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PubMed1992

The role of adrenocorticotropin testing in evaluating girls with premature adrenarche and hirsutism/oligomenorrhea.

To identify biochemical predictors for future development of hirsutism and/or oligomenorrhea (H/O) in girls with premature adrenarche (PA), we performed dexamethasone-suppressed ACTH stimulation tests in girls with PA (n = 46), young women (n = 44) with H/O, and adult women (n = 31). Cortisol, androstenedione, dehydroepiandrosterone, and 17-hydroxyprogesterone were measured. Seven girls with PA (15%) and seven with H/O (16%) had evidence of nonclassical adrenal steroid biosynthetic defects [nonclassical congenital adrenal hyperplasia (NCAH)]. Twenty-five girls with PA (54%) and 28 girls with H/O (64%) had the moderately elevated 17-hydroxyprogesterone response to ACTH that has been reported in obligate heterozygotes for 21-hydroxylase deficiency. There were no clinical features that distinguished the girls with NCAH from the others. ACTH testing is an important tool in distinguishing those girls with PA and H/O who have NCAH. Although we could find no differences in other adrenal steroid hormones that might predict which of the other girls with PA might late develop H/O, black girls comprised a substantially smaller fraction of the population with H/O than of the population with PA (2% vs. 26%; chi 2 = 8.5; P less than 0.005). This observation suggests that PA, in blacks who do not have NCAH, is more likely to be a benign condition/than in other ethnic groups.

17-alpha-Hydroxyprogesterone↗
PubMed1992

Fertility in women with late-onset adrenal hyperplasia due to 21-hydroxylase deficiency.

Fertility was evaluated in 53 female patients with late-onset adrenal hyperplasia (LAH) due to 21-hydroxylase deficiency. The majority of patients (n = 33) were seen for isolated postpubertal hirsutism, 9 patients consulted for sterility, and 11 for irregular menstrual cycles. At the time of diagnosis, the ages of patients ranged from 15-40 yr (mean +/- SD, 24.6 +/- 5.2). No patient had major signs of virilization. The plasma 17-hydroxyprogesterone level was higher than normal in all patients (26.8 +/- 18.9 nmol/L; range, 3.4-139.4) and dramatically increased to 140.1 +/- 80.6 nmol/L (range, 35.2-324.2) after ACTH treatment. Plasma androgen levels were high (testosterone, 3.25 +/- 2.03 nmol/L; delta 4-androstenedione, 13.65 +/- 5.60 nmol/L). Plasma basal and LHRH-stimulated values were normal for FSH and high for LH. Basal and TRH-stimulated plasma PRL levels were normal. Among these 53 LAH patients, only 20 desired a pregnancy. These had a total of 38 pregnancies. Ten patients became pregnant before the diagnosis of LAH and without any treatment; they had a total of 18 pregnancies, 12 of which were successful. Moreover, 19 normal pregnancies without any spontaneous abortion were carried to term by 14 of 16 hydrocortisone-treated patients. One patient needed the association of one cure of clomiphene citrate. Hypofertility in LAH patients seems, therefore, to be relative. Its mechanism is hormonal, with anovulation or dysovulation, due to the continuous steroid feedback of adrenal origin on the hypothalamo-pituitary axis. Hydrocortisone is the appropriate treatment in most cases, reducing adrenal androgen overproduction and relieving hypothalamic-pituitary gonadotropin function, thereby making possible cyclic ovarian activity and ovulations.

17-alpha-Hydroxyprogesterone↗
PubMed1992

Adrenal incidentaloma and patients with homozygous or heterozygous congenital adrenal hyperplasia.

Adrenal tumors are being detected more frequently in consequence of the wider application of increasingly sensitive radiological investigation techniques. According to the working hypothesis that more silent adenomas could develop from hyperplastic tissue areas under increased stimulation of the adrenal cortex, heterozygous and homozygous patients with congenital adrenal hyperplasia (CAH) were studied. A high incidence of adrenal masses, nearly 82% in homozygous and 45% in heterozygous patients, was found. There was no correlation between tumor size and serum 17-hydroxyprogesterone concentrations. These tumors are, therefore, probably silent adenomas. On the basis of these results, CAH should always be ruled out in the case of incidentally detected adrenal masses. Since CAH is a relatively frequent disease, and the adrenal carcinoma belongs to the rarest malignant tumors, a malignant transformation of these tumors seems to be unlikely.

17-alpha-Hydroxyprogesterone↗
PubMed1992

An abnormality of the growth hormone/insulin-like growth factor-I axis in women with polycystic ovary syndrome due to coexistent obesity.

In order to evaluate the GH/insulin-like growth factor-I (IGF-I) axis in the polycystic ovary syndrome (PCO), 21 women aged 18-38 yr were studied. The GH responses to the GH-releasing hormone (GHRH), and plasma concentrations of IGF-I were measured in seven obese women with PCO, seven obese healthy controls without PCO, and in seven nonobese subjects. Total GH secretion, as expressed by the integrated GH response to GHRH, in PCO obese women (617.4 +/- 150 micrograms/L.min) and in obese women without PCO (327.1 +/- 161.4 micrograms/L.min) were lower than that in nonobese healthy controls (3181.4 +/- 644.3 micrograms/L.min, P less than 0.001 and P less than 0.001, respectively). Plasma concentrations of IGF-I in obese PCO women (199.5 +/- 39.1 micrograms/L), and in obese women without PCO (192.4 +/- 36.8 micrograms/L) were similar to the IGF-I levels in nonobese controls (224.3 +/- 33.2 micrograms/L). In obese women with and without PCO, a negative correlation was found between the body mass index and the peak GH responses to GHRH (r = -0.639, P less than 0.02) and between age and IGF-I levels (r = -0.520, P less than 0.05). These findings suggest that an abnormality of the GH/IGF-I axis in PCO women may be due to coexistent obesity.

17-alpha-Hydroxyprogesterone↗
PubMed1992

Hormonal profiles in Italian late-onset adrenal hyperplasia correlate with HLA class III polymorphisms.

To investigate the genetic polymorphisms of the HLA region in late-onset adrenal hyperplasia, 13 Italian patients affected by the disease were analyzed for: (1) HLA-A and -B typing; (2) restriction fragment length polymorphism (RFLP) of DR beta, DQ beta, DQ alpha, 21-hydroxylase A and B genes; (3) fourth complement fraction loci A and B (C4A and C4B), second complement fraction (C2) and properdin B factor (Bf) complement typing; (4) hormonal characteristics associated with some HLA haplotypes. HLA alleles B14 and DR beta 1 were found to be significantly more frequent in patients with respect to controls (relative risk: 8.7 and 7.2, p less than 0.001 and p less than 0.0001, respectively). Also C4B*2, 1 duplication was more frequent in patients than in normal subjects (23% vs. 1.5%, p less than 0.0001). Moreover, patients carrying a duplicated C4B (as well as those having the B14 antigen) showed higher 17-hydroxyprogesterone levels after ACTH stimulation. RFLP analysis of 21-hydroxylase genes with a specific probe revealed a duplication of 21-hydroxylase A gene in 40% of patients. All these individuals carried the C4A*2 B*2,1 phenotype and 75% of them displayed a clearly recognizable duplication at the C4B locus. These data support the hypothesis that in late-onset adrenal hyperplasia the 21-hydroxylase A pseudogene, even if inactive, may play a negative role in the regulation of 21-hydroxylase biosynthesis. Furthermore, we suggest analyzing class III phenotypes to screen the enzymatic defect.

17-alpha-Hydroxyprogesterone↗
PubMed1992

Estradiol, progesterone, 17-hydroxyprogesterone, androstenedione and CA125 in patients with ovarian carcinoma.

Estradiol, progesterone, 17-hydroxyprogesterone, androstenedione and CA125 were assayed in 25 women (12 oophorectomized before entering the study) with ovarian carcinoma. The data from patients were ordered according to the presence or absence of the gonads. The patients with ovaries (Group A) showed significantly higher levels of estradiol (p less than 0.01), progesterone (p less than 0.01) and 17-hydroxyprogesterone (p less than 0.01) than controls. This difference was not observed between oophorectomized patients (Group B) and controls. CA125 levels were significantly higher in patients that in controls (p less than 0.001) irrespective of the ovarian status of the patients. Eleven patients were followed during chemotherapy. Significant reductions of estradiol (p less than 0.01) and CA125 (p less than 0.001) levels after three courses of chemotherapy were observed. These data confirm that women with ovarian carcinoma produce an abnormal amount of steroids. Nevertheless, a marked difference between patients with and without ovaries was observed, suggesting that reported data might be biased by the presence of gonadal tissue. Thus the clinical application of steroids as tumor markers in unselected patients is limited.

17-alpha-Hydroxyprogesterone↗
PubMed1992

The newborn with ambiguous genitalia.

The unexpectedness of genital ambiguity in an infant creates an urgent and stressful situation. A logical approach, using a team of specialists together with nursery staff and physicians, allows each member to contribute expertise and unnecessary overlap of investigations. The psychological needs of the parents should be recognized, because their relation with the infant will determine the success of the assigned gender role in the future.

17-alpha-Hydroxyprogesterone↗
PubMedDate not supplied

Flutamide: a rational approach to hirsutism.

The Authors would show the effectiveness of flutamide, a potent selective antiandrogen, by an analysis of 30 patients with moderate to severe hirsutism. This therapy caused a marked improvement of clinic symptoms.

17-alpha-Hydroxyprogesterone↗
PubMed1992

[A genetic and hormonal study of 5 patients with the nonclassical form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency].

BACKGROUND: To study the association between the 21-hydroxylase deficiency with the HLA histocompatibility complex in a mediterranean ethnic group. METHODS: 5 patients with late-onset 21-hydroxylase deficiency, diagnosed on the basis of a high plasma level of 17-hydroxyprogesterone, along with 23 family members were typed. 17-hydroxyprogesterone response to iv ACTH stimulus was measured too in the family members. RESULTS: We found a genetic linkage disequilibrium between the late-onset 21-hydroxylase deficiency and the HLA antigen B51. Moreover, similar biologic profiles were observed in the patients and those of their siblings who were HLA identical. The heterozygous carriers showed a intermediate 17-hydroxyprogesterone response to ACTH between propositus and homozygotes and their family members who had no HLA haplotype identical to those of the propositus. CONCLUSIONS: These observations tend to confirm that a close linkage exits between the gene (or genes) for 21-hydroxylase deficiency in late-onset adrenal hyperplasia and the HLA genes. This association may change in the different ethnic groups.

17-alpha-Hydroxyprogesterone↗
PubMedDate not supplied

Comparison of the adrenocorticotropic hormone stimulation test in the follicular and luteal phases of the menstrual cycle.

A comparison was made of the ACTH stimulation test in the proliferative and luteal phases of the menstrual cycle in 13 subjects, each of whom served as her own control. The test yielded a 53.9% false-positive rate in the luteal phase. The study, therefore, clearly shows that from a practical, clinical point of view, the test is completely unreliable in the luteal phase, and is only valid when carried out in the follicular phase of the cycle.

17-alpha-Hydroxyprogesterone↗
PubMed1992

Potentiation by epidermal growth factor of the in vitro HCG stimulation of testicular steroidogenesis in hamsters.

Epidermal Growth Factor (EGF) has been reported to stimulate or inhibit steroidogenesis in murid Leydig cells depending on the experimental conditions used. In the present study, testicular fragments from an adult cricetid rodent, the Syrian hamster, were incubated with various doses of mouse EGF (0-2.0 micrograms/ml media), in the presence or absence of HCG (0-12.5 mlU/ml media). Although EGF alone did not affect in vitro testicular steroidogenesis, it significantly potentiated the HCG-induced elevation of the accumulation of testosterone and 17-hydroxyprogesterone in the media. In contrast, the effect of HCG on media progesterone concentration was not affected by EGF. Since in the Syrian hamster intracellular calcium loading functions as a gonadotropic stimulus, the present results could be a consequence of the EGF-induced increase in cellular calcium levels.

17-alpha-Hydroxyprogesterone↗
PubMed1992

[Relationship between functional activity of the adrenal glands and gonads in monkeys during puberty].

Testicular and adrenal cortex endocrine functions were simultaneously tested in pubertal baboons (papio hamadryas) during one year. Concentrations of androgens (testosterone, 5 alpha-dihydrotestosterone, dehydroepiandrosterone), corticosteroids (cortisol, progesterone, 17-hydroxyprogesterone, 17-hydroxypregnenolone) and aldosterone were determined in blood of the experimental monkeys by radioimmunoassay. It was shown that with increasing androgen (testosterone and dihydrotestosterone) levels in blood of the pubertal monkeys there was a significant decrease of corticosteroid concentration which was most pronounced in the monkeys with maximum increase of testosterone level. Described hormonal changes did not influence aldosterone concentration.

17-alpha-Hydroxyprogesterone↗
PubMed1992

Corpus luteum function in successful in vitro fertilization cycles.

The function of the corpus luteum in early pregnancy has been subject to some controversy. The purpose of our study was to determine the life span of the corpus luteum in early pregnancy after successful GnRH-a/hMG stimulation in IVF-ET. The study consisted of a retrospective analysis of patients after 12 successful singleton intrauterine IVF-ET cycles. Serum samples were obtained during early pregnancy beginning 14 days after hCG administration. The levels of 17 alpha-OHP, hCG, P, and E2 were measured in each sample. A significant negative correlation was noted between 17 alpha-OHP and date from hCG. The x-intercept of the regression line allowed estimation of the life span of the corpus luteum to be 72 +/- 25 days. In conclusion, in GnRH-a/hMG-stimulated IVF-ET cycles that result in a singleton pregnancy, the functional life span of the corpus luteum averages 72 days.

17-alpha-Hydroxyprogesterone↗
PubMed1992

[Recovery of ovarian function during postpartum period].

To determine the effect of serum prolactin (PRL) on the recovery of ovarian function in the postpartum period, FSH, PRL, estradiol (E2), and 17 alpha-OH-progesterone (17-P) levels were measured in postpartum women and the levels were compared with those in patients treated with bromocriptine. In addition, hMG was given for two days on the 10th and 30th postpartum days to the mothers treated with/without bromocriptine. On the 10th day, FSH levels tended to increase and the E2 and 17-P levels were significantly increased by bromocriptine treatment and these levels are compatible to those on the 30th day in the control group. Although no apparent change in E2 and 17-P levels was observed before and after hMG administration in the control, a significant increase in E2 on the 30th day and in 17-P on the 10th and 30th day was observed when the patients were treated with bromocriptine. These results suggest that high concentrations of PRL in the postpartum period suppressed the ovarian function not only due to the low gonadotropin secretion but also to the poor ovarian response to gonadotropin. 17-P seems to be preceded by estradiol secretion in the recovery of ovarian function during the postpartum period.

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