mean dexamethasone suppression test cortisol: 7.13 ± 4.82 μg/dL). Adrenal venous sampling lateralization corresponded to the larger or unilateral nodule in 5 patients, was nonlateralizing in 3, and correctly lateralized to the smaller nodule in 1 patient with similarly sized lesions (1.9 cm versus 2.0 cm), enabling correct-side surgery and resolution of symptoms of overt Cushing's. Seven isolated hypercortisolism patients underwent adrenalectomy, all with benign pathology. Nine studies were included in the scoping review, demonstrating heterogeneous adrenal venous sampling lateralization criteria. CONCLUSION/CONCLUSIONS:Adrenal venous sampling may be useful in select patients with adrenocorticotropic hormone-independent hypercortisolism and similarly sized bilateral adrenal nodules in order to prevent incorrect-side adrenalectomy or unnecessary bilateral adrenalectomy.

BACKGROUND:Mild autonomous cortisol secretion causes substantial cardiometabolic morbidity, yet evidence for benefits following adrenalectomy remains mixed. Prior studies are limited by small sample sizes and heterogeneous definitions. This study evaluates the metabolic impact of adrenalectomy compared with nonoperative management in mild autonomous cortisol secretion using standardized biochemical criteria from the Epic Cosmos database. METHODS:Mild autonomous cortisol secretion was defined biochemically using dexamethasone suppression test cortisol 1.8-10 μg/dL, dexamethasone, and adrenocorticotropic hormone levels. Surgical patients underwent unilateral adrenalectomy with biochemical resolution of hypercortisolism. Inverse probability of treatment weighting was performed, adjusting for demographics, baseline cardiometabolic parameters, dexamethasone suppression test cortisol level, and glucagon-like peptide-1 receptor agonist use. The starting time point was the adrenalectomy date or, for nonoperative patients, the dexamethasone suppression test date plus the median time to surgery. Follow-up outcomes (A1C, lipid profile, body mass index, and blood pressure) were assessed for categorical improvement at last follow-up within 3 years using a weighted logistic regression model. RESULTS:From 2018 to 2025, 395 patients met inclusion criteria (54 surgical, 341 nonoperative). Surgical patients had a higher adjusted likelihood of categorical improvements in A1C (25.6% vs 9.5%, odds ratio, 3.30; P = .002), total cholesterol (14.6% vs 3.9%, odds ratio, 4.25; P = .004), and body mass index (24.9% vs 12.1%, odds ratio, 2.42; P = .018). There were no differences in blood pressure between groups (28.4% vs 26.7%, odds ratio, 1.09; P = .803). CONCLUSION/CONCLUSIONS:This is the largest cohort study to date evaluating metabolic outcomes after surgery for mild autonomous cortisol secretion. Adrenalectomy was associated with categorical improvement in A1C, body mass index, and total cholesterol, supporting more widespread consideration for selective operative management.

BACKGROUND:Although most adrenal incidentalomas are benign, many are identified by single-phase contrast-enhanced computed tomography, which is unreliable for excluding malignancy. Virtual noncontrast computed tomography is a newer modality with the potential to better characterize adrenal nodules. METHODS:Virtual noncontrast computed tomography of adrenal nodules with available reference standard of true noncontrast computed tomography were identified (2016-2024). Images were evaluated for nodule characteristics including Hounsfield unit attenuation and variability. Nodules were classified as benign (≤10 Hounsfield units) or indeterminate/suspicious (>10 Hounsfield units) by true noncontrast computed tomography. Hounsfield units were compared between virtual noncontrast computed tomography and true noncontrast computed tomography. Variability in attenuation measurements was compared by evaluating Hounsfield unit differences 1 slice up and down from the chosen mid-depth image. Receiver operating characteristic analysis was used to define optimal virtual noncontrast computed tomography accuracy thresholds. RESULTS:After excluding 5 adrenal nodules due to suboptimal imaging, 67 nodules were identified. Based on true noncontrast computed tomography Hounsfield units, 23 nodules (34.3%) were benign, and 44 (65.7%) were indeterminate/suspicious. Hounsfield unit measurements for each nodule exhibited wide variability by both virtual noncontrast computed tomography and true noncontrast computed tomography. Virtual noncontrast computed tomography and true noncontrast computed tomography were significantly correlated with moderate effect size (Pearson coefficient 0.69, P < .001). Conflicting impressions occurred for 6 nodules (9.0%). Overall, virtual noncontrast computed tomography exhibited outstanding discrimination between benign and indeterminate/suspicious nodules (area under the curve 0.94). Maintaining a threshold of ≤10 Hounsfield units achieved 93% sensitivity, 76% specificity, and 84% negative predictive value, whereas ≤7 Hounsfield units achieved 100% negative predictive value. The functional utility of virtual noncontrast computed tomography as a rule-out test applied to 16% of nodules. CONCLUSION/CONCLUSIONS:Despite wide variability in Hounsfield unit measurements, adrenal nodules are well defined by both virtual noncontrast computed tomography and true noncontrast computed tomography. Well-reconstructed virtual noncontrast computed tomography images can accurately rule out malignancy in selected patients, potentially obviating the need for additional imaging.

BACKGROUND:Guidelines do not recommend routine screening for thyroid nodules when starting a glucagon-like peptide-1 receptor agonist. Patients, however, increasingly present with incidental nodules from imaging ordered at glucagon-like peptide-1 receptor agonist initiation. METHODS:This retrospective case-control study examined patients in a single academic health system from 1 January 2019 to 31 December, 2024 who underwent thyroid ultrasound, fine-needle aspiration biopsy, molecular testing, and/or surgery with glucagon-like peptide-1 receptor agonist initiation compared with patients not prescribed a glucagon-like peptide-1 receptor agonist. Patient, prescription, and intervention data were collected. Chart review was also performed for a subset of patients. RESULTS:From 2019 to 2024, 2,523 patients prescribed a glucagon-like peptide-1 receptor agonist underwent thyroid ultrasound; from 2020 to 2023, there was a higher growth rate of ultrasound scans ordered for them. A random sample of 415 patients prescribed a glucagon-like peptide-1 receptor agonist showed that most ultrasounds were ordered for "thyroid nodules" by the endocrinologist who prescribed glucagon-like peptide-1 receptor agonist. In this subset, 757 nodules were detected on ultrasound; 10.6% (80/757) had fine-needle aspiration biopsy. Cytology showed 3.8% were Bethesda I (3/80), 72.5% Bethesda II (58/80), 15% Bethesda III (12/80), 0% Bethesda IV (0/80), 2.5% Bethesda V (2/80), and 6.6% Bethesda VI (5/80). Of 15 indeterminate nodules, 11 had molecular testing: 5 were positive or suspicious, including fusions, alterations, RAS and BRAF mutations. Sixteen patients had thyroid surgery after glucagon-like peptide-1 receptor agonist initiation (8 total thyroidectomies, 8 hemithyroidectomies, 1 completion). Final pathology demonstrated 6 benign, 10 malignant, 1 NIFTP. The rate of malignancy in the subset was 2.4% (10/415). CONCLUSION/CONCLUSIONS:The malignancy rate in patients prescribed a glucagon-like peptide-1 receptor agonist remains low, but ultrasound screening rates increased for a period. Strong clinical suspicion should govern screening.

INTRODUCTION/BACKGROUND:Papillary thyroid cancer (PTC) often follows an indolent course with a favorable prognosis. This has led to evolving guideline-based, low-intensity treatment options for low-risk patients. Recently, the purported benefit of total thyroidectomy (TT) over unilateral lobectomy for PTC with clinical lateral neck nodal metastasis (cN1b) has come into question. MATERIALS AND METHODS/METHODS:A retrospective analysis of the National Cancer Institute's Surveillance, Epidemiology, and End Results database was performed to study patients with PTC with ipsilateral cN1b disease from 1975 to 2020. Kaplan-Meier curves and log-rank tests were used to compare disease-specific survival (DSS) difference between lobectomy and TT at 10 y. Multivariable Cox proportional hazards analysis was performed to determine the independent association of lobectomy versus TT with DSS, correcting for age and lymph node ratio, defined as the ratio of pathologically positive lymph nodes to total number examined. RESULTS:Among 2943 patients (median [interquartile range] age, 45 [26] y), 42 underwent lobectomy and 2901 underwent TT. Unadjusted DSS at 10 y in the lobectomy and TT groups were 51.0% (95% confidence interval, 31.4%-82.8%) and 86.8% (95% confidence interval, 84.8%-88.9%), respectively. On multivariable analysis of all patients, older age (hazard ratio [HR], 1.08; P < 0.001) and male gender (HR, 1.74; P < 0.001) were associated with lower adjusted DSS, whereas treatment with TT (HR, 0.387; P = 0.005) and receipt of radioactive iodine (RAI) (HR, 0.604; P < 0.001) were associated with improved adjusted DSS. In addition, we observed that the magnitude of survival benefit conferred by RAI and TT were reduced with decreasing age (P < 0.001). CONCLUSIONS:This longitudinal cohort study suggests that, while TT is associated with a DSS benefit in most patients with PTC and ipsilateral cN1b disease, this association may not exist in a smaller cohort of younger patients. These findings raise the possibility that unilateral surgical clearance without RAI could offer adequate oncologic outcomes in selected younger individuals; however, further investigation is warranted to confirm these observations and inform clinical decision-making.

PURPOSE/OBJECTIVE:Primary aldosteronism (PA) is an underdiagnosed cause of secondary hypertension with significant health consequences. Expanding screening criteria may improve case detection and reduce the number of untreated patients. METHODS:We assessed PA screening rates in a cohort of 457 adults with comorbid obstructive sleep apnea (OSA) and hypertension (HTN). PA screening in a subset of the cohort (n = 97, 21%) was conducted using serum aldosterone, aldosterone-to-plasma renin activity ratio (ARR), and plasma renin activity (PRA). Screening results were compared between the 2016 Endocrine Society guidelines (serum aldosterone and ARR) and the Vaidya & Carey algorithm (serum aldosterone and PRA). RESULTS:The screened patients were predominantly male (mean age 58.6 years), with common comorbidities including hyperlipidemia (80%) and diabetes mellitus (31%). PA positivity rates differed significantly between screening criteria: 7% tested positive using Endocrine Society guidelines, while 33% screened positive using the Vaidya & Carey algorithm. Notably, 26% of patients with negative screens by Endocrine Society criteria were reclassified as positive, and 11 previously indeterminate cases were classified as negative due to absent renin suppression. Using the Vaidya & Carey algorithm with a stricter PRA suppression threshold, 25% of patients screened positive. CONCLUSION/CONCLUSIONS:The Vaidya & Carey algorithm may be an important tool in increasing detection of previously unidentified cases and clarifying the diagnosis of cases that were previously deemed indeterminate. Given the morbidity of untreated PA, more robust screening approaches are warranted. Prospective studies are needed to validate these findings across diverse populations.

BACKGROUND:Four-dimensional computed tomography is routinely used to localize parathyroid disease, with consistently excellent parathyroid gland localization rates reported. This study evaluated whether pairing 4-dimensional computed tomography results with preoperative clinical variables can accurately predict single-gland disease in primary hyperparathyroidism. METHODS:Patients with primary hyperparathyroidism who underwent both 4-dimensional computed tomography imaging and parathyroidectomy between January 2019 and September 2021 at a large academic health system were included. Patient demographics, preoperative characteristics, and peri- and postoperative data were collected. The accuracy of 4-dimensional computed tomography in correctly identifying patients with single-gland disease with and without preoperative calcium and parathyroid hormone levels was calculated. Single-gland disease was defined by intraoperative parathyroid hormone decrease >50% and a hypercellular gland on pathology. RESULTS:One hundred seventy-five patients had 4-dimensional computed tomography results suggestive of single gland disease. One hundred fifty-two patients (87%) were predicted correctly to have single-gland disease. The predictive accuracy increased when stratifying by preoperative calcium (≥10.5 mg/dL, ≥11 mg/dL, and ≥12 mg/dL) and parathyroid hormone levels (≥65 pg/mL, ≥100 pg/mL, and ≥200 pg/dL). The accuracy further increased when stratifying by age (≤50 years). Accuracy for single gland disease was 100% when combined with any of the following: (1) calcium ≥12 mg/dL, (2) parathyroid hormone ≥200 pg/dL, or (3) calcium ≥11 mg/dL in patients ≤50 years. CONCLUSION/CONCLUSIONS:Four-dimensional computed tomography alone accurately predicted single gland disease in 87% of patients with primary hyperparathyroidism. When combined with preoperative calcium, parathyroid hormone and age thresholds, predictive accuracy for single-gland disease approached 100%. Given the high likelihood of single-gland disease in these scenarios, clinicians may consider offering focused unilateral parathyroidectomy without intraoperative parathyroid hormone monitoring in selected patients.