A ZNRF3-dependent Wnt/ß-catenin signaling gradient is required for adrenal homeostasis.

Spatiotemporal control of Wnt signaling is essential for the development and homeostasis of many tissues. The transmembrane E3 ubiquitin ligases ZNRF3 (zinc and ring finger 3) and RNF43 (ring finger protein 43) antagonize Wnt signaling by promoting degradation of frizzled receptors. ZNRF3 and RNF43 are frequently inactivated in human cancer, but the molecular and therapeutic implications remain unclear. Here, we demonstrate that adrenocortical-specific loss of ZNRF3, but not RNF43, results in adrenal hyperplasia that depends on Porcupine-mediated Wnt ligand secretion. Furthermore, we discovered a Wnt/ß-catenin signaling gradient in the adrenal cortex that is disrupted upon loss of ZNRF3. Unlike ß-catenin gain-of-function models, which induce high Wnt/ß-catenin activation and expansion of the peripheral cortex, ZNRF3 loss triggers activation of moderate-level Wnt/ß-catenin signaling that drives proliferative expansion of only the histologically and functionally distinct inner cortex. Genetically reducing ß-catenin dosage significantly reverses the ZNRF3-deficient phenotype. Thus, homeostatic maintenance of the adrenal cortex is dependent on varying levels of Wnt/ß-catenin activation, which is regulated by ZNRF3.

Primary Aldosteronism and the Role of Mineralocorticoid Receptor Antagonists for the Heart and Kidneys.

Primary aldosteronism (PA) is the most common cause of secondary hypertension but is frequently underrecognized and undertreated. Patients with PA are at a markedly increased risk for target organ damage to the heart and kidneys. While patients with unilateral PA can be treated surgically, many patients with PA are not eligible or willing to undergo surgery. Steroidal mineralocorticoid receptor antagonists (MRAs) are highly effective for treating PA and reducing the risk of target organ damage. However, steroidal MRAs are often underprescribed and can be poorly tolerated by some patients due to side effects. Nonsteroidal MRAs reduce adverse renal and cardiovascular outcomes among patients with diabetic kidney disease and are bettertolerated than steroidal MRAs. While their blood pressure-lowering effects remain unclear, these agents may have a potential role in reducing target organ damage in patients with PA.

Adrenal disorders in pregnancy.

Progress in our understanding of adrenal disorders affecting pregnant women has been hindered by three major hurdles: the phenotypical and biochemical overlap between pregnancy and adrenal pathology, the infrequent presentation of adrenal disorders during pregnancy, and the scarcity of human studies that include pregnant women. Pregnancy-specific adrenal hormone calibrations are lacking. Thus, the evaluation and management of adrenal disorders presenting during pregnancy are challenging. In this thematic issue, prominent experts in adrenal physiology and pathology have joined forces to offer a comprehensive collection of articles covering the current knowledge on adrenal disorders affecting reproductive-age women. This superb collection of reviews makes the perfect clinical companion on pregnancy-related adrenal pathology for a broad range of healthcare providers, from primary care physicians and internists to endocrinologists and gynecologist-obstetricians, regardless of career stage or practice setting.

Personalized Treatment of Patients With Primary Aldosteronism.

Primary aldosteronism (PA) is a highly prevalent yet underdiagnosed secondary cause of hypertension. PA is associated with increased cardiovascular and renal morbidity compared with patients with primary hypertension. Thus, prompt identification and targeted therapy of PA are essential to reduce cardiovascular and renal morbidity and mortality in a large population with hypertension. Unilateral adrenalectomy is preferred for lateralized PA as the only potentially curative therapy. Surgery also mitigates the risk of cardiovascular and renal complications associated with PA. Targeted medical therapy, commonly including a mineralocorticoid receptor antagonist, is offered to patients with bilateral PA and those who are not surgical candidates. Novel therapies, including nonsteroidal mineralocorticoid receptor antagonists and aldosterone synthase inhibitors, are being developed as alternative options for PA treatment. In this review article, we discuss how to best individualize therapy for patients with PA.

Management of Anastomotic Leakage after Low Anterior Rectal Resections with Total Mesorectal Excision - A Retrospective Study.

Background: This study sought to investigate the diagnostic procedures, treatment modalities, and consequences of anastomotic leakage (AL) in low anterior resection rectal cancer patients. Methods: A retrospective analysis was conducted on 186 patients consecutively admitted and treated in the 1st Department of Surgery in Craiova, between January 2018 and June 2022, all of whom had undergone surgical interventions for adenocarcinoma of the rectum. Among this cohort, 106 patients who had undergone scheduled low and ultralow anterior rectal resections with total mesorectal excision were selected for further analysis. Twenty-four patients were diagnosed with postoperative AL and underwent diverse management strategies based on the severity of their condition. Results: The study revealed an incidence of 22.6% for postoperative AL, with all of them being classified as grade B and C, according to the 2010 International Study Group of Rectal Cancer Classification, which were associated with significant morbidity and mortality. Notably, patients exhibited various comorbidities, including obesity, arterial hypertension, type 2 diabetes mellitus, and kidney failure. The management approach depended on the severity of the clinical presentation and the availability of treatment options. Early diagnosis and conservative management constituted the initial therapeutic strategy for grade B AL, with surgical reintervention or transanal vacuum therapy being used in grade C AL. Conclusions: The incidence and mortality associated with AF following low anterior resections were notably elevated. Grade B AL were successfully managed through conservative treatment, whereas grade C AL required either surgical reintervention for drainage or diversion procedures, or transanal vacuum therapy.

High Prevalence of Autonomous Aldosterone Production in Hypertension: How to Identify and Treat It.

PURPOSE OF REVIEW: Primary aldosteronism (PA) affects millions of individuals worldwide. When unrecognized, PA leads to cardiovascular and renal complications via mechanisms independent from those mediated by hypertension. In this review, we emphasize the importance of PA screening in at-risk populations, and we provide options for customized PA therapy, with consideration for a variety of clinical care settings. RECENT FINDINGS: Compelling evidence puts PA at the forefront of secondary hypertension etiologies. Cardiovascular and renal damage likely begins in early stages of renin-independent aldosterone excess. PA must be considered not only in patients with resistant hypertension or hypokalemia, but also when hypertension is associated with obstructive sleep apnea or atrial fibrillation, or in those with early-onset hypertension. Screening with plasma aldosterone and renin is widely accessible, and targeted PA therapy can successfully circumvent the excess cardiorenal risk relative to equivalent primary hypertension. Identifying and treating PA in early stages provide opportunities for personalized hypertension therapy in a large number of patients. Additionally, early targeted therapy of PA is essential for pivoting the care of such patients from reactive to preventive of cardiovascular and renal morbidity and mortality.

Development of Human Adrenocortical Adenoma (HAA1) Cell Line from Zona Reticularis.

The human adrenal cortex is composed of distinct zones that are the main source of steroid hormone production. The mechanism of adrenocortical cell differentiation into several functionally organized populations with distinctive identities remains poorly understood. Human adrenal disease has been difficult to study, in part due to the absence of cultured cell lines that faithfully represent adrenal cell precursors in the early stages of transformation. Here, Human Adrenocortical Adenoma (HAA1) cell line derived from a patient's macronodular adrenocortical hyperplasia and was treated with histone deacetylase inhibitors (HDACis) and gene expression was examined. We describe a patient-derived HAA1 cell line derived from the zona reticularis, the innermost zone of the adrenal cortex. The HAA1 cell line is unique in its ability to exit a latent state and respond with steroidogenic gene expression upon treatment with histone deacetylase inhibitors. The gene expression pattern of differentiated HAA1 cells partially recreates the roster of genes in the adrenal layer that they have been derived from. Gene ontology analysis of whole genome RNA-seq corroborated increased expression of steroidogenic genes upon HDAC inhibition. Surprisingly, HDACi treatment induced broad activation of the Tumor Necrosis Factor (TNF) alpha pathway. This novel cell line we developed will hopefully be instrumental in understanding the molecular and biochemical mechanisms controlling adrenocortical differentiation and steroidogenesis.

Primary Aldosteronism: a Continuum from Normotension to Hypertension.

PURPOSE OF REVIEW: Primary aldosteronism (PA) is the most common cause of secondary hypertension. Emerging evidence suggests that PA is associated with cardiovascular, metabolic, and renal complications, that likely develop insidiously, due to prolonged inappropriate mineralocorticoid receptor activation. In this review, we discuss the expanding clinical and pathological spectrum of PA. RECENT FINDINGS: Clinical and molecular studies conducted over the recent years reveal that PA traverses a series of contiguous stages. Pre-clinical, but hormonally overt PA has been identified in patients with normal blood pressure, and such patients harbor an increased risk of developing hypertension. Similarly, genetic and histopathological advancements have exposed a spectrum of PA pathology that corresponds to a continuum that spans from pre-clinical stages to florid PA. PA evolves from pre-hypertensive stages to resistant hypertension, along with serious cardiovascular and renal consequences. Early recognition of PA and targeted therapy will be essential for cardiovascular morbidity and mortality prevention in a large number of patients.

Developments in Primary Aldosteronism Subtyping Using Steroid Profiling.

Adrenal venous sampling is the standard of care for identifying patients with unilateral primary aldosteronism, which is often caused by an aldosterone producing adenoma and can be cured with surgery. The numerous limitations of adrenal venous sampling, including its high cost, scarce availability, technical challenges, and lack of standardized protocols, have driven efforts to develop alternative, non-invasive tools for the diagnosis of aldosterone producing adenomas. Seminal discoveries regarding the pathogenesis of aldosterone producing adenomas made over the past decade have leveraged hypotheses-driven research of steroid phenotypes characteristic of various aldosterone producing adenomas. In parallel, the expanding availability of mass spectrometry has enabled the simultaneous quantitation of many steroids in single assays from small volume biosamples. Steroid profiling has contributed to our evolving understanding about the pathophysiology of primary aldosteronism and its subtypes. Herein, we review the current state of knowledge regarding the application of multi-steroid panels in assisting with primary aldosteronism subtyping.

Mineralocorticoid Receptor Antagonists Decrease the Rates of Positive Screening for Primary Aldosteronism.

OBJECTIVE: Mineralocorticoid receptor antagonists (MRAs) are effective in patients with resistant hypertension and/or primary aldosteronism (PA). Screening for PA should ideally be conducted after stopping medications that might interfere with the renin-angiotensin-aldosterone system, but this is challenging in patients with recalcitrant hypertension or hypokalemia. Herein, we aimed to evaluate the impact of MRAs on PA screening in clinical practice. METHODS: We conducted a retrospective cohort study of patients with hypertension who had plasma aldosterone and renin measurements before and after MRA use in a tertiary referral center, over 19 years. RESULTS: A total of 146 patients, 91 with PA, were included and followed for up to 18 months. Overall, both plasma renin and aldosterone increased after MRA initiation (from median, interquartile range: 0.5 [0.1, 0.8] to 1.2 [0.6, 4.8] ng/mL/hour and from 19.1 [12.9, 27.7] to 26.4 [17.1, 42.3] ng/dL, respectively; P<.0001 for both), while the aldosterone/renin ratio (ARR) decreased from 40.3 (18.5, 102.7) to 23.1 (8.6, 58.7) ng/dL per ng/mL/hour (P<.0001). Similar changes occurred irrespective of the MRA treatment duration and other antihypertensives used. Positive PA screening abrogation after MRA initiation was found in 45/94 (48%) patients. Conversely, 17% of patients had positive PA screening only after MRA treatment, mostly due to correction of hypokalemia. An initially positive screening test was more likely altered by high MRA doses and more likely persistent in patients with confirmed PA or taking beta-blockers. CONCLUSION: MRAs commonly reduce ARR and the proportion of positive PA screening results. When PA is suspected, screening should be repeated off MRAs. ABBREVIATIONS: ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; ARR = aldosterone/renin ratio; DRC = direct renin concentration; MRA = mineralocorticoid receptor antagonist; PA = primary aldosteronism; PAC = plasma aldosterone concentration; PRA = plasma renin activity; RAAS = renin-angiotensin-aldosterone system.

Primary Aldosteronism: Practical Approach to Diagnosis and Management.

Primary aldosteronism (PA) is the most common form of secondary hypertension. In many cases, somatic mutations in ion channels and pumps within adrenal cells initiate the pathogenesis of PA, and this mechanism might explain why PA is so common and suggests that milder and evolving forms of PA must exist. Compared with primary hypertension, PA causes more end-organ damage and is associated with excess cardiovascular morbidity, including heart failure, stroke, nonfatal myocardial infarction, and atrial fibrillation. Screening is simple and readily available, and targeted therapy improves blood pressure control and mitigates cardiovascular morbidity. Despite these imperatives, screening rates for PA are low, and mineralocorticoid-receptor antagonists are underused for hypertension treatment. After the evidence for the prevalence of PA and its associated cardiovascular morbidity is summarized, a practical approach to PA screening, referral, and management is described. All physicians who treat hypertension should routinely screen appropriate patients for PA.

The Clinical Impact of [68 Ga]-DOTATATE PET/CT for the Diagnosis and Management of Ectopic Adrenocorticotropic Hormone - Secreting Tumours.

OBJECTIVES: Localization of ectopic ACTH-secreting tumours causing Cushing syndrome (ECS) is essential for clinical management, yet often difficult. [68 Ga]-DOTATATE PET/CT ([68 Ga]-DOTA-(Tyr3 )-octreotate)] is an FDA-approved high-resolution diagnostic tool for imaging neuroendocrine tumours. Data on the clinical utility of [68 Ga]-DOTATATE in patients with ECS, however, are scarce. The objectives of this study were to determine the efficacy for ECS localization and the clinical benefit of [68 Ga]-DOTATATE imaging. METHOD: We conducted a retrospective review of all cases with ECS evaluated with [68 Ga]-DOTATATE from November 2016 through October 2018 at three referral centres. The clinical benefit of [68 Ga]-DOTATATE was based on detection of new tumours and resultant changes in management. RESULTS: Over the study period, 28 patients with ECS underwent [68 Ga]-DOTATATE: 17 for identification of the primary tumour and 11 during follow-up. [68 Ga]-DOTATATE identified the suspected primary ECS in 11/17 patients (65%). Of these, nine patients underwent surgery: eight with confirmed ECS (5 bronchial, 1 thymic, 1 pancreatic and 1 metastatic neuroendocrine tumour of unknown primary origin) and one patient with a false-positive scan (adrenal gland). Of the 11 patients with ECS who underwent [68 Ga]-DOTATATE evaluation during follow-up, the study led to changes in clinical management in 7/11 (64%) patients. CONCLUSIONS: [68 Ga]-DOTATATE is sensitive in detecting primary and metastatic ECS, often identifies occult tumours after conventional imaging, and impacts clinical care in the majority of patients.

Mifepristone in the treatment of the ectopic adrenocorticotropic hormone syndrome.

OBJECTIVES: Mifepristone, a glucocorticoid receptor antagonist, can be used to manage hypercortisolism in patients with ectopic adrenocorticotropic hormone syndrome (EAS) when surgical cure is not feasible. Outcomes of EAS patients treated with mifepristone have been limited to reports of isolated cases. We aimed to determine the efficacy and limitations of mifepristone in the treatment of EAS and to compare outcomes with those of patients who underwent bilateral adrenalectomy. METHOD: A retrospective cohort study of EAS patients from the University of Michigan between 1997 and 2017 was conducted. RESULTS: Of the 55 patients with EAS, 16 were treated with mifepristone: eight neuroendocrine tumours, two carcinomas and six occult tumours. Treatment with mifepristone was most commonly prompted by psychosis, uncontrolled glucose and/or hypertension. The median maintenance dose was 600 mg/d. Amelioration of psychosis was observed within 48 hours in 3/3 patients, and the glycaemic control was improved in 14/16 patients. The median duration of treatment was 9 months, and three patients were treated for more than 24 months. The overall survival at 24 months was equivalent between patients with EAS treated with mifepristone vs bilateral adrenalectomy (N = 12) (P = 0.6). CONCLUSIONS: Mifepristone is effective in treating EAS for over 2 years, and survival was not different from that of patients treated with bilateral adrenalectomy. Aggressive concomitant therapy for hypokalaemia and hypertension is necessary.

Discordance between imaging and immunohistochemistry in unilateral primary aldosteronism.

OBJECTIVE: Correct subtyping of primary aldosteronism (PA) is essential for good surgical outcomes. Adrenal vein sampling (AVS) and/or computed tomography (CT) are used for PA subclassification. Clinical and/or biochemical improvement after surgery, however, is not always achieved in patients with presumed unilateral PA. We aimed to identify the pitfalls in PA subclassification leading to surgical treatment failures. PATIENTS AND DESIGN: We retrospectively studied 208 patients who underwent adrenal vein sampling (AVS) for PA subclassification in a tertiary referral centre, between January 2009 and August 2016. Simultaneous bilateral AVS was performed before and after cosyntropin administration. We implemented immunohistochemistry for aldosterone synthase (CYP11B2) and 17α-hydroxylase/17,20 lyase (CYP17A1) in adrenal glands resected from patients without improvement of PA after surgical treatment and from those with limitations in AVS interpretation. RESULTS: Of 55 patients who underwent adrenalectomy, three (5.5%) had no improvement of PA. All three patients underwent partial adrenalectomy to remove a CT-detected nodule present on the same side with AVS lateralization. Immunohistochemistry revealed a CYP11B2-negative nodule in both cases available. All patients who underwent total adrenalectomy based on AVS lateralization benefitted from surgery, including three patients with unilateral unsuccessful AVS and aldosterone suppression in the catheterized side vs inferior vena cava. CONCLUSIONS: Radiographically identified adrenal nodules are not always a source of PA, even when ipsilateral with AVS lateralization. These data caution against reliance on imaging findings, either alone or in conjunction with AVS, to guide surgery for PA.

GLUCOCORTICOID REPLACEMENT REGIMENS IN CHRONIC ADRENAL INSUFFICIENCY: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVE: Various glucocorticoid (GC) regimens have been used in the treatment of patients with adrenal insufficiency, yet the differences between such regimens on health outcomes are unclear. We performed a systematic review and meta-analysis to compare the effects of GC regimens on quality of life (QoL), bone density, incidence of adrenal crisis, and death. In pediatric studies, we also searched for final adult height. METHODS: We searched 6 databases through July 2016. Studies were selected and appraised by independent reviewers. Data were pooled using the profile likelihood random-effects model. RESULTS: We included 34 studies. We found no difference in QoL scores between higher (≥30 mg/day of hydrocortisone [HC] equivalence) vs. lower daily doses (<30 mg/day of HC equivalence) (P = .15) or based on frequency of daily dosing (once, twice or thrice daily). Extended-release (1 study), dual-/modified-release (3 studies), and continuous subcutaneous (3 studies) forms of GCs were associated with higher QoL scores. There was no significant association between dose and type of GC and the incidence of adrenal crises. The effect on bone mineral density was heterogeneous. No data were available on mortality or final adult height in children. The quality of evidence was low due to increased risk of bias, imprecision, and heterogeneity. CONCLUSION: Extended-/dual-release, and continuous subcutaneous forms of GC may be associated with higher QoL scores. However, this is derived from short-term and imprecise evidence, warranting low confidence. ABBREVIATIONS: AI = adrenal insufficiency BMD = bone mineral density GC = glucocorticoids HC = hydrocortisone QoL = quality of life RCT = randomized controlled trial.

Cytochrome b5 Activates the 17,20-Lyase Activity of Human Cytochrome P450 17A1 by Increasing the Coupling of NADPH Consumption to Androgen Production.

Human cytochrome P450 17A1 is required for all androgen biosynthesis and is the target of abiraterone, a drug used widely to treat advanced prostate cancer. P450 17A1 catalyzes both 17-hydroxylation and subsequent 17,20-lyase reactions with pregnenolone, progesterone, and allopregnanolone. The presence of cytochrome b5 (b5) markedly stimulates the 17,20-lyase reaction, with little effect on 17-hydroxylation; however, the mechanism of this b5 effect is not known. We determined the influence of b5 on coupling efficiency-defined as the ratio of product formation to NADPH consumption-in a reconstituted system using these 3 pairs of substrates for the 2 reactions. Rates of NADPH consumption ranged from 4 to 13 nmol/min/nmol P450 with wild-type P450 17A1. For the 17-hydroxylase reaction, progesterone oxidation was the most tightly coupled (∼50%) and negligibly changed upon addition of b5. Rates of NADPH consumption were similar for the 17-hydroxylase and corresponding 17,20-lyase reactions for each steroid series, and b5 only slightly increased NADPH consumption. For the 17,20-lyase reactions, b5 markedly increased product formation and coupling in parallel with all substrates, from 6% to 44% with the major substrate 17-hydroxypregnenolone. For the naturally occurring P450 17A1 mutations E305G and R347H, which impair 17,20-lyase activity, b5 failed to rescue the poor coupling with 17-hydroxypregnenolone (2-4%). When the conserved active-site threonine was mutated to alanine (T306A), both the activity and coupling were markedly decreased with all substrates. We conclude that b5 stimulation of the 17,20-lyase reaction primarily derives from more efficient use of NADPH for product formation rather than side products.

LINGUAL THYROID: 35-YEAR EXPERIENCE AT A TERTIARY CARE REFERRAL CENTER.

OBJECTIVE: Lingual thyroid (LT) results from a developmental abnormality due to failure of the thyroid gland to descend to its pretracheal position. Given the low incidence of this disease, standardized management recommendations are lacking. We aimed to describe our institution's experience in LT management and to suggest a practice algorithm. METHODS: We conducted a retrospective review of LT diagnosed at Mayo Clinic, Rochester, Minnesota, between 1976 and 2010. Demographics, clinical presentation, laboratory data, treatment received, and outcomes were collected. RESULTS: We identified 29 patients with LT. Eighty-three percent were female; age at diagnosis ranged from 2 weeks to 68 years. Almost one-third of patients were symptomatic, with the most common symptoms being cough and hoarseness. The diagnosis of LT was incidental in 9 patients (31%). Seventy-two percent of patients developed hypothyroidism. Levothyroxine was the treatment of choice, followed by thyroidectomy. Two asymptomatic euthyroid patients were followed without any intervention. CONCLUSION: Management of patients with LT should be individualized and guided by the patient's symptoms and thyroid hormone status.

Biomarkers to Guide Medical Therapy in Primary Aldosteronism.

Primary aldosteronism (PA) is an endocrinopathy characterized by dysregulated aldosterone production that occurs despite suppression of renin and angiotensin II, and that is non-suppressible by volume and sodium loading. The effectiveness of surgical adrenalectomy for patients with lateralizing PA is characterized by the attenuation of excess aldosterone production leading to blood pressure reduction, correction of hypokalemia, and increases in renin-biomarkers that collectively indicate a reversal of PA pathophysiology and restoration of normal physiology. Even though the vast majority of patients with PA will ultimately be treated medically rather than surgically, there is a lack of guidance on how to optimize medical therapy and on key metrics of success. Herein, we review the evidence justifying approaches to medical management of PA and biomarkers that reflect endocrine principles of restoring normal physiology. We review the current arsenal of medical therapies, including dietary sodium restriction, steroidal and nonsteroidal mineralocorticoid receptor antagonists, epithelial sodium channel inhibitors, and aldosterone synthase inhibitors. It is crucial that clinicians recognize that multimodal medical treatment for PA can be highly effective at reducing the risk for adverse cardiovascular and kidney outcomes when titrated with intention. The key biomarkers reflective of optimized medical therapy are unsurprisingly similar to the physiologic expectations following surgical adrenalectomy: control of blood pressure with the fewest number of antihypertensive agents, normalization of serum potassium without supplementation, and a rise in renin. Pragmatic approaches to achieve these objectives while mitigating adverse effects are reviewed.

Evaluation of a Best-Practice Advisory for Primary Aldosteronism Screening.

Importance: Primary aldosteronism (PA) is a common cause of secondary hypertension and an independent risk factor for cardiovascular morbidity and mortality. Fewer than 2% to 4% of patients at risk are evaluated for PA. Objective: To develop and evaluate an electronic health record best-practice advisory (BPA) that assists with PA screening. Design, Setting, and Participants: This prospective quality improvement study was conducted at academic center outpatient clinics. Data analysis was performed between February and June 2023 and included adults with hypertension and at least 1 of the following: 4 or more current antihypertensive medications; hypokalemia; age younger than 35 years; or adrenal nodule(s). Patients previously tested for PA were excluded. Exposure: A noninterruptive BPA was developed to trigger for PA screening candidates seen in outpatient setting by clinicians who treat hypertension. The BPA included an order set for PA screening and a link to results interpretation guidance. Main Outcomes and Measures: (1) The number of PA screening candidates identified by the BPA between October 1, 2021, and December 31, 2022; (2) the rates of PA screening; and (3) the BPA use patterns, stratified by physician specialty were assessed. Results: Over 15 months, the BPA identified 14 603 unique candidates (mean [SD] age, 65.5 [16.9] years; 7300 women [49.9%]; 371 [2.5%] Asian, 2383 [16.3%] Black, and 11 225 [76.9%] White individuals) for PA screening, including 7028 (48.1%) with treatment-resistant hypertension, 6351 (43.5%) with hypokalemia, 1537 (10.5%) younger than 35 years, and 445 (3.1%) with adrenal nodule(s). In total, 2040 patients (14.0%) received orders for PA screening. Of these, 1439 patients (70.5%) completed the recommended screening within the system, and 250 (17.4%) had positive screening results. Most screening orders were placed by internists (40.0%) and family medicine physicians (28.1%). Family practitioners (80.3%) and internists (68.9%) placed most orders via the embedded order set, while specialists placed most orders (83.0%-95.4%) outside the BPA. Patients who received screening were younger and included more women and Black patients than those not screened. The likelihood of screening was higher among patients with obesity and dyslipidemia and lower in those with chronic kidney disease and established cardiovascular complications. Conclusions and Relevance: The study results suggest that noninterruptive BPAs are potentially promising PA screening-assistance tools, particularly among primary care physicians. Combined with artificial intelligence algorithms that optimize the detection yield, refined BPAs may contribute to personalized hypertension care.

Abiraterone in Classic Congenital Adrenal Hyperplasia: Results of Medical Therapy Before Adrenalectomy.

We present the case of a 20-year-old woman with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, with uncontrolled hyperandrogenemia despite supraphysiological glucocorticoid therapy. We used abiraterone acetate, an inhibitor of the 17-hydroxylase/17,20-lyase enzyme, to suppress adrenal androgen synthesis and allow physiological glucocorticoid and mineralocorticoid therapy, as a proof-of-concept, before proceeding to bilateral adrenalectomy. We report the patient's clinical course, the changes in adrenal steroids, and the immunohistochemistry of the adrenals.