Background: Current dogma states that in autoimmune Addisons disease (AAD), all adrenocortical function eventually is lost. Yet growing evidence suggests that a subgroup of patients retain some self-production.
Aim: To explore whether residual production of adrenocortical steroids is present in a subgroup of AAD patients.
Material and methods: In an open non-randomized cross-sectional study, an interim of 22 AAD patients delivered a medication-fasting morning blood sample for analysis of adrenocortical steroids by the highly sensitive and specific liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Before sampling, patients abstained from cortisone acetate or hydrocortisone and fludrocortisone for at least 18 and 24 hours, respectively. Residual function was defined as morning serum cortisol (s-cortisol) and/ and or aldosterone (s-aldosterone) above their corresponding lower limit of quantification (LLOQ). Dehydroepiandrosterone (DHEA) and corticosteroid precursors were also measured.
Results: Twenty-two patients (8 males, 14 females) aged 49.7 (±14.3) years with verified autoimmune adrenal insufficiency were included. Mean disease duration was 18.1 (±13.9) years. Twelve of 22 (54%) patients had morning s-cortisol exceeding the LLOQ of 0.91 nmol/l. Median s-cortisol was low (3.19 nmol/l [0.92339.6]), but three patients presented with s-cortisol 71, 204 and 339 nmol/l. They had disease durations of 44, 5, and 5 years, respectively. There was no significant correlation between measurable s-cortisol and age (P<0.899), sex (P<0.254) or disease duration (P<0.350). S-aldosterone surpassed the LLOQ of 2.3 pmol/l in three patients (3, 14 and 217 pmol/l, respectively) in which all had detectable s-cortisol as well. Seven patients (32%) had measurable levels of DHEA (median 0.86 nmol/l [0.651.65]). Corticosteroid precursors were detected in 5 patients (23%) for 11-deoxycorticosterone (median 0.11 nmol/l [0.030.92]), 5 (23%) for 18-hydroxycorticosterone (median 0.25 nmol/l [0.073.40]), 5 (23%) for corticosterone (median 4.00 nmol/l [0.1750.84]), and 4 (18%) for 11-deoxycortisol (median 1.96 nmol/l [0-182.15]). All precursors were present in the three patients with the highest fasting s-cortisol. In seven patients (33%) with measurable s-cortisol less than 3.5 nmol/L, none of the precursors were detected.
Conclusion: More than half of the patients had detectable levels of adrenal steroid hormones even years after the diagnosis; three had clinically significant levels of cortisol as well as detectable precursors. Patients with preserved steroid producing-capacity could be candidates for therapy aimed at regenerating and restoring adrenocortical function.
18 - 21 May 2019
European Society of Endocrinology