Impaired Aldosterone Production in “Salt-losing” Congenital Adrenal Hyperplasia*

Bryan, George T.; Kliman, Bernard; Bartter, Frederic C.

doi:10.1172/jci105213

Cited by 59 publications

(20 citation statements)

References 13 publications

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“…In contrast, the control patient showed no significant change between the secretion rates with sodium loading before and during prednisone therapy but demonstrated a significant increase in the secretion rate during sodium depreviation and prednisone therapy (Fig. 4) 4 Design of experiment and results of study of control subject both with and without steroid suppression on low and high sodium intake.…”

Section: Methodsmentioning

confidence: 97%

“…3). A third child (a The radiochemical purity of the final eluate of aldosmale pseudohermaphrodite with normal adrenal func-terone monoacetate used to measure secretion rates was tion) was studied in an identical manner as shown in verified on 15 specimens by measurement of the 14C/5H ratio and that of various derivatives, purified through adAldosterone secretion rate was measured as described ditional chromatographic procedures; in particular some previously (4). In this study, all collections were carried of the specimens allowed as many as three additional out for complete 24-hr periods, and the metabolite of al-chromatographic separations (or a total of seven).…”

Section: Methodsmentioning

confidence: 99%

“…A simple defect in the 21-hydroxylation of 17a-hydroxyprogesterone will not explain the difference between the "salt-losing" form of congenital adrenal hyperplasia, in which secretion of aldosterone is defective (4), and the "non-salt-losing" form, in which there is no defect in aldosterone secretion (see below). We have suggested (4) that patients with the "salt-losing" variety of the disorder may have a second enzymatic defect, namely, a relative inability to perform 21-hydroxylation of progesterone.…”

Section: Introductionmentioning

confidence: 99%

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Aldosterone hypersecretion in “non-salt-losing” congenital adrenal hyperplasia

Bartter¹,

Henkin²,

Bryan³

1968

J. Clin. Invest.

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A B S T R A C T Patients with the "non-salt-losing" form of the adrenogenital syndrome were studied before and after suppression of adrenal cortical activity with carbohydrate-active steroids. The response of aldosterone secretion to sodium deprivation was measured; in some patients response to adrenocorticotropic hormone (ACTH) was measured as well.The aldosterone secretion was normal and responded normally to sodium deprivation in all patients studied during suppression with carbohydrate-active steroids. This finding suggests that 21-hydroxylation of progesterone is normal in this syndrome.The sole abnormality in the production of aldosterone in these patients was found to be excessive secretion of aldosterone while they were not receiving suppressive doses of carbohydrate-active steroids. This finding strongly supports the view that the biogenetic pathways through which aldosterone is produced from progesterone are intact in this syndrome.No patient showed hypertension or hypokalemic alkalosis despite very high aldosterone secretion rates. This observation suggests that the hyperaldosteronism is secondary to a tendency to sodium loss in the patient whose ACTH production is not suppressed.

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Section: Methodsmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Aldosterone hypersecretion in “non-salt-losing” congenital adrenal hyperplasia

Bartter¹,

Henkin²,

Bryan³

1968

J. Clin. Invest.

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“…After the patient had breakfast, he walked to the metabolic clearance room where the MCR was measured by the constant infusion method with the patient in the supine position over a 2-hr period. A "primer" dose of 2.5 /xCi scribed from this laboratory [5]. Plasma renin was measured by a modification of the method of Boucher [2] as previously described from this laboratory [10].…”

Section: Methodsmentioning

confidence: 99%

The Renin-Angiotensin-Aldosterone System in Patients with Cystic Fibrosis of the Pancreas

et al. 1971

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ExtractPatients with cystic fibrosis of the pancreas (CFP) have elevated plasma renin activity, supine renin 497-595 compared with a normal value of 228 ± 133 ng/100 ml plasma on 109 mEq sodium intake/24 hr, but have normal renin release mechanisms as far as postural changes are concerned, since the renin activity increases normally with the upright posture; upright renin, 594-875 compared with a normal value of 359 ± 210 ng/100 ml plasma on the same sodium intake. The high aldosterone secretion rates (ASR), 161 -4-45 compared with a normal value of 90 ± 31 /jg/24 hr, seen on 109 mEq sodium intake were probably secondary to the abnormally high renin release. The same can be said for the lack of adequate suppression to normal of both renin and ASR on 249 mEq sodium intake/24 hr, supine renin 205-544 compared with a normal value of 97 ± 71 ng/100 ml plasma; upright renin 845-893 compared with a normal value of 212 ±61 ng/100 ml plasma; ASR on the same intake, 93-333 compared with a normal value of 62.15 ± 27.8 /ug/24 hr. The low metabolic clearance rates and the high calculated plasma aldosterone concentrations on the 109 mEq sodium intake indicate that a state of secondary hypcraldosteronism exists in patients with CFP, probably as an adaptation to frequent, excessive sodium losses via the sweat and consequent contraction of intravascular volume. SpeculationIn all the patients that we studied with cystic fibrosis of the pancreas a state of secondary hyperaldosteronism appears to exist. This state of hyperaldosteronism, secondary to increased renin release, probably results from adaptation to frequent, excessive sodium losses via the sweat, leading to depletion of extracellular fluid volume.

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“…Salt-losing congenital adrenal hyperplasia (SL-CAH) is an inherited defect in steroid C 21-hydroxylation, characterized by deficiency in the secretion of cortisol, hypersecretion of androgens and progestins (2), and complete (3,12) or partial (6,10) defects in the synthesis of aldosterone. Salt-wasting in this disorder appears to be the result both of defective aldosterone synthesis and of increased production of steroids which antagonize the effects of aldosterone (9,10).…”

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confidence: 99%

Plasma Renin Activity and the Response to Sodium Depletion in Salt-Losing Congenital Adrenal Hyperplasia

et al. 1982

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SummaryMineralocorticoid therapy was discontinued in 14 subjects, ages 7-17 years, with salt-losing congenital adrenal hyperplasia. The level of plasma renin activity (PRA) was determined in relation to the cumulative loss of sodium (intake-urinary output) over 4-12 days. Although the magnitude and rate of response varied, PRA increased in all subjects. There was a significant positive correlation between cumulative sodium loss and PRA (r = 0.585, P < 0.001, n = 76), and a significant negative correlation between serum sodium concentration and PRA (r = -0.736, P < 0.001, n = 76). Significant sodium loss and elevation of PRA were seen prior to the development of hyponatremia. Thus, elevated PRA appeared to be a more sensitive indicator of sodium loss than serum sodium concentration.Fifteen infants, ages 1-33 months with salt-losing congenital adrenal hyperplasia, who were treated with subcutaneous pellets of 11-deoxycorticosterone acetate (DOCA), were also studied. PRA decreased following implantation of the DOCA pellets over 1-6 months. In most instances there was a subsequent increase in PRA, beginning at 1-8 months post implantation. There was a significant negative correlation between serum sodium and PRA (r = -0.669, P < 0.001, n = 78) in these infants. However, there were four instances in which elevated PRA was associated with normal serum sodium.Sodium balance studies were also performed on 14 of these infants during 29 admissions. All balance studies were performed at approximately 3 or 6 months after DOCA pellet implantation. On a diet containing 2 mEq Na/kg body weight per day, sodium balance was positive and there was no significant change in sodium excretion over the 3 days of observation. When a 1 mEq Na/kg/ day diet was given, sodium balance was neutral on day 3 of the study, and fractional urinary sodium excretion (FeN,) decreased from 0.49 + 0.33, S.D. on day 1 to 0.23 + .09% on day 3 ( P < 0.001, n = 19). This change was statistically significant. Net sodium balance on either diet was independent of PRA. Elevated PRA was not necessarily associated with adverse symptomatology.Thus in infants treated with DOCA pellets, elevated PRA was associated with indices of sodium depletion and decreased availability of DOCA. The dietary sodium requirement for infants treated with DOCA appeared to be 1-2 mEq/kg body weight/day.

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Impaired Aldosterone Production in “Salt-losing” Congenital Adrenal Hyperplasia*

Cited by 59 publications

References 13 publications

Aldosterone hypersecretion in “non-salt-losing” congenital adrenal hyperplasia

Aldosterone hypersecretion in “non-salt-losing” congenital adrenal hyperplasia

The Renin-Angiotensin-Aldosterone System in Patients with Cystic Fibrosis of the Pancreas

Plasma Renin Activity and the Response to Sodium Depletion in Salt-Losing Congenital Adrenal Hyperplasia

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