Measurements of Serum DHEA and DHEA Sulphate Levels Improve the Accuracy of the Low-Dose Cosyntropin Test in the Diagnosis of Central Adrenal Insufficiency

Abstract

The diagnosis of central adrenal insufficiency (AI) continues to be challenging, especially when it is partial. We have recently demonstrated the value of measuring serum dehydroepiandrosterone sulfate (DHEA-S) in establishing the diagnosis of central AI. The current investigation examined the added value of measuring serum dehydroepiandrosterone (DHEA) levels during low-dose (1 μg) cosyntropin (LDC) stimulation in patients suspected to have central AI. Baseline and LDC-stimulated cortisol, DHEA, and DHEA-S were measured preoperatively in 155 consecutive patients with pituitary masses and 63 healthy subjects. Hypothalamic-pituitary adrenal (HPA) function was normal (NL-HPA) in 97 of the patients and was impaired (impaired HPA) in 58 patients. Patients with NL-HPA underwent surgical removal of the sellar masses and received no glucocorticoids before, during, or after surgery. Baseline and LDC-stimulated serum cortisol, DHEA, and DHEA-S in patients with NL-HPA were similar to those of normal subjects. In contrast, patients with impaired HPA had lower baseline and LDC-stimulated serum cortisol, DHEA, and DHEA-S levels. There were 18 subjects in the latter group whose LDC-stimulated serum cortisol levels were greater than 18.0 μg/dl. In those 18 subjects, baseline and LDC-stimulated DHEA and DHEA-S levels were similar to the whole group of patients with impaired HPA function. The molar ratio of cortisol to DHEA did not change with LDC stimulation in normal subjects and those with NL-HPA. In contrast, patients with impaired HPA had a higher baseline cortisol to DHEA molar ratio that increased further with LDC stimulation. Patients with impaired HPA function have a more severe loss in DHEA secretion than that of glucocorticoids. Measurements of serum DHEA levels during LDC simulation provide additional valuable information that improves the diagnostic accuracy of LDC in patients suspected to have central AI. We recommend the inclusion of DHEA and DHEA-S measurements in the laboratory assessment of HPA function.