Critical Analysis of Methods for Measurement of Pregnane-3-alpha, 17-alpha, 20-alpha-Triol in Human Urine

Bongiovanni, Alfred M.; Eberlein, Walter R.

doi:10.1021/ac60135a023

Cited by 95 publications

(12 citation statements)

References 17 publications

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“…Case VI represents a partial deficiency of 3,/-hydroxysteroid dehydrogenase, since significant quantities of tetrahydro-E were present in the urine. In addition, in this last subject, pregnanetriol was present in quantities which might be regarded as normal for the age (22). Nonetheless, the dominant pattern of urinary steroids is identical with that of the other cases.…”

Section: Discussionsupporting

confidence: 54%

The ADRENOGENITAL SYNDROME WITH DEFICIENCY OF 3β-Hydroxysteroid DEHYDROGENASE*

Bongiovanni¹

1962

J. Clin. Invest.

293

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A brief account of three cases of the adrenogenital syndrome due to a deficiency of 3,8-hydroxysteroid dehydrogenase has been published (1, 2). It is the purpose of this report to extend the original observations, detail the methodological aspects, and present certain clinical correlations.'The deficiency of 11,8-hydroxylase or 21-hydroxylase as two possible causes of the adrenogenital syndrome with adrenocortical hyperplasia is now well recognized. These aspects have been reviewed in detail recently (2). A direct demonstration of an enzymatic defect in adrenocortical tissue has been possible with respect to 21-hydroxylase in only two instances (3). Such experiments are not generally possible because of the obvious difficulties in obtaining suitable tissue from human subjects with this disorder. The evidence is generally indirect and depends upon the demonstration of "abnormal metabolites" in relatively large amount in the urine or blood. The nature of these metabolites provides the clue to the site of the defect, hence the indirect evidence for the deficient enzymatic transaction. A deficiency of the enzyme 3,/-hydroxysteroid dehydrogenase represents a third basis for the dis-* This work has been supported by Grants A-619 (C7) and 2A-5197 (C2) from the National Institute of Arthritis and Metabolic Diseases, U. S. Public Health Service.1 The following abbreviations have been employed for the steroids under discussion: dehydroepiandrosterone= 3,B-hydroxy-A5-androstene-17-one; androsterone = 3a-hydroxyandrostane-17-one; etiocholanolone = 3a-hydroxyetiocholane-17-one; pregnanetriol = pregnane-3a,17a,20a-triol; 11-ketopregnanetriol = 3a,17a,20a-trihydroxypregnane -11 -one; tetrahydro -E = 3a,17a,21 -trihydroxypregnane-11,20-dione; pregnenetriol = AY-pregnene-3fi,17a,20a-triol; pregnenediolone = 3,8,17a-dihydroxy-A'-pregnene-20-one; pregnenediol = A'-pregnene-3#,20a-diol; pregnenetetrol = ,17a,20,8,8, Six cases of this new form of the disorder are herein reported and compared with five cases due to a deficiency of 21-hydroxylase and five normal subjects. MATERIALS AND METHODSA summary of the clinical data on six cases of the adrenogenital syndrome due to a deficiency of 3#-hydroxysteroid dehydrogenase (I-VI), five due to a deficiency of 21-hydroxylase (VII-XI), and five normal individuals (XII-XVI) is presented in Table I. The post-mortem findings in four (I, III, IV, and V) were consistent with those of adrenocortical hyperplasia. The sex of the cases with the adrenal disorders was determined by examination of the sex chromatin in cells from the buccal mucosa, examination of the internal ducts by X ray, and histologic examination of the gonads in Case VI and in those who succumbed. Cases III and IV were known to have one prior affected sibling who died and showed bilateral adrenal hyperplasia at autopsy.Urine specimens were frozen immediately upon the completion of the 24-hour collection and stored at -100 C until analysis. The urinary steroidal compounds were first hydrolyzed with beta glucuronidase (Ketodase, War...

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Section: Discussionsupporting

confidence: 54%

The ADRENOGENITAL SYNDROME WITH DEFICIENCY OF 3β-Hydroxysteroid DEHYDROGENASE*

Bongiovanni¹

1962

J. Clin. Invest.

293

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“…The determinations of urinary pregnanediol and pregnanetriol were carried out by the techniques of KLOP-PER et al [17] and of BONGIOVANNI and EBERLEIN [6], respectively. The concentrations of cortisol and corticosterone in plasma were determined by the double isotope dilution techniques of PETERSON [22].…”

Section: Methodsmentioning

confidence: 99%

The Syndrome of Congenital Adrenocortical Unresponsiveness to ACTH. Report of Six Cases

et al. 1968

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Six patients with the syndrome of congenital adrenocortical unresponsiveness to ACTH are reported. This syndrome is characterized by feeding problems early in life, hypoglycemic episodes and hyperpigmentation of the skin (table I). Blood pressure and levels of electrolytes in serum were normal (table II). PPD and histoplasmin skin tests were negative, while antibodies to adrenal, thyroid, and gastric tissues were undetectable. Urinary excretion of 17-hydroxycorticosteroids and cortisol production rates were low and did not respond to administration of ACTH (table III). While receiving a low sodium diet, the patients were able to conserve sodium (figs. 2, 3 and 4) and to increase the rate of aldosterone secretion (tables IV and V).In one case, adrenal pathology showed a normal zona glomerulosa with atrophy of the zonae fasciculata and reticularis.This isolated deficiency in cortisol secretion is not due to a defect in pituitary function or a deficiency of one of the enzymes directly involved in steroid biosynthesis. The most probable pathogenesis is an abnormality at the site (or one of the sites) of ACTH action on cortisol biosynthesis. Speculation

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“…(1) normal linear growth; (2) normal bone age and normal rate of advancement of bone age; (3) no evidence of ongoing inappropriate virilization such as premature appearance of pubic hair or phallic or clitoral enlargement; (4) urinary 17 ketosteroids at or below age-related upper limits (14); (5) serum concentration of 17-hydroxyprogesterone (17-OHP) below 500 ng/dl (one patient with a serum level of 17-OHP of 757 ng/ dl was considered adequately controlled because the rest of the criteria were fulfilled); and (6) normal testicular size for age or regular menses in adolescent male and female subjects, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Urinary concentrations of 17-ketosteroids (10) and preganetriol (3) were measured by conventional methods.…”

Section: Methodsmentioning

confidence: 99%

Disproportionate Supression of Dehydroepiandrosterone Sulfate (DHEAS) in Treated Patients with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

et al. 1983

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SummarySerum concentrations of dehydroepiandrosterone sulfate (DHEAS) were measured in 28 patients (18 females, 10 males) with congenital adrenal hyperplasia due to 21-hydroxylase deficiency who were treated with oral hydrocortisone (non-salt losers) or hydrocortisone and 9-a-fluorohydrocortisone (salt-losers). Adequacy of therapy was assessed by clinical findings, determination of bone age, urinary excretion of 17-ketosteroids, and serum concentration of 17-hydroxyprogesterone. These allowed the separation of patients into three groups: poorly controlled, adequately controlled and overtreated. Individual values for serum levels of DHEAS were compared to mean normal values for age. In the adequately controlled and overtreated patients, mean serum concentrations of DHEAS were significantly lower than normal values for age ( P < 0.05). In the poorly treated patients, the mean serum concentration of DHEAS was not significantly different from normal values for age ( P = 0.50).These data indicate that the serum concentration of DHEAS is overly suppressed in treated patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. This finding suggests that measurement of the serum levels of DHEAS has limited value in assessing the adequacy of therapy in this disease. Abbreviations CAH, congenital adrenal hyperplasia due to 21-hydroxylase deficiency DHEAS, dehydroepiandrosterone sulfate 17-OHP, 17-hydroxyprogesterone SDS, standard deviation score A major goal in long term management of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) is to suppress the effects of excessive adrenal androgens. The adequacy of suppression has been traditionally monitored by periodic measurement of 24-h urinary excretion of 17-ketosteroids and pregnanetriol. The reliability of these assays, however, is hampered by inaccuracies in collection of 24-h urine specimens. A suitable compound that can be measured in blood, therefore, has been searched for by several investigators. Dehydroepiandrosterone sulfate (DHEAS), the most abundant adrenal androgen, seems to be a likely candidate for this purpose because it is almost exclusively synthesized by the adrenal glands (17,19). Moreover, as DHEAS has a long half-life (24, 26), its concentration in serum is less susceptible to diurnal variations (25).Recent studies have demonstrated that serum levels of DHEAS are increased in patients with untreated CAH (1 1, 15,23); however, data on the serum concentration of the hormone during therapy are very limited. Serum levels of DHEAS did not increase in six patients with CAH when therapy was discontinued for 3 days (33). Golden et al. (1 1) found elevated levels of serum DHEAS in patients with CAH only when they were overtly undertreated, but values for serum levels of DHEAS were not correlated with the age of the patients. Because secretion of DHEAS is age dependent (8,15,23), its role in the management of patients with CAH cannot be quantitated unless appropriate age-matched control values are applied. The ...

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Critical Analysis of Methods for Measurement of Pregnane-3-alpha, 17-alpha, 20-alpha-Triol in Human Urine

Cited by 95 publications

References 17 publications

The ADRENOGENITAL SYNDROME WITH DEFICIENCY OF 3β-Hydroxysteroid DEHYDROGENASE*

The ADRENOGENITAL SYNDROME WITH DEFICIENCY OF 3β-Hydroxysteroid DEHYDROGENASE*

The Syndrome of Congenital Adrenocortical Unresponsiveness to ACTH. Report of Six Cases

Disproportionate Supression of Dehydroepiandrosterone Sulfate (DHEAS) in Treated Patients with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

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