cortodoxone and Testicular-Neoplasms

Patients with 21-hydroxylase deficiency (21OHD) have long-term complications, resulting from poor disease control and/or glucocorticoid overtreatment. Lack of optimal biomarkers has made it challenging to tailor therapy and predict long-term outcomes.. To identify biomarkers of disease control and long-term complications in 21OHD.. Cross-sectional study of 114 patients (70 males), ages 2 to 67 years (median, 15 years), seen in a tertiary referral center.. We correlated a mass-spectrometry panel of 23 steroids, obtained before first morning medication, with bone age advancement (children), adrenal volume (adults), testicular adrenal rest tumors (TART), hirsutism, menstrual disorders, and pituitary hormones.. Total adrenal volume correlated positively with 18 steroids, most prominently 21-deoxycortisol and four 11-oxygenated-C19 (11oxC19) steroids: 11β-hydroxyandrostenedione (11OHA4), 11-ketoandrostenedione (11ketoA4), 11β-hydroxytestosterone (11OHT), and 11-ketotestosterone (11ketoT) (r ≈ 0.7, P < 0.0001). Nine steroids were significantly higher (P ≤ 0.01) in males with TART compared with those without TART, including 11OHA4 (6.8-fold), 11OHT (4.9-fold), 11ketoT (3.6-fold), 11ketoA4 (3.3-fold), and pregnenolone sulfate (PregS; 4.8-fold). PregS (28.5-fold) and 17-hydroxypregnenolone sulfate (19-fold) levels were higher (P < 0.01) in postpubertal females with menstrual disorders. In males, testosterone levels correlated positively with all 11oxC19 steroids in Tanner stages 1 and 2 (r ≈ 0.7; P < 0.001) but negatively in Tanner stage 5 (r = -0.3 and P < 0.05 for 11ketoA4 and 11ketoT). In females, testosterone level correlated positively with all four 11oxC19 steroids across all Tanner stages (r ≈ 0.8; P < 0.0001).. 11oxC19 steroids and PregS might serve as clinically useful biomarkers of disease control and long-term complications in 21OHD.

Topics: 17-alpha-Hydroxypregnenolone; Adolescent; Adrenal Glands; Adrenal Hyperplasia, Congenital; Adrenal Rest Tumor; Adult; Age Determination by Skeleton; Aged; Androgens; Androstenedione; Androstenes; Child; Child, Preschool; Cortodoxone; Cross-Sectional Studies; Female; Hirsutism; Humans; Hydroxytestosterones; Male; Menstruation Disturbances; Middle Aged; Organ Size; Pregnenolone; Testicular Neoplasms; Testosterone; Young Adult

Marked elevations of 17-hydroxyprogesterone (17OHP) are characteristic of classic 21-hydroxylase deficiency (21OHD). Testing of 17OHP provides the basis for 21OHD diagnosis, although it suffers from several pitfalls. False-positive or false-negative results and poor discrimination of nonclassic 21OHD from carriers limit the utility of serum 17OHP and necessitate dynamic testing after cosyntropin stimulation when values are indeterminate.. The objective was to provide a detailed characterization of 21-carbon (C21) steroids in classic 21OHD, which might identify other candidate steroids that could be employed for the diagnosis of 21OHD.. Patients (11 women, 10 men) with classic 21OHD and 21 sex- and age-matched controls seen in a tertiary referral center were studied.. C21 steroids in the peripheral sera from all subjects, as well as in media from cultured testicular adrenal rest tumor (TART) cells and normal adrenal (NA) cells, were analyzed using liquid chromatography/tandem mass spectrometry (10 steroids). Additionally, the dynamics of C21 steroid metabolism in TART and NA cells were assessed with radiotracer studies.. Five C21 steroids were significantly higher in 21OHD patients: 17OHP (67-fold; P < .01), 21-deoxycortisol (21dF; 35-fold; P < .01), 16α-hydroxyprogesterone (16OHP; 28-fold; P < .01), progesterone (2-fold; P < .01), and 11β-hydroxyprogesterone (11OHP; not detected in controls; P < .01). The same steroids were the highest in media from TART cells relative to the NA cells: 11OHP, 58- to 65-fold; 21dF, 30- to 41-fold; 17OHP, 9-fold; progesterone, 9- to 12-fold; and 16OHP, 7-fold.. Measurement of 16OHP and 11OHP along with 17OHP and 21dF by liquid chromatography/tandem mass spectrometry might comprise a biomarker panel to accurately diagnose all forms of 21OHD.

Topics: 17-alpha-Hydroxyprogesterone; Adrenal Hyperplasia, Congenital; Adrenal Rest Tumor; Adult; Case-Control Studies; Cells, Cultured; Cortodoxone; Female; Humans; Hydroxyprogesterones; Male; Metabolome; Middle Aged; Progesterone; Testicular Neoplasms; Young Adult

Topics: Adrenal Hyperplasia, Congenital; Adrenocorticotropic Hormone; Adrenogenital Syndrome; Anti-Inflammatory Agents; Child, Preschool; Cortodoxone; Dehydroepiandrosterone Sulfate; Diagnosis, Differential; Follow-Up Studies; Humans; Hydrocortisone; Leydig Cell Tumor; Male; Testicular Neoplasms; Testis; Testosterone; Ultrasonography