The behaviour of plasma levels of ACTH was studied in five untreated patients with pituitary-dependent Cushing's syndrome, with blood samples taken every half an hour for a total period of 24 hours; plasma cortisol, corticosterone, deoxycorticosterone (DOC) and aldosterone were also measured simultaneously. In all cases, above normal secretory impulses of ACTH and cortisol, at approximately the same height, were present throughout the day, while between these peaks the levels were in the normal range. Few peaks of ACTH and cortisol were simultaneous and rare secretory impulses of corticosterone, and deoxycorticosterone were in synchrony with those of ACTH or cortisol. DOC levels were found to have some peaks above normal levels while corticosterone levels presented rare elevated peaks during the day. Plasma aldosterone values on the other hand, were extremely low in all except in one case, where the variations may be interpreted as pure fluctuations. These findings confirm that: 1) In a number of cases, multiple samples of ACTH and cortisol (during the 24 hrs.) appear to be essential in order to distinguish pituitary-dependent Cushing's syndrome from normal; 2) In conditions of ACTH excess, DOC and corticosterone secretion seems to become progressively less ACTH-dependent as we proceed down the biosynthetic chain towards aldosterone, which is suppressed in most cases.

1. In previous studies, baseline and ACTH-stimulated hormone levels, plus HLA genotyping, have been used to detect heterozygous carriers in congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHDS). 2. In the present study similar parameters were determined in a family of four including two children with CAH due to 11 beta-hydroxylase deficiency (11-OHDS), and a family of twelve including three sibs (two females, one genotypically male) with CAH due to 17 alpha-hydroxylase deficiency (17-OHDS). 3. HLA typing showed affected sibs with 11-OHDS to differ in one of their haplotypes. No significant differences in basal and ACTH-stimulated steroid levels were seen between the parents (obligate heterozygotes) and the general population. 4. In 17-OHDS, affected members differed from one another in one to two haplotypes; one patient had identical HLA profiles with two of the normal siblings, as did the genotypically male patient with two others; each of the other healthy siblings had one haplotype found in two of the affected subjects. The genes responsible for 11-OHDS and 17-OHDS--in contrast with 21-OHDS--do not appear to be HLA-linked. However, the measurement of ACTH-stimulated corticosterone levels may be useful, since the gene responsible for 17-OHDS seems to be expressed hormonally in the heterozygous state.

The effect of a synthetic long acting corticotropin (al-18 ACTH) on glucocorticoid and mineralocorticoid function and water and electrolyte balance in normal subjects has been studied. 0.5 mg of al-18 ACTH was administered i.v. to 4 normal subjects for 3 consecutive days. Plasma Cortisol (F), corticosterone (B), deoxycorticosterone (DOC) aldosterone and renin activity (PRA) were measured, at various intervals: on the preceding day, on the 3 days of therapy and on the following day. Urinary 17-OH steroids and aldosterone as well as water and electrolyte balance were also evaluated.Results: on the first day of treatment, F, B and DOC increased to their maximal values 2-4 hours after administering the drug and remained at this level for 10 hours thereafter. The values remained above basal values even on the following morning. The higher values of F and DOC were reached on the 2nd day of therapy, whereas B did not show any further increase.The plasma aldosterone showed a net increase after 4 hours on the first day but had little variation on the second day and remained unchanged or lowered on the third day as did the urinary aldosterone. PRA was not modified; there was a slight reduction in serum potassium concomitant with a decrease of urinary sodium/potassium ratio.The blood pressure remained more or less unchanged.Conclusion: the corticostimulatory action of al -18 ACTH seemed to be protracted over a 24 hour period. The therapeutic implications are discussed.