Citations

AbstractObjectiveThe 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.Design and PatientsA cohort with 25 patients underwent AVS and surgical management.MeasurementsCortisol 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 characteristic curves were generated to determine the specificity of revised AV/IVC cortisol ratio and CLR in differentiating unilateral from bilateral disease.ResultsPatients 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.ConclusionsAmong 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.

AbstractBackgroundBilateral idiopathic hyperaldosteronism (IHA) is responsible for 60% of primary aldosteronism (PA) cases. Medical management is standard of care for IHA. Unilateral adrenalectomy (UA) with the intent of debulking total aldosterone production as a palliative measure remains controversial.MethodsSingle‐center retrospective review (2010–2020) of patients undergoing UA with a diagnosis of PA due to IHA (lateralization index [LI] on adrenal venous sampling [AVS] < 4). Demographic, pre‐operative, intra‐operative, and post‐operative variables were assessed. Hypertensive regimens were converted to the WHO Defined Daily Dose (DDD).ResultsTwenty‐four patients were identified, 14, 58% male and mean age 52 ± 10 years. Preoperative hypokalemia was present in 22, 92% of patients. Median number of antihypertensives taken was 3 (interquartile range [IQR], 2–4) and median DDD was 4 (IQR, 3–5.3). Median lateralization index on AVS was 3.52 (range, 1.19–3.88). All operations were performed in minimally invasive fashion. There were no conversions to open procedure, ICU admissions, or post‐operative complications. Median follow‐up was 10.5 months (range, 1–145 months). Hypokalemia resolved in 17, 76% of patients at last follow‐up. Post‐operative median number of antihypertensives taken was 1 (IQR, 1–3) and median DDD was 2 (IQR, 0.5–2.75) from 4, P = 0.003. Three (%) patients required continuation of mineralocorticoid receptor antagonists post‐operatively. Blood pressure control improved in 65% of patients.ConclusionUnilateral adrenalectomy in the setting of bilateral hyperaldosteronism can improve blood pressure control and stabilize potassium levels in selected patients. Further prospective studies in larger cohorts will be necessary to further define the role of unilateral adrenalectomy in the setting of PA due to bilateral adrenal disease.

Abstract Objective Prolactinomas are treated with dopamine agonists (DAs) as first-line therapy and transsphenoidal surgery as an alternative approach for medically failed tumors. We sought to summarize the efficacy of stereotactic radiosurgery (SRS) in the medically and surgically failed prolactinomas as well as in nonsurgical candidates with medically failed prolactinomas by systematic review and meta-analysis. Method A literature search was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guideline. Results A total of 11 articles (total N = 709) met inclusion criteria. Thirty-three percent of patients were able to achieve endocrine remission at a mean follow-up of 54.2 ± 42.2 months with no association between stopping DA and endocrine remission. Sixty-two percent of patients were able to achieve endocrine control with DA therapy and 34% of patients were able to decrease the dose of DA dose when compared with pre-SRS DA dose at the end of the follow-up period. However, 54% of patients required DA at the end of the follow-up to control hyperprolactinemia. Ninety percent of patients were able to achieve radiologic control at the end of the follow-up in comparison to pre-SRS imagings. Furthermore, 26% of patients newly developed hypopituitarism (one or more pituitary hormones) post-SRS throughout the follow-up period. Conclusion This systematic review and meta-analysis demonstrates SRS as an effective adjunct therapy in medically failed nonsurgical candidates or surgically and medically recalcitrant prolactinomas with a 33% chance of achieving endocrine remission, 62% of patients achieved hormonal control with DA and GKRS (gamma knife radio-surgery), with a 34% chance of decreasing DA dose and 90% chance of achieving radiologic control.

ImportanceAdrenalectomy is the definitive treatment for multiple adrenal abnormalities. Advances in technology and genomics and an improved understanding of adrenal pathophysiology have altered operative techniques and indications.ObjectiveTo develop evidence-based recommendations to enhance the appropriate, safe, and effective approaches to adrenalectomy.Evidence ReviewA multidisciplinary panel identified and investigated 7 categories of relevant clinical concern to practicing surgeons. Questions were structured in the framework Population, Intervention/Exposure, Comparison, and Outcome, and a guided review of medical literature from PubMed and/or Embase from 1980 to 2021 was performed. Recommendations were developed using Grading of Recommendations, Assessment, Development and Evaluation methodology and were discussed until consensus, and patient advocacy representation was included.FindingsPatients with an adrenal incidentaloma 1 cm or larger should undergo biochemical testing and further imaging characterization. Adrenal protocol computed tomography (CT) should be used to stratify malignancy risk and concern for pheochromocytoma. Routine scheduled follow-up of a nonfunctional adrenal nodule with benign imaging characteristics and unenhanced CT with Hounsfield units less than 10 is not suggested. When unilateral disease is present, laparoscopic adrenalectomy is recommended for patients with primary aldosteronism or autonomous cortisol secretion. Patients with clinical and radiographic findings consistent with adrenocortical carcinoma should be treated at high-volume multidisciplinary centers to optimize outcomes, including, when possible, a complete R0 resection without tumor disruption, which may require en bloc radical resection. Selective or nonselective α blockade can be used to safely prepare patients for surgical resection of paraganglioma/pheochromocytoma. Empirical perioperative glucocorticoid replacement therapy is indicated for patients with overt Cushing syndrome, but for patients with mild autonomous cortisol secretion, postoperative day 1 morning cortisol or cosyntropin stimulation testing can be used to determine the need for glucocorticoid replacement therapy. When patient and tumor variables are appropriate, we recommend minimally invasive adrenalectomy over open adrenalectomy because of improved perioperative morbidity. Minimally invasive adrenalectomy can be achieved either via a retroperitoneal or transperitoneal approach depending on surgeon expertise, as well as tumor and patient characteristics.Conclusions and RelevanceTwenty-six clinically relevant and evidence-based recommendations are provided to assist surgeons with perioperative adrenal care.

Abstract Context Urinary bladder paraganglioma (UBPGL) is rare. Objective We aimed to characterize the presentation and outcomes of patients diagnosed with UBPGL. Methods We conducted a multicenter study of consecutive patients with pathologically confirmed UBPGL evaluated between 1971 and 2021. Outcomes included repeat bladder surgery, metastases, and disease-specific mortality. Results Patients (n=110 total; n=56 [51%] women) were diagnosed with UBPGL at a median age of 50 years (interquartile range [IQR], 36-61 years). Median tumor size was 2 cm (IQR, 1-4 cm). UBPGL was diagnosed prior to biopsy in only 37 (34%), and only 69 (63%) patients had evaluation for catecholamine excess. In addition to the initial bladder surgery, 26 (25%) required multiple therapies, including repeat surgery in 10 (9%). Synchronous metastases were present in 9 (8%) patients, and 24 (22%) other patients with UBPGL developed metachronous metastases at a median of 4 years (IQR, 2-10 years) after the initial diagnosis. Development of metachronous metastases was associated with younger age (hazard ratio [HR] 0.97; 95% CI, 0.94-0.99), UBPGL size (HR 1.69; 95% CI, 1.31-2.17), and a higher degree of catecholamine excess (HR 5.48; 95% CI, 1.40-21.39). Disease-specific mortality was higher in patients with synchronous metastases (HR 20.80; 95% CI, 1.30-332.91). Choice of initial surgery, genetic association, sex, or presence of muscular involvement on pathology were not associated with development of metastases or mortality. Conclusions Only a minority of patients were diagnosed before biopsy/surgery, reflecting need for better diagnostic strategies. All patients with UBPGL should have lifelong monitoring for development of recurrence and metastases.

Objective Benign adrenal cysts are rare lesions of the adrenal glands. Limited data are available to guide management. We aimed to describe the presentation and outcomes of patients with benign adrenal cysts. Design Retrospective longitudinal cohort study. Methods Consecutive patients with histologically or radiologically confirmed adrenal cysts between 1995 and 2021 were identified. Pheochromocytomas and malignancy were excluded. Results Benign adrenal cysts were diagnosed in 92 patients (53, 57% women) at a median age of 45 years. Mode of discovery was incidental on imaging in 81 (88%), symptoms of mass effect in 9 (9.8%), and others in 2 (2.2%). Majority (89, 97%) of patients had unilateral cysts (45 right, 44 left) with a median size of 48 mm (range 4–200) at diagnosis. On imaging, most cysts were round/oval (85.4%), homogenous (83.2%) lesions with calcifications (64.0%) and no vascular enhancement (97.7%). During a median follow-up of 65 months (range 7–288), adrenal cysts demonstrated minimal enlargement (median size change 6 mm, median growth rate 2 mm/year). On hormonal evaluation, 10% (5/50 tested) had an abnormal overnight dexamethasone suppression test, and 9.5% (4/42 tested) had an abnormal case detection testing for primary aldosteronism. Patients treated with adrenalectomy (46, 50%) were younger (36.9 years vs 50.8 years, P = 0.0009) and had more rapidly enlarging cysts (median growth rate 5.5 mm/year vs 0.4 mm/year, P = 0.0002). Conclusion Benign adrenal cysts are usually incidentally discovered, non-functional, homogenous lesions without vascular enhancement that demonstrate minimal growth. Adrenalectomy should be reserved for patients with heterogeneous lesions, abnormal hormonal evaluation, or those with mass effect symptoms.

Background Accumulating evidence suggests that primary aldosteronism (PA) is associated with several features of the metabolic syndrome, in particular with obesity, type 2 diabetes mellitus, and dyslipidemia. Whether these manifestations are primarily linked to aldosterone-producing adenoma (APA) or bilateral idiopathic hyperaldosteronism (IHA) remains unclear. The aim of the present study was to investigate differences in metabolic parameters between APA and IHA patients and to assess the impact of treatment on these clinical characteristics. Methods We conducted a retrospective multicenter study including 3566 patients with APA or IHA of Caucasian and Asian origin. We compared the prevalence of metabolic disorders between APA and IHA patients at the time of diagnosis and 1-year post-intervention, with special references to sex differences. Furthermore, correlations between metabolic parameters and plasma aldosterone, renin, or plasma cortisol levels after 1 mg dexamethasone (DST) were performed. Results As expected, APA patients were characterized by higher plasma aldosterone and lower serum potassium levels. Only female IHA patients demonstrated significantly worse metabolic parameters than age-matched female APA patients, which were associated with lower cortisol levels upon DST. One-year post-intervention, female adrenalectomized patients showed deterioration of their lipid profile, when compared to patients treated with mineralocorticoid receptor antagonists. Plasma aldosterone levels negatively correlated with the BMI only in APA patients. Conclusions Metabolic alterations appear more prominent in women with IHA. Although IHA patients have worse metabolic profiles, a correlation with cortisol autonomy is documented only in APAs, suggesting an uncoupling of cortisol action from metabolic traits in IHA patients.

Abstract Context Due to its rare incidence, molecular features of primary aldosteronism (PA) in young adults are largely unknown. Recently developed targeted mutational analysis identified aldosterone-driver somatic mutations in aldosterone-producing lesions, including aldosterone-producing adenomas (APAs), aldosterone-producing nodules (APNs), and aldosterone-producing micronodules, formerly known as aldosterone-producing cell clusters. Objective To investigate histologic and genetic characteristics of lateralized PA in young adults. Methods Formalin-fixed, paraffin-embedded adrenal tissue sections from 74 young patients with lateralized PA (&lt;35 years old) were used for this study. Immunohistochemistry (IHC) for aldosterone synthase (CYP11B2) was performed to define the histopathologic diagnosis. Somatic mutations in aldosterone-producing lesions were further determined by CYP11B2 IHC-guided DNA sequencing. Results Based on the CYP11B2 IHC results, histopathologic classification was made as follows: 48 APAs, 20 APNs, 2 multiple aldosterone-producing nodules (MAPN), 1 double APN, 1 APA with MAPN, and 2 nonfunctioning adenomas (NFAs). Of 45 APAs with successful sequencing, 43 (96%) had somatic mutations, with KCNJ5 mutations being the most common genetic cause of young-onset APA (35/45, 78%). Of 18 APNs with successful sequencing, all of them harbored somatic mutations, with CACNA1D mutations being the most frequent genetic alteration in young-onset APN (8/18, 44%). Multiple CYP11B2-expressing lesions in patients with MAPN showed several aldosterone-driver mutations. No somatic mutations were identified in NFAs. Conclusion APA is the most common histologic feature of lateralized PA in young adults. Somatic KCNJ5 mutations are common in APAs, whereas CACNA1D mutations are often seen in APNs in this young PA population.

Abstract Objective Cystic adrenal mass is a rare imaging presentation of pheochromocytoma. We aimed to describe the clinical, biochemical and imaging characteristics of patients with cystic pheochromocytoma. Design Single‐centre, retrospective study, 2000−2020. Patients Consecutive patients with cystic pheochromocytoma were identified from our institutional pathology and adrenal tumour database. Results Of the 638 patients with pheochromocytomas, 21 (3.2%) had cystic pheochromocytomas (median age: 57 years, 57% women). Most pheochromocytomas were discovered incidentally (57%) or due to symptoms of catecholamine excess (24%). The median tumour size was 6.4 cm. On imaging, cystic pheochromocytomas were round or oval (90%), heterogeneous lesions (86%) with a thick solid rim (median rim thickness 13.9 mm, unenhanced computed tomography (CT) attenuation 40 Hounsfield units (HU), venous‐phase CT attenuation 83 HU), and a median cystic component of 40% (unenhanced CT attenuation 17.6 HU, venous‐phase CT attenuation 20.4 HU), and rarely with calcifications (15%). All 20 patients with biochemical testing had functioning tumours (adrenergic in 80%, noradrenergic in 20%). Total urinary metanephrine excretion correlated with the volume of the solid component ( R 2 = .75, p < .0001) but not the cystic component ( R 2 = .04, p = .4386). All patients underwent adrenalectomy (48% laparoscopic, 52% open), and the median duration of hospital stay was 4 days. Conclusions Cystic pheochromocytomas are rare, large tumours with a phenotypic appearance that can masquerade as other adrenal cystic lesions. The degree of biochemical abnormality in cystic pheochromocytomas is associated with the volume of the solid component. All patients with adrenal cysts that have a solid component or an unenhanced attenuation >10 HU should undergo biochemical testing for pheochromocytoma.