Serum 17-OHP Research Articles

Adrenal Contribution to Polycystic Ovary Syndrome

Objective: To examine further the dynamics of adrenal steroidogenesis in selected groups of patients with polycystic ovary syndrome (PCOS) compared to normal ovulatory women of the same age. Materials and Methods: Serum cortisol, testosterone, dehydroepiandrosterone sulphate (DHEAS), androstenedione (A), luteinizing hormone (LH), follicle-stimulating hormone, prolactin, 17-hydroxyprogesterone (17-OHP) and sex hormone-binding globulin (SHBG) were measured in the early follicular phase of the period. In addition, 2-day dexamethasone suppression and short adrenotropic hormone (ACTH) stimulation tests were performed for the study group and controls. Results: Serum testosterone (4.3 ± 1.8 nmol/l), LH (7.6 ± 1.9 IU/l), and 17-OHP (4.7 ± 2.3 nmol/l) were higher while SHBG (24.7 ± 14.2 nmol/l) was lower in patients than the control. Testosterone was significantly suppressed after dexamethasone suppression test while the level of 17-OHP increased significantly in patients more than the control after 60 min of ACTH stimulation. In the PCOS, the ratio of 17-OHP/A showed a significant increase after ACTH stimulation while that of DHEAS/A decreased when compared to controls. Conclusion: The study suggests a contribution of adrenal cytochrome P-450C dysregulation in PCOS. This suggestion could lead to another method of treating some PCOS patients when the usual anti-androgens might not be fully effective in controlling most of the symptoms.

Effect of treatment on growth in congenital adrenal hyperplasia.

In 22 patients with congenital adrenal hyperplasia (CAH), the effect of treatment on growth was evaluated retrospectively. The degree of control with treatment had generally been assessed by measurements of serum 17-hydroxyprogesterone (17-OHP) and/or urinary pregnanetriol levels. In 20 patients, there were no significant differences in both height SDS for bone age (-2.05 +/- 1.89 vs -1.85 +/- 1.30) and height SDS for chronological age (CA) (0.23 +/- 1.94 vs -0.36 +/- 1.81) in a mean uninterrupted treatment period of 5.80 +/- 3.58 years. Further analysis in salt-losers and nonsalt-losers separately showed that height SDS for bone age had decreased in the salt-losers and had increased in the nonsalt-losers. Six patients had signs of early puberty. In 22 patients, there was a negative correlation between the prednisolone dose on one hand and height velocity SDS for CA and bone age velocity on the other. It was also found that the mean serum levels of 17-OHP did not always reflect the degree of long term control measured by auxological parameters. These findings indicate that our treatment in the patients did not result in a significant improvement in height prognosis. We can conclude that growth prognosis in CAH patients can be improved by relying on auxological parameters rather than serum 17-OHP and urinary pregnanetriol levels for monitoring control. Special attention should be paid to salt-losers in this respect.

The effect of chronic treatment with GH on gonadal function in men with isolated GH deficiency.

Eleven adult males, previously submitted to neurosurgery because of a pituitary lesion (three with craniopharyngioma, three with clinically non-functioning adenoma and five with macroprolactinoma) were treated with recombinant GH for 12 months after the diagnosis of GH deficiency was made. Circulating FSH, LH, prolactin, testosterone, 17 beta-estradiol (E2), dehyroepiandrosterone (DHEA-S), androstenedione. 17-OH-progesterone (17OHP), IFG-I, and steroid hormone-binding protein (SHBG) levels were assayed before and after CG test at study entry and 6 and 12 months after GH treatment. A significant increase in plasma IGF-I levels was obtained after 6 and 12 months of GH treatment. In addition, CG-stimulated, but not baseline, testosterone levels showed a significant increase after 6 and 12 months of GH treatment when compared with study entry (9.6 +/- 0.5 and 9.9 +/- 0.5 vs 7.9 +/- 0.5 ng/ml; P < 0.05). Baseline, but not CG-stimulated, serum 17OHP levels were significantly increased only after 12 months of GH treatment (1.7 +/- 0.1 vs 1.4 +/- 0.1 ng/ml; P < 0.05). No significant difference was found as far as both basal and CG-stimulated E2, androstenedione, DHEA-S and SHBG were concerned. With regards to the semen analysis, only seminal plasma volume was significantly increased after 12 months of GH treatment (2.9 +/- 0.3 vs 1.7 +/- 0.3 ml; P < 0.05). No significant change in sperm count, motility and abnormal forms was observed. These data show that GH treatment displays a clear-cut effect upon Leydig cell function and increases the production of seminal plasma volume in fertile adult males with isolated GH deficiency.

Do hyperandrogenic women with normal menses have polycystic ovary syndrome?

Objective: To determine the prevalence of polycystic ovary syndrome (PCOS) among hyperandrogenic women who report normal menses. Design: Prospective observational study. Setting: Academic practice in reproductive endocrinology. Patient(s): Fifty-eight consecutively seen new patients with hyperandrogenism who reported normal menses. Intervention(s): Ovulatory status was assessed with timed serum progesterone measurements. The following tests also were carried out: vaginal ultrasound examination; measurement of the ovarian response of 17-hydroxyprogesterone (17-OHP) after the administration of leuprolide acetate, 1 mg SC; and determination of fasting serum LH, FSH, E 2, 17-OHP, insulin, and androgen levels. Main Outcome Measure(s): Determination of ovulatory status, polycystic appearance of ovaries, and increased response of 17-OHP to leuprolide acetate. Result(s): Twelve (20.7%) of the hyperandrogenic women were anovulatory and met the usual criteria for the diagnosis of PCOS. The ovulatory patients had lower serum total and unbound testosterone levels. Thirty-one (53.4%) of the ovulatory women had polycystic ovaries on ultrasound examination and/or an increased 17-OHP response to leuprolide acetate, suggesting the diagnosis of PCOS despite the presence of ovulation. Considering both the anovulatory and ovulatory patients, 74% of the hyperandrogenic women studied could have PCOS. Conclusion(s): The data suggest that most (74%) hyperandrogenic women who report normal menses have evidence for the diagnosis of PCOS.

Adrenal androgenic response to 2-hour ACTH stimulation test in women with PCOS

Adrenal function may be abnormal in women with polycystic ovary syndrome (PCOS). This study aims to evaluate adrenal steroid response to the adrenocorticotropic hormone (ACTH) stimulation test and to find out the effect of high serum testosterone levels on adrenal response. We have also investigated any subtle enzyme deficiency by extending blood sampling to 2 h with 30 min intervals following ACTH administration. Twenty-eight women with PCOS and 18 healthy controls without hirsutism and oligomenorrhea were included in the study. After determining their serum basal levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone (17-OHP), and progesterone, ACTH stimulation test was performed. The change in serum 17-OHP and the summed rate of change in serum 17-OHP and progesterone levels were estimated and 95th percentile for each value was computed. Women with PCOS were heavier and more hirsute than controls (p < 0.01 p < 0.001 respectively). Serum basal LH, LH : FSH ratio, testosterone (p < 0.001 for all), DHEAS (p < 0.01) and 17-OHP (p < 0.05) were higher in women with PCOS. All of the 17-OHP measurements, including basal and each 30 min interval after the administration of ACTH, were higher in women with PCOS than those of healthy controls (p < 0.05 p< 0.002 p< 0.001 p< 0.015 p< 0.018 respectively). However, the incremental changes in serum 17-OHP30-0 17-OHP60-0 17-OHP90-0 17-OHP120-0 and the summed rate of change in serum 17-OHP and progesterone in women with PCOS were not different from those in healthy controls. The incremental response in terms of serum progesterone, DHEAS, and testosterone levels to the ACTH stimulation test for each 30 min interval was not different in women with PCOS than in healthy controls. We were not able to show any critical value for serum basal testosterone and DHEAS levels that would effect response to ACTH stimulation in terms of 17-OHP levels. We have concluded that extending the duration of blood sampling up to 2 h has no advantage in evaluating adrenal steroid response to ACTH stimulation. Since serum 17-OHP levels remain within normal limits in response to ACTH stimulation, the origin of elevated serum basal 17-OHP levels may be polycystic ovaries. Elevated serum testosterone level does not have any adverse effect on adrenal function. Serum progesterone measurement seems to have no place in the diagnosis of 21-hydroxylase deficiency. Adrenal androgenic response to ACTH stimulation is normal in women with PCOS.

Chemiluminescent flow injection determination of alkaline phosphatase and its applications to enzyme immunoassays

A Chemiluminescent flow injection method based on the reaction of cortisol-21-phosphate with alkaline phosphatase (ALP) is described. The cortisol produced by the enzyme-catalyzed reaction reacts with lucigenin ( N, N′-dimethyl-9,9′-biacridinium dinitrate) in basic aqueous solution to give intense chemiluminescence. The method allows ALP to be determined in the range 4 × 10 −12–5 × 10 −11 mol 1 −1. The detection limit for ALP is 1 × 10 −12 mol 1 −1. Experimental conditions, such as flow rates, pH, incubation time and reactant concentrations have been studied. The applications of the method to enzyme immunoassay were demonstrated by the determination of 17 α-hydroxyprogesterone (17-OHP) and human chorionic gonadotropin (hCG) in urine or serum samples using ALP as the enzyme label. Good correlations were obtained between the results of serum hCG or 17-OHP assay by the proposed method and other methods.

Serum and urinary markers of exogenous testosterone administration

In an attempt to find optimal markers of exogenous testosterone (T) administration in male athletes, a number of compounds were measured in 11 healthy men before and after 3, 6 and 9 months of weekly administration of 250 mg i.m. T enanthate and in age-matched untreated controls. The following variables were measured in serum: T, 17α-hydroxyprogesterone (17-OHP), sex hormone-binding globulin (SHBG), estradiol-17β, estrone (free + conjugated) and luteinizing hormone (LH). The following variables were measured in urine: T glucuronide (urinary T), epitestosterone glucuronide (urinary epiT), estrone (free + conjugated) and LH. Serum T, serum T 17-OHP ratio, serum T LH ratio, serum T SHBG ratio, serum and urinary estrogens, urinary T creatinine- , T epiT- and T LH ratios increased whereas serum 17-OHP, SHBG and LH and urinary epiT creatinine- and LH creatinine-ratios decreased significantly during treatment. Levels above the upper reference limit were found in all subjects at 3, 6 and 9 months for serum T 17- OHP and serum and urinary T LH ratios and at 6 months for the urinary T epiT ratio. Levels below the lower reference limit were found in all subjects at 3, 6 and 9 months for serum LH and the urinary LH creatinine ratio, at 3 months for the urinary epiT creatinine ratio and at 9 months for serum 17-OHP. No other variable showed abnormal values in all subjects at the same occasion. Despite significant changes during treatment, steroid concentrations as such are poor indicators of T doping. Serum and urinary LH levels, T LH ratios and serum T 17- OHP ratios seem to be the most reliable markers of exogenous T administration in mal

Endocrinology: Ultrasonographic appearance of polycystic ovaries is associated with exaggerated ovarian androgen and oestradiol responses to gonadotrophin-releasing hormone agonist in women undergoing assisted reproduction treatment

While no single biochemical test is diagnostic of polycystic ovary syndrome (PCOS), most patients show a characteristic ovarian ultrasonographic appearance. It has been proposed that a dysfunction of cytochrome P-450c17 alpha in PCOS leads to an increased 17-hydroxyprogesterone (17-OHP) response to a gonadotrophin-releasing hormone (GnRH) agonist-induced gonadotrophin rise. We postulated that this abnormality of steroid metabolism might influence the ovarian response during assisted reproduction treatment. We investigated 106 patients undergoing a short 'boost' stimulation regimen for assisted reproduction treatment, including in-vitro fertilization and gamete intra-Fallopian transfers. The ovarian ultrasound pattern was correlated with serum testosterone, 17-OHP, androstenedione and oestradiol responses, and with the clinical outcome. Polycystic ovaries, defined ultrasonographically as the presence of > or = 10 follicles between 2 and 10 mm diameter in either ovary, were found in 48% of the whole study population. Dexamethasone was given to suppress adrenal androgen secretion. Functional ovarian hyperandrogenism (FOH) was defined as serum testosterone > 0.5 nmol/l after dexamethasone. There was a significantly (P < 0.001) higher prevalence of FOH in patients with polycystic ovaries (23%) compared with normal ovaries (7%). Patients with polycystic ovaries had approximately double the 17-OHP, androstenedione and oestradiol responses to a GnRH agonist as patients with non-polycystic ovaries. Exaggerated 17-OHP and oestradiol responses to GnRH agonist were found in 89% of patients with clinically diagnosed PCOS. The number of oocytes retrieved was positively correlated (r = 0.51, P < 0.001) with the oestradiol responses in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary 17 alpha-hydroxyprogesterone in management of 21-hydroxylase deficiency.

The study was designed to assess the reliability of measurement of 24-hour urinary 17 alpha-hydroxyprogesterone (17-OHP) by radio-immunoassay (RIA) as an alternative biochemical assessment for monitoring the treatment of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) and to assess the need for sample purification by column chromatography to improve assay specificity. Morning serum 17-OHP was measured using RIA and 24-hour urinary pregnanetriol using gas chromatography. Twenty-four-hour urinary 17-OHP was measured in samples from 17 prepubertal patients with CAH due to 21-OHD, and 20 normal prepubertal children as controls. In 24 urine samples, RIA of 17-OHP was performed with and without column chromatography. There was a good correlation between 24-hour urinary 17-OHP and 24-hour urinary pregnanetriol (r = 0.962, P < 0.01) and between 24-hour urinary 17-OHP and morning serum 17-OHP (r = 0.955, P < 0.01). There was no significant difference in the RIA of the urine samples with and without purification by column chromatography. The measurement of 24-hour urinary 17-OHP is a reliable alternative for the biochemical monitoring of 21-OHD, and RIA specificity is unaffected by omission of column chromatography.

Augmented 17α‐hydroxyprogesterone response to ACTH stimulation as evidence of decreased 21‐hydroxylase activity in patients with incidentally discovered adrenal tumours ('incidentalomas')

Recent studies have indicated that the syndrome of congenital adrenal hyperplasia due to 21-hydroxylase deficiency is closely associated with the development of benign adrenocortical tumours. Tumour formation is thought to be a consequence of ACTH hypersecretion which results from the lack of glucocorticoid synthesis. The aim of this study was to evaluate 21-hydroxylase activity in patients with an incidentally discovered adrenal mass ('incidentaloma') without a history of congenital adrenal hyperplasia. A prospective study of 52 patients admitted to a single hospital. Fifty-two consecutive subjects (mean age 56.0 years, range 24-81 years) with an incidentally discovered adrenal tumour were studied. The 21-hydroxylase reserve was assessed by intravenous bolus administration of 1-24 ACTH (tetracosactrin) with measurement of basal and stimulated serum 17 alpha-hydroxyprogesterone (17-OHP) concentrations. Impaired 21-hydroxylase activity was defined as an exaggerated 17-OHP response, with a 17-OHP increment exceeding 7.9 nmol/l. Basal and stimulated cortisol concentrations, and basal ACTH were also measured. Baseline levels of 17-OHP were normal in 44 and elevated in 8 subjects. In 37 patients (71.2%), the 17-OHP increment following ACTH administration exceeded 7.9 nmol/l, demonstrating mildly decreased 21-hydroxylase activity. In these subjects, the peak serum 17-OHP correlated with the tumour diameter. In the patients with apparently normal 21-hydroxylase activity, no significant correlation was found between 17-OHP concentrations and tumour size. All patients had a stimulated serum cortisol above 550 nmol/l reflecting intact adrenal glucocorticoid reserve. There were no other differences between the group with exaggerated and the group with normal 17-OHP increment. The tumours were removed from two women with augmented 17-OHP responses and this was followed by normalization of 17-OHP dynamics. Biochemical evidence for partial 21-hydroxylase defiency is a common finding in patients with an adrenal incidentaloma, even in the absence of a congenital adrenal hyperplasia history. Exaggerated 17-OHP increment is not accompanied by decreased adrenal glucocorticoid reserve. Normalization of the 17-OHP response after surgical treatment suggests that the phenomenon results from reduced 21-hydroxylase activity in the tumour, which retains ACTH responsiveness.

Isolated precocious pubarche: an approach.

Precocious pubarche (PP) is most often a benign condition secondary to the early appearance of adrenarche. However, PP may be a manifestation of nonclassical adrenal hyperplasia. The incidence of nonclassical adrenal hyperplasia in patients with PP ranges from about 0-40% of cases. Controversy exists as to whether all children with PP should undergo an ACTH stimulation test. The aim of this study was 1) to determine the frequency of mild adrenal enzyme defects in a very large and ethnically homogeneous group of children with isolated PP (typical pubarche); 2) to determine whether clinical data, in particular bone age, and basal hormonal values can help to distinguish patients who are at risk for having adrenal enzymatic defects and thus should have an ACTH test; and 3) to determine which patients diagnosed as having a mild adrenal enzyme defect might require treatment. We studied 171 subjects (135 girls and 36 boys), aged 7 +/- 1.2 (SD) yr, with isolated PP. Thirty-eight normal subjects (18 age-matched and 20 pubertal) were studied as controls. An ACTH stimulation test (Synacthen, 0.25-mg iv bolus) was performed. Blood samples were drawn at baseline and 1 h postinjection. 17 alpha-Hydroxyprogesterone (17OHP), 17 alpha-hydroxypregnenolone (17PGN), dehydroepiandrosterone, androstenedione, testosterone, 11-deoxycortisol, and cortisol were evaluated. Haplotype (HLA) typing was performed in the patients who were diagnosed with nonclassical 21-hydroxylase deficiency (NC21OHD). Using published nomogram standards for the serum 17OHP response to ACTH, 10 patients (5.8%) were diagnosed as having NC21OHD. Seven of 112 patients (6.2%) were diagnosed as having nonclassical 3 beta-hydroxysteroid dehydrogenase deficiency (NC3HSD) on the basis of the following three criteria: stimulated 17PGN levels and stimulated 17PGN/17OHP and 17PGN/cortisol ratios higher than 2 SD above the mean for pubertal controls. None of the patients had stimulated 11-deoxycortisol values greater than 2 SD above the mean of pubertal controls. Nineteen patients (11%) had a stimulated 17OHP response characteristic of the heterozygotes for 21-hydroxylase deficiency. One hundred and thirty-five of 171 patients with no biochemical evidence of an adrenal biosynthetic defect were diagnosed as having precocious adrenarche. Bone age was advanced (> 2 SD for chronological age) in 80% of the patients with NC21OHD, in 71.4% of the patients with NC3HSD, in 58% of the patients classified as heterozygotes, and in 32.6% of the patients with precocious adrenarche. Basal hormone levels were helpful in detecting NC21OHD, but not NC3HSD. All patients with NC21OHD and only 1 with NC3HSD underwent glucocorticoid suppression treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

MINERALOCORTICOIDS (MC) IN THE TREATMENT OF CONGENITAL ADRENAL HYPERPLASIA DUE TO 21-HYDROXYLASE DEFICIENCY (21-OHD)

Plasma renin activity (PRA), ACTH, serum 17-OHP, aldosterone (A) and testosterone (T) levels were monitored in 48 children with 21-OHD. There were 37 girls and 11 boys aged from 1.5 months to 14.5 years, 34 salt-losers (SL) and 14 simple-virilizers (SV). Initially, 25/34 SL received glucocorticoids (GC) combined with MC, 9/34 SL and 9/14 SV - only GC, and 5/14 SV - no treatment. To evaluate effect of MC on hormonal control 20/34 SL and 8/14 SV were followed in whom during the study therapy with MC was initiated or intensified, while doses of GC were reduced or not changed. 3-4 weeks after modification of the therapy in these two subgroups both in SL and SV PRA fell from 20.4±3.31 to 2.1±0.49 (p<0.001), and from 6.5±3.93 to 3.5±1.33 ng/ml/hr (p>0.05), while A decreased from 0.5±0.14 to 0.2±0.11 (p<0.05), and from 1.4±0.37 to 0.5±0.21 nmol/l (p=0.01), respectively. The inhibition of PRA and A was associated with slight decrease of mean ACTH, 17-OHP, and T, however all these changes were not significant (p>0.05). Thus, MC normalize renin-angiotensin system activity in patients with 21-OHD, however their effect on adrenal steroidogenesis may be not so dramatic.

Incidental adrenal nodules: association with exaggerated 17-hydroxyprogesterone response to adrenocorticotropic hormone.

The etiology of incidentally discovered, nonfunctional adrenal nodules was evaluated by using the 17-hydroxyprogesterone (17-OHP) response to synthetic adrenocorticotrophin (cosyntropin) (ACTH) administration. Patients who were discovered to have adrenal nodules and age-matched volunteers were studied. A total of 12 patients with adrenal nodules and 10 control subjects were studied. None of the patients with adrenal nodules had any evidence of hormonal hypersecretion consistent with pheochromocytoma, Cushing's syndrome or hyperaldosteronism. All subjects had serum 17-OHP and cortisol responses measured at baseline and at 30 and 60 min following the intravenous administration of 250 micrograms of ACTH. Baseline 17-OHP levels in patients with adrenal nodules were not significantly different from those of the normal controls (adrenal nodules 17-OHP: 75 +/- 13 vs control 68 +/- 11 ng/dl). After stimulation with ACTH, both 30 min and 60 min 17-OHP levels in patients with adrenal nodules (322 +/- 47 and 361 +/- 54 ng/dl, respectively) were significantly elevated over the responses seen with the controls (169 +/- 29 ng/dl at 30 min, p < 0.015, and 158 +/- 20 ng/dl at 60 min, p < 0.004). Baseline and post-ACTH serum cortisol levels were similar in both groups. Out of these twelve patients with adrenal nodules, nine were reevaluated twelve months later. In this group the basal 17-OHP remained comparable to normal levels (72 +/- 8.4 ng/dl) whereas the post-ACTH levels still remained exaggerated (30 and 60 min values 327 +/- 37 and 373 +/- 39 ng/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

3α-Androstanediol Glucuronide in Virilizing Congenital Adrenal Hyperplasia

To determine whether serum 3a-androstanediol glucuronide (3AG) reflects the overall effect of integrated adrenal androgen secretion in the virilizing form of congenital adrenal hyperplasia (CVAH), circadian levels (0800, 1200, 1600, and 2000 h) of serum 3AG and 17-hydroxyprogesterone (17OHP) or 11-deoxycortisol (S), androstenedione (A), testosterone (T), and 24-h urinary 17-ketosteroids (17KS) were examined in seven patients (pts) with classical 21-hydroxylase deficiency (21OHD) and one pt with classical 11β-hydroxylase deficiency (11βOHD). Hormonal studies were conducted during the baseline day (off glucocorticoid therapy for 2 days) and during the second day of dexamethasone (Dex) administration (2 mg/day). In five poorly controlled CVAH pts, including the 11βOHD pt, highly elevated baseline morning (AM) serum 17OHP or S as well as A levels, and elevated AM T levels in three pts decreased markedly in the evening (PM), while elevated serum 3AG showed no significant circadian changes; 17KS levels were mar...

3α-Androstanediol Glucuronide in Virilizing Congenital Adrenal Hyperplasia: A Useful Serum Metabolic Marker of Integrated Adrenal Androgen Secretion*

To determine whether serum 3 alpha-androstanediol glucuronide (3AG) reflects the overall effect of integrated adrenal androgen secretion in the virilizing form of congenital adrenal hyperplasia (CVAH), circadian levels (0800, 1200, 1600, and 2000 h) of serum 3AG and 17-hydroxyprogesterone (17OHP) or 11-deoxycortisol (S), androstenedione (A), testosterone (T), and 24-h urinary 17-ketosteroids (17KS) were examined in seven patients (pts) with classical 21-hydroxylase deficiency (21OHD) and one pt with classical 11 beta-hydroxylase deficiency (11 beta OHD). Hormonal studies were conducted during the second day of dexamethasone (Dex) administration (2 mg/day). In five poorly controlled CVAH pts, including the 11 beta OHD pt, highly elevated baseline morning (AM) serum 17OHP or S as well as A levels, and elevated AM T levels in three pts decreased markedly in the evening (PM), while elevated serum 3AG showed no significant circadian changes; 17KS levels were markedly elevated for age. During Dex, moderately or slightly elevated AM 17OHP, A, or T in two to four pts with 21OHD decreased to the normal range in the PM. In the pt with 11 beta OHD, S, A, and T levels were suppressed. 3AG levels were modestly elevated or normal, without circadian changes, in these pts; 17KS levels were elevated or normal. In two other 21OHD pts, modestly elevated AM baseline 17OHP and A levels decreased in the PM; elevated AM T decreased in one pt in the PM; modestly elevated 3AG levels showed no circadian changes; 17KS levels were modestly elevated. During Dex, normal or slightly elevated serum steroids and 17KS levels were associated with normal or high normal 3AG levels without circadian changes. In one postpubertal female with 21OHD, modestly elevated AM baseline 17OHP levels decreased at 2000 h; normal A and T levels throughout the day and low normal 17KS were associated with slightly low 3AG levels, without circadian variation. During Dex treatment, normal 17OHP, A, T, and low 17KS levels were associated with low 3AG levels without circadian variation. In all pts as a group, an excellent correlation (r = 0.9) was found between either 0800 h or mean, or 2000 h serum 3AG levels and 17KS. In addition, AM and PM serum 3AG levels in five normal women were similar. We conclude that the high correlation between serum 3AG and urinary 17KS and the absence of a significant circadian variation in 3AG indicate that serum 3AG, regardless of sample time, is a useful metabolic index of integrated adrenal androgen secretion in CVAH.

Determination of Urinary 17α-Hydroxyprogesterone Excretion Using ELISA

The utility of urinary 17 alpha-hydroxyprogesterone (U-17-OHP) in the diagnosis and management of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) was evaluated in 16 patients with 21-OHD. The normal values for U-17-OHP in relation to age and other physiological conditions were investigated in 96 normal subjects and 7 low birth weight infants. Levels of U-17-OHP, serum 17-OHP (S-17-OHP) and urinary free cortisol (U-FC) were simultaneously determined using enzyme-linked immunosolvent assay (ELISA) combined with fractionation by high performance liquid chromatography (HPLC). Pregnanetriol (PT) levels in the same urine specimens were determined using glass capillary gas chromatography (GC). The results were as follows: 1) Normal subjects and low birth weight infants. A significant correlation between U-17-OHP excretions corrected for body surface area (BSA) in 2-h urine specimens and S-17-OHP concentrations at the midpoint of the urine sampling period was observed in normal subjects (r = 0.768, p less than 0.01). Circadian U-17-OHP excretion in 6 adult males was synchronous with that of U-FC. Age-related changes in actual U-17-OHP excretions (Mean +/- SD ng/day) were as follows: neonates: 31.9 +/- 10.3, children aged 2 to 4 years old: 29.1 +/- 14.5, 5 to 8 years old: 68.6 +/- 29.9, 9 to 11 years old: 151.3 +/- 50.0, 12 to 15 years old: 222.7 +/- 82.0, adult males: 400.1 +/- 62.5, adult females (luteal phase): 339.1 +/- 109.7, and adult females (follicular phase): 185.6 +/- 72.3, respectively. Correlation between U-17-OHP and PT excretions in 24-h urine specimens from normal subjects greater than 2 years of age was highly significant (r = 0.871, p less than 0.01). Although U-17-OHP values were measurable in neonates, those of PT were not detectable by GC in the same specimens because of low conversion of 17-OHP to PT. 2) Cases of 21-OHD. In 4 cases of 21-OHD diagnosed in the neonatal period (aged 11 to 15 days, all were of the salt-losing type), the U-17-OHP concentration in a single urine specimen was significantly higher than that of age-matched controls, whereas the PT concentration in one case was low and therefore had no diagnostic value. In 12 patients with 21-OHD receiving suppressive therapy, correlation between S-17-OHP concentrations and 24-h U-17-OHP excretions corrected for BSA was significant (r = 0.847, p less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of 17-hydroxyprogesterone caproate (17-OHPC) administration to pregnant squirrel monkeys (Saimiri boliviensis boliviensis).

Poor reproductive performance of the squirrel monkey (Saimiri boliviensis boliviensis) in captivity and a relative progesterone (P) deficiency in pregnancy have been reported. Since premature births may contribute to pregnancy wastage, we attempted to measure the effectiveness of 17-hydroxyprogesterone caproate (17-OHPC) treatment of pregnant squirrel monkeys to prevent early deliveries. Based on clearance studies of nonpregnant animals, 25 mg of 17-OHPC was administered at 6-day intervals to a test group of 31 pregnant monkeys while the control group of 29 received saline. Venous blood was obtained at 6- to 12-day intervals for measurement of 17-hydroxyprogesterone (17-OHP), P, 17-B estradiol (E), and androstenedione (A), and dihydroepiandrosterone (DHEA) levels by radioimmunoassays. The treated group had a significant increase in serum 17-OHP (P < 0.001), P (P < 0.01), and DHEA (P < 0.05) levels compared to controls. The numbers of live births, stillbirths, or neonatal deaths did not differ significantly between groups. Although 17-OHPC administration appeared to increase P and 17-OHP levels, this did not alter the duration of pregnancy nor delay the onset of labor. A significant fall in 17-OHP, P, and E levels was observed 6-12 days before delivery.

Absence of Nonclassical Congenital Adrenal Hyperplasia in Patients with Precocious Adrenarche

We studied 31 patients (28 girls and 3 boys), ranging in age from 3.2-7.9 yr, with precocious adrenarche defined by the presence of early sexual hair development, no signs of virilization, and bone age within +3 SD of the mean for chronological age. To determine if this symptom complex stemmed from any form of nonclassical (late-onset) congenital adrenal hyperplasia, an ACTH stimulation test was performed on each patient using a standard 0.25-mg dose of Cortrosyn, given as an iv bolus. Twelve pubertal children (7 girls and 5 boys) and 18 prepubertal children (11 girls and 7 boys) served as normal controls. Baseline and stimulated 17-hydroxypregnenolone (17-OHPreg), 17-hydroxyprogesterone, (17-OHP), 11-deoxycortisol, dehydroepiandrosterone, androstenedione, testosterone, and cortisol levels were measured. Using published nomogram standards for serum 17-OHP response to ACTH, no child with precocious adrenarche was diagnosed as having nonclassical 21-hydroxylase deficiency. Eight girls, however, had a stimulated 17-OHP value that exceeded the mean response for pubertal and prepubertal controls by more than +2 SD [range, 295-670 ng/dL (8.94-20.3 nmol/L)]. Stimulated 11-deoxycortisol values [less than 400 ng/dL (11.6 nmol/L)] ruled out any cases of nonclassical 11 beta-hydroxylase deficiency. No patient had nonclassical 3 beta-hydroxysteroid dehydrogenase deficiency, as defined by both the stimulated 17-OHPreg and the 17-OHPreg/17-OHP ratio to be more than +2 SD above the mean for pubertal children [1354 ng/dL (41.0 nmol/L) and 10.4, respectively]. In conclusion, we could not provide any biochemical evidence for nonclassical congenital adrenal hyperplasia in a large group of children with precocious adrenarche.

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.

Detection of late-onset adrenal hyperplasia in girls with peripubertal virilization

We investigated the value of serum levels of adrenal steroids (dehydroepiandrosterone sulphate, testosterone, 17-hydroxyprogesterone, cortisol) in the identification in peripubertal females with late-onset congenital adrenal hyperplasia owing to 21-hydroxylase deficiency. Among 68 females (age 3-18 years) with virilization in childhood, peripubertally or postpubertally, we selected 21 girls for an ACTH test by measurement of basal blood-spot or serum 17-hydroxyprogesterone (17-OHP) levels. Eight of 21 patients had supranormal post-ACTH serum 17-OHP concentration (57-153 nmol/l) with low normal cortisol concentration. All of them had supranormal basal and post-ACTH 17-OHP to cortisol ratios. These data show a relatively high incidence (about 12%) of mild 21-hydroxylase deficiency among prepubertal and adolescent girls with virilization. It is concluded that the first step in the investigation of peripubertally virilized girls should be the determination of serum 17-OHP and cortisol. Patients with basal morning 17-OHP concentration and 17-OHP to cortisol ratio above reference range should be given an ACTH test.