ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 P431 | DOI: 10.1530/endoabs.63.P431

Residual adrenocortical function in autoimmune addison's disease: interim results of a cross-sectional study

Æse Bjorvatn Sævik1,2, Anna-Karin Ækermann3,4, Paal Methlie1,2,5, Nedrebø Bjørn Gunnar1,6, Anne Lise Dahle6, Siri Carlsen7, Aneta Tomkowicz8, Synnøve Emblem Holte9, Aleksandra Debowska10, Stina Therese Sollid11, Anders Jørgensen12, Ingrid Nermone13, Kaja Grønning13, Trine Finnes14, Guri Grimnes15,16, Charlotte Höybye17,4, Jakob Skov17, Per Dahlqvist18, Jeanette Wahlberg19, Magnus Isaksson20, Marcus Quinkler21, Sophie Bensing4,17, Marianne Øksnes1,2,5 & Eystein Husebye1,2,5

1Department of Clinical Science, University of Bergen, Bergen, Norway; 2K.G. Jebsen Center for Autoimmune Disorders, University of Bergen, Bergen, Norway; 3Department of Medicine, Örebro University Hospital, Örebro, Sweden; 4Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; 5Department of Medicine, Haukeland University Hospital, Bergen, Norway; 6Department of Internal Medicine, Haugesund Hospital, Haugesund, Norway; 7Department of Endocrinology, Stavanger University Hospital, Stavanger, Norway; 8Department of Medicine, Sørlandet Hospital Kristianand, Kristiansand, Norway; 9Department of Medicine, Sørlandet Hospital Arendal, Arendal, Norway; 10Department of Medicine, Vestfold Hospital Trust, Tønsberg, Norway; 11Department of Medicine, Vestre Viken Hospital, Drammen, Norway; 12Department of Endocrinology, Oslo University Hospital, Oslo, Norway; 13Division of Medicine, Akershus University Hospital, Lørenskog, Norway; 14Division of Endocrinology, Innlandet Hospital Trust, Hamar, Norway; 15Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway; 16Tromsø Endocrine Research Group, Department of Clinical Medicine, UiT the Arctic University of Norway, Tromsø, Norway; 17Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden; 18Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden; 19Department of Endocrinology, Department of Medical and Health Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Norway; 20Department of Medical Sciences, Uppsala University, Uppsala, Sweden; 21Endocrinology in Charlottenburg, Berlin, Germany.

Background: Current dogma states that in autoimmune Addison’s 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 [0.92–339.6]), 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 [0.65–1.65]). Corticosteroid precursors were detected in 5 patients (23%) for 11-deoxycorticosterone (median 0.11 nmol/l [0.03–0.92]), 5 (23%) for 18-hydroxycorticosterone (median 0.25 nmol/l [0.07–3.40]), 5 (23%) for corticosterone (median 4.00 nmol/l [0.17–50.84]), and 4 (18%) for 11-deoxycortisol (median 1.96 nmol/l [0-18–2.15]). 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.

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