Adrenocorticotropin, Glucocorticoid, and Androgen Secretion in Patients with New Onset Synovitis/Rheumatoid Arthritis: Relations with Indices of Inflammation1

• Published in: The journal of clinical endocrinology and metabolism Vol. 85; no. 4; pp. 1461 - 1466
• Main Authors: Kanik, Keith S., Chrousos, George P., Schumacher, H. Ralph, Crane, Marianna L., Yarboro, Cheryl H., Wilder, Ronald L.
• Format: Journal Article
• Language: English
• Published: Endocrine Society 01-04-2000
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jcem.85.4.6534

To determine whether alterations in adrenocortical function occur early
in the development of inflammatory joint disease, we examined patients
with new onset synovitis (<1 yr) prior to treatment with
corticosteroids or other disease-modifying antirheumatic drugs.
Thirty-two patients with new onset synovitis, including 15 fitting
criteria for rheumatoid arthritis (RA), taking no medications, were
referred for study by local rheumatologists; 32 age- and sex-matched
healthy individuals were recruited as controls. Patients and controls
had blood drawn under identical conditions between 0900 and 1100
h. Plasma ACTH, cortisol, dehydroepiandrosterone (DHEA),
DHEA sulfate, free and total testosterone, erythrocyte sedimentation
rate, C-reactive protein, and rheumatoid factor were measured. Compared
with controls, patients had higher inflammatory indices (erythrocyte
sedimentation rate, C-reactive protein) and lower basal morning levels
of free testosterone (lower in males age ≥45 yr), but similar levels
of ACTH, cortisol, DHEA, DHEA sulfate, and total
testosterone. In addition, the positive correlations between
ACTH-cortisol, ACTH-DHEA, and cortisol-DHEA,
observed in the normal controls, were weakened or abolished in the
patients (both total and RA subset). No positive relations between
inflammatory indices and ACTH or cortisol were noted, yet an inverse
correlation between these indices and DHEA and
testosterone was observed. Moreover, a steeper age-associated
decline in DHEA was observed in our cross-sectional sample
of patients with new onset synovitis. We conclude that patients with
synovitis (including those fitting criteria for RA) have adrenocortical
hormone alterations within a year of disease onset. Paradoxically,
these patients have no positive relation between indices of
inflammation and ACTH or cortisol, but rather serum androgen levels are
inversely correlated with these indices. In addition, the relations
between ACTH, the classic stimulus of cortisol and adrenal androgens,
and these hormones are weakened or abolished, whereas the negative
relation between age and zona reticularis function is
steeper than that of controls.