Ambiguous genitalia and hypertension in a patient with congenital adrenal hyperplasia

Congenital adrenal hyperplasia (CAH) is an uncommon condition. Its clinical presentation with hypertension is rare. Deficiency of the steroid 11‐beta‐hydroxylase accounts for less than 10% of CAH. We report a case of a 19‐year‐old patient who presents with hypertension with ambiguous genitalia secondary to adrenal steroidogenesis dysfunction. We also discuss the defects in adrenal steroidogenesis and clinical phenotypes of CAH.     

Chronic hepatic cytolysis revealing a pheochromocytoma

We report here the first case of chronic cytolysis that led to the diagnosis of pheochromocytoma, in a 48-year-old woman with a recent onset of hypertension. The etiological research ruled out the common causes of raised transaminase levels, and led to the discovery of a left adrenal pheochromocytoma. The sustained normalization of liver function tests after the removal of the tumour strongly suggests that hepatocyte injury was due to catecholamine hyperproduction. The present original clinical case, linking pheochromocytoma and liver dysfunction, raises important mechanistic questions concerning the relationship between catecholamines and liver function. It may also have clinical implications. Indeed, pheochromocytoma should be considered as a possible cause in case of unexplained transaminase increase associated with the recent onset of hypertension.     

Inappropriate secretion of antidiuretic hormone in a patient with chronic inflammatory demyelinating polyneuropathy

A 54-year-old man suffered from a relapse of chronic inflammatory demyelinating polyneuropathy (CIDP), and developed quadriplegia and somnolence requiring mechanical ventilation for respiratory failure. Serum Na concentration remained at low levels during the clinical course, and a diagnosis of inappropriate secretion of antidiuretic hormone (SIADH) was made. The present case had not only acute aggravation of CIDP with autonomic dysfunction but also intracranial hypertension caused by increased CSF protein (maximum level, 1,315 mg/dl). It seemed likely that injury of the afferent fibers of the baroregulatory pathway or intracranial hypertension might have contributed to SIADH in this patient.     

Idiopathic portal hypertension associated with high serum titer of antoantibodies and liver dysfunction

Idiopathic portal hypertension (IPH) is a condition marked by unexplained portal hypertension. Although a number of immunological abnormalities occur in patients with IPH, liver function is usually normal. We experienced an unusual case of IPH in a 49-year-old woman, who had pronounced splenomegaly. Laboratory data revealed pancytopenia, hypergammaglobulinemia, and liver dysfunction. Antinuclear antibodies were positive, with high titer at 1280 dilutions of sera. LE cell phenomena were also positive. Histological examination of biopsied liver showed only mild changes, but portal venous pressure was markedly elevated, at 38 cm H₂O. This case was thus characterized by both a high serum titer of autoantibodies and liver dysfunction.     

Obesity, sleep apnea, and hypertension

Obesity has a high and rising prevalence and represents a major public health problem. Obstructive sleep apnea (OSA) is also common, affecting an estimated 15 million Americans, with a prevalence that is probably also rising as a consequence of increasing obesity. Epidemiologic data support a link between obesity and hypertension as well as between OSA and hypertension. For example, untreated OSA predisposes to an increased risk of new hypertension, and treatment of OSA lowers blood pressure, even during the daytime. Possible mechanisms whereby OSA may contribute to hypertension in obese individuals include sympathetic activation, hyperleptinemia, insulin resistance, elevated angiotensin II and aldosterone levels, oxidative and inflammatory stress, endothelial dysfunction, impaired baroreflex function, and perhaps by effects on renal function. The coexistence of OSA and obesity may have more widespread implications for cardiovascular control and dysfunction in obese individuals and may contribute to some of the clustering of abnormalities broadly defined as the metabolic syndrome. From the clinical and therapeutic perspectives, the presence of resistant hypertension and the absence of a nocturnal decrease in blood pressure in obese individuals should prompt the clinician to consider the diagnosis of OSA, especially if clinical symptoms suggestive of OSA (such as poor sleep quality, witnessed apnea, excessive daytime somnolence, and so forth) are also present.     

Successfully treated "accelerated" renovascular hypertension with intravascular stenting.

A 76-year-old man developed progressive renal dysfunction with refractory hypertension. Bilateral renal artery stenosis due to atherosclerosis was revealed. Both the hypertension and renal dysfunction were improved by percutaneous transluminal renal angioplasty with stenting. Based on the rapidly progressive elevation of plasma renin activity and the improvement of both renal dysfunction and hypertension after stenting, this was considered a case of "accelerated" renovascular hypertension. There have been an increasing number of patients with bilateral renal artery stenosis due to atherosclerosis. The present case reminds us that a rapid progression of renal dysfunction suggests, in addition to besides rapidly progressive glomerulonephritis with crescent formation, bilateral renal artery stenosis, the incidence of which is on the rise. In the present case, angioplasty with stenting was effective for blood pressure control and preservation of renal function.     

Right ventricular failure in patients with preserved ejection fraction and diastolic dysfunction: an underrecognized clinical entity

It is well recognized that patients with severe left ventricular (LV) systolic dysfunction develop pulmonary venous hypertension or postcapillary pulmonary hypertension, which leads to an increase in pulmonary vascular resistance (PVR) and right ventricular (RV) systolic failure. It is often underrecognized, however, that patients with heart failure with preserved LV ejection fraction and diastolic dysfunction may also develop postcapillary pulmonary hypertension with elevated PVR leading to RV systolic failure. This form of biventricular failure is a result of diastolic failure on the left in patients with preserved LV ejection fraction and systolic failure on the right. At this time, there are no randomized trials or guidelines addressing the management of patients with diastolic heart failure with and without resultant RV failure. The authors review the pathophysiology, clinical presentation, and suggested treatment of this underrecognized clinical entity.     

The Risk Factors That Predict Chronic Hypertension After Delivery in Women With a History of Hypertensive Disorders of Pregnancy

Hypertensive disorders of pregnancy (HDP) is one of the most important lethal complications in pregnant mothers. It is also associated with the subsequent development of chronic hypertension. The objective of this study was to identify the clinical risk factors of postpartum chronic hypertension in women diagnosed with HDP.Six hundred patients as HDP, who diagnosed and followed-up at least 6 month after delivery, were included in the study. We divided the included subjects in 2 groups based on the development of postpartum chronic hypertension: presenting with the chronic hypertension, “case group” (n = 41) and without chronic hypertension, “control group” (n = 559).Clinical and demographic factors were evaluated. By multiple regression analysis, early onset hypertension with end-organ dysfunction, smoking, higher prepregnancy body mass index (BMI), and comorbidities, systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APLS), were associated with progression to chronic hypertension in the postpartum period. The value of area under the curves (AUC) for the 5 models, that generated to combine the significant factors, increased from 0.645 to 0.831, which indicated improved prediction of progression to the chronic hypertension. Additional multivariate analysis revealed significant specific risk factors.This retrospective single hospital-based study demonstrated that the clinical risk factors, that is early onset hypertension with end-organ dysfunction, smoking, and higher prepregnancy BMI, were significant independent predictors of chronic hypertension in women after delivery. Identification of risk factors allowed us to narrow the subject field for monitoring and managing high blood pressure in the postpartum period.     

An Unusual Cause of Neonatal Heart Failure

Hypertension is an important and under-recognized cause of acquired cardiomyopathy in newborns. Half the etiologies of neonatal hypertension are undetermined. We present a rare case of severe neonatal hypertension with ventricular dysfunction secondary to substance exposure during pregnancy. This case report emphasizes the importance of a well-focused prenatal history on maternal medications and substance use.     

Malignant Histiocytosis in a Patient Presenting with Hepatic Dysfunction and Peliosis Hepatis

In this article, we report the case of a 36-yr-old patient presenting with manifestations of portal hypertension, hepatic dysfunction, and fever who proved to have peliosis hepatis on liver biopsy. A thorough work-up revealed no obvious etiology. At autopsy, malignant histiocytosis of the liver and bone marrow was diagnosed. This case represents the first report of the association of peliosis hepatis with this rare histiocytic neoplasm and exemplifies the need for persistence in the search for malignancy, particularly hematological malignancy, in the patient with unexplained peliosis. The clinical similarity of peliosis hepatis associated with hematological malignancy and bacillary peliosis is also discussed.     

Apparent mineralocorticoid excess manifested in an elderly patient with hypothyroidism

The syndrome of apparent mineralocorticoid excess (AME) is characterized by persistent hypertension and hypokalemia, which is caused by impaired inactivation of cortisol (F) to cortisone (E). The thyroid hormone has been known to influence the F to E conversion leading to efficacious inactivation of F into E. However, there have been no reports regarding the clinical manifestation of secondary AME due to hypothyroidism. Here we report an elderly patient who manifested AME, showing persistent hypertension with hypokalemia induced by primary hypothyroidism. Maintenance of euthyroid conditions ameliorated the concurrent AME and restored adrenal secretion of aldosterone after the recovery of the F to E shuttle. This case report would broaden our clinical recognition regarding acquired AME in relation to thyroid dysfunction.     

The molecular sources of reactive oxygen species in hypertension

In both animal models and humans, increased blood pressure has been associated with oxidative stress in the vasculature, i.e. an excessive endothelial production of reactive oxygen species (ROS), which may be both a cause and an effect of hypertension. In addition to NADPH oxidase, the best characterized source of ROS, several other enzymes may contribute to ROS generation, including nitric oxide synthase, lipoxygenases, cyclo-oxygenases, xanthine oxidase and cytochrome P450 enzymes. It has been suggested that also mitochondria could be considered a major source of ROS: in situations of metabolic perturbation, increased mitochondrial ROS generation might trigger endothelial dysfunction, possibly contributing to the development of hypertension. However, the use of antioxidants in the clinical setting induced only limited effects on human hypertension or cardiovascular endpoints. More clinical studies are needed to fully elucidate this so called "oxidative paradox" of hypertension.     

Endothelial function and hypertension

PURPOSE OF REVIEW: Endothelial dysfunction, in particular a reduced vascular availability of endothelium-derived nitric oxide, has been analysed in numerous experimental and clinical studies as a potential mechanism mediating the adverse vascular effects of hypertension. This paper outlines some notable studies in this dynamic field published recently. RECENT FINDINGS: The understanding of mechanisms underlying endothelial dysfunction in hypertension has been substantially advanced recently. Increased oxidant stress is thought to represent a major mechanism leading to reduced vascular availability of endothelium-derived nitric oxide. Vascular nicotinamide adenine dinucleotide phosphate oxidases, uncoupled nitric oxide synthase and xanthine oxidase have been identified as major sources of reactive oxygen species in hypertension. Endothelial dysfunction has been implicated in the macrovascular complications of hypertension, such as stroke or myocardial infarction, coronary microvascular dysfunction and increased arterial stiffness, probably at least partly resulting from loss of the antiatherogenic and vasculoprotective effects of endothelium-derived nitric oxide. SUMMARY: Recent research on endothelial dysfunction supports its clinical significance in hypertension, and has led to important insights into the pathophysiology of the disease. These observations suggest that targeting endothelial dysfunction, in particular reduced nitric oxide availability, would exert beneficial effects in hypertensive patients. This concept needs further evaluation in clinical studies.     

Diagnosis and therapeutic guidance of diastolic heart failure

Despite diastolic dysfunction is recognized to play a major role in the pathophysiology of heart failure, the importance of an accurate diagnosis and treatment of this syndrome in clinical practice is poorly established. Recent publications suggest that diastolic dysfunction is the primary cause of heart failure in 30-50% of patients. Several studies also show that, in a significant number of patients with systolic dysfunction, diastolic function is the major determinant of their symptomatic status, their response to treatment and their outcome. Other preliminary data suggest that diastolic dysfunction is an important cause of exercise intolerance in patients with chronic hypertension. This paper discusses the most recent concepts related to the mechanisms, the diagnosis and the treatment of diastolic dysfunction based on diagnostic imaging techniques.     

Renovascular hypertension from the BCR‐ABL tyrosine kinase inhibitor ponatinib

Drug‐induced hypertension is one of the commonest causes of secondary hypertension. In the last few years, secondary hypertension due to tyrosine kinase inhibitors, from the vascular endothelial growth factor class, has been recognized to be an important cause of hypertension, as well as proteinuria, and occasionally kidney dysfunction in some cases. Less well‐recognized is that BCR‐ABL tyrosine kinase inhibitors also have adverse vascular effects. These manifest as vascular stenoses in large vessels, which may sometimes cause renal artery stenosis and subsequent hypertension. We describe a case report which presented as classical bilateral renal artery stenosis, and responded to revascularization. Increased awareness of these effects, as well as research into the pathogenesis, may provide more insight into vascular biology.     

A 25-year clinical history of portopulmonary hypertension associated with latent myeloproliferative disorder

Pulmonary hypertension associated with increased pulmonary vascular resistance occurring in the setting of portal hypertension, referred to as "portopulmonary hypertension", is a complication of chronic liver disease, and occurs in 2% to 3% of patients with portal hypertension. Portal hypertension is a relatively common finding in patients with chronic myeloproliferative disorder (CMPD). Pulmonary hypertension is also an occasional finding in CMPD patients. Latent myeloproliferative disorder, on the other hand does not fulfill the diagnostic criteria of classical CMPD and is characterized by younger age of onset, slow disease progression, a high risk of thrombosis, platelet dysfunction, and normal or increased platelet count in spite of the presence of splenomegaly. We report findings in a 50-year-old woman with portal hypertension for which there were three major etiological findings-increased splenic blood flow, infiltration of hematopoietic cells in the liver, and thrombosis in the portal or hepatic vein-over a 25-year clinical course, during which there was also reversible stenosis of the portal vein. Twenty-three years after her first admission, her condition was diagnosed as latent myeloproliferative disorder, and she developed pulmonary hypertension. Her clinical history and data indicated that the portopulmonary hypertension was due to the latent myeloproliferative disorder.     

Right-sided heart failure: Diagnosis and treatment strategies

Right ventricular (RV) dysfunction in the setting of cardiomyopathy, ischemia, and pulmonary hypertension is associated with high morbidity and mortality, but therapeutic clinical trials examining RV failure as a primary outcome are lacking. This review focuses on the ontologic, morphologic, and microscopic differences between the right and left ventricles. It also discusses the rationale and potential risks associated with the extrapolation of medical therapies used in left ventricular failure and pulmonary arterial hypertension management to the treatment of RV failure. Finally, it introduces the reader to new echocardiographic techniques that may be used to diagnose clinical and subclinical RV systolic and diastolic dysfunction. Given the anticipated rise in the prevalence of RV dysfunction, more studies are needed to gain a better understanding of RV cellular and subcellular function and its response to pathologic stressors and disease so that therapeutic targets can be devised to improve RV failure morbidity and mortality.     

Is mild essential hypertension without obvious organ complications and risk factors associated with increased levels of circulating markers of endothelial dysfunction? Effect of ACE inhibitor therapy

The objective of the investigation was to assess whether circulating adhesion molecules, von Willebrand factor (vWf) and endothelin-1 are elevated in patients with mild uncomplicated essential hypertension without further risk factors of atherosclerosis and whether they could serve as indicators of endothelial dysfunction in this form of hypertension. Furthermore the authors investigated the effect of ACE inhibitor treatment (ACEI), quinapril, on the level of these markers of endothelial dysfunction. The level of adhesion molecules [intercellular cytoadhesion molecule-1 (ICAM-1), E-selectin, P-selectin], von Willebrand s factor (vWf) and endothelin-1 were assessed in patients with mild essential hypertension without further cardiovascular risk factors or clinical manifestations of atherosclerosis before and after quinapril treatment (n = 25) and compared with normotensive controls (n = 29). The results of the examinations provided evidence that contrary to controls the hypertensive subjects had significantly higher ICAM-1 levels (237.8 vs. 207.8 ng/ml, P = 0.02) vWf (118 vs. 106 IU/dl, p < 0.05) and endothelin-1 (5.81 vs. 5.15 fmol/ml, p < 0.05). Three-month treatment of hypertensive patients with ACEI led to a significant drop of endothelin-1 levels (5.81 vs. 5.26 fmol/ml, p = 0.01). The authors proved also an unequivocal declining trend of other cytoadhesion molecules and vWf after ACEI treatment, the changes however were not statistically significant. From the investigation it may be concluded that also patients with uncomplicated essential hypertension without other cardiovascular risk factors or clinical manifestations of atherosclerosis have significantly elevated plasma levels of ICAM-1, vWf and endothelin-1. Higher concentrations of these factors suggest endothelial dysfunction already in mild forms of essential hypertension without further risk factors or cardiovascular complications. A significant drop of endothelin-1 and declining trend of the other investigated indicators suggest that ACEI treatment can favourably influence endothelial dysfunction in hypertensive patients also independently on reduction of the BP.     

Intravital microscopy reveals endothelial dysfunction in resistance arterioles in Angiotensin II-induced hypertension

It is known that hypertension is associated with endothelial dysfunction and that Angiotensin II (Ang II) is a key player in the pathogenesis of hypertension. We aimed to elucidate whether endothelial dysfunction is a specific feature of Ang II-mediated hypertension or a common finding of hypertension, independently of underlying etiology. We studied endothelial-dependent vasorelaxation in precapillary resistance arterioles and in various large-caliber conductance arteries in wild-type mice with Ang II-dependent hypertension (2-kidney 1-clip (2K1C) model) or Ang II-independent (volume overload) hypertension (1-kidney 1-clip model (1K1C)). Normotensive sham mice were used as controls. Aortic mechanical properties were also evaluated. Intravital microscopy of precapillary arterioles revealed a significantly impaired endothelium-dependent vasorelaxation in 2K1C mice compared with sham mice, as quantified by the ratio of acetylcholine (ACh)-induced over S-nitroso-N-acetyl-D,L-penicillamine (SNAP)-induced vasorelaxation (2K1C: 0.49±0.12 vs. sham: 0.87±0.11, P=0.018). In contrast, the ACh/SNAP ratio in volume-overload hypertension 1K1C mice was not significantly different from sham mice, indicating no specific endothelial dysfunction (1K1C: 0.77±0.27 vs. sham: 0.87±0.11, P=0.138). Mechanical aortic wall properties and endothelium-dependent vasorelaxation, assessed ex vivo in rings of large-caliber conductance (abdominal and thoracic aorta, carotid and femoral arteries), were not different between 2K1C, 1K1C and sham mice. Endothelial dysfunction is an early feature of Ang II- but not volume-overload-mediated hypertension. This occurs exclusively at the level of precapillary arterioles and not in conduit arteries. Our findings, if confirmed in clinical studies, will provide a better understanding of the pathophysiological mechanisms of hypertension.     

Obesity-Related Cardiorenal Syndrome

J Clin Hypertens (Greenwich). 2010;12:59–63. ^© 2009 Wiley Periodicals, Inc.
The term obesity cardiomyopathy has previously been used to describe a clinical syndrome in obese patients typically consisting of eccentric left ventricular hypertrophy with preserved ejection fraction and diastolic dysfunction and is often associated with right ventricular dysfunction independent of the presence of the obstructive sleep apnea syndrome. Although several publications have described the early stages of this syndrome, little is known about the end stages of the disease. The authors conducted a retrospective study of a subset of edematous obese patients with multiple common medical comorbidities who present with a clinical syndrome in the setting of physiologic stress or infection. Under severe physiologic stress these patients developed pulmonary hypertension, right-sided volume overload, decreased effective arterial blood volume, and renal failure. Often, these findings were in the setting of obstructive sleep apnea. This retrospective study focuses on an obesity-related cardiorenal syndrome but also serves to provide a foreground for acknowledging the broad spectrum of cardiovascular pathology, including pulmonary hypertension, diastolic dysfunction, and sleep apnea, seen in the obese.