Abstract
ObjectiveThis study aimed at comparing precursors of endogenous corticosteroid production in patients with primary adrenal insufficiency and in secondary adrenal insufficiency.DesignTwenty patients with primary adrenal insufficiency and matched controls and 19 patients with secondary adrenal insufficiency participated in this ancillary analysis of two different studies.Patients and measurementsPatients with primary adrenal insufficiency were on stable hydrocortisone and fludrocortisone therapy. Patients with secondary adrenal insufficiency received two different doses of hydrocortisone in a randomized crossover study. Main outcome measures were concentrations of precursors of cortisol and aldosterone measured by LC‐MS/MSResultsCompared to controls, progressively lower concentrations of the glucocorticoid precursors 11‐deoxycortisol, 11‐deoxycorticosterone and corticosterone concentrations were found in patients with secondary adrenal insufficiency on lower hydrocortisone dose, secondary adrenal insufficiency on higher hydrocortisone dose and primary adrenal insufficiency, respectively. Half of the primary adrenal insufficient patients showed evidence of residual endogenous cortisol or aldosterone synthesis, as determined by quantifiable 11‐deoxycortisol, 11‐deoxycorticosterone and corticosterone concentrations. In secondary adrenal insufficient patients with higher endogenous cortisol production, as indicated by 11‐deoxycortisol concentrations above the median, no increased cortisol exposure was observed both by plasma pharmacokinetic parameters and 24‐hour free cortisol excretion in urine.ConclusionsAdrenal corticosteroid production is likely to continue during treatment in a considerable percentage of patients with both primary and secondary adrenal insufficiency. In patients with secondary adrenal insufficiency, this synthesis appears to be sensitive to the dose of hydrocortisone. However, the residual corticosteroid concentrations were quantitatively low and its clinical significance remains therefore to be determined.
Highlights
Patients with primary adrenal insufficiency (PAI) due to autoimmune adrenalitis are thought to have no adrenal cortical function after long‐standing disease as a consequence of progressive destruction of the adrenal gland
This study demonstrates that adrenal cortisol production is likely to continue in almost all patients with secondary adrenal insufficiency (SAI)
Remarkable is that all patients had long‐standing disease on average 15‐20 years
Summary
Patients with primary adrenal insufficiency (PAI) due to autoimmune adrenalitis are thought to have no adrenal cortical function after long‐standing disease as a consequence of progressive destruction of the adrenal gland. This is difficult because the chemical composition of hydrocortisone tablets and endogenous cortisol is identical, and usually the strategy is chosen to temporarily withdraw hydrocortisone substitution This problem can be circumvented by using stable isotope dilution/mass spectrometry, but these techniques are difficult and only a few research centres are equipped to do such studies.[11,12] A candidate approach to determine residual endogenous cortisol or aldosterone production may be the measurement of precursors of these corticosteroids. To explore this option, we recently developed a LC‐MS/MS assay capable of measuring cortisol and cortisone in one run and several precursor corticosteroids including 11‐deoxycortisol (11S), 11‐deoxycorticosterone (11DOC) and corticosterone (B) concentrations. The aim of this study was to assess the applicability of these techniques in estimating the residual function of the adrenal cortex in patients with adrenal insufficiency
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