Excretion Of 17-ketogenic Steroids Research Articles

Adrenal Function in females with low plasma HDL-C due to mutations in ABCA1 and LCAT.

IntroductionAdrenal steroidogenesis is essential for human survival and depends on the availability of the precursor cholesterol. Male subjects with low plasma levels of high density lipoprotein (HDL) cholesterol are characterized by decreased adrenal function. Whether this is also the case in female subjects with low plasma HDL-C levels is unresolved to date.Findings15 female ATP binding cassette transporter AI (ABCAI) and 14 female lecithin-cholesterol acyltransferase (LCAT) were included in the study. HDL-C levels were 38% and 41% lower in ABCA1 and LCAT mutation carriers compared to controls, respectively. Urinary steroid excretion of 17-ketogenic steroids or 17-hydroxy corticosteroids did not differ between 15 female ABCA1 mutation carriers (p = 0.27 vs 0.30 respectively) and 30 matched normolipidemic controls or between 14 female LCAT mutation carriers and 28 matched normolipidemic controls (p = 0.10 and 0.14, respectively). Cosyntropin testing in an unselected subgroup of 8 ABCA1 mutation carriers and 3 LCAT mutation carriers did not reveal differences between carriers and controls.ConclusionAdrenal function in females with molecularly defined low HDL-C levels is not different from controls. The discrepancy with the finding of impaired steroidogenesis in males with molecularly defined low HDL-C levels underscores the importance of gender specific analyses in cholesterol-related research.

High density lipoprotein as a source of cholesterol for adrenal steroidogenesis: a study in individuals with low plasma HDL-C

Few studies have addressed the delivery of lipoprotein-derived cholesterol to the adrenals for steroid production in humans. While there is evidence against a role for low-density lipoprotein (LDL), it is unresolved whether high density lipoprotein (HDL) contributes to adrenal steroidogenesis. To study this, steroid hormone profiles in urine were assessed in male subjects suffering from functional mutations in ATP binding cassette transporter A1 (ABCA1) (n = 24), lecithin:cholesterol acyltransferase (LCAT) (n = 40), as well as in 11 subjects with low HDL cholesterol (HDL-C) without ABCA1/LCAT mutations. HDL-C levels were 39% lower in the ABCA1, LCAT, and low HDL-C groups compared with controls (all P < 0.001). In all groups with low HDL-C levels, urinary excretion of 17-ketogenic steroids was reduced by 33%, 27%, and 32% compared with controls (all P < 0.04). In seven carriers of either type of mutation, adrenocorticotropic hormone (ACTH) stimulation did not reveal differences from normolipidemic controls. In conclusion, this study shows that basal but not stimulated corticosteroid metabolism is attenuated in subjects with low HDL-C, irrespective of its molecular origin. These findings lend support to a role for HDL as a cholesterol donor for basal adrenal steroidogenesis in humans.

XYY males found in a general male population. Cytogenetic and physical examination.

Five males with karyotype 47,XYY were found among 3840 men examined for military service, giving a prevalence of 1.30 per 1000. The five XYY males had a normal male phenotype and no physical abnormalities, except for minor columna vertebralis aberrations. There was a slight increase of the β1 fraction of alkaline phosphatases. Testis histology showed impairment of spermatogenesis in all four in whom this examination was made. Electroencephalogram was slightly abnormal in two of the five males. There was a comparatively low urinary excretion of pituitary gonadotrophins, dehydroepiandrosterones and oestrogenes and a comparatively high urinary excretion of 17-ketogenic steroids; these deviations in hormone excretion were, however, not very pronounced.

Treatment of seasonal allergic rhinitis with once-daily intranasal fluticasone propionate therapy in children

Purpose: To evaluate the efficacy and tolerability of intranasally administered fluticasone propionate, 200 μg or 100 μg (half the adult dosage) when administered once daily for 4 weeks to children with seasonal allergic rhinitis. Design and setting: Double-blind, randomized, placebo-controlled, parallel-group clinical study in 10 pediatric outpatient centers. Subjects: Children (n = 249), 4 to 11 years of age, with moderate to severe symptoms of seasonal allergic rhinitis, positive skin test reaction to a local autumn allergen, and a history of seasonal allergic rhinitis. Measurements: Clinician- and patient-rated nasal symptom scores (obstruction, rhinorrhea, sneezing, itching), clinician-rated assessment of overall response to treatment, patient-rated nasal obstruction on awakening, and use of rescue medication. Clinicians questioned patients (or parents) regarding symptoms and adverse events. Morning plasma cortisol concentrations and 24-hour urinary excretion of cortisol and 17-ketogenic steroids were evaluated. Results: Intranasal fluticasone propionate, 200 μg or 100 μg once daily, was significantly more effective than placebo in the treatment of seasonal allergic rhinitis in children. Clinician- and patient-rated symptom scores indicated greater improvement in nasal symptoms, including nasal obstruction on awakening, among patients receiving intranasal fluticasone propionate. Overall response to treatment was also significantly greater in the active treatment groups. The two fluticasone propionate groups were not statistically different. Mean morning plasma cortisol concentrations and 24-hour urinary excretion of free cortisol and 17-ketogenic steroids were similar across all groups both before and after treatment. Conclusions: Intranasal fluticasone propionate, 100 μg (half the adult dose) or 200 μg given once daily for 4 weeks is effective and well tolerated in children 4 to 11 years of age with seasonal allergic rhinitis. (J P EDIATR 1994;125:628-34)

Plasma prolactin response to submaximal stimulation by TRH and endogenous corticosteroids in man.

Recent studies suggest that submaximal plasma prolactin responses to TRH may reflect the effects of endogenous dopamine on prolactin release more accurately than basal plasma prolactin levels or maximal plasma prolactin responses to TRH. In the present study the plasma prolactin response to 12.5 micrograms i.v. TRH in 25 male subjects was significantly correlated with 24-hour urinary 17-ketogenic steroid excretion (= "total" 17-hydroxy corticosteroids). With regard to the basal plasma prolactin level or the prolactin response to 200 micrograms i.v. TRH, no such relation with corticosteroid excretion was detected. It is concluded that the plasma prolactin response to 12.5 micrograms i.v. TRH may provide a new, useful investigative tool with which to study corticosteroid-dopamine interactions and central dopamine activity in man.

Role of androgens in menstrual disorders of nonhirsute and hirsute women, and the effect of glucocorticoid therapy on androgen levels in hirsute hyperandrogenic women

The plasma concentrations of total testosterone, free testosterone index, androstenedione, 17β-estradiol, luteinizing hormone, follicle-stimulating hormone, prolactin, and urinary 17-ketosteroid and 17-ketogenic steroid excretion were measured in 48 nonhirsute and 119 hirsute patients. Hormone data were compared within and between groups according to whether the menstrual cycles were eumenorrheic, amenorrheic, or oligomenorrheic. Eleven hirsute women treated with prednisone were followed for 6 months. It was concluded that: (1) androstenedione, testosterone, free testosterone index, and adrenal androgens alone or in combination play a role in the pathogenesis of the hirsutism observed in eumenorrheic women and in the amenorrhea and oligomenorrhea of both hirsute and nonhirsute women; (2) body weight correlated with adrenal adrogens (17-ketosteroids) in nonhirsute women and with androstenedione in hirsute women; (3) prednisone significantly suppressed androstenedione and 17-ketosteroids (p < 0.05), with a decline of testosterone to 65% and luteinizing hormone to 51% of pretreatment values, with favorable clinical effects on the hirsutism, menstrual dysfunction, and infertility; (4) concentrations of 17β-estradiol were lower in amenorrheic than in eumenorrheic and oligomenorrheic women of both groups.

Comparative study of the effect of oral contraceptives containing 50 μg of estrogen and those containing 20 μg of estrogen on adrenal cortical function

Because the adrenal cortex is an endocrine gland essential to life, its function was studied in women who were taking an oral contraceptive that contained either 50 μg or 20 μg of estrogen. Of 32 healthy women studied, 18 used an oral contraceptive that contained 50 μg of estrogen, and 14 used an oral contraceptive that contained 20 μg of estrogen. With 50 μg of estrogen, the total plasma cortisol level rose significantly, the level of urinary cortisol excretion did not change significantly, and the levels of 17-ketosteroids and 17-ketogenic steroids were significantly reduced. With 20 μg of estrogen, there were no significant changes in the levels of total plasma cortisol, urinary cortisol excretion, and the excretion of 17-ketosteroids and 17-ketogenic steroids. Thus, adrenal cortical function was altered in women who used an oral contraceptive that contained 50 μg of estrogen, but there was no significant effect with the use of an oral contraceptive that contained only 20 μg of estrogen. Our findings confirm previous ones in regard to the effects of 50 μg of estrogen on adrenal cortical function, although no studies had been carried out previously on the effects of 20 μg of estrogen.

SERUM TESTOSTERONE, FSH/LH AND URINARY EXCRETION OF ESTROGENS AND CORTICOIDS DURING TREATMENT WITH AN INJECTABLE, LONGACTING ESTROGEN‐DHEA PREPARATION

Ten weeks after total hysterectomy and bilateral salpingo-oophorectomy, nine women were treated with injections of Gynodian, composed of 4 mg estradiol valerate and 200 mg dehydroepiandrosterone enanthate, followed by injections of Primodian, composed of 4 mg estradiol valerate and 90.27 mg testosterone enanthate. Before commencement of treatment estimation of serum FSH, LH and testosterone, and analyses for total estrogen, 17-ketogenic steroids and fractionated 17-ketosteroids in 24-hour urine samples were carried out in all patients. The same serum and urine analyses were made 2 weeks after the first Gynodian injection and the first Primodian injection respectively. Serum testosterone concentrations did not change during treatment with Gynodian, whereas they rose markedly after administration of Primodian. Two weeks after the first injection of Gynodian and also of Primodian, the total estrogen excretion was only slightly increased in comparison with the value measured before start of treatment, and the serum FSH/LH ratio was only slightly depressed. The daily urinary excretion of 17-ketogenic steroids and of fractionated 17-ketosteroids were unchanged during treatment.

ADRENOCORTICAL RESPONSE UPON REPEATED STIMULATION WITH CORTICOTROPHIN IN PATIENTS LACKING ENDOGENOUS CORTICOTROPHIN SECRETION

ABSTRACT The role played by a normal endogenous corticotrophin secretion in the mechanism by which adrenocortical steroidogenic response to ACTH increases as a result of previous administration of the peptide, was assessed by repeated ACTH administration in 25 patients under prolonged cortico-therapy and in 13 patients with anterior hypophyseal insufficiency. The response to ACTH (250 μg tetracosapeptide iv over 8 h) was evaluated on the basis of changes in plasma cortisol and in the urinary excretion of cortisol and 17-ketogenic steroids. The steroidogenic response to the first ACTH infusion was markedly reduced in these patients when compared to control subjects, or even to subjects on short-term dexametasone. However, in these patients as in normals, acute ACTH administration was followed by a phase, lasting for 3 days at least, during which the steroidogenic response to further ACTH stimulation was increased. When ACTH was infused repeatedly on 4 consecutive days in patients on long-term cortico-therapy, adrenocortical responsiveness was rapidly restored to normal. By contrast, when ACTH was administered every fourth day, a less pronounced enhancement of adrenocortical responsiveness occurred, the secretory activity returning to previous hypo-adrenal state between each stimulation.. These data indicate that the mechanism of amplified adrenocortical response to ACTH does not require continuous endogenous corticotrophin secretion. They further suggest that intermittent corticotrophin therapy may be more adequate in promoting recovery of adrenocortical function on steroid withdrawal than a schedule consisting of daily ACTH administration, since the latter is thought to slow down hypothalamic-pituitary activity because of concomitant sustained enhancement of steroidogenesis.

Critical Evaluation of the 5-Day Metyrapone Test

Different parameters of the response to the 5-day metyrapone test were evaluated for their diagnostic accuracy in tests given to 58 children and adolescents as part of an investigation for short stature. Insulin test, vasopressin test and ACTH test were used for diagnostic reference. A log transformation of the data was clearly appropriate. The maximal daily excretion of 17-ketogenic steroids was distinctly positively correlated with the basal excretion. Consequently, the most correct parameter of the response is the SD score of the deviation of the maximal excretion from the regression of the maximal excretion on the basal excretion in the reference population. This parameter, 'relative maximal excretion' was shown to be the diagnostically most accurate index of the response of 11 parameters studied.

CONVENTIONAL PITUITARY IRRADIATION IN ACROMEGALY

Thirty-one patients who had been treated for acromegaly for 1-21 years with conventional pituitary irradiation were re-examined. Immunoreactive growth hormone (GH) was measured in connection with an oral glucose load. Adrenal and gonadal functions were assessed on the basis of plasma cortisol and the urinary excretion of 17-ketogenic steroids, 17-ketosteroids and gonadotrophins. In evaluating the thyroid-pituitary axis the thyrotrophin-releasing hormone stimulation test (TRH) was used. Initially 30 patients had experienced definite benefit from the treatment but at the time of re-examination 10 still had clinically active disease and required another type of treatment. Normal GH levels (less than 5 ng/ml/1) were seen in only 12 patients. Skin thickness was normal in 15 out of 30. Thus the remission rate can be evaluated as being 67% as regards clinical activity, 50% with regard to skin thickness and 39% in terms of GH levels. Hypogonadism occurred in 12 patients (39%) and adrenal and thyroid failure in 5 patients each (16%). The response to TRH was within the normal range in 2 of the hypothyroid patients. In 22 euthyroid patients the mean increment in serum TSH in response to 200 mug of synthetic TRH was only 5.8 mU/1 which was significantly below the normal mean 12.5 mU/1. Furthermore, in 7 of these patients (32%) the response was absent or subnormal (less than 3.0 mU/1). This indicated that the pituitary is capable of secreting enough TSH for maintenance of an euthyroid state but that its capacity is limited. Conventional pituitary irradiation is not a very effective treatment in acromegaly but may still be recommended in selected cases.

Influence of aging upon the urinary hormone excretion in the male.

The urinary excretion of LH, low polar oestrogens, neutral C19 and C21 steroids was measured in normal healthy males aged 20-79 years. No significant changes could be noted for the excretion of LH, pregnanediol and 17-ketogenic steroids between 50 and 79 years. The excretion of androsterone and aeticholanolone was significantly lower in the oldest group (70-79 years). A significant drop in the excretion of DHA was noted at approx. 60 years. The excretion of low polar oestrogens remained constant from 20 to 55-59 years, but showed a highly significant (P less than 0.001) decrease at about 60 years. This drop might reflect a sudden decrease in the plasma levels of oestrone sulphate due to a decreased sulphurylating activity in the liver.

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.

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.

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.

A CASE OF ADRENOCORTICAL HYPERFUNCTION NORMALIZED DURING THE SECOND AND THIRD TRIMESTERS OF THREE PREGNANCIES

ABSTRACT Detailed hormonal studies were performed before, during and after three pregnancies in an untreated patient with adrenocortical hyperfunction due to hyperplasia. The patient was clinically characterized by oligomenorrhoea and moderate hirsutism, but showed no signs of virilization or of Cushing's disease. In the non-pregnant state her 17-ketosteroid excretion was elevated to twice the normal value, the androsterone fraction being moderately and the aetiocholanolone fraction greatly elevated, whereas the excretion of dehydroepiandrosterone was essentially normal. In the non-pregnant state the excretion of 17-ketogenic steroids, tetrahydrocortisol, tetrahydrocortisone, cortisone and tetrahydrocorticosterone was also considerably elevated. On high doses of dexamethasone (8 mg daily) or cortisone (100 mg daily) all fractions of 17-ketosteroids as well as the cortisol metabolites were suppressed to about one-half. Without preceding or simultaneous steroid treatment the patient conceived three times. During all three pregnancies every sign of excessive hormone production ceased. The excretion of 17-ketosteroids in all fractions fell to 20–30%, that of 17-ketogenic steroids to between 30% and 35 %, and that of cortisol metabolites to between 5 % and 46 % of the levels found before and after the pregnancies. The considerable endocrine activity of the foeto-placental unit may have "normalized" the maternal hypothalamic-pituitary-adrenocortical feed-back mechanism, either by suppressing or by altering the sensitivity of the feed-back system. An alternative theory might be an accelerated rate of cortisol metabolism by the liver in the non-pregnant state which is normalized during the last two trimesters of the pregnancies. The findings are being published as a contribution to the elucidation of the endocrinology of pregnancy.

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.

Adrenal cortical function in severe burns.

Severely burned patients have prolonged high levels of free plasma cortisol and a decrease in plasma corticosteroid binding globulin. The four consistent changes in the urinary corticosteroid excretion pattern were as follows: (1) prolonged increase in cortisol excretion, which may reflect the sustained high free plasma levels; (2) temporary increase of the 17-ketosteroids, followed by return to normal levels; (3) similar rise and fall in the Porter-Silber chromogen levels; and (4) prolonged increased excretion of 17-ketogenic steroids. The sustained increase of 17-ketogenic steroids, as opposed to the rapid decrease of Porter-Silber chromogens, suggests that corticosteroids other than cortisol are secreted in larger than normal quantities, in response to the prolonged stress of severe burns. The increased amounts of alpha-ketolytic corticosteroids in the plasma of these patients would support this hypothesis.

Plasma steroids in two subjects with ovarian androgen-producing tumors arrhenoblastoma and gynandroblastoma.

Two virilized women with gonadal stromal tumors, one histologically an arrhenoblastoma and the other a gynandroblastoma, were investigated. Routine urine steroid analyses showed normal excretion of 17-ketosteroids and 17-ketogenic steroids and a normal response to ACTH administration. Dexamethasone dministration was without major effect on the excretion of 17-ketosteroids. Analyses of plasma neutral steroid sulfates revealed a pattern which was quite similar in these two patients but very different from that seen in normal subjects. Dehydroepiandrosterone sulfate was present in normal concentrations, whereas the levels of androsterone and epiandrosterone sulfates were clearly elevated. Androsterone sulfate was the main plasma neutral steroid sulfate. The oncentrations of androsterone and epiandrosterone sulfates were unaffected by dexamethasone but increased greatly in response to treatment with human chorionic gonadotropin. Testosterone was the main unconjugated steroid secreted by both tumorous ovaries....