Early discharge after enhanced recovery rectal resection does not increase emergency department visits and readmissions: a single institution analysis.

BACKGROUND: Same-day discharge after colectomy in enhanced recovery pathways has been shown to be feasible. It is not clear how early patients with rectal resections may be safely discharged. The study aim was to determine if patients discharged ≤ 3 days after rectal resections are associated with increased rates of emergency department (ED) visits and hospital readmissions. METHODS: Retrospective analysis of enhanced recovery low anterior resection, abdominoperineal resection, and proctocolectomy patients in a prospectively maintained single institution colorectal surgery database from 01/01/2018 to 07/15/2022. Clinic visits were scheduled within 4-7 days and at 30 days after discharge, and every 1-2 weeks for stoma patients until no longer needed. Logistic regression models were used to analyze the association of discharge on postoperative days (POD)-1-3, POD-4-5, and POD ≥ 6 days with incidence of ED visits and readmissions. RESULTS: A total of 118 patients met inclusion criteria, 76 with stomas. Median postoperative length of stay was 5 [IQR 6.5] days. Mean age was 58.6 years; 59.3% were ASA-3; and 69.5% had a minimally invasive surgical approach. ED visits were not significantly different between discharge-day groups (p = 0.096). No patients were discharged same-day, one without a stoma was discharged on POD-1, ten patients (2 with stomas) on POD-2, and twenty-four patients (13 with stomas) on POD-3. ED visits were lowest for the POD-1-3 group (14.3%) but not significantly different than later discharge groups (p = 0.166). Readmission rate was also lowest for the POD-1-3 group (11.4%) and also not significantly different than later discharge groups (p = 0.261) and this was confirmed with logistic regression. Complication rate was lowest in the POD-1-3 group (p < 0.001). CONCLUSION: Early discharge after enhanced recovery partial or complete proctectomy is not associated with increased ED visits and readmissions. Follow up studies should identify post-discharge resources that allow safe early discharge and that may be standardized and generalizable.

Early Discharge after Enhanced Recovery Colectomy Does Not Increase Emergency Department Visits and Readmissions: A Single Institution Analysis.

BACKGROUND: Same-day discharge after colorectal surgery in enhanced recovery pathways is increasing. This study aimed to determine if discharge on postoperative days (POD) one or two is associated with increased rates of emergency department (ED) visits and hospital readmissions after left and right colectomy. METHODS: Single institution retrospective analysis of prospective institutional colorectal surgery database between 07/01/2018 and 07/15/2022. Primary outcomes were ED visit and readmission rates for enhanced recovery open and minimally invasive right and left colectomy using logistic regressions models. RESULTS: 820 patients met inclusion criteria. There were significant differences in discharge-day by diagnosis-58.5% of patients with Crohn's disease were discharged on POD ≥4 and 21.6% with benign colon neoplasia were discharged on POD-0-1 (P < .001). ED visits occurred in 12.9% of the study population and were not significantly different between discharge-day groups (P = .096). Overall readmission rate was 8.5% and significantly different between discharge-day groups (0% POD-0 vs 8.3% POD-1 vs 5.8% POD-2 vs 6.9% POD-3 vs 12.9% POD ≥4, P = .041). Logistic regression showed that ED visits and readmissions for longer discharge-days (POD-2, POD-3, POD ≥4) were not significantly different than POD-0-1. Readmission diagnoses for the study population were higher for ileus (17.1%) and surgical site infection (SSI) type-III (22.9%) than for acute kidney injury (1.4%) and SSI type-I/II (1.4%). CONCLUSION: Early discharge after left and right colectomy is not associated with increased rates of ED visits and readmissions. Same-day discharge may be feasible in selected enhanced recovery patients. Standardized post-discharge resources that safely allow same-day discharge require further investigation.

Pain and opioid use after colorectal resection for benign versus malignant disease: A single institution analysis.

BACKGROUND: Studies comparing opioid needs between benign and malignant colorectal diseases are inconclusive. METHODS: Single institution analysis of prospectively maintained colorectal surgery database. Multiple regression analyses done on perioperative numeric pain scores (NPS) and opioids prescribed at discharge. RESULTS: 641 patients in Benign and 276 patients in the Malignant group. Unadjusted comparison revealed significantly higher NPS for the Benign than the Malignant group preoperative and postoperative day 0 (after surgery), 1, 2, and 3 (all p â€‹≤ â€‹0.001). Opioids prescribed at discharge were significantly higher in the Benign group (60.0% vs 51.1%, p â€‹= â€‹0.018). After regression analysis, there was no longer a significant difference in NPS (B â€‹= â€‹0.703, p â€‹= â€‹0.095) and opioids prescribed between groups [OR â€‹= â€‹0.803 (95%CI 0.586, 1.1), p â€‹= â€‹0.173]. CONCLUSIONS: Pain and opioids prescribed at discharge are not significantly different between benign and malignant diseases in an enhanced recovery pain management pathway that maximizes non-opioid multimodal analgesic strategies.

Operative trends following the adoption of nonoperative management of rectal cancer.

BACKGROUND: Differentiating clinical near-complete and complete responses (cCR) after neoadjuvant therapy (NT) is challenging in rectal cancer patients. We hypothesized that magnetic resonance imaging staging limitations for low rectal cancers may increase the proportion of abdominoperineal resection (APR) with permanent colostomy for those without a cCR. METHODS: Single institution retrospective analysis of rectal cancer cases before and after adoption of nonoperative "watch and wait" (W&W) pathway. APR as a percentage of rectal resections was the primary outcome. RESULTS: There were 76 total mesorectal excisions (TME) in the pre-W&W group and 98 in the post-W&W group. NT was significantly more common in the post-W&W group. There was no significant difference in the APR primary outcome (pre-W&W APR 33.3% vs. post-W&W APR 26.5%, p = 0.482). APR patients had fewer complete TME grades (69.2% vs. 46.2%) and more pathologic complete responses (0% vs. 26.9%) in the post-W&W period. The cCR rate for patients with nonoperative management was 51.4% (n = 37) and 13.5% (n = 5) had regrowths, all of whom underwent salvage surgery. CONCLUSION: APR for those without a cCR to NT has not increased in the nonoperative management era. Balancing the pathologic complete response rate may require restaging some patients with clinical near-complete responses.

Postoperative Oral Rehydration and Regimented Follow-up Decrease Readmissions After Colorectal Surgery That Includes Ileostomies.

BACKGROUND: Ileostomies constitute 15% to 43% of readmissions after colorectal surgery, often due to dehydration and acute kidney injury. Prior institutional interventions decreased readmissions but not among patients who underwent new ileostomies. OBJECTIVE: To evaluate readmissions among patients who underwent new ileostomies after postoperative oral rehydration solution and standardized clinic visits. DESIGN: Retrospective analysis of prospective database. SETTINGS: Enhanced recovery colorectal surgery service. PATIENTS: Patients who underwent new ileostomy before and after intervention. INTERVENTIONS: Postoperative oral rehydration solution and postdischarge clinic visits with review of inputs/outputs, antimotility and appliance needs, and trained nurse reeducation 4 to 7 days after discharge, 30 days postoperatively, and every 1 to 2 weeks thereafter as needed. MAIN OUTCOME MEASURES: Readmission rate due to dehydration/acute kidney injury (primary), emergency department visits, and readmission rates overall and for specific diagnoses. Analysis used univariate and weighted techniques. RESULTS: A total of 312 patients (199 preintervention; 113 postintervention) were included, with a mean age of 59.0 years. Patients were predominantly White (94.9%) and evenly split between men and women. The most common diagnosis was diverticulitis (43.3%). The most common procedure was high anterior resection (38.8%), followed by low anterior resection (16.35%). Patient and procedure characteristics were well matched between groups. Multivariate analysis demonstrated that readmission rate due to dehydration/acute kidney injury significantly decreased between pre- and postintervention study groups (45.7% vs 16.5%, p = 0.039). Emergency department visits due to dehydration/acute kidney injury (12.0% vs 1.7%, p < 0.001) and readmissions from all causes (24.33% vs 10.6%, p = 0.005) also significantly decreased. Other complications were not significantly different between groups. Average stoma output 24 hours before (776 vs 625 mL, p = 0.005) and after (993 vs 890 mL, p = 0.025) discharge was significantly decreased in the postintervention group. LIMITATIONS: Retrospective single-center study. CONCLUSIONS: An oral rehydration solution and frequent standardized postdischarge visits led by trained nursing staff decreased readmissions and emergency department visits among patients who underwent new ileostomies after colorectal surgery. See Video Abstract . LA REHIDRATACIN ORAL POSOPERATORIA Y EL SEGUIMIENTO REGLAMENTADO REDUCEN LOS REINGRESOS EN PACIENTES DE CIRUGA COLORRECTAL CON ILEOSTOMAS: ANTECEDENTES:Las ileostomías constituyen del 15 al 43% de los reingresos después de la cirugía colorrectal, a menudo debido a la deshidratación y la lesión renal aguda. Las intervenciones institucionales previas redujeron los reingresos, pero no entre los pacientes con nuevas ileostomías.OBJETIVO:Evaluar los reingresos entre pacientes con nuevas ileostomías después del uso de solución de rehidratación oral postoperatoria y visitas clínicas estandarizadas.DISEÑO:Análisis retrospectivo de base de datos prospectiva.AJUSTES:Servicio de cirugía colorrectal de recuperación mejorada.PACIENTES:Pacientes con ileostomía nueva antes y después de la intervención.INTERVENCIÓN(ES):Solución de rehidratación oral posoperatoria y visitas clínicas posteriores al alta con revisión de entradas/salidas, antimotilidad y necesidades de aparatos, y reeducación de enfermeras capacitadas 4-7 días después del alta, 30 días después de la operación y cada 1-2 semanas después, según sea necesario.PRINCIPALES MEDIDAS DE RESULTADO:Tasa de readmisión debido a deshidratación/lesión renal aguda (primaria), tasa de urgencias y de readmisión en general y para diagnósticos específicos. El análisis utilizó técnicas univariadas y ponderadas.RESULTADOS:Se incluyeron un total de 312 pacientes (199 preintervención; 113 postintervención), con una edad media de 59,0 años. Los pacientes eran predominantemente blancos (94,9%) y se dividieron equitativamente entre hombres y mujeres. El diagnóstico más frecuente fue diverticulitis (43,3%). El procedimiento más común fue la resección anterior alta (38,8 %) seguida de la resección anterior baja (16,35 %). Las características del paciente y del procedimiento coincidieron bien entre los grupos. El análisis multivariante demostró que la tasa de reingreso debido a deshidratación/lesión renal aguda disminuyó significativamente entre los grupos de estudio antes y después de la intervención (45,7 % frente a 16,5 %, p = 0,039). Las visitas a urgencias por deshidratación/insuficiencia renal aguda (12,0 % frente a 1,7 %, p < 0,001) y los reingresos por todas las causas (24,33 % frente a 10,6 %, p = 0,005) también disminuyeron significativamente. Otras complicaciones no fueron significativamente diferentes entre los grupos. El gasto medio del estoma 24 horas antes (776 ml frente a 625 ml, p = 0,005) y después (993 ml frente a 890 ml, p = 0,025) del alta disminuyó significativamente en el grupo posterior a la intervención.LIMITACIONES:Estudio retrospectivo de centro único.CONCLUSIONES:Una solución de rehidratación oral y frecuentes visitas estandarizadas posteriores al alta dirigidas por personal de enfermería capacitado redujeron los reingresos y las visitas al servicio de urgencias entre los pacientes con nuevas ileostomías después de la cirugía colorrectal. ( Traducción-Dr. Yolanda Colorado ).

Alvimopan is associated with favorable outcomes in open and minimally invasive colorectal surgery: a regional database analysis.

BACKGROUND: Alvimopan is a µ-opioid receptor antagonist associated with shorter time to gastrointestinal recovery in patients having open colorectal surgery. Data demonstrating the benefit of perioperative alvimopan for the minimally invasive surgical approach are inconsistent. The aim of this study is to determine colorectal surgery groups that benefit from perioperative alvimopan. METHODS: This is a retrospective cohort analysis of colorectal surgery patients who had, and patients who did not have, perioperative alvimopan in the Michigan Surgical Quality Collaborative regional risk-adjusted database from 2018 through 2021. Main outcome measures were postoperative length of hospital stay, time to return of bowel function, and postoperative ileus. RESULTS: There were 10,010 patients (30.3% open, 40.5% laparoscopic, 12.7% hand-assist laparoscopic, 43.5% robotic) who met inclusion criteria-4919 received alvimopan in the perioperative period and 5091 did not. When compared to those not receiving alvimopan, unadjusted outcomes showed that the alvimopan group had significantly shorter postoperative length of stay (4.75 days vs 5.5 days, p < 0.001), shorter time to return of bowel function (1.61 days vs 2.01 days, p < 0.001) and less postoperative ileus (5.45% vs 7.94%, p < 0.001). After adjustment, regression models confirmed that alvimopan was associated with an 9.6% reduction in hospital length of stay (p < 0.001), a 14.9% shorter time to return of bowel function (p < 0.001), and a 42.1% reduction in postoperative ileus (p < 0.001). Subgroup analysis showed significant benefit of alvimopan for all three outcomes in patients having the minimally invasive approach. CONCLUSIONS: Alvimopan is associated with shorter hospital length of stay, shorter time to return of bowel function, and decreased postoperative ileus when administered to patients undergoing colorectal surgery. Benefit is not limited to the open approach and includes minimally invasive laparoscopic and robotic colorectal procedures.

Comparison of surgeon and pathologist total mesorectal excision grade after rectal cancer resection: A single institution analysis.

BACKGROUND: A Michigan Surgical Quality Collaborative Colorectal Cancer Project initiative sought to increase adoption of surgeon total mesorectal excision (TME) grading through standardized education and synoptic operative reporting. Our study aim was to assess initiative impact and level of agreement between surgeon and pathologist-determined TME grades. METHODS: This is a retrospective comparison of surgeon and pathologist TME grades before and after initiative implementation using a prospectively maintained enhanced recovery colorectal surgery database. RESULTS: There were 112 TMEs before, and 53 TMEs following initiative implementation. There was a significant increase in surgeon TME-grade reporting in the postinitiative period (25.0% pre- vs. 81.1% post-, p < 0.001). Pathologist TME-grade reporting was high in both time periods and there was no significant change (91.1% pre- vs. 88.7% post-, p = 0.84). Surgeon and pathologist agreement was 59.3% in the preinitiative period (Κ "minimal"   0.356) and 65.0% in the postinitiative period (Κ "moderate" = 0.605, p = 0.827). There was no significant association between clinical T-stage and surgeon or pathologist TME grade. CONCLUSION: Surgeon TME grading improves with education and synoptic operative reporting. There is only moderate agreement between surgeon and pathologist, a finding that requires further study. Organized regional initiatives are effective at implementing rectal cancer management quality improvement.

Lack of Complete Pretreatment Staging Is Associated With Omission of Neoadjuvant Therapy for Rectal Cancer: A Statewide Study.

BACKGROUND: Standardized local staging and neoadjuvant therapy are rectal cancer management quality measures supported by the Commission on Cancer and National Accreditation Program for Rectal Cancer for the management of rectal cancer. Previous studies suggested that up to 25% of patients with stage II/III rectal cancer patients do not receive neoadjuvant therapy. We hypothesized that failure to receive neoadjuvant therapy may be caused by failure to properly stage patients before surgery. OBJECTIVE: This study aimed to determine whether lack of local rectal cancer staging is associated with underutilization of neoadjuvant therapy and to determine risk factors for omission of neoadjuvant therapy. DESIGN: Retrospective cohort study. Bivariate and multivariable analyses were performed on patient, tumor, and 30-day outcome factors associated with neoadjuvant therapy and staging. SETTINGS: hospitals participated in the Michigan Surgical Quality Collaborative Colorectal Cancer Project from January 2014 to December 2019. PATIENTS: Elective, clinical stage II/III, mid-to-low rectal cancer resections. Patients with upper rectal cancer were excluded. MAIN OUTCOME MEASURES: Percentage of patients receiving neoadjuvant therapy. RESULTS: The final cohort included 350 patients with clinical stage II/III mid or low rectal cancer-80.9% of patients who had received neoadjuvant therapy and 83.2% of patients who had MRI and/or endoscopic ultrasound. A significant association was found between receiving neoadjuvant therapy and MRI/endorectal ultrasound staging ( p < 0.0001). Eighty-seven percent of patients who had MRI/endorectal ultrasound received neoadjuvant chemoradiotherapy; 49% of patients who did not have MRI/endorectal ultrasound staging received neoadjuvant chemoradiotherapy. Multivariate analysis revealed that risk factors for the omission of neoadjuvant therapy were older age and incomplete staging. LIMITATIONS: Observational study with the possibility of unmeasured confounding variables. CONCLUSIONS: Neoadjuvant therapy is underused in patients with stage II/III rectal cancer. Omission of pretreatment staging with MRI/endorectal ultrasound is associated with omission of neoadjuvant therapy. These data suggest the need for regional and national quality improvement strategies to standardize the multidisciplinary management of rectal cancer. See Video Abstract at http://links.lww.com/DCR/B923 . LA FALTA DE ESTADIFICACIN COMPLETA PREVIA AL TRATAMIENTO SE ASOCIA CON LA OMISIN DE LA TERAPIA NEOADYUVANTE PARA EL CNCER DE RECTO UN ESTUDIO ESTATAL: ANTECEDENTES: La estadificación local estandarizada y la terapia neoadyuvante son medidas de calidad de la Comisión sobre el Cáncer y el Programa Nacional de Acreditación para el Cáncer de Recto para el tratamiento del cáncer de recto. Estudios previos sugirieron que hasta el 25% de los pacientes con cáncer de recto en estadio II/III no reciben terapia neoadyuvante. Planteamos la hipótesis de que la falla en recibir la terapia neoadyuvante puede deberse a la falla en la estadificación adecuada de los pacientes antes de la cirugía.OBJETIVO: El propósito de este estudio es determinar si la falta de estadificación local del cáncer de recto está asociada con la infrautilización de la terapia neoadyuvante y determinar los factores de riesgo para la omisión de la terapia neoadyuvante.DISEÑO: Estudio de cohorte retrospectivo. Se realizaron análisis bivariados y multivariados sobre el paciente, el tumor y los factores de resultado a los 30 días asociados con la terapia neoadyuvante y la estadificación.AJUSTE: Un total de 31 hospitales que participaron en el Proyecto Quirugico Colaborativo de Cáncer Colorrectal de Calidad de Michigan desde enero de 2014 hasta diciembre de 2019.PACIENTES: Resecciones electivas, en estadio clínico II/III, de cáncer de recto medio a bajo. Se excluyeron los pacientes con cáncer de recto superior.MEDIDA DE RESULTADO PRINCIPAL: Porcentaje de pacientes que reciben terapia neoadyuvante. Porcentaje de pacientes que reciben terapia neoadyuvante.RESULTADOS: La cohorte final fue de 350 casos con cáncer de recto medio o bajo en estadio clínico II/III. El 80,9% tenía terapia neoadyuvante y el 83,2%, resonancia magnética y/o ultrasonido endoscópico. Hubo una asociación significativa entre recibir terapia neoadyuvante y la estadificación MRI/ERUS ( p < 0,0001). El 87% de los pacientes a los que se les realizaron imágenes con MRI/ERUS recibieron NT, mientras que el 49% de los pacientes a los que no se les realizó la estadificación con MRI/ERUS tuvieron NT. El análisis multivariante reveló que los factores de riesgo para la omisión de la terapia neoadyuvante fueron la edad avanzada y la estadificación incompleta.LIMITACIONES: Estudio observacional con posibilidad de confusión de variables no medidas.CONCLUSIONES: La terapia neoadyuvante está infrautilizada en pacientes con cáncer de recto en estadio II/III. La omisión de la estadificación previa al tratamiento con MRI/ERUS se asocia con la omisión de la terapia neoadyuvante. Estos datos sugieren la necesidad de estrategias regionales y nacionales de mejora de la calidad para estandarizar el manejo multidisciplinario del cáncer de recto. Consulte Video Resumen en http://links.lww.com/DCR/B923 . (Traducción-Dr Yolanda Colorado ).

Single-Dose Study of a Corticotropin-Releasing Factor Receptor-1 Antagonist in Women With 21-Hydroxylase Deficiency.

CONTEXT: Treatment of 21-hydroxylase deficiency (21OHD) is difficult to optimize. Normalization of excessive ACTH and adrenal steroid production commonly requires supraphysiologic doses of glucocorticoids. OBJECTIVES: We evaluated the safety and tolerability of the selective corticotropin releasing factor type 1 (CRF1) receptor antagonist NBI-77860 in women with classic 21OHD and tested the hypothesis that CRF1 receptor blockade decreases early-morning ACTH and 17α-hydroxyprogesterone (17OHP) in these patients. PARTICIPANTS: The study enrolled eight classic 21OHD females, ages 18-58 years, seen at a single tertiary referral university setting. DESIGN: This was a phase Ib, single-blind, placebo-controlled, fixed-sequence, single-dose trial. During three treatment periods separated by 3-week washout intervals, patients sequentially received placebo, NBI-77860 300 mg, and NBI-77860 600 mg at 10 pm; glucocorticoid therapy was withheld for 20 hours. We evaluated ACTH, 17OHP, androstenedione, and testosterone as well as NBI-77860 pharmacokinetics over 24 hours. RESULTS: Dose-dependent reductions of ACTH and/or 17OHP were observed in six of eight subjects. Relative to placebo, NBI-77860 led to an ACTH and 17OHP reduction by a mean of 43% and 0.7% for the 300 mg dose, respectively, and by 41% and 27% for the 600 mg dose, respectively. Both NBI-77860 doses were well tolerated. CONCLUSION: The meaningful reductions in ACTH and 17OHP following NBI-77860 dosing in 21OHD patients demonstrate target engagement and proof of principle in this disorder. These promising data provide a rationale for additional investigations of CRF1 receptor antagonists added to physiologic doses of hydrocortisone and fludrocortisone acetate for the treatment of classic 21OHD.

The combination of insulin-like growth factor receptor 1 (IGF1R) antibody cixutumumab and mitotane as a first-line therapy for patients with recurrent/metastatic adrenocortical carcinoma: a multi-institutional NCI-sponsored trial.

Adrenocortical carcinoma (ACC) is an aggressive malignancy, which lacks an effective systemic treatment. Abnormal activation of insulin-like growth factor receptor 1 (IGF1R) has been frequently observed. Preclinical studies demonstrated that pharmacological inhibition of IGF1R signaling in ACC has antiproliferative effects. A previous phase I trial with an IGF1R inhibitor has demonstrated biological activity against ACC. The objective of this study is to assess the efficacy of the combination of the IGF1R inhibitor cixutumumab (IMC-A12) in association with mitotane as a first-line treatment for advanced/metastatic ACC. We conducted a multicenter, randomized double-arm phase II trial in patients with irresectable recurrent/metastatic ACC. The original protocol included two treatment groups: IMC-A12 + mitotane and mitotane as a single agent, after an initial single-arm phase for safety evaluation with IMC-A12 + mitotane. IMC-A12 was dosed at 10 mg/kg intravenously every 2 weeks. The starting dose for mitotane was 2 g daily, subsequently adjusted according to serum levels/symptoms. The primary endpoint was progression-free survival (PFS) according to RECIST (Response Evaluation Criteria in Solid Tumors). This study was terminated before the randomization phase due to slow accrual and limited efficacy. Twenty patients (13 males, 7 females) with a median age of 50.2 years (range 21.9-79.6) were enrolled for the single-arm phase. Therapeutic effects were observed in 8/20 patients, including one partial response and seven stable diseases. The median PFS was 6 weeks (range 2.66-48). Toxic events included two grade 4 (hyperglycemia and hyponatremia) and one grade 5 (multiorgan failure). Although the regimen demonstrated activity in some patients, the relatively low therapeutic efficacy precluded further studies with this combination of drugs.

Abiraterone acetate to lower androgens in women with classic 21-hydroxylase deficiency.

CONTEXT: Chronic supraphysiological glucocorticoid therapy controls the androgen excess of 21-hydroxylase deficiency (21OHD) but contributes to the high prevalence of obesity, glucose intolerance, and reduced bone mass in these patients. Abiraterone acetate (AA) is a prodrug for abiraterone, a potent CYP17A1 inhibitor used to suppress androgens in the treatment of prostate cancer. OBJECTIVE: The objective of the study was to test the hypothesis that AA added to physiological hydrocortisone and 9α-fludrocortisone acetate corrects androgen excess in women with 21OHD without causing hypertension or hypokalemia. DESIGN: This was a phase 1 dose-escalation study. SETTING: The study was conducted at university clinical research centers. PARTICIPANTS: We screened 14 women with classic 21OHD taking hydrocortisone 12.5-20 mg/d to enroll six participants with serum androstenedione greater than 345 ng/dL (>12 nmol/L). INTERVENTION: AA was administered for 6 days at 100 or 250 mg every morning with 20 mg/d hydrocortisone and 9α-fludrocortisone acetate. MAIN OUTCOME MEASURE: The primary endpoint was normalization of mean predose androstenedione on days 6 and 7 (< 230 ng/dL [<8 nmol/L)] in greater than 80% of participants. Secondary end points included serum 17-hydroxyprogesterone and testosterone (T), electrolytes, plasma renin activity, and urine androsterone and etiocholanolone glucuronides. RESULTS: With 100 mg/d AA, mean predose androstenedione fell from 764 to 254 ng/dL (26.7-8.9 nmol/L). At 250 mg/d AA, mean androstenedione normalized in five participants (83%) and decreased from 664 to 126 ng/dL (23.2-4.4 nmol/L), meeting the primary end point. Mean androstenedione declined further during day 6 to 66 and 38 ng/dL (2.3 and 1.3 nmol/L) at 100 and 250 mg/d, respectively. Serum T and urinary metabolites declined similarly. Abiraterone exposure was strongly negatively correlated with mean androstenedione. Hypertension and hypokalemia were not observed. CONCLUSION: AA 100-250 mg/d added to replacement hydrocortisone normalized several measures of androgen excess in women with classic 21OHD and elevated serum androstenedione.