SAT-461 Adrenal Venous Sampling in Bilateral Adrenal Adenomas with ACTH Independent Autonomous Cortisol Secretion

Disclosure: J.J. Mao: None. K.C. McCowen: None. C. Choe: None. Jimmy J. Mao, MD (1); Karen C. McCowen (1); Charles H. Choe (1)(1) Division of Endocrinology, Diabetes, and Metabolism, University of California San Diego, La Jolla, CA. Background: Over 80% of adrenal incidentalomas are benign adrenal cortical adenomas, of which 30-50% are found to have mild autonomous cortisol secretion (MACS). Bone fragility is a known complication of MACS. Clinical Case: A 57-year-old postmenopausal female with no prior history of fracture, venous thromboembolism, and atherosclerotic cardiovascular disease, was referred for incidental bilateral adrenal nodules. Body mass index was normal at 21 kg/m2, and no clinical stigmata of Cushing syndrome were noted on physical exam. Unenhanced computed tomography scan revealed a 4.6 cm right adrenal nodule and a 3.3 cm left adrenal nodule; both nodules measured less than -18 Hounsfield Units. Biochemical work-up for pheochromocytoma, primary aldosteronism, and non-classical congenital adrenal hyperplasia was negative. Evaluation for hypercortisolism revealed a morning cortisol of 20.3 mcg/dL (ref. 4-22 mcg/dL) with concurrent adrenocorticotropic hormone of <5 pg/mL (ref. 6-50 pg/mL), 24-hour urine free cortisol of 16.9 mcg (ref. 4-50 mcg), and midnight salivary cortisol of 0.07 mcg/dL (ref. <0.09 mcg/dL). A 1 mg dexamethasone suppression test measured on two separate occasions was elevated at 6.3 mcg/dL and 7.9 mcg/dL (ref. <1.8 mcg/dL). A subsequent 8 mg dexamethasone suppression test was also elevated at 6.1 mcg/dL (ref. <1.8 mcg/dL). The diagnosis of MACS was made. A bone mineral density (BMD) scan revealed T-scores at the right femoral neck, left femoral neck, and lumbar spine at -1.6, -1.3, and -0.8, respectively. Ten-year probability of major osteoporotic fracture and hip fracture were 8.3% and 1.0%, respectively. To reduce the risk for future fractures, the decision was made to proceed with adrenal vein sampling (AVS) in preparation for potential adrenalectomy. Conclusion: MACS is the most frequent hormonal abnormality in adrenal incidentalomas, with an estimated prevalence of 0.8-2 cases per 1000 persons. A previous prospective study found that surgical cure of unilateral MACS may lead to a substantial risk reduction (up to 15-fold) of future incident asymptomatic vertebral fractures. Additionally, the highest risk for clinical fracture in those with adrenal adenomas (either nonfunctional or with cortisol hypersecretion) appears to occur at 7-10 years after initial diagnosis. BMD does not perfectly correlate with fracture risk, so unilateral adrenalectomy (if lateralization is observed on AVS) and/or pharmacotherapy should be strongly considered in patients with an expected longevity of >10 years even with mild osteopenia and low fracture risk assessment tool scores. Presentation: Saturday, June 17, 2023

Disclosure: M. Neff: None. J. Lin: None. J. Foster: None. N. Sharma: None. E. Garcia: None. J. Sandhu: None. E. Hilborn: None. S. Rodgers: None. A. Ayala: None. Z. Hannoush: None. Z. Miller: None.Introduction or Background: Mild autonomous cortisol secretion (MACS) is characterized by subtle hypercortisolism without overt Cushingoid features. The clinical significance and management of MACS remain controversial, particularly in patients with adrenal adenomas. Adrenal vein sampling (AVS) may aid in determining lateralization and guiding surgical decisions, but post-adrenalectomy (adrenalX) outcomes vary. Objectives: To present 2 cases of MACS evaluated by AVS, highlighting procedural outcomes, surgical outcomes, and post-adrenalX improvements. Methods: 2 patients diagnosed with MACS underwent AVS to assess cortisol secretion and guide adrenalX. Preoperative clinical, biochemical, and imaging data were reviewed. Post-op outcomes, including hypertension (HTN) control, BMI changes, and biochemical markers, were assessed at follow-up. Results: Case 1: 64yo male with bilateral adrenal adenomas (left: 1.8 cm, right: 1.3 cm and 1.1 cm). Dexamethasone suppression cortisol value was 5.7, and patient demonstrated no clinical features of overt Cushing’s syndrome. AVS indicated left-sided lateralization. Preoperatively, systolic BP was 154, diastolic BP 100 and BMI 31.1. Hypertension medications included amlodipine/benazepril 10-40mg, clonidine 0.1mg twice a day, and hydralazine 10mg 3 times a day. He underwent left adrenalectomy on 10/2022. Postoperative day 2, BP improved to systolic 141 and diastolic 96 but remained uncontrolled. Day 9 post-op, he experienced retroperitoneal hematoma in the adrenalectomy bed, anemia, and transient hypoglycemia, necessitating medication adjustments. 1-month post-op, BP was 136/88 without complaints or ongoing pain. By 5/2023, BP continued improving to 129/78, BMI decreased to 29.7 and medications included amlodipine/benazepril 10-40mg, hydralazine 50mg 3 times daily, and doxazosin 4mg. Case 2: 55yo male with a right adrenal nodule (1.0 × 0.6 cm). Dexamethasone suppression cortisol value was 2.5 with no Cushingoid features. AVS indicated right-sided lateralization. Preoperatively, systolic BP was 174, diastolic BP 95, and BMI 24.9. Pre-op hypertension medications included nifedipine 30mg, olmesartan 40mg, hydralazine 100mg in AM, 50mg in afternoon, and 50mg in PM, and labetolol 200mg twice daily. He underwent right adrenalectomy on 8/2024. At 2 months post-op, BP was well controlled on only nifedipine 30mg and doxazosin 4mg once daily. BMI decreased slightly to 24.3. Sodium, potassium, and renal function remained normal, and the patient reported significant clinical improvement. Conclusions: AVS guided adrenalX in MACS resulted in BP improvement and stable BMI, with varying degrees of antihypertensive reduction. AVS remains a promising tool for guiding surgical decisions in adrenal nodules with subclinical cortisol excess. With additional research the full potential of AVS in guiding adrenalX may be realized.Presentation: Monday, July 14, 2025

Bilateral Adrenal Nodules Presenting With Mild Autonomous Cortisol Secretion.

Background: Glucocorticoid-induced myopathy is well-recognized in overt Cushing syndrome (CS), but the impact of mild cortisol secretion on muscle is unclear. Recent data suggest that patients with mild autonomous cortisol secretion (MACS) are frailer and report more weakness than patients with non-functioning adrenal adenomas. We hypothesized that MACS is associated with 1) objective measures of impaired muscle strength and performance and 2) increased tissue accumulation of advanced glycation end products (AGEs), a measure of accelerated aging. Aim: To determine the effect of MACS on muscle mass, strength, performance, and tissue accumulation of AGEs. Methods: We conducted a cross-sectional analysis as part of an ongoing cohort study in patients with MACS compared to age and sex-matched referent subjects without cortisol excess. MACS was defined as serum cortisol >1.8 mcg/dL after the 1 mg overnight dexamethasone suppression test (DST), in the absence of overt signs and symptoms of CS. We measured hand grip strength with hand grip dynamometer and evaluated functional performance on the timed up and go test, 6 minute walk test, and gait speed assessment. Tissue accumulation of AGEs was measured with point-of-care AGE reader. Appendicular lean mass was calculated and adjusted for height in participants who underwent body composition scan. Results: A total of 23 patients with MACS and 23 age and sex-matched referent subjects without cortisol excess were enrolled. The median age of diagnosis was 63 years (range, 51–81), and 26 (56%) were women. In the MACS cohort, median cortisol following 1 mg DST was 2.6 µg/dL (range, 1.9–13.0), median DHEA-S 37 µg/dL (range, 5.0- 141.0), and median ACTH 8.5 pg/mL (range, 5.0–38.0). Patients with MACS had lower hand grip strength (median 29.3 vs. 32.5 kg, p=0.052), slower gait speed (median 1.1 vs. 1.4 m/s, p=0.001), covered less distance during the 6 minute walk test (median 453 vs. 510 m, p=0.001), and took longer to complete the timed up and go test (median 10.1 vs. 8.6 s, p=0.04) than referent subjects without cortisol excess. Accumulation of AGEs was higher in patients with MACS (median 2.9 vs. 2.4, p=0.01). No significant difference was observed in appendicular lean mass (n=19 pairs, 7.8 vs. 7.5 kg/m2, p=0.57). Conclusions: MACS is associated with decreased muscle strength and performance without a significant change in muscle mass, suggesting poor muscle quality. We also observed increased tissue accumulation of AGEs in MACS patients, consistent with our hypothesis of MACS-induced accelerated aging. These findings may help explain the increased frailty observed in MACS, and suggest muscle assessment be considered in all patients with autonomous cortisol secretion. Further studies should examine the impact of muscle and functional impairments on morbidity in MACS, and its possible reversal with either a structured exercise intervention or adrenalectomy.

Disclosure: H. Tayyab: None. R. Subramani: None. A. Ullah: None. F. Manas: None. T. Hammad: None. J. Pamula: None.Introduction: Cushing’s syndrome (CS) results from chronic excessive cortisol secretion and is associated with significant morbidity and mortality. Endogenous CS can be ACTH-dependent or ACTH-independent, with the latter comprising 15-20% of cases, commonly due to adrenal adenomas or carcinomas with autonomous cortisol production. Mild autonomous cortisol secretion (MACS), a subset of ACTH-independent CS, has been associated with metabolic and cardiovascular complications. Surgical management, such as adrenalectomy, has shown promise in mitigating these comorbidities, though further research is needed to establish long-term outcomes. Case Presentation: A 59-year-old Caucasian female with a history of hypertension, GERD, coronary artery disease (CAD) and heart failure with reduced ejection fraction (EF 40-45%) presented for evaluation of a right adrenal mass incidentally discovered during a CT chest for pulmonary embolism. Imaging revealed a bilobed right adrenal nodule (3.1 — 1.8 cm superiorly and 1.9 cm inferiorly) with Hounsfield units of 7. She reported a 30-pound weight gain despite a low-carb diet and exercise, as well as elevated home blood pressure readings. Laboratory testing showed an HbA1c of 6%, consistent with prediabetes. On examination, her BMI was 33.6, and physical findings included hyperpigmentation of the anterior and posterior neck and striae. There was no evidence of proximal muscle weakness. Initial labs confirmed hypercortisolism: 24-hour urine-free cortisol: 28 mcg/24h; ACTH: 5 pg/mL, Dexamethasone suppression test: Cortisol failed to suppress (2.4 µg/dL), DHEA-S: 17 mcg/dL; Salivary cortisol and catecholamine levels were within normal limits. MRI revealed bilateral adrenal involvement with mild left adrenal adenomatous hyperplasia. Adrenal vein sampling confirmed cortisol lateralization to the right gland (right adrenal vein cortisol/IVC cortisol = 25.7, left adrenal vein cortisol/IVC cortisol = 6.09), indicating autonomous cortisol secretion from the right adrenal gland. The patient underwent laparoscopic right adrenalectomy. Postoperatively, she was started on glucocorticoid replacement therapy. Follow-up labs showed ACTH recovery (47 pg/mL) and cortisol normalization (16 µg/dL). Discussion: MACS, also known as subclinical Cushing’s syndrome, presents diagnostic challenges due to its overlap with overt CS. It is characterized by low ACTH, failure of cortisol suppression during dexamethasone testing, and low DHEA-S levels, while standard tests such as 24-hour urinary cortisol may remain normal. Evidence suggests surgical management improves metabolic and cardiovascular outcomes in MACS compared to conservative therapy. This case highlights the importance of early diagnosis and the role of adrenalectomy in managing MACS- associated comorbidities.Presentation: Sunday, July 13, 2025

ObjectivesGlucocorticoid cosecretion is more common in primary aldosteronism (PA) than previously thought. Chronic subtle cortisol excess in patients with mild autonomous cortisol secretion (MACS) negatively affects bone health. This study aimed to evaluate the impact of MACS on bone density and turnover markers in PA patients.MethodsPatients with PA and MACS (n = 50), confirmed by a 1-mg dexamethasone suppression test (DST) with a cortisol cutoff of ≥1.8 µg/dL without symptoms of overt Cushing, were compared to age- and sex-matched patients with PA without MACS (non-MACS, n = 50). Lumbar volumetric bone mineral density (vBMD) was extracted by a novel convolutional neural network (CNN)-based framework (SpineQ software v1.0) applied to routine CT data, incorporated into the diagnostic protocol for PA. Additionally, bone turnover markers—including osteocalcin, bone-specific alkaline phosphatase, N-terminal propeptide of type I collagen, and carboxy-terminal crosslinked telopeptide of type I collagen were evaluated between the groups.ResultsMedian cortisol after DST was 1.1 µg/dL (30.3 nmol/L) [IQR: 0.5 µg/dL (13.8 nmol/L)] in the non-MACS group and 2.5 µg/dL (69.0 nmol/L) [IQR: 1.4 µg/dL (38.5 nmol/L)] in the MACS group (p < 0.001). Patients with MACS had significantly lower vBMD values compared to the non-MACS group (106.4 mg/cm³ vs. 116.6 mg/cm³, p = 0.038). Cortisol after DST negatively correlated with vBMD (Spearman’s r=−0.33, p=0.00042). No significant differences in bone turnover markers were found, and classifications based on visible lesions on CT or PA-lateralization via adrenal venous sampling did not reveal any significant differences in these markers (p > 0.05 for all comparisons).ConclusionDespite non-significant differences in bone turnover markers between patients with PA with or without MACS, CT scans revealed significantly reduced vBMD in PA and MACS patients, indicating compromised bone health and vBMD significantly negatively correlated with cortisol post DST. Thus, opportunistic evaluation of vBMD in routine CT screenings could aid in the early detection of bone alterations in MACS and help mitigate potential long-term adverse effects on bone health.

Background: Cognitive deficits in memory, language, and executive function have been described in Cushing’s syndrome, but the impact of mild cortisol secretion on cognition is unclear. Rather than overt hypercortisolism, mild autonomous cortisol secretion (MACS) is typically associated with abnormal circadian cortisol production. Aim: To characterize the effect of MACS on cognitive performance. Methods: We conducted a cross-sectional analysis as part of an ongoing cohort study in patients with MACS compared to age and sex-matched referent subjects without cortisol excess. MACS was defined as serum cortisol concentration &amp;gt;1.8 mcg/dL after the 1 mg overnight dexamethasone suppression test (DST), in the absence of signs and symptoms of overt Cushing syndrome. We used the National Institute of Health Toolbox Cognition Battery to assess cognitive performance. A series of seven IPad-based tests were administered to evaluate five key domains: 1) executive function, 2) episodic memory, 3) working memory, 4) language, and 5) processing speed. Performance was reported using fully corrected T-scores for age, sex, education, and race with a normative mean of 50 and a standard deviation of 10. T-scores were generated for the individual components as well as three summary measures: 1) fluid cognition (includes executive function, episodic memory, working memory, and processing speed), 2) crystallized cognition (includes language), and 3) total cognition (composite of fluid and crystalized cognition). Results: A total of 23 patients with MACS and 23 age and sex-matched referent subjects without cortisol excess were enrolled. The median age of diagnosis was 63 years (range, 51–81), and 26 (56%) were women. In the MACS cohort, median cortisol following 1 mg DST was 2.6 ug/dL (range, 1.9–13.0) with median ACTH of 8.5 pg/mL (range, 5.0–38.0) and median DHEA-S of 37 mcg/dL (range, 5.0- 141.0). On cognitive assessment, patients with MACS had lower total cognition (T-scores 50 vs. 54, p=0.05) and fluid cognition (T-scores 48 vs. 53, p=0.01) composite scores compared to referent subjects without cortisol excess. In particular, patients with MACS performed worse on tests of executive function (Dimensional Change Card Sort: T-scores 55 vs. 63, p= 0.02 and Flanker Inhibitory Control and Attention: T-scores 45 vs. 52, p=0.01). There were no significant differences observed in the remaining individual domains of language, processing speed, working memory, and episodic memory, or crystallized cognition. Conclusions: MACS is associated with impaired total cognition, and in particular, executive function and fluid cognition. These findings suggest that patients with MACS are susceptible to cortisol-mediated changes in the brain. Additional studies should examine the contribution of neuropsychiatric symptoms on cognition in MACS, and possible improvement following treatment for cortisol excess.

Case 9 - Primary Aldosteronism With Bilateral Adrenal Nodules on Computed Tomography

BackgroundCushing syndrome (CS) is recognized to have multisystem morbidity, but data on the effect of mild autonomous cortisol secretion (MACS) are limited. We hypothesized that MACS is associated with impairments in objective measures of muscle strength and self-reported measures of physical and mental functioning.MethodsWe conducted a cross-sectional analysis of a prospective cohort of patients with confirmed hypercortisolism enrolled between 8/01/2019 and 12/31/2021. MACS was defined as serum cortisol greater than 1.8 mcg/dL after the 1 mg dexamethasone suppression test (DST) and lack of typical signs and symptoms of CS. Clinical outcomes were assessed prior to intervention. We measured hand grip strength with hand grip dynamometer and lower extremity muscle function with the chair rise test (number of sit-to-stands completed in 30 seconds). We assessed health-related quality of life with the Short Form-36 (SF-36) questionnaire. Performance was reported using age- and sex-adjusted z-scores based on normative data from the USA population.ResultsA total of 81 patients with MACS (median age 55 years, 49% women) and 85 patients with CS (median age 48 years, 51% women—adrenal CS in 14, pituitary CS in 62, and ectopic CS in 9) were enrolled. In the MACS cohort, median cortisol following 1 mg DST was 3.4 µg/dL (IQR 2.6-5.7), DHEA-S 37.0 µg/dL (IQR 21.5-58.5), ACTH 8.1 pg/mL (IQR, 5.6-13.0; normal 10-60), and 24-hour urinary cortisol 25.0 µg/24h (IQR 15.8-43.3, normal <45). In the CS cohort, median cortisol following 1 mg DST was 11.2 µg/dL (IQR 5.1-15.3), 24-hour urinary cortisol 156.0 µg/24h (IQR 65.5-356.5), and late-night salivary cortisol 251.0 ng/dL (IQR 158.8-430.3; normal <100). Z-scores for hand grip strength (0.13 ± 1.1 vs. 0.07 ± 1.1, p=0.73) and chair rise test performance (-0.25 ± 1.3 vs. -0.39 ± 2.0, p=0.63) were similar between patients with MACS and those with CS. On the SF-36 questionnaire, z-scores for all subdomains were negative in both groups. Patients with CS had lower z-scores on physical functioning (-1.71 ± 1.38 vs. -0.97 ± 1.44, p=0.001), role-physical limitation (-1.75 ± 1.19 vs. -1.15 ± 1.17 p =0.002), general health (-1.54 ± 1.16 vs. -1.03 ± 1.07, p=0.004), social functioning (-1.59 ± 1.27 vs. -0.97 ± 1.28, p= 0.002), and vitality subdomains (-1.67 ± 0.87 vs. -1.28 ± 1.11, p=0.01), but similar physical and mental component summary scores compared to patients with MACS. Chair rise test performance correlated with physical but not mental component summary scores.ConclusionsPatients with MACS have impaired chair rise test performance and health-related quality of life when compared to the general age and sex specific population. Remarkably, when compared to patients with CS, patients with MACS had no significant differences in muscle strength, SF-36 physical component summary score, or SF-36 mental component summary score.Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Background/Objective: The overnight 1-mg dexamethasone suppression test (DST) represents the conventional/standard tool for endogenous hypercortisolemia screening, typically in relationship with adrenal and pituitary masses. Nevertheless, an associated spectrum of challenges and pitfalls is found in daily practice. This analysis aimed to evaluate: (I.) the diagnosis relevance of 1-mg DST in patients with adrenal incidentalomas (AIs) with/without mild autonomous cortisol secretion (MACS) exploring different cutoffs of the second-day plasma cortisol after dexamethasone administration (cs-DST) with respect to cardio-metabolic outcomes; (II.) the potential utility of adding other biomarkers to DST [plasma morning adrenocorticotropic hormone (ACTH), 24-h urinary free cortisol (UFC), late-night salivary cortisol (LNSC), dehydroepiandrosterone sulfate (DHEAS)]; and (III.) DST variability in time. Methods: This narrative analysis was based on searching full-text, English articles in PubMed (between January 2023 and April 2025) via using different term combinations: "dexamethasone suppression test" (n = 239), "diagnosis test for autonomous cortisol secretion" (n = 22), "diagnosis test for mild autonomous cortisol secretion" (n = 13) and "diagnosis test for Cushing Syndrome" (n = 61). We manually checked the title and abstract and finally included only the studies that provided hormonal testing results in adults with non-functional adenomas (NFAs) ± MACS. We excluded: reviews, meta-analyses, editorials, conference abstracts, case reports, and case series; non-human research; studies that did not provide clear criteria for distinguishing between Cushing syndrome and MACS; primary aldosteronism. Results: The sample-focused analysis (n = 13 studies) involved various designs: cross-sectional (n = 4), prospective (n = 1), retrospective (n = 7), and cohort (n = 1); a total of 4203 patients (female-to-male ratio = 1.45), mean age of 59.92 years. I. Cs-DST cutoffs varied among the studies (n = 6), specifically, 0.87, 0.9, 1.2, and 1.4 µg/dL in relationship with the cardio-metabolic outcomes. After adjusting for age (n = 1), only the prevalence of cardiovascular disease remained significantly higher in >0.9 µg/dL vs. ≤0.9 group (OR = 2.23). Multivariate analysis (n = 1) found cs-DST between 1.2 and 1.79 µg/dL was independently associated with hypertension (OR = 1.55, 95%CI: 1.08-2.23, p = 0.018), diabetes (OR = 1.60, 95%CI: 1.01-2.57, p = 0.045), and their combination (OR = 1.96, 95%CI:1.12-3.41, p = 0.018) after adjusting for age, gender, obesity, and dyslipidemia. A higher cs-DST was associated with a lower estimated glomerular filtration rate (eGFR), independently of traditional cardiovascular risk factors. Post-adrenalectomy eGFR improvement was more pronounced in younger individuals, those with lower eGFR before surgery, and with a longer post-operative follow-up. Cs-DST (n = 1) was strongly associated with AIs size and weakly associated with age, body mass index and eGFR. Cortisol level increased by 9% (95% CI: 6-11%) for each 10 mL/min/1.73 m2 decrease in eGFR. A lower cs-DST was associated with a faster post-adrenalectomy function recovery; the co-diagnosis of diabetes reduced the likelihood of this recovery (OR = 24.55, p = 0.036). II. Additional biomarkers assays (n = 5) showed effectiveness only for lower DHEAS to pinpoint MACS amid AIs (n = 2, cutoffs of <49.31 µg/dL, respectively, <75 µg/dL), and lower ACTH (n = 1, <12.6 pmol/L). III. Longitudinal analysis of DST's results (n = 3): 22% of NFAS switch to MACS after a median of 35.7 months (n = 1), respectively, 29% (n = 1) after 48.6 ± 12.5 months, 11.8% (n = 1) after 40.4 ± 51.17 months. A multifactorial model of prediction showed the lowest risk of switch (2.4%) in individuals < 50 years with unilateral tumor and cs-DST < 0.45 µg/dL. In the subgroup of subjects without cardio-metabolic comorbidities at presentation, 25.6% developed ≥1 comorbidities during surveillance. Conclusions: The importance of exploring the domain of AIs/NFAs/MACS relates to an increasing detection in aging population, hence, the importance of their optimum hormonal characterization and identifying/forestalling cardio-metabolic consequences. The spectrum of additional biomarkers in MACS (other than DST) remains heterogeneous and still controversial, noting the importance of their cost-effectiveness, and availability in daily practice. Cs-DST serves as an independent predictor of cardio-metabolic outcomes, kidney dysfunction, while adrenalectomy may correct them in both MACS and NFAs, especially in younger population. Moreover, it serves as a predictor of switching the NFA into MACS category during surveillance. Changing the hormonal behavior over time implies awareness, since it increases the overall disease burden.

Management of the patient with incidental bilateral adrenal nodules

The objective of this study was to evaluate the role of adrenal venous sampling (AVS) in guiding the management of patients with corticotropin (ACTH)-independent glucocorticoid secretory autonomy and bilateral adrenal masses. A cohort with 25 patients underwent AVS and surgical management. Cortisol was measured from the adrenal veins (AVs) and inferior vena cava (IVC). AV/IVC cortisol ratio and cortisol lateralization ratio (CLR) (dominant AV cortisol concentration divided by the nondominant AV cortisol concentration) were calculated. Posthoc receiver-operating characteristiccurves were generated to determine the specificity of revised AV/IVC cortisol ratio and CLR in differentiating unilateral from bilateral disease. Patients underwent unilateral (n = 21) or bilateral (n = 4) adrenalectomy. The mean AV/IVC cortisol ratio for unilateral adrenalectomy was 12.1 ± 9.6 (dominant) and 4.7 ± 3.8 (contralateral) with a mean CLR of 3.6 ± 3.5. The mean AV/IVC cortisol ratio for bilateral adrenalectomy was 7.5 ± 2.1, with a mean CLR of 1.1 ± 0.6. At a mean follow-up of 22 months, one patient who underwent unilateral adrenalectomy for the predicted bilateral disease developed recurrent mild autonomous cortisol secretion. Posthoc analyses demonstrated a specificity of 95%-100% for unilateral disease with AV/IVC cortisol ratio >9 for one side, <2.0 for the opposite side and a CLR > 2.3. The specificity was 80%-90% for bilateral disease with AV/IVC cortisol ratio >5.1 bilaterally and a CLR < 1.1. Among patients with bilateral adrenal masses and ACTH-independent autonomous cortisol secretion, AVS can distinguish between unilateral and bilateral disease with high specificity and may guide surgical management.

PurposeTo study the usefulness of adrenal venous sampling (AVS) in distinguishing unilateral from bilateral cortisol production in patients with ACTH-independent hypercortisolism and bilateral adrenal lesions, or morphologically normal adrenal glands.MethodsA retrospective analysis of ten consecutive patients with ACTH-independent hypercortisolism who underwent AVS at our institution between 2009 and 2017. Unilateral dominant cortisol production was defined as a side-to-side cortisol/aldosterone lateralization ratio >2.ResultsFour of ten patients had overt Cushing’s syndrome. Of these, two had bilateral adrenal lesions on computed tomography and two had normal adrenal glands. One of the two patients with bilateral adrenal lesions had, based on the AVS, a unilateral dominant cortisol production. Following unilateral adrenalectomy the patient developed adrenal insufficiency. The other three patients were considered to have bilateral cortisol production and underwent bilateral adrenalectomy. Six patients had a mild autonomous cortisol secretion and bilateral adrenal lesions. Based on AVS, one patient was considered to have unilateral dominant cortisol production, underwent unilateral adrenalectomy and developed transient adrenal insufficiency postoperatively.ConclusionsAVS may contribute to appropriate treatment in patients with ACTH-independent hypercortisolism and bilateral adrenal lesions. In our series, AVS was helpful in the decision-making of two out of ten patients, avoiding chronic treatment with steroidogenesis inhibitors, or inappropriate bilateral adrenalectomy.

The primary aldosteronism (PA) subtype is usually confirmed by CT and adrenal venous sampling (AVS). However, the subtype diagnosis by AVS is not necessarily consistent with the subtype diagnosis by CT. Patients with PA who show bilateral lesions (normal-appearing adrenals or bilateral adrenal nodules) on CT but unilateral disease on AVS are often found. The aim of this study was to evaluate whether patients with PA subtype discordance between CT and AVS obtain benefits from unilateral adrenalectomy. We retrospectively analyzed 362 consecutive patients with PA who underwent both CT and adrenocorticotropic hormone-unstimulated AVS at Kanazawa University Hospital. Surgical outcomes for unilateral PA were evaluated according to the criteria of the Primary Aldosteronism Surgical Outcome study. In our study, the success rate of AVS in patients with bilateral lesions on CT was 89% (191/214). Furthermore, the discordance rate between CT and AVS in patients with bilateral lesions on CT was 39% (74/191). After surgery, patients with bilateral lesions on CT but unilateral disease on AVS (n = 17) had a lower complete biochemical success rate than those with unilateral lesions on CT and ipsilateral disease on AVS (n = 30) (41% vs. 80%, p = 0.01), but clinical and biochemical benefits (the complete and partial success combined) were not significantly different between them (76% vs. 93% (p = 0.11) and 70% vs. 90% (p = 0.10), respectively). In conclusion, patients with bilateral lesions on CT but unilateral disease on AVS benefited from surgery, and AVS should be performed for patients who pursue surgical management when the CT findings suggest bilateral lesions.

Background/Objectives: Mild autonomous cortisol secretion (MACS) can coexist with primary aldosteronism (PA). The purpose of our study was to evaluate whether (MACS) influences parameters analyzed during adrenal venous sampling (AVS) in patients with PA. Methods: Patients with PA from the SPAIN-ALDO Registry and the German Conn's Registry with available 1 mg-dexamethasone suppression test (DST) and AVS were included. MACS was defined as a post-DST cortisol > 1.8 µg/dL in the absence of specific signs and symptoms of Cushing's syndrome. Results: Two-hundred and twenty-five patients were included, 98 (43.6%) of whom had concomitant MACS. The mean age was 54 ± 10 years and 37.3% were women. AVS was performed by simultaneous catheterization of both adrenal veins and analysis of basal samples in 157 patients (69.8%), with both basal and post-ACTH samples in 15 patients (6.7%), and during continuous ACTH infusion in 53 patients (23.6%). AVS was considered technically unsuccessful in 40 cases (17.8%), suggesting unilateral secretion in 106 (47.1%) and bilateral secretion in 79 (35.1%). We did not find significant differences in the percentage of unilateral and bilateral results, cortisol, corrected aldosterone, or selectivity indices in the dominant and non-dominant veins, nor in the lateralization index or the contralateral suppression index between patients with and without MACS. They also had similar rates of surgical treatment and biochemical and clinical response. Conclusions: Although pathophysiological reasoning suggests that MACS could hinder AVS identification of unilateral forms of PA, our data suggest that such interference, if it exists, is of moderate clinical relevance.