Study Examines Natural History of Autoimmune Addison Disease

adrenal glands
Kidney and adrenal glands highlighted inside human body, computer illustration.
In patients with autoimmune Addison disease, there is a rapid decline in steroidogenic capacity once replacement glucocorticoid medication is started.

In patients with newly diagnosed autoimmune Addison disease, there is a rapid decline in steroidogenic capacity once replacement glucocorticoid medication is started, according to study results published in The Journal of Clinical Endocrinology & Metabolism. In a sizeable minority of patients with established Addison disease, however, there is evidence of residual adrenal function.

The goal of the current study was to report the early natural history of autoimmune Addison disease during the first few weeks of treatment and assess the prevalence of residual adrenal steroidogenesis in these patients. The researchers completed measurements of adrenocorticotropic hormone (ACTH)1-24-stimulated serum cortisol, as well as comprehensive urine steroid metabolite profiling by tandem mass spectrometry.

The study included 20 newly presenting patients with autoimmune Addison disease (aged 17-64 years; 13 female). In 19 patients, there was a significant decrease in serum cortisol over the first few weeks of hydrocortisone treatment, from a median of 125 nmol/L (range, <23-257 nmol/L) to 39.5 nmol/L (range, <23-265 nmol/L; P <.007). These findings indicated that serum cortisol concentrations drop rapidly within 4 weeks after diagnosis and treatment of autoimmune Addison disease.

The study also included 37 patients (aged 17-75 years; 26 female) with established autoimmune Addison disease treated for >6 months prior to study participation. After written informed consent was obtained, patients omitted their regular glucocorticoid and mineralocorticoid medication over a 24-hour period, leading to a 36- to 40-hour medication-free window. The researchers did not report any adverse events during steroid withdrawal. On the evening of the steroid-free day, the participants were started on overnight urine collection for analysis of the steroid metabolome. The following morning, they had blood taken for plasma ACTH and serum steroid hormone measurement, as well as a short synacthen test using 250 µg of ACTH1-24 and repeat cortisol measurements at 30 and 60 minutes.

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In 6 of 37 patients (16.7%), there was some evidence of residual adrenal function with detectable serum cortisol and urine glucocorticoid and mineralocorticoid metabolites. In these 6 patients, peak serum cortisol was clearly above the 20 nmol/L threshold for detection, whereas in the remaining 31 patients, serum cortisol was <30 nmol/L throughout. Analysis of the steroid metabolome in the overnight urine collection showed that individuals with detectable serum cortisol also had secretion of several other glucocorticoid and mineralocorticoids. At least 1 other participant had clearly detectable urine steroid metabolites despite the absence of a significant serum cortisol response.

“These observations should help plan future intervention studies that could target specifically patients with residual adrenal function to ameliorate this chronic condition,” concluded the researchers. They noted that their results may have been limited by the relatively small sample and assessment of patients at only a single time point.

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Napier C, Allinson K, Gan EH, et al. Natural history of adrenal steroidogenesis in autoimmune Addison’s disease following diagnosis and treatment [published online April 17, 2020]. J Clin Endocrinol Metab. doi:10.1210/clinem/dgaa187