SUMMARY In 11 children aged between 2 and 17 years with (nonsalt-losing) congenital adrenal hyperplasia (21-hydroxylase deficiency) blood was drawn at 90-minute intervals during a 24-hour period and levels of 17-hydroxyprogesterone, testosterone, and cortisol were measured. Levels of 1 7-ketosteroids and pregnanetriol were measured too in 24-hour urine samples. These measurements were taken under different regimens of treatment and after interruption of treatment. Cortisol levels rose and fell rapidly after administered corticosteroid, and reached unphysiologically high levels. Testosterone levels showed pronounced variations but stayed in the normal range for most of the time even in untreated patients; thus testosterone provides a poor control parameter. Levels of 1 7-hydroxyprogesterone showed extreme fluctuations and very high peak levels in untreated patients; standard treatment with two or three daily doses of corticosteroids did not prevent a pronounced rise in its level after midnight. After the first morning dose of hydrocortisone a very steep fall was observed. The 24-hour pregnanetriol excretion correlated well with the corresponding total integrated 1 7-hydroxyprogesterone area. It is concluded that single 1 7-hydroxyprogesterone values are unlikely to give adequate information about the quality of treatment.In patients with congenital adrenal hyperplasia control of glucocorticoid substitution therapy is governed by clinical parameters (growth velocity, bone age, pubertal stage) together with biochemical data on 17-ketosteroids (17-KS) and pregnanetriol. Recent advances have drawn attention to the plasma levels of cortisol precursors, especially of 17-hydroxyprogesterone (17-OHP),1 the value of monitoring this steroid in the management of congenital adrenal hyperplasia having been investigated2-9 and found to be limited by the well-known circadian rhythm.'0 The effect of the time lag between ingesting the drug and blood sampling has not been fully studied, and the same applies to the circadian rhythm. Information on plasma levels of cortisol under substitution therapy is also lacking. Therefore we have studied the circadian patterns of cortisol, 1 7-OHP, and testosterone under glucocorticoid therapy, and in addition, using the urinary parameters of 17-KS and pregnanetriol, we have assessed the usefulness of single 17-OHP values in the monitoring of treatment. Patients and methodsIn 9 girls and 2 boys aged between 2j and 16j years under treatment for congenital adrenal hyperplasia due to 21-hydroxylase-deficiency, blood was drawn at 90-minute intervals during a 24-hour period to determine the levels of 17-OHP, cortisol, and testosterone. Levels of 17-KS and pregnanetriol were measured in the corresponding 24-hour urine samples. Three patients (Cases 8,10, 11) were also studied after stopping treatment for 3 days; one newly diagnosed boy (Case 9) was studied before treatment began and then 2 weeks later. Informed consent for the investigation was obtained from the parents.

Helicobacter pylori (H. pylori) infections affect roughly one-half of the world’s population. Although many standard regimens, including triple-drug therapy, eradicate H. pylori, the success rate and efficacy have been declining due to associated side effects and symptom severity. The addition of probiotics to a standard regimen can considerably increase eradication rates. The objective is to find the efficacy of a probiotic Lactobacillus reuteri (L. reuteri) in eradicating human H. pylori infection and effect on symptoms regression and side effects associated with triple therapy. This prospective interventional study was conducted in 90 H. pylori-positive patients. 45 patients received standard triple treatment (group-I) for 14 days. Another 45 patients received a combination of standard triple therapy and L. reuteri (group-II) for 14 days. After the completion of treatment, H. pylori status was evaluated using a 13-C Urea-Breath Test (UBT). Each subject is interviewed with a validated Gastrointestinal Symptoms Rating Scale (GSRS) questionnaire to record symptoms and symptom severity before and after the therapy. Group-II patients showed a significantly higher eradication rate (86.67%) than group-I patients (66.67%). The absolute values of 13C-UBT (group-I: 14.02± 5.4, group-II: 11.9±3.73) revealed that a more substantial reduction in H. Pylori load was observed in group II. Statistical analysis proved that group II patients had a significant reduction in GSRS mean scores (baseline score: 15.39±4.52 to end score: 5.33±2.34) compared to group-I patients (baseline score: 14.47±3.67 to end score: 9.86±4.78). Addition of L. reuteri has reduced side effects associated with triple drug therapy except bloating. In conclusion,  supplementation of  L. reuteri to standard triple drug therapy significantly  improved the eradication rate of H. pylori, reduced intensity of gastrointestinal symptoms and also treatment related side effects.

An accurate and relatively simple radioimmunoassay for the determination of aldosterone concentration in peripheral plasma has been developed. 0.5–2.0 ml plasma with added [1,2-3H] aldosterone is extracted with dichloromethane. Purification of the extract is achieved by thin layer chromatography in the system benzene-acetone 1:1. Recovery of [1,2-3H] aldosterone is 58 ± 6 (sd) %. Bound and free fractions are separated by dextran-coated charcoal. The intra-assay reproducibility is 8.8 % and the inter-assay reproducibility varies from 11.4–16.1 %. The sensitivity of the assay for a 5 ml plasma sample can be put at 0.2 ng/100 ml. Normal values determined in 52 healthy children of different age groups are presented. Furthermore the aldosterone stimulating effect of low sodium diet (17 children), severe and prolonged vomiting (19 children) and synthetic ACTH (10 children) has been studied by our modified method.

Plasma levels of aldosterne and 17-hydroxyprogesterone were determined in 5 just diagnosed cases of congenital adrenal hyperplasia due to 21-hydroxylase deficiency without salt-loss before onset of therapy, and in 14 children suffering from the same disorder, under glucocorticoid therapy before and after withdrawal of therapy for one week as well as before and after ACTH-stimulation. Furthermore, urinary pregnanetriol, pregnanetriolone, 17-ketosteroids and 17-ketogenic steroids were determined with and without therapy. Serum concentrations of 17-hydroxyprogesterone in patients before onset of therapy were at least 40 times above the normal range (normal range: 0.39 ± 0.23 ng/ml determined in 19 children of age 1–12 years), aldosterone was also elevated (range 16.5–84.4 ng/100 ml, normal aldosterone being 7.3 ± 4.7 ng/ml). In contrast, well controlled patients (judged on urinary pregnanetriol-excretion) had normal aldosterone (one exception) and 17-hydroxyprogesterone levels below 5 ng/ml. Both steroids were well stimulated by ACTH. In 3 poorly controlled cases elevated pregnanetriol and 17-hydroxyprogesterone values up to 130.9 ng/ml were found. Withdrawal of therapy resulted in pronounced rise of aldosterone and 17-hydroxyprogesterone. Exogenous ACTH had no detectable effect in 7 cases leading to further stimulation in the other children. We found an excellent correlation between plasma 17-hydroxyprogesterone and urinary pregnanetriol (r = 0.84, P < 0.003, n = 14). Fairly good correlation also exists between aldosterone and 17-hydroxyprogesterone values (r = 0.65, P < 0.01, n = 14) in patients before the onset and after withdrawal of therapy. The data confirm the value of 17-hydroxyprogesterone determinations for diagnosis and management of congenital adrenal hyperplasia on the one hand, and the compensatory elevated aldosterone production in the non-salt-losing form of the disorder on the other.

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