Impaired potassium-stimulated aldosterone production: a possible explanation for normokalemic glucocorticoid-remediable aldosteronism.
Unlike other forms of primary aldosteronism, recent prospective studies have paradoxically revealed that glucocorticoid-remediable aldosteronism (GRA) is usually characterized by normal potassium (K+) levels. To evaluate this paradox we studied 10 GRA subjects and 14 healthy controls in two protocols: 1) the renal K+ excretory response to acute oral administration of 50 mmol K+ chloride and to fludrocortisone, 0.2 mg p.o. q12 h x 4 doses; and 2) the aldosterone response to administration of 50 mmol K+ chloride. The K+ excretion rate (KER) in GRA subjects (n = 6) at baseline (45.6 +/- 8.3 microEq/min), after K+ (134 +/- 34.2 microEq/min), and after fludrocortisone (100 +/- 35.0 microEq/min) was not significantly different than that seen in the control (n = 8) subjects (54.9 +/- 19.0, 154 +/- 35.5, 112 +/- 45.8 microEq/min, respectively). Thus the renal kaliuretic response to K+ ingestion and exogenous mineralocorticoid is normal in GRA. Serum aldosterone increased from 5.0 +/- 3.8 at baseline to a maximum of 13.1 +/- 6.6 ng/dL 60 min after K+ ingestion in control subjects (n = 7), but failed to increase in GRA subjects (n = 14), going from 8.7 +/- 3.8 (baseline) to 8.8 +/- 5.4 ng/dL at 60 min (P = 0.004 vs. control). The blunted aldosterone response to K+ in GRA in association with the sharp diurnal decline in aldosterone in this ACTH-regulated syndrome probably results in a milder degree of hyperaldosteronism compared with other forms of primary aldosteronism, thereby producing volume expansion with minimal renal K+ wasting.
Litchfield
W R
WR
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Coolidge
C
C
Silva
P
P
Lifton
R P
RP
Fallo
F
F
Williams
G H
GH
Dluhy
R G
RG
D000328:Adult; D000450:Aldosterone / Q000096:biosynthesis*; D005260:Female; D005438:Fludrocortisone; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006929:Hyperaldosteronism / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008901:Mineralocorticoids; D011188:Potassium / Q000097:blood* / Q000494:pharmacology* / Q000652:urine; D011189:Potassium Chloride; D012083:Renin / Q000097:blood
D005938:Glucocorticoids; D008901:Mineralocorticoids; D000450:Aldosterone; D011189:Potassium Chloride; D012083:Renin; D011188:Potassium; D005438:Fludrocortisone; D006854:Hydrocortisone