ETIOCHOLANOLONE FEVER. REPORT OF A CASE IN CHILDHOOD WITH PERIODIC PERITONITIS ASSOCIATED WITH ELEVATED SERUM ETIOCHOLANOLONE.
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17-Ketosteroids↗
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Periodic fever associated with increased plasma unconjugated etiocholanolone and granulomatous liver disease: case report and studies in etiocholanolone and cortisol conjugation.
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Anatomy↗
Effects of etiocholanolone-induced fever on plasma antipyrine half-lives and metabolic clearance.
The plasma half-life and metabolic clearance rate of antipyrine, a drug metabolized by hepatic microsomal enzymes, were determined in 33 normal volunteers during a basal state and during fever induced with a single intramuscular injection of etiocholanolone. Of the 14 normal volunteers who achieved significant fever (fever index greater than 50), in 11 plasma antipyrine half-life was prolonged after a single oral dose of 10 mg/kg and antipyrine metabolic clearance rate was decreased. There was no significant change of these mean values in 19 normal volunteers who failed to develop significant fever (fever index smaller than 50). Therefore, under the conditions of this study plasma antipyrine half-life was prolonged, probably due to impaired hepatic metabolism, during etiocholanolone-induced fever, although no correlation was observed between the magnitude of fever and the extent to which plasma antipyrine half-life was prolonged. Failure to obtain such a correlation may be attributable to the very small range of temperature elevation, extending from 37.9 degrees C to 39.2 degrees C, in the group of 14 subjects achieving significant etiocholanolone-induced fever (fever index greater than 50). A higher dose of antipyrine (18 mg/kg) suppressed induction of fever by etiocholanolone; antipyrine is the only orally administered drug thus far shown to be effective in repressing etiocholanolone-induced fever.
Adolescent↗
Radioimmunoassay for etiocholanolone.
A sensitive and reliable radioimmunoassay for serum unconjugated etiocholanolone (3alpha-hydroxy-5beta-androstan-17-one) is reported. The antiserum was obtained from rabbits by immunization of etiocholanolone-17-(O-carboxymethyl) oxime [CMO]-bovine serum albumin [BSA]. Two ml of serum with 3H-etiocholanolone added for recovery was extracted with ether, and etiocholanolone was separated from cross-reacting steroids by Sephadex LH-20 column chromatography. The mean recovery after extraction and chromatography was 80.7 +/- 6.8 (S.D.)%. The sensitivity of the assay was less than 40 pg. The intraassay and interassay coefficients of variation were 9.2% and 10.9%, respectively. The mean of serum unconjugated etiocholanolone concentration determined by the present method was 0.39 +/- 0.10 (S.D.) ng/ml (n = 50) in normal men and 0.36 +/- 0.08 (S.D.) ng/ml (n = 20) in women in the follicular phase of the menstrual cycle.
Adult↗
The urinary dehydroepiandrosterone, androsterone and etiocholanolone excretion of healthy women and women with benign and malignant breast disease.
The 24-h urinary excretion of dehydroepiandrosterone, androsterone and etiocholanolone was followed in healthy women (n = 50) and in women with benign-fibroadenoma (n = 32), microcysts (n = 32), macrocysts (n = 25) and malignant (n = 35) breast disease aged 35-50 years. The data were analysed in three groups each covering 5 years (35-39, 40-44 and 45-49). A significant decrease in the excretion of etiocholanolone and dehydroepiandrosterone was found in women with benign and malignant breast disease when compared to controls. There was no significant decrease in androsterone excretion in women with benign and malignant breast disease when compared to a control group. A high correlation was found between excretion of etiocholanolone and its precursor dehydroepiandrosterone both in women with benign-fibroadenoma (r = 0.7683) or macrocysts (r = 0.7337) and in women with malignant (r = 0.805) breast disease. Dehydroepiandrosterone and, in particular, etiocholanolone excretions were found to decrease significantly with age in women affected by malignant breast disease.
Adenofibroma↗
Comparison of agents producing a neutrophilic leukocytosis in man. Hydrocortisone, prednisone, endotoxin, and etiocholanolone.
To study the potential application of glucocorticosteroid administration for the measurement of the bone marrow neutrophil reserve response, blood neutrophil count changes were measured in normal subjects after the administration of intravenous hydrocortisone (25, 50, 100, 200, and 400 mg) and oral prednisone (5, 10, 20, 40, and 80 mg). The upper three doses of both steroids increased the blood neutrophil count by approximately 4,000 cells/mm3. The neutrophilia occurring after hydrocortisone (200 mg) and/or prednisone (40 mg) was compared with that observed after endotoxin (0.8 ng/kg) and etiocholanolone (0.1 mg/kg) in 14 normal subjects, 7 patients with Wegener's granulomatosis on cyclophosphamide therapy and 10 patients with chronic idiopathic neutropenia. The normal responses (mean increase of blood neutrophils/mm3 above base line +/- 1 SEM) were: hydrocortisone 4,220 +/- 320, prednisone 4,610 +/- 360, endotoxin 6,060 +/- 880, and etiocholanolone 3,780 +/- 440. In the patient studies, etiocholanolone gave the smallest mean responses, but, in general, the results were similar for all agents. These data indicate that these glucocorticosteroids can be used as equivalent agents to endotoxin and etiocholanolone for measuring the neutrophil reserve response.
Adult↗
Recurrent fever of unknown etiology: failure to demonstrate association between fever and plasma unconjugated etiocholanolone.
A sensitive method for determination of plasma unconjugated etiocholanolone by double-isotope-derivative dilution has been described. The mean values for normal subjects was 0.038+/-0.003 (SEM) mug/100 ml.40 patients, 20 with familial Mediterranean fever and 20 with other diseases characterized by recurrent fever were studied. The over-all mean concentration of plasma unconjugated etiocholanolone for the patients (febrile or afebrile) was 0.101 +/-0.012 mug/100 ml, significantly above that of normals. Mean plasma values for the patients while they were febrile did not differ from the mean values when they were afebrile. It is suggested that the concentration of plasma unconjugated etiocholanolone is not related to fever in these patients.
Carbon Isotopes↗
Alcohol and marrow granulocyte reserve response to etiocholanolone.
Measurement of the size of marrow granulocyte reserve (MGR) was performed in ten alcoholic patients with clinically uncomplicated Laennec's cirrhosis and in ten healthy subjects by etiocholanolone injection before and during oral 95% ethyl alcohol administration (30 to 60 ml in orange juice every 6 hours for 48 hours). No significant differences in bone marrow response to etiocholanolone were found between normal subjects studied before and during alcohol administration. The group of cirrhotic patients failed to demonstrate a reduction of MGR when compared to control subjects and alcohol administration did not result in an abnormal response to etiocholanolone. It is suggested that the MGR is normal in most alcoholic patients with clinically uncomplicated Laennec's cirrhosis and is not influenced by acute alcohol ingestion. These results are in contrast to other previous reports in which bacterial endotoxin was used to estimate granulocyte reserve.
Adult↗
Studies on steroid fever: I. Production of leukocyte pyrogen in vitro by etiocholanolone.
When a serum-buffer solution of etiocholanolone is incubated with human blood leukocytes in vitro, a pyrogen is released. Like endogenous pyrogen of leukocyte origin, this pyrogen produces prompt monophasic fevers in rabbits, does not induce fever tolerance when given daily, and is inactivated by trypsin. In many respects, the characteristics of the in vitro reaction resemble experimental steroid-induced fever. For example, release of pyrogen varies directly with the concentration of steroid. 4-8 hr of contact between steroid and leukocyte is required for activation of the cell. Rabbit leukocytes are not activated by etiocholanolone. Finally, androsterone, the 5alpha-isomer of etiocholanolone, does not induce pyrogen release in vitro. These studies suggest that experimental steroid fever in man may be mediated by an endogenous pyrogen released from leukocytes.
Journal Article↗
The uptake of etiocholanolone by human bone marrow immature granulocytes.
A cell fraction enriched in immature granulocytes was obtained after fractionation of human bone marrow by a three-step procedure. This fraction sediments at an average density of 1.073 and has a high content of myelocytes and metamyelocytes. It showed the highest specific uptake of etiocholanolone when compared to other bone marrow cell fractions. Autoradiographic studies demonstrated a higher number of silver grains over myelocytes and metamyelocytes than in other cell types. These results suggest the presence in human bone marrow of a target cell for etiocholanolone, located in the late mitotic or postmitotic pool or granulocytes.
Autoradiography↗
A case of periodic fever--reevaluation of etiocholanolone fever as an established clinical entity.
A case of periodic fever is reported in a 28-year-old male. The patient's clinical and laboratory findings fulfilled diagnostic criteria for etiocholanolone fever (EF). The most crucial endocrine data comprised higher values of both urinary etiocholanolone/androsterone ratio and plasma unconjugated etiocholanolone on febrile days, as compared to the values on afebrile days. However, the author hesitates to promptly diagnose him as EF, because of arguments against EF as an isolated clinical entity, and also because of the presence of auto-antibodies suggestive of an early stage of collagen disease(s). If the patient should develop a florid collagen disease in later clinical course, this case could be another evidence against EF as an established clinical entity, thus a careful follow-up is needed.
17-Hydroxycorticosteroids↗
Changes in human serum amyloid A and C-reactive protein after etiocholanolone-induced inflammation.
Secondary amyloidosis is a complication of diseases characterized by recurrent acute inflammation. In this study, a standardized stimulus which induced fever and inflammation was given to six normal subjects (19-24 yr old) to follow the fluctuation in concentration of serum amyloid A (SAA), the precursor of the secondary amyloid fibril protein. After a single intramuscular injection of etiocholanolone (0.3 mg/kg), blood samples were drawn twice a day for 12 days for determination of SAA by solid phase radioimmunoassay. From a base line of <100 mug/ml, the SAA concentration began rising within 12 h to a maximum value at about 48 h of 1,350-1,800 mug/ml in three males and 380-900 mug/ml in three females and returned to base line by 4-5 days. The SAA response showed a similar time response to C-reactive protein (CRP), a well-documented acute phase protein which was assayed semiquantitatively by capillary tube precipitin reaction. CRP, but not SAA, showed a quantitative correlation with the amount of fever induced by etiocholanolone. One subject exhibited a second rise in SAA and CRP concentrations after acute over-indulgence with alcohol, suggesting that acute liver damage may have caused an acute phase reaction. Thus, a controlled episode of fever and inflammation produced a prompt and prolonged elevation of SAA and CRP concentrations. Unlike SAA, CRP has not been implicated in the pathogenesis of amyloidosis, although its relationship to the P component of amyloid has recently been established.
Amyloid↗
Some aspects of the circadian rhythm of the urinary excretion of etiocholanolone, androsterone and dehydroepiandrosterone.
The circadian rhythm in the urinary excretion of etiocholanolone, of androsterone and of dehydroepiandrosterone in normal menstruating women was studied. The excretion patterns of etiocholanolone and androsterone seem to be nearly synchronous, but not equal, thus resulting in a diurnal variation.
Adult↗
Effects on erythroid colony formation of beta(beta)-agonists, etiocholanolone and spleen extract from irradiated rats.
Erythroid colony formation in vitro was enhanced by beta-agonist, etiocholanolone and spleen extract from irradiated rats. While propranolol completely blocked the effect of beta-agonists, the effect of etiocholanolone was little, and that of spleen extract was not affected by this beta-blocker.
Adrenergic beta-Agonists↗
Effects of etiocholanolone and prednisolone on intravascular granulocyte kinetics in horses.
The functional capacity of the marrow granulocyte reserve (MGR) in 4 adult horses was studied, using 51Cr-labeled leukocytes. The mean increase in the peripheral granulocyte count following injections of etiocholanolone (0.3 mg/kg) was 870 granulocytes/mm3, and the mean increase following prednisolone administration (200 mg) was 5,880 granulocytes/mm3. Etiocholanolone failed to mobilize the MGR and decreased the rate of granulocyte egress from the blood. Prednisolone rapidly mobilized the MGR and markedly decreased the granulocyte specific activity during the first 3 hours after injection.
Animals↗
A rapid screening assay for measuring urinary androsterone and etiocholanolone delta(13)C ( per thousand) values by gas chromatography/combustion/isotope ratio mass spectrometry.
A gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) method is described and validated for measurement of delta(13)C values of the acetate derivatives of urinary etiocholanolone and androsterone. The analysis was performed with only 2 mL of urine. The sample preparation consisted of deconjugation with beta-glucuronidase, solid phase extraction, and derivatization with acetic anhydride and pyridine. The within-assay precision of two quality control (QC) urine samples ranged from 0.5 to 2.1 CV%. The between-assay precision in the same QC urines ranged from 1.7 to 3.4 CV%. Administration of testosterone enanthate to a subject resulted in a 6 per thousand decrease in delta(13)C values from -25 per thousand (baseline) to -31 per thousand. Two weeks after testosterone administration was discontinued, the delta(13)C values remained abnormally low while the urine testosterone/epitestosterone (T/E) ratio returned to less than 6. This relatively simple method is useful for rapidly screening a large number of urine samples, including those with T/E <6.
Adult↗
Successful treatment of severe refractory aplastic anemia with 3-beta etiocholanolone and nandrolone decanoate.
A patient with aplastic anemia, who had been unresponsive to androgens, antithymocyte globulin, high-dose methylprednisolone, and cyclosporine, responded to treatment with 3-beta-etiocholanolone, nandrolone decanoate, and prednisolone acetate. Six months following initiation of therapy, she became red cell and platelet transfusion independent with neutrophils persistently over 1,000/microliters. A sustained partial remission has persisted for over 2 years. This observation suggests that a combined hematostimulatory approach may be of benefit, even in patients with long-standing refractory aplasia.
Anemia, Aplastic↗
Urinary etiocholanolone and prognosis in early carcinoma of the breast.
Etiocholanolone levels have been measured in both premastectomy and postoperative urines from 86 women with early breast cancer. Levels did not differ between patients subsequently surviving five years following mastectomy and those dying from recurrent disease within this period.
Breast Neoplasms↗