Assessment of the accuracy and reproducibility of adrenal volume measurements using MRI and its relationship with corticosteroid phenotype: a normal volunteer pilot study.

OBJECTIVE: The significant role of corticosteroids in hypertension and cardiovascular disease highlights the importance of the adrenal gland in these disorders. The ability to correlate corticosteroid production with adrenal volume offers a novel research tool and intermediate phenotype in cardiovascular disease. The aim of this study was to develop and validate the use of magnetic resonance imaging (MRI) in adrenal volume assessment and investigate whether this associates with corticosteroid production. DESIGN/METHODS: Twenty normotensive men underwent noncontrast 1·5T MRI scanning of adrenals, measurement of blood pressure and plasma corticosteroids. Left adrenal volume was calculated twice using standard segmentation software by four independent observers with differing levels of clinical expertise and segmentation experience. To optimize this process, adrenal 'phantoms' with known fixed volumes underwent MRI scanning and analysis by two observers. RESULTS: Intra-observer coefficients of repeatability (CoRs) in phantoms ranged from 0·23 to 0·43 ml (interobserver CoR 0·48 ml). In the subject group, mean adrenal volumes were 3·99-5·82 ml with intra-observer CoRs 0·27-1·94 ml. Interobserver variability was 2·73 ml. Segmentation expertise was the main factor affecting variability, with experienced observers having the lowest CoRs; clinical knowledge was a factor when combined with segmentation experience. Mean adrenal volume correlated with plasma glucocorticoids (r = 0·523, P < 0·05) and aldosterone (r = 0·515, P < 0·05) for the most experienced observer only. CONCLUSIONS: Measurement of adrenal volume using MRI is challenging; most accurate volumes are achieved using a single observer with both segmentation experience and anatomical knowledge. The data also provide novel preliminary evidence that adrenal gland volume may be associated with plasma corticosteroid concentrations supporting further study of adrenal volume and steroid production across a range of blood pressures.

Urinary sodium excretion is the main determinant of mineralocorticoid excretion rates in patients with chronic kidney disease.

BACKGROUND: Blockade of the mineralocorticoid receptor (MR) in patients with chronic kidney disease (CKD) improves surrogate cardiovascular outcomes, such as left ventricular mass. Animal models of renal disease support a pathological role of mineralocorticoids, in the context of a high sodium intake. We aimed to assess the regulation of mineralocorticoid biosynthesis in patients with CKD. METHODS: Seventy patients with CKD stages 3/4 and 30 patients with essential hypertension (EH) were recruited. Patients underwent detailed clinical phenotyping, drug history and biochemical assessment. Patients completed a 24-h urine collection for measurement of urinary tetrahydroaldosterone (THALDO) and tetrahydrocorticosterone (THDOC) excretion rates (measured using gas chromatography-mass spectrometry) and urinary electrolytes. The factors which correlated significantly with THALDO and THDOC excretion were entered into linear regression models. RESULTS: Patients with EH and CKD were well matched with no significant differences in gender, age or weight. The mean estimated glomerular filtration rate (eGFR) in CKD patients was 38.6/min/1.73 m(2). The mean urinary excretion rates of THALDO, THDOC and 24-h urinary sodium (24-h USod) were not significantly different between CKD and EH patients. The level of renal function did not correlate with THALDO or THDOC excretion. In patients with CKD, 24-h USodium (r = 0.614, P < 0.001) and 24-h UPotassium (r = 0.538, P < 0.001) were positively correlated with THALDO excretion. On multivariate linear regression analysis, 24-h USod was the strongest independent predictor (P = 0.004) of THALDO and THDOC excretion in CKD. In patients with EH, no relationship was seen between mineralocorticoid excretion and 24-h urinary sodium excretion. CONCLUSIONS: In patients with CKD, 24-h urinary sodium excretion is the strongest positive predictor of urinary mineralocorticoid excretion. The nature of this relationship is unexpected, novel, not seen in patients with EH and may explain the association seen between high urinary sodium excretion, mineralocorticoids and poor outcomes in patients with CKD.

Serum chloride is an independent predictor of mortality in hypertensive patients.

Chloride (Cl-) is the major extracellular anion in the body, accompanying sodium (Na+), and is primarily derived from dietary sources. Data suggest that increased dietary Cl- intake increases blood pressure, yet paradoxically, higher serum Cl- appears associated with lower mortality and cardiovascular risk. This implies that serum Cl- also reflects risk pathways independent of blood pressure, serum Na+, and bicarbonate (HCO3-). We analyzed 12,968 hypertensive individuals followed up for 35 years, using Cox proportional hazards model to test whether baseline serum Cl- was an independent predictor of mortality. To distinguish the effect of Cl- from Na+ and HCO3-, we adjusted for these electrolytes and also performed the analysis stratified by Na+ /HCO3- and Cl- levels. Generalized estimating equation was used to determine the effect of baseline Cl- on follow-up blood pressure. The total time at risk was 19,7101 person-years. The lowest quintile of serum Cl- (<100 mEq/L) was associated with a 20% higher mortality (all-cause, cardiovascular and noncardiovascular) compared with the remainder of the subjects. A 1 mEq/L increase in serum Cl- was associated with a 1.5% (hazard ratio, 0.985; 95% confidence interval, 0.98-0.99) reduction in all-cause mortality, after adjustment for baseline confounding variables and Na+, K+ , and HCO3- levels. The group with Na+ > 135 and Cl- > 100 had the best survival, and compared with this group, the Na+ >135 and Cl- <100 group had significantly higher mortality (hazard ratio, 1.21; 95% confidence interval, 1.11-1.31). Low, not high Serum Cl- (<100 mEq/L), is associated with greater mortality risk independent of obvious confounders. Further studies are needed to elucidate the relation between Cl- and risk.