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

[congenital adrenal hyperplasia]

Chronic supraphysiological glucocorticoid therapy controls the androgen excess of 21 -hydroxylase deficiency (21 OHD ) 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 CYP 17 A 1 inhibitor used to suppress androgens in the treatment of prostate cancer .The objective of the study was to test the hypothesis that AA added to physiological hydrocortisone and 9 α-fludrocortisone acetate corrects androgen excess in women with 21 OHD without causing hypertension or hypokalemia .This was a phase 1 dose-escalation study .The study was conducted at university clinical research centers .We screened 14 women with classic 21 OHD taking hydrocortisone 12 .5 -20 mg /d to enroll six participants with serum androstenedione greater than 345 ng /dL (>12 nmol /L ).AA was administered for 6 days at 100 or 250 mg every morning with 20 mg /d hydrocortisone and 9 α-fludrocortisone acetate .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 .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 .AA 100 -250 mg /d added to replacement hydrocortisone normalized several measures of androgen excess in women with classic 21 OHD and elevated serum androstenedione .

Diseases
Validation

Diseases presenting "hypertension" symptom

achondroplasia

acute rheumatic fever

adrenal incidentaloma

aniridia

aromatase deficiency

cadasil

child syndrome

cohen syndrome

congenital adrenal hyperplasia

congenital diaphragmatic hernia

cushing syndrome

cystinuria

erdheim-chester disease

erythropoietic protoporphyria

esophageal adenocarcinoma

fabry disease

familial hypocalciuric hypercalcemia

gm1 gangliosidosis

heparin-induced thrombocytopenia

hereditary cerebral hemorrhage with amyloidosis

holt-oram syndrome

homocystinuria without methylmalonic aciduria

hydrocephalus with stenosis of the aqueduct of sylvius

inclusion body myositis

kallmann syndrome

kindler syndrome

lamellar ichthyosis

lymphangioleiomyomatosis

pendred syndrome

primary effusion lymphoma

scrub typhus

severe combined immunodeficiency

sneddon syndrome

typhoid

von hippel-lindau disease

well-differentiated liposarcoma

werner syndrome

x-linked adrenoleukodystrophy

zellweger syndrome

This symptom has already been validated