Primary vs secondary adrenal insufficiency: ACTH-stimulated aldosterone diagnostic cut-off values by tandem mass spectrometry

• Published in: Clinical endocrinology (Oxford) 2015-09, Vol.83 (3), p.308-314
• Main Authors: Abraham, Smita Baid, Abel, Brent S., Sinaii, Ninet, Saverino, Elizabeth, Wade, Matthew, Nieman, Lynnette K.
• Format: Article
• Language: English
• Subjects: Adrenal Insufficiency - blood; Adrenal Insufficiency - diagnosis; Adrenal Insufficiency - urine; Adrenocorticotropic Hormone - administration & dosage; Adrenocorticotropic Hormone - blood; Adult; Aldosterone - blood; Cosyntropin - administration & dosage; Cosyntropin - blood; Cross-Sectional Studies; Female; Humans; Hydrocortisone - blood; Male; Middle Aged; Pituitary-Adrenal Function Tests - methods; Reference Values; Renin - blood; Reproducibility of Results; Sensitivity and Specificity; Sodium - urine; Tandem Mass Spectrometry - methods
• ISSN: 0300-0664; 1365-2265
• DOI: 10.1111/cen.12726

Summary Objectives To validate the diagnostic utility of Cortrosyn™ stimulated aldosterone in the differentiation of primary (PAI) and secondary adrenal insufficiency (SAI) and to evaluate the effect of urine sodium levels and posture on test performance. Design Cross‐sectional study. Methods Healthy volunteers (HV; n = 46) and patients with PAI (n = 26) and SAI (n = 29) participated in the study. Testing included cortisol and aldosterone (by liquid‐chromatography tandem mass spectrometry) measurements at baseline and 30 and 60 min after 250 μg Cortrosyn™. Plasma corticotropin (ACTH), renin activity (PRA) and urine spot sodium as a proxy for 24‐h urine sodium excretion were measured at baseline. The effect of a sitting or semifowlers posture was evaluated in healthy volunteers. Results A Cortrosyn™‐stimulated aldosterone level of 5 ng/dl (0·14 nmol/l) had 88% sensitivity and positive predictive value and 89·7% specificity and negative predictive value for distinguishing PAI from SAI. Spot urine sodium levels showed a strong correlation with peak aldosterone levels (r = −0·55, P = 0·02, n = 18) in the SAI but not PAI or HV groups. Posture did not have a significant effect on results. Conclusions Once diagnosed with adrenal insufficiency, a stimulated aldosterone value of 5 ng/dl (0·14 nmol/l) works well to differentiate PAI from SAI. However, clinicians should be aware of the possible effect of total body sodium as reflected by spot urine sodium levels on aldosterone results. A 24‐h urine sodium measurement may be helpful in interpretation.