Resistant Hypertension Research Articles

Challenges in diagnosing and treating Liddle syndrome in resource-limited settings: A case report from Indonesia

Liddle syndrome, a rare form of monogenic hypertension, poses significant diagnostic and therapeutic challenges due to its phenotypic variability and the need for genetic testing. The rarity of the condition, coupled with the limited availability of first-line treatments such as epithelial sodium channel (ENaC) blockers, makes this case report particularly urgent and novel, highlighting alternative management strategies in resource-limited settings. The aim of this case report was to present the diagnostic challenges, therapeutic strategies, and clinical outcomes of a patient with Liddle syndrome who did not have access to ENaC blockers, emphasizing the importance of early recognition and personalized treatment. A 35-year-old female presented with resistant hypertension (190/100 mmHg) and bilateral limb weakness. Laboratory results revealed persistent hypokalemia, hypernatremia, and metabolic alkalosis. Low aldosterone levels, alongside clinical and family history, led to the diagnosis of Liddle syndrome. Genetic testing was not conducted due to resource limitations, and ENaC blockers were unavailable. The patients were managed with a combination of alternative antihypertensive agents, potassium supplementation, and a low-sodium diet. Although this approach led to modest improvements in blood pressure and motor strength, persistent hypokalemia and hypernatremia underscored the suboptimal control of the syndrome's underlying pathophysiology in the absence of ENaC blockers. This case highlights the challenges faced in resource-limited settings and the need for innovative strategies to manage rare conditions like Liddle syndrome. Liddle syndrome's diagnostic and therapeutic challenges underscore the critical importance of early recognition and access to targeted therapies. In the absence of ENaC blockers, alternative treatment strategies can provide some benefit, but they often fall short of optimal management. This case emphasizes the need for enhanced clinical awareness, improved access to genetic testing, and the development of personalized treatment approaches to achieve better patient outcomes.

A sham-controlled randomised pilot trial on baroreflex activation therapy in patients with resistant hypertension: What will the future hold?

A sham-controlled randomised pilot trial on baroreflex activation therapy in patients with resistant hypertension: What will the future hold?

Long-term safety and efficacy of endovascular ultrasound renal denervation in resistant hypertension: 8-year results from the ACHIEVE study.

Ultrasound renal sympathetic denervation (uRDN) reduces blood pressure (BP) in the absence and presence of antihypertensive treatment at 2months. Beyond 3years, there is a lack of follow-up data. This study investigated the long-term safety and efficacy of uRDN. This prospective observational study recruited patients previously included in the international multicenter ACHIEVE study, with office systolic blood pressure (SBP) ≥160 mmHg, 24h ambulatory SBP ≥130mmHg, ≥3 antihypertensive drugs and estimated Glomerular Filtration Rate (eGFR) ≥45 ml/min/1.73m2 undergoing uRDN. The primary efficacy outcome was 24h ambulatory SBP, adjusted for the number of defined daily dosages (DDD) of antihypertensive drugs. Statistical analyses were performed using linear mixed-effects models and inverse probability weighting. A total of 27 out of the initially enrolled 96 patients underwent prospective follow-up at a median of 8.2 [7.6-8.9]years. Mean age was 62.6±9.3years (37.0% female). Preprocedural 24h ambulatory BP was 151.9/84.1±11.5/11.1 mmHg and the median number of DDDs was 5.0 [4.3-7.0]. At 8years after uRDN, the change in 24h ambulatory SBP was -19.5 [95%CI -26.7,-12.4] mmHg (p<0.001). The 8-year change in the number of DDDs was -1.7 [-2.8,-0.6] (p = 0.003). The 8-year decline in eGFR was -8.9 [-13.2,-4.7] ml/min/1.73m2 (p<0.001). Clinical event data were available for all 96 patients (median follow-up 3.5 [1.0-8.0]years). Renal failure occurred in one patient and no cases of renal artery stenosis were detected. A significant BP reduction was observed up until 8years following uRDN in parallel to a decrease in drug burden over time, in the absence of procedure-related adverse events.

Sympathetic activity markers in patients with resistant hypertension with renal dysfunction

Aim. To study the informativeness of sympathetic activity markers and perirenal adipose tissue (PRAT) in assessing renal function decline in patients with resistant hypertension (RH).Material and methods. The study included 63 patients with RH of both sexes aged 40-80 years. The main group included 19 patients with chronic kidney disease (CKD). The control group consisted of 44 patients with RH without CKD. All patients were assessed for uric acid, blood lipid profile, beta-adrenergic reactivity of erythrocyte mem­branes, free metanephrine and normetanephrine in plasma and 24-hour urine. The renal function was assessed by the glomerular filtra­tion rate calculated using the CKD-EPI equation. Twenty-four hour blood pressure monitoring was performed on the brachial artery of one arm at intervals of 15 minutes during the day and 30 minutes at night. Kidney size and PRAT were calculated based on the magnetic reso­nance imaging.Results. In both groups of patients, a significant increase in blood normetanephrine and beta-adrenergic reactivity of erythrocyte mem­branes relative to the reference values was shown. Blood and 24-hour urine metanephrine were within the reference intervals. No differences were found between the sympathetic activity indices in the main and control groups. In the main group patients, the PRAT thickness was greater (p=0,013), and the kidney diameter was smaller (p=0,046) than in the control group patients.Conclusion. CKD in RH patients is not accompanied by additional significant changes in sympathetic regulation, assessed by the blood and 24-hour urine catecholamine levels, the degree of beta-adrenergic receptor desensitization and variability of blood pressure. PRAT increase according to magnetic resonance imaging in patients with RH is associated with a decrease in renal filtration function.

Primary and "Pre-Primary" Aldosteronism in Resistant Hypertension: A Practical, Pragmatic, and Prudent Approach in Resource-Limited Milieu.

Introduction Primary aldosteronism (PA), once considered rare, is now recognized as the most common cause of secondary hypertension, accounting for almost a quarter of resistant hypertension (RH) cases. Despite this, PA remains underdiagnosed, with an extremely low percentage of RH patients undergoing screening. Methods In a specialty diabetes-endocrinology clinic, the aldosterone:renin ratio (ARR) was assessed in 115 consecutive RH patients (ages 21-93 years; 47% male; 87% with type 2 diabetes). Fasting blood samples were drawn in a standing position after 30 minutes of walking. Adrenal imaging (CT/MRI) was performed for those with an ARR >20. Results ARR values ranged from 0.4 to 227 (ARR <10 (35%); 11-20 (19%), 21-40 (25%), and >40 (21%)), with corresponding stepwise decreasing plasma renin activity (PRA) (P= 1E-6) and increasing serum aldosterone (SA) (P= 8E-7). Increasing ARR tended to be associated with an increase in serum creatinine (R= 0.23; P= 0.03) and a decrease in estimated glomerular filtration rate (eGFR) (R= -0.24; P= 0.02) and an increase in urine albumin: creatinine ratio. The ARR> 40 group displayed the highest serum creatinine, lowest eGFR, higher urine albumin: creatinine ratio, highest serum sodium, lowest serum potassium, and highest (44%) abnormal adrenal imaging (bilateral hyperplasia diffuse/nodular; solitary adenoma), reflecting a later stage of the pathological spectrum. PA treatment with mineralocorticoid receptor antagonists (MRAs) had a salutary effect. Conclusions Our observations further reinforce that PA is not a binary condition, but exists as a spectrum disorder responsive to MRAs, even in patients with mildly elevated or normal aldosterone levels. Early disease detection/recognition ("renin-independent aldosterone production") can be facilitated by marking "pre-primary" aldosteronism (ARR 11-20), followed by monitoring progression (periodic rescreening) and optimizing treatment, with hopeful mitigation of end-organ damage in RH.

The Paradise Renal Denervation System: An FDA-approved catheter-based treatment option for resistant hypertension

Resistant hypertension is defined as office blood pressure &gt;140/90 mm Hg with a mean 24-hour ambulatory blood pressure of &gt;130/80 mm Hg in patients who are compliant with 3 or more antihypertensive medications. Those who persistently fail pharmaceutical therapy may benefit from interventional treatment, such as renal denervation. Sympathetic nervous activity in the kidney is a known contributor to increased blood pressure because it results in efferent and afferent arteriole vasoconstriction, reduced renal blood flow, increased sodium and water reabsorption, and the release of renin. The Recor Paradise Renal Denervation System is designed to target renal sympathetic nerves via ultrasound ablation. The RADIANCE trials have demonstrated that patients who underwent renal denervation had a significant decrease in systolic blood pressure as compared with those who underwent a sham procedure. Furthermore, the device was found to have a favorable safety profile, with minimal major adverse events. The Food and Drug Administration granted approval to Recor, and the Paradise system is expected to serve as an adjunctive therapy for patients with true-resistant hypertension.

Resistant Hypertension: A Brief Review of Pathophysiology.

A 52-year-old male comes to the internal medicine clinic for a follow-up for the management of hypertension. He was initially diagnosed with hypertension 5 years ago. His other past medical history includes obesity and hyperlipidemia. His current medications currently include losartan 100 mg daily, hydrochlorothiazide 25 mg, and amlodipine 10 mg. His physical exam is significant for an elevated in-office blood pressure of 160/105 mmHg, BMI 38, and neck circumference >40 cm. He also reports snoring at night and having significant daytime sleepiness despite getting over 8 hours of sleep each night. This patient meets the most recent diagnostic criteria per the American Heart Association for resistant hypertension. Resistant hypertension is an increasingly prevalent phenotype encountered in both primary care and subspecialty clinics. Multiple comorbidities, including obesity, sleep apnea, chronic kidney disease, heart failure, and diabetes mellitus, are associated with resistant hypertension. Our understanding of the potential etiologies for this condition continues to evolve rapidly. We used a narrative review to explore four research areas in the pathophysiology of resistant hypertension (the sympathetic nervous system, aldosterone excess, endothelial dysfunction, and inflammation) and explore the novel therapies currently in development.

Diagnostic and Therapeutic Approach to the Major Secondary Causes of Arterial Hypertension in Young Adults: A Narrative Review

Arterial hypertension in young adults, which includes patients between 19 and 40 years of age, has been increasing in recent years and is associated with a significantly higher risk of target organ damage and short-term mortality. It has been reported that up to 10% of these cases are due to a potentially reversible secondary cause, mainly of endocrine (primary aldosteronism, Cushing’s syndrome, and pheochromocytoma/paraganglioma), renal (renovascular hypertension due to fibromuscular dysplasia and renal parenchymal disease), or cardiac (coarctation of the aorta) origin. It is recommended to rule out a secondary cause of high blood pressure (BP) in those patients with early onset of grade 2 or 3 hypertension, acute worsening of previously controlled hypertension, resistant hypertension, hypertensive emergency, severe target organ damage disproportionate to the grade of hypertension, or in the face of clinical or biochemical characteristics suggestive of a secondary cause of hypertension. The 2023 Guideline of the European Society of Hypertension recommends starting pharmacological therapy from grade 1 hypertension (BP ≥140/90 mm Hg), with the aim of achieving BP control of less than 130/80 mm Hg. It is important to highlight that the prevalence of secondary hypertension in these patients could be underestimated, given that there is little evidence available on the management of high BP in young adults, which is why we developed this narrative review on the diagnostic and therapeutic approach to the major secondary causes of arterial hypertension in young adults.

Systematic Review and Meta-Analysis of Second-Generation Sham-Controlled Randomized Trials of Renal Denervation Therapy for Patients with Hypertension.

Renal denervation has been associated with substantial and sustained blood pressure reduction and is considered to serve as an alternative treatment for patients with resistant hypertension. However, the first published SHAM-controlled trial assessing RDN safety and efficacy showed no difference between groups. We aimed to perform a meta-analysis quantifying the magnitude of blood pressure decrease secondary to renal denervation in patients with resistant hypertension. Databases were searched for RCTs that compared RDN therapy to SHAM procedure and reported the outcomes of (1) 24-hour ambulatory blood pressure; (2) Office systolic blood pressure; (3) Daytime systolic blood pressure; and (4) Night-time systolic blood pressure. Mean differences with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was examined with I² statistics. P values of < 0.05 were considered statistically significant. Statistical analyses were performed using RStudio 4.2.3. Nine studies and 1622 patients were included. The AMBP [MD -3.72 95%CI -5.44, -2.00 p < 0.001; I²=34%] and DSBP [MD -4.10 95%CI -5.84, -2.37 p < 0.001; I²=0%] were significantly reduced in the RDN arm. ODBP [MD -6.04 95%CI -11.31, -0.78 p = 0.024; I²=90%] and NSBP [MD -1.81 95%CI -3.90, 0.27 p = 0.08; I²=0%] did not reach a statistically significant difference between groups. Renal denervation demonstrates greater efficacy in reducing 24-hour ambulatory and daytime systolic blood pressure in patients diagnosed with resistant hypertension.

Hipertensão arterial resistente: um desafio diagnóstico

Introduction: Primary hyperaldosteronism is a leading cause of secondary arterial hypertension, affecting approximately 10% to 20% of the hypertensive population worldwide and in Brazil. This condition involves excessive aldosterone production due to factors such as adrenal adenoma, hyperplasia, or, less commonly, adrenal carcinoma and familial hyperaldosteronism. This study reports a case of resistant hypertension secondary to aldosterone-producing adenoma. Clinical Case: A 70-year-old male patient presented with episodes of dizziness, syncope, cramps, and asthenia. His medical history included resistant hypertension for over 30 years, despite treatment with five classes of antihypertensive medications. Additionally, he had a history of dyslipidemia, type 2 diabetes mellitus, non-dialysis chronic renal failure, and obstructive coronary arterydisease. Physical examination showed a BMI of 29 kg/m² (overweight), mean blood pressure of 140/90 mmHg (right arm) and 150/100 mmHg (left arm), and palpable nodules in both thyroid lobes, classified as Bethesda V based on aspiration cytopathology. Subsequently, he underwent total thyroidectomy and lymph node dissection. Laboratory tests revealed high plasma aldosterone levels with suppressed renin and an elevated aldosterone-renin ratio, raising suspicion of primary hyperaldosteronism. This diagnosis was confirmed by a computed tomography scan, which identified a 1.2 cm nodule in the right adrenal gland consistent with an adenoma. The patient underwent unilateral laparoscopic adrenalectomy. Two years post-surgery, the patient’s blood pressure was well-controlled with three antihypertensive medications, and his blood sugar, aldosterone, and renin levels were normal. Discussion and Conclusion: Most patients undergoing unilateral adrenalectomy for aldosterone-producing adenomas experience significant clinical improvement. Early screening and diagnosis of primary hyperaldosteronism are crucial for effective management, reducing the risk of complications in the cardiovascular and renal systems.

8688 Pseudopheochromocytoma Due To Severe Obstructive Sleep Apnea

Abstract Disclosure: L.M. José: None. M. Ataide: None. F. Aratani: None. S. Beeby: None. G.F. Fagundes: None. F. Coelho: None. F. Ledesma: None. A. Latronico: None. B.B. Mendonca: None. M.C. Fragoso: None. M.Q. Almeida: None. Background: Obstructive sleep apnea (OSA) represents an independent risk factor for cardiovascular disease, and it is associated with a wide range of conditions, such as resistant hypertension and primary aldosteronism (PA). Patients with sleep apnea have a higher sympathetic activity during wakefulness due to chronic hypoxia. We present the case of pseudopheochromocytoma caused by severe OSA in an obese patient with RH and PA.Clinical Case: A 58-year-old female Brazilian patient was referred to an endocrinologist to investigate a 1.8 cm right adrenal nodule at computed tomography (CT) performed to investigate abdominal pain. Her medical history includes resistant hypertension diagnosed at 27 years of age, type 2 diabetes, dyslipidemia, Class II obesity, a previous acute myocardial infarction, and severe OSA (apnea-hypopnea index 61.6/hour). She has used irregularly the continuous positive airway pressure (CPAP) therapy at night. She is currently using carvedilol 50 mg bid, chlorthalidone 25 mg, olmesartan 40 mg, amlodipine 10 mg, spironolactone 50 mg, clonidine 0.2 mg tid, hydralazine 50 mg every 6 hours, acetylsalicylic acid 100 mg, atorvastatin 80 mg, and metformin XR 1000 mg. At physical examination, she had BMI 37 kg/m2, BP 150 x 90 mmHg, HR 64 bpm, and no signs of Cushing syndrome. Abdominal CT revealed a right adrenal nodule measuring 1.8 cm with 18 Hounsfield unit (HU) in the pre-contrast phase, reaching a density of 117 HU at the arterial phase and showing an absolute washout of 65% and a relative washout of 56%. A nodular thickening of 1.4 cm (-4 HU) at the left adrenal gland was also displayed at CT scan. Hormone evaluation showed basal cortisol 7 µg/dL, ACTH 15.7 pg/mL, DHEAS 1152 ng/mL (189-2050 ng/mL), 1 mg overnight dexamethasone suppression test 2.3 ug/dL, aldosterone 9.9 ng/dL, direct renin concentration 36.8 uIU/mL, plasma metanephrines 0.3 nmol/L (&amp;lt;0.5 nmol/L) and plasma normetanephrines 1.3 nmol/L (&amp;lt;0.9 nmol/L). It was not possible to change anti-hypertensive medications to investigate PA. A 0.3 mg clonidine suppression test did not suppress normetanephrine levels, confirming the biochemical diagnosis of pheochromocytoma. Then, alpha-blockade with doxazosin 4 mg was started and the patient underwent right adrenalectomy. Pathological examination revealed an adenoma with immunohistochemistry positive for CYP11B2. BP control was achieved with only two medications and aldosterone decreased to 3 ng/dL confirming PA. Plasma normetanephrine levels remained elevated post-surgery and only normalized after the CPAP regular use.Clinical lessons: Chronic activation of sympathetic autonomic drive in OSA can increase norepinephrine and normetanephrine levels. OSA is a very prevalent disease and it is frequently associated with RH. Therefore, OSA should be considered a possible cause of pseudopheochromocytoma in hypertensive patients. Presentation: 6/3/2024

8014 Cushing’s Syndrome: Two Sides of The Spectrum

Abstract Disclosure: M. Aguilera: None. A. Vu: None. J. Shakil: None. R. Al-Ward: None. Introduction: Cushing’s syndrome (CS) is a rare condition with an annual incidence of 2-8 per million. Endogenous CS is mainly due to corticotroph adenoma of the pituitary followed by excessive glucocorticoid production from adrenal and ectopic sources. CS has significant morbidity and mortality hence the need for timely diagnosis. The varied presentations often pose great challenges in identifying the source of hypercortisolism. We present two unusual cases of CS with distinct clinical presentations and atypical laboratory profiles. Case 1: 25-year-old male with no medical history presented with 9 months of facial puffiness, weight gain, fluid retention, hypertension and blurred vision. Physical examination revealed round facies, bilateral supraclavicular fat pads and wide abdominal striae. Laboratory workup showed markedly elevated ACTH 537 pg/mL [7.2-63 pg/mL], serum cortisol 8.5 ug/dL [6.2-19.4 ug/dl], 24-hour urine free cortisol (UFC) 30 [5-62 ug/24H] and normal late-night salivary cortisol (LNSC). Repeat workup a month later showed serum cortisol of 56ug/dL, ACTH 874 pg/dL, 24-hour UFC of 11880ug/24H and elevated LNSC. Pituitary MRI showed a large heterogenous 3.1 cm partially cystic sellar mass with suprasellar extension. Due to significantly elevated ACTH and short duration of symptoms, we suspected an ectopic source. Due to initial negative testing, except for high ACTH level, a silent corticotroph adenoma was also considered. The patient underwent transsphenoidal resection resulting in significant decrease of cortisol and ACTH postoperatively. Pathology showed a corticotroph adenoma with Ki-67 index of &amp;lt;1%. Case 2: 47-year-old woman with medical history of obesity, polycystic ovary syndrome and a stable 1 cm lung nodule since 2020, presented with fluid retention, worsening acne and resistant hypertension over a 1-year period. She required hospitalization for hypertensive emergency and hypokalemia. Laboratory data showed morning serum cortisol 28 ug/dL, ACTH of 90.1 pg/mL, 24-hour UFC 346 ug/24H, elevated LNSC on two occasions and cortisol 24.3 ug/dl after a 1mg dexamethasone suppression. MRI did not show a pituitary mass. PET dotatate scan revealed a tracer avid 1 cm right upper lobe pulmonary nodule. She underwent a right upper lobe lobectomy, resulting in a significant decrease in cortisol and ACTH levels on postoperative day 1. Pathology confirmed a typical carcinoid tumor. Discussion: High ACTH levels and a short symptom duration often point to ectopic production, paraneoplastic syndromes or corticotroph carcinomas. Cushing's disease typically exhibits mildly elevated ACTH levels, but our cases deviate from this norm, complicating source identification. This atypical presentation highlights the complexity of Cushing's syndrome, challenging conventional diagnostic paradigms. Presentation: 6/1/2024

5042 The Prevalence of Primary Aldosteronism in Incidentally Discovered Adrenocortical Adenomas Irrespective of Blood Pressure: A Prospective Cohort Study

Abstract Disclosure: T. Uslar: None. A. Burnier: None. B. Sanfuentes: None. P. Böhm: None. M. Orellana: None. F.J. Guarda: None. R.I. Olmos: None. Á. Huete: None. N. Mertens: None. C. Besa: None. A. Majerson: None. J. Cartes: None. C.E. Fardella: None. F. Allende: None. S. Solari: None. A. Vaidya: Consulting Fee; Self; Corcept Therapeutics, HRA Pharmaceuticals. R. Baudrand: None. Background: Incidental adrenocortical adenomas are commonly found on imaging. Guidelines recommend screening for primary aldosteronism (PA) only when adrenocortical adenomas are accompanied by hypertension or unexplained hypokalemia. Objective: To prospectively evaluate the prevalence of PA in consecutive patients with incidentally discovered adrenocortical adenomas. Design: Prospective, longitudinal, single-center study. Methods: 254 consecutive patients with incidentally discovered adrenocortical adenomas were studied, without any evidence of autonomous cortisol secretion, excluded via 1mg dexamethasone suppression test. A structured protocol was followed, which involved measurement of plasma aldosterone (PAC), 24h-urinary aldosterone and sodium, plasma renin activity (PRA) and/or direct renin (DRC). Samples were collected in the morning, in a seated posture, after withdrawing interfering medications. Possible PA was defined across a continuum by having a low renin (DRC &amp;lt;10 uIU/mL or PRA &amp;lt; 1ng/mL/hr) in addition to one of the following 3 criteria reflecting the severity of PA: 1) overt PA: aldosterone/renin ratio (ARR) &amp;gt;30, PA &amp;gt;15 ng/dL, and/or 24h urinary aldosterone &amp;gt;10 ug/24h; 2) moderate PA: ARR 20-30 and PAC 10-15 ng/dL; 3) mild PA: ARR &amp;lt;20 and PAC 5-10ng/dL. Adjusted linear regressions were performed. Patients were followed longitudinally to evaluate treatment outcomes with paired T-test. Results: Among patients with incidentally discovered adrenocortical adenomas, 35% (n=89/254) had possible PA. Overt, moderate, and mild PA were identified in 10%, 12%, and 13% of the overall sample, respectively. Notably, one in five of these individuals (20%) were normotensive. There were trends across the 3 phenotypes of PA indicating a continuum of severity, including: systolic blood pressure (152 ±19, 144 ±13, 142 ±16 mmHg, p-trend=0.02), resistant hypertension (56%, 38%, 33% p-trend=0.034), daily defined dose of antihypertensives (DDD) (2.9 ±1.8, 2.1 ±1.5, 1.0 ±0.8 p-trend=0.001), higher PAC (30.7 ±29.4, 10.3 ± 2.7, 7.9 ±2.5ng/dL p-trend&amp;lt;0.001) and urinary aldosterone (18.2 ±12, 5.6 ±3.6, 5.5 ±3.9 ug/24h p-trend&amp;lt;0.001). In longitudinal treatment follow-up (mean 28-months), 83% had a favorable response to treatment (84% medical, 16% adrenalectomy). After treatment, there was a decrease in SBP of -31.3 ±23 mmHg in overt PA, -13.2 ±19 mmHg in moderate PA, and -9.4 ±18 mmHg in mild PA (p&amp;lt;0.001 in all groups). Similar trends were observed for DDD, with a significant increase in renin in all groups. Conclusions: Overt PA, as well as a continuum of PA, was frequently seen in up to 35% of incidentally discovered adrenocortical adenomas. These findings underscore the importance of screening for PA in all patients with adrenocortical adenomas, irrespective of blood pressure and/or hypokalemia. Presentation: 6/1/2024

8571 Co existence of aldosterone excess in adrenal myelolipomas

Abstract Disclosure: I. Mishra: None. A. Baliarsinha: None. Co existence of aldosterone excess in adrenal myelolipomas Abstract: Adrenal myelolipomas are benign, lipomatous tumours, most of which present as adrenal incidentalomas.Co existence of cortisol excess states and aldosterone producing carcinomas is reported with adrenal myelolipomas,however isolated aldosterone excess without imaging features of adrenal malignancy is rare.We describe 3 cases presenting for evaluation of hyperaldosteronism but with imaging features consistent with myelolipomas. Case 1;58 year female presented with hypertension and spontaneous hypokalemia.On evaluation BMI was 25.3kg/m2,Gr 2 hypertensive retinopathy with systemic examination within normal limits.Biochemical evaluation revealed; Pl.Aldo(ng/dl)32.5; PRA(ng/ml/hr)0.54; ARR 60.5; SIT Pl.Aldo(ng/ml)27.8; AVS- not done; IMAGING(CT) Left adrenal fat attenuating 16×13mm lesion baseline HU &amp;lt; - 20 ?adrenal myelolipoma; Mx Left adrenalectomy H/P Adrenocortical hyperplasia;post op-resolution of hypokalemia with persistence of hypertension controlled with decreased number of drugs. Case 2;38 year male presented with resistant hypertension ,cerebro vascular accident,right hemiparesis and diuretic induced hypokalemia.On evaluation BMI was 31 kg/m2,Gr 1 hypertensive retinopathy with right hemiparesis.Biochemical evaluation revealed; Pl.Aldo(ng/dl)12.3; PRA(ng/ml/hr) 0.82; ARR 15; SIT Pl.Aldo(ng/ml)7.79; AVS- not done; IMAGING(CT) Left adrenal fat attenuating 28×30mmlesion baseline HU &amp;lt; -20? adrenal myelolipoma; Mx Left adrenalectomy H/P adrenal myelolipoma;post op-resolution of hypokalemia ,recovery of weakness and normalization of hypertension without drugs. Case 3;49 year male presented with hypertension ,incidental detection of adrenal lesion on ultrasound for pain abdomen and normokalemia.On evaluation BMI was 27 kg/m2,no significant findings on general examination with systemic examination within normal limits. Biochemical evaluation revealed; Pl.Aldo(ng/dl)12.2; PRA(ng/ml/hr) 0.58; ARR 20.2; SIT Pl.Aldo(ng/ml)11; AVS- not done; IMAGING(CT) Left adrenal fat attenuating 22x 26 mm lesion baseline HU &amp;lt; -20? adrenal myelolipoma; Mx drug therapy for hypertension due to refusal for surgical therapy with monitoring of blood pressure. In surgically treated adrenal myelolipomas, adrenal hormone excess is reported in 5-6% of cases, with autonomous cortisol secretion being most common .Even on the background of CT findings consistent with myelolipomas, patients fulfilling the screening and confirmatory criterias of primary hyperaldosteronism must be subjected to apt therapeutic modality.The presence of aldosterone clusters with excessive aldosterone synthase activity in these lesions could be reason for occurrence of primary hyperaldosteronism in myelolipomas. Presentation: 6/3/2024

8563 Pheochromocytoma Screening In A Patient With Neurofibromatosis Type I And Medication-Resistant Hypertension

Abstract Disclosure: E. Mora: None. A. Bolduc, MD: None. G. Elshimy: None. Title: Pheochromocytoma Screening in a Patient With Neurofibromatosis Type I and Medication-Resistant Hypertension Background: Patients with neurofibromatosis type I (NF1) have a higher risk of pheochromocytoma and it may be missed if no screening done, thus placing the patient at risk of stroke and/or myocardial infarction. The prevalence of pheochromocytoma in patients with NF1 is 2.9% according to a retrospective cohort study by Gruber et al. We present a case of biochemically silent pheochromocytoma in a patient with NF1 and resistant hypertension Clinical case: A 74-year woman with NF1 presented with episodic headaches and labile systolic blood pressure (BP) in the 170-200s mm Hg on three different antihypertensives consistent with pheochromocytoma. Initial tests for renal artery stenosis and pheochromocytoma showed normal plasma MN (0.43 nmol/L, n&amp;lt; 0.50 nmol/L) and NM (0.86 nmol/L, n&amp;lt; 0.90 nmol/L), and normal flow in both renal hila by color Doppler and no large suprarenal masses identified on retroperitoneal US. Duplex imaging of the bilateral kidneys showed no evidence of renal artery stenosis. CT of abdomen/pelvis with and without IV contrast showed a 1.6 cm nodule on Right (RT) adrenal gland that measured 36 HU on unenhanced phase with an absolute washout of 67%. No discrete nodule in Lt adrenal gland. Dotatate PET/CT revealed a Rt adrenal nodule with elevated asymmetric activity (measured 28.1 standardized uptake values (SUV), n for liver: max 12.3, spleen: max 23.5) relative to the normal physiologic activity of the Leftt adrenal gland, which is concerning for pheochromocytoma. The patient was then referred to our endocrine clinic for further evaluation 6 months after the initial presentation. Labs showed normal aldosterone (5.8 ng/dL, n≤39.2 ng/dL), cortisol (7.66 mcg/dL, n: 3.09-22.40 mcg/dL), ACTH (20 pg/mL, n: 7.2-63 (AM collection), and DHEA-S (28 mcg/dL, n:5.3-124 mcg/dL). Normal repeat plasma MN (0.38 nmol/L, n&amp;lt; 0.50 nmol/L) and NM (0.46 nmol/L, n&amp;lt; 0.90 nmol/L). Repeat CT adrenal washout redemonstrated 1.4 cm Rt adrenal nodule that measured 39 HU on non- contrast image with an absolute washout of 68%. Patient will have a surgical resection of the Rt adrenal biochemically silent pheochromocytoma next week and she has been receiving an alpha-blocker prior to surgery to decrease risk for labile BP. Discussion and Conclusion: This case illustrates how CT and DOtatate scan findings can alert providers to the presence of a pheochromocytoma, even in biochemically negative patients. We recommend pheochromocytoma screening in all patients with NF1 to prevent delayed diagnosis and complications of untreated pheochromocytoma. Presentation: 6/1/2024

6574 Pheochromocytoma In A Patient With ESRD; Clinical Challenges And Lessons From A Successful Evaluation

Abstract Disclosure: S. Younes: None. A. Sayed: None. K. Selk: None. L.A. Willard: None. Introduction: Pheochromocytomas are rare tumors that arise from the chromaffin cells in the adrenal medulla, that secrete norepinephrine, epinephrine and dopamine. Common presentations include resistant hypertension (HTN) and adrenergic spells with headaches, sweating and tachycardia. The literature has few cases of pheochromocytoma in the setting of end stage renal disease (ESRD). Case: A 46-year-old male with a history of resistant HTN on amlodipine, lisinopril, and labetalol, complicated by ESRD on hemodialysis (HD) and secondary hyperparathyroidism initially presented with gross hematuria. The patient reported sporadic, intermittent headaches associated with palpitations and sweating. A renal ultrasound revealed a left-sided complex renal cystic mass. CT abdomen/pelvis demonstrated an enhancing left adrenal lesion and MRI abdomen/pelvis confirmed an enhancing 4.6 x 2.8 cm adrenal mass. Laboratory studies revealed elevated normetanephrine of 1186 pg/mL (ref &amp;lt;149 pg/mL), elevated metanephrine at 139 pg/mL (ref &amp;lt;57 pg/mL) and elevated epinephrine at 128 pg/mL (ref &amp;lt;95 pg/mL). Given the laboratory and imaging findings in conjunction with clinical presentation, an excision of the adrenal mass was set. Two weeks prior to the surgery, alpha blockade was started with doxazosin 1mg daily with a goal blood pressure &amp;lt;130/80. He was admitted to the hospital with a goal to keep him 1-1.5kg above his dry weight. His dry weight was 81.5kg close to admission weight, so he was started on gentle IV hydration. He had a left robotic assisted adrenalectomy and was given stress dose steroids and a steroid taper given no preoperative Cushing’s screen was completed. No postoperative complications reported, and doxazosin was discontinued. 2 weeks later, he reported his adrenergic spells had resolved. Surgical pathology confirmed pheochromocytoma and he was referred for genetic consultation. Conclusion: Although there is little in the literature regarding management of a pheochromocytoma in patients with ESRD, similar principles of management in patients with normal renal function apply, including blood pressure control, alpha blockade, and establishment of euvolemia with recommendation of a high-sodium diet and 1-2 liters of saline the day prior to the procedure. This case highlights successful perioperative management with traditional use of alpha blockade but also incorporated maintaining the patient 1-1.5 kg above their dry weight for surgery to limit postoperative hypotension. Presentation: 6/3/2024

6568 A Novel Case of Liddle Syndrome in Siblings: Insights into a Rare Genetic Mutation

Abstract Disclosure: A.B. Humrickhouse: None. M. Peltsverger: None. Introduction: Liddle syndrome (LS) is an inherited form of hypertension caused by a mutation in the epithelialsodium channel (ENaC). This condition is characterized by hypertension (HTN), hypokalemia,hyporeninemia, and metabolic alkalosis, although clinical presentation can vary. Asymptomaticearly-onset HTN is common, and if left undiagnosed, it can lead to advanced renal disease,cardiovascular complications, stroke, and even sudden death. Treatment typically involves theadministration of ENaC blockers such as amiloride and triamterene. We present a novel case ofLS in two siblings resulting from a missense mutation in the SCNN1B gene. Case Presentation: The patient is a 24-year-old Hispanic female who presented for evaluation of poorly controlledHTN and severe hypokalemia of 2.9 mmol/L during the first trimester of pregnancy. She wasdiagnosed with HTN at age eighteen. The family history was notable for resistant HTN in herfather and younger brother. Biochemical evaluation revealed normal plasma-free metanephrinesand 24-hour urine-free cortisol. Low plasma renin activity (0.530 ng/mL/hr) and aldosterone(&amp;lt;1.0 ng/dL) were detected on multiple tests. The urine-free cortisol-to-cortisone ratio was &amp;lt;0.5,excluding the diagnosis of apparent mineralocorticoid excess syndrome. The diagnosis of LS wasconfirmed by genetic analysis, which identified a novel heterozygous mutation, c.1859 A&amp;gt;G(Tyr620Cys), in the SCNN1B gene, which had not been reported in the literature to date. Thesame mutation was identified in her brother. The patient was treated with a high dose ofamiloride (15 mg daily), which controlled her HTN and hypokalemia throughout her pregnancy. Discussion: LS is an autosomal dominant disorder with genetic heterogeneity. It is characterized by HTN,low plasma aldosterone and renin activity, and increased potassium excretion. This leads tohypokalemia and metabolic alkalosis. LS is caused by germline mutations found in theSCNN1A, SCNN1B, and SCNN1G genes, which encode the alpha, beta, and gamma subunits ofthe ENaC channel. These mutations lead to enhanced sodium reabsorption in the kidneys,independent of aldosterone. Our patient was diagnosed with hypertension at the age of 18.However, the diagnosis of LS was not made until six years later when she presented during herfirst trimester of pregnancy. Treatment with amiloride effectively controlled her hypertension andhypokalemia, which allowed her to deliver a healthy child. Amiloride was also prescribed for thepatient's brother. A combination of biochemical analysis and genetic testing enables a betterunderstanding of the various clinical presentations, ensuring appropriate treatment andprevention of end-organ damage. Genetic counseling is essential for families affected by LS. Presentation: 6/1/2024

Prognostic impact of fibrinogen in patients with resistant hypertension.

In this study, we investigated the long-term prognostic effects of fibrinogen levels in patients with resistant hypertension. A total of 266 patients with resistant hypertension who had serum fibrinogen measurements and 5 years of follow-up information were retrospectively included in the study. The patients were stratified according to their fibrinogen levels, which were then divided into tertiles. Clinical outcomes for major adverse cardiovascular events (MACE) were assessed at 5 years. MACE was defined as all-cause mortality, cardiovascular mortality, non-fatal myocardial infarction (MI), non-fatal stroke, a new diagnosis of heart failure, or hospitalization for heart failure and peripheral arterial disease. The incidence of MACE at 5 years in patients with resistant hypertension was higher in the highest tertile of fibrinogen. Multivariate analysis identified fibrinogen as an independent predictor of MACE in patients with resistant hypertension (odds ratio = 1.002; 95% CI: 1.001-1.004; p = 0.009). Compared to the lowest tertile, MACE was approximately 2.5 times higher in tertile 2 and approximately 6.9 times higher in the highest tertile. Fibrinogen was able to predict MACE in patients with resistant hypertension (AUC for MACE 0.662 (95% CI 0.596-0.727; p < 0.001) based on receiver operating characteristic curve analysis. In the Kaplan-Meier curve showing follow-up without MACE (MACE-free) according to the fibrinogen cut-off value, the 5-year incidence of MACE was significantly higher in the high fibrinogen group (p < 0.001). Fibrinogen is a risk marker for MACE in patients with resistant hypertension. Antihypertensive therapy aimed at lowering fibrinogen levels may improve prognosis.

The Increasing Problem of Resistant Hypertension: We'll Manage till Help Comes!

Arterial hypertension remains the major cardiovascular risk worldwide. It is estimated that under 50 years of age one in every three adults is hypertensive while beyond the age of 50 the prevalence is almost 50% globally. The latest World Health Organization (WHO) Global Report on Hypertension indicated that the global number of hypertensive patients almost doubled in the last three decades, with related increasing deaths, disability, and costs annually. Because of this global increase, early diagnosis and timely treatment is of great importance. However, based on the WHO Global Report, it is estimated that up to 46% of individuals were never diagnosed. Of those diagnosed, less than 50% were on treatment, with nearly half among these at target according to the current guidelines. It is also important to note that an increasing number of hypertensive patients, despite the use of three or more drugs, still do not achieve a blood pressure normalization, thus defining the clinical scenario of resistant hypertension (RH). This condition is associated to a higher risk of hypertension-mediated organ damage and hospitalization due to acute cardiovascular events. Current guidelines recommend a triple combination therapy (renin angiotensin system blocking agent + a thiazide or thiazide-like diuretic + a dihydropyridinic calcium-channel blocker) to all patients with RH. Beta-blockers and mineralocorticoid receptor antagonists, alone or in combination, should be also considered based on concomitant conditions and potential contraindications. Finally, the renal denervation is also proposed in patients with preserved kidney function that remain hypertensive despite the use of maximum tolerated medical treatment. However, the failure of this procedure in the long term and the contraindication in patients with kidney failure is a strong call for a new therapeutic approach. In the present review, we will discuss the pharmacological novelties to come for the management of hypertension and RH in the next future.

Identifying pseudo-resistant hypertension and optimizing diuretic therapy for confirmed resistant cases in primary care.

Approximately 10% of individuals with hypertension are expected to have resistant hypertension (RH). Many have pseudo-resistant hypertension (p-RH) due to a variety of factors. To date, the prevalence of p-RH and optimal diuretic therapy in primary care have not been studied. A retrospective chart review was conducted, including patients referred to the hypertension clinic at the Centre for Family Medicine (CFFM) Family Health Team in Kitchener, ON, from January 2010 to September 2020. Individuals ≥18 years old referred to clinic by their family physician or other health care provider with 2 consecutive blood pressure (BP) readings of ≥140/90 mmHg despite using ≥3 antihypertensive agents were included. Fifty-one patients taking ≥3 antihypertensive agents were referred during the study timeframe. Forty-one patients had ≥2 consecutive BP readings of ≥140/90 and were classified as having presumed RH. Of these, 24 patients (59%) had p-RH after BP was measured systematically in the hypertension clinic. Of the 17 with RH, 5 (29%) were prescribed optimal diuretic therapy upon referral. Most common clinic interventions included initiating or adjusting the dose of a diuretic (47%), adding a different antihypertensive agent (27%) or discontinuing an antihypertensive agent due to side effects (24%). To our knowledge, this is the first time that the prevalence of p-RH and optimal diuretic therapy have been studied in primary care. p-RH was common and diuretic therapy was underused in RH. This study suggests that p-RH is prevalent and diuretic therapy underused in primary care. Systematic BP measurement and optimization of diuretic therapy should be prioritized prior to specialist referral.