title: Increased disorderliness and amplified basal and pulsatile aldosterone secretion in patients with primary aldosteronism.
abstract: To investigate the pathophysiology of altered aldosterone secretion in patients with primary aldosteronism, the pulsatile mode of in vivo aldosterone and cortisol release was examined by quantitative deconvolution analysis in 5 normal subjects (controls) and 10 patients with aldosterone-producing adenomas (APA) under conditions of sodium (150 meq/day) balance. Episodic release of aldosterone and cortisol was assessed by sampling blood at 10-min intervals for 24 h. A waveform-independent deconvolution algorithm was used to calculate endogenous aldosterone and cortisol secretion rates on a sample by sample basis in each subject. There were no differences in the number of aldosterone or cortisol secretory bursts per day or their mean interpulse intervals between normal subjects and patients with primary aldosteronism. A 24-h rhythmicity in serum aldosterone concentrations was maintained in APA patients. Patients with primary aldosteronism had significantly higher (P < 0.01) aldosterone mean secretory rates, mean mass of aldosterone secreted per burst, maximal aldosterone secretion rates attained within each burst, and mean basal (nadir) aldosterone secretion rates. A recently introduced regularity statistic, approximate entropy (ApEn), was used to test for orderliness (small ApEn) vs. randomness (large ApEn) in the aldosterone time series. ApEn was significantly larger for the APA patients (1.433 +/- 0.148) than for normal subjects (0.306 +/- 0.098; P < 0.001), with complete group segmentation yielding 100% sensitivity and specificity. In contrast, a scale-invariant form of this measure, normalized ApEn, showed no significant distinction between tumoral and normal aldosterone release patterns. These ApEn findings taken together are consistent with the deconvolution results from an entirely distinct perspective, reinforcing an amplitude difference, but no frequency difference, between normal subjects and APA patients. Unexpectedly, patients with APA had significantly lower mean cortisol secretory rates, reduced cortisol secretory burst mass, and attenuated maximal cortisol secretory rates than normal subjects (P < 0.01). Plasma cortisol and aldosterone concentrations in patients remained positively correlated over short time lags. In summary, the present findings demonstrate that in normal subjects and patients with APA, both aldosterone and cortisol are secreted in a burst-like mode. The presence of substantial basal aldosterone release and increased irregularity of serial aldosterone concentrations distinguishes APA from normal subjects.(ABSTRACT TRUNCATED AT 400 WORDS)
authors: Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville 22908.
authors: H M
authors: HM
authors: Siragy
authors: W V
authors: WV
authors: Vieweg
authors: S
authors: S
authors: Pincus
authors: J D
authors: JD
authors: Veldhuis
mesh_terms: D000328:Adult; D000450:Aldosterone / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism; D006929:Hyperaldosteronism / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D011673:Pulsatile Flow
chemical_list: D000450:Aldosterone; D006854:Hydrocortisone