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1.
24-Hour Profiles of 11-Oxygenated C19 Steroids and Δ5-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency.
Turcu, AF, Mallappa, A, Nella, AA, Chen, X, Zhao, L, Nanba, AT, Byrd, JB, Auchus, RJ, Merke, DP
Frontiers in endocrinology. 2021;:751191
Abstract
BACKGROUND Optimal management of androgen excess in 21-hydroxylase deficiency (21OHD) remains challenging. 11-oxygenated-C19 steroids (11-oxyandrogens) have emerged as promising biomarkers of disease control, but data regarding their response to treatment are lacking. OBJECTIVE To compare the dynamic response of a broad set of steroids to both conventional oral glucocorticoids (OG) and circadian cortisol replacement via continuous subcutaneous hydrocortisone infusion (CSHI) in patients with 21OHD based on 24-hour serial sampling. PARTICIPANTS AND METHODS We studied 8 adults (5 women), ages 19-43 years, with poorly controlled classic 21OHD who participated in a single-center open-label phase I-II study comparing OG with CSHI. We used mass spectrometry to measure 15 steroids (including 11-oxyandrogens and Δ5 steroid sulfates) in serum samples obtained every 2 h for 24 h after 3 months of stable OG, and 6 months into ongoing CSHI. RESULTS In response to OG therapy, androstenedione, testosterone (T), and their four 11-oxyandrogen metabolites:11β-hydroxyandrostenedione, 11-ketoandrostenedione, 11β-hydroxytestosterone and 11-ketotestosterone (11KT) demonstrated a delayed decline in serum concentrations, and they achieved a nadir between 0100-0300. Unlike DHEAS, which had little diurnal variation, pregnenolone sulfate (PregS) and 17-hydoxypregnenolone sulfate peaked in early morning and declined progressively throughout the day. CSHI dampened the early ACTH and androgen rise, allowing the ACTH-driven adrenal steroids to return closer to baseline before mid-day. 11KT concentrations displayed the most consistent difference between OG and CSHI across all time segments. While T was lowered by CSHI as compared with OG in women, T increased in men, suggesting an improvement of the testicular function in parallel with 21OHD control in men. CONCLUSION 11-oxyandrogens and PregS could serve as biomarkers of disease control in 21OHD. The development of normative data for these promising novel biomarkers must consider their diurnal variability.
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Effects of anabolic androgenic steroids on chylomicron metabolism.
Morikawa, AT, Maranhão, RC, Alves, MJ, Negrão, CE, da Silva, JL, Vinagre, CG
Steroids. 2012;(13):1321-6
Abstract
OBJECTIVE To evaluate the effects of anabolic androgenic steroids (AAS) on chylomicron metabolism. METHODS An artificial lipid emulsion labeled with radioactive cholesteryl ester (CE) and triglycerides (TG) mimicking chylomicrons was intravenously injected into individuals who regularly weight trained and made regular use of AAS (WT+AAS group), normolipidemic sedentary individuals (SDT group) and individuals who also regularly weight trained but did not use AAS (WT group). Fractional clearance rates (FCR) were determined by compartmental analysis for emulsion plasma decay curves. RESULTS FCR-CE for the WT+AAS group was reduced (0.0073 ± 0.0079 min(-1), 0.0155 ± 0.0100 min(-1), 0.0149 ± 0.0160 min(-1), respectively; p<0.05), FCR-TG was similar for both the WT and SDT groups. HDL-C plasma concentrations were lower in the WT+AAS group when compared to the WT and SDT groups (22 ± 13; 41 ± 7; 38 ± 13 mg/dL, respectively; p<0.001). Hepatic triglyceride lipase activity was greater in the WT+AAS group when compared to the WT and SDT groups (7243 ± 1822; 3898 ± 1232; 2058 ± 749, respectively; p<0.001). However, no difference was observed for lipoprotein lipase activity. CONCLUSIONS Data strongly suggest that AAS may reduce the removal from the plasma of chylomicron remnants, which are known atherogenic factors.
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Loss of endothelial thrombomodulin predicts response to steroid therapy and survival in acute intestinal graft-versus-host disease.
Andrulis, M, Dietrich, S, Longerich, T, Koschny, R, Burian, M, Schmitt-Gräf, A, Schirmacher, P, Ho, AD, Dreger, P, Luft, T
Haematologica. 2012;(11):1674-7
Abstract
Steroid-refractory graft-versus-host disease causes significant morbidity and mortality after allogeneic stem cell transplantation. The pathomechanism of steroid resistance is currently not understood, but it has been suggested that endothelial cell dysfunction plays a role. Endothelial thrombomodulin was quantified along with histological markers of epithelial damage and cytotoxic T cells in colon biopsies from 51 allografted patients, and retrospectively correlated with response to steroids and survival. Loss of endothelial thrombomodulin was the strongest predictor of response to steroids (P=0.02) and nonrelapse mortality (P=0.01) in multivariate analyses adjusting for T-cell infiltrates, histological grading, vessel density, disease status, donor type, and conditioning therapy. Our data provide evidence that at disease onset, loss of endothelial thrombomodulin expression rather than excessive T-cell infiltration associates with steroid-refractory graft-versus-host disease and mortality. Prospective histological investigations are now warranted to improve diagnosis and prognostication of this core complication of stem cell transplantation.
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Mycophenolate mofetil therapy for children with steroid-resistant nephrotic syndrome.
Li, Z, Duan, C, He, J, Wu, T, Xun, M, Zhang, Y, Yin, Y
Pediatric nephrology (Berlin, Germany). 2010;(5):883-8
Abstract
Treating children with steroid-resistant nephrotic syndrome (SRNS) has been a clinical challenge for pediatricians. We recruited 24 children (18 boys and six girls) with steroid-resistant idiopathic nephrotic syndrome (SRINS) who were <2 years. All patients were administered prednisone 2 mg/kg per day prior to mycophenolate mofetil (MMF). By the end of the eighth week, MMF was initiated at 25-30 mg/kg daily for 6- 12 months. Prednisone dose was reduced stepwise. Biochemical assays were performed every 2 months. Complete remission was achieved in 15 patients, partial remission in six, and no response to MMF was noted in three. With MMF treatment, the levels of urinary protein and serum cholesterol decreased and that of serum albumin increased in a time-dependant manner. We demonstrated the MMF could reduce proteinuria in SRINS children <2 years. Our study suggests that MMF therapy might be an effective strategy for treating SRINS in children <2 years.
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Mycophenolate mofetil treatment in primary glomerular disease: one-year follow-up in steroid dependent and resistant nephrotic syndrome.
Tasanarong, A, Thitiarchakul, S
Journal of the Medical Association of Thailand = Chotmaihet thangphaet. 2006;:S218-27
Abstract
OBJECTIVE Treatment of primary nephrotic syndrome (NS) with steroid and cyclophosphamide may be unsuccessful and have much toxicity. Therefore, the authors evaluated the outcome of mycophenolate mofetil (MMF) treatment in these patients. MATERIAL AND METHOD Fourteen primary NS patients who had failure to steroid and/or cyclophosphamide therapy were treated by MMF for at least 3 months as alternative treatment. Median +/- SD (range) of urine protein to creatinine index (UPCI), serum albumin, serum creatinine, serum cholesterol and dose of prednisolone at the start, 1mo, 3 mo, 6mo, and 12 mo after MMF therapy were compared. RESULTS In the study group, the mean of UPCI decreased significantly from 2.79 +/- 8.1 to 1.81 +/- 1.54 (p = 0.02) at 12 months after the MMF therapy with no significant change in the mean serum creatinine from 1.14 +/- 0.45 to 1.27 +/- 0.67 mg/dL. The mean serum albumin increased significantly from 2.87 +/- 0.56 to 3.46 +/- 0.76 g/dL (p = 0.05) and the mean of prednisolone dosage decreased significantly from 34.64 +/- 19.16 to 11.11 +/- 8.58 mg/day (p = 0.004). For patients with IgM Nephropathy (IgMN), one of three steroid dependent patients presented with improved renal function. One of two patients with focal segmental glomerulosclerosis (FSGS) had a complete remission and one of two patients with IgA nephropathy (IgAN) had improved renal function with partial remission. CONCLUSION MMF therapy in NS patients with primary glomerular disease was well tolerated and safe. These efficacies can improve NS, stabilize renal function, and achieve steroid withdrawal.
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[Treatment of hemolytic uremic syndrome after acute stage].
Ye, LY, Yu, ZH, Huang, ZX, Chen, XM, Ren, RN, Chen, GM, Wang, CF, Xia, GZ, Huang, J, Wang, FJ
Zhonghua er ke za zhi = Chinese journal of pediatrics. 2006;(3):206-9
Abstract
OBJECTIVE Hemolytic uremic syndrome (HUS) is a common primary disease that can cause acute renal failure in childhood. Renal disease is the most important long-term complication in patients who survived the acute stage of HUS. Use of angiotensin-converting enzyme inhibitors (ACEI) and a restricted protein intake may be beneficial to the patients. However, it is not established whether such patients should be treated with steroids and immunosuppressors. The present study aimed to probe into the benefit of using steroid and immunosuppressor in patients after acute stage of HUS. METHODS The subjects included 17 patients (aged 9 months to 15 years, 12 males, 5 females) with HUS. Thirteen patients recovered from the acute stage of HUS, and underwent continuative treatment and follow-up. All the patients were treated with ACEI and early restriction of protein intake. Additionally, 2 children manifested as glomerulonephritis, one was treated with triperygium glycosides. Other 11 children who manifested as nephrotic syndrome were treated with prednisone, among them 5 children had no response or had incomplete response to prednisone, for these children short-term high dose cyclophosphamide or methylprednisolone pulse treatment were added; in 3 of the children short-term high dose methylprednisolone treatment was applied additionally for membranoproliferative glomerulonephritis and/or focal segmental glomerulosclerosis and crescentic glomerulonephritis. RESULTS After follow-up for 2 months to 8 years, 4 patients with milder disease recovered, their blood pressure, renal function and urinalysis became normal, but 1 patient had recurrence. Among 9 patients with severe disease, 6 maintained normal blood pressure, recovered renal function and urinalysis, the other 3 patients failed to comply with treatment protocol and died during the 3rd, 9th and 13th month. The remainder (4 cases) gave up therapy and died on the 27th to 48th days of the course. CONCLUSION The treatment applied in this study could improve the prognosis of patients after acute phase of HUS evidently by using the steroid and immuno suppressor according to clinical classification and pathological findings. It is recommended that triperygium glycosides is beneficial to children with glomerulonephritis, proteinuria and hematuria after acute stage of HUS. Adjustment of therapeutic schedule based on pathological findings after renal biopsy is helpful. To the patients with progressive renal failure who have no response to the steroid and immunosuppressors, steroid and immunosuppressor should be discontinued and dialysis treatment should be applied. Protocol compliance is also an important factor.
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A multicenter pilot study of early (4-day) steroid cessation in renal transplant recipients under simulect, tacrolimus and sirolimus.
Woodle, ES, Vincenti, F, Lorber, MI, Gritsch, HA, Hricik, D, Washburn, K, Matas, AJ, Gallichio, M, Neylan, J
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2005;(1):157-66
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Abstract
This study presents the first prospective multicenter study assessing sirolimus-based immunosuppression with early (4-day) corticosteroid withdrawal (CSWD) in renal transplantation. Immunosuppression included: anti-IL-2 receptor antibody and tacrolimus/sirolimus. Inclusion criteria included adult primary recipients. Exclusion criteria included: (i) African Americans, (ii) current PRA >50%, (iii) multiple organ transplants, (iv) WBC < 3000 cells/microL and (v) fasting hypercholesterolemia/hypertriglyceridemia. The primary endpoints were acute rejection and the proportion of patients off corticosteroids. Seventy-seven patients were enrolled: mean age of 49.7 +/- 12 years. Transplants included: cadaveric (26%) and living donor (74%). Patient and graft survival were 100%. Biopsy proven acute rejection occurred in 13%; presumptive rejection in 10.5%. Banff grades included: IA (seven patients), IB (one patient), IIA (one patient) and IIB (one patient). Renal function at 1 year: serum creatinine (1.18 +/- 0.06 mg/dL). Mean weight gain was minimal at 1 year: 3 +/- 2 kg/patient. Mild increases in total, LDL and HDL cholesterol were observed and new antilipid agent use occurred in 26 patients. In conclusion, early CSWD under tacrolimus/sirolimus-based immunosuppression in selected, low-risk renal transplant recipients provides: (i) excellent patient and graft survival, (ii) good renal function, (iii) reduced hyperlipidemia and antilipid agent use and (iv) low acute rejection rates.
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Urinary excretion of steroid metabolites after chronic androstenedione ingestion.
Brown, GA, Vukovich, MD, King, DS
The Journal of clinical endocrinology and metabolism. 2004;(12):6235-8
Abstract
Urinary steroid excretion after androstenedione intake has been examined after a single dose of 50 mg and single doses of 100 or 300 mg/d for 7 d. We evaluated the effects of 28 d of 100 mg three times a day (t.i.d.) androstenedione intake on urinary steroid excretion. Twenty healthy men, ages 30-39 yr (33.5 +/- 0.6), consumed 100 mg androstenedione t.i.d. or placebo for 28 d. Urine samples were analyzed for testosterone, epitestosterone, androsterone, and etiocholanolone via HPLC/tandem mass spectrometry on d 0 and 28. Androstenedione intake increased (P < 0.05) urinary testosterone 35.1 +/- 10.5 ng/ml vs. 251.6 +/- 87.5 ng/ml, epitestosterone 35.3 +/- 8.8 ng/ml vs. 99.7 +/- 28.7 ng/ml, androsterone 2,102 +/- 383 ng/ml vs. 15,767 +/- 3,358 ng/ml, and etiocholanolone 1,698 +/- 409 ng/ml vs. 11,329 +/- 2,656 ng/ml (means +/- se). Although the testosterone to epitestosterone ratio (T/E) tended to increase with androstenedione intake (1.2 +/- 0.3 vs. 4.0 +/- 1.6; P = 0.12), only one subject had a urinary T/E greater than the current Olympic criteria (>6.0) for a positive drug test. Chronic intake of 100 mg androstenedione t.i.d. increases the urinary excretion of steroid metabolites. Due to inconsistent increases in the T/E ratio, the T/E ratio may not effectively detect androstenedione use.
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Perioperative steroids in tonsillectomy using electrocautery and sharp dissection techniques.
Hanasono, MM, Lalakea, ML, Mikulec, AA, Shepard, KG, Wellis, V, Messner, AH
Archives of otolaryngology--head & neck surgery. 2004;(8):917-21
Abstract
OBJECTIVE To determine the effect of preoperative dexamethasone sodium phosphate administration on posttonsillectomy morbidity for electrocautery ("hot") and sharp ("cold") dissection techniques. DESIGN Prospective, randomized, double-blind study. SETTING University pediatric hospital and county teaching hospital. Subjects A total of 219 children, aged 9 months to 12 years, undergoing tonsillectomy. Intervention Participants who underwent tonsillectomy were randomly assigned to receive either intravenous dexamethasone sodium phosphate (1 mg/kg) or placebo. OUTCOME MEASURES Pain scores, oral intake, and emesis on postoperative day (POD) 1. RESULTS A total of 106 subjects (62 undergoing hot and 44 cold tonsillectomies) received preoperative steroids, and 113 (56 hot and 57 cold tonsillectomies) received placebo. On POD 1, pain scores reported by patients (P =.02), parents (P =.002), and physicians (P<.001) were significantly lower in subjects receiving steroids than in those receiving placebo. Emesis was reduced from a mean of 2.1 (placebo group) to 1.2 episodes (steroid group) (P =.02). Oral intake improved from 24.5% of normal diet (placebo) to 31.7% (steroid group) (P =.004). When all 4 groups were compared (cold placebo, cold steroid, hot placebo, and hot steroid), pain scores reported by physicians and parents were significantly lower in the cold steroid group than in the other groups. CONCLUSIONS Perioperative dexamethasone use reduces posttonsillectomy morbidity in pediatric patients in the early postoperative period after hot or cold tonsillectomy. The combination of steroid and cold dissection technique provided the greatest advantage in reducing posttonsillectomy subjective pain levels.
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[Influence of treating atopic dermatitis with oral antihistamine and topical steroids on selected parameters of cell and humoral immunity].
Guzik, TJ, Adamek-Guzik, T, Bzowska, M, Miedzobrodzki, J, Czerniawska-Mysik, G, Pryjma, J
Folia medica Cracoviensia. 2002;(1-2):79-93
Abstract
UNLABELLED Pathogenesis of atopic dermatitis (AD) is multifactorial, therefore despite many different treatment protocols none of the available methods is effective enough. In the present study we analysed the effects of oral antihistamines and topical steroids on selected parameters of humoral (immunoglobulin levels) and cellular (lymphocyte proliferation index, granulocyte oxidative burst, lymphocyte phenotype CD4:CD8) immunity. These parameters were analysed in 34 AD subjects during the exacerbation of the disease and after 4 and 12 weeks of the treatment. RESULTS Along with the clinical status improvement (change form 3.17 +/- 0.1 to 1.3 +/- 0.2; 0-4 scale; p < 0.001), total serum IgE levels decreased significantly from 1563 +/- 459 to 1266 +/- +/- 364 IU/ml (p < 0.05). Other immunoglobulin levels did not change. Total blood chemiluminescence in response to latex stimulation was relatively higher during exacerbation than during remission, but this difference was not significant (p = 0.1). Mean spontaneous or PMA stimulated chemiluminescence did not differ either. CD4:CD8 index decreased significantly during the treatment (from 2.7 +/- 0.3 to 1.8 +/- 0.2; p = 0.03). Lymphocyte proliferation in response to PHA was significantly lower during exacerbation than during remission (10.4 +/- 2.8 vs. 27.1 +/- +/- 5.2; p < 0.03) and the improvement was observed after first 4 weeks of the treatment reaching the levels found in healthy controls. Proliferation index in response to anti-CD3 mAb (OKT-3) was in turn significantly higher during exacerbation (19.1 +/- 3.4 vs. 11.2 +/- 2.0; p = 0.04). CONCLUSIONS Oral antihistamine in combination with topical steroids leads to several significant changes in the immune parameters (IgE levels, CD4:CD8 and proliferation indexes) which may explain its high effectiveness in majority of patients with AD.