Renal clearance and daily excretion of cortisol and adrenal androgens in patients with rheumatoid arthritis and systemic lupus erythematosus

Abstract

Background: In rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), patients demonstrate low levels of adrenal hormones.

Objective: To investigate whether increased renal clearance and daily excretion contribute to this phenomenon.

Methods: Thirty patients with RA, 32 with SLE, and 54 healthy subjects (HS) participated. Serum and urinary levels of cortisol, cortisone, 17-hydroxyprogesterone (17OHP), androstenedione, dehydroepiandrosterone (DHEA), and DHEA sulphate (DHEAS) were measured.

Results: Clearance of DHEAS and DHEA was lower in patients than in HS, and clearance of androstenedione was somewhat higher in patients than in HS, but daily excretion of this latter hormone was low. Clearance of cortisol, cortisone, and 17OHP was similar between the groups. The total molar amount per hour of excreted DHEA, DHEAS, and androstenedione was lower in patients than HS (but similar for cortisol). Serum DHEAS levels correlated with urinary DHEAS levels in HS and patients, whereby HS excreted 5-10 times more of this hormone than excreted by patients. Low serum levels of adrenal androgens and cortisol in patients as compared with HS were confirmed, and proteinuria was not associated with changes of measured renal parameters.

Conclusions: This study in patients with RA and SLE demonstrates that low serum levels of adrenal androgens and cortisol are not due to increased renal clearance and daily loss of these hormones. Decreased adrenal production or increased conversion or conjugation to downstream hormones are the most likely causes of inadequately low serum levels of adrenal hormones in RA and SLE.

Figure 1

Cascades of adrenal steroidogenesis. A line with an arrow at the end indicates that the respective mediator stimulates the enzyme step (ACTH, IL6), a line with a bar at the end demonstrates that the respective mediator inhibits the enzyme step (IL1, TNF, TGFß). Enzymes and abbreviations: 1, P450scc = side chain cleavage enzyme; 2, 3ß-hydroxysteroid dehydrogenase; 3, P450c21 = 21α-hydroxylase; 4, P450c11 = 11ß-hydroxylase; 5 and 6, P450c17 = 17α-hydroxylase and 17/20-lyase (double enzyme step); 7, DHEA sulphotransferase and DHEAS sulphatase; 8, 11ß-hydroxysteroid dehydrogenase types I and II; 9, aromatase complex; ACTH, adrenocorticotrophic hormone; DHEA, dehydroepiandrosterone; DHEAS, DHEA sulphate; IL1, interleukin 1; IL6, interleukin 6; TGFß, transforming growth factor ß1; TNF, tumour necrosis factor.

Figure 2

Serum hormone concentration of adrenal steroid hormones. (A-C) Data of patients with RA; (D-F) results of patients with SLE. Data are given as means (SEM). *p<0.05; †p<0.005; ‡p<0.001 for the comparison of the respective group with HS. CSN, cortisone; DHEAS, DHEA sulphate; 17OHP, 17-hydroxyprogesterone; ASD, androstenedione; DHEA, dehydroepiandrosterone.

Figure 3

Urinary hormone concentration of adrenal steroid hormones. (A-C) Data of patients with RA; (D-F) results of patients with SLE. Data are given as means (SEM). *p<0.05; **p<0.01; †p<0.005; ‡p<0.001 for the comparison of the respective group with HS. For abbreviations see the legend to fig 2.

Figure 4

Interrelation between serum DHEAS and urinary DHEAS in HS, patients with RA, and patients with SLE, including those with prednisolone treatment. The x axis and the y axis were adjusted to the different numerical levels because the HS had clearly higher serum and urine concentrations than both patient groups. The panels include the linear regression line, the Spearman rank correlation coefficient, and the respective p value.

Figure 5

Substance clearance of adrenal steroid hormones. (A) Data of patients with RA; (B) results of patients with SLE. Open bars denote healthy subjects, light grey bars represent patients without prednisolone treatment, and dark grey bars demonstrate data of prednisolone pretreated patients. Data are given as means (SEM). *p<0.05; **p<0.01; †p<0.005; ‡p<0.001 for the comparison of the respective group versus HS. Crea, creatinine; for other abbreviations see the legend to fig 2,