Publications by authors named "Irina Bancos"

167 Publications

The metabolic phenotype of patients with primary aldosteronism: impact of subtype and sex - a multicenter-study of 3566 Caucasian and Asian subjects.

Eur J Endocrinol 2022 Sep 21;187(3):361-372. Epub 2022 Jul 21.

Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany.

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.
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http://dx.doi.org/10.1530/EJE-22-0040DOI Listing
September 2022

Clinical course and imaging characteristics of benign adrenal cysts: a single-center study of 92 patients.

Eur J Endocrinol 2022 Sep 25;187(3):429-437. Epub 2022 Jul 25.

Division of Endocrinology, Diabetes, Metabolism and Nutrition.

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.
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http://dx.doi.org/10.1530/EJE-22-0285DOI Listing
September 2022

Presentation, Management, and Outcomes of Urinary Bladder Paraganglioma: Results from a Multi-center Study.

J Clin Endocrinol Metab 2022 Jul 26. Epub 2022 Jul 26.

Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, MN, USA.

Context And Objectives: Urinary bladder paraganglioma (UBPGL) is rare. We aimed to characterize the presentation and outcomes of patients diagnosed with UBPGL.

Methods: We conducted a multi-center study of consecutive patients with pathologically-confirmed UBPGL evaluated between 1971 and 2021. Outcomes included repeat bladder surgery, metastases, and disease-specific mortality.

Results: 110 patients (56, 51% women) were diagnosed with UBPGL at a median age of 50 years (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 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 of 1.69, 95%CI of 1.31-2.17), and a higher degree of catecholamine excess (HR of 5.48, 95%CI of 1.40-21.39). Disease-specific mortality was higher in patients with synchronous metastases (HR of 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 the need of better diagnostic strategies. All patients with UBPGL should be monitored life-long for development of recurrence and metastases.
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http://dx.doi.org/10.1210/clinem/dgac427DOI Listing
July 2022

Histopathology and Genetic Causes of Primary Aldosteronism in Young Adults.

J Clin Endocrinol Metab 2022 Jul 2. Epub 2022 Jul 2.

Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.

Context: Due to its rare incidence, molecular features of 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 (FFPE) adrenal tissue sections from 74 young patients with lateralized PA (<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 (MAPNs), 1 double APN, 1 APA with MAPN, and 2 non-functioning 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.

Conclusions: 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.
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http://dx.doi.org/10.1210/clinem/dgac408DOI Listing
July 2022

Pituitary Adenoma Incidence, Management Trends, and Long-term Outcomes: A 30-Year Population-Based Analysis.

Mayo Clin Proc 2022 Jun 23. Epub 2022 Jun 23.

Department of Neurologic Surgery, Mayo Clinic, Rochester MN; Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester MN. Electronic address:

Objective: To perform a population-based study of pituitary adenoma epidemiology, including longitudinal trends in disease incidence, treatment patterns, and outcomes.

Patients And Methods: In this study of incident pituitary adenomas in Olmsted County, Minnesota, from January 1, 1989, through December 31, 2019, we identified 785 patients who underwent primary screening, 435 of whom were confirmed as harboring incident pituitary adenomas and were included. Primary outcomes of interest included demographic characteristics, presenting features, and disease outcomes (tumor control, biochemical control, and complications).

Results: Among our 435 study patients, 438 unique pituitary adenomas were diagnosed at a median patient age of 39 years (interquartile range [IQR], 27 to 58 years). Adenomas were incidentally identified in 164 of the 438 tumors (37%). Common symptomatic presentations included hyperprolactinemia (188 of 438 [43%]) and visual field deficit (47 of 438 [11%]). Laboratory tests confirmed pituitary hormone hypersecretion in 238 of the 435 patients (55%), which was symptomatic in 222. The median tumor diameter was 8 mm (IQR, 5 to 17 mm). Primary management strategies were observation (156 of 438 tumors [36%]), medication (162 of 438 tumors [37%]), and transsphenoidal resection (120 of 438 tumors [27%]). Tumor and biochemical control were achieved in 398 (95%) and 216 (91%) secreting tumors, respectively. New posttreatment pituitary or visual deficits were noted in 43 (11%) and 8 (2%); apoplexy occurred in 28 (6%). Median clinical follow-up was 98 months (IQR, 47 to 189 months). Standardized incidence rates were 3.77 to 16.87 per 100,000 population, demonstrating linear expansion over time (R=0.67). The mean overall standardized incidence rate was 10.1 per 100,000 population; final point prevalence was 175.1 per 100,000 population.

Conclusion: Pituitary adenoma is a highly incident disease, with prolactin-secreting and incidental lesions representing the majority of tumors. Incidence rates and asymptomatic detection appear to be increasing over time. Presenting symptoms and treatment pathways are variable; however, most patients achieve favorable outcomes with observation or a single treatment modality.
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http://dx.doi.org/10.1016/j.mayocp.2022.03.017DOI Listing
June 2022

Age-dependent and sex-dependent disparity in mortality in patients with adrenal incidentalomas and autonomous cortisol secretion: an international, retrospective, cohort study.

Lancet Diabetes Endocrinol 2022 07 6;10(7):499-508. Epub 2022 May 6.

Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, MN, USA.

Background: The association between cortisol secretion and mortality in patients with adrenal incidentalomas is controversial. We aimed to assess all-cause mortality, prevalence of comorbidities, and occurrence of cardiovascular events in uniformly stratified patients with adrenal incidentalomas and cortisol autonomy (defined as non-suppressible serum cortisol on dexamethasone suppression testing).

Methods: We conducted an international, retrospective, cohort study (NAPACA Outcome) at 30 centres in 16 countries. Eligible patients were aged 18 years or older with an adrenal incidentaloma (diameter ≥1 cm) detected between Jan 1, 1996, and Dec 31, 2015, and availability of a 1 mg dexamethasone suppression test result from the time of the initial diagnosis. Patients with clinically apparent hormone excess, active malignancy, or follow-up of less than 36 months were excluded. Patients were stratified according to the 0800-0900 h serum cortisol values after an overnight 1 mg dexamethasone suppression test; less than 50 nmol/L was classed as non-functioning adenoma, 50-138 nmol/L as possible autonomous cortisol secretion, and greater than 138 nmol/L as autonomous cortisol secretion. The primary endpoint was all-cause mortality. Secondary endpoints were the prevalence of cardiometabolic comorbidities, cardiovascular events, and cause-specific mortality. The primary and secondary endpoints were assessed in all study participants.

Findings: Of 4374 potentially eligible patients, 3656 (2089 [57·1%] with non-functioning adenoma, 1320 [36·1%] with possible autonomous cortisol secretion, and 247 [6·8%] with autonomous cortisol secretion) were included in the study cohort for mortality analysis (2350 [64·3%] women and 1306 [35·7%] men; median age 61 years [IQR 53-68]; median follow-up 7·0 years [IQR 4·7-10·2]). During follow-up, 352 (9·6%) patients died. All-cause mortality (adjusted for age, sex, comorbidities, and previous cardiovascular events) was significantly increased in patients with possible autonomous cortisol secretion (HR 1·52, 95% CI 1·19-1·94) and autonomous cortisol secretion (1·77, 1·20-2·62) compared with patients with non-functioning adenoma. In women younger than 65 years, autonomous cortisol secretion was associated with higher all-cause mortality than non-functioning adenoma (HR 4·39, 95% CI 1·93-9·96), although this was not observed in men. Cardiometabolic comorbidities were significantly less frequent with non-functioning adenoma than with possible autonomous cortisol secretion and autonomous cortisol secretion (hypertension occurred in 1186 [58·6%] of 2024 patients with non-functioning adenoma, 944 [74·0%] of 1275 with possible autonomous cortisol secretion, and 179 [75·2%] of 238 with autonomous cortisol secretion; dyslipidaemia occurred in 724 [36·2%] of 1999 patients, 547 [43·8%] of 1250, and 123 [51·9%] of 237; and any diabetes occurred in 365 [18·2%] of 2002, 288 [23·0%] of 1250, and 62 [26·7%] of 232; all p values <0·001).

Interpretation: Cortisol autonomy is associated with increased all-cause mortality, particularly in women younger than 65 years. However, until results from randomised interventional trials are available, a conservative therapeutic approach seems to be justified in most patients with adrenal incidentaloma.

Funding: Deutsche Forschungsgemeinschaft, Associazione Italiana per la Ricerca sul Cancro, Università di Torino.
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http://dx.doi.org/10.1016/S2213-8587(22)00100-0DOI Listing
July 2022

Hemodynamics in Patients With Pheochromocytoma or Paraganglioma Undergoing Non-neuroendocrine Operations.

J Surg Res 2022 Sep 29;277:189-199. Epub 2022 Apr 29.

Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota. Electronic address:

Introduction: Surgical resection of pheochromocytoma and paraganglioma (PPGL) may be associated with excessive hemodynamic variability. Whether hemodynamic variability occurs in patients with undiagnosed PPGL undergoing unrelated, non-neuroendocrine, operations is unknown.

Methods: We identified patients who underwent non-neuroendocrine surgical procedures up to 5 y before pathologic diagnosis of PPGL. For each PPGL, two non-PPGL patients were matched based on sex, age, type, and year of operation. Electronic medical records were reviewed for intraoperative blood pressures, heart rates, and hemodynamic variability was assessed with range (maximum-minimum), standard deviation, coefficient of variation, and average real variability.

Results: Thirty-seven PPGL patients underwent operations preceding the diagnosis of PPGL: 25 pheochromocytomas, 11 paragangliomas, and one metastatic pheochromocytoma. Median interquartile range tumor size at diagnosis was 35 mm (23 to 60). The time from index operation to PPGL diagnosis was ≤12 mo in 21 (56.8%) patients. In 23 (62.2%) patients, the subsequently diagnosed PPGL was functional. Fifteen (40.5%) PPGL and 20 (27.0%) control patients were preoperatively treated for hypertension (P = 0.149). Maximum intraoperative systolic BP was >180 mmHg for 4 (10.8%) PPGL patients and 3 (4.1%) controls (P = 0.219). Two PPGL patients had intraoperative systolic BP >230 mmHg. No significant differences were found with all other measures of intraoperative hemodynamic variability. Similarly, in secondary analysis there was no significant difference in intraoperative hemodynamic variability between biochemically active PPGL and their respective controls.

Conclusions: Patients with undiagnosed PPGL undergoing a wide variety of non-neuroendocrine operations had intraoperative hemodynamic variability comparable to non-PPGL patients undergoing the same type of procedures.
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http://dx.doi.org/10.1016/j.jss.2022.04.016DOI Listing
September 2022

American Association of Clinical Endocrinology Disease State Clinical Review: Evaluation and Management of Immune Checkpoint Inhibitor-Mediated Endocrinopathies: A Practical Case-Based Clinical Approach.

Endocr Pract 2022 Jul 25;28(7):719-731. Epub 2022 Apr 25.

ASCO Representative, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York.

Objective: The aim of this case-based clinical review was to provide a practical approach for clinicians regarding the management of patients with immune checkpoint inhibitor (ICI)-mediated endocrinopathies.

Methods: A literature search of PubMed, Embase, and Scopus was conducted using appropriate keywords. The discussions and strategies for the diagnosis and management of ICI-mediated endocrinopathies are based on evidence available from prospective, randomized clinical studies; cohort studies; cross-sectional studies; case-based studies; and an expert consensus.

Results: Immunotherapy with ICIs has transformed the treatment landscape of diverse types of cancers but frequently results in immune-mediated endocrinopathies that can cause acute and persistent morbidity and, rarely, death. The patterns of endocrinopathies differ between the inhibitors of the cytotoxic T-lymphocyte antigen 4 and programmed cell death protein 1 or programmed cell death protein 1 ligand pathways but most often involve the thyroid and pituitary glands. The less common but important presentations include insulin-deficient diabetes mellitus, primary adrenal insufficiency, primary hypoparathyroidism, central diabetes insipidus, primary hypogonadism, and pancreatitis, with or without subsequent progression to diabetes mellitus or exocrine insufficiency.

Conclusion: In recent years, with increasing numbers of patients with cancer being treated with ICIs, more clinicians in a variety of specialties have been called upon to diagnose and treat ICI-mediated endocrinopathies. Herein, we reviewed case scenarios of various clinical manifestations and emphasized the need for a high index of clinical suspicion by all clinicians caring for these patients, including endocrinologists, oncologists, primary care providers, and emergency department physicians. We also provided diagnostic and therapeutic approaches for ICI-induced endocrinopathies and proposed that patients on ICI therapy be evaluated and treated by a multidisciplinary team in collaboration with endocrinologists.
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http://dx.doi.org/10.1016/j.eprac.2022.04.010DOI Listing
July 2022

Clinical, imaging and biochemical presentation of cystic pheochromocytomas.

Clin Endocrinol (Oxf) 2022 Apr 21. Epub 2022 Apr 21.

Division of Endocrinology, Diabetes, and Nutrition, Mayo Clinic, Rochester, Minnesota, USA.

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  = .75, p < .0001) but not the cystic component (R  = .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.
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http://dx.doi.org/10.1111/cen.14743DOI Listing
April 2022

Quality of Life and its Determinants in Patients With Adrenal Insufficiency: A Survey Study at 3 Centers in the United States.

J Clin Endocrinol Metab 2022 06;107(7):e2851-e2861

Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, Minnesota 55905, USA.

Context: Current evidence on determinants of quality of life (QoL) in patients with adrenal insufficiency (AI) is limited.

Objective: This work aimed to identify the determinants of QoL in different subtypes of AI.

Methods: This multicenter cross-sectional survey study was conducted using a patient-centered questionnaire, the Short Form-36.

Results: Of 529 participants, 223 (42.2%) had primary AI, 190 (35.9%) had secondary AI, and 116 (21.9%) had glucocorticoid-induced AI. Median age was 58 years (interquartile range: 43-68 years) and 342 (64.8%) were women. In multivariable analyses, patients were more likely to report worse physical scores if they were women (odds ratio [OR]: 3.3; 95% CI, 1.8-6.0), had secondary AI or glucocorticoid-induced AI (OR: 2.5; 95% CI, 1.4-4.3), had shorter duration of AI (OR: 2.0; 95% CI, 1.1-3.6), were treated with more than 25 mg hydrocortisone equivalent daily (OR: 2.3; 95% CI, 1.2-4.6), had more comorbidities related to glucocorticoid excess (OR: 2.3; 95% CI, 1.3-4.0), reported a higher financial burden from AI (OR: 2.1; 95% CI, 1.3-3.6), and reported difficulties with AI management (OR: 2.5; 95% CI, 1.2-5.2). Women (OR: 2.1; 95% CI, 1.08-4.0), shorter duration of AI (OR: 2.4; 95% CI, 1.4-4.3), higher financial burden (OR: 2.3; 95% CI, 1.3-4.0), difficulties with AI management (OR: 2.6; 95% CI, 1.4-4.9), and lack of family support (OR: 9.1; 95% CI, 2.3-33.3) were associated with worse mental component scores.

Conclusion: In patients with AI, QoL could be improved by addressing certain determinants, such as avoiding GC overreplacement, providing in-depth education on self-management, offering more comprehensive insurance coverage, and ensuring better family support.
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http://dx.doi.org/10.1210/clinem/dgac175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202727PMC
June 2022

Web Exclusive. Annals On Call - Are Adrenal Incidentalomas Clinically Important?

Ann Intern Med 2022 Mar;175(3):OC1

Institute of Metabolism and Systems Research, University of Birmingham, Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, and Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom (A.P.).

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http://dx.doi.org/10.7326/A21-0007DOI Listing
March 2022

Pheochromocytomas and Abdominal Paragangliomas: A Practical Guidance.

Cancers (Basel) 2022 Feb 12;14(4). Epub 2022 Feb 12.

Department of Endocrinology, Karolinska University Hospital, 171 76 Stockholm, Sweden.

Pheochromocytomas and abdominal paragangliomas (PPGLs) are rare tumors arising from the adrenal medulla or the sympathetic nervous system. This review presents a practical guidance for clinicians dealing with PPGLs. The incidence of PPGLs has risen. Most cases are detected via imaging and less present with symptoms of catecholamine excess. Most PPGLs secrete catecholamines, with diffuse symptoms. Diagnosis is made by imaging and tests of catecholamines. Localized disease can be cured by surgery. PPGLs are the most heritable of all human tumors, and germline variants are found in approximately 30-50% of cases. Such variants can give information regarding the risk of developing recurrence or metastases as well as the risk of developing other tumors and may identify relatives at risk for disease. All PPGLs harbor malignant potential, and current histological and immunohistochemical algorithms can aid in the identification of indolent vs. aggressive tumors. While most patients with metastatic PPGL have slowly progressive disease, a proportion of patients present with an aggressive course, highlighting the need for more effective therapies in these cases. We conclude that PPGLs are rare but increasing in incidence and management should be guided by a multidisciplinary team.
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http://dx.doi.org/10.3390/cancers14040917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8869962PMC
February 2022

Outcomes of Initial Management Strategies in Patients With Autoimmune Lymphocytic Hypophysitis: A Systematic Review and Meta-analysis.

J Clin Endocrinol Metab 2022 03;107(4):1170-1190

Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, Minnesota 55905, USA.

Context: Lymphocytic hypophysitis (LyHy) is characterized by inflammation of the pituitary and or neuroinfundibulum and is uncommon. Treatment options include observation, high-dose glucocorticoids (HD-GCs) or surgery. Optimal first-line management strategy, however, remains unknown.

Objective: This work aimed to assess response to first-line treatment options (observation, HD-GCs, or surgery) of clinically relevant outcomes (symptomatic, hormonal, and radiographic improvement) among patients with LyHy.

Methods: A systematic review was conducted in 6 databases through 2020. Meta-analysis was conducted when feasible using a random-effects model.

Results: We included 33 studies reporting on 591 patients (423 women, 72%) with LyHy. Improvement/resolution of anterior pituitary dysfunction was highest when HD-GCs was first-line treatment. Surgery was associated with the greatest proportion of patients who had regression on imaging. Subgroup analysis comparing HD-GCs to observation showed the odds of anterior pituitary hormone recovery (OR 3.41; 95% CI, 1.68-6.94) or radiographic regression (OR 3.13; 95% CI, 1.54-6.36) were higher with HD-GCs, but so was the need for additional forms of treatment (OR 4.37; 95% CI, 1.70-11.22). No statistically significant difference was seen in recovery of diabetes insipidus (OR 0.9; 95% CI, 0.26-3.10). Certainty in these estimates was very low.

Conclusion: Observation and use of HD-GCs both are successful first-line management strategies in LyHy. Although use of HD-GCs was associated with increased recovery of anterior pituitary hormone deficit, it also was associated with greater likelihood of additional treatment after withdrawal. Optimal dosing and duration of HD-GCs remains unknown.
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http://dx.doi.org/10.1210/clinem/dgab839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8947799PMC
March 2022

The Effect of Curative Treatment on Hyperglycemia in Patients With Cushing Syndrome.

J Endocr Soc 2022 Jan 2;6(1):bvab169. Epub 2021 Dec 2.

Division of Endocrinology, Diabetes and Nutrition, Mayo Clinic, Rochester, Minnesota 55905, USA.

Context: Hyperglycemia is a common complication of Cushing syndrome (CS).

Objective: We aimed to determine the impact of curative procedure on hyperglycemia and its management in patients with CS.

Methods: This retrospective longitudinal cohort study took place 2000 to 2019 in a referral center among adults with endogenous CS and hyperglycemia. Main outcome measures included glycated hemoglobin A (HbA1c), intensity of hyperglycemia therapy, and improvement of hyperglycemia.

Results: In 174 patients with CS (pituitary in 106, ectopic in 25, adrenal in 43), baseline median HbA was 6.9% (range, 4.9-13.1), with 41 (24%) patients not on any therapy for hyperglycemia, 93 (52%) on oral medications, and 64 (37%) on insulin (median daily units of 58; range, 10-360). Following CS remission, at the end of follow-up (median 10.5 months), 37 (21%) patients demonstrated resolution of hyperglycemia, 82 (47%) demonstrated improvement, and 55 (32%) had no change or worsening in hyperglycemia. At the end of follow-up, HbA decreased by 0.84% ( < .001) and daily insulin dose decreased by a mean of 30 units ( < .001). Biochemical hypercortisolism severity score (severe vs moderate/mild: odds ratio [OR] of 2.4 [95% CI, 1.1-4.9]), and CS subtype (nonadrenal vs adrenal: OR of 2.9 [95% CI, 1.3-6.4]), but not type of hyperglycemia (diabetes vs prediabetes: OR of 2.1 [0.9-4.9]) were associated with hyperglycemia improvement at the end of follow-up.

Conclusion: Two-thirds of patients with CS and hyperglycemia demonstrate resolution or improvement of hyperglycemia after a curative procedure. Close monitoring during CS recovery is needed to ensure appropriate therapy modification.
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http://dx.doi.org/10.1210/jendso/bvab169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8694519PMC
January 2022

Cardiometabolic Disease Burden and Steroid Excretion in Benign Adrenal Tumors : A Cross-Sectional Multicenter Study.

Ann Intern Med 2022 Mar 4;175(3):325-334. Epub 2022 Jan 4.

Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital Würzburg, University of Würzburg, Würzburg, Germany (M.F.).

Background: Benign adrenal tumors are commonly discovered on cross-sectional imaging. Mild autonomous cortisol secretion (MACS) is regularly diagnosed, but its effect on cardiometabolic disease in affected persons is ill defined.

Objective: To determine cardiometabolic disease burden and steroid excretion in persons with benign adrenal tumors with and without MACS.

Design: Cross-sectional study.

Setting: 14 endocrine secondary and tertiary care centers (recruitment from 2011 to 2016).

Participants: 1305 prospectively recruited persons with benign adrenal tumors.

Measurements: Cortisol excess was defined by clinical assessment and the 1-mg overnight dexamethasone-suppression test (serum cortisol: <50 nmol/L, nonfunctioning adrenal tumor [NFAT]; 50 to 138 nmol/L, possible MACS [MACS-1]; >138 nmol/L and absence of typical clinical Cushing syndrome [CS] features, definitive MACS [MACS-2]). Net steroid production was assessed by multisteroid profiling of 24-hour urine by tandem mass spectrometry.

Results: Of the 1305 participants, 49.7% had NFAT ( = 649; 64.1% women), 34.6% had MACS-1 ( = 451; 67.2% women), 10.7% had MACS-2 ( = 140; 73.6% women), and 5.0% had CS ( = 65; 86.2% women). Prevalence and severity of hypertension were higher in MACS-2 and CS than NFAT (adjusted prevalence ratios [aPRs] for hypertension: MACS-2, 1.15 [95% CI, 1.04 to 1.27], and CS, 1.37 [CI, 1.16 to 1.62]; aPRs for use of ≥3 antihypertensives: MACS-2, 1.31 [CI, 1.02 to 1.68], and CS, 2.22 [CI, 1.62 to 3.05]). Type 2 diabetes was more prevalent in CS than NFAT (aPR, 1.62 [CI, 1.08 to 2.42]) and more likely to require insulin therapy for MACS-2 (aPR, 1.89 [CI, 1.01 to 3.52]) and CS (aPR, 3.06 [CI, 1.60 to 5.85]). Urinary multisteroid profiling revealed an increase in glucocorticoid excretion from NFAT over MACS-1 and MACS-2 to CS, whereas androgen excretion decreased.

Limitations: Cross-sectional design; possible selection bias.

Conclusion: A cardiometabolic risk condition, MACS predominantly affects women and warrants regular assessment for hypertension and type 2 diabetes.

Primary Funding Source: Diabetes UK, the European Commission, U.K. Medical Research Council, the U.K. Academy of Medical Sciences, the Wellcome Trust, the U.K. National Institute for Health Research, the U.S. National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.
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http://dx.doi.org/10.7326/M21-1737DOI Listing
March 2022

Cytoreductive Surgery of the Primary Tumor in Metastatic Adrenocortical Carcinoma: Impact on Patients' Survival.

J Clin Endocrinol Metab 2022 03;107(4):964-971

Unidade de Suprarrenal, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

Context: The role of cytoreduction of adrenocortical carcinoma (ACC) remains poorly understood.

Objective: To analyze the impact of cytoreductive surgery of the primary tumor in patients with metastatic ACC.

Design And Setting: We performed a multicentric, retrospective paired cohort study comparing the overall survival (OS) in patients with metastatic ACC who were treated either with cytoreductive surgery (CR group) or without cytoreductive surgery (no-CR group) of the primary tumor. Data were retrieved from 9 referral centers in the American-Australian-Asian Adrenal Alliance collaborative research group.

Patients: Patients aged ≥18 years with metastatic ACC at initial presentation who were treated between January 1, 1995, and May 31, 2019.

Intervention: Performance (or not) of cytoreductive surgery of the primary tumor.

Main Outcome And Measures: A propensity score match was done using age and the number of organs with metastasis (≤2 or >2). The main outcome was OS, determined from the date of diagnosis until death or until last follow-up for living patients.

Results: Of 339 patients pooled, 239 were paired and included: 128 in the CR group and 111 in the no-CR group. The mean follow-up was 67 months. Patients in the no-CR group had greater risk of death than did patients in the CR group (hazard ratio [HR] = 3.18; 95% CI, 2.34-4.32). Independent predictors of survival included age (HR = 1.02; 95% CI, 1.00-1.03), hormone excess (HR = 2.56; 95% CI, 1.66-3.92), and local metastasis therapy (HR = 0.41; 95% CI, 0.47-0.65).

Conclusion: Cytoreductive surgery of the primary tumor in patients with metastatic ACC is associated with prolonged survival.
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http://dx.doi.org/10.1210/clinem/dgab865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9122637PMC
March 2022

Diagnosis and treatment of primary aldosteronism.

Lancet Diabetes Endocrinol 2021 12;9(12):876-892

Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany; Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Turin, Italy.

Primary aldosteronism is a common cause of secondary hypertension associated with excess cardiovascular morbidities. Primary aldosteronism is underdiagnosed because it does not have a specific, easily identifiable feature and clinicians can be poorly aware of the disease. The diagnostic investigation is a multistep process of screening, confirmatory testing, and subtype differentiation of unilateral from bilateral forms for therapeutic management. Adrenal venous sampling is key for reliable subtype identification, but can be bypassed in patients with specific characteristics. For unilateral disease, surgery offers the possibility of cure, with total laparoscopic unilateral adrenalectomy being the treatment of choice. Bilateral forms are treated mainly with mineralocorticoid receptor antagonists. The goals of treatment are to normalise both blood pressure and excessive aldosterone production, and the primary aims are to reduce associated comorbidities, improve quality of life, and reduce mortality. Prompt diagnosis of primary aldosteronism and the use of targeted treatment strategies mitigate aldosterone-specific target organ damage and with appropriate patient management outcomes can be excellent. Advances in molecular histopathology challenge the traditional concept of primary aldosteronism as a binary disease, caused by either a unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia. Somatic mutations drive autonomous aldosterone production in most adenomas. Many of these same mutations have been identified in nodular lesions adjacent to an aldosterone-producing adenoma and in patients with bilateral disease. In addition, germline mutations cause rare familial forms of aldosteronism (familial hyperaldosteronism types 1-4). Genetic testing for inherited forms in suspected cases of familial hyperaldosteronism avoids the burdensome diagnostic investigation in positive patients. In this Review, we discuss advances and future management approaches in the diagnosis of primary aldosteronism.
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http://dx.doi.org/10.1016/S2213-8587(21)00210-2DOI Listing
December 2021

Informing therapeutic lymphadenectomy: Location of regional metastatic lymph nodes in adrenocortical carcinoma.

Am J Surg 2022 06 19;223(6):1042-1045. Epub 2021 Oct 19.

Department of Surgery, Mayo Clinic, 200th 1st Street, Rochester, MN, 55905, USA. Electronic address:

Background: The anatomic boundaries of lymphadenectomy for adrenocortical carcinoma (ACC) are not defined.

Methods: Adults undergoing resection of ACC were included. Locations were categorized based on positive LN locations on final pathology.

Results: Of 231 resected ACC, 6% had positive LN during initial resection. Positive LN in left ACC (n = 7) were: 2 para-aortic, 2 left renal-hilar, 1 para-aortic and left renal-hilar and 1 unknown, while for right ACC (n = 7): 2 para-caval, 1 para-caval and right renal-hilar, 1 inter-aortocaval, 1 celiac, 1 para-aortic, and 1 unknown. Of 55 resections for recurrent ACC, positive LN in left ACC (n = 2) were: 1 para-aortic, and 1 para-aortic with left renal-hilar, while LN for right ACC (n = 7): 2 inter-aortocaval, 2 right renal-hilar, 2 para-caval and one retrocrural.

Conclusion: The most common LN metastases are para-caval for right, and para-aortic and left renal-hilar for left ACC. Further studies are necessary to determine the boundaries of lymphadenectomy in ACC resection.
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http://dx.doi.org/10.1016/j.amjsurg.2021.10.014DOI Listing
June 2022

Consensus on diagnosis and management of Cushing's disease: a guideline update.

Lancet Diabetes Endocrinol 2021 12 20;9(12):847-875. Epub 2021 Oct 20.

San Raffaele Vita-Salute University, Milan, Italy.

Cushing's disease requires accurate diagnosis, careful treatment selection, and long-term management to optimise patient outcomes. The Pituitary Society convened a consensus workshop comprising more than 50 academic researchers and clinical experts to discuss the application of recent evidence to clinical practice. In advance of the virtual meeting, data from 2015 to present about screening and diagnosis; surgery, medical, and radiation therapy; and disease-related and treatment-related complications of Cushing's disease summarised in recorded lectures were reviewed by all participants. During the meeting, concise summaries of the recorded lectures were presented, followed by small group breakout discussions. Consensus opinions from each group were collated into a draft document, which was reviewed and approved by all participants. Recommendations regarding use of laboratory tests, imaging, and treatment options are presented, along with algorithms for diagnosis of Cushing's syndrome and management of Cushing's disease. Topics considered most important to address in future research are also identified.
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http://dx.doi.org/10.1016/S2213-8587(21)00235-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8743006PMC
December 2021

Interpretation of Abnormal Dexamethasone Suppression Test is Enhanced With Use of Synchronous Free Cortisol Assessment.

J Clin Endocrinol Metab 2022 02;107(3):e1221-e1230

Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, MN 55905, USA.

Context: Interpretation of dexamethasone suppression test (DST) may be influenced by dexamethasone absorption and metabolism and by the altered cortisol binding.

Objective: We aimed to determine the normal ranges of free cortisol during DST in participants without adrenal disorders and to identify the population of patients where post-DST free cortisol measurements add value to the diagnostic workup.

Design And Setting: Cross-sectional study conducted in a tertiary medical center.

Participants: Adult volunteers without adrenal disorders (n = 168; 47 women on oral contraceptive therapy [OCP], 66 women not on OCP, 55 men) and patients undergoing evaluation for hypercortisolism (n = 196; 16 women on OCP).

Measurements: Post-DST dexamethasone and free cortisol (mass spectrometry) and total cortisol (immunoassay).

Main Outcome Measures: Reference range for post-DST free cortisol, diagnostic accuracy of post-DST total cortisol.

Results: Adequate dexamethasone concentrations (≥0.1 mcg/dL) were seen in 97.6% volunteers and 96.3% patients. Only 25.5% of women volunteers on OCP had abnormal post-DST total cortisol (>1.8 mcg/dL). In volunteers, the upper post-DST free cortisol range was 48 ng/dL in men and women not on OCP, and 79 ng/dL in women on OCP. When compared with post-DST free cortisol, diagnostic accuracy of post-DST total cortisol was 87.3% (95% CI, 81.7-91.7); all false-positive results occurred in patients with post-DST cortisol between 1.8 and 5 mcg/dL. OCP use was the only factor associated with false-positive results (21.1% vs 4.9%, P = 0.02).

Conclusions: Post-DST free cortisol measurements are valuable in patients with optimal dexamethasone concentrations and post-DST total cortisol between 1.8 and 5 mcg/dL.
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http://dx.doi.org/10.1210/clinem/dgab724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9006975PMC
February 2022

Secondary Adrenal Insufficiency: Recent Updates and New Directions for Diagnosis and Management.

Endocr Pract 2022 Jan 2;28(1):110-117. Epub 2021 Oct 2.

Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, Minnesota; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota. Electronic address:

Secondary adrenal insufficiency is the most common subtype of adrenal insufficiency; it is caused by certain medications and pituitary destruction (pituitary masses, inflammation, or infiltration) and is rarely associated with certain germline variants. In this review, we discuss the etiology, epidemiology, and clinical presentation of secondary adrenal insufficiency and focus on the diagnostic and management challenges. We also review the management of selected special populations of patients and discuss patient-important outcomes associated with secondary adrenal insufficiency.
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http://dx.doi.org/10.1016/j.eprac.2021.09.011DOI Listing
January 2022

Surgical outcomes of medically failed prolactinomas: a systematic review and meta-analysis.

Pituitary 2021 Dec 27;24(6):978-988. Epub 2021 Sep 27.

Department of Neurological Surgery, Mayo Clinic, 200 First Street Southwest, Rochester, MN, 55905, USA.

Purpose: In Prolactinomas, surgery or radiation are reserved for DA failure due to tumor resistance, intolerance to medication-induced side-effects, or patient preference. This systematic review and meta-analysis summarizes the currently available literature regarding the effectiveness of surgery to treat prolactinomas in patients who have failed DA therapy.

Method: A literature search was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for studies that reported outcomes of medically resistant and intolerant prolactinoma treated surgically.

Results: 10 articles (Total N = 816, Surgery N = 657) met the inclusion criteria. 38% of patients who underwent surgery following DA failure achieved remission without need for further treatment (p < 0.001, I = 67.09%) with a median follow-up of 49.2 +/- 40 months. 62% achieved remission with multimodal treatment (p < 0.001, I = 93.28%) with a median follow-up of 53 +/- 39.8 months. 16% of cases demonstrated recurrence after early remission (p = 0.02, I = 62.91%) with recurrence occurring on average at 27 +/- 9 months. Overall, 46% of patients required reinstitution of postoperative DA therapy at last follow up (p < 0.001, I = 82.57%). Subgroup analysis of macroprolactinoma and microprolactinoma has demonstrated that there is no statistical significance in achieving long-term remission with surgery stand-alone in macroprolactinoma group (p = 0.49) although 43% of patients were able to achieve remission with multimodal therapy at last follow-up in the same group (p < 0.001, I = 86.34%).

Conclusions: This systematic review and meta-analysis revealed 38% of operated patients achieved remission, while 62% achieved remission when additional modes of therapy were implemented. Therefore, although surgery has not been initial therapeutic choice for prolactinoma, it plays a significant role in medically failed prolactinoma care.
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http://dx.doi.org/10.1007/s11102-021-01188-7DOI Listing
December 2021

Adrenal myelolipomas.

Lancet Diabetes Endocrinol 2021 11 24;9(11):767-775. Epub 2021 Aug 24.

Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

Adrenal myelolipomas are benign, lipomatous tumours with elements of myeloid cells, most of which present as adrenal incidentalomas and comprise 3·3-6·5% of all adrenal masses. Adrenal myelolipomas are usually unilateral (in 95% of cases), variable in size, most often found during midlife, and affect both sexes almost equally. On imaging, adrenal myelolipomas show pathognomonic imaging features consistent with the presence of macroscopic fat. Large adrenal myelolipomas can cause symptoms of mass effect, and can occasionally be complicated by haemorrhage. In the event of a concomitant adrenal cortical adenoma or hyperplasia, adrenal hormone excess might be detected in patients with adrenal myelolipoma. Patients with congenital adrenal hyperplasia exhibit a higher prevalence of adrenal myelolipomas than other patient groups, and are at risk of developing large and bilateral lesions. This Review discusses the pathogenesis, clinical presentation, and management of adrenal myelolipomas.
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http://dx.doi.org/10.1016/S2213-8587(21)00178-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851410PMC
November 2021

Abnormal body composition in patients with adrenal adenomas.

Eur J Endocrinol 2021 Oct 8;185(5):653-662. Epub 2021 Oct 8.

Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota, USA.

Objective: Increased visceral fat and sarcopenia are cardiovascular risk factors that may explain increased cardiovascular morbidity and frailty in patients with adrenal adenomas. Our objective was to compare body composition measurement of patients with adrenal adenomas to referent subjects without adrenal disease.

Design: Cross-sectional study, 2014-2018.

Methods: Participants were adults with nonfunctioning adrenal tumor (NFAT), mild autonomous cortisol secretion (MACS), and Cushing syndrome (CS) and age, sex, and BMI 1:1 matched referent subjects without adrenal disorders. Main outcome measures were body composition measurements calculated from abdominal CT imaging. Intra-abdominal adipose tissue and muscle mass measurements were performed at the third lumbar spine level.

Results: Of 227 patients with adrenal adenomas, 20 were diagnosed with CS, 76 with MACS, and 131 with NFAT. Median age was 56 years (range: 18-89), and 67% were women. When compared to referent subjects, patients with CS, MACS, and NFAT demonstrated a higher visceral fat (odds ratio (OR): 2.2 (95% CI: 0.9-6.5), 2.0 (1.3-3.2), and 1.8 (1.2-2.7) and a lower skeletal muscle area (OR: 0.01 (95% CI: 0-0.09), 0.31 (0.18-0.49), and 0.3 (1.2-2.7)) respectively. For every 1 µg/dL cortisol increase after overnight dexamethasone, visceral fat/muscle area ratio increased by 2.3 (P = 0.02) and mean total skeletal muscle area decreased by 2.2 cm2 (P = 0.03).

Conclusion: Patients with adrenal adenomas demonstrate a lower muscle mass and a higher proportion of visceral fat when compared to referent subjects, including patients with NFAT. Even a subtle abnormality in cortisol secretion may impact health of patients with adenomas.
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http://dx.doi.org/10.1530/EJE-21-0458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511231PMC
October 2021

Relacorilant, a Selective Glucocorticoid Receptor Modulator, Induces Clinical Improvements in Patients With Cushing Syndrome: Results From A Prospective, Open-Label Phase 2 Study.

Front Endocrinol (Lausanne) 2021 14;12:662865. Epub 2021 Jul 14.

Drug Research and Development, Corcept Therapeutics, Menlo Park, CA, United States.

Introduction/purpose: Relacorilant is a selective glucocorticoid receptor modulator (SGRM) with no progesterone receptor activity. We evaluated the efficacy and safety of relacorilant in patients with endogenous Cushing syndrome (CS).

Materials And Methods: A single-arm, open-label, phase 2, dose-finding study with 2 dose groups (NCT02804750, https://clinicaltrials.gov/ct2/show/NCT02804750) was conducted at 19 sites in the U.S. and Europe. Low-dose relacorilant (100-200 mg/d; n = 17) was administered for 12 weeks or high-dose relacorilant (250-400 mg/d; n = 18) for 16 weeks; doses were up-titrated by 50 mg every 4 weeks. Outcome measures included proportion of patients with clinically meaningful changes in hypertension and/or hyperglycemia from baseline to last observed visit. For patients with hypertension, clinical response was defined as a ≥5-mmHg decrease in mean systolic or diastolic blood pressure, measured by a standardized and validated 24-h ABPM. For patients with hyperglycemia, clinical response was defined ad-hoc as ≥0.5% decrease in HbA1c, normalization or ≥50-mg/dL decrease in 2-h plasma glucose value on oral glucose tolerance test, or decrease in daily insulin (≥25%) or sulfonylurea dose (≥50%).

Results: 35 adults with CS and hypertension and/or hyperglycemia (impaired glucose tolerance or type 2 diabetes mellitus) were enrolled, of which 34 (24 women/10 men) received treatment and had postbaseline data. In the low-dose group, 5/12 patients (41.7%) with hypertension and 2/13 patients (15.4%) with hyperglycemia achieved response. In the high-dose group, 7/11 patients (63.6%) with hypertension and 6/12 patients (50%) with hyperglycemia achieved response. Common (≥20%) adverse events included back pain, headache, peripheral edema, nausea, pain at extremities, diarrhea, and dizziness. No drug-induced vaginal bleeding or hypokalemia occurred.

Conclusions: The SGRM relacorilant provided clinical benefit to patients with CS without undesirable antiprogesterone effects or drug-induced hypokalemia.
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http://dx.doi.org/10.3389/fendo.2021.662865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317576PMC
December 2021

Approach to the Patient With Adrenal Incidentaloma.

J Clin Endocrinol Metab 2021 10;106(11):3331-3353

Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, B15 2TT, UK.

Adrenal tumors are commonly discovered incidentally on cross-sectional abdominal imaging performed for reasons other than adrenal mass. Incidence of adrenal tumors increased 10-fold in the past 2 decades, with most diagnosed in older adults. In any patient with a newly discovered adrenal mass, determining whether the adrenal mass is malignant and whether it is hormonally active is equally important to guide the best management. Malignancy is diagnosed in 5% to 8% of patients with adrenal tumors, with a higher risk in young patients, if history of extra-adrenal malignancy, in those with large adrenal tumors with indeterminate imaging characteristics, and in bilateral adrenal tumors. Although overt hormone excess is uncommon in adrenal incidentalomas, mild autonomous cortisol secretion can be diagnosed in up to 30% to 50% of patients. Because autonomous cortisol secretion is associated with increased cardiovascular morbidity and metabolic abnormalities, all patients with adrenal incidentalomas require work up with dexamethasone suppression test. Management of adrenal tumors varies based on etiology, associated comorbidities, and patient's preference. This article reviews the current evidence on the diagnosis and evaluation of patients with adrenal mass and focuses on management of the most common etiologies of adrenal incidentalomas.
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http://dx.doi.org/10.1210/clinem/dgab512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8530736PMC
October 2021

Concomitant Pheochromocytoma and Primary Aldosteronism: A Case Series and Literature Review.

J Endocr Soc 2021 Aug 16;5(8):bvab107. Epub 2021 Jun 16.

Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN, USA.

Context: The detection and management of concomitant pheochromocytoma (PHEO) and primary aldosteronism (PA) is not well understood.

Objective: To investigate varying presentations and outcomes of cases with coexisting PHEO and PA to provide an approach to its diagnosis and management.

Methods: We conducted a retrospective case series of adult patients with concomitant PHEO and PA at Mayo Clinic from 2000-2020 and an additional review of cases before 2000 and from the medical literature. Clinical, biochemical, radiologic, and histologic parameters were measured.

Results: Fifteen patients (53% men, median age 53 years) were diagnosed with concomitant PHEO and PA. The majority presented with hypertension (13, 87%) and hypokalemia (13, 87%), and 6 (40%) presented with symptoms suggestive of catecholamine excess. All patients who underwent preoperative workup for catecholamine excess (14, 93%) were found to have biochemical levels above the upper limits of normal. Adrenal vein sampling (AVS) was performed in 9 patients (60%), where 5 (56%) were diagnosed with bilateral PA, and 4 (44%) with unilateral PA. Patients underwent either unilateral (12, 80%) or bilateral (3, 20%) adrenalectomy. Biochemical improvement or resolution of catecholamine excess was confirmed in all cases with documented measurements. Recurrence of PHEO was not observed. Six patients (40%) displayed persistent PA postoperatively.

Conclusion: Concomitant PHEO and PA is a rare but likely underreported condition. Hypertension with or without hypokalemia should prompt evaluation for PA, while any indeterminate adrenal mass should be assessed for PHEO. Coexisting disease warrants consideration of AVS to determine the laterality of PA to ensure appropriate management.
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http://dx.doi.org/10.1210/jendso/bvab107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271195PMC
August 2021
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