Response of plasma adrenocortical steroids to low doses adrenocorticotrophic hormone compared to standard dose in normal Egyptian subjects

ABSTRACT

The short ACTH stimulation test, using 250 micro g synthetic adrenocorticotropic hormone [ACTH], has been advocated as a safe alternative procedure to the dangerous insulin stress test, for assessment of the function of the hypothalamic-pituitary-adrenal [HPA] axis. However, it has been suggested that a maximal cortisol response can be achieved with a much lower ACTH dose, hinting at the possibility that reducing the dose might further enhance the sensitivity of the procedure. Aim of work The aim of this study was to assess the potential role of the low dose ACTFI challenge in the evaluation of the HPA axis function, compared to the standard 250.micro g ACTH test in normal adults. Subjects and The study was conducted on 21 apparently healthy Egyptian adult volunteers, who underwent stimulation with three different doses [1 micro g, 5 micro g and 250 micro g] of synthetic ACTH [1-24]. Blood samples were obtained at 0, 15, 30 and 60mm for measurement of serum cortisol concentration and 0. 60min serum samples were also used to measure adrenal precursors Delta-4-androstendione [delta-4A], Dehydroepiandrosterone [DHEA] and 17- hydroxyprogesterone [17 OHP] levels, to investigate the efficiency of the low doses of ACTH for detection of late-onset congenital adrenal hyperplasia [LOCAH]. The study revealed no significant difference between mean cortisol level at 15, 30 and 60min in response to the three different doses. Using the 1 or 5 micro g doses, all subjects [100%] reached adequate cortisol response at 30min, while using 250 micro g dose, 90% of subjects reached adequate cortisol response at 60min. The steroid precursors showed no significant difference at 60min in response to the three doses. During the study, 4 cases, two males and two females, were accidentally found to have elevated steroid precursors in response to ACTH. These cases were found to have 21- hydroxylase deficiency, as evidenced by the elevated levels of stimulated 17 OHP, thus, were diagnosed as LOCAH. The low doses [1micro g and 5 micro g] ACTH test responses were found almost comparable to the 250 micro g doses on normal subjects, and can be used to induce adequate adrenal stimulation. They were also useful in detecting latent cases of congenital adrenal hyperplasia