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

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

Serum osteocalcin and urinary deoxypyridinoline: response prediction in children on recombinant human growth hormone replacement therapy

In children and adolescents, markers of bone and collagen metabolism reflect the dynamics of skeletal growth and development. Treatment with recombinant human growth hormone [rhGH] has a marked effect on bone formation and resorption. This bone remodeling is well reflected on specific markers that can be measured in blood and urine. The aim of this study was to assess the potential role of bone remodeling markers in the assessment of the response to rhGH in GHD children. The study included 35 children and adolescents, 20 of which had GHD [14 boys and 6 girls], with a mean age of 14.46 +/- 2.47 years and 15 controls [8 boys and 7 girls], 11.3 +/- 2.01 years old, Anthropometric measurements were performed, and blood and morning urine samples were collected for estimation of total serum calcium, inorganic phosphorus, total ALP, OC and urinary DPD. DPD values were corrected to urinary creatinine concentrations and expressed as deoxypyridinoline/creatinine [DPD/cr] ratio. Patients started rhGH therapy, laboratory assays were repeated after 3 months, and anthropometric measurements were repeated at 3-monthly intervals for one full year. Bone turnover markers [calcium, phosphate, ALP, OC, and urinary DPD] were measured before and after 3 months of onset of rhGH. The results showed that in all patients, rhGH evoked continuous improvements in height standard deviation scores [SDS], with no significant effect on weight SDS. Height velocity SDS [HVSDS] was high during the first 3 months of rhGH, decreased thereafter, supporting the waning of rhGH, Pre-treatment Level of the ALP and OC were lower in patients than controls. Differences in serum OC levels between patients and controls were high enough to discriminate between the two groups [p<0.0001]. Both increased substantially after rhGH, Basal and after 3 months value of ALP, OC and DPDlcr ratio was 106.95 +/- 32.76 and 144.75 +/- 38.20 IUIL; 6.80 +/- /- 3.74 and 31.78 +/- 26.12 nglml; 23.69 +/- 22.49 and 37.75 +/- 29.28; with p=0.008, p=0.0001 and p>0.05, respectively. There was a significant positive correlation between the both serum ALP basal and after 3 months and overall 1st year HVSDS [r=0.69, p=0.019, p=0.86, p=0.001, respectively]. There was a significant positive correlation between serum levels of OC and urinary DPDlcr ratio in both, patients before rhGH [r=0.538, p=0.014] and controls [r=0.654, p=0.008]. Basal values of DPD/cr were positively correlated with HVSDS after 3 months [r=0.48, p0.034] and after 3 months of rhGH DPD/cr were positively correlated with height SDS [r=0.46, p=0.04]

Conclusion: bone formation markers, namely ALP and OC and bone resorption markers, namely DPD increase during growth hormone [GH] therapy. At least, one full year of observation is mandatory to detect the impact of rhGH on height measurements, while bone-remodeling markers may be used as early predictors of the long-term response to the expensive rhGH in a child with GHD. OC measurement may be used as an adjuvant assay, together with height measurements and GH stimulation tests, in the initial diagnosis of GHD as it could differentiate between patients and controls

Study of direct and indirect tests of vasopressin function in diagnosis of diabetes insipidus

This study was conducted on 16 patients with diabetes insipidus [DI]. Direct and indirect tests of vasopressin function were performed for the patients and compared with ten matched control subjects. The study showed that the standard indirect test was enough for diagnosis of DI when present in its severe, complete and classic form. Yet, the need for plasma AVP assay becomes necessary to differentiate between the types of DI when present in partial or incomplete form due to the extensive overlap values obtained by the standard indirect test