title: Primary vs secondary adrenal insufficiency: ACTH-stimulated aldosterone diagnostic cut-off values by tandem mass spectrometry.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: The Program in Reproductive and Adult Endocrinology, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Smita Baid
authors.initials: SB
authors.lastname: Abraham
authors.affiliation: The Program in Reproductive and Adult Endocrinology, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Brent S
authors.initials: BS
authors.lastname: Abel
authors.affiliation: Biostatistics and Clinical Epidemiology Service, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Ninet
authors.initials: N
authors.lastname: Sinaii
authors.affiliation: The Program in Reproductive and Adult Endocrinology, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Saverino
authors.affiliation: The Program in Reproductive and Adult Endocrinology, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Wade
authors.affiliation: The Program in Reproductive and Adult Endocrinology, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Lynnette K
authors.initials: LK
authors.lastname: Nieman
mesh_terms: D000309:Adrenal Insufficiency / Q000097:blood* / Q000175:diagnosis / Q000652:urine; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000097:blood*; D000328:Adult; D000450:Aldosterone / Q000097:blood; D003366:Cosyntropin / Q000008:administration & dosage / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D010912:Pituitary-Adrenal Function Tests / Q000379:methods*; D012016:Reference Values; D012083:Renin / Q000097:blood; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012964:Sodium / Q000652:urine; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D003366:Cosyntropin; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D012964:Sodium; D012083:Renin; D006854:Hydrocortisone