Glucocorticoid receptor abnormalities in fibroblasts from patients with idiopathic resistance to dexamethasone diagnosed when evaluated for adrenocortical disorders.
A retrospective survey was accomplished on 420 consecutive patients who had undergone dexamethasone suppression tests between 1975-1988 due to suspected adrenal disorders. We found 7 patients in whom glucocorticoid resistance was apparent. They showed 4-6 abnormalities of the 7 investigations used: insensitivity to dexamethasone inhibition (n = 7), increased urinary cortisol (n = 3), glucocorticoid receptor (GR) thermolability (n = 4), decreased number of glucocorticoid receptors (n = 4), abnormal ligand affinity of GR (n = 4), abnormal basal GR mRNA expression (n = 4), and abnormal down-regulation of basal GR mRNA levels by dexamethasone (n = 1). The four patients with GR thermolability also showed increased basal GR mRNA levels. In the other patients the number of GR per cell was decreased without an up-regulation of GR mRNA. It is concluded that the syndromes of glucocorticoid resistance vary notably, clinically as well as biochemically; in patients evaluated for adrenocortical disorders the syndrome is apparently encountered in 1-2% of the patients.
Werner
S
S
Department of Endocrinology, Karolinska Hospital, Stockholm, Sweden.
Thorén
M
M
Gustafsson
J A
JA
Brönnegård
M
M
D000303:Adrenal Cortex Diseases / Q000378:metabolism*; D000328:Adult; D002478:Cells, Cultured; D003907:Dexamethasone; D004351:Drug Resistance; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D008875:Middle Aged; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism*; D012189:Retrospective Studies
D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D006854:Hydrocortisone