Characterization of Cortisol Secretion Rate in Secondary Adrenal Insufficiency

In secondary adrenal insufficiency (SAI), chronic deficiency of adrenocorticotropin (ACTH) is believed to result in secondary changes in adrenocortical function, causing an altered dose-response relationship between ACTH concentration and cortisol secretion rate (CSR).

We sought to characterize maximal cortisol secretion rate (CSR_max) and free cortisol half-life in patients with SAI, compare results with those of age-matched healthy controls, and examine the influence of predictor variables on ACTH-stimulated cortisol concentrations.

CSR_max was estimated from ACTH_1-24 (250 μg)_-stimulated cortisol time-concentration data. Estimates for CSR_max and free cortisol half-life were obtained for both dexamethasone (DEX) and placebo pretreatment conditions for all subjects.

Single academic medical center.

Patients with SAI (n = 10) compared with age-matched healthy controls (n = 21).

The order of DEX vs placebo pretreatment was randomized and double-blind. Cortisol concentrations were obtained at baseline and at intervals for 120 minutes after ACTH_1-24.

CSR_max and free cortisol half-life were obtained by numerical modeling analysis. Predictors of stimulated cortisol concentrations were evaluated using a multivariate model.

CSR_max was significantly (P < 0.001) reduced in patients with SAI compared with controls for both placebo (0.17 ± 0.09 vs 0.46 ± 0.14 nM/s) and DEX (0.18 ± 0.13 vs 0.43 ± 0.13 nM/s) conditions. Significant predictors of ACTH_1-24-stimulated total cortisol concentrations included CSR_max, free cortisol half-life, and baseline total cortisol, corticosteroid-binding globulin, and albumin concentrations (all P < 0.05).

Our finding of significantly decreased CSR_max confirms that SAI is associated with alterations in the CSR-ACTH dose-response curve. Decreased CSR_max contributes importantly to the laboratory diagnosis of SAI.