Aldosterone Excretion in Virilizing Adrenal Hyperplasia *

Abstract

Sodium depletion with concomitant dehydration occurs as a complicating factor in approximately one-third of patients with virilizing adrenal hyperplasia (1). A number of writers have discussed certain differences between the electrolyte disturbance occurring in this syndrome and that of Addison's disease (2-5) and several hypotheses have been offered to explain the sodium loss and potassium retention which occur (1, 4, 6, 7). Although the role of aldosterone is pertinent in many of these hypotheses, the only reported study of aldosterone excretion in patients with virilizing adrenal hyperplasia is that of Prader, Spahr and Neher (6).In order further to elucidate aldosterone metabolism in this syndrome the present studies were undertaken utilizing subjects both with and without defects of sodium regulation. Accumulated data indicate that patients with virilizing adrenal hyperplasia without associated salt loss excrete normal, or high levels of aldosterone on an ad lib. salt intake, and respond with significant increases in aldosterone excretion when placed on limited sodium diets. In contrast, patients with salt loss probably excrete deficient quantities of aldosterone as compared to the normal individual, and are unable to respond with significant increases in aldosterone excretion when sodium intake is limited. Ancillary studies compare the ability of normal infants and adults to excrete aldosterone, both with ingestion of a normal and a sodium deficient diet. day specimens from infants were pooled. In preparation for assay the urine was acidified to pH 1.0 and allowed to stand at room temperature for 24 hours. The "free" steroids were then extracted with dichloromethane. The extracts were washed with aqueous sodium carbonate, dehydrated with sodium sulfate, and evaporated to dryness under a stream of nitrogen. The residues were redissolved in ethanol. These crude extracts were either: 1) injected into adrenalectomized dogs for assays of aldosterone content by the method of Liddle, Cornfield, Casper and Bartter (8) ; 2) subjected to multiple systems of paper chromatography following which the aldosterone fraction was assayed by the same method; or 3) fractionated and assayed for aldosterone content by the isotope-derivative method of Kliman and Peterson (9). The three methods yielded comparable results when run in parallel on the same urine specimens (Table I). Assays carried out only in adrenalectomized dogs were subject to the limitation of relative lack of sensitivity of this method, i.e., a minimum dose of 1 lAg. of aldosterone (per assay animal) was required to induce a distinct response. As a rule an attempt was made to assay each specimen in at least three or four animals. As a result, unless a specimen contained a total of at least 3 or 4 ,ug. of aldosterone, the responses would be negligible. Under such circumstances it was possible to say only that the amount of aldosterone was "less than" a certain value. In such instances (indicated in the tables and graphs by the symbol < or J) the specimen might h...

Aldosterone Secretion Rate in Congenital Adrenal Hyperplasia. A Discussion of the Theories on the Pathogenesis of the Salt-losing Form of the Syndrome*

“…Furthermore, the high aldosterone excretion in the nonsalt losers led these authors to suggest that a"sodium-losing" factor was produced by the adrenals of the patients with adrenal hyperplasia, but that compensation occurred only if aldosterone could be secreted above the normal level. The data mentioned above (17) did not confirm earlier results of Prader, Spahr, and Neher (18), but generally agreed with studies published later by De Graeff and Moolenaar (19) and Mattox, Hayles, Salassa, and Dion (20).…”

“…In previous studies on aldosterone excretion in patients with congenital adrenal hyperplasia (17)(18)(19)(20), conclusions were drawn on the assumption that aldosterone excretion is proportional to its secretion. This assumption is not always valid (25), but it seems to be generally justified in congenital adrenal hyperplasia.…”

Aldosterone excretion in normal children and in children with adrenal hyperplasia.

“…Blizzard, Liddle, Migeon, and Wilkins (27), in a comprehensive study of normal children and children with salt-losing and simple virilizing adrenal hyperplasia, found that when salt was restricted normal children and simple virilizers showed an increase in aldosterone excretion, but salt losers did not.…”

“…The conclusion reached by most of the research investigations (16,(26)(27)(28)(29)(31)(32)(33)(34)(35) is that an aldosterone deficiency does exist in congenital hyperplasia of the salt-losing variety, but not in the simple virilizing form.…”

“…The bioassay method (23,26,27) and the paper visualization method (21-25, 29, 36) lack the sensitivity necessary to determine aldosterone at very low levels, and specificity of the methods usually was not adequately' evaluated (37). Greatest reliance can be placed on those studies that properly utilized the highly sensitive and specific double dilution isotope derivative assay (1).…”