Comparison of Basal and Adrenocorticotropin- Stimulated Plasma 21-Deoxycortisol and 17-Hydroxyprogesterone Values as Biological Markers of Late-Onset Adrenal Hyperplasia

Abstract

Plasma 21-deoxycortisol (21-DOF) and 17-hydroxyprogesterone (17-OHP) concentrations were assayed before (basal) and 1 h after ACTH stimulation in 4 groups of normal subjects (35 follicular phase women, 22 luteal phase women, 33 adult men, and 15 prepubertal children) and in a group of 31 patients with the late-onset form of congenital adrenal hyperplasia (LOCAH) due to 21-hydroxylase deficiency as well as in 31 LOCAH) heterozygotes. The mean basal plasma 21-DOF concentrations in each of the 4 groups of normal subjects were between 8 ng/dL (0.23 nmol/L) and 11 ng/dL (0.31 nmol/L), and they increased significantly after ACTH stimulation to between 36 ng/dL (1.04 nmol/L) and 44 ng/dL (1.27 nmol/L). There were no differences in basal or ACTH-stimulated plasma 21-DOF levels in these 4 groups, whereas their basal and post-ACTH plasma 17-OHP levels did vary. Among the LOCAH patients, 83.8% had basal plasma 21-DOF levels and 61.2% had basal plasma 17-OHP levels higher than the highest basal 21-DOF [30 ng/dL (0.86 nmol/L)] and 17-OHP [450 ng/dL (13.61 nmol/L)] concentrations in the normal subjects, and all individual 21-DOF and 17-OHP levels after ACTH stimulation [greater than or equal to 404 ng/dL (11.67 nmol/L) and greater than or equal to 1040 ng/dL (31.47 nmol/L), respectively] were markedly higher than the highest 21-DOF [76 ng/dL (2.19 nmol/L)] and 17-OHP [580 ng/dL (17.55 nmol/L)] levels in the normal subjects. The mean post-ACTH/basal plasma level ratios among the LOCAH patients were 19.75 for 21-DOF and 8.03 for 17-OHP. In LOCAH heterozygotes, basal 21-DOF values were higher than normal in 48.3%, and post-ACTH values were higher than normal in 93.5% of the cases. In contrast, basal plasma 17-OHP levels were similar in LOCAH heterozygotes and normal subjects, and only 16.1% of the LOCAH heterozygotes had post-ACTH plasma 17-OHP levels higher than the highest normal value. If sex and phase of the menstrual cycle are taken into account, along with the incremental responses (post-ACTH minus baseline value) of plasma 21-DOF and 17-OHP, to compare LOCAH heterozygotes and normal subjects, the discriminating power for detection of heterozygocity was somewhat increased for 21-DOF (to 100%) and appreciably increased for 17-OHP (to 30%).(ABSTRACT TRUNCATED AT 400 WORDS)

Apparent activities of 21-hydroxylase, 17alpha-hydroxylase and 17,20-lyase are impaired in adrenal incidentalomas

“…Impaired 21-hydroxylase activity was assumed when the poststimulation 17-OHP level exceeded 15 nmol/l (22). Poststimulated 21-DF levels over 2.2 nmol/l were taken as indicative of 21-hydroxylase impairment (20,21). A post-stimulative S/F ratio above 0.12 was taken as indicative of an altered 11b-hydroxylase activity; this cut-off value was determined from previously published studies (12,(23)(24)(25).…”

“…Conversely, only one subject displayed a peak 21-DF value in the normal range whereas ten had levels above 2.2 nmol/l, a cut off that has been shown to separate normal subjects from heterozygous or homozygous carriers of 21-hydroxylase deficiency (20,21). Although peak 17-OHP and peak 21-DF provide comparable results, we suggest that for individual patients peak 21-DF determination is better given its greater specificity (20,21). This study did not identify predictive parameters indicating an impaired 21-hydroxylase activity.…”

“…The aim of this study was, therefore, to define more clearly the apparent activities of these steroidogenic enzymes in adrenal incidentalomas. Moreover, the investigation of the serum 21-deoxycortisol (21-DF) response to ACTH, which is believed to be a more sensitive marker of 21-hydroxylase potency (20), has been -to the best of our knowledge -introduced in this setting for the first time.…”

MANAGEMENT OF ENDOCRINE DISEASE Hyperandrogenic states in women: pitfalls in laboratory diagnosis

“…With a >10 ng/ml cut-off, Morel and Tardy (101) showed that nearly 100% of patients with genetically proven NCAH, regardless of the type of mutation, could be identified. This very accurate cut-off value is routinely used for NCAH screening in hyperandrogenic women (102,103,104,105,106). In the near future, the development of sequencing platforms should enable routine sequencing of the CYP21A2 gene.…”

Hirsutismo en niñas adolescentes: Estudio clínico y de laboratorio

“…Estos trastornos pueden confundirse con cierta frecuencia con el sindrome de ovario poliqufstico porque, ademas de signos clinicos de hiperandrogenismo, la ecografia ovarica revela a veces imagenes qui'sticas similares en ambas enfermedades 12 ' 13 . Solo un acucioso estudio hormonal en condiciones basales, con pruebas de estimulacion con ACTH y luego frenacion, permiten en la mayoria de los casos el diagnostico correcto 6 ' 7 ' Hl 1S . A continuacion se describe una estrategia realizada para detectar, en un grupo de pacientes con hirsutismo de etiologi'a no precisada, aquellas en que la causa puede ser de origen suprarrenal y sus resultados.…”