Peter A. Lee

Plasma Progesterone, 17-Hydroxyprogesterone, Androstenedione and Testosterone in Prepubertal, Pubertal and Adult Subjects with Congenital Virilizing Adrenal Hyperplasia as Indicators of Adrenal Suppression

To determine whether a single morning plasma level of 17-hydroxyprogesterone (17OH-P), androstenedione, testosterone and progesterone reflected the degree of control of 21-hydroxylase congenital virilizing adrenal hyperplasia (CVAH) as indicated by 24-hour urinary 17-ketosteroid and pregnanetriol excretion, 142 simultaneous 24-hour urine and morning blood collections were made from 65 patients with CVAH. Patients were grouped into five categories on the basis of age, skeletal age, and sex. Paired blood and urinary data were analyzed. The results suggest that androstenedione is the most reliable indicator for all patient categories. Testosterone is an excellent indicator for children of both sexes and for adolescent and adult females. Levels of 17OH-P are difficult to interpret, as they can be several fold higher than the normal values when adrenal suppression appears adequate on the basis of urinary data. In general, progesterone is a poor indicator.

Are Constitutional Delay of Growth and Familial Short Stature Different Conditions

Children between 2 and 4 standard deviations below the mean height for age with no specific cause to account for their short stature are usually considered to represent either constitutional delay of growth (CDG) or familial short stat ure (FSS). This study was undertaken to determine whether 167 patients who were referred to our clinic for short stature could be divided into two distinct populations that fit the criteria of CDG and FSS. When the patients were arti ficially divided into 2 subgroups based on skeletal age greater or less than 2 standard deviations below the mean, no significant difference in growth rates or midparental heights could be found between them. Height ages were sig nificantly more delayed in the group with greater skeletal age delay. Mid parental height of our total population of short children was less than the mean midparental height of normal American children. It was concluded that our patients did not distribute into these two clear-cut entities. Whether they repre sented one continuum or two largely overlapping populations could not be decided on the basis of our data.

Persistence of the enzymatic block in adolescent patients with salt-losing congenital adrenal hyperplasia.

The 24-hour integrated concentration of aldosterone, plasma renin activity, and 17-hydroxprogesteronewas measured simultaneously in 12 patients with congenital virilizing adrenal hyperplasia due to 21-hydroxylase deficiency. Eight were salt-losers and four nonsalt-lowers. Seven normal children served as control subjects. All patients were receiving glucocorticoid replacement therapy (32 mg/m 2 /day). All but one of the SL-CVAH patients were also being treated with 9α-fluorocortisol. The mean (±SD) IC-PRA of the control subjects was 1.6±0.7 ng/ml/hour and in the NSL-CVAH patients was similar (1.6±0.7 and 2.2±1.0 ng/ml/hour). The IC-PRA of the SL-CVAH patients (21.1±28.8 ng/ml/hour) was significantly ( P P

HCG Stimulation in Children With Cryptorchidism

Fifty-eight children with cryptorchidism have been given hCG stimulation testing, 31 with bilateral cryptorchidism, 22 with unilateral, and 5 with prior unsuccessful orchiopexy. Hormonal studies were carried out prior to and following stimulation. In bilateral cryptorchidism, bilateral descent was observed in 32 percent of cases and in unilateral, the success rate was 55 percent. From their data, the authors concluded that hCG is not indicated if patients present elevated LH and FSH levels or if the basal T levels are in the pubertal range. In the other subjects, the hCG test will permit the determination of the presence or absence of testosterone production and in some cases it results in testicular descent. Finally, in cases of failure that require surgery, the hCG will stimulate tissue growth enhancing the success of orchiopexy.

Intra-HLA recombinations localizing the 21-hydroxylase deficiency gene within the HLA complex

Close linkage between HLA and the gene for 21-OH deficiency causing congenital virilizing adrenal hyperplasia (CVAH) has been well documented. HLA-A/B and HLA/GLO recombination data placed the CVAH gene within the HLA-A to GLO interval, with CVAH invariably segregating with HLA. HLA-A,B,C,DR and GLO typing and ACTH stimulation to determine carrier status was done on seven families. Carrier status correlated with the appropriate HLA haplotypes in all offspring, with two exceptions. Two intra-HLA recombinants were detected in one three-generation family. The father of the proband is homozygous for HLA-A2,Cw2,B27 but is a DR2/DR4 heterozygote. The CVAH gene segregated with DR2 in all but one of his offspring who is a carrier and is DR4. This finding is consistent with recombination between the CVAH gene and DR. Study of the fathers family confirmed synteny of the CVAH gene and DR2. Three of four sibs of the father inherited this haplotype and were CVAH carrier, as was the paternal grandmother, whose other haplotype was A1, Bw44,DR1. One of the fathers sibs was shown serologically to be a HLA-B/D maternal recombinant and a noncarrier. she inherited the A1,Bw44 of one maternal haplotype, but the DR2 of the other. In both recombinants in this family the CVAH gene segregated with the A to B interval, separate from D. While we cannot determine whether the CVAH gene is in the HLA-A to B or B to D interval, this is the first report of two intra-HLA recombinations in one family that unequivocally map the CVAH gene inside HLA-D.

DECREASED LH RESPONSE TO THE SECOND OF CONSECUTIVE DAY LUTEINIZING HORMONE RELEASING HORMONE (LHRH) INFUSIONS AMONG PATIENTS WITH CONSTITUTIONAL DELAY OF PUBERTY: A PHENOMENON OF PUBERTAL MATURATION?

Consecutive day LHRH stimulation by continuous infusion has been used to evaluate pituitary reserve. Different responses on the 2 days were not present among non‐pubertal hypopituitary patients, pubertal growth hormone deficient patients or adult males. However, patients with constitutionally delayed puberty demonstrated a greater serum LH response on day 1 than day 2. Urinary LH responses suggest a similar but not statistically significant pattern. This response may be a normal phenomenon of puberty or may represent part of the reason for constitutionally delayed puberty.