von Hippel-Lindau Syndrome and Secondary Hypertension: A Case Report.

von Hippel-Lindau (VHL) syndrome (OMIM #193300) is an autosomal dominant disorder with incomplete penetrance occurring due to a mutation in the VHL gene present on chromosome 3. We present the case of a 21-year-old male with a history of retinoblastoma presenting with intermittent headaches for one month. He was a known hypertensive and his blood pressure on presentation was 180/100 mmHg. A secondary cause for his hypertension was sought. Multiple cysts in his pancreas, both his kidneys, and a mass in the right suprarenal fossa were detected on an abdominal ultrasonogram and a subsequent computed tomography scan of the abdomen. VHL and a pheochromocytoma were suspected, and a positron emission tomography-computed tomography scan was done which collaborated with the above findings. The presence of multiple cystic lesions in the pancreas and kidneys, especially in an individual with a family history of VHL syndrome, should alert the physician to the possibility of VHL syndrome. The need for evaluation of causes for hypertension, especially in young individuals with resistant hypertension, is also highlighted.

Beta-2 Glycoprotein I IgA Isotype: An Important Consideration in Secondary Hypertension.

Anti-beta-2 glycoprotein I antibodies are an important player in hypercoagulable states, including those that lead to antiphospholipid syndrome. Traditionally, assays have only detected IgG and IgM isotypes of this antibody. However, newer assays also detect the IgA isotype. The problem lies in the largely unknown significance of this IgA isotype. This paper describes a middle-aged male who presented with hypertensive emergency and was later found to have IgA anti-beta-2 glycoprotein I antibodies. He was treated with multiple anti-hypertensives, aspirin, and statin therapy. In addition to the case, we discuss the implications of this IgA isotype and how it may relate to antiphospholipid syndrome, despite not currently being included in the laboratory diagnostic criteria for the disease.

Evaluation of the Canonical Wnt Signaling Pathway in the Hearts of Hypertensive Rats of Various Etiologies.

Wnt/ß-catenin signaling dysregulation is associated with the pathogenesis of many human diseases, including hypertension and heart disease. The aim of this study was to immunohistochemically evaluate and compare the expression of the Fzd8, WNT1, GSK-3ß, and ß-catenin genes in the hearts of rats with spontaneous hypertension (SHRs) and deoxycorticosterone acetate (DOCA)-salt-induced hypertension. The myocardial expression of Fzd8, WNT1, GSK-3ß, and ß-catenin was detected by immunohistochemistry, and the gene expression was assessed with a real-time PCR method. In SHRs, the immunoreactivity of Fzd8, WNT1, GSK-3ß, and ß-catenin was attenuated in comparison to that in normotensive animals. In DOCA-salt-induced hypertension, the immunoreactivity of Fzd8, WNT1, GSK-3ß, and ß-catenin was enhanced. In SHRs, decreases in the expression of the genes encoding Fzd8, WNT1, GSK-3ß, and ß-catenin were observed compared to the control group. Increased expression of the genes encoding Fzd8, WNT1, GSK-3ß, and ß-catenin was demonstrated in the hearts of rats with DOCA-salt-induced hypertension. Wnt signaling may play an essential role in the pathogenesis of arterial hypertension and the accompanying heart damage. The obtained results may constitute the basis for further research aimed at better understanding the role of the Wnt/ß-catenin pathway in the functioning of the heart.

Comparison between screening for primary aldosteronism with and without drug adjustment.

OBJECTIVE: Few studies have evaluated the performance of non-drug-adjusted primary aldosteronism (PA) screening. Therefore, we aimed to examine the consistency between PA screening results with and without drug adjustment and to explore the effectiveness of screening without drug adjustment. METHODS: This prospective study included 650 consecutive patients with a high risk of incidence PA. Patients who initially screened positive underwent rescreening with drug adjustments and confirmatory tests. Regarding the remaining patients, one of every three consecutive patients underwent rescreening with drug adjustments and confirmatory tests. The changes in aldosterone and renin concentrations were compared between patients with essential hypertension (EH) and those with PA before and after drug adjustment. Sensitivity and specificity were used to assess the diagnostic performance of screening without drug adjustment, using the confirmatory test results as the reference. RESULTS: We screened 650 patients with hypertension for PA. Forty-nine patients were diagnosed with PA and 195 with EH. Regarding drugs, 519 patients were taking angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), or diuretics alone or in combination. Forty-one patients were taking beta-blockers. Ninety patients were taking beta-blockers in combination with other drugs. In patients treated with ACEIs, ARBs, CCBs, or diuretics alone, or in combination, or beta-blockers alone, PA positivity was determined using the criteria, aldosterone-to-renin ratio (ARR) >38 pg/mL/pg/mL and plasma aldosterone concentration (PAC) >100 pg/mL, and negativity, using the criteria, ARR <9 pg/mL/pg/mL; the sensitivity and specificity were 94.7% and 94.5%, respectively. After drug adjustment, the sensitivity and specificity of screening were 92.1% and 89%, respectively. CONCLUSIONS: In patients not treated with beta-blockers combined with others, when ARR >38 pg/mL/pg/mL and plasma aldosterone concentration (PAC) >100 pg/mL, or, ARR <9 pg/mL/pg/mL, non-drug-adjusted screening results were identical to with drug adjustment. Non-drug-adjusted screening could reduce the chance of medication adjustment, enable patients to continue their treatments and avoiding adverse effects, is of clinical importance.

Primary aldosteronism (PA) is the most common form of endocrine hypertension. The risk of stroke, myocardial infarction, heart failure, atrial fibrillation, and deterioration of kidney function is higher in PA than in essential hypertension (EH), even with the same blood pressure (BP) levels. However, many patients remain undiagnosed because most antihypertensive drugs substantially interfere with PA screening results, which makes drug adjustment necessary. This can be a time-consuming and unsafe process, requiring 4­6 weeks, and could lead to a hypertensive crisis and other complications. Some studies have suggested that certain antihypertensive drugs can be continued during PR screening. However, few studies have evaluated the performance of non-drug-adjusted PA screening. Therefore, in this prospective study, we aimed to compare patients with hypertension and a high risk of PA before and after drug adjustment and to use confirmatory test results as a reference to explore the diagnostic or exclusion effect. We found that non-drug-adjusted screening performs similarly to drug-adjusted screening in a particular group of patients. Our findings could aid in preventing unnecessary drug adjustment for PA screening, thereby reducing the risk in these patients.

Exploration of Hypertension Following Traumatic Renal Hematoma Formation and Page Kidney Discussion.

Page kidney is defined as a rare cause of secondary hypertension due to a subcapsular hematoma externally compressing the kidney resulting in the activation of the renin-angiotensin-aldosterone system (RAAS). This phenomenon consists of numerous etiologies including acute or chronic traumatic or non-traumatic events. In this case, we report on an acute unilateral hematoma following blunt renal trauma as the result of a fall from standing height treated with tissue plasminogen activator (tPA) infusion and image-guided drainage. Qualities within this case and how they are paralleled in the diagnosis of a Page kidney are explored. A brief review of current etiologies and management plans per the literature review will also be discussed.

Secondary hypertension and aortic coarctation in a young adult: A case report.

Aortic coarctation is a rare cause of secondary hypertension (<1% cases) and can be challenging to detect due to its few clinical manifestations. Early diagnosis and treatment are important because patients with unmanaged aortic coarctation are at increased risk of cardiovascular complications and have a reduced life expectancy. We describe a case of secondary hypertension in a young adult female caused by aortic coarctation, first detected in a general practitioner setting, resulting in the need for a left subclavian-carotid bypass vascular surgery and a descending aortic stent vascular surgery. This case highlights the critical role that proximity medicine in general practice can have in improving the early detection of clinically silent conditions by routinely monitoring blood pressure and other vital parameters, and the increasing importance of medical imaging in assisting early diagnosis and guiding the surgical management of complex cases.

Diagnostic challenges in patients with reninomas and extrarenal renin-producing tumours.

Renin-secreting tumours are rare causes of secondary hypertension and hypokalaemia. They are usually surgically curable, hence proper diagnostic work-up and tumour localisation is essential. In this paper, we present three Swedish patients recently diagnosed with renin secreting tumours, two with reninomas and one with an extrarenal renin-producing tumour, to illustrate diagnostic challenges. We also discuss the biochemical work-up, the pros and cons of different imaging techniques (computer tomography [CT], magnetic resonance imaging and [18F]fluorodeoxyglucose-positron emission tomography-CT), as well as how renal vein sampling (RVC) may contribute to localisation of the tumour.

Selective venous sampling for secondary hypertension.

Selective venous sampling (SVS), an invasive radiographic procedure that depends on contrast media, holds a unique role in diagnosing and guiding the treatment of certain types of secondary hypertension, particularly in patients who may be candidates for curative surgery. The adrenal venous sampling (AVS), in particular, is established as the gold standard for localizing and subtyping primary aldosteronism (PA). Throughout decades of clinical practice, AVS could be applied not only to PA but also to other endocrine diseases, such as adrenal Cushing syndrome (ACS) and Pheochromocytomas (PCCs). Notably, the application of AVS in ACS and PCCs remains less recognized compared to PA, with the low success rate of catheterization, the controversy of results interpretation, and the absence of a standardized protocol. Additionally, the AVS procedure necessitates enhancements to boost its success rate, with several helpful but imperfect methods emerging, yet continued exploration remains essential. We also observed renal venous sampling (RVS), an operation akin to AVS in principle, serves as an effective means of diagnosing renin-dependent hypertension, aiding in the identification of precise sources of renin excess and helping the selection of surgical candidates with renin angiotensin aldosterone system (RAAS) abnormal activation. Nonetheless, further basic and clinical research is needed. Selective venous sampling (SVS) can be used in identifying cases of secondary hypertension that are curable by surgical intervention. Adrenal venous sampling (AVS) and aldosterone measurement for classificatory diagnosis of primary aldosteronism (PA) are established worldwide. While its primary application is for PA, AVS also holds the potential for diagnosing other endocrine disorders, including adrenal Cushing's syndrome (ACS) and pheochromocytomas (PCCs) through the measurements of cortisol and catecholamine respectively. In addition, renal venous sampling and renin measurement can help to diagnose renovascular hypertension and reninoma.

Abiraterone-Induced Secondary Hypertension: Two Wrongs Don't Make a Right.

Abiraterone, an inhibitor of both 17α-hydroxylase and 17,20-lyase, is considered a novel, state-of-the-art, life-prolonging therapy in the urologists' arsenal when treating prostate cancer. Despite its efficacy, it is linked with an increased risk of cardiovascular adverse effects. Herein, we report a case in which the administration of abiraterone resulted in a full-blown syndrome of apparent mineralocorticoid excess despite the concomitant administration of prednisolone; that is, secondary hypertension, hypokalemia, metabolic alkalosis, as well as elevated levels of adrenocorticotropic hormone (ACTH).

An Uncommon Presentation of Renal Angiomyolipoma: A Case Report.

Renal angiomyolipoma (AML) is a rare benign tumor of the kidney that can occur as a sporadic lesion or a part of tuberous sclerosis. A 77-year-old female patient with a history of hypertension, hyperlipidemia, and an unclear history of left nephrectomy in 1999 presented with progressive shortness of breath and palpitations. Her vital signs showed elevated blood pressure, and the examination was benign and non-focal. A work-up showed multiple lesions in her lungs and right kidney, representing lymphangioleiomyomatosis. The patient was diagnosed with tuberous sclerosis and was followed up by pulmonology and nephrology. She underwent embolization of the renal AML, after which her blood pressure (BP) was more controlled, and she reported feeling well and symptom-free. Renal AML, as a part of tuberous sclerosis, is a rare cause of secondary hypertension. Embolization of AML is effective in controlling BP.

Feasibility of primary aldosteronism diagnosis in initial evaluation without medication withdrawal or confirmatory tests.

PURPOSE: Primary aldosteronism (PA), a frequent cause of hypertension, is highly associated with cardiovascular risk and mortality. PA diagnosis is often difficult due to the need to discontinue antihypertensive medication interfering with the renin-angiotensin-aldosterone system (I-RAAS). Our objective was to ascertain diagnosis of PA through biochemical assessments during screening while maintaining I-RAAS medications. METHODS: Hypertensive patients assessed for PA were involved. Patients were grouped according to the use of I-RAAS drugs during screening and the presence of PA. The diagnostic accuracy of the aldosterone-to-renin ratio (ARR), and other biochemical features were evaluated. RESULTS: 265 patients included, 122/265 with PA, and 192/265 were on I-RAAS therapy. The area under ROC curve (AUROC) of ARR for PA in patients without I-RAAS was 0.769 (95%CI: 0.66-0.877), and was 0.877 (95%CI: 0.828-0.926) in those with I-RAAS drugs. Sensitivity, specificity, positive predictive value, and negative predictive value (PPV) of cut-off of ARR > 50 were: 76%, 81%, 77.5%, and 79.6%. ARR > 50 plus hypokalemia had a PPV of 92.6% for PA. AUROC values of ARR evaluated in each group of antihypertensive drugs were >0.850 in all cases. CONCLUSIONS: ARR during I-RAAS therapy demonstrates reliability and accuracy for PA diagnosis. An ARR > 50 combined with hypokalemia while on I-RAAS medication could be considered indicative of PA diagnosis.

A fatal misdiagnosis of page kidney - case report.

Page kidney is a condition where external compression of the renal artery and renal parenchyma leads to subsequent ischaemia and activation of renin-angiotensin-aldosterone axis. A 42-year-old female with hirsutism, hypertension and diabetes was diagnosed with a right adrenal mass and underwent laparoscopic adrenalectomy. Her hypertension worsened postoperatively and was managed medically. Subsequently she developed a right flank pain on the fifth postoperative day and died suddenly the next day. Autopsy revealed a pale body with cushingoid appearance. Surgical scars were healthy. Internal examination of the abdomen revealed a haemoperitoneum of 500 ml together with a large subcapsular haematoma measuring 1000 ml surrounding the right kidney, compressing the right renal artery. Kidneys were pale and the right kidney was soft and friable. Cortical surface of the right kidney demonstrated a possible surgical puncture site with an overlying thrombus together with a contused inferior vena cava. Other organs were pale but appeared otherwise normal. Histology revealed diffuse cortical necrosis of right kidney and features of adult respiratory distress syndrome in the lungs. Haemorrhagic shock following laparoscopic adrenalectomy for right adrenal tumor was declared as the cause of death, contributed by the development of the Page kidney. Trauma of several aetiologies including laparoscopic abdominal surgery may contribute to Page kidney. It presents with flank pain, hypertension and renal mass. Since postoperative blood loss usually manifests as hypotension, resulting hypertension may mislead the attending clinicians. Once diagnosed, it can be managed with surgical drainage and antihypertensives.

The Rise and Fall of Well-Controlled Blood Pressure: Labile Hypertension Following Repair of a Ruptured Abdominal Aortic Aneurysm.

Hypertension is a common pathology with several etiologies. If left uncontrolled, severe and even fatal complications can develop, including heart disease, vascular damage, and stroke. Primary hypertension is most commonly seen without an underlying etiology; however, several contributing factors can lead to the development of hypertension. There have been limited cases reporting the effects of an abdominal aortic dissection treated with endovascular aortic repair (EVAR) on the development of labile hypertension. We report a case of uncontrolled, labile hypertension following an EVAR of an abdominal aortic aneurysm in a patient without prior medical history of hypertension.

Clinical diagnosis of pheochromocytoma and paraganglioma-induced secondary hypertension through UPLC-MS/MS analysis of plasma catecholamines and their metabolites.

This study aimed to elucidate the clinical diagnostic value of plasma catecholamines and their metabolites for pheochromocytoma and paraganglioma (PPGL)-induced secondary hypertension using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS). The study population included 155 patients with PPGL that were divided into the PPGL with hypertension (n = 79) and a PPGL without hypertension (n = 76) groups, and 90 healthy volunteers and 90 patients with primary hypertension as the control groups. UPLC-MS/MS was performed to detect plasma levels of catecholamines and their metabolites, including dopamine, vanillylmandelic acid (VMA), norepinephrine, metanephrine, and normetanephrine. Receiver operating characteristic curves were generated to analyze the diagnostic value of the plasma levels of catecholamines and their metabolites in PPGL-induced secondary hypertension. Patients in the primary hypertension and PPGL without hypertension groups had higher levels of dopamine, VMA, norepinephrine, metanephrine, and normetanephrine than patients in the normal group (all p < .05). On the other hand, patients in the PPGL with hypertension group had higher levels of dopamine, VMA, norepinephrine, metanephrine, and normetanephrine than patients in the normal, primary hypertension, and PPGL without hypertension groups (all p < .05). Collectively, our findings showed that dopamine, VMA, norepinephrine, metanephrine, and normetanephrine are all effective biomarkers for the diagnosis of PPGL and PPGL-induced secondary hypertension.

Onco-Hypertension: A Continuously Developing Field between Cancer and Hypertension.

The prognosis of cancer patients has greatly improved in the last years, owing to the development of novel chemotherapeutic agents. However, this progress comes with an increasing occurrence of cardiovascular adverse reactions. A serious side effect is arterial hypertension (HT), which is the most frequent comorbidity encountered in cancer patients, influencing the outcomes in cancer survivors. Even though secondary HT related to specific chemotherapeutic agents, such as vascular endothelial growth factor inhibitors, is usually mild and reversible, in rare instances it can be severe, leading to discontinuation of chemotherapy. In addition, HT per se has been studied as a potential risk factor for cancer development. The relationship is even more complex than previously thought, as concerning evidence recently highlighted the potential oncogenic effects of antihypertensive drugs, particularly thiazide diuretics, which may increase the risk of skin cancer. As a result, in light of the similar risk factors and overlapping pathophysiological mechanisms between HT and cancer, a promising concept of onco-hypertension has emerged, aiming to improve the understanding of the complicated interplay between these two pathologies and maintain a balance between the efficacy and risks of both antihypertensive drugs and chemotherapy agents.

A Case Report of Primary Aldosteronism and Extensive Hypertension-Mediated Organ Damage.

Primary aldosteronism, the most common curable form of secondary hypertension, is associated with greater hypertension-related organ damage and cardiovascular complications compared to primary essential hypertension. The authors present a case involving a 41-year-old Black male admitted to the emergency department with left hemiparesis and blurred vision persisting for one hour, accompanied by markedly elevated blood pressure (220/140 mmHg). The patient was asymptomatic by then, and, aside from a history of tobacco smoking and occasional cannabis use, lacked significant medical comorbidities. Further investigations revealed a right acute hemorrhagic stroke, bilateral grade 4 hypertensive retinopathy, chronic kidney disease with end-stage renal disease, hypokalemia, and an elevated aldosterone/renin ratio. An abdominal CT scan showed bilateral adrenal hyperplasia. The patient was diagnosed with primary aldosteronism with extensive hypertension-mediated organ damage. This case highlights the significant harm caused by undiagnosed primary aldosteronism-induced secondary hypertension, emphasizing the importance of timely diagnosis and intervention to prevent organ damage.

Delayed symptomatic renal arteriovenous fistula in a 24 years old male following renal biopsy.

We report a case of a 24-year-old male with a history of kidney biopsy at young age due to chronic renal dysfunction and challenging hypertension, who presented with flank pain and hematuria. Initial imaging suggested renal pelvis enlargement, but MRI revealed a massive renal arteriovenous malformation (AVM). Angiographic embolization was abandoned due to extensive effluent flow, followed by successful surgical resection preserving healthy kidney tissue. This case underscores the importance of considering renal AVMs in the differential diagnosis of young patients with gross hematuria or refractory hypertension to prevent complications and improve patient outcomes.

A 120-Minute Saline Infusion Test for the Confirmation of Primary Aldosteronism: A Pilot Study.

BACKGROUND: The saline infusion test (SIT) to confirm primary aldosteronism requires infusing 2 L of normal saline over 240 minutes. Previous studies raised concerns regarding increased blood pressure and worsening hypokalemia during SIT. We aimed to evaluate the diagnostic applicability of a SIT that requires 1 L of saline infusion over 120 minutes. METHODS: A cross-sectional study, including all patients in a large medical center who underwent SIT from 1 January 2015 to 30 April 2023. Blood samples were drawn for baseline renin and aldosterone (t = 0) after 2 hours (t = 120 min) and after 4 hours (t = 240 min) of saline infusion. We used ROC analysis to evaluate the sensitivity and specificity of various aldosterone cut-off values at t = 120 to confirm primary aldosteronism. RESULTS: The final analysis included 62 patients. A ROC analysis yielded 97% specificity and 90% sensitivity for a plasma aldosterone concentration (PAC) of 397 pmol/L (14 ng/dL) at t = 120 to confirm primary aldosteronism, and an area under the curve of 0.97 (95% CI [0.93, 1.00], P < 0.001). Almost half (44%) of the patients did not suppress PAC below 397 pmol/L (14 ng/dL) at t = 120. Of them, only one (4%) patient suppressed PAC below 276 pmol/L (10 ng/dL) at t = 240. Mean systolic blood pressure increased from 140.1 ±â€…21.3 mm Hg at t = 0 to 147.6 ±â€…14.5 mm Hg at t = 240 (P = 0.011). CONCLUSIONS: A PAC of 397 pmol/L (14 ng/dL) at t = 120 has high sensitivity and specificity for primary aldosteronism confirmation.

Case report: Page kidney with multiple serosal effusions caused by bilateral spontaneous renal subcapsular hemorrhage.

Page kidney is caused by the perirenal or subcapsular accumulation of blood or fluid pressing on the renal parenchyma and is a rare cause of secondary hypertension. In this study, we report a case of Page caused by bilateral spontaneous subcapsular renal hematoma, the main manifestations of which were secondary hypertension, multiple serous effusions, and renal insufficiency. After admission, drug blood pressure control was ineffective. After bilateral perirenal effusion puncture and drainage were performed to relieve bilateral perirenal compression, blood pressure gradually dropped to normal, multi-serous cavity effusion (pericardial, thoracic, and abdominal effusion) gradually disappeared, and kidney function returned to normal. Secondary hypertension caused by Page kidney can be treated. When Page kidney is complicated with multiple serous effusions, the effect of antihypertensive drugs alone is poor, and early perineal puncture drainage can achieve better clinical efficacy.

Device's design and clinical perspectives for resistant hypertension therapy.

Introduction: Hypertension is the leading cause of death in the cardiovascular system. Indeed, untreated hypertension can affect one's general health, but medicine can help hypertensive people reduce their chance of developing high blood pressure. However, secondary hypertension remains an unresolved illness. Areas covered: This review will go through the typical and unusual device-based therapies for resistant hypertension that have arisen in recent years. Further to that, the innovations developed in device-based RH treatment will be covered, as well as the research and studies assessing these novel technologies. Expert opinion: The innovative device-based techniques that target resistant hypertension provide a potential therapy that has been backed by a number of studies and clinical trials, whereas pharmacological non-adherence and increased sympathetic activity are recognized to be the primary causes of resistant hypertension. Nevertheless, some limitations will be critical for the future of these RH systems, with the device's design and larger RCTs playing a significant role in determining whether a position in routine treatment could be warranted.