Cardiac Remodeling in Hypertension: Clinical Impact on Brain, Heart, and Kidney Function.

Hypertension is the most common causative factor of cardiac remodeling, which, in turn, has been associated with changes in brain and kidney function. Currently, the role of blood biomarkers as indices of cardiac remodeling remains unclear. In contrast, cardiac imaging, including echocardiography and cardiovascular magnetic resonance (CMR), has been a valuable noninvasive tool to assess cardiac remodeling. Cardiac remodeling during the course of systemic hypertension is not the sole effect of the latter. "Remodeling" of other vital organs, such as brain and kidney, also takes place. Therefore, it will be more accurate if we discuss about "hypertensive remodeling" involving the heart, the brain, and the kidneys, rather than isolated cardiac remodeling. This supports the idea of their simultaneous assessment to identify the early, silent lesions of total "hypertensive remodeling". In this context, magnetic resonance imaging is the ideal modality to provide useful information about these organs in a noninvasive fashion and without radiation. For this purpose, we propose a combined protocol to employ MRI in the simultaneous assessment of the heart, brain and kidneys. This protocol should include all necessary indices for the evaluation of "hypertensive remodeling" in these 3 organs, and could be performed within a reasonable time, not exceeding one hour, so that it remains patient-friendly. Furthermore, a combined protocol may offer "all in one examination" and save time. Finally, the amount of contrast agent used will be limited granted that post-contrast evaluations of the three organs will be performed after 1 injection.

Prevalence of Primary Aldosteronism Across the Stages of Hypertension Based on a New Combined Overnight Test.

Primary aldosteronism (PA) is the most common endocrine cause of arterial hypertension. Despite the increasing incidence of hypertension worldwide, the true prevalence of PA in hypertension was only recently recognized. The objective of the work was to estimate the prevalence of PA in patients at different stages of hypertension based on a newly developed screening-diagnostic overnight test. This is a prospective study with hypertensive patients (n=265) at stage I (n=100), II (n=88), and III (n=77) of hypertension. A group of 103 patients with essential hypertension without PA was used as controls. PA diagnosis was based on a combined screening-diagnostic overnight test, the Dexamethasone-Captopril-Valsartan Test (DCVT) that evaluates aldosterone secretion after pharmaceutical blockade of angiotensin-II and adrenocorticotropic hormone. DCVT was performed in all participants independently of the basal aldosterone to renin ratio (ARR). The calculated upper normal limits for post-DCVT aldosterone levels [3 ng/dl (85 pmol/l)] and post-DCVT ARR [0.32 ng/dl/µU/ml (9 pmol/IU)] from controls, were applied together to establish PA diagnosis. Using these criteria PA was confirmed in 80 of 265 (30%) hypertensives. The prevalence of PA was: 21% (21/100) in stage I, 33% (29/88) in stage II, and 39% (30/77) in stage III. Serum K+ levels were negatively correlated and urinary K+ was positively correlated in PA patients with post-DCVT ARR (r=-0.349, p <0.01, and r=0.27, p <0.05 respectively). In conclusion, DCVT revealed that PA is a highly prevalent cause of hypertension. DCVT could be employed as a diagnostic tool in all subjects with arterial hypertension of unknown cause.

Five Reasons for the Failure to Diagnose Aldosterone Excess in Hypertension.

Primary hyperaldosteronism (PA) is a well-known cause of hypertension although its exact prevalence amongst patients with apparent essential hypertension has been a matter of debate. A number of recent studies have suggested that mild forms of PA may be relatively common taking into consideration factors that were previously either overestimated or ignored when developing diagnostic tests of PA and when applying these tests into normotensive individuals. The performance characteristics and diagnostic accuracy of such tests are substantially increased when the adrenocorticotrophin effect, inappropriate potassium levels and their application in carefully selected normotensive individuals are considered. In the present review, we critically analyze these issues and provide evidence that several, particularly mild, forms of PA can be effectively identified exhibiting potentially important clinical implications.

Concomitant alterations of metabolic parameters, cardiovascular risk factors and altered cortisol secretion in patients with adrenal incidentalomas during prolonged follow-up.

OBJECTIVE: Adrenal incidentalomas (AI) are associated with metabolic and hormonal abnormalities, most commonly autonomous cortisol secretion (ACS). Data regarding alterations of insulin resistance (IR) and ACS after prolonged follow-up are limited. We investigated the evolution of IR, cortisol secretion and ACS development in patients with AI during prolonged follow-up. DESIGN: Prospective study in a tertiary hospital. PATIENTS AND MEASUREMENTS: Seventy-one patients with AI [51 nonfunctioning (NFAI) and 20 ACS] and 5·54 ± 1·7 years follow-up underwent testing for ACS and oral glucose tolerance test to determine IR indices and adrenal imaging. RESULTS: At follow-up, 16/51 (31%) NFAI patients converted to ACS, while two with previous ACS reverted to NFAI; 21% (7/33) of patients who did not covert to ACS exhibited high urinary-free cortisol (H-UFC) levels. All AI patients developed deterioration of IR irrespective of their cortisol secretory status. Eight patients developed newly diagnosed type 2 diabetes (9·8% NFAI and 15% ACS, respectively) and 14 IR (17·6% NFAI and 25% ACS, respectively). Adenoma size increased from 2·1 ± 0·8 to 2·3 ± 0·8 cm, whereas IR correlated with postdexamethasone cortisol level and adenoma size increase. IR showed an incremental continuum trend from normal UFC (Ν-UFC), to H-UFC, C-ACS and ACS patients. CONCLUSIONS: New-onset ACS developed in 31% patients with NFAI, whereas 21% of NFAI patients had H-UFC levels. All AI patients as a group and the subgroups of N-UFC, H-UFC, C-ACS and ACS patients developed deterioration of metabolic parameters during follow-up that was more prominent in ACS patients.

Functional characterization of two novel germline mutations of the KCNJ5 gene in hypertensive patients without primary aldosteronism but with ACTH-dependent aldosterone hypersecretion.

BACKGROUND: Germline mutations of the KCNJ5 gene encoding Kir3·4, a member of the inwardly rectifying K+ channel, have been identified in 'normal' adrenal glands, patients with familial hyperaldosteronism (FH) type III, aldosterone-producing adenomas (APAs) and sporadic cases of primary aldosteronism (PA). OBJECTIVE: To present two novel KCNJ5 gene mutations in hypertensive patients without PA, but with Adrenocorticotropic hormone (ACTH)-dependent aldosterone hypersecretion. DESIGN AND PATIENTS: Two hypertensive patients without PA, who exhibited enhanced ACTH-dependent response of aldosterone secretion, underwent genetic testing for the presence of the CYP11B1/CYP11B2 chimeric gene and KCNJ5 gene mutations. Genomic DNA was isolated from peripheral white blood cells, and the exons of the entire coding regions of the above genes were amplified and sequenced. Electrophysiological studies were performed to determine the effect of identified mutation(s) on the membrane reversal potentials. Structural biology studies were also carried out. RESULTS: Two novel germline heterozygous KCNJ5 mutations, p.V259M and p.Y348N, were detected in the two subjects. Electrophysiological studies showed that the Y348N mutation resulted in significantly less negative reversal potentials, suggesting loss of ion selectivity, while the V259M mutation did not affect the Kir3.4 current. In the mutated structural biology model, the N348 mutant resulted in significant loss of the ability for hydrogen bonding, while the M259 mutant was capable of establishing weaker interactions. The CYP11B1/CYP11B2 chimeric gene was not detected. CONCLUSIONS: These findings expand on the clinical spectrum of phenotypes associated with KCNJ5 mutations and implicate these mutations in the pathogenesis of hypertension associated with increased aldosterone response to ACTH stimulation.

Primary aldosteronism in hypertensive patients: clinical implications and target therapy.

BACKGROUND: The prevalence of primary aldosteronism (PA) in hypertensive patients varies according to diagnostic testing and ascertained normal cut-offs. The aim of this case-control study was to confirm the high prevalence of PA in a large hypertensive population and evaluate the antihypertensive effect of mineralocorticoid receptor antagonists (MRA) treatment. MATERIAL AND METHODS: We investigated 327 hypertensive and 90 matched normotensive subjects with normal adrenal imaging. Serum aldosterone (ALD), active renin (REN) levels and aldosterone/active renin (ALD/REN) ratio were measured before and after a combined sodium chloride, fludrocortisone and dexamethasone suppression test (FDST). Post-FDST values were compared to cut-offs obtained from controls (post-FDST ALD 2·96 ng/dL and post-FDST ALD/REN 0·93 ng/dL/µU/mL). PA patients received MRA treatment. RESULTS: By applying the combination of post-FDST ALD levels and ALD/REN ratio, 28·7% of the hypertensive patients had PA. There was a positive, albeit weak, correlation between systolic (SBP) and diastolic blood pressure (DBP) and ALD levels and/or ALD/REN ratio after the FDST (P < 0·0001). SBP was associated with a post-FDST ALD of 3·24 ng/dL and ALD/REN ratio of 0·90 ng/dL/µU/mL, whereas post-FDST ALD had an inverse association at serum K+ values of less than 3·9 mEq/L. MRA treatment in 69 PA patients, resulted in a significant reduction in the maximum SBP and DBP values (28 ± 15 and 14 ± 7 mmHg, respectively, P < 0·0001). CONCLUSIONS: Using the FDST, an increased prevalence of PA in hypertensives was observed. Α significant blood pressure lowering effect was obtained with MRA treatment, implying that these agents may be beneficial in a significant number of hypertensive patients.

Laparoscopic adrenalectomy in patients with subclinical Cushing syndrome.

BACKGROUND: Subclinical Cushing syndrome in patients with adrenal incidentalomas has been associated with an increased prevalence of the metabolic syndrome and cardiovascular risk. The management of these patients, be it conservative or surgical, is still debated, but there is accumulating evidence that surgery is best and that laparoscopic adrenalectomy, when possible, is the most preferred procedure. Here we present the short- and long-term results of laparoscopic adrenalectomy for subclinical Cushing syndrome and determine the effect of this procedure on components of the metabolic syndrome. METHODS: Twenty-nine patients, 8 men and 21 women with adrenal incidentalomas and subclinical Cushing syndrome who underwent laparoscopic adrenalectomy, were studied retrospectively. They had undergone postoperative follow-up for improvement or worsening of their arterial blood pressure, body weight, and fasting glucose level for a mean period of 77 months. RESULTS: Preoperatively, 17 patients (58.6 %) had arterial hypertension, 14 (48.3 %) had a body mass index exceeding 27 kg/m(2), and 12 (41.4 %) had diabetes mellitus. Postoperatively, a decrease in mean arterial pressure was found in 12 patients (70.6 %), a decrease in body mass index in 6 patients (42.9 %), and an improvement in glycemic control in 5 patients (41.7 %). CONCLUSIONS: Laparoscopic adrenalectomy is beneficial in many patients with subclinical Cushing syndrome because it reduces arterial blood pressure, body weight, and fasting glucose levels. Prospective randomized studies are needed to compare laparoscopic adrenalectomy with a conservative approach and to confirm these results.

International multicenter survey on screening and confirmatory testing in primary aldosteronism.

OBJECTIVE: Primary aldosteronism (PA) is one of the most frequent causes of secondary hypertension. Although clinical practice guidelines recommend a diagnostic process, details of the steps remain incompletely standardized. DESIGN: In the present SCOT-PA survey, we have investigated the diversity of approaches utilized for each diagnostic step in different expert centers through a survey using Google questionnaires. A total of 33 centers from 3 continents participated. RESULTS: We demonstrated a prominent diversity in the conditions of blood sampling, assay methods for aldosterone and renin, and the methods and diagnostic cutoff for screening and confirmatory tests. The most standard measures were modification of antihypertensive medication and sitting posture for blood sampling, measurement of plasma aldosterone concentration (PAC) and active renin concentration by chemiluminescence enzyme immunoassay, a combination of aldosterone-to-renin ratio with PAC as an index for screening, and saline infusion test in a seated position for confirmatory testing. The cutoff values for screening and confirmatory testing showed significant variation among centers. CONCLUSIONS: Diversity of the diagnostic steps may lead to an inconsistent diagnosis of PA among centers and limit comparison of evidence for PA between different centers. We expect the impact of this diversity to be most prominent in patients with mild PA. The survey raises 2 issues: the need for standardization of the diagnostic process and revisiting the concept of mild PA. Further standardization of the diagnostic process/criteria will improve the quality of evidence and management of patients with PA.

Nonalcoholic fatty liver disease in subjects with adrenal incidentaloma.

BACKGROUND: Adrenal incidentalomas (AI) are associated with several parameters of the metabolic syndrome (MS). Although nonalcoholic fatty liver disease (NAFLD) is considered a cardiometabolic risk factor, no data exist on its prevalence and clinical relevance in AI. The aim was to investigate the presence of MS and NAFLD in AI subjects. PATIENTS AND METHODS: Fifty-six AI subjects and 30 age-, sex- and body mass index (BMI)-matched controls were evaluated. All subjects underwent abdominal computerized tomography scan and hepatic and spleen attenuation measurements. The presence of NAFLD was defined as a mean hepatic minus mean spleen attenuation difference (ΔL-ΔS) <-10HU. Anthropometric variables [BMI and waist-to-hip ratio (W/H)] were recorded, and biochemical parameters were measured. An oral glucose tolerance test was performed, and several insulin resistance (IR) indices were determined. All subjects underwent testing to reveal autonomous cortisol and/or aldosterone (ALD) secretion, while the diagnosis of pheochromocytoma was ruled out. RESULTS: Adrenal incidentaloma subjects' mean age (± standard deviation) was 59.64 (± 8.68) years, BMI 29.84 (± 5.85) kg/m(2) and W/H 0.90 (± 0.07). Twelve subjects with AI had subtle autonomous cortisol, five autonomous ALD and three combined cortisol and ALD secretion. AI subjects exhibited higher IR indices than controls. NAFLD was present in three AI subjects and two controls. In the multiple regression analysis, W/H and triglycerides were independently associated with a low ΔL-ΔS and, hence, degree of hepatic steatosis. CONCLUSIONS: There was no significant difference in the presence of NAFLD between AI patients and controls. ΔL-ΔS, an inverse index of NAFLD, was independently associated with abdominal obesity and increased triglycerides.

Pattern of adrenal morphology and function in patients with acromegaly.

BACKGROUND: Acromegaly is well known to induce hypertrophic and hyperplastic changes in various organs and is commonly accompanied by arterial hypertension. In our study, we assess the adrenal morphology and function in a series of patients with acromegaly and possible associations with the activity of the disease and arterial hypertension. MATERIALS AND METHODS: Sixty patients with acromegaly, admitted to two endocrinology departments in the time period 2005-2010, were studied prospectively. Basal IGF-1 and growth hormone levels after oral glucose tolerance test were used to assess the disease activity. All subjects underwent adrenal CT scan, basal adrenal hormonal investigation and evaluation with 24-h urinary free cortisol and cortisol levels following low-dose dexamethasone suppression test. In 33 acromegalics, the 'modified' saline infusion test (MSI), i.e. saline infusion after dexamethasone administration, was performed to identify autonomous aldosterone (ALD) secretion. RESULTS: Abnormal adrenal morphology was present in 48% of our patients, and a significant association was found between the presence of arterial hypertension and adrenal morphology. Among patients with adrenal morphological changes, 55% exhibited no adrenal secretory hyperactivity, 34% autonomous cortisol, 7% ALD and 4% combined autonomous cortisol and ALD secretion, when applying recently proposed modified cut-off levels compared to widely used criteria. An increased prevalence of autonomous ALD secretion was shown among the subgroup of patients with acromegaly tested with MSI. CONCLUSIONS: This study provides evidence of an increased prevalence of anatomic and functional adrenal alterations in patients with acromegaly; further studies will clarify the importance of evaluating these subjects with baseline hormonal investigation along with dynamic testing and modified cut-offs.

Genetic screening of hypertensive patients with aldosterone hypersecretion under conditions of stress.

PURPOSE: Although ACTH is considered a secondary regulator of aldosterone production, patients with apparent essential hypertension have been treated with mineralocorticoid receptor antagonists (MRAs). In this study, we aimed to identify potentially damaging variants that might be implicated in the phenotype of a well-characterized cohort of 21 hypertensive patients without PA but with stress-induced aldosterone hypersecretion. The patients' blood pressure was normalized though MRA administration. METHODS: Genetic screening was performed through whole-exome sequencing (WES), and variants in PA-associated or in ion-channels of aldosterone-regulating genes were prioritized. Variants with population frequency < 0.01, predicted to alter protein structure and classified as likely pathogenic by in silico tools, were retained. RESULTS: Qualifying variants were identified in nine of the 21 patients screened. Seven patients were carriers of six potentially damaging variants in six genes associated with PA (KCNK9, KCNK5, ATP13A3, SLC26A2, CACNA1H, and CACNA1D). A novel variant in the KCNK9 gene (p.V221M) is reported. Our analysis revealed two variants in two novel susceptibility genes for aldosterone hypersecretion, namely, KCNK16 (p.P255H) and CACNA2D3 (p.V557I). CONCLUSION: WES revealed potentially damaging germline variants in genes participating in aldosterone synthesis/regulating pathways in 9/21 patients of our cohort. The variants identified might play a role in aldosterone hypersecretion under conditions of stress. The potential pathogenicity of these variants should be examined in future functional studies.

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

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

The functional status of incidentally discovered bilateral adrenal lesions.

OBJECTIVE: To investigate autonomous cortisol and aldosterone secretion and insulin resistance (IR) indices, in patients with incidentally discovered bilateral adrenal lesions (BA). PATIENTS: Thirty-six patients with BA, 113 patients with unilateral adrenal incidentalomas (UA) and 89 healthy subjects (C) with normal adrenal imaging. MEASUREMENTS: All participants underwent adrenal imaging, baseline biochemical and hormonal measurements and the following investigations on consecutive days: (i) A 2-h oral glucose tolerance test (OGTT) (75 g) with glucose and insulin measurements every 30 min. (ii) An adrenocorticotrophin (ACTH) stimulation test with intravenous (i.v.) bolus administration of 250 µg of ACTH (1-24) and measurement of serum cortisol and aldosterone before and after 30 and 60 min. (iii) A low-dose dexamethasone suppression test (LDDST) (0·5 mg of dexamethasone every 6-h for 2 days) with cortisol measurement 6 h after the last dexamethasone dose and (iv) A NaCl (0·9%) postdexamethasone saline infusion test (PD-SIT) (2 l of NaCl 0·9% iv in 4 h) following the LDDST, with aldosterone measurement at the end of the test. RESULTS: Cortisol and aldosterone cut-offs based on the mean + 2 SD values obtained from the C group following the LDDST and PD-SITs were calculated (34·11 nm and 74·83 pm, respectively). Based on the above cut-offs, autonomous cortisol and aldosterone secretion was found in 42·5 and 15·9% of patients with UA, and in 41·7 and 19·4% of patients with BA, respectively. In addition, 17·7% of patients with UA and 19·4% of patients with BA had concomitant autonomous cortisol and aldosterone secretion. Cortisol and aldosterone levels following the LDDST and PD-SIT were significantly higher in the BA compared to the UA group, respectively. Furthermore, patients with BA had more pronounced glucose levels and insulin resistance (IR) indices compared to patients with UA. CONCLUSIONS: Patients with BA have more pronounced autonomous cortisol and aldosterone secretion and glucose metabolism alterations than patients with UA. Further studies are needed to evaluate the potential long-term consequences of these findings.

The clinical significance of adrenal incidentalomas.

BACKGROUND: The term adrenal incidentaloma (AI) indicates an adrenal mass lesion > 1 cm in diameter discovered during testing for conditions unrelated to adrenal disease. The overall prevalence of these lesions ranges between 3% and 10%. Their incidence increases with age, and it is clinically important to identify AI associated with hormonal activity and/or malignant potential. DESIGN: A detailed Medline search of all English language articles related to AI was carried out, and the clinical implications related to their hormonal activity and malignant potential are discussed. RESULTS: The subclinical hypercortisolism observed in a significant percentage of patients with AI is associated with some of the detrimental effects of continuous autonomous cortisol secretion, including a higher prevalence of hypertension, dyslipidaemia, impaired glucose tolerance or type 2 diabetes mellitus and an increased risk for osteoporotic fractures. However, it remains to be proven whether treatment to reverse subtle glucocorticoid excess is beneficial. Clinically silent phaeochromocytomas and primary adrenal cancer are conditions associated with significantly high morbidity and mortality and require urgent treatment, while the prevalence and clinical significance of autonomous mineralocorticoid secretion are less clearly defined. Size and radiological features are the main predictors of malignant potential. CONCLUSIONS: Patients harbouring AI should be evaluated for the possibility of malignancy and/or subclinical hypercortisolism which is associated with cardiovascular risk and bone loss. However, in the absence of prospective controlled studies correlating biochemical activity with end-organ complications, the long-term consequences of AI remain uncertain and their management remains largely pragmatic.

Unravelling the Genetic Basis of Primary Aldosteronism.

Primary aldosteronism (PA), a condition characterized by autonomous aldosterone hypersecretion, constitutes the most common cause of secondary hypertension. Over the last decade, major breakthroughs have been made in the field of genetics underpinning PA. The advent and wide application of Next Generation Sequencing (NGS) technology led to the identification of several somatic and germline mutations associated with sporadic and familial forms of PA. Somatic mutations in ion-channel genes that participate in aldosterone biosynthesis, including KCNJ5, CACNA1D, ATP1A1, and ATP2B3, have been implicated in the development of aldosterone-producing adenomas (APAs). On the other hand, germline variants in CLCN2, KCNJ5, CACNA1H, and CACNA1D genes have been implicated in the pathogenesis of the familial forms of PA, FH-II, FH-III, and F-IV, as well as PA associated with seizures and neurological abnormalities. However, recent studies have shown that the prevalence of PA is higher than previously thought, indicating the need for an improvement of our diagnostic tools. Further research is required to recognize mild forms of PA and to investigate the underlying molecular mechanisms.

Transcriptomics, Epigenetics, and Metabolomics of Primary Aldosteronism.

INTRODUCTION: Primary aldosteronism (PA) is the most common cause of endocrine hypertension, mainly caused by aldosterone-producing adenomas or hyperplasia; understanding its pathophysiological background is important in order to provide ameliorative treatment strategies. Over the past several years, significant progress has been documented in this field, in particular in the clarification of the genetic and molecular mechanisms responsible for the pathogenesis of aldosterone-producing adenomas (APAs). METHODS: Systematic searches of the PubMed and Cochrane databases were performed for all human studies applying transcriptomic, epigenetic or metabolomic analyses to PA subjects. Studies involving serial analysis of gene expression and microarray, epigenetic studies with methylome analyses and micro-RNA expression profiles, and metabolomic studies focused on improving understanding of the regulation of autonomous aldosterone production in PA were all included. RESULTS: In this review we summarize the main findings in this area and analyze the interplay between primary aldosteronism and several signaling pathways with differential regulation of the RNA and protein expression of several factors involved in, among others, steroidogenesis, calcium signaling, and nuclear, membrane and G-coupled protein receptors. Distinct transcriptomic and metabolomic patterns are also presented herein, depending on the mutational status of APAs. In particular, two partially opposite transcriptional and steroidogenic profiles appear to distinguish APAs carrying a KCNJ5 mutation from all other APAs, which carry different mutations. CONCLUSIONS: These findings can substantially contribute to the development of personalized treatment in patients with PA.

Hyperparathyroidism in patients with overt and mild primary aldosteronism.

INTRODUCTION: Increased prevalence of hyperparathyroidism (HP) has been observed in primary aldosteronism (PA) patients. However, HP prevalence in milder forms of PA has not to date been evaluated. OBJECTIVES: The objectives of this study were to assess the prevalence of primary and secondary HP in overt and milder misdiagnosed cases of PA and to investigate the effect of treatment on parathormone (PTH) secretion. PATIENTS AND METHODS: Seventy PA patients with normal renal function were included prospectively. Specifically, patients with biochemically overt PA (increased basal aldosterone/renin ratio (ARR) and a positive diagnostic suppression test (DCVT)) and patients with mild PA (normal basal ARR and a positive DCVT) were analyzed. Mean blood pressure and mineral metabolism were evaluated at diagnosis and after treatment. RESULTS: Primary and secondary HP were found in 4.3% (3/70) and 51.4% (36/70) of patients, respectively, and biochemically overt and mild PA in 47.1% (33/70) and 52.9% (37/70) of patients, respectively. Sixty-three PA patients were followed up after treatment without receiving calcium or vitamin D. There was a decrease of mean blood pressure (p < 0.001), PTH (p < 0.001), and 24-h urinary calcium (p < 0.001), and an increase of serum potassium (p < 0.001) and calcium (p = 0.018) levels in secondary HP patients. There was no significant difference between biochemically overt and mild PA patients as concerned serum PTH, calcium, and 25-hydroxyvitamin-D levels either before or after treatment. Aldosterone levels before treatment were positively correlated with serum PTH levels. CONCLUSIONS: HP prevalence was high in both overt and mild PA patients, whereas the effect of treatment on serum and urinary calcium and PTH levels was similar in both groups.

Surgical treatment outcome of primary aldosteronism assessed using new modified diagnostic tests.

PURPOSE: Primary aldosteronism (PA) is the most frequent type of endocrine hypertension. In our previous studies, we introduced two modified diagnostic tests for PA, the post-dexamethasone saline infusion test (DSIT) and the overnight dexamethasone, captopril, and valsartan test (DCVT). In this study, we aimed to validate both tests in respect to the biochemical and clinical response of a cohort of hypertensive patients in pre- and post-surgical setting. METHODS: We retrospectively studied 41 hypertensive patients (16 males), with a median (IQR, range) age of 50 (16, 35-74) years and positive histology for adrenal adenoma. Preoperatively, all patients had a single adenoma on CT and a diagnosis of PA with either DSIT or DCVT. The defined daily dose (DDD) of hypertensive drugs was assessed pre- and postoperatively. DSIT or DCVT and basal ARR were reassessed postoperatively. RESULTS: Two of the 41 patients failed to suppress aldosterone post-surgery, leading to a post-adrenalectomy biochemical cure rate of 95%, while blood pressure was improved in 36 patients, leading to a clinical cure rate of 88% as assessed by the DDD methodology. CONCLUSIONS: The present study was a proof-of-concept process to validate two modified diagnostic tests for PA in clinical practice. These tests, used to diagnose a group of patients with PA, successfully assessed their biochemical cure post-adrenalectomy at rates similar to those reported in the literature.

Oncology and complications.

This collection of cases describes some unusual urological tumors and complications related to urological tumors and their treatment. Case 1: A case of uretero-arterial fistula in a patient with long-term ureteral stenting for ureteral oncological stricture and a second case associated to retroperitoneal fibrosis were described. Abdominal CT, pyelography, cystoscopy were useful to show the origin of the bleeding. Angiography is useful for confirming the diagnosis and for subsequent positioning of an endovascular prosthesis which represents a safe approach with reduced post-procedural complications. Case 2: A case of patient who suffered from interstitial pneumonitis during a cycle of intravesical BCG instillations for urothelial cancer. The patient was hospitalized for more than two weeks in a COVID ward for a suspected of COVID-19 pneumonia, but he did not show any evidence of SARS-CoV-2 infection during his hospital stay. Case 3: A case of a young man with a functional urinary bladder paraganglioma who was successfully managed with complete removal of the tumor, leaving the urinary bladder intact. Case 4: A case of a 61 year old male suffering from muscle invasive bladder cancer who was admitted for a radical cystectomy and on the eighth postoperative day developed microangiopathic hemolytic anemia and thrombocytopenia, which clinically defines thrombotic microangiopathy.