Abstract
Patients with chronic primary adrenal insufficiency (PAI) depend on lifelong replacement therapy with gluco- (GC) and mineralocorticoids (MC). Monitoring is based on clinical parameters assessing hemodynamic stability, electrolyte status and plasma renin concentration (PRC). Reduced subjective well-being is however often described by these patients in absence of objectifiable abnormalities, thus suggesting a gap between the concept of adequate hormone substitution and physiological requirements. This study investigated the potential role of 23Na-MRI for noninvasive assessment of sodium status in PAI. Tissue sodium was initially analyzed both in the calf muscle and in the skin of 16 patients with chronic PAI and 16 sex-, age- and BMI-matched controls. Patients were classified into 3 groups (optimal/subtherapeutic/supraphysiological) according to the quality of GC and MC substitution assessed separately by clinical scores based on subjective wellbeing and clinical/laboratory parameters. We additionally performed a longitudinal analysis in 8 patients with newly diagnosed PAI. Muscle and skin sodium content (Muscle-SC, Skin-SC) were determined using a 23NA-MRI protocol on a 3T scanner implementing a 3D sequence. A vial with 100mmol/L of sodium was scanned with every participant. Tissue sodium is presented as the ratio of tissue sodium signal intensity to sodium signal intensity of the reference vial. Muscle-SC was significantly higher in patients with chronic PAI compared to controls (19.1 vs. 16.0, p<0.05), whereas Skin-SC was similar between the two groups (16.1 vs. 17.1). These results were replicated in the subgroups classified as receiving optimal GC and MC replacement, respectively. Skin-SC was significantly correlated with 24h-urine sodium level in the whole cohort. When comparing Muscle-SC and Skin-SC with obtained clinical scores a trend from lower SC for low scores to higher SC for higher scores was observed. The longitudinal analysis of 8 patients with newly diagnosed PAI revealed that Skin-SC was significantly lower at primary diagnosis compared to sex-, age- and BMI-matched controls (12.1 vs. 15.8, p=0.05), whereas the difference in Muscle-SC was less pronounced (14 vs. 16.1, p=0.18). A significant increase in both Muscle- and Skin-SC at follow-up compared to first diagnosis was detected (19.4 vs. 14, p<0.05 and 19.3 vs. 12.1, p<0.05), consistent with a significant decrease in PRC (200 vs. 31.2 ng/l, p<0.05). Interestingly, patients with chronic PAI under replacement therapy exhibited significantly higher Muscle-SC compared to controls. The agreement between tissue SC and clinical scores as well as the significant increase in tissue SC under replacement therapy in newly diagnosed patients indicate that 23Na-MRI might be a quantitative method to assess steroid replacement. Further studies on a larger cohort are, however, needed to prove these initial findings.
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