Cause Of Endocrine Hypertension Research Articles

Exploring the Spectrum of Comorbidities Associated with Primary Aldosteronism: Insights from a Large Real-World Case-Control Study

Background: Primary aldosteronism (PA) is a common cause of endocrine hypertension, characterized by excessive aldosterone secretion leading to hypertension, hypokalemia, and metabolic alkalosis. While historically diagnosed based on this classic triad of symptoms, current understanding reveals a more nuanced presentation. This study aimed to investigate the prevalence of PA-associated diseases in a large German population. Methods: Medical records from the IQVIATM Disease Analyzer database were analyzed retrospectively. PA patients (n = 860) were matched with non-PA individuals (n = 4300) by age and sex. Associations between PA and predefined chronic diseases were examined using multivariable logistic regression. Results: PA was significantly associated with hypokalemia (7.8% vs. 1.6%, odds ratio (OR): 3.45; 95% confidence intervals (CIs): 2.41–4.96), hypertension (56.1% vs. 28.5%; OR: 2.37; 95% CIs: 2.00–2.81), hepatic steatosis (11.3% vs. 3.0%; OR: 1.85; 95% CIs: 1.34–2.57), gout (8.3% vs. 2.2%; OR: 1.64; 95% CIs: 1.15–2.35), chronic kidney disease (6.3% vs. 2.2%; OR: 1.59; 95% CIs: 1.10–2.31), diabetes mellitus not otherwise specified (7.9% vs. 2.9%; OR: 1.49; 95% CIs: 1.06–2.09), obesity (13.5% vs. 5.1%; OR: 1.38; 95% CIs: 1.05–1.82), and depression (14.8% vs. 6.2%; OR: 1.37; 95% CIs: 1.07–1.77). Conclusions: While the study design had limitations, including reliance on ICD codes for diagnosis, these findings underscore the critical need for early detection and personalized management strategies for PA to reduce associated risks and improve patient outcomes.

8399 Adherens Junctions Regulate Aldosterone Production and Zona Glomerulosa Morphogenesis

Abstract Disclosure: M. Berber: None. N.A. Guagliardo: None. P.Q. Barrett: None. B. Haykir: None. V. Chortis: None. K.S. Borges: None. D.L. Carlone: None. D.T. Breault: None. Primary aldosteronism (PA) caused by the autonomous production of aldosterone by zona Glomerulosa (zG) cells of the adrenal gland is the most common cause of endocrine hypertension, which increases the risk of cardiovascular and renal disease, independent of blood pressure. Current treatments with mineralocorticoid receptor antagonists do not fully mitigate these risks. Thus, a better understanding of the mechanisms underlying PA pathogenesis is important for the development of new therapeutic strategies. zG cells are organized in multicellular rosette structures, which are the functional aldosterone-producing units. Rosettes are stabilized by intercellular adherens junctions (AJs) comprised of cadherins, beta-catenin (βCat) and alpha-catenin (αCat), which link to the actin non-muscle myosin II (NMII) network. Recent data implicate AJs and rosettes in aldosterone-producing cell clusters and an unbiased proteomic analysis of aldosterone-producing adenomas detected an upregulation of the GTPase RhoC, an important regulator of AJ stability.We hypothesized that AJs are potent modulators of aldosterone production and zG morphogenesis with important implications for PA. Using the NCI-H295R cell line with confocal microscopic and co-immunoprecipitation assays, we found that potassium (K+) and angiotensin II (AngII) stimulation markedly enhanced the formation and maintenance of AJs. In addition, treatment with inhibitors of Rho-associated kinase (ROCK) (Y-27632) and NMII (blebbistatin) largely abrogated the effects of K+ and AngII stimulation on AJs, suggesting the Rho-ROCK-NMII pathway regulates AJ stability in the zG. Moreover, disruption of AJs, using either blebbistatin or deletion of αCat using CRISPR, blunted the aldosterone response to K+ stimulation (100% and 50%, respectively). Furthermore, zG-specific deletion of αCat (αCat-LOF) in mice led to disruption of AJs, impaired rosette formation and decreased 24-hour urinary aldosterone excretion on standard (Control 5.6±1.7 ng/mg; αCat-LOF 2.9±0.7 ng/mg (aldosterone/creatinine)) or high K+ (Control: 34.7±13.7 ng/mg; αCat-LOF 19.4±9.5 ng/mg (aldosterone/creatinine)) diets. Finally, mice with zG-specific βcat-GOF demonstrated enhanced AJ stability, increased rosette size and zG hyperplasia, which was abrogated in zG-specific bigenic βCat-GOF::αCat-LOF mice, without affecting gene expression of canonical βcat targets. These data indicate that AJs modulate aldosterone production and zG morphology, revealing AJs as a novel molecular target for the treatment of high-risk patients with PA. Presentation: 6/3/2024

Exploration of the shared gene signatures and comorbidity mechanisms of primary aldosteronism and atrial fibrillation.

Primary aldosteronism (PA) is a prevalent cause of endocrine hypertension characterized by an excess of aldosterone that can induce proinflammatory, prooxidant, and profibrotic effects on the heart. Emerging evidence indicates a heightened incidence of atrial fibrillation (AF) in patients with PA, suggesting a significant association between the two conditions. However, the underlying mechanisms remain unclear. The purpose of this study was to investigate the molecular networks associated with the development of both PA and AF. Datasets were obtained from the Gene Expression Omnibus (GEO) database. Hub genes were identified by enrichment and protein‒protein interaction analysis. These hub genes were subsequently validated via two independent external datasets: GSE60042 and GSE41177. Following the identification of shared genes, quantitative real-time polymerase chain reaction (qPCR) was employed to verify the reliability of the dataset and to further confirm the presence of shared genes in clinical samples. The results of the common gene analysis revealed that immune and inflammatory responses may be shared features in the pathophysiology of PA and AF. One hub gene, specifically tumor necrosis factor superfamily member 10 (TNFSF10), was identified through various analyses and subsequently validated via qPCR. Compared with that in healthy controls, the expression level of TNFSF10 was lower in PA patients with AF. Our findings indicate that TNFSF10 may play a role in the pathophysiology of AF complications associated with PA conditions, suggesting that it could serve as a potential target for the diagnosis or treatment of PA patients complicated with AF.

Aldosterone-Cortisol co-secretion in different adrenal tumors: A case series

Primary aldosteronism is the most common cause of endocrine hypertension. It commonly presents as refractory hypertension, carrying an elevated risk of cardiac and renal complications. Concurrent hypercortisolemia exacerbates the susceptibility to metabolic disorders, including obesity, dyslipidemia, abnormal blood glucose levels, and cardiovascular and renal diseases. Among the reported patients with co-secretion of aldosterone, the majority are aldosterone producing adenoma. Cases of bilateral adrenal hyperplasia secreting both aldosterone and cortisol are rarely reported. In this study, we conducted a comparative analysis of the clinical manifestations, laboratory tests, and imaging findings in two cases involving unilateral aldosterone-producing adenomas and bilateral macronodular adrenal hyperplasia respectively. Notably, our patients exhibited a cortisol circadian rhythm during the initial screening, complicating the diagnosis of Cushing's syndrome. The incorporation of early or routine low-dose dexamethasone suppression tests may prove beneficial in identifying co-secretory lesions promptly, assessing the risk of perioperative adrenal insufficiency, and guiding subsequent treatment and prognosis evaluation.

Captopril challenge test: an underutilized test in the diagnosis of primary aldosteronism.

Primary aldosteronism (PA) is the most common cause of endocrine hypertension and is often underdiagnosed. This condition is associated with increased cardiovascular morbidity and mortality in comparison to age and blood pressure matched individuals with essential hypertension (EH). The diagnostic pathway for PA consists of three phases: screening, confirmatory testing, and subtyping. The lack of specificity in the screening step, which relies on the aldosterone to renin ratio, necessitates confirmatory testing. The Endocrine Society's clinical practice guideline suggests four confirmatory tests, including the fludrocortisone suppression test (FST), saline suppression test (SST), captopril challenge test (CCT), and oral sodium loading test (SLT). There is no universally accepted choice of confirmatory test, with practices varying among centers. The SST and FST are commonly used, but they can be resource-intensive, carry risks such as volume overload or hypokalemia, and are contraindicated in severe/uncontrolled HTN as well as in cardiac and renal impairment. In contrast, CCT is a safe and inexpensive alternative that can be performed in an outpatient setting and can be applied when other tests are contraindicated. Despite its simplicity and convenience, the variability in captopril dose, testing posture, and diagnostic threshold limit its widespread use. This narrative review evaluates the diagnostic accuracy of the CCT across different populations, addresses controversies in its usage, and proposes recommendations for its use in the diagnosis of PA. Furthermore, suggestions for future research aimed at promoting the wider utilization of the CCT as a simpler, safer, and more cost-effective diagnostic test are discussed.

Endocrine causes of hypertension: literature review and practical approach.

Hypertension (HTN) affects more than 30% of adults worldwide. It is the most frequent modifiable cardiovascular (CV) risk factor, and is responsible for more than 10 million death every year. Among patients with HTN, we usually distinguish secondary HTN, that is HTN due to an identified cause, and primary HTN, in which no underlying cause has been found. It is estimated that secondary hypertension represents between 5 and 15% of hypertensive patients [1]. Therefore, routine screening of patients for secondary HTN would be too costly and is not recommended. In addition to the presence of signs suggesting a specific secondary cause, screening is based on specific criteria. Identifying secondary HTN can be beneficial for patients in certain situations, because it may lead to specific treatments, and allow better control of blood pressure and sometimes even a cure. Besides, it is now known that secondary HTN are more associated with morbidity and mortality than primary HTN. The main causes of secondary HTN are endocrine and renovascular (mainly due to renal arteries abnormalities). The most frequent endocrine cause is primary aldosteronism, which diagnosis can lead to specific therapies. Pheochromocytoma and Cushing syndrome also are important causes, and can have serious complications. Other causes are less frequent and can be suspected on specific situations. In this article, we will describe the endocrine causes of HTN and discuss their treatments.

FRI137 Histologic And Genetic Characteristics Of Primary Aldosteronism In Late Adulthood

Abstract Disclosure: A. Blinder: None. K. Nanba: None. D. Sapiro: None. J. Baker: None. C. Liu: None. I. Bancos: None. M. Lyden: None. W. Young: None. H. Wachtel: None. D. Cohen: None. J. Luther: None. T.A. Williams: None. M. Reincke: None. T. Else: None. T.J. Giordano: None. A. Udager: None. W.E. Rainey: None. Background: There is accumulating evidence that changes in adrenal histology and regulation of renin-angiotensin-aldosterone system occur with age. Primary aldosteronism (PA) is the most common cause of endocrine hypertension. Recent clinical studies suggest unique characteristics of PA in elderly patients, including high prevalence of comorbidities and low clinical cure rate after adrenalectomy. However, histologic and genetic features of PA in late adulthood have not been well elucidated. Objective: To determine histologic and genetic characteristics of PA in late adulthood. Methods: Seventy-six patients who underwent unilateral adrenalectomy at the age of 60 or older were included in this study. Formalin-fixed, paraffin-embedded (FFPE) sections of resected adrenal tissue were used for the analysis. Aldosterone synthase (CYP11B2) immunohistochemistry (IHC) was performed to identify the source of inappropriate aldosterone production. Histologic classification was made according to the HISTALDO (histopathology of primary aldosteronism) consensus. CYP11B2 IHC-guided DNA capture followed by sequencing analysis using direct Sanger sequencing or ion torrent based next-generation sequencing (NGS) was performed. Results: Median age of the studied patients was 70 (interquartile range: 64-73). Based on the CYP11B2 IHC, histologic diagnosis was made as follows; aldosterone-producing adenoma (APA, n=23), aldosterone-producing nodule (APN, n=41), and non-functioning adrenocortical adenoma (NFA, n=6). The remaining six cases had multiple CYP11B2-expressing neoplastic lesions, including APA with APN (n=2) and multiple APNs (n=4). Co-existence of NFA with APA or APN(s) was also observed in 13. Sequencing analysis revealed that somatic KCNJ5 mutation was the most frequent genetic alteration in APA (7/23, 30%), whereas somatic CACNA1D mutation was the most common genetic cause of APN (20/39 with successful sequencing, 51%). Of the 18 sequenced NFA DNA samples, two had somatic mutations in CTNNB1 (n=1) and GNAS (n=1). Conclusion: APN is the major histologic feature of PA in late adulthood. Co-existence of NFA also appears to be a frequent observation in this age population. Somatic CACNA1D and KCNJ5 mutations are common in APN and APA, respectively. Presentation: Friday, June 16, 2023

FRI122 Determinants Of Primary Aldosteronism Screening In The US: A Nationwide Physician Survey Study

Abstract Disclosure: A.F. Turcu: None. Z. Salman: None. S.M. Konzen: None. L. Zhang: None. H. Liu: None. L. Zhao: None. T. Suzer Gurtekin: None. M. Papaleontiou: None. Background: Primary aldosteronism (PA) is the most common cause of endocrine hypertension, affecting up to 25% of patients with treatment-resistant hypertension. PA contributes to cardiovascular and renal morbidity and mortality, via mechanisms additive to hypertension. Early detection and targeted therapy of PA mitigate the risk of such complications. Despite this, only a minute fraction of patients at risk are ever screened for PA. Objective: To ascertain triggers and barriers for PA screening across US practices. Methods: Physicians treating hypertension, including internists, family practitioners, cardiologists, nephrologists, and endocrinologists, were randomly selected from active members of the American Medical Association. Physicians were surveyed on their practice of PA screening. Multivariable logistic regression was performed to determine factors associated with PA screening. Results: Of 633 response-eligible physicians, 425 (67%) completed the survey, including 32.4% family practitioners, 26.9% internists, 13.2% cardiologists, 12.2% endocrinologists, and 11.8% Nephrologists. Of the respondents, 230 (55.2%) were men; 63% identified as White, 24% Asian, and 6% Black. Most participants reported that resistant hypertension (84.5%), and hypertension and spontaneous hypokalemia (81.4%) prompt them to screen for PA. Conversely, a minority reported diuretic-induced hypokalemia (26%), obstructive sleep apnea (10%), or atrial fibrillation (6.2%) as triggers for PA screening. Compared with internists, endocrinologists and nephrologists were more likely, and family practitioners were less likely to screen for PA in patients with hypertension and hypokalemia, early-onset hypertension, or adrenal nodules. Barriers to PA screening included clinic visit time constraints (37.4%), poor ancillary support (28.1%), testing logistic concerns (26.2%), ability to control hypertension with medications (20.5%), and belief that PA is rare (20.2%). Female physicians and family practitioners were more likely to report not being familiar with results’ interpretation and next steps, and not having time to keep abreast with expert guidelines; private practitioners were most likely to report reimbursement concerns. Conclusions: Heterogeneity in screening for PA exists among physicians at the frontline of hypertension care. Increasing awareness and developing tools to facilitate PA screening are crucial for the recognition and adequate care of millions of patients with hypertension. Presentation: Friday, June 16, 2023

Abstract 025: Role Of The C-C Motif Chemokine Ligand 5 (CCL5) And Its Receptor, C-C Motif Chemokine Receptor 5 (CCR5) In The Genesis Of Aldosterone-induced Hypertension, Vascular Dysfunction, And End-organ Damage

Background: Hyperaldosteronism (HA) is the most common cause of endocrine hypertension. CCL5 is a pro-inflammatory chemokine acting primarily via C-C Motif Chemokine Receptor 5 (CCR5). We hypothesize that HA leads to hypertension, vascular injury, and renal demage via CCL5/CCR5 and Nox1-dependent mechanisms. Methods: 10-12-weeks-old male wild type (CCR5+/+) and CCR5 receptor knockout (CCR5-/-) mice were infused with aldosterone for 14 days (600ug/Kg/day, osmotic mini-pump). Endothelial function was studied in aortae and blood pressure was analyzed by radiotelemetry. Mouse endothelial cells (MEC) were used to examine the molecular mechanisms. Results: HA increased circulating CCL5 levels [Vehicle: 7.41±1.6 vs. HA: 13.2±1.4 (pg/mL)] and reduced acetylcholine (ACH)-induced vasodilation (% relaxation) in CCR5+/+, which was abolished by inhibiting Nox1 (NOXA1ds, 10 μM) [Vehicle: 91.2±2.1 vs. HA: 42.7±3.9 vs. HA+NOXA1ds: 89.7±1.9]. To understand if CCL5 induces endothelial dysfunction via CCR5 and Nox1, aortae were incubated with CCL5 (100 ng/mL for 24 h) with vehicle or CCR5 antagonist (Maraviroc, 40 μM) or NOXA1ds and endothelial function and Nox1 expression were analyzed. CCL5 treatment induced endothelial dysfunction [ACH response, Vehicle: 90.1±1.9 vs. CCL5: 31.9±2.7] and increased Nox1 expression, which were blunted by Maraviroc or NOXA1ds, indicating that CCL5 affects endothelial function dependent on CCR5 and Nox1. We found that CCR5-/- mice are protected from HA-induced endothelial dysfunction, hypertension [mean arterial pressure (mmHg) - CCR5+/+: 154.8±3.7 vs. CCR5-/-: 104.5±2.9], and renal damage (analyzed by NGAL, Synaptopodin, and Colagen III gene expressions). On mechanistic levels, we found that CCL5 decreases nitric oxide production, leads to NF-κB activation, induces oxidative stress (elevated superoxide anion and H2O2) and ICAM and VCAM expressions in MEC, which were associated with higher macrophage adhesion, such effects were prevented by Maraviroc. Conclusion: These findings reveal a novel signaling pathway in HA-associated vascular and renal injuries and hypertension, CCL5 activates CCR5 stimulating NF-κB and Nox1 activities, and place CCR5 as a pharmacological target for cardiovascular outcomes in HA.

Endocrine Hypertension: Overview of Current Understanding

Hypertension is a leading cardiovascular risk factor with significant morbidity and mortality. Sometimes it remains difficult to find out the actual cause and to manage in a large segment of population. So, the ability to identify a contributing or secondary cause that is potentially curable for all patient with hypertension is of great importance and challenging. Endocrine hypertension is one of the common forms of secondary hypertension. Primary aldosteronism, pheochromocytoma, and other causes of mineralocorticoid excess are among the common causes of endocrine hypertension. Published literature were reviewed about their prevalence, clinical presentation, screening methods and specific management. Now day by day it’s become more challenging for the clinicians to understand the pathophysiology, clinical spectrum of these diseases and improvement of the management protocol because of newer clinical, biochemical, and modern radiological approach. Cardiovasc j 2023; 15(2): 159-174

PS-BPR03-11: A CASE OF MALIGNANT PHASE HYPERTENSION ASSOCIATED WITH PRIMARY ALDOSTERONISM

Background: Primary aldosteronism is associated with low plasma renin levels, while malignant phase hypertension is generally associated with raised renin activity. Therefore, these two conditions are at opposite ends of the renin spectrum, so in theory their co-existence would be unusual. Case presentation: We present a case of a 41-year-old male with uncontrolled hypertension on multiple antihypertensive drugs. He discontinued these drugs for three days, thereafter he admitted to our hospital with congestive heart failure and acute ischemic stroke. He manifested malignant phase hypertension (blood pressure 216/130 mmHg; Keith-Wagener IV) accompanying renal dysfunction (serum creatinine 2.4 mg/dL), high plasma aldosterone concentration (PAC, 221 pg/mL) and mildly elevated plasma renin activity (PRA, 3.0 ng/mL/hr). A computed tomography did not reveal the presence of adrenal mass. After the treatment for congestive heart failure, the reassessment for endocrine causes of hypertension showed high level of PAC (468 pg/mL) and low level of PRA (0.2 ng/mL/hr), resulting in a high PAC/PRA ratio under the treatment with angiotensin-converting enzyme inhibitor. Adrenal venous sampling (AVS) confirmed the excessive aldosterone secretion from bilateral adrenal glands. Given these findings, we diagnosed him with idiopathic aldosteronism. After an addition of the mineralocorticoid receptor antagonist, he could keep his blood pressure under control. Conclusions: PRA in patients with primary aldosteronism could be increased under the conditions in which renin release from the kidney is overstimulated by glomerular ischemia, leading to an incorrect diagnosis of primary aldosteronism. Repeated endocrine assessment including the measurement of PRA and PAC should be considered to reveal the cause of malignant phase hypertension.

Biochemical Evaluation by Confirmatory Tests after Unilateral Adrenalectomy for Primary Aldosteronism.

Primary aldosteronism (PA) is the most common cause of endocrine hypertension. Unilateral PA can be cured using unilateral adrenalectomy (Adx). PA surgery outcome (PASO) criteria, which include clinical and biochemical outcomes, have been proposed to evaluate PA cure after Adx. However, clinical outcomes are often inconsistent with biochemical outcomes. In addition, although confirmatory tests are included as endpoints of biochemical outcomes in the PASO criteria, their clinical usefulness has not yet been established. We evaluated clinical parameters and confirmatory test results before and after Adx in 16 patients with PA and assessed the usefulness of the confirmatory tests. The following were the clinical outcomes after Adx: 37.5% complete success, 62.5% partial success, and 0% absent success. The ratio of biochemical complete success was as follows: 69% aldosterone/renin ratio and basal plasma aldosterone concentration, 19% as assessed by the captopril challenge test, 47% as assessed by the saline infusion test, 30% as assessed by the furosemide upright test, and 100% urine aldosterone. Of these, biochemical complete success was judged in four cases by aldosterone/renin ratio and basal plasma aldosterone concentration, one case by captopril challenge test, five cases by saline infusion test, and one case by furosemide upright test. Although clinical outcomes and urine aldosterone levels improved after Adx, confirmatory tests failed to improve in some cases. The current criteria are not considered useful for biochemical evaluation after Adx. To determine whether additional treatment with mineralocorticoid receptor antagonists is required, more accurate biochemical criteria should be established after Adx.

Endocrine Hypertension: The Urgent Need for Greater Global Awareness.

Hypertension affects about 1.28 billion adults globally, and significantly increases the risk of chronic morbidity and mortality among sufferers. About 15% of these individuals have secondary hypertension, the majority of whom have dysfunction of one or more endocrine systems as the cause of hypertension. Although adrenal disorders are often identified as the cause of endocrine hypertension, extra-adrenal disease and pituitary disorders also can cause the disease. Timely diagnosis is of paramount importance, because of the potential for a surgical cure or optimal disease control with pharmacotherapy to prevent hypertensive complications. Even with its relatively high prevalence compared with many other chronic illnesses, the diagnosis of endocrine hypertension is often delayed or never made because of poor awareness about the disease among physicians. This review attempts to provide an overview of the disease, with some practical aspects of diagnosis and management of a few of the important disorders causing endocrine hypertension.

A Case of Phaeochromocytoma with Normal Metanephrine but High Plasma Aldosterone

Pheochromocytoma is one of the causes of endocrine hypertension leading to stroke in young patients. The tumor secretes not only catecholamines but also other hormones in rare occasions. Besides, symptomatic tumors may come with normal catecholamine metabolite levels. Here is a case of a 28-year-old male featuring these exceptions who was managed at Dhaka Medical College Hospital.

LBSAT65 Search For A Duplicitous Pheochromocytoma

Abstract Introduction Pheochromocytomas are discovered during work up of adrenal incidentalomas and can be biochemically and clinically silent. We present a case of a patient who presented with typical "adrenergic spells" suggestive of pheochromocytoma but negative biochemical testing and non-confirmatory imaging findings. Case Report 39-year-old male presented with 4 weeks history of episodes of throbbing headaches, palpitations, sweating. He was found to be hypertensive, blood pressure of 220/110 mm Hg. Losartan was initiated, but symptoms persisted. Work-up for endocrine causes of hypertension revealed normal plasma renin activity 1.123 ng/ml/hr (0.167 to 5.380) and undetectable aldosterone level <1 ng/dl (0. 0-3. 0), mildly elevated random plasma normetanephrine 270 pg/ml (0-210), normal plasma metanephrines 49 pg/ml (0-88). Low-dose dexamethasone suppression test showed unsuppressed morning cortisol of 2.1ug/dl, undetectable ACTH <5 pg/ml, dexamethasone level 486 ng/dl. 24 urinary cortisol and 2 midnight salivary cortisol samples failed to confirm the diagnosis. 24-hr urine studies showed mildly elevated 24-hr normetanephrine 735 ug/24 hr (156-729), normal 24-hr metanephrines 197 ug/L (58-276), normal 24 hr epinephrine and dopamine levels. Repeat testing revealed normal plasma metanephrines levels and mildly elevated plasma normetanephrine levels 287 pg/ml (less than twice above the upper limit of normal). Dopamine and Chromogranin A levels were undetectable. Abdominal CT showed 2 cm round soft tissue density 42HU in right adrenal gland. Left adrenal gland contained 3 nodules measuring 11, 15 and 16 mm–all with density <10HU. MRI findings for the 2.2 cm right adrenal nodule was without significant drop in signal intensity on the in and out of phase sequences appearing moderately T2 hyperintense and T1 hypointense. Differential included atypical/fat poor adenoma, pheochromocytoma, or metastasis. On GA 68 Dotatate PET-CT this 2.2cm adrenal nodule had minimal to low radiotracer uptake. Since a pheochromocytoma could not be ruled out, patient was started on alpha blockade. Preoperative genetic testing was negative for common mutations associated with pheochromocytoma/paraganglioma syndromes. Patient underwent laparoscopic right adrenalectomy. Histopathology report confirmed 2.8 cm pheochromocytoma with a low PASS (2/20) and low GAPP score. Conclusion and Discussion Patients with borderline nor metanephrine elevations represent a diagnostic and therapeutic dilemma. The patient presented with adrenergic paroxysms strongly suggestive of underlying pheochromocytoma. Labs and imaging were not typical for pheochromocytoma and were indeterminate. Given strong clinical suspicion for a pheochromocytoma, we decided to proceed with adrenalectomy after pre-treatment with alpha blockers. Final histopathologic report confirmed the diagnosis of pheochromocytoma. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Impact of dedicated multidisciplinary service on patient selection and outcomes for surgical treatment of primary aldosteronism

BackgroundPrimary aldosteronism is the most common surgically curable cause of endocrine hypertension. Management of the unilateral subtype of primary aldosteronism with adrenalectomy requires multidisciplinary input. It is unclear if a dedicated endocrine hypertension service confers better outcomes compared to standard care offered by individual clinicians. MethodsIn this retrospective study, patients from the Monash University Endocrine Surgery Database were divided into either the endocrine hypertension service group, where patients were managed by a dedicated multidisciplinary team, or the standard group, where patients were managed by individual clinicians. The comparisons included patient selection for surgery, perioperative blood pressure control, and surgical cure rate. ResultsDespite similar perioperative blood pressure, patients in the endocrine hypertension service group (n = 41) were on fewer antihypertensive medications (1 vs 2, P = .011) compared to the standard group (n = 55). A larger proportion of patients in the endocrine hypertension service group had either bilateral adrenal nodules or no adrenal lesions on computed tomography (41% vs 18%, P = .013). Patients in the standard group had larger adrenal lesions on computed tomography (median 15 mm vs 10 mm, P = .032). Postoperatively, the biochemical cure rate was higher in the endocrine hypertension service group at 6 to 12 months (97% vs 76%, P = .021). ConclusionPatients managed by endocrine hypertension service were more likely to be diagnosed with surgically curable primary aldosteronism without a unilateral adrenal adenoma on imaging, required fewer medications for perioperative blood pressure control, and experienced superior postoperative outcomes. Referral to a dedicated endocrine hypertension service is recommended for patients with primary aldosteronism who wish to pursue a surgical cure.

High Prevalence of Primary Aldosteronism in Patients with Type 2 Diabetes Mellitus and Hypertension.

Primary aldosteronism (PA) is the most common cause of endocrine hypertension. The prevalence of hypertension is higher in patients with diabetes mellitus-2 (DM-2). Following the limited existing data, we prospectively investigated the prevalence of aldosterone excess either as autonomous secretion (PA) or as a hyper-response to stress in hypertensive patients with DM-2 (HDM-2). A total of 137 HDM-2 patients and 61 non-diabetics with essential hypertension who served as controls (EH-C) underwent a combined, overnight diagnostic test, the Dexamethasone–captopril–valsartan test (DCVT) used for the diagnosis of PA and an ultralow dose (0.3 μg) ACTH stimulation test to identify an exaggerated aldosterone response to ACTH stimulation. Twenty-three normotensive individuals served as controls (NC) to define the normal response of aldosterone (ALD) and aldosterone-to-renin ratio (ARR) to the ultralow dose ACTH test. Using post-DCVTALD and ARR from the EH-C, and post-ACTH peak ALD and ARR from the NC, 47 (34.3%) HDM-2 patients were found to have PA, whereas 6 (10.4%) HDM-2 patients without PA (DCVT-negative) exhibited an exaggerated aldosterone response to stress—a prevalence much higher than ever reported. Treatment with mineralocorticoid receptor antagonists (MRAs) induced a significant and permanent reduction of BP in all HDM-2 patients. Early diagnosis and targeted treatment of PA is crucial to prevent any aggravating effect on chronic diabetic complications.

11-deoxycorticosterone producing adrenal hyperplasia as a very unusual cause of endocrine hypertension: case report and systematic review of the literature

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Serum Metabolomic Patterns in Patients With Aldosterone-Producing Adenoma.

Aldosterone-producing adenoma (APA), the main cause of endocrine hypertension, has recently been reported to be associated with other diseases, such as metabolic syndrome, but the detailed mechanism underlying this association remains unclear. Here, we used untargeted metabolomics and compared the abundance of serum metabolites between essential hypertension (EHT) and APA patients, as well as the serum metabolites of APA patients before and after adrenalectomy. Our results revealed 44 differential metabolites between APA and EHT patients and 39 differential metabolites between pre- and postoperative APA patients. Several metabolites involved in cardiovascular disease, obesity, and diabetes were dysregulated in APA patients compared to EHT patients, including arachidonic acid metabolites [e.g., 5(S)-HpETE and 12-HETE], amino acids (e.g., L-carnitine, taurine, and L-arginine), nucleotide metabolites (e.g., hypoxanthine) and cholesterol 3-sulfate. Importantly, the levels of hypoxanthine and cholesterol 3-sulfate, two metabolites that promote the development of atherosclerotic lesions and obesity, were originally increased in APA patients, but those elevated levels were reversed by adrenalectomy. Conversely, levels of L-carnitine and (3-carboxypropyl) trimethylammonium cation, two metabolites participating in lipid metabolism, were decreased in APA patients but increased postoperatively. We conclude that APA might participate in cardiovascular and metabolic diseases by regulating serum metabolites.

Prognostic value of contralateral suppression for remission after surgery in patients with primary aldosteronism.

Primary aldosteronism (PA) is the most common cause of endocrine hypertensionand adrenalectomy is the firstline treatment for unilateral PA. Suppression of aldosterone secretion of the nondominant adrenal gland at adrenal venous sampling (AVS), that is, contralateral suppression (CLS)has been suggested as a marker of disease severity. However, whether factors such as CLS, age, genderor comorbidities are associated with remission after surgery is controversial. The objective of this study is to investigate the prognostic value of CLS, age, gender, aldosterone-to-renin ratio, antihypertensives and comorbidities for clinical and biochemical remission following unilateral adrenalectomy in patients with PA. A retrospective study of patients with PA referred for AVS at Rigshospitalet from May 2011 to September 2020, who subsequently underwent adrenalectomy. Clinical remission was defined according to the PA surgical outcome criteria, whereascomplete biochemical remission was defined as normalization of hypokalaemia without potassium substitution. Eighty-four patients were available for analysis of primary outcome. Among patients with CLS, 28/58 (48.3%) obtained complete clinical remission after surgery compared with 10/26 (38.5%) without CLS (p = .40). Complete biochemical remission was obtained in 55/58 (94.8%) of patients with CLS compared with 25/28 (89.3%) without CLS (p = .44). Female gender and lower number of antihypertensives at baseline were associated with higher odds for complete clinical remission, whereasnone of the investigated variables were associated with biochemical remission. CLS was not significantly associated with complete clinical or biochemical remission in this cohort. Our results confirmed that female gender and lower number of antihypertensives were predictors of clinical remission.