Endocrine Abstracts

Background: Adrenal crises (AC) still occur even in educated patients with adrenal insufficiency. Identifying predisposing factors can improve risk assessment and facilitate prevention in this patient population.

Objectives: Investigating clinical and biochemical fingerprints of increased susceptibility to AC.

Material and methods: Our study population included 71 patients with adrenal insufficiency, classified in high and low risk according to the frequency of experienced AC per patient-years. Besides classical clinical and biochemical data, following parameters were assessed: morning serum cortisol prior to as well as 60 and 120 min following the morning glucocorticoid replacement dose, 24h urinary cortisol, salivary cortisol day profile, hair cortisol, plasma and urinary catecholamines and polymorphisms (SNP) of the glucocorticoid- and mineralocorticoid receptor, HSD11B1 and HSD11B2 enzymes and FKBP5 co-chaperone.

Results: 52% of the patients were classified as having a high risk for AC. This group received higher glucocorticoid replacement doses (15.2 (4.2-26.4) vs. 11.5 (7-20) mg hydrocortisone-equivalent /m², P = 0.01) and had higher hair cortisol (0.05 (0.006-1.3) vs. 0.03 (0.004-0.3) pg/mg, P = 0.02) and higher plasma metanephrine (MN) levels (23 (6-110) vs 15 (3-59) ng/l, P = 0.04) compared to the low risk group. Hair cortisol and plasma MN concentrations significantly correlated with both glucocorticoid replacement dose and AC-frequency in the whole cohort. AC occured more often in carriers of the CC genotype for HSD11B1 SNP rs2235543 (CC vs TC+TT, 97% vs 3%, P = 0.02).

Conclusion: The higher glucocorticoid replacement dose seen in high risk patients fits to previous observations and most probably reflects dose adjustments to AC events but may also be regarded as an indicator of increased vulnerability. The higher doses correlate with accumulation of cortisol in the hair follicle. Higher metanephrine levels may be due to increased conversion of normetanephrine to metanephrine. The high risk for frequent AC associated with HSD11B1 SNP rs2235543 implies a certain genetic susceptibility.