cortodoxone and Cardiovascular-Diseases

Steroid profiling by mass spectrometry has shown implications for diagnosis and subtyping of adrenal tumors.. To investigate steroid profiles and their cardiovascular correlates in a large cohort of patients with nonsecreting (NS) adrenal incidentalomas and autonomous cortisol secretion (ACS).. Cohort study.. University hospital.. 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.. Analysis of 10-steroid panel by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and clinical data (mean follow-up 39 months).. Difference in baseline and post-DST steroid profiles between groups. Correlation with cardiovascular profile.. 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.. Patients with adrenal incidentalomas showed different steroid profiles, depending on functional status and adrenal morphology, with implications for their cardiovascular status.

Topics: Adrenal Gland Neoplasms; Aged; Cardiovascular Diseases; Chromatography, Liquid; Corticosterone; Cortodoxone; Dehydroepiandrosterone; Female; Humans; Hydrocortisone; Male; Middle Aged; Risk Factors; Tandem Mass Spectrometry

Based on the concept of glucocorticoid-receptor induction of angiotensin-converting enzyme (ACE), approaches to inhibiting enzyme induction with drugs that suppress the function of type II cytoplasmic glucocorticoid receptors, (genuine glucocorticoid receptors), are suggested. Three types of inhibiting the function of type II glucocorticoid receptors by drugs were distinguished. Type I is characterized by competition of the drugs with natural and synthetic glucocorticoids for interaction with glucocorticoid receptors (cortexolone, progesterone); type II is determined by irreversible inactivation of type II glucocorticoid receptors (aminazine, tisercin); type III is related to an increase of interaction of transcorticoid receptors with natural glucocorticoids which is accompanied by a reduction of the interaction of natural glucocorticoids with genuine glucocorticoid receptors (analgin, amidopyrine). It has been established that the drugs that provoke irreversible inactivation of the function of type II glucocorticoid receptors decrease ACE activity in blood plasma and in the lungs, that may serve the main reason for their high hypotensive effect in arterial hypertension. A concept is advanced, providing evidence for the use of the classical ACE inhibitors and of type II glucocorticoid receptor inhibitors.

Topics: Aminopyrine; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Chlorpromazine; Cortodoxone; Dipyrone; Glucocorticoids; Humans; Hypertension; Methotrimeprazine; Peptidyl-Dipeptidase A; Progesterone; Receptors, Glucocorticoid