Association Between Aldosterone and Hypertension Among Patients With Overt and Subclinical Hypercortisolism

INTRODUCTION: Hypertension is one of the most common clinical features of patients with overt and subclinical hypercortisolism. Although previous studies have shown the coexistence of autonomous cortisol and aldosterone secretion, it is unclear whether aldosterone plays a role in hypertension among patients with hypercortisolism. Therefore, we examined the associations of plasma aldosterone concentrations (PACs) with hypertension among patients with overt and subclinical hypercortisolism. METHODS: This single-center retrospective cohort study included patients with adrenal tumor and serum cortisol levels after 1-mg dexamethasone suppression test >1.8 µg/dL (50 nmol/L). Using multivariable regression models adjusting for baseline characteristics, we investigated the association of PACs with systolic blood pressure and postoperative improvement of hypertension after the adrenalectomy. RESULTS: Among 89 patients enrolled in this study (median age, 51 years), 21 showed clinical signs of Cushing syndrome (overt hypercortisolism) and 68 did not show clinical presentations (subclinical hypercortisolism). We found that higher PACs were significantly associated with elevated systolic blood pressure among patients with subclinical hypercortisolism (adjusted difference [95% CI] = +0.59 [0.19-0.99], P = 0.008) but not among those with overt hypercortisolism. Among 33 patients with subclinical hypercortisolism and hypertension who underwent adrenalectomy, the postoperative improvement of hypertension was significantly associated with higher PACs at baseline (adjusted risk difference [95% CI] = +1.45% [0.35-2.55], P = 0.01). CONCLUSION: These findings indicate that aldosterone may contribute to hypertension among patients with subclinical hypercortisolism. Further multi-institutional and population-based studies are required to validate our findings and examine the clinical effectiveness of the intervention targeting aldosterone for such patients

Radiological characteristics and diagnostic impact of duplicated right adrenal veins on adrenal venous sampling in primary aldosteronism

PURPOSEWe aimed to analyze the prevalence and radiological characteristics of duplicated right adrenal veins (DRAVs) and evaluate the diagnostic impact of adrenal venous sampling (AVS) in primary aldosteronism.METHODSDRAVs were retrospectively identified among patients who underwent segmental AVS between April 2017 and March 2020. DRAVs were defined as main or accessory according to the drainage area. The diameter, position, hormone levels, and treatment plan based on AVS were compared between main and accessory RAVs, using the Wilcoxon rank-sum test.RESULTSFourteen of 432 patients (3.2%) were diagnosed with DRAVs. On venography, the mean diameters of the main and accessory side were 3±0.63 mm and 2.1±0.41 mm, respectively, and were significantly different (p < 0.001). The mean relative position in craniocaudal direction of main and accessory veins from the adrenal caudal edge on computed tomography was 65.5%±16.0%, and 48.1%±16.8%, respectively, which was significantly different (p = 0.007). The left–right positions and hormone levels were not significantly different. Based on conventional AVS, the treatment plan between DRAVs was not changed in six of eight patients, but changed from surgery to medication in two patients with right aldosterone-producing adenoma (APA)/microadenoma based on segmental AVS findings.CONCLUSIONDRAVs, in which the main RAV was thicker and more cranially located than the accessory RAV were rare. Depending on blood sampled from either of DRAVs, the diagnosis made through conventional AVS might change treatment approach from surgery to medication, especially with right APA. Hence, their identification is important to make an accurate subtyping by AVS

An Angiotensin II Type 1 Receptor Blocker Prevents Renal Injury via Inhibition of the Notch Pathway in Ins2 Akita Diabetic Mice

Recently, it has been reported that the Notch pathway is involved in the pathogenesis of diabetic nephropathy. In this study, we investigated the activation of the Notch pathway in Ins2 Akita diabetic mouse (Akita mouse) and the effects of telmisartan, an angiotensin II type1 receptor blocker, on the Notch pathway. The intracellular domain of Notch1 (ICN1) is proteolytically cleaved from the cell plasma membrane in the course of Notch activation. The expression of ICN1 and its ligand, Jagged1, were increased in the glomeruli of Akita mice, especially in the podocytes. Administration of telmisartan significantly ameliorated the expression of ICN1 and Jagged1. Telmisartan inhibited the angiotensin II-induced increased expression of transforming growth factor β and vascular endothelial growth factor A which could directly activate the Notch signaling pathway in cultured podocytes. Our results indicate that the telmisartan prevents diabetic nephropathy through the inhibition of the Notch pathway

PPAR beta/delta activation of CD300a controls intestinal immunity

Macrophages are important for maintaining intestinal immune homeostasis. Here, we show that PPAR beta/delta (peroxisome proliferator-activated receptor beta/delta) directly regulates CD300a in macrophages that express the immunoreceptor tyrosine based-inhibitory motif (ITIM)-containing receptor. In mice lacking CD300a, high-fat diet (HFD) causes chronic intestinal inflammation with low numbers of intestinal lymph capillaries and dramatically expanded mesenteric lymph nodes. As a result, these mice exhibit triglyceride malabsorption and reduced body weight gain on HFD. Peritoneal macrophages from Cd300a(-/-) mice on HFD are classically M1 activated. Activation of toll-like receptor 4 (TLR4)/MyD88 signaling by lipopolysaccharide (LPS) results in prolonged IL-6 secretion in Cd300a(-/-) macrophages. Bone marrow transplantation confirmed that the phenotype originates from CD300a deficiency in leucocytes. These results identify CD300a-mediated inhibitory signaling in macrophages as a critical regulator of intestinal immune homeostasis

Clinical Utility of the Adrenocorticotropin Stimulation Test with/without Dexamethasone Suppression for Definitive and Subtype Diagnosis of Primary Aldosteronism

The adrenocorticotropin (ACTH) stimulation test (AST) has been reported to be useful for diagnosing primary aldosteronism (PA), particularly for differentiating PA subtypes under 1-mg dexamethasone suppression (DS). The aim of our study was to clarify the effect of 1-mg DS on AST results. A retrospective cohort study was conducted using data for 48 patients (PA: 30/48). We estimated the difference in plasma aldosterone concentration (PAC) responsiveness to ACTH stimulation with single (AST alone) and combined (AST under 1-mg DS) tests within the same patient. We compared the diagnostic accuracy of these two tests for PA and the laterality of hyperaldosteronism. We found no differences in PAC responsiveness to ACTH stimulation between single and combined tests, and observed a significant positive linear relationship (30 min, R2 = 0.75, p-value &lt; 0.01). Both tests showed the highest diagnostic accuracy for PA following 30 min of ACTH stimulation. The ability to detect the laterality of hyperaldosteronism was inconsistent and differed according to the two definitions: lateralization ratio and the absolute aldosterone levels in adrenal venous sampling. PAC responsiveness to ACTH stimulation was similar for AST with and without 1-mg DS. AST can be performed under both conditions with similar accuracy to detect PA

Segmental low-density area on contrast-enhanced CT is a possible clue to diagnosing branch artery fibromuscular dysplasia

Fibromuscular dysplasia can cause renovascular hypertension. Since fibromuscular dysplasia may be underdiagnosed, precise diagnosis and management are crucial, especially for young women. A 20-year-old woman with hypertension and hypokalemia was referred to our hospital for further evaluation of secondary hypertension. At the previous hospital, her blood pressure was 160/110 mmHg and the serum potassium level was 2.9 mEq/L. The equilibrium phase on contrast-enhanced computed tomography revealed a low-density area in the upper median portion of the right kidney. On admission to our hospital, her blood pressure was 141/96 mmHg under 5 mg of amlodipine. Laboratory tests revealed plasma renin activity of 11.3 ng/mL/h and plasma aldosterone concentration of 117.1 pg/mL. Renal venous sampling of active renin concentration showed a right-to-left renin ratio of 3.13, confirming a significant increase in renin secretion from the right kidney. Selective reno-angiography detected focal stenosis with adjacent aneurysmal dilation and tortuosity in the proximal branch of the right renal artery. She was diagnosed with branch artery fibromuscular dysplasia and successfully treated with percutaneous transluminal angioplasty. After the treatment, she was free from hypertension and hypokalemia without any medications. Since branch artery fibromuscular dysplasia is sometimes difficult to diagnose, contrast-enhanced computed tomography can be a promising diagnostic tool as shown in this case. Concerning treatment, our patient was treated with percutaneous transluminal angioplasty, which should be considered for women of reproductive age because recommended antihypertensive medications can be teratogenic even in the first trimester of pregnancy

Efficacy and Safety of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin on Atherosclerosis, β-Cell Function, and Glycemic Control in Japanese Patients with Type 2 Diabetes Mellitus Who are Treatment Naïve or Poorly Responsive to Antidiabetes Agents: A Multicenter, Prospective Observational, Uncontrolled Study

Background: Sitagliptin, a dipeptidyl peptidase-4 inhibitor, is widely used in patients with type 2 diabetes. However, the pleiotropic effects of sitagliptin is not well understood. Objective: To assess the clinical efficacy and safety of sitagliptin on atherosclerosis, β-cell function, and glycemic control in Japanese patients with type 2 diabetes. Methods: A prospective observational study of 270 patients with type 2 diabetes mellitus was carried out. Patients (aged 64.3 [12.4] years, body mas index 25.2 [4.3]) with glycated hemoglobin >6.9% (52 mmol/mol) or fasting plasma glucose >130 mg/dL were treated with sitagliptin for 12 months. The primary end point was glycated hemoglobin level changes from baseline to 3 months. The secondary end points included changes in several biomarkers related to inflammation and β-cell function from baseline to 3 months, as well as changes in glycated hemoglobin level from baseline to 12 months. Results: Glycated hemoglobin levels were significantly lower in patients treated with sitagliptin for 3 months than at baseline (8.1% [1.4%]–7.3% [1.2%]) (65 [16.9]–56 [13.1] mmol/mol]) (P < 0.0001), which continued after 12 months (7.4% [1.3%]) (56 [15.2] mmol/mol) (P < 0.0001). In addition, a marker of vascular-specific inflammation, pentraxin-3, and a marker of β-cell function (proinsulin/insulin ratio), respectively, were lower after treatment with sitagliptin for 3 months than at baseline (1.88 [0.78]–1.65 [0.63] ng/mL [P = 0.0038] and 0.20 [0.14]–0.17 [0.11] [P = 0.01], respectively). On the other hand, a biomarker reflecting whole body inflammation; that is, high-sensitivity C-reactive protein level, was unchanged. Adverse events occurred in 14 patients (5.18%). Conclusions: Sitagliptin may have beneficial effects on vascular inflammation and β-cell function in Japanese patients with type 2 diabetes. Pentraxin-3 may be an early predictive marker for detecting the antiatherosclerotic effects of dipeptidyl peptidase-4