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Serum androgens testosterone (T), testosterone-like-substances (TLS), delta4-androstenedione (delta4), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA) were measured in 85 normal girls and 101 normal boys grouped according to pubic hair development in Tanner stages I to IV/V. The pattern of change with puberty differed for each androgen. In boys T and TLS rose with the onset of puberty but showed a more abrupt rise later in puberty. DHT also was higher in boys in late puberty but did not demonstrate a steep rise. The other androgens did not show a sex difference at any stage of puberty. While delta4 steroids did not show an increase in the years before onset of puberty, DHEA was significantly higher in prepubertal children over 7 years than in those under 7 years (mean +/- SD 166 +/- 110 vs. 31 +/- 25, P less than 0.005). The most rapid increase of DHEA concentrations was observed with the appearance of pubic hair (Stage II) in boys and girls. This contrasted with the more gradual rise of delta4 in both sexes. The oldest boys and girls (Tanner stages IV/V) had mean concentrations of all androgens in the adult range except for DHT. Twenty-two girls with precocious adrenarche (PA) aged 3-8 years had mean concentrations of T, DHT, delta4 and DHEA that were significantly higher (P less than 0.05) than in prepubertal children, but similar to those of girls in stage II and significantly lower (P less than 0.02) than in late pubertal girls (stage IV/V). Longitudinal studies in 12 of the girls indicated fluctuation of androgen concentrations, especially DHEA, but in general no increase during the years of followup. Precocious adrenarche appears to be a non-progressive disorder associated with an advanced maturation of adrenal androgen to an early pubertal stage. A rise in all androgens measured was correlated with the development of sexual hair.

Extensive hormonal evaluation was performed in a girl with adrenal carcinoma during the primary tumor stage, following adrenalectomy, during the period when metastases were evident and while on treatment with o,p'-DDD. At the age of 14 months a diagnosis of congenital adrenal hyperplasia was made and treatment with dexamethasone (0.125 to 0.25 mg/day) resulted in a fall-off in growth rate, normal advancement in bone age, decrease in virilization and suppression of 17- ketosteroid excretion which continued until 4 3/12 years of age when virilization increased. At five years of age elevated serum and urinary androgen levels unsuppressible with dexamethasone were noted. Following removal of a large right adrenal carcinoma, serum and urinary hormone levels returned to normal. There months following surgery, liver metastases were documented associated with elevated levels of serum androgens. With o,p'-DDD treatment, serum dehydroepiandrosterone sulfate (DS) and urinary 17-ketosteroid (17-KS) excretion fell rapidly while there was a delay in the fall of free androgens. The persistence of free steroid secretion with decreased formation of DS suggests that the o,p'-DDD may have altered sulfatase activity before causing tumor necrosis and total decrease in steroidogenesis.

The diagnosis of psychosocial dwarfism (PSD) was made in a 7 year old boy upon admission to the hospital. In the period following admission, he grew at a slightly accelerated rate of 0.6 cm in 24 days (extrapolated growth rate--9.1 cm/yr); his caloric intake was 1663 calories/day (147 cal/kg/day), stimulable growth hormone was 5.9 ng/ml and somatomedin activity was in the hypopituitary range (0.24, 0.05 U/ml). In the following period of marked catch-up growth of 8.6 cm in 102 days (extrapolated growth rate 30.8 cm/yr), his caloric intake decreased significantly to 1514 cal/day (106 cal/kg/day, 0.005 less than p less than 0.01), stimulable growth hormone in this period was 13.6 ng/ml and somatomedin activity normalized (0.98 U/ml). While under continued observation, with separation from his favorite nurse, his growth velocity dropped significantly to the rate immediately following admission, but there was no change in his stimulable growth hormone or in somatomedin activity. With the return of his favorite nurse, he resumed his previous rapid catch-up growth with no change in caloric intake (p equals not significant), growth hormone level, or somatomedin activity. Upon transient return to his depriving home, his growth rate decreased to 1.4 cm in 70 days (extrapolated growth rate 7.2 cm/yr); growth hormone remained in the normal range. Somatomedin activity was in the low normal range (0.57 U/ml) and rose to high normal activity (1.31 U/ml) as rapid catch-up growth resumed after he had been readmitted. We conclude from these data that: 1. Serum somatomedin in longstanding untreated PSD may be in the hypopituitary range. 2. Markedly fluctuating growth rates during recovery in this patient with PSD were not due to changes in caloric nutrition, growth hormone release or somatomedin activity, but to an as yet unidentified factor affecting growth during emotional stress.

Endocrinologic and serologic studies of a 2-year-old child with the chromosomal complement 46,XX and ambiguous genitalia suggested the preoperative diagnosis of true hermaphroditism. Urinary and serum androgen production in response to human chorionic gonadotrophin was in the range expected for normal males, implying presence of cryptic testicular tissue. Moreover, detection of H-Y antigen, a cell surface component associated with testicular differentiation and coded or regulated by a Y-chromosomal gene, indicated presence of Y-chromosomal material. The diagnosis of true hermaphroditism was confirmed at surgery. Assuming a constant association of H-Y antigen and testicular differentiation is established, human H-Y serology may be an important adjunct to the endocrinologic evaluation of intersex patients. Our studies support the interpretation that a Y-chromosomal translocation too small for cytologic detection accounts for testicular differentiation in 46,XX true hermaphroditism. Expression of H-Y antigen remained positive after castration.

Clinicians still encounter patients suffering from prolonged episodes of primary angle-closure glaucoma. These patients often have been misdiagnosed or neglected initially. While laser iridotomies have proven most effective in the treatment of acute angle-closure glaucoma, there is a diversity of opinion regarding the treatment of chronic forms, in particular when the congestive phase has been of long duration (e.g., 3 to 14 days). The fact that ophthalmologists must still contend with the dreaded complication of malignant glaucoma attests to the difficulty of treating this condition. A series of cases have been collected during the past 15 years, all having prolonged episodes of primary angle-closure glaucoma, where the anterior-chamber angles could not be opened medically before surgery. We found that laser iridotomy is not efficacious in this situation, and indeed often impossible to perform due to corneal edema. Our patients were treated surgically with sector iridectomies, with an extremely high degree of success, and a minimal complication rate. The results are presented in tabular form. The mechanism of action is described, and the reasons for the success of this procedure explained.

The effect of testosterone on compensatory renal hypertrophy (CRH) remains controversial. We therefore examined the effect of exogenous testosterone on CRH in adult male and female rats after unilateral nephrectomy. The influence of endogenous testosterone was studied by comparing the degree of CRH in normal male, castrated male, and in testosterone receptor deficient male pseudohermaphrodite rats. Furthermore, serial determinations of serum testosterone levels were performed after unilateral nephrectomy in male rats. Compensatory renal hypertrophy was comparable between male rats--with or without exogenous testosterone administration--and between normal male, castrated male, and psuedohermaphrodite male rats. In contrast, exogenous testosterone administration in female rats enhanced CRH. Serum testosterone levels fell markedly after unilateral nephrectomy or sham surgery, but increased to 183% and 234% of control values at 1 and 2 days after surgery in the unilaterally nephrectomized rats. At no time, however, did they exceed the range of normal values. The results indicate a different effect of testosterone on CRH in male and female rats.

In order to determine the source of androgens in precocious adrenarche, serum androgens were determined in 8 girls with precocious adrenarche and 5 agonadal children in adrenarche under conditions of adrenal and gonadal stimulation and suppression. All androgens increased with ACTH stimulation in both groups. Stimulability of serum androgens in girls with precocious adrenarche with ACTH was more consistent than in 13 prepubertal children. Human chorionic gonadotrophin administration increased serum delta4-androstenedione, testosterone and dihydrotestosterone in the girls with precocious adrenarche but not in the agonadal children, demonstrating the failure of HCG to stimulate adrenals. Dexamethasone suppression decreased levels of all androgens in both groups, whereas Norlutin or Ovral produced variable changes. These studies support the adrenal origin of androgens in precocious adrenarche and the lack of ovarian contributions in this condition.