Reduced lymphocyte beta 2-adrenoceptor density and impaired diastolic left ventricular function in patients with glucocorticoid deficiency.
OBJECTIVE
Patients with adrenal crisis are at risk of severe hypotension not responding to administration of catecholamines. As glucocorticoids may be a prerequisite for intact beta-adrenoceptor function, impaired adrenoceptor activity may explain the hypotension and reduced cardiac performance in adrenal insufficiency. The aim of our study was, therefore, to further elucidate the permissive action of glucocorticoids on adrenergic function and cardiac performance.


METHODS
Prospective randomized controlled study.


METHODS
Nine patients with adrenal insufficiency were investigated before and 48 hours after glucocorticoid withdrawal. Mineralocorticoid therapy remained unchanged during the study period.


METHODS
Lymphocyte beta 2-adrenoceptor density, intracellular c-AMP response to isoprenaline, platelet alpha 2-receptor density, plasma catecholamines, serum cortisol, plasma ACTH, echocardiography.


RESULTS
Glucocorticoid depletion was demonstrated by a fall in serum cortisol from mean +/- SEM 441 +/- 62 to 45 +/- 18 nmol/l. Glucocorticoid withdrawal decreased lymphocyte beta 2-receptor density from 798 +/- 111 to 498 +/- 54 binding sites/cell (P < 0.05) and the intracellular c-AMP response to isoprenaline from 15.0 +/- 4.2 to 8.2 +/- 1.7 pmol/10(6) cells (P < 0.05). Echocardiography showed impaired diastolic relaxation after glucocorticoid withdrawal with prolongation of the rapid filling period (80.3 +/- 12.5 vs 138.3 +/- 11.8 ms, P < 0.05). Plasma catecholamines, platelet alpha 2-receptor density and systolic left ventricular function were not affected by glucocorticoid deficiency.


CONCLUSIONS
This study demonstrates the importance of normal glucocorticoid levels for beta 2-adrenoceptor function and helps to explain the decreased responsiveness to catecholamines and the impaired cardiac performance in adrenal crisis.
Medizinische Universitätsklinik Würzburg, Germany.
B
B
Allolio
W
W
Ehses
H M
HM
Steffen
R
R
Müller
D000293:Adolescent; D000309:Adrenal Insufficiency / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D000242:Cyclic AMP / Q000378:metabolism; D004452:Echocardiography; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D007545:Isoproterenol; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D016277:Ventricular Function, Left / Q000502:physiology*
D005938:Glucocorticoids; D011943:Receptors, Adrenergic, beta; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D007545:Isoproterenol