Studies on cortisol deficiency with focus on biochemical and clinical characteristics and self-management

Background: Autoimmune Addison's disease (AAD) develops gradually with vague symptoms, which contributes to delayed diagnosis. However, systematic investigations of the clinical presentation are scare. Early detection could help prevent adrenal crisis (AC). The course of AAD has been considered irreversible, but case reports suggest that some patients retain corticosteroid production. Whether residual adrenocortical function (RAF) in patients with AAD is of importance for adrenomedullary function is not known. In adrenal insufficiency (AI) replacement therapy with glucocorticoids (GCs), requires ability to self-management, and patient education. However, few studies have evaluated GC education group meetings regarding its effectiveness and even fewer have involved relatives.

Aim: Study I, to characterize changes in routine blood tests, and clinical signs of undiagnosed AAD. Study II, to evaluate RAF and potential clinical implications in patients with AAD. Study III, to investigate any influence of RAF on adrenomedullary function. Study IV, to assess the perceived safety and level of knowledge regarding appropriate GC dose adjustments in patients with AI and their relatives. Design: I retrospective multicenter study. II, III a two-staged cross-sectional clinical multicenter study. IV an observational, multicenter study.

Results: At time of AAD diagnosis, hyponatremia was present in 84% of patients, hyperkalemia in one-third, 52 % had an elevated TSH level. RAF was observed in 30.2% of patients with AAD, more common in men and patients with shorter disease duration. Among 70 patients with AAD, metanephrine (MN) was detectable in 33% and positively correlated to the level of cortisol. After the GC education group meeting, significant improvements were observed in safety, knowledge of GC dose adjustments and correct actions in high-risk situations of developing AC. Unexplained hyponatremia and/or elevated TSH should raise suspicion of AAD. One-third of patients with AAD retain RAF even years after diagnosis, with small amounts of endogenous cortisol affecting MN levels. Perceived safety in self-management and GC dose adjustments improved in patients with AAD and their relatives following GC education group meeting.

List of scientific papers

I. Sævik Å.B*, Åkerman A-K*, Grønning K, Nermoen I, Valland S.F, Finnes T.E, Isaksson M, Dahlqvist P, Bergthorsdottir R, Ekwall O, Skov J, Nedrebø B.G, Hulting A-L, Svartberg J, Hoybye C, Bleskestad I.H, Jørgensen A.P, Kämpe O, Øksnes M, Bensing S, Husebye E.S. Clues to detect undiagnosed autoimmune Addison's disease - myths and realities J Intern Med 2017 Nov 283 (2): 190-199. * Equally contributed to the paper https://doi.org/10.1111/joim.12699

II. Sævik Å.B, Åkerman A-K, Methlie P, Quinkler M, Palmstrøm Jørgensen A, Höybye C, Debowska A.J, Nedrebø B.G, Dahle A.L, Carlsen S, Tomkowicz A. Sollid S.T, Nermoen I, Grønning K, Dahlqvist P, Grimnes G, Skov J, Finnes T, Valland S.F, Wahlberg J, Emblem Holte S, Simunkova K, Kampe O, Husebye E.S, Bensing S, Øksnes M. Residual corticosteroid production in autoimmune Addisons's disease J Clin Endocrinol Metab. 2020 July 105 (7):2430-2441. https://doi.org/10.1210/clinem/dgaa256

III. Åkerman A-K, Sævik Å.B, Medbøe Thorsby P, Methlie P, Quinkler M, Palmstrøm Jørgensen A.P, Höybye C, Debowska A.J, Nedrebø B.G, Dahle A.L, Carlsen S, Tomkowicz A. Sollid S.T, Nermoen I, Grønning K, Dahlqvist P, Grimnes G, Skov J, Finnes T, Wahlberg J, Emblem Holte S, Simunkova K, Kämpe O, Husebye E.S, Øksnes M, Bensing S. Plasma-metanephrines in patients with autoimmune Addison's disease with and without residual adrenocortical function J Clin Med 2023 May 12 (10):3602. https://doi.org/10.3390/jcm12103602

IV. Åkerman A-K, Höybye C, Berinder K, Wahlberg J, Petersson M, Dahlqvist P, Bensing S. Self-management and quality of life in Swedish patients with adrenal insufficiency, and their relatives. [Manuscript]