The Subcutaneous Adipose Microenvironment as a Determinant of Body Fat Development in Polycystic Ovary Syndrome.

Context: Adipose steroid metabolism modifies body fat development in polycystic ovary syndrome (PCOS).

Objective: To determine whether subcutaneous (SC) abdominal adipose aldo-keto reductase 1C3 (AKR1C3; a marker of testosterone generation) is increased in normal-weight women with PCOS vs age- and body mass index (BMI)-matched normoandrogenic ovulatory women (controls) and is related to SC abdominal adipose activator protein-1 (AP-1; a marker of adipocyte differentiation) and/or androgen receptor (AR) protein expression in predicting fat accretion.

Design: Prospective cohort study.

Non-canonical Wnt signaling triggered by WNT2B drives adrenal aldosterone production.

The steroid hormone aldosterone, produced by the zona glomerulosa (zG) of the adrenal gland, is a master regulator of plasma electrolytes and blood pressure. While aldosterone control by the renin-angiotensin system is well understood, other key regulatory factors have remained elusive. Here, we replicated a prior association between a non-coding variant in and an increased risk of primary aldosteronism, a prevalent and debilitating disease caused by excessive aldosterone production.

Human Gonads Do Not Contribute to the Circulating Pool of 11-Oxygenated Androgens.

Context: Androstenedione (A4) and testosterone (T) are produced by both the adrenal glands and the gonads. The adrenal enzyme 11β-hydroxylase (CYP11B1) executes the final step in cortisol synthesis; CYP11B1 also uses A4 and T as substrates, generating 11-hydroxyandrostenedione and 11-hydroxytestosterone, respectively. It has been suggested that CYP11B1 is expressed in the gonads, yet the circulating levels of all 11-oxygenated androgens (11-oxyandrogens) are similar in males and females of reproductive ages, despite enormous differences in T.

An in Vitro triple screen model for human mineralocorticoid receptor activity.

The mineralocorticoid receptor (MR, NR3C2) mediates ion and water homeostasis in epithelial cells of the distal nephron and other tissues. Aldosterone, the prototypical mineralocorticoid, regulates electrolyte and fluid balance. Cortisol binds to MR with equal affinity to aldosterone, but many MR-expressing tissues inactivate cortisol to cortisone via 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2).

Control of Physiologic Glucose Homeostasis via the Hypothalamic Modulation of Gluconeogenic Substrate Availability.

The brain augments glucose production during fasting, but the mechanisms are poorly understood. Here, we show that -expressing neurons in the ventromedial hypothalamic nucleus (VMN cells) prevent low blood glucose during fasting through sympathetic nervous system (SNS)-mediated augmentation of adipose tissue lipolysis and substrate release. Activating VMN neurons mobilized gluconeogenic substrates without altering glycogenolysis or gluconeogenic enzyme expression.

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.

The Spectrum of Dysregulated Aldosterone Production: An International Human Physiology Study.

Context: Primary aldosteronism is a form of low-renin hypertension characterized by dysregulated aldosterone production.

Objective: To investigate the contributions of renin-independent aldosteronism and ACTH-mediated aldosteronism in individuals with a low-renin phenotype representing the entire continuum of blood pressure.

Design/participants: Human physiology study of 348 participants with a low-renin phenotype with severe and/or resistant hypertension, hypertension with hypokalemia, elevated blood pressure and stage I/II hypertension, and normal blood pressure.

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.

Multifocal, Asymmetric Bilateral Primary Aldosteronism Cannot be Excluded by Strong Adrenal Vein Sampling Lateralization: An International Retrospective Cohort Study.

Background: Primary aldosteronism (PA) has been broadly dichotomized into unilateral and bilateral forms. Adrenal vein sampling (AVS) lateralization indices (LI) ≥2 to 4 are the standard-of-care to recommend unilateral adrenalectomy for presumed unilateral PA. We aimed to assess the rates and characteristics of residual PA after AVS-guided adrenalectomy.

Somatic SLC30A1 mutations altering zinc transporter ZnT1 cause aldosterone-producing adenomas and primary aldosteronism.

Primary aldosteronism (PA) is the most common form of endocrine hypertension and is characterized by inappropriately elevated aldosterone production via a renin-independent mechanism. Driver somatic mutations for aldosterone excess have been found in approximately 90% of aldosterone-producing adenomas (APAs). Other causes of lateralized adrenal PA include aldosterone-producing nodules (APNs).

Long-term efficacy and safety of osilodrostat in patients with Cushing's disease: results from the LINC 4 study extension.

Objective: To evaluate the long-term efficacy and safety of osilodrostat in patients with Cushing's disease.

Methods: The multicenter, 48-week, Phase III LINC 4 clinical trial had an optional extension period that was initially intended to continue to week 96. Patients could continue in the extension until a managed-access program or alternative treatment became available locally, or until a protocol amendment was approved at their site that specified that patients should come for an end-of-treatment visit within 4 weeks or by week 96, whichever occurred first.

Primary Aldosteronism in Chronic Kidney Disease: Blood Pressure Control and Kidney and Cardiovascular Outcomes After Surgical Versus Medical Management.

Background: Diagnosis and treatment of primary aldosteronism (PA) in chronic kidney disease (CKD) may be deferred due to limited evidence supporting safety and efficacy of treatment. Our goal was to assess clinical outcomes in patients with PA and CKD who received surgical or medical management.

Methods: We conducted a multicenter, retrospective cohort study of patients with PA and CKD who underwent adrenal vein sampling from 2009-2019.

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.

Interplay of Cortisol, Testosterone, and Abdominal Fat Mass in Normal-weight Women With Polycystic Ovary Syndrome.

Context: Ovarian and adrenal steroidogenesis underlie endocrine-metabolic dysfunction in polycystic ovary syndrome (PCOS). Adipocytes express aldo-keto reductase 1C3 and type 1 11β-hydroxysteroid dehydrogenase, which modulate peripheral androgen and cortisol production.

Objectives: To compare serum adrenal steroids, including 11-oxygenated androgens (11-oxyandrogens), cortisol, and cortisone between normal-weight women with PCOS and body mass index- and age-matched ovulatory women with normal-androgenic profiles (controls), and assess whether adrenal steroids associate with abdominal adipose deposition.

Primary Aldosteronism Prevalence - An Unfolding Story.

Primary aldosteronism (PA) is characterized by dysregulated, renin-independent aldosterone excess. Long perceived as rare, PA has emerged as one of the most common causes of secondary hypertension. Failure to recognize and treat PA results in cardiovascular and renal complications, through processes mediated by both direct target tissue insults and indirectly, by hypertension.

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.

Rates of Pheochromocytoma/Paraganglioma Screening in At-Risk Populations.

Context: Pheochromocytomas and paragangliomas (PPGL) are rare causes of secondary hypertension, but when unrecognized, they can lead to serious complications. Data regarding PPGL screening are lacking.

Objective: This study aimed to assess the rates and patterns of PPGL screening among eligible patients.

11-Oxygenated Androgen Metabolite Concentrations Are Affected by Pubertal Progression and Obesity.

Introduction: 11-oxygenated C19 steroids (11-oxyandrogens) have been shown to rise during adrenarche and remain higher throughout adulthood than in early childhood. The patterns of circulating 11-oxyandrogens throughout normal puberty have not yet been described.

Methods: We conducted a secondary analysis of healthy youth participants, both males and females, enrolled in six prior endocrine studies (N = 249).

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.

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.

Primary aldosteronism - a multidimensional syndrome.

Primary aldosteronism is a common cause of hypertension and is a risk factor for cardiovascular and renal morbidity and mortality, via mechanisms mediated by both hypertension and direct insults to target organs. Despite its high prevalence and associated complications, primary aldosteronism remains largely under-recognized, with less than 2% of people in at-risk populations ever tested. Fundamental progress made over the past decade has transformed our understanding of the pathogenesis of primary aldosteronism and of its clinical phenotypes.