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PubMed1995

Home monitoring of 17 alpha-hydroxyprogesterone levels by filter paper blood spots in patients with 21-hydroxylase deficiency.

BACKGROUND: 21-Hydroxylase (21-OH) deficiency is characterized by an excess of androgen in both sexes and premature skeletal maturation resulting in short adult stature and male infertility. To achieve optimal height in children and fertility in adults, the replacement treatment of 21-OH deficiency with glucocorticoids should be regulated in order to adequately reduce the excess of androgens while minimizing the dose of glucocorticoids required. Neonatal screening for 21-OH deficiency is based on the measurement of the 17 alpha-hydroxyprogesterone (17-OHP) level from blood spotted on filter paper. The aim of this study was to examine whether repeated daily blood sampling on filter paper can assist in improving the monitoring of, and compliance to, 21-OH deficiency treatment. METHODS: During a 5-year period (1989-1994) we instructed 8 patients with 21-OH deficiency (2 males with salt losing, 2 males and 1 female simple virilizing, and 1 male and 2 females with nonclassical 21-OH deficiency) aged 1.3-36 years to sample blood on filter papers 1-4 times a day and send the papers to our neonatal screening laboratory by mail. On 62 occasions we measured both serum and filter paper 17-OHP levels in order to assess the degree of correlation between the two methods. RESULTS: Comparison between the filter paper and serum 17-OHP levels showed a correlation coefficient of r = 0.87. The filter paper levels were almost always higher than the serum levels. The serum 17-OHP levels were < 1 ng/ml whenever the filter paper levels were < 3 ng/ml. On long-term follow-up of 17-OHP filter paper levels we observed major diurnal and day-to-day fluctuations which might not have been noticed on routine follow-up clinic visits. CONCLUSIONS: Filter paper follow-up of 17-OHP levels can assist in optimizing the replacement treatment in patients with 21-OH deficiency while reinforcing compliance and decreasing the need for frequent clinic visits and hospitalizations. By adjusting the glucocorticoid type, dose, and time of administration to each patient we should be able to achieve optimal growth without bone age acceleration in children, to avoid overtreatment, and to improve fertility in adults.

17-alpha-Hydroxyprogesterone↗
PubMed1993

Origin of first trimester 17-hydroxyprogesterone levels as determined in pregnancies by donor oocyte fertilization.

The study presented herein measured 17-hydroxyprogesterone (17-OHP) levels in women with ovarian failure who conceived by transfer of embryos which resulted from donor oocytes fertilization. A significant increase in 17-OHP during the first trimester was seen compared to baseline nonpregnant levels. The 17-OHP levels increased from a baseline average of 47.7 +/- 9.7 ng/dl to a first-trimester average of 175.8 +/- 80.6 ng/dl in the donor oocytes recipients vs. 63.0 +/- 38.0 ng/dl baseline to 295.0 +/- 83.9 ng/dl first-trimester in the control group. Initially these data may appear to contradict previous findings demonstrating a lack of 17-OHP secretion by the first-trimester placenta. However, by comparing the first-trimester progesterone (P) levels of normal pregnant women, and also measuring 17-OHP in patients with natural menopause and surgical menopause given exogenous P we concluded the following about the origin of first-trimester sera 17-OHP levels: hydroxylation of P to 17-OHP by the ovaries, some secretion by the first trimester placenta; and also increased adrenal conversion of P to 17-OHP. Contributing to the total serum 17-OHP level is the fact that there is cross-reactivity with P to 17-OHP.

17-alpha-Hydroxyprogesterone↗
PubMed1987

Radioimmunoassay of blood-spot 17 alpha-hydroxyprogesterone in the management of congenital adrenal hyperplasia.

A robust assay for routine measurement of blood-spot 17 alpha-hydroxyprogesterone (17-OHP) concentrations has been developed using a magnetizable, solid-phase antiserum and an 125I-radioligand. The working range of this assay (13.5-500 nmol/L) is well suited for the initial diagnosis of congenital adrenal hyperplasia (CAH) and for monitoring replacement therapy in CAH patients. Data derived from multiple blood-spot samples, collected on two consecutive days, provide 17-OHP profiles. These profiles have been used to construct a chart allowing a rapid visual assessment of the efficacy of replacement therapy in CAH patients. Measurement of 17-OHP in the blood-spots of overtreated patients and accurate determination of normal range values in healthy infants relied on development of a sensitive assay (range 1.7-34 nmol/L). In the blood-spots of normal male (n = 50) and female (n = 50) infants collected 5-7 days after birth, 17-OHP concentrations were 7.62 +/- 2.55 nmol/L and 7.32 +/- 2.87 nmol/L respectively. Retrospective measurement of this steroid in samples from known CAH patients (n = 4), which had values ranging from 224 to 2145 nmol/L, support a role for measurement of blood-spot 17-OHP in high-risk screening programmes.

17-alpha-Hydroxyprogesterone↗
PubMed1988

Development of a direct fluoroimmunoassay for serum levels of 17-hydroxyprogesterone.

A direct, rapid and highly specific fluoroimmunoassay for determining serum levels of 17-hydroxyprogesterone has been developed. It is based on the use of a sheep antiserum covalently coupled to magnetisable particles and fluorescein-labelled steroid. Sodium salicylate is employed to eliminate interference from endogenous binding proteins in serum. The sensitivity of 0.5 nmol/L is adequate for clinical purposes. Analytical recovery, linearity and precision are satisfactory and the results obtained correlate closely with those of an established radioimmuno-assay using 3H-labelled steroid and the same antiserum after initial sample extraction and chromatography. The values found for serum from normal adult subjects ranged from 1.0 to 12.6 nmol/L while those from treated and untreated patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency were 1.5 to 19.0 and 28.0 to 655 nmol/L, respectively.

17-alpha-Hydroxyprogesterone↗
PubMed2004

Functional effects of 17alpha-hydroxyprogesterone caproate (17P) on human myometrial contractility in vitro.

BACKGROUND: 17 alpha-hydroxyprogesterone caproate (17P) administration reportedly improves outcome for women with a previous spontaneous preterm delivery. This study, using in vitro strips of human uterine smooth muscle, aimed to investigate the direct non-genomic effects of 17P on spontaneous and induced contractions in tissues obtained during pregnancy, and in the non-pregnant state. METHODS: Biopsies of human myometrium were obtained at elective cesarean section, and from hysterectomy specimens, and dissected strips suspended for isometric recordings. The effects of 17P (1 nmol/L -10 micro mol/L) on spontaneous and agonist-induced (oxytocin 0.5 nmol/L for pregnant, phenylephrine 10 micromol/L for non-pregnant) contractions were measured. Integrals of contractile activity, including the mean maximal inhibition values (MMI) observed at the maximal concentration, were compared with those from simultaneously run control strips. RESULTS: There was no significant direct effect exerted by 17P on pregnant or non-pregnant human myometrial contractility. The MMI +/- SEM for spontaneous contractions in pregnant myometrium was 4.9% +/- 7.2 (n = 6; P = 0.309) and for oxytocin-induced contractions was 2.2% +/- 1.3 (n = 6; P = 0.128). For non-pregnant myometrium, the MMI +/- SEM for spontaneous contractions was 8.8% +/- 11.0 (n = 6; P = 0.121) and for phenylephrine induced contractions was -7.9% +/- 6.5 (n = 6; P = 0.966). CONCLUSIONS: The putative benefits of 17P for preterm labor prevention are not achieved, even partially, by a direct utero-relaxant effect. These findings outline the possibility that genomic effects of 17P, achieved over long periods of administration, are required for its reported therapeutic benefits.

17 alpha-Hydroxyprogesterone Caproate↗
PubMed1978

Longitudinal studies of plasma aldosterone, corticosterone, deoxycorticosterone, progesterone, 17-hydroxyprogesterone, cortisol, and cortisone determined simultaneously in mother and child at birth and during the early neonatal period. I. Spontaneous delivery.

In order to obtain the still lacking reference data of individual plasma steroids in the immediate postnatal period needed for the assessment of adrenocortical function in various neonatal maladaptation syndromes, aldosterone (A), corticosterone, deoxycorticosterone (DOC), progesterone (P), 17-hydroxyprogesterone (17-OHP), cortisol, and cortisone were simultaneously followed in the same human newborn in a single 250-500 microliters peripheral plasma sample obtained at constant times during the first week of life using a mechanized Sephadex LH-20 multicolumn chromatography and standardized RIAs. Mean concentrations in 12 spontaneously delivered full term newborns of either sex and in paired umbilical (UV) and peripheral maternal (MV) venous plasma are given in the table. Besides significant maternoumbilical gradients in each steroid, DOC, P, 17-OHP, and cortisone, originating predominantly from the fetoplacental unit, disappear rapidly with steadily increasing half-lives. A, corticosterone, and cortisol, however, remain elevated in comparison with later infancy, with the exception of a marked "glucocorticoid dip" in cortisol and corticosterone levels between 2 and 12 h after birth.

17-alpha-Hydroxyprogesterone↗
PubMed1983

Salivary and plasma androstenedione and 17-hydroxyprogesterone levels in congenital adrenal hyperplasia.

Androstenedione (A-dione) and 17-hydroxyprogesterone (17-OHP) levels were measured in matched samples of saliva and of plasma collected from patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (eight patients) and 11-hydroxylase deficiency (one patient). Positive correlations were found between salivary and plasma values of either steroid with correlation coefficients of 0.968 for A-dione and 0.935 for 17-OHP. All five inadequately treated patients with 21-hydroxylase deficiency had greatly elevated plasma and salivary 17-OHP concentrations compared to values in age matched controls. In two of three well controlled patients plasma 17-OHP levels were less than 40 nmol/liter and salivary levels were less than 1.5 nmol/liter, the upper limits which have been formulated as a guideline for monitoring control in treated CAH patients. Patients in good control had A-dione levels in plasma (0.6-2.2 nmol/liter) and saliva (0.04-0.15 nmol/liter) which were both within the normal range for prepubertal children (0.14-2.40 nmol/liter and 0.02-0.25 nmol/liter respectively). Patients in poor control had A-dione levels in plasma of 5.2-25.4 nmol and in saliva of 0.50-2.21 nmol/liter. These values exceeded without exception the normal ranges for their respective ages. Salivary A-dione and 17-OHP determinations are a useful adjunct in the diagnosis and the monitoring of CAH patients since they can be obtained easily and nonstressfully.

17-alpha-Hydroxyprogesterone↗
PubMed1985

17-Hydroxyprogesterone responses to adrenocorticotropin in children with premature adrenarche.

The adrenal secretory response to an iv bolus dose of ACTH was measured in 10 girls (4-8 yr of age), 5 boys (4-9 yr) with premature adrenarche (PA), and 20 normal children. The evening before the ACTH test, each subject took dexamethasone (1 mg at bedtime) to suppress the early morning surge of ACTH. The next morning, 2 serum samples were obtained before the administration of ACTH (Cortrosyn; 0.25 mg), and 2 samples were collected 30 and 45 min after ACTH administration. All samples were assayed for cortisol, dehydroepiandrosterone (DHEA), DHEA sulfate, 17-hydroxyprogesterone (17-OHP), and androstenedione. There was no significant difference in the dexamethasone-suppressed steroid levels between the children with PA and the normal children. After ACTH injection, cortisol, DHEA, 17-OHP, and androstenedione increased significantly. There was no significant change in DHEA sulfate. The mean 17-OHP response to ACTH in girls with PA was significantly higher than that in girls and women whose pubertal development was normal. This response was similar in magnitude to that in a group (n = 5) of obligate heterozygotes for congenital adrenal hyperplasia (CAH). These data suggest that many girls with PA have a mild adrenal steroid secretory defect that resembles the response in adult obligate heterozygotes for CAH due to 21-hydroxylase deficiency. In contrast to the girls, none of the boys with PA had an exaggerated 17-OHP response to ACTH. Thus, these boys had no evidence for an adrenal steroid secretory defect. In summary, although the clinical presentation of boys with PA is similar to that of girls with PA, there is a significant difference in the adrenal steroid secretory response to ACTH. Thus, the biochemical events that cause PA in boys may be different from the corresponding events in girls.

17-alpha-Hydroxyprogesterone↗
PubMed1985

Spermatic and peripheral venous plasma concentrations of testosterone, 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone, delta 5-androstene-3 beta,17 beta-diol, dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol, 5 alpha-androstane-3 beta,17 beta-diol, and estradiol in boys with idiopathic varicocele in different stages of puberty.

Serum testosterone (T), 17-hydroxyprogesterone (17P), androstenedione (delta 4-dione), dehydroepiandrosterone (DHA), delta 5-androstene-3 beta, 17 beta-diol (delta 5-diol), estradiol (E2), dihydrotestosterone (DHT),5 alpha-androstane-3 alpha,17 beta-diol (3 alpha diol), and 5 alpha-androstane-3 beta,17 beta-diol (3 beta diol) were measured in the peripheral and spermatic venous blood of 21 boys undergoing surgery for idiopathic left varicocele. The boys were divided into 3 groups according to their pubertal development: prepubertal (group 1 or P1; n = 8), pubertal stage 2 (group II or P2; n = 6), and pubertal stages 3-4 (group III or P3-4; n = 7). The testes of the prepubertal boys secreted T, 17P, DHA, delta 5-diol, DHT, and 3 alpha diol, but not delta 4-dione, E2, and 3 beta diol. In pubertal stage P2, the mean spermatic-peripheral secretory gradients of T, 17P, DHA, delta 5-diol, DHT, and 3 alpha diol were significantly higher than those in the prepubertal stage, and there was testicular secretion of delta 4-dione, E2, and 3 beta diol. In pubertal stage P3-4, the mean spermatic-peripheral secretory gradients of most of these steroids, even if increased, were not significantly different from those in stage P2 (with the exception of 17P, delta 5-diol, and DHA). We suggest that after the important modifications of testicular secretion occurring in pubertal stage P2, the testicular secretory pattern of the pubertal testis is similar to the pattern of the adult testis. We suggest also that these results, obtained in boys with idiopathic varicocele, can probably be extended to the secretory activity of the testes of normal pubertal boys.

17-alpha-Hydroxyprogesterone↗
PubMed1987

Morning salivary 17-hydroxyprogesterone is a useful screening test for nonclassical 21-hydroxylase deficiency.

A screening test for nonclassical 21-hydroxylase deficiency (NC 21-OHD) has been established based on early morning salivary 17-hydroxyprogesterone (17-OHP) measurements. Saliva and serum samples were collected simultaneously between 0700 and 1100 h from 57 normal subjects (37 women and 20 men) and from 15 untreated patients (6 women and 9 men) with NC 21-OHD. The salivary (mean +/- SD, 524 +/- 508 pg/mL) and serum (10,548 +/- 5,998 pg/mL) 17-OHP concentrations in all 15 patients were unequivocally higher than the levels in normal subjects (saliva, 51 +/- 24 pg/mL; serum, 1,564 +/- 787 pg/mL). Salivary 17-OHP levels in patients with NC 21-OHD were significantly higher at 0700-0900 h (828 +/- 653 pg/mL) than at 0900-1100 h (314 +/- 227 pg/mL), while no such change was found in normal subjects. The salivary 17-OHP concentration was 1.3-6.9% of its serum concentration, and there was an excellent correlation (r = 0.93) between salivary and serum concentration in both normal subjects and patients with NC 21-OHD. In conclusion, early morning salivary 17-OHP measurement is an excellent screening test for the diagnosis of NC 21-OHD, since it accurately reflects serum 17-OHP levels, and sample collection is easy and noninvasive. We propose that salivary 17-OHP determination be used in population screening programs for NC 21-OHD to establish the true frequency of this disease.

17-alpha-Hydroxyprogesterone↗
PubMed1988

Prenatal diagnosis of 21-hydroxylase deficiency congenital adrenal hyperplasia by simultaneous radioimmunoassay of 21-deoxycortisol and 17-hydroxyprogesterone in amniotic fluid.

Amniotic fluid levels of 21-deoxycortisol (21-DOF) and 17-hydroxyprogesterone (17-OHP) were measured in 49 pregnancies, including 31 pregnancies at risk for CAH. The results were compared with those obtained by HLA typing and linkage analysis to a HLA DNA probe. The mean amniotic fluid levels in the control pregnancies were 0.28 nmol/L for 21-DOF and 4.1 nmol/L for 17-OHP. The levels were similar in early and midpregnancy for 21-DOF (0.29 vs. 0.27 nmol/L) and 17-OHP (3.4 vs. 4.2 nmol/L). The amniotic fluid 21-DOF level was 1.75 nmol/L in affected pregnancies, significantly higher than in the control pregnancies (mean, 0.28 nmol/L). The mean amniotic fluid 17-OHP level in the affected pregnancies (30.5 nmol/L) also was significantly higher than that in the control pregnancies (4.10 nmol/L). Simultaneous measurement of 21-DOF and 17-OHP levels in amniotic fluid from 10-18 weeks of gestation can be used for early diagnosis of congenital adrenal hyperplasia.

17-Hydroxycorticosteroids↗
PubMed1988

Comparison of basal and adrenocorticotropin-stimulated plasma 21-deoxycortisol and 17-hydroxyprogesterone values as biological markers of late-onset adrenal hyperplasia.

Plasma 21-deoxycortisol (21-DOF) and 17-hydroxyprogesterone (17-OHP) concentrations were assayed before (basal) and 1 h after ACTH stimulation in 4 groups of normal subjects (35 follicular phase women, 22 luteal phase women, 33 adult men, and 15 prepubertal children) and in a group of 31 patients with the late-onset form of congenital adrenal hyperplasia (LOCAH) due to 21-hydroxylase deficiency as well as in 31 LOCAH) heterozygotes. The mean basal plasma 21-DOF concentrations in each of the 4 groups of normal subjects were between 8 ng/dL (0.23 nmol/L) and 11 ng/dL (0.31 nmol/L), and they increased significantly after ACTH stimulation to between 36 ng/dL (1.04 nmol/L) and 44 ng/dL (1.27 nmol/L). There were no differences in basal or ACTH-stimulated plasma 21-DOF levels in these 4 groups, whereas their basal and post-ACTH plasma 17-OHP levels did vary. Among the LOCAH patients, 83.8% had basal plasma 21-DOF levels and 61.2% had basal plasma 17-OHP levels higher than the highest basal 21-DOF [30 ng/dL (0.86 nmol/L)] and 17-OHP [450 ng/dL (13.61 nmol/L)] concentrations in the normal subjects, and all individual 21-DOF and 17-OHP levels after ACTH stimulation [greater than or equal to 404 ng/dL (11.67 nmol/L) and greater than or equal to 1040 ng/dL (31.47 nmol/L), respectively] were markedly higher than the highest 21-DOF [76 ng/dL (2.19 nmol/L)] and 17-OHP [580 ng/dL (17.55 nmol/L)] levels in the normal subjects. The mean post-ACTH/basal plasma level ratios among the LOCAH patients were 19.75 for 21-DOF and 8.03 for 17-OHP. In LOCAH heterozygotes, basal 21-DOF values were higher than normal in 48.3%, and post-ACTH values were higher than normal in 93.5% of the cases. In contrast, basal plasma 17-OHP levels were similar in LOCAH heterozygotes and normal subjects, and only 16.1% of the LOCAH heterozygotes had post-ACTH plasma 17-OHP levels higher than the highest normal value. If sex and phase of the menstrual cycle are taken into account, along with the incremental responses (post-ACTH minus baseline value) of plasma 21-DOF and 17-OHP, to compare LOCAH heterozygotes and normal subjects, the discriminating power for detection of heterozygocity was somewhat increased for 21-DOF (to 100%) and appreciably increased for 17-OHP (to 30%).(ABSTRACT TRUNCATED AT 400 WORDS)

17-Hydroxycorticosteroids↗
PubMed1990

On the origin of the elevated 17-hydroxyprogesterone levels after adrenal stimulation in hyperandrogenism.

Hyperandrogenic women appear to demonstrate an exaggerated 17-hydroxyprogesterone (17-HP) response to adrenal stimulation which is not due to the marked 21-hydroxylase deficiency of late-onset adrenal hyperplasia (LOAH). Furthermore, in hyperandrogenism the ovary also appears to secrete excessive amounts of 17-HP. It is not clear to what extent the elevated 17-HP levels after ACTH stimulation are due to extraadrenal production of the steroid. This investigation was undertaken to assess the adrenal contribution to the elevated 17-HP levels after ACTH stimulation observed in non-LOAH hyperandrogenism. One hundred and sixty consecutive unselected women with hirsutism and/or hyperandrogenic oligomenorrhea formed the clinical population. Excluded were 4 women with LOAH and all patients with hyperprolactinemia. For the purpose of investigating the relationship between adrenal response and clinical symptoms, hyperandrogenic patients were divided into 3 subgroups: hirsute only (n = 23), hirsute oligomenorrheic (n = 84), and oligomenorrheic only (n = 24). Subclassification for an additional 29 patients (18%) with hyperandrogenemia was not possible, since their symptomatology was not clearly stated in the record. However, these individuals were included in the patient group as a whole. Controls consisted of 21 healthy, regularly menstruating, nonhirsute female volunteers. Both patients and controls underwent acute adrenal stimulation with 1 mg ACTH-(1-24), and serum was obtained before and 30 min after ACTH administration. Hyperandrogenic patients had higher mean basal total testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHS), 17-HP, and LH/FSH levels, but not cortisol (F), compared to normal subjects (P less than 0.02). Oligomenorrheic only women had higher mean A and progesterone (P) levels than other hyperandrogenic patients (P less than 0.02). No correlation was noted between body mass index (BMI) and the levels of DHS, P, or A, while a weak positive association was noted between the BMI and the mean T (r = 0.31; P less than 0.002) and a weak negative correlation between the mean F and BMI (r = -0.21; P less than 0.05). The mean 17-HP level 30 min after ACTH administration (17-HP30) was significantly higher in hyperandrogenic women than in normal subjects whether analyzed in separate subgroups or together and was due to the higher basal 17-HP levels. Basal 17-HP correlated with the circulating levels of T, A, and P, steroids largely of ovarian origin. Alternatively, the net increment in 17-HP from 0-30 min after ACTH (delta 17-HP30) was not significantly higher in hyperandrogenic women than normal subjects and did not correlate with the basal levels of T, A, and P. Neither the basal level of 17-HP nor its response to ACTH correlated with circulating DHS levels.(ABSTRACT TRUNCATED AT 400 WORDS)

17-alpha-Hydroxyprogesterone↗
PubMed1990

Prevalence of nonclassical steroid 21-hydroxylase deficiency based on a morning salivary 17-hydroxyprogesterone screening test: a small sample study.

Early morning salivary 17 alpha-hydroxyprogesterone (17-OHP) determination differentiates patients with non-classical 21-hydroxylase deficiency (NC21OHD) from those who are not affected. Using this test, we have conducted a trial screening study for NC21OHD and have compared the study results with previously reported figures for the frequency of this disorder. Testing was performed on 258 subjects recruited from among the medical students and employees of the New York Hospital-Cornell Medical Center. In 2 of the 249 admissible subjects, the 0700-0900 h salivary 17-OHP level was within the range for NC21OHD patients (0.72-6.7 nmol/L; n = 8). These 2 individuals were subsequently confirmed to be affected by ACTH testing. Of the subjects with morning salivary 17-OHP levels below the cut-off point of 0.72 nmol/L, 29 were recalled for ACTH testing and were confirmed to be unaffected. Prevalence of NC21OHD in the test population was determined according to ethnic group. Our study gives a prevalence by screening of 1.14% among caucasians, which agrees with values of 0.81% and 1.06% obtained by different analytical methods. Further, both affected subjects were Ashkenazi Jews, and the prevalence of 3.23% among study members from this group concurs with increased rates of 3.64% and 4.97% already reported. On the basis of a small population sample, screening so far confirms the claim that NC21OHD is the most common autosomal recessive human disorder. Using values from ACTH-proven unaffected subjects (n = 47) and NC21OHD patients (n = 10), we establish preliminary normative data for morning salivary 17-OHP levels of 0.172 nmol/L for unaffected subjects (95% confidence interval, 0.05-0.54 nmol/L) and 1.76 nmol/L for NC21OHD-affected subjects (95% confidence interval, 0.42-7.32 nmol/L).

17-alpha-Hydroxyprogesterone↗
PubMed1991

Abnormalities of 21-hydroxylase gene ratio and adrenal steroidogenesis in hyperandrogenic women with an exaggerated 17-hydroxyprogesterone response to acute adrenal stimulation.

One to 2% of hyperandrogenic women demonstrate a 17-hydroxyprogesterone (17-HP) level greater than 36.3 nmol/L (1200 ng/dL) after acute ACTH-(1-24) adrenal stimulation, consistent with 21-hydroxylase (21-OH) deficient late-onset adrenal hyperplasia (LOAH). The following study was undertaken to endocrinologically and genetically define hyperandrogenic patients with an exaggerated 17-HP response to ACTH stimulation, and which do not represent LOAH. Of 265 consecutive patients suffering from hirsutism and/or hyperandrogenic oligomenorrhea, 23 (8.7%) demonstrated a 17-HP level 30 min post stimulation greater than 9.6 nmol/L or 316 ng/dL (the upper 95th percentile in 41 eumenorrheic nonhirsute healthy control women). Seven patients or five separate families (1.8% of total) demonstrated poststimulation 17-HP levels consistent with LOAH. Of the remaining 16 patients, the net increment in 17-HP (delta 17-HP0-30) was within normal limits in seven (2.6%) and these women were assumed to have a normal 17-HP adrenocortical response superimposed on an elevated basal level of nonadrenal (e.g. ovarian) origin. In the remaining nine hyperandrogenic patients (3.4%) various abnormalities of adrenal response were noted in all but one patient, consistent with adrenal hyper-responsiveness. One patient demonstrated an 11-deoxycortisol poststimulation level greater than 3-fold the upper 95th percentile of normal, consistent with 11-hydroxylase LOAH and was excluded from further study. Six of these women were available for further genetic characterization, all Caucasian and unrelated. Three were heterozygotes for HLA-B14, three for B40, and one for B35 antigen, HLA-types associated with the inheritance of 21-OH deficiencies. Although, normally there are two 21-OH genes (a pseudogene and a functional gene) present in a 1:1 ratio, we have previously reported a high frequency of 21-OH gene ratio abnormalities in LOAH. All but one of our patients demonstrated an abnormal 21-OH gene ratio. In conclusion, 3.4% of our hyperandrogenic population demonstrated an exaggerated 17-HP increment after ACTH stimulation, not consistent with LOAH or increased extraadrenal 17-HP production. The increased prevalence of HLA alleles known to be linked to inherited defects of 21-OH function and the increased frequency in 21-OH gene ratio abnormalities suggest that a majority of these individuals may be carriers for these genetic disorders. However, the adrenocortical abnormalities noted were more consistent with a generalized hyperreactivity of the adrenal to ACTH stimulation, than a specific enzyme deficiency, implying that carrier status for 21-OH deficiency may be incidental to the hyperandrogenism.

17-alpha-Hydroxyprogesterone↗
PubMed1994

Studies of the nature of 17-hydroxyprogesterone hyperresonsiveness to gonadotropin-releasing hormone agonist challenge in functional ovarian hyperandrogenism.

Plasma 17-hydroxyprogesterone (17PROG) hyperresponsiveness to GnRH agonist (nafarelin) testing is typical of polycystic ovary syndrome and other functional ovarian hyperandrogenism (FOH) that does not meet customary criteria for the diagnosis of polycystic ovary syndrome. We have postulated that this results from abnormal regulation of androgen secretion. Whether this dysregulation is the result of a normal physiological response to ovarian hyperstimulation or escape from down-regulation of steroidogenesis is unknown. To distinguish between these possibilities, we have analyzed the ovarian steroid responses to nafarelin for the apparent efficiency of the steroidogenic steps and the apparent dose-response relationships between blood LH and steroid levels. We compared normal women (n = 18) with three groups of hyperandrogenic women (n = 15-19/group): patients with 17PROG hyperresponsiveness with or without elevated LH levels (type 1 and type 2 FOH, respectively) and patients with normal 17PROG responses to nafarelin (nafarelin negative). Subjects were pretreated with dexamethasone to suppress coincidental adrenal contributions to plasma steroid levels. The pattern of steroid secretion was similarly abnormal in both types of FOH, with the high LH group having generally more severe abnormalities in the levels of steroid intermediates. Baseline 17PROG and 17-hydroxypregnenolone and the ratio of 17PROG to androstenedione (AD) were increased (P < 0.05). In addition, the apparent slope of the 17PROG response to LH was significantly increased. Baseline levels of both AD and dehydroepiandrosterone and the AD response to nafarelin were increased, yet the ratio of peak minus baseline (delta) AD/delta 17PROG (another index of 17,20-lyase activity) was subnormal in FOH. The apparent slope of the testosterone (T) response to LH was significantly increased, and indexes of aromatase activity [estradiol (E2)/T and delta estradiol/delta T] were significantly decreased. Nafarelin stimulated plasma E2 in all groups to rise along an apparently similar LH-E2 dose-response slope. We interpret these results as indicating that FOH patients have generalized overactivity of thecal steroidogenesis, but nevertheless compensate so as to maintain a normal dose-response relationship between blood levels of LH and E2. FOH patients, whether they have LH excess or not, seen to form excessive 17PROG and incompletely dampen (down-regulate) thecal cell 17PROG, AD, and T secretion in response to LH stimulation. 17PROG hyperresponsiveness to nafarelin seems to be prominent both because it is formed in excess and because 17,20-lyase efficiency is rate limiting. The T elevation seems to arise mainly from overactive steroidogenesis, but also partly from an additional functional decrease in aromatase efficiency, which is secondary to negative feedback by the substrate-driven tendency toward estrogen excess.(ABSTRACT TRUNCATED AT 400 WORDS)

17-alpha-Hydroxypregnenolone↗
PubMed1983

[Neonatal mass-screening for congenital adrenal hyperplasia due to 21-hydroxylase deficiency. I. Microfilter paper methods for radioimmunoassay of 17 alpha-hydroxyprogesterone].

In order to perform neonatal mass-screening for 21-hydroxylase deficiency (21-OHD), two simplified radioimmunoassay (RIA) methods to estimate 17 alpha-hydroxyprogesterone (17-OHP) were devised, using discs 3 mm in diameter cut from filter paper impregnated with whole blood. One was a direct method to use assay buffer eluent as a sample, and the other was an extraction method to use diethyl ether extract. One disc in the direct method and one-fourth to four discs in the extraction method were used. We used [1, 2, 6, 7-3H(N)]-17-OHP as a tracer, anti-17-OHP-3-carboxymethyloxime-BSA serum as an antiserum and saturated ammonium sulfate to separate the bound from free 17-OHP. The specificity of the antiserum was nearly satisfactory, except for an unnegligible cross-reactivity with 17 alpha-hydroxypregnenolone (17-OH-delta 5P). Both methods were practically easy and rapid, and had satisfactory accuracy and precision. A significant correlation (p less than 0.005) was observed between "Disc-17-OHP" values by both methods and plasma 17-OHP concentrations measured by highly specific RIA, although the values obtained by the direct method were significantly higher (p less than 0.005) than plasma 17-OHP concentrations, which presumably resulted from the cross-reactivity of the antiserum with 17-OH-delta 5P-sulfate. "Disc-17-OHP" values of the untreated or poorly controlled patients with 21-OHD were extremely high compared with normal neonates and children. However, as most premature infants also showed high values, the possibility of giving false-positive results had to be considered.(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone↗
PubMed1983

[The age-related changes in serum 17-hydroxyprogesterone secretion in men].

In order to clarify the age-related changes in serum 17-hydroxyprogesterone (17-OHP) secretion in men, serum basal 17-OHP levels were determined in 203 healthy male subjects from 10 months to 116 years of age, and serum 17-OHP responses to dexamethasone (Dex), fluoxymesterone (FM), HCG and ACTH were compared between the young and elderly groups. The mean basal 17-OHP level remarkably increased from pubescence to the third decade and gradually decreased with advance in age after fifty. Basal serum 17-OHP level was correlated more closely with serum testosterone (T) than cortisol (F), and was suppressed more remarkably after the administration of FM than Dex in both groups. Serum 17-OHP increased with 2 peaks at 6 and 24 hours after HCG injection, and serum 17-OHP response to HCG was significantly greater in the young than in the elderly group. Furthermore, in the aged subjects with low serum T levels, serum 17-OHP response to HCG was remarkably decreased. Within 3 hours after ACTH injection, serum 17-OHP response to ACTH was significantly lower in the elderly than in the young group. On the other hand, 12 hours after ACTH administration, serum 17-OHP response was remarkably greater in the elderly group, and the F/17-OHP ratio was significantly lower than in the young. These data indicate a decline of Leydig cell function in the testis of the elderly male and also suggest the occurrence of enzyme deficiencies, especially impaired C17, 20 lyase activity, in adrenal steroid hormone synthesis with aging.

17-alpha-Hydroxyprogesterone↗