Salt-losing Form Research Articles

先天性副腎過形成(塩類喪失型)の内分泌学的検討

先天性副腎過形成(塩類喪失型)の内分泌学的検討

Electrolyte metabolism of muscle in the salt-losing form of congenital adrenal hyperplasia

The study of metabolism of muscle electrolyte in children with the salt-losing form of congenital adrenal hyperplasia reveals two types of alterations. After admission and during initial therapy with salt and desoxycorticosterone, the changes are typical of those seen in experimental animals with adrenalectomy and excessive replacement therapy. Discontinuation of the sodium supplement after three months of therapy resulted in a return of muscle electrolyte values to normal. During the period of poor growth common to these patients a different pattern was observed. Sodium and water accumulated without alteration in tissue potassium. The mechanism of this alteration is not clear; however, it is consistent with the known effects of excess cortisone on muscle composition. These observations permit the conclusion that at least two fractions of sodium are present in muscle fibers, that which exchanges potassium and that which is independent of potassium metabolism.

Renal Tubular Acidosis in Salt-Losing Syndrome of Congenital Adrenal Hyperplasia (CAH)

ABSTRACT In a 22-month-old patient with the salt-losing form of CAH, renal contribution to acid-base balance was assessed both in a decompensated state 5 days after withholding 9-alpha-fluorohydrocortisone and in the compensated state one week after reinstitution of therapy. Renal bicarbonate threshold was 13 mmoles serum in decompensation and 20.5 mmoles serum in compensation. Acidification of the urine was appropriate in both states, although a slight quantitative difference in the 2 situations was observed. The data suggest that the renal acidosis in decompensated salt-losing form of CAH is mainly proximal tubular in origin.

On the metabolism of 16-alpha-hydroxy-C21-steroids. 3. Evidence for high rates of production of 16-alpha-hydroxyprogesterone and 16-alpha-hydroxypregnenolone in the salt-losing form of congenital adrenal hyperplasia.

The possibility that precursors of urinary 16α-hydroxypregnanes may be hypersecreted in salt-losing congenital adrenal hyperplasia is suggested by the isolation of increased quantities of these metabolites from the urine of such patients. The most likely precursors are 16α-hydroxyprogesterone and 16α-hydroxypregnenolone. The production rates of each of these steroids were determined in 2 patients after suppressive glucocorticoid therapy had been discontinued for a prolonged period. Both patients had elevated urinary 17-ketosteroids and pregnanetriol and displayed a tendency toward natriuresis. The production rate of 16α-hydroxyprogesterone was 24 and 28 mg/day, whereas only 310 and 315 μg of 16α-hydroxypregnenolone was produced during the same period. In another experiment, the rate of production of 16α-hydroxyprogesterone was 0.6 and 7.9 mg/day when the effects of suppressive glucocorticoid therapy were operative. From both experiments, it appears that elaboration of 16α-hydroxyprogesterone is decreased during suppressive therapy and increased when therapy is discontinued. Values of about 1 mg/day have been reported for the rate of production of 16α-hydroxyprogesterone in normal subjects. The rate of production of 16α-hydroxypregnenolone in a normal adult man was<50 μg/day.

Letter to the Editor

We find Doctor Cohen's observations interesting. He has reported a recent incidence in his clinic of the salt-losing form of congenital adrenal hyperplasia at an even higher level than we reported. The purpose of our original letter was not only to present our own findings but also to find out what other centers were observing with regard to their distribution of patients with congenital adrenal hyperplasia. Further reports from other investigators may require a change in the stated incidence of the various forms of this disease.

Adreno-genital syndrome.

Two cases of adrenogenital syndrome are presented. Case 1 was a 2-month-old female infant with the salt-losing form of C21-hydroxy-lase deficiency. She died after three bouts of generalised sepsis. Postmortem was performed. Case 2 was a 5-year old girl with the nonsaltlosing from of C21/hydroxylase deficiency. The problems in diagnosis and treatment are discussed.

Incidence of the Salt-Losing Form of Congenital Adrenal Hyperplasia

We have been impressed by the high mcidence of the salt-losing form of congenital adrenal hyperplasia (CAH) in the patients seen at the Children Medical Center in Dallas when compared to the quoted figures in the literature. The latest published figures from Johns Hopkins1 show 45 salt losers in a total of 131 patients, on 34%. Prader and co-workers2 reported 64 salt losers in 163 patients and affected siblings (39%), and Raiti and Newns3 report 28 salt losers in 58, or 48%. Two other series do not list numbers but give estimates of "as high as 30%" and "approximately one-half" for the incidence of the salt-losing form.

Hypertensive Encephalopathy and Desoxycorticosterone

Doctor Monteleone reports a patient with congenital adrenal hyperplasia who had permanent severe neurologic sequellae following DOC-induced hypertensive encephalopathy. Since the preparation of our previous manuscript, we have seen three additional children who have suffered from mineralocorticoid-induced hypertension following the implantation of DOC pellets. Our experience would indicate that this complication of mineralocorticoid therapy is much more common than previously recognized. The administration of some long-acting form of salt-retaining hormone is necessary in the infant with the salt-losing form of adrenal hyper plasia.

Statural growth in congenital adrenalhyperplasia treated with hydrocortisone

The analysis of 16 patients with the salt-losing form of congenital adrenalhyperplasia who were followed in our clinic for a period of 14 months to 8 years showed that these patients had abnormal growth. The growth failure was maximal during the first year of life; its main cause seemed to be overdosage of oral hydrocortisone. It would appear that the optimal dosage for complete adrenal suppression and normal linear growth is approximately 30 to 40 mg. per square meter per 24 hours. It is also possible that timing of administration of the oral hydrocortisone might permit decreasing the effective dose.

PLASMA RENIN ACTIVITY IN CONGENITAL VIRILIZING ADRENAL HYPERPLASIA

Peripheral plasma renin activity was markedly elevated in two cases of the salt-losing form of congenital virilizing adrenal hyperplasia. The renin activity was reduced after treatment with deoxycorticosterone and sodium chloride. In the hypertensive form of the plasma renin activity was suppressed.

PROLONGED HYPERTENSION FOLLOWING CESSATION OF DESOXYCORTICOSTERONE THERAPY IN CONGENITAL ADRENAL HYPERPLASIA

Three children with the salt-losing form of congenital adrenal hyperplasia developed hypertension during the course of therapy with desoxycorticosterone (DOC). The hypertension persisted for a much longer period of time than could be explained by the usual duration of the pharmacological action of the medication. The three children received DOC trimethylacetate. In none could other causes of hypertension be implicated. No other cases of persistent hypertension in children related to DOC administration were found.

Studies of androgens in patients with congenital adrenal hyperplasia.

ABSTRACT Six patients with the simple vitalizing form of congenital adrenal hyperplasia, 4 patients with the salt-losing form of the disease, and 1 patient with a partial 3β-hydroxysteroid dehydrogenase defect have been studied. In all patients with the simple and salt-losing form of the disease, peripheral plasma concentrations of testosterone (T) and particularly of androstenedione (Δ) were elevated. Plasma concentrations of dehydroepiandrosterone (D) and its sulfate (DS) were elevated in some of these patients. In 2 non-salt-losing patients, blood production of T and Δ was determined by the constant infusion technique. The blood production rate of Δ was very high. The blood production of T was also elevated for the age and sex of the 2 patients and approximately 50% of it arose from peripheral interconversion of Δ to T. There was a marked disagreement between blood and urinary production of T. The discrepancy could be accounted for by the contribution of the blood production of Δ to urinary T glucuroni...

Cortisol production rate: V. Congenital virilizing adrenal hyperplasia

Cortisol secretion rates were estimated by the in vivo isotope dilution technique in 16 patients with congenital virilizing adrenal hyperplasia; the data presented includes those of 2 salt losers previously published. The data were compared with those from age-matched controls. Six patients with the typical pattern of the salt-losing form had low CPR's. A seventh patient, the appearance of whose clinical manifestations was somewhat delayed and who had relatively mild salt loss, had a normal rate. Seven patients with the simple virilizing form had CPR's within the normal range. The eighth and youngest patient, aged 16 days, had a low CPR at a time when moderate transient salt loss was detected. The ninth patient was under ACTH stimulation for one week and had a CPR similar to those of the untreated patients.

ALDOSTERONE SECRETION RATE IN CONGENITAL ADRENAL HYPERPLASIA. A DISCUSSION OF THE THEORIES ON THE PATHOGENESIS OF THE SALT-LOSING FORM OF THE SYNDROME.

ALDOSTERONE SECRETION RATE IN CONGENITAL ADRENAL HYPERPLASIA. A DISCUSSION OF THE THEORIES ON THE PATHOGENESIS OF THE SALT-LOSING FORM OF THE SYNDROME.

ISOLATION, IDENTIFICATION AND MEASUREMENT OF 3-ALPHA,17-ALPHA-DIHYDROXYPREGNANE-11,20-DIONE IN CONGENITAL ADRENAL HYPERPLASIA.

11-Keto-17-hydroxypregnanolone was isolated from the urine of patients with congenital virilizing adrenal hyperplasia. The identification was based on: its mobility on paper chromatograms and the pink spot obtained when treated with the Zimmermann reagent; the product of oxidation with sodium bismuthate had an Rf value and a color reaction with the Zimmermann reagent similar to that of 11-ketoetiocholanolone; its ultraviolet spectrum as a sulfuric acid chromogen, and its infrared spectrum. A method for the measurement of this steroid based on its ltravioletabsorption as a sulfuric acid chromogen is described. In the simple virilizing form, patients of 5 to 39 years of age excreted 1.1–4.9 mg/24 hr of 11-keto-17-hydroxypregnanolone, while 2 infants under 1 year excreted 0.8 and 0.9 mg. In the salt-losing form, 5 patients under 1 year of age excreted 0.3–0.8 mg/24 hr. In subjects with the hypertensive form this steroid could not be detected.

Some effects of abnormalities of pituitary, adrenal or thyroid function on excretion of aldosterone and the response to corticotropin or sodium deprivation.

ABSTRACT Aldosterone was measured in the urine of 16 normal subjects and 35 patients with various abnormalities of pituitaiy, adrenal or thyroid function. Considerable diversity was noted in the quantity of aldosterone and other adrenal steroids in the urine of individual patients with clinical signs and metabolic findings of Cushing's syndrome or mineralocorticoid excess. In infants with the salt-losing form of congenital adrenal hyperplasia, aldosterone and cortisol metabolites appeared in smaller amounts than might be anticipated in normal children under similar conditions. Although patients with hypopituitarism and hypothyroidism excreted normal amounts of aldosterone under ordinary circumstances, the administration of corticotropin failed to elicit the usual acute rise in aldosterone excretion in these cases. Certain patients with hypopituitarism failed to respond adequately to sodium deprivation. It is suggested that chronic deficiency of corticotropin or other pituitary secretion may reduce or abol...