Urinary Steroid Excretion Research Articles

Congenital adrenal hyperplasia caused by 11β-hydroxylase deficiency with onset of symptoms after one spontaneous pregnancy

A case of adrenogenital syndrome due to 11β-hydroxylase deficiency is described in a mother, 25 years of age, who had experienced a successful pregnancy 5 years previously. At that time no abnormality had been suspected and pregnancy was achieved without therapy. Subsequently the patient was examined because of secondary sterility. The menstrual cycles were anovulatory. Only slight virilization was observed and blood pressure was normal. Diagnosis was based on the observation of highly increased urinary excretion of 17-ketosteroids and 17-ketogenic steroids, with especially high excretion of tetrahydro-11-deoxycortisol. Following suppression with dexamethasone and adequate maintenance treatment, the patient conceived and had an uneventful pregnancy. This is apparently the first report of pregnancy in adrenogenital syndrome due to 11β-hydroxylase deficiency.

VIRILIZING ADRENOCORTICAL ADENOMA RESPONSIVE TO GONADOTROPHIN

A virilizing adrenocortical adenoma was demonstrated in a yound female. Urinary 17-ketosteroid excretion and subfractions, plasma testosterone level and urinary 17-ketogenic steroid excretion were markedly increased. Dehydroepiandrosterone was the main constituent of the androgen excess. Otherwise the adrenocortical function was found to be normal as evaluated from measurements of cortisol, corticosterone and their metabolites under basal conditions and during dynamic tests. The androgen excess showed an unexpected response to trophic hormones. Human chorionic gonadotrophin stimulation resulted in a pronounced increase in androgen production, whereas no gonadotrophin-dependency could be demonstrated by means of the oestrogen suppression test. Similarly, no corticotrophin-dependency could be demonstrated by corticotrophin stimulation and suppression tests. Removal of the tumour resulted in normalization of the androgen production and no abnormal response upon human chorionic gonadotrophin administration could now be found. The inappropriate response of tumours to trophic hormones is discussed. It is concluded that the reliability of stimulation and suppression tests in determining the site of excessive androgen production should be accepted with reservation.

Studies on steroids in urine of the male newborn.

Four different methods of isolation and purification were utilized to study steroids in urine of male newborns which was collected during the first 5 days of life. These methods included celite column, ion exchange column and thin-layer chromatography, solvolysis and enzyme hydrolysis with beta-glucuronidase and aryl sulfatase. Procedural losses were evaluated by using radioactive internal standards. Final quantitation of each steroid was achieved by comparison of its chromatographic and quantitative behavior with the respective standard steroids on various gas-liquid chromatography systems, either as parent compound or as trimethylsilyl ether derivative. The following steroids were found in the amounts indicated: progesterone, 2.1 mug/1 (pool I), 4.6 mug/1 (pool III); pregnanediol, 625.0 mug/1 (pool IIa), 605.0 mug/1 (pool IIb glucuronide), 25.4 mug/1 (pool IIb sulfate), 4.2 mug/1 (pool IIb free), 729.0 mug/1 (pool III); 16alpha-hydroxyprogesterone, 713.0 mug/1 (pool III), 16alpha-hydroxypregnenolone, 14,000.0 mug/1 (pool III); 16alpha-hydroxydehydroepiandrosterone, 2,350.0 mug/1 (pool III); 16-dehydroprogesterone, 155.0 mug/1 (pool I), 21.2 mug/1 (pool IIb glucuronide), 97.5 mug/1 (pool IIb sulfate), 5.3 mug/1 (pool III); 16-dehydropregnenolone, 382.0 mug/1 (pool I), 1,380 mug/1 (pool IIb glucuronide), 172.0 mug/1 (pool IIb sulfate), 174.0 mug/1 (pool III); 16-dehydropregnanolone, 8.3 mug/1 (pool I), 239.0 mug/1 (pool IIb sulfate). Pregnenolone, pregnanolone, 17alpha-hydroxyprogesterone and 17alpha-hydroxypregnenolone could not be detected. The results support the concept that the steroid patterns of urine of the newborn and amniotic fluid are very similar and that the amniotic fluid steroid content is mainly dependent on fetal urinary steroid excretion. The data on delta16-C21-steroids are discussed.

Adrenal function in patients receiving medroxyprogesterone acetate

Adrenal and pituitary function studies consisting of ACTH stimulation and SU-4885 tests were performed on ten patients before and during medroxyprogesterone acetate injections for one year. Plasma cortisols and urinary excretion rates of 17-ketosteroid and 17-ketogenic steroids were measured before and during the test. The following observations were noted: (a) baseline plasma cortisol levels were lower after receiving medroxyprogesterone acetate injections; (b) with ACTH stimulation, 17-ketogenic steroids and plasma cortisol showed a normal response, whereas the excretion rates of urinary 17-ketosteroids showed variable responses; (c) with SU-4885, the increases in urinary 17-ketogenic steroid excretion rates in subjects receiving MPA was less than that observed prior to MPA, again, the 17-ketosteroid excretion rates were variable.

Carcinoma of the adrenal gland in children

Five cases of functioning adrenocortical carcinoma in children aged 8 mo to 11 yr have been treated in Manchester since 1953. Their endocrine signs and symptoms were those of either Cushing's syndrome or virilization or both. Differentiation of these patients from those with adrenocortical carcinoma was best accomplished by means of measurement of the 24-hr urinary steroid excretion and its response to dexamethazone infusion as well as by the use of an intravenous pyelogram and an angiogram. All children were treated by surgical removal of the tumor and postoperative irradiation with careful management of their steroid balance before, during, and after operation. Four of the five are living and free of recurrence for from 1 to 12 yr after operation.

Effects of a low-oestrogen oral contraceptive on urinary excretion of luteinizing hormone and ovarian steroids.

The urinary gonadotrophin and ovarian steroid excretion pattern was studied in five women taking an oral contraceptive formulation consisting of mestranol 50 mug and norethisterone 1 mg. Both the pretreatment and post-treatment cycles were normal. The ovulatory peak of luteinizing hormone (LH) during the treatment cycles was uniformly suppressed, but LH continued to be excreted within the normal range. In one fifth of the treatment cycles there was a pronounced and sustained rise of oestrogen output in the absence of ovulation, and in many of the other treatment cycles oestrogen levels suggested that active ovarian steroidogenesis was taking place.

Metabolic effects of ACTH in the sheep.

Metabolic effects of ACTH in the sheep.

Non-specific factors that may influence significance of urinary steroid excretion in breast cancer.

The urinary excretion of corticosteroids (17-oxogenic steroids) and adrenal androgens (11-deoxy-17-oxosteroids) was studied in women below the age of 50 in a variety of clinical situations for comparison with a normal group. The conditions studied were: chronic debility from non-malignant disease, weight reduction, admission to hospital and surgery for varicose veins, hepatic non-malignant disease, and non-mammary cancer.The objective of the study was to determine whether the changes found in early and advanced breast cancer and used to judge the prognosis of the disease are specific to the disease or are merely incidental to the degree of illness caused by the disease.Similar changes to those found in breast cancer-principally a reduction in the excretion of the androgens-were found in the women with severe hepatic disease and in advanced non-mammary cancer. These were also found to follow the effects of severe surgical stress.It is concluded that the changes found in breast cancer are a measure of the general systemic disturbance caused by the disease and are not due specifically to it. Nevertheless, the value of their prognostic significance remains unchallenged.

Relationships between some psychological assessments, body-build, and physiological stress responses.

A number of physiological responses to the psychological stress of an oral academic examination were observed, including heart rate, respiration rate, blood pressure, urinary 17-oxogenic steroid excretion, and plasma corticosteroid concentration. The results were related to body-build and to four psychological tests: Eysenck Personality Inventory, Taylor Manifest Anxiety Scale, IPAT Anxiety Scale, and Stimulus-Response Inventory. No significant associations were found between the psychological test results and anticipatory physiological activity just before the examination began, including excretion of 17-oxogenic steroids. Respiration rate was not increased by anticipatory stress, unlike the other variables, which were significantly higher than control values taken under resting conditions three months later. The students of primarily linear physique had significantly higher plasma corticosteroid values than the predominantly muscular subjects at the time of the examination, as found previously. They also had significantly higher analogue measures of the degree of anxiety experienced at the examination (assessed both by the subject and by an observer). Therefore, linear subjects appear to experience more anxiety than muscular students in a similar situation of psychological stress. Both the IPAT Scale and S-R Inventory results were significantly higher for the linear group but there were no significant differences for the EPI and TMAS scores, as used in previous studies. The importance of constitutional factors associated with body-build in relation to at least some aspects of personality is strongly suggested by the findings.

Urinary corticosteriod and diphenylhydantoin metabolite patterns in neonates exposed to anticonvulsant drugs in utero.

Five newborn infants, whose mothers had received anticonvulsant therapy throughout gestation (diphenylhydantoin and a barbiturate [4] or diphenylhydantoin alone [1]), were studied. Urinary steroids (6β‐OH‐cortisol, tetrahydrocortisone, 16α‐OH‐pregnenolone, and 16α‐OH‐dehydroepiandrosterone) and urinary 5‐parahydroxyphenyl, 5‐phenylhydantoin (HPPH, conjugated and unconjugated) were quantitatively assayed during the early neonatal period. The urinary steroid excretions were found not to be significantly different from those of normal full‐term newborn infants. Total HPPH excretion and the unconjugated/total metabolite ratios showed no correlation with urinary steroid excretion. Thus, the enhanced 6β‐hydroxylation of cortisol seen in adults after barbiturate or diphenylhydantoin was not observed in newborns exposed to these drugs in utero.

Blood "Cortisol" Levels From Spironolactone

To the Editor.— The recent report of Greenblatt and Koch-Weser 1 describing gynecomastia and impotence as complications of spironolactone therapy reminded us of a patient with another endocrine complication. In a 40-year-old man with progressive anasarca for two months, investigations suggested a diagnosis of idiopathic cardiomyopathy with passive congestion of the liver. A plasma cortisol level was obtained because of truncal obesity, abdominal striae, and impaired glucose tolerance. Plasma cortisol levels of 212 to 600μg/100 ml were reported (normal values 7-27). The patient had been receiving as much as 400 mg of spironolactone a day. The plasma cortisol concentrations were performed by the Mattingly method. Urinary steroid excretion was normal. The spurious elevation of plasma cortisol levels as determined by the Mattingly method in patients treated with spironolactone has been well established. 2,3 Awareness of this complication will prevent unnecessary investigation of abnormally elevated plasma cortisol. Wood et al 3

Tryptophan metabolism in breast cancer. Correlation with urinary steroid excretion.

Urinary excretion of t ryptophan metabolites, etiocholanolone, androsterone, and 17-hydroxycorticosteroids (17-OHc.s.), was measured in 25 patients with breast cancer a n d i n 12 similarly aged control women. Twelve of the 25 patients had elevated excretions of metabolites of the kynurenine-niacin pa thway, and, in these patients, t he excretion of etiocholanolone was significantly lower t h a n in controls or in patients with normal t ryp tophan metabolism.

Detailed hormonal studies during and after pregnancy in a previously hypophysectomized patient.

ABSTRACT This is a report on detailed hormonal studies before, during, and after pregnancy in a hypophysectomized patient who conceived after treatment with human gonadotrophins. On the basis of the results the following conclusions were drawn: In a patient who, judging by numerous investigations, no longer had any production of pituitary gonadotrophic hormones, it was possible by treatment with human gonadotrophic hormones to induce ovulation, without further stimulation to attain conception and preserve the conceptus, to carry through a normal pregnancy, ending at term in vaginal delivery of a normal infant. In this patient, whose pituitary corticotrophin production had totally ceased or had been negligible before the pregnancy, the endocrine state appeared to be completely normalized during pregnancy; thus: on unchanged corticosteroid medication the mean plasma corticoid concentration as well as the urinary excretion of corticoid metabolites, 17-ketogenic steroids, and 17-ketosteroids were considerably higher during than after the pregnancy, the urinary excretion of pregnanediol, oestriol and chorionic gonadotrophin was normal during the pregnancy. Moreover, the results of metyrapone tests before, during and after the pregnancy, ACTH stimulation test after delivery, and measurements of diurnal fluctuations in the concentration of plasma cortisol during the pregnancy are reported. The increased steroid production during pregnancy may be partially explained as a consequence of the activity in the foeto-placental unit which, however, can hardly have been quantitatively decisive. It must be presumed, therefore, that as a result of the pregnancy ACTH or an ACTH-like factor has been secreted, stimulating the maternal adrenal. It is assumed that the corticotrophin has been produced in the placenta and that it has passed to the maternal circulation.

Malignant melanoma with ectopic production of adrenocorticotropic hormone. Palliative treatment with inhibitors of adrenal steroid biosynthesis.

A 56-yr-old woman developed severe Cushing's syndrome and recurrent malignant melanoma three years after the removal of the primary lesion. She had elevated plasma cortisol levels which showed no normal diurnal rhythm. Neither these nor her elevated urinary steroid excretion were suppressed by administration of high doses of dexamethasone. She had markedly elevated plasma immunoreactive ACTH levels. Bioactive and immunoreactive ACTH was present in an extract of the metastic tumor tissue. This is the first documented case of ectopic ACTH syndrome caused by malignant melanoma. The patient, who was moribund from the effects of severe hypercortisolism, was cured of her Cushing's syndrome by the combined administration of aminoglutethimide, metyrapone, and o,p'DDD. She was dramatically improved clinically, despite steady progression of tumor growth. It appears that the use of o,p'DDD, especially in combination with inhibitors of adrenal steroid biosynthesis, is an effective means for correcting hypercortisolis...

Urinary steroid levels in newborn infants with intrauterine growth retardation.

Urinary steroid excretion of 6β-OH-cortisol (6β-OH-F), tetrahydrocortisone (THE), l6α-OH-pregnenolone (16α-0H-PG) and 16a-OH-dehydroepiandrosterone (16α-OH-DHA) was determined in 23 full-term normal newborn infants, 8 normally grown premature and 8 intra-uterine growth retarded (IUGR) newborns. The method used measured free, glucuronide- and sulfate-conjugated steroids. Labeled internal standards were used for each steroid measured. The excretions were expressed in relation to urinary creatinine levels. Steroid excretion values in the normally grown full-term and premature groups were quite similar. On comparison of steroid excretion values in the IUGR and normal full-term groups by the Mann-Whitney (two-tailed) test, there were no significant differences in 6β-OH-F and THE excretions but the excretions of 16α-0H-PG and 16α-0H-DHA were significantly less (p < 0.02 and p < 0.01, respectively) in the IUGR group. The ratio 6β-OH-F + THE/16α-OH-PG + 16α-OH-DHA was significantly greater in the IUGR infants tha...

Effect of vitamin e on urine porphyrin and steroid profiles in porphyria cutanea tarda; report of four cases

Four patients with porphyria cutanea tarda were treated with high oral doses of vitamin E for a period of three months. Their urinary excretion of porphyrins and steroids was studied before and during treatment. Administration of vitamin E decreased urinary porphyrins. It also lowered the amounts of excreted pregnandiol, which had been abnormally high beforehand. The relationship between vitamin E and the metabolism of steroids and porphyrins is discussed. It is suggested that vitamin E may promote greater utilization of porphyrins in hemeproteins, and so might increase the synthesis of the heme-containing enzymes involved in steroid metabolism.

Pituitary gonadotrophic and ovarian function in women treated with clomiphene citrate.

Serial estimations of follicle-stimulating hormone (FSH) and luteinising hormone (LH), as well as of oestrogens and pregnanediol have been performed in the urine of 5 women suffering from a variety of gynaecological conditions associated with infertility who were treated with clomiphene citrate at different dose levels. One subject became pregnant following medication; in the other 4 evidence for ovulation was present in one and was at best equivocal in the remaining 3. The effect of the compound on urinary FSH and LH levels was variable as was the pattern of urinary steroid excretion following medication; in 2 subjects a rise of oestrogen output preceded that of LH excretion. The study confirms previous observations indicating that atypical luteal function may follow clomiphene administration and underlines the fact that wide variations of hormonal response to the compound can occur.

Metabolic responses to acute and chronic L-dopa administration in patients with parkinsonism.

Abstract The metabolic effects of L-dopa were studied in 23 patients with Parkinsonism. Levels of plasma growth hormone were elevated two hours after administration of 0.5 to 1.0 g of L-dopa, and this response persisted for at least one year. Plasma glucose was increased at two hours, and free fatty acids at four hours. Chronic therapy significantly increased serum cholesterol (approximately 10 per cent), but no change in serum triglycerides, thyroxine, fasting blood sugar, and 24-hour urinary excretion of 17-keto and 17-ketogenic steroids was observed. After one year of chronic L-dopa therapy, there was a decrease in glucose tolerance associated with a delayed and exaggerated insulin response. The changes in growth hormone and carbohydrate tolerance suggest that patients receiving L-dopa for long periods should be monitored for the possible development of frank acromegaly.

Vitesses des processus de renouvellement du cholestérol contenu dans son espace de transfert, chez le rat: IV. Influence de l'âge, du poids, du sexe, de la gestation et de la lactation

The isotopic equilibrium method was applied to 24-month-old male rats of varied weights and to virgin, pregnant or lactating female rats. Compared with young adult rats (350 g), the rate of cholesterol synthesis decreases (50%) in old rats whose weights were kept constant (335 g) by a restricted caloric intake. This decrease is explained mainly by this restriction. The synthetic rate expressed per 100 kcal and 100 g of body weight is only 25% lower than that of young adult rats. The same result is obtained with old rats fed ad libitum and weighing 560 g. In both groups, the turnover time of cholesterol is increased (35 and 37 days) as compared to that of young adult male rats (24 days). The cholesterol turnover time of female rats is practically equal to that of male rats, but its dynamic equilibrium differs on three points: (1) synthesis rate, expressed as percentage of total body weight and of caloric intake, is lower (35%), (2) proportionally to the external secretion, the fecal excretion of cholesterol is higher, (3) the urinary excretion of steroids must be take into account for the balance. These two last points are more important in pregnant or lactating rats. For these females, the synthetic rates of cholesterol are increased 2- and 3-fold, respectively. The contributions of placenta, mammary glands, intestine and liver to these increases are considered and discussed.

Symposium on Mammary Neoplasia

An international conference on mammary neoplasia sponsored by the Institute for Medical Research and the National Institutes of Health was held in Cherry Hill New Jersey on November 11-13 1971. 2 reports given focused on the genetic aspects of breast cancer. Bulbrook reported on the urinary steroid excretion patterns in women while Brennan and Wolfe studied the usefulness of xeroradiography in detecting ductal hyperplasia. Paymaster reviewed the epidemiology of breast cancer in India while Ozzello suggested that human breast cancer cells may perform a variety of synthetic and secretory activities. Sarkar suggested that there may be a connection between human breast cancer and RNA viruses and Dalton presented the ultrastructural detail of the mouse feline and human RNA virus. Nandi discussed his recent studies which attempt to locate the mammary tumor virus activity in blood. Concerning tissue and organ culture Lasfargues outlined a new method of growing human breast cancer cells in suspension cultures. Concerning immunology and interferon Blair attempted to elucidate the observation that immunodepression depressed MTV-induced mammary tumor development. Studies have shown striking regression of spontaneous breast cancers in animals following the administration of interferon inducers. Although the role of specific RNA viruses in the oncogenesis of many animal tumors is widely accepted the exact genetic mechanisms by which the viral RNA is expressed causes malignant transformation in the intact animals are not clear. The recent discovery of the enzyme reverse transcriptase and the subsequent demonstration that it is an integral part of all RNA tumor virions has opened a new field of investigation. Spiegelman Schlom Gallo and Temin all reported on it. Muhlbock reported on the influence of prolactin and estrogen on breast cancer as did Meites and Pearson. Thus the relation of an oncogenic virus to breast cancer and the role of reverse transcriptase in tumor viruses were thoroughly discussed at the conference.