Association Between Aldosterone and Parathyroid Hormone Levels in Patients With Adrenocortical Tumors.

OBJECTIVE: Patients with primary aldosteronism (PA) can present with high PTH levels and negative calcium balance, with some studies speculating that aldosterone could directly stimulate PTH secretion. Either adrenalectomy or mineralocorticoid receptor blockers could reduce PTH levels in patients with PA. The aim of this study was to assess the relationship between aldosterone levels and parathyroid hormone (PTH)-vitamin D-calcium axis in a cohort of patients with PA, compared with patients with nonsecreting adrenocortical tumors in conditions of vitamin D sufficiency. METHODS: We enrolled a series of 243 patients retrospectively, of whom 66 had PA and 177 had nonsecreting adrenal tumors, and selected those with full mineral metabolism evaluation and 25(OH) vitamin D levels >20 ng/mL at the time of initial endocrine screening. The final cohort was composed of 26 patients with PA and 39 patients, used as controls, with nonsecreting adrenal tumors. The relationships between aldosterone, PTH levels, and biochemistries of mineral metabolism were assessed. RESULTS: Aldosterone was positively associated with PTH levels (r = 0.260, P < .05) in the whole cohort and in the PA cohort alone (r = 0.450; P = .02). In the multivariate analysis, both aldosterone concentrations and urinary calcium excretion were significantly related to PTH levels, with no effect of 25(OH) vitamin D or other parameters of bone metabolism. CONCLUSION: PTH level is associated with aldosterone, probably independent of 25(OH) vitamin D levels and urinary calcium. Whether aldosterone interacts directly with the parathyroid glands remains to be established.

Prevalence and Incidence of Atrial Fibrillation in a Large Cohort of Adrenal Incidentalomas: A Long-Term Study.

CONTEXT: Chronic glucocorticoids excess leads to morphological and functional cardiac alterations, a substrate for arrhythmias. Autonomous cortisol secretion (ACS) in adrenal incidentalomas is a model of chronic endogenous hypercortisolism. OBJECTIVE: To investigate prevalence and incidence of atrial fibrillation (AF) in a large cohort of patients with ACS. DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: Patients evaluated between 1990 and 2018 for adrenal incidentalomas (n = 632), without pheochromocytoma, primary aldosteronism, Cushing syndrome, congenital adrenal hyperplasia, and adrenal malignancy. Cortisol after 1-mg dexamethasone suppression test < or > 50 nmol/L defined nonsecreting tumors (NST) (n = 420) and ACS (n = 212), respectively. INTERVENTION: Assessment of AF at baseline (n = 632) and during a median follow-up of 7.7 years retrospectively (NST, n = 249; ACS, n = 108). Comparison with general population. MAIN OUTCOME MEASURE: Prevalence and incidence of AF. RESULTS: AF prevalence was higher in patients with ACS (8.5%) than NST (3.1%, P = 0.003) and the general population (1.7%; P < 0.001 vs ACS, P = 0.034 vs NST). The age-adjusted rate ratio to the general population was 1.0 for NST and 2.6 for ACS. AF was associated with ACS (odds ratio, 2.40; 95% confidence interval [CI], 1.07-5.39; P = 0.035). The proportion of patients with AF at last evaluation was higher in ACS (20.0%) than NST (11.9%; P = 0.026). ACS showed a higher risk of incident AF than NST (hazard ratio, 2.95; 95% CI, 1.27-6.86; P = 0.012), which was associated with post-dexamethasone cortisol (hazard ratio, 1.15; 95% CI, 1.07-1.24; P < 0.001), independently of known contributing factors. CONCLUSIONS: Patients with adrenal incidentalomas and ACS are at risk of AF. Electrocardiogram monitoring may be recommended during follow-up.

The Steroid Profile of Adrenal Incidentalomas: Subtyping Subjects With High Cardiovascular Risk.

CONTEXT: Steroid profiling by mass spectrometry has shown implications for diagnosis and subtyping of adrenal tumors. OBJECTIVES: To investigate steroid profiles and their cardiovascular correlates in a large cohort of patients with nonsecreting (NS) adrenal incidentalomas and autonomous cortisol secretion (ACS). DESIGN: Cohort study. SETTING: University hospital. PATIENTS: Patients (n = 302) with incidentally discovered adrenal masses, divided into unilateral adenoma and hyperplasia with ACS (n = 46 and n = 52, respectively) and NS (n = 120 and n = 84, respectively). Post-dexamethasone suppression test (DST) cortisol <50 or >50 nmol/L defined NS and ACS, respectively. INTERVENTION: Analysis of 10-steroid panel by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and clinical data (mean follow-up 39 months). MAIN OUTCOME MEASURES: Difference in baseline and post-DST steroid profiles between groups. Correlation with cardiovascular profile. RESULTS: Patients with unilateral adenomas and ACS showed higher cortisol, 11-deoxycortisol, and corticosterone and lower dehydroepiandrosterone than those with NS adenomas. Patients with ACS hyperplasia showed higher cortisol and lower androgens in women than those with NS. Patients with ACS had reduced suppression of post-DST cortisol, 11-deoxycortisol, and corticosterone, irrespective of adrenal morphology. Post-DST cortisol and corticosterone were associated with higher prevalence of severe/resistant hypertension. Patients with ACS unilateral adenomas showed higher incidence of worsening of hypertensive disease and novel cardiovascular events than those with NS, with post-DST cortisol [hazard ratio (HR) 1.02; 95% CI, 1.01 to 1.03; P < 0.001] and baseline corticosterone (HR 1.06; 95% CI, 1.01 to 1.12; P = 0.031) among the main predictors. CONCLUSIONS: Patients with adrenal incidentalomas showed different steroid profiles, depending on functional status and adrenal morphology, with implications for their cardiovascular status.

Sclerosing Angiomatoid Nodular Transformation of the Adrenal Gland: A Case Report of a Novel Histopathological Entity.

The finding of an indeterminate adrenal mass at radiological investigations is a challenge for physicians. Complex diagnostic work-up, periodic follow-up, or surgical intervention are therefore needed to rule out malignant lesions. Tertiary care hospitals are provided with 18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET) and 18F-dihydroxyphenylalanine (18F-DOPA) PET, which aid in the characterization of indeterminate adrenal masses. Nevertheless, the histopathological examination may be required to exclude malignancy or rare etiologies. A 54-year-old woman presented to our clinic 6 months after a cerebral hemorrhage. She was hypertensive and had recently discovered a left adrenal mass of 15 mm during an abdominal ultrasound. Contrast-enhanced CT, following adrenal protocol, revealed a 14-mm adrenal mass without characteristics suggestive of an adrenal adenoma. Tumor markers were negative. Functional tests excluded hormone hypersecretion. An 18F-DOPA PET was negative. An 18F-FDG PET showed mild uptake of both the adrenal glands, with a more circumscribed pattern in the left one (maximum standardized uptake value = 4). As the clinical diagnosis was still indeterminate, we performed laparoscopic left adrenalectomy. The histopathological examination described a sclerosing angiomatoid nodular transformation (SANT) of the adrenal gland, a benign lesion already described as a rare occurrence only in the spleen. IgG4 levels were reduced. In conclusion, this is a report of a SANT of the adrenal gland, a novel entity that should be taken into consideration in the differential diagnosis of indeterminate adrenal masses at CT scan.

Sacubitril/valsartan improves both functional and echocardiographic parameters in patients with chronic heart failure with reduced ejection fraction.

OBJECTIVE: We evaluated the clinical efficacy of sacubitril/valsartan in a group of ambulatory patients with heart failure (HF) with reduced ejection fraction (HFrEF) referred to our HF clinic. METHODS: Patients (n = 29; 72% males; mean age 76 years) with HFrEF in New York Heart Association (NYHA) classes II-III were included in the present study. We evaluated clinical as well as echocardiographic parameters (e.g. haemodynamics, such as blood pressure and heart rate, metabolic status, echocardiographic ventricular volumes and ejection fraction [EF]), at baseline and after 6 months of treatment with sacubitril/valsartan. RESULTS: After 6 months of sacubitril/valsartan treatment, several parameters were significantly improved. For example, EF and ventricular volumes (both diastolic and systolic) and atrial dimensions, as well as NYHA functional class (only 1 patient was still in NYHA class III) and renal impairment improved. There was no hospitalization for HF or other causes during the 6 month follow-up and no patient died. CONCLUSIONS: Based on our real-life experience, in HFrEF patients with NYHA class II-III, the new angiotensin receptor-neprilysin inhibitor (ARNi) sacubitril/valsartan was effective in improving HF management, both from the clinical and the echocardiographic perspective.

Effects of allopurinol and febuxostat on cardiovascular mortality in elderly heart failure patients.

Hyperuricemia is an emerging risk factor for the development of heart failure (HF) and is associated with a worsen prognosis of the disease. The effect of urate lowering drugs (ULT) and, in particular, the xanthine oxidase inhibitor in patients with HF is controversial. The aim of the study is to compare the effects of treatment with two different xanthine oxidase inhibitors (allopurinol or febuxostat) on cardiovascular mortality in elderly patients with chronic HF in a setting of clinical practice. In this observational trial, 255 elderly patients affected by chronic HF and treated with ULT on top of optimal medical treatment for HF. The sample included only outpatients with mild-to-moderate HF mainly secondary to chronic arterial hypertension or coronary artery disease and not previously hospitalized for HF. Patient treated with febuxostat (N. 120) and allopurinol (N. 135) were balanced for most of the baseline variables. In particular age, NYHA class distribution, drug treatment and renal function were comparable at the baseline and during the observation in both groups (p > 0.05). After a mean follow-up period of 5.1 years, the cumulative cardiovascular survival was 0.96 (95% CI 0.93-0.99) in febuxostat-treated patients and 0.89 (95% CI 0.84-0.93) in those treated with allopurinol. The between group difference, adjusted for the main confounding risk factors, was statistically significant (p = 0.04). Our study results suggest that possibility that febuxostat, a selective XO inhibitor, may favorably affect cardiovascular mortality in comparison with allopurinol in elderly patients with mild-to-moderate HF. This preliminary observation deserves further evaluation in the next future.

Morbidity and mortality in a population of patients affected by heart failure and chronic obstructive pulmonary disease: an observational study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) often coexist. Moreover, elderly patients suffering from HF have a higher incidence of COPD, which further complicates their clinical condition. Indacaterol/glycopirronium has shown benefits in the treatment of COPD, with few cardiologic adverse effects. We evaluated the safety and efficacy of this therapy in patients with history of HF. METHODS: We enrolled 56 patients with a history of HF (New York Heart Association [NYHA] classes II and III) and stable COPD. We evaluated blood samples, clinical assessment, echocardiograms and basal spirometry at baseline and after 6 months of therapy with indacaterol/glycopirronium. In addition, the number of re-hospitalizations during the treatment period was evaluated. RESULTS: The treatment was well tolerated. Brain natriuretic peptide (BNP) levels were significantly reduced compared with baseline (p < 0.001) after 6 months of treatment, and a higher percentage of patients improved their clinical status compared with baseline (p < 0.001). Minor changes were noted in the hemodynamic and metabolic parameters. Significant improvements in the echocardiographic parameters were noted in HF with reduced ejection fraction (HFrEF) patients. All respiratory parameters (forced expiratory volume in 1 s [FEV1], FEV1/forced vital capacity [FVC] ratio and COPD Assessment Test [CAT] scores) improved significantly (p < 0.001). No hospitalizations owing to HF or COPD exacerbation occurred. One patient died of respiratory failure. CONCLUSION: Indacaterol/glycopirronium was well-tolerated and effective in the treatment of COPD in this cohort of patients with a history of HF. Further studies are needed to clarify whether this compound can have a direct role in improving overall cardiovascular function.

Coexisting Heart Failure and Chronic Obstructive Pulmonary Disease: Report of Two Cases Treated with Indacaterol/Glycopyrronium.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide, and it is associated with a high economic burden. Heart failure shares some general symptoms with COPD; thus, diagnosing COPD is difficult in subjects with a history of heart failure, and spi-rometry is mandatory for confirmation. Moreover, COPD is a highly prevalent comorbidity negatively impacting the outcome of heart failure patients. We document here the treatment with indacaterol/glycopyrronium in 2 patients with concomitant COPD and heart failure. Overall, the combination of indacaterol and glycopyrronium resulted in a reciprocal potentiation with a maximal bronchodilatory effect.

Management of a Multicomorbid Patient with Heart Failure.

The optimal use of sacubitril/valsartan in clinical practice needs further investigation, in particular for patients with multiple comorbidities, as such patients are usually poorly represented in clinical trials. To this end, well-documented case reports may add further evidence to the bulk of "field practice" experience on sacubitril/valsartan. We report here the case of a patient with heart failure with reduced ejection refraction with multiple comorbidities treated with sacubitril/valsartan. Overall, sacubitril/valsartan led to a prompt (within a few months) improvement in LVEF (+15%, from 38 to 53%), without any noticeable adverse events. This therapy also allowed the patient to discontinue furosemide.

Effect of zofenopril and ramipril on cardiovascular mortality in patients with chronic heart failure.

A head-to-head evaluation of the effect of ramipril and zofenopril on the cardiovascular mortality rate of patients with chronic heart failure (HF) in the setting of clinical practice is not yet available. We prospectively enrolled 224 patients with all-cause HF, who were untreated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. These patients were then assigned to zofenopril 15 to 30 mg/day or ramipril 5 to 10 mg/day on the basis of a prospective, randomized, open, blinded, end point trial. The primary outcome of the trial was patient survival during the follow-up period. The groups were similar in a large number of clinical parameters. The mean follow-up of this cohort was 6.1 ± 1.2 years. Overall, during the follow-up period, we observed 45 deaths in the zofenopril-treated group and 48 in the ramipril-treated group (p = 0.251). Zofenopril and ramipril appears to be equivalent regarding the effects on cardiovascular mortality in the entire sample. Zofenopril was a significant predictor of better survival in patients who were the median age or older (odds ratio 0.56, 95% confidence interval 0.35 to 0.91), in men (odds ratio 0.57, 95% confidence interval 0.30 to 0.98), and in patients with a lower ejection fraction (odds ratio 0.52, 95% confidence interval 0.26 to 0.97). In conclusion, in the clinical practice setting, ramipril and zofenopril seem to have similar effects on cardiovascular mortality. However zofenopril might be more efficacious in elderly patients, male patients, and patients with a lower ejection fraction.