Study Examines Steroidogenic Function in Autoimmune Addison Disease

Among a small cohort of patients with newly diagnosed autoimmune Addison disease, there is a rapid decline in steroidogenic capacity once replacement glucocorticoid medication is started. In a sizeable minority of patients with established Addison disease, however, there is evidence of residual adrenal function. The findings were published online in The Journal of Clinical Endocrinology & Metabolism.

The researchers measured ACTH_1-24-stimulated serum cortisol in all patients and carried out 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 women). In 19 patients, there was a substantial 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). The researchers noted that the findings indicated that serum cortisol concentration drops rapidly within 4 weeks following diagnosis and treatment.
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The study also included 37 patients (aged 17-75 years, 26 women) with established autoimmune Addison disease treated for >6 months prior to study enrollment. After written, informed consent was obtained, patients omitted their regular glucocorticoid and mineralocorticoid medication for a 24-hour period, leading to a 36- to 40-hour medication-free window. There were no adverse events reported during steroid withdrawal. On the evening of the steroid-free day, the participants were started on overnight urine collection for analysis of the serum steroid hormone measurement. The following morning, they had blood taken for plasma ACTH and serum steroid hormone measurement, and a short synacthen test using 250 μg ACTH_1-24-, with repeat cortisol measurements at 30 and 60 minutes.

Variable degrees of residual adrenal function in 6 of 37 patients (16.7%) with detectable serum cortisol glucocorticoid and mineralocorticoid metabolites were found. In these patients, peak serum cortisol was above the 20 nmol/L threshold for detection, whereas the remaining 31 patients showed serum cortisol <30 nmol/L throughout. Analysis of the steroid metabolome in the overnight urine collection showed that patients with detectable serum cortisol also had secretion of several other glucocorticoid and mineralocorticoids.

“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.

—Eileen Koutnik-Fotopoulos

Reference

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