The Effects of Adrenocorticotropic Hormone and Cortisone in the Adrenogenital Syndrome Associated With Congenital Adrenal Hyperplasia: An Attempt to Explain and Correct Its Disordered Hormonal Pattern 12

Bartter, Frederic C.; Albright, Fuller; Forbes, Alexander; Leaf, Alexander; Dempsey, Eleanor; Carroll, Evelyn L.

doi:10.1172/jci102438

Cited by 169 publications

(36 citation statements)

References 7 publications

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“…3) Genital defects produced in the offspring of animals to whom androgens have been administered during pregnancy may be similar to those exhibited by patients with virilizing adrenal hyperplasia, but these are fixed at birth, and no further virilization ensues (10, 11). 4) There is a striking similarity between the proposed pathogenesis of this disease (6,(12)(13)(14)(15)(16)(17), and biochemical defects in a variety of organisms for which there is excellent evidence for gene control.…”

Section: Resultsmentioning

confidence: 80%

“…Evidence has recently been presented to indicate that the primary defect in virilizing adrenal hyperplasia consists of failure of the adrenal cortex in the synthesis of compound F (12)(13)(14)(15)(16). In accordance with the scheme of adrenocorticosteroid biogenesis suggested by Hechter and his coworkers (25), Jailer has suggested that a block exists in the conversion of 17a hydroxyprogesterone into compound F (17).…”

Section: Expression In Possible Heterozygotesmentioning

confidence: 79%

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Virilizing Adrenal Hyperplasia; A Genetic and Hormonal Study 1

Childs¹,

Grumbach²,

Wyk³

1956

J. Clin. Invest.

160

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It is not at all unusual to find other affected children among the brothers and sisters of patients with virilizing adrenal hyperplasia. Such familial aggregations of affected children suggest, at least, a genetic basis for the condition at hand, and when the affected individuals are distributed in one generation only, there is a possibility that the condition is due to a mutant gene which finds obvious expression in the homozygote. This mode of inheritance for a possible gene responsible for virilizing adrenal hyperplasia has been suggested (1-3). Knudson (2) obtained information on 8 families, including 11 affected children. To these he added 26 families taken from the literature in which there were 32 affected children. Comparison of the observed number of affected sibs of index cases with that expected indicated sufficient agreement to favor the hypothesis of a recessive gene. All of Knudson's cases, however, were patients who showed evidence of electrolyte disturbance, and there appears to be no study which includes all types of cases which fall into this syndrome. This paper consists of information pertaining to a possible genetic etiology of this disease, obtained from 56 families containing one or more affected individuals, and an hormonal study of a group of parents of affected children. An exhaustive review of the literature is not relevant here, since our interpretations are based only upon the results of the analysis of our own data and not upon information from families that has been presented in other articles. MATERIALS AND METHODSThe data were obtained from the families of all patients with virilizing adrenal hyperplasia who were examined and diagnosed in the endocrine clinic of the Harriet Lane Home since 1945. Diagnostic criteria are those given by Wilkins (4). In each instance the information was given by the mother or responsible parent, and in a few cases by the patient himself. Some questions were put by means of a questionnaire which was mailed to all families, but since in some cases parents failed to answer the questionnaire and were otherwise unavailable, the data are in certain aspects incomplete.The data consist of information pertaining to: disease in sibs and other relatives, together with intra-family characteristics of the disease; age of sibs, their sex, maternal age at birth, birth order, death, age, cause, and place of death; maternal gestation and parturition; parental consanguinity; and size of the families of both parents.In some families all affected children were patients of the endocrine clinic, but there were 12 sibs of endocrine clinic patients who are presumed to have or have had the disease, who have never been seen in the Harriet Lane Home. Of these, 3 are still living, and detailed inquiry reveals that a firm diagnosis has been made on all three. The remaining 9 were dead by the time the index case was seen here. A diagnosis, either during life or at autopsy, was made elsewhere on 5 of these. This leaves 4 cases who were dead and who were not diagnosed as patients ...

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Section: Resultsmentioning

confidence: 80%

Section: Expression In Possible Heterozygotesmentioning

confidence: 79%

Virilizing Adrenal Hyperplasia; A Genetic and Hormonal Study 1

Childs¹,

Grumbach²,

Wyk³

1956

J. Clin. Invest.

160

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“…Thus, it appears clear on clinical grounds that one of two situations must obtain: either the actual production rate of aldosterone is not accurately reflected by the aldosterone secretion rate procedure based upon a urinary metabolite, or the action of aldosterone is inhibited in these patients. Increased excretion of urinary estriol is well documented in patients with congenital adrenal hyperplasia (1 in turn leads to an increase in the production of progesterone and of 17-hydroxyprogesterone as demonstrated by the excretion of pregnanediol (13), pregnanetriol, and pregnanetriolone in increased quantities (1). The sequence of events in the "non-salt-losing" form of the adrenogenital syndrome might be explained in two different ways (Fig.…”

Section: Methodsmentioning

confidence: 99%

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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“…DISCUSSION The experiments of Hechter and Pincus (19) by perfusion of beef adrenal glands with various precursors, and of Hayano and Dorfman (10,11) with adrenal homogenates in vitro, gave impetus to the studies described herein. Perusal of these contributions, previous work from this laboratory, and that of many others cited elsewhere (1)(2)(3)(4)(5) had suggested that in the nonhypertensive form of the adrenogenital syndrome due to congenital adrenal hyperplasia, the inability to hydroxylate the steroid nucleus at carbon 21 (deficiency of 21-hydroxylase) represented the basis of this disorder. This study gives direct evidence of a deficiency of 21-hydroxylation: Two diseased adrenal glands were unable to convert 17-hydroxyprogesterone into either 11-desoxycortisol or cortisol; a large quantity of 17-hydroxyprogesterone was initially present in each of these glands, and there were no alpha-ketolic steroids as in normal glands.…”

Section: -Desoxycortisol As Substratementioning

confidence: 96%

In Vitro Hydroxylation of Steroids by Whole Adrenal Homogenates of Beef, Normal Man, and Patients with the Adrenogenital Syndrome1

Bongiovanni¹

1958

J. Clin. Invest.

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The Effects of Adrenocorticotropic Hormone and Cortisone in the Adrenogenital Syndrome Associated With Congenital Adrenal Hyperplasia: An Attempt to Explain and Correct Its Disordered Hormonal Pattern 12

Cited by 169 publications

References 7 publications

Virilizing Adrenal Hyperplasia; A Genetic and Hormonal Study 1

Virilizing Adrenal Hyperplasia; A Genetic and Hormonal Study 1

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

In Vitro Hydroxylation of Steroids by Whole Adrenal Homogenates of Beef, Normal Man, and Patients with the Adrenogenital Syndrome1

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