To describe the presence of dysregulations in steroid biosynthesis and the risk of functional ovarian hyperandrogenism (FOH) and polycystic ovary syndrome (PCOS)-like development in children with hyperandrogenism, 28 girls were studied. Adrenal steroidogenic profile was defined by basal and ACTH-stimulated levels of <em>17OHP</em>, cortisol, DHEAS and androstenedione, and delta precursor/delta product ratios. Ovarian hyperandrogenism was defined by <em>17OHP</em> response to LHRH stimulation, and pelvic ultrasonography (US) was performed to evaluate ovarian morphology. Basal and ACTH-stimulated hormonal results revealed non-classical 21-hydroxylase deficiency-like status in one patient (3.6%), and 21-hydroxylase deficiency heterozygote carrier-like state in four patients (14.3%), while the other 23 patients (82.1%) had functional adrenal hyperandrogenism (FAH). Among these patients with FAH, 47.83% had FOH; when these patients were evaluated by pelvic US, 30.4% had morphological changes which were not concordant with their age. We suggest that even mild forms of hyperandrogenism must be considered seriously and dysregulations of the steroidogenic pathway and ovarian abnormalities must be evaluated carefully to determine the risk of FOH/PCOS.

Congenital adrenal hyperplasia (CAH) is a severe inherited disorder of cortisol biosynthesis that is potentially lethal or can seriously affect quality of life. For the first time, we aimed to assess the stability of 21-deoxycortisol (21Deox), 11-deoxycortisol (11Deox), 4-androstenedione (4AD), 17-hydroxyprogesterone (<em>17OHP</em>) and cortisol (Cort), diagnostic for CAH, in dried blood spots (DBSs) during a 1 year storage at different temperatures. Spiked DBS samples were stored at room temperature, 4 °C, -20 °C or -70 °C, respectively and analyzed in triplicates using liquid chromatography-tandem mass spectrometry at Weeks 0, 1, 2, 3 and 4, Month 6 and Year 1. Analyte levels within ±15% vs the baseline were considered stable. Our observations show that 21Deox, 4AD and <em>17OHP</em> were not significantly changed for 1 year even at room temperature at either analyte levels. In contrast, Cort required storage at 4 °C, -20 °C or -70 °C for long-term stability, being significantly decreased at room temperature from Month 6 (p<0.01) in both the 30(60) nM and the 90(180) nM samples. 11Deox was significantly decreased at room temperature at Year 1 (p<0.01) and only in the 30(60) nM samples. Thus, all biomarkers were stable for up to 1 year at 4 °C, -20 °C or -70 °C and at least for 4 weeks at room temperature. These findings have implications for analyses of stored DBS samples in 2nd-tier assays in newborn screening and for retrospective CAH studies.

A single measurement of serum 17α-hydroxyprogesterone (<em>17OHP</em>) level can be unreliable because of its marked diurnal variation. We investigated the relationship of serum level of <em>17OHP</em> with that of androstenedione (AD), which shows a smaller diurnal variation. And we tested whether the responses of these two hormones to low-dose ACTH stimulation are correlated in patients with 21-hydroxylase deficiency. Baseline serum <em>17OHP</em> and AD levels were measured in 87 patients and a low-dose ACTH stimulation test was performed in 41 patients. The basal <em>17OHP</em> level correlated positively with the basal AD level independently of sex, type of 21-hydroxylase deficiency, and the time of day of blood sampling (n = 87, R(2) = 0.75, P < 0.001). The area under the curve of <em>17OHP</em> and AD correlated positively with their respective basal levels. The fold-change increase in <em>17OHP</em> after ACTH injection correlated negatively with the basal <em>17OHP</em> level, but that of AD did not correlate with the basal AD level. The random serum <em>17OHP</em> level, used in the clinic, is a reliable guide and a low-dose ACTH stimulation test provides no extra benefit for assessing the treatment adequacy in patients with 21-hydroxylase deficiency.

Variations in phenotype in 21-hydroxylase deficiency (21OHD) have cautioned against initiating treatment in the absence of abnormal clinical features. We report 2 Caucasian brothers with compound heterozygous mutations of the CYP21 gene and mild clinical and biochemical features of late-presenting 21OHD. The index case presented aged 8.5 years with mild genital virilization and bone age advanced by 5 years. Elevated basal and synacthen-stimulated 17-hydroxyprogesterone (<em>17OHP</em>; 22.4 and 246 nmol/l) and androstenedione (10.9 and 19.9 nmol/l) levels confirmed 21OHD. His younger brother was investigated at age 7.3 years, and although examination showed normal pre-pubertal genitalia, basal and synacthen-stimulated <em>17OHP</em> (32.4 and 281 nmol/l) and androstenedione (6.2 and 9.0 nmol/l) were abnormal, and bone age was advanced by 1.5 years. Because of actual or incipient virilization, both patients were treated with glucocorticoid replacement 8-12 mg/m(2)/day. This decision is discussed in the context of published guidelines for the management of 21OHD.

In Australia, all newborns born in New South Wales (NSW) and the Australia Capital Territory (ACT) have been offered screening for rare congenital conditions through the NSW Newborn Screening Programme since 1964. Following the development of the Australian Newborn Bloodspot Screening National Policy Framework, screening for congenital adrenal hyperplasia (CAH) was included in May 2018. As part of the assessment for addition of CAH, the national working group recommended a two-tier screening protocol determining 17α-hydroxyprogesterone (<em>17OHP</em>) concentration by immunoassay followed by steroid profile. A total of 202,960 newborns were screened from the 1 May 2018 to the 30 April 2020. A threshold level of <em>17OHP</em> from first tier immunoassay over 22 nmol/L and/or top 2% of the daily assay was further tested using liquid chromatography tandem mass spectrometry (LC-MS/MS) steroid profiling for <em>17OHP</em> (MS<em>17OHP</em>), androstenedione (A4) and cortisol. Samples with a ratio of (MS<em>17OHP</em> + A4)/cortisol > 2 and MS<em>17OHP</em> > 200 nmol/L were considered as presumptive positive. These newborns were referred for clinical review with a request for diagnostic testing and a confirmatory repeat dried blood spot (DBS). There were 10 newborns diagnosed with CAH, (9 newborns with salt wasting CAH). So far, no known false negatives have been notified, and the protocol has a sensitivity of 100%, specificity of 99.9% and a positive predictive value of 71.4%. All confirmed cases commenced treatment by day 11, with none reported as having an adrenal crisis by the start of treatment.

Keywords: 17-α hydroxyprogesterone; congenital adrenal hyperplasia; immunoassay; liquid chromatography tandem mass spectrometry; newborn screening; screening pathway.

We describe the occurrence of hypothyroidism and hypogonadotropic hypogonadism in an XY pseudohermaphrodite subject affected by beta-thalassemia. The patient, reared as female, diagnosed at 14 months of age as having a beta 39/Lepore hemoglobinopathy, treated with multiple transfusion therapy, was referred at age of 15 years because of delayed puberty. Complete endocrine evaluation showed low levels, both basal and after combined LHRH-TRH and hCG stimuli, of FSH, LH, TSH, estradiol (E2), testosterone (T), progesterone (P), androstenedione (A), and FT4 levels, and normal PRL, cortisol, <em>17OHP</em> and ACTH levels. Imaging studies (ultrasound, magnetic resonance, radioisotope scanning and gonadal vessels phlebography) did not show internal genitalia and gonads. Karyotype resulted 46,XY. PCR amplification of the SRY gene confirmed the presence of the Y chromosome. Female genitalia without uterus in a subject with Y chromosome SRY gene, and no detectable testes indicate a condition of male pseudohermaphroditism associated with testicular regression. Low gonadotropin and sex steroid levels are suggestive of combined acquired hypothalamic-pituitary and gonadal impairment, due to iron deposition in both organs. We cannot exclude congenital failure of testosterone synthesis and action in this case, because lack of gonads is an unusual finding in thalassemic hypogonadic subjects.

Synthesis by hamster corpora lutea (CL) in vitro and serum levels of progesterone (P4), 17 alpha-hydroxyprogesterone (<em>17OHP</em>) and 20 alpha-dihydroprogesterone (20DHP) were assessed for different days of pregnancy (Day 1=day of sperm; Day 16=day of delivery). Highest serum levels of the progestins were observed on Day 14 (P4=33 ng/ml; <em>17OHP</em>=2 ng/ml; 20DHP=3 ng/ml), followed by precipitous declines on Day 16. The highest in vitro levels of luteal P4 and <em>17OHP</em> were attained on Days 2-6 (production rates of P4=9-30 ng/mg CL/h; <em>17OHP</em>=0.6-1.5 ng/mg CL/h), and dropped gradually thereafter. In contrast, the production rate of luteal 20DHP was extremely low on Days 2-8 but abruptly increased on Day 10 and was maintained through Day 14 (4-8 ng/mg CL/h). The in vitro production rates of all 3 progestins dropped abruptly on Day 16. Thus, in the pregnant hamster on the day of parturition (Day 16) there was good agreement between in vivo and in vitro levels of the progestins, contrary to the situation in the rat, where on Day 22 the CL in vitro produce large quantities of P4 and 20DHP while the serum levels are very low (Taya and Greenwald, 1981). Addition of 25 ng/ml of ovine LH to the incubation media containing hamster CL increased production rates of P4 (18-55 ng/mg CL/h) and <em>17OHP</em> (1.5-2.4 ng/mg CL/h) on Days 2, 4 and 14 of pregnancy but the CL were refractory to this dose of LH from Days 6 to 12. The production rate of luteal 20DHP ws never stimulated by the addition of 25 ng LH. These results indicate that P4 is the principal progestin in the pregnant hamster with <em>17OHP</em> and 20DHP as minor metabolites. The latter 2 progestins have been measured for the first time in the pregnant hamster and the levels are very low in comparison to the pregnant rat.

Odontocete cetaceans bioaccumulate high concentrations of endocrine disrupting persistent organic pollutants (POPs), including dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyltrichloroethylene (DDE), and dichlorodiphenyldichloroethane (DDD) - collectively DDTs - but few studies have explored DDTs-mediated endocrine disruption in cetaceans. Herein, we use remotely collected blubber biopsies from common bottlenose dolphins (Tursiops truncatus) inhabiting a site with high localized DDTs contamination to study the relationships between DDTs exposure and steroid hormone homeostasis in cetaceans. We quantified blubber steroid hormone concentrations by liquid chromatography-tandem mass spectrometry and blubber POP concentrations by gas chromatography-mass spectrometry. We detected six steroid hormones in blubber, including progesterone (P₄), 17-hydroxyprogesterone (<em>17OHP</em>₄), androstenedione (AE), testosterone (T), cortisol (F), and cortisone (E). Sampled dolphins (n = 62) exhibited exposure to DDT, DDE, DDD, chlordanes (CHLDs), mirex, dieldrin, hexachlorobenzene, polychlorinated biphenyls (PCBs), and brominated diphenyl ethers (BDEs). Using principal components analysis (PCA), we determined that blubber DDTs primarily loaded to the first principal component (PC1) explaining 81.6% of the total variance in POP exposure, while the remaining POPs primarily loaded to the PC2 (10.4% of variance). PC1 scores were negatively correlated with blubber T in males and blubber F in females, suggesting that exposure to DDTs impacted androgen and corticosteroid homeostasis. These conclusions were further supported by observed negative correlations between T and o,p'-DDE, o,p'-DDD, and p,p'-DDD in males sampled in the fall, and between F and the six individual DDTs and ∑₆DDTs in females. Overall, these results suggest that POP-mediated endocrine disruption may have occurred in this stock of dolphins, which could negatively impact their health and fitness. However, this study relied on uncontrolled incidental exposures, making it impossible to establish a causal relationship between DDTs exposure and endocrine effects. Importantly, this study demonstrates that remotely collected blubber biopsies are a useful matrix for studying endocrine disruption in marine mammals.

<AbstractText>To assess provider practice patterns on type of progesterone prescribed and barriers specific to 17 α-hydroxyprogesterone caproate utilization for preterm birth prevention.</AbstractText><AbstractText>A survey mailed to providers assessed utilization and barriers to long-acting reversible contraception and progesterone for preterm birth prevention. Data analysis included chi-square tests for homogeneity followed by post hoc tests of proportions to detect significant pairwise differences.</AbstractText><AbstractText>Five hundred sixty-three of 1,695 respondents who provide prenatal care were included in the analysis. More obstetric than family medicine and midwife providers (87.4% vs 31.4% and 72.6%, respectively; P < .001) prescribed any progesterone for preterm birth prevention. More obstetric providers prescribed 17a-hydroxyprogesterone caproate (<em>17OHP</em>-C) compared with family medicine and midwife providers (98.1% vs 77.8% and 80.5%, respectively; P < .0001). Family medicine and midwife providers prescribed oral progestertone more often than obstetric providers (40.7% and 24.4% vs 13.1 %; P < .05). System-level barriers to <em>17OHP</em>-C were reported more often than patient-level barriers at a rate that was highest among family medicine and midwife providers.</AbstractText><AbstractText><em>17OHP</em>-C has been demonstrated to be an effective method for prevention of recurrent preterm birth. It is used significantly less-and oral progesterone is used significantly more-by family medicine and midwife providers, emphasizing the need for increased education and decreased treatment barriers for its utilization for preterm birth prevention.</AbstractText>

19-nor-progesterone (19NP) is a potent progestagen which possesses a high affinity for the progesterone receptor (PgR). In contrast, 17 alpha-hydroxylated-progesterone (<em>17OHP</em>) shows no hormonal activity and does not compete with progesterone (P) for the PgR. The aim of the present work was to analyse in parallel the structure-affinity and the structure-activity relationships for new molecules obtained by modifications of 19NP and <em>17OHP</em>. The attachment of a 17 alpha-hydroxyl group on 19NP led to a dramatic decrease in both affinity and activity for the end-product, 17 alpha-hydroxylated-19-nor-progesterone (17OH-19NP). The further addition of a methyl group combined with the formation of a double-bound at C6 on 17OH-19NP results in nomegestrol (NOM), the relative affinity of which remained low. Negligible activity was also associated with this affinity in comparison to the parent 19NP. Strikingly, the protection of the free 17 alpha-hydroxyl group of NOM by an acetate led to a potent progestin with high affinity for PgR. It is concluded that the sum of the modifications brought into the <em>17OHP</em>-19NP molecule reestablishes both affinity and activity of the original 19NP molecule. The same conclusion holds if P is considered as the parent compound, as already stated in the literature.

We present a case report of a two and a half-year-old boy who presented with precocious puberty. A clinical diagnosis of congenital adrenal hyperplasia was made. Patient was investigated and found to have an adrenocortical tumor. The tumor was about 7 cms in diameter. The tumor was secreting androgens, <em>17OHP</em> and cortisol. This is an unusual array of hormones to be secreted by an adrenal tumor.

Fifty-four hyperandrogenized women were studied to evaluate the importance of the adrenal or ovarian contribution to androgen secretion. Forty-six had the polycystic ovarian (PCOD) syndrome. Eight normal women represented a control group. The endocrine study was performed during the follicular phase. The plasma samples were collected at 7.00 am (A1) and at 11.00 pm (A3). Dexamethasone 2 mg was administered orally at 11.30 pm and blood samples were collected the day after, at 7.00 am (B). The adrenocorticotropic hormone (ACTH) was injected, 250 micrograms i.v. and samples were collected after 60 min. Cortisol dehydroepiandrosterone-sulfate (DHEAS), androstenedione, testosterone and 17-hydroxyprogesterone (<em>17OHP</em>) were measured. The hyperandrogenized patients had A1 androgen levels higher than the controls (p less than 0.01). <em>17OHP</em> and androstenedione A3 values showed a cortisol-related decrease. After dexamethasone, androgen levels, since DHEAS, were normalized in all patients. We found that baseline androgen levels and circadian and dexamethasone-inhibited amounts were strongly correlated (p less than 0.01). The ACTH test revealed five cases of enzymatic adrenal deficiencies. Moreover, the amplitude of the response of <em>17OHP</em> and androstenedione to ACTH is predictable in relation to both circadian and dexamethasone-inhibited amounts (p less than 0.01). In conclusion, our study confirms and makes quantifiable the importance of the adrenal contribution to androgen secretion in hyperandrogenized patients. The ACTH test is important for detecting the presence of mild enzymatic adrenal defects.

The standard method of primary neonatal screening for congenital adrenal hyperlasia (CAH), determination of 17-hydroxyprogesterone (<em>17OHP</em>) in heelprick blood, is the object of recurrent controversy because of its poor diagnostic and economic efficiency. The superior ability of urinary pregnanetriolone levels to discriminate between infants with and without classical CAH has been known for some time, but has not hitherto been exploited for primary screening. Here we propose an economical neonatal CAH-screening system based on fluorimetric determination of the product of reaction between urinary pregnanetriolone and phosphoric acid.

Abnormal adrenal response is often observed in girls with precocious adrenarche (1). We studied the adrenal response in 112 girls with idiopathic true central precocious puberty (CPP) at early stages of puberty compared to that in 21 girls with normal puberty (controls). The aims of this study were to determine the prevalence of abnormal adrenal response at early stages of puberty, the possible correlation of abnormal adrenal response with pubertal signs at onset of puberty and with plasma androgen levels, and a possible association with the activity of the hypothalamic-pituitary-gonadal (HPG) axis. All participants underwent a combined i.v. adrenocorticotropic hormone (ACTH)-gonadotropin-releasing hormone (GnRH) test at Tanner stage 2-3: 62 of the CPP girls before and 50 during treatment with GnRH analog. The stimulated levels of 17-hydroxypregnenolone (<em>17OHP</em>reg) and the stimulated <em>17OHP</em>reg/17-hydroxyprogesterone ratio were analyzed and compared to previously reported norms. The result revealed three patterns of adrenal response: normal (<em>17OHP</em>reg < or = 24 nmol/l and <em>17OHP</em>reg/<em>17OHP</em> ratio < or = 7) in 50/112 (44.6%) CPP patients and 17/21 (80.9%) controls; exaggerated (<em>17OHP</em>reg>> 24 nmol/l, <em>17OHP</em>reg/<em>17OHP</em> ratio < or = 7) in 50/112 (44.6%) CPP patients and 3/21 (14.3%) controls; and non-classical 3 beta-hydroxysteroid dehydrogenase deficiency (<em>17OHP</em>reg>> 24 nmol/l and <em>17OHP</em>reg/<em>17OHP</em> ratio>> 7) in 12/112 (10.8%) CPP patients and 1/21 (4.8%) controls. The clinical features at onset of puberty were comparable in all girls with the CPP in spite of the different adrenal response patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

Hybridomas secreting monoclonal antibodies (MAbs) against 17alpha-hydroxyprogesterone (<em>17OHP</em>) have been generated. These MAbs are highly specific and have an affinity of 7-12 x 10(7) M(1). The hybridomas were obtained by fusion of spleen cells from immunized mice with mouse myeloma P3X63 Ag8.653 cells. The antigen used for immunization was <em>17OHP</em> conjugated to bovine serum albumin (<em>17OHP</em>:BSA). Fused cells were plated and cloned in 96-well microtiter plates. Wells containing hybridomas were screened simultaneously for specific gamma globulin (IgG) and anti-<em>17OHP</em> activity using an enzyme-linked immunosorbent assay (ELISA)-based method, which is faster than the conventional radioimmunoassay (RIA) screening procedure. Limiting dilution methods were used to obtain single hybridoma clones producing MAb. The stable hybridomas secreting anti-<em>17OHP</em> MAbs were expanded into bioreactors or ascites fluid for large-scale production of the required antibodies. These MAbs will be used in the formulation of a <em>17OHP</em> assay kit to screen for congenital adrenal hyperplasia (CAH) in local newborn human population.

<AbstractText>We aimed at defining the most effective routine immunoassay- or liquid chromatography-tandem mass spectrometry (LC-MS/MS)-determined steroid biomarkers for identifying non-classic adrenal hyperplasia due to 21-hydroxylase deficiency (21-NCAH) in a PCOS-like population before genotyping.</AbstractText><p><div><b>METHODS</b></div>Seventy PCOS-like patients in reproductive age with immunoassay-determined follicular 17OH-progesterone (<em>17OHP</em>) ≥ 2.00 ng/mL underwent CYP21A2 gene analysis and _1-24ACTH test. Serum steroids were measured by immunoassays at baseline and 60 min after ACTH stimulation; basal steroid profile was measured by LC-MS/MS.</p><p><div><b>RESULTS</b></div>Genotyping revealed 23 21-NCAH, 15 single allele heterozygous CYP21A2 mutations (21-HTZ) and 32 PCOS patients displaying similar clinical and metabolic features. Immunoassays revealed higher baseline <em>17OHP</em> and testosterone, and after ACTH stimulation, higher <em>17OHP</em> (<em>17OHP</em>₆₀) and lower cortisol, whereas LC-MS/MS revealed higher <em>17OHP</em> (<em>17OHP</em>_LC-MS/MS), progesterone and 21-deoxycortisol and lower corticosterone in 21-NCAH compared with both 21-HTZ and PCOS patients. Steroid thresholds best discriminating 21-NCAH from 21-HTZ and PCOS were estimated, and their diagnostic accuracy in identifying 21-NCAH from PCOS was established by ROC analysis. The highest accuracy was observed for 21-deoxycortisol ≥ 0.087 ng/mL, showing 100% sensitivity, while the combination of <em>17OHP</em>_LC-MS/MS ≥ 1.79 ng/mL and corticosterone ≤ 8.76 ng/mL, as well as the combination of ACTH-stimulated <em>17OHP</em> ≥ 6.77 ng/mL and cortisol ≤ 240 ng/mL by immunoassay, showed 100% specificity.</p><AbstractText>LC-MS/MS measurement of basal follicular 21-deoxycortisol, <em>17OHP</em> and corticosterone seems the most convenient method for diagnosing 21-NCAH in a population of PCOS with a positive first level screening, providing high accuracy and reducing the need for ACTH stimulation test.</AbstractText>

BACKGROUND

Treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency can be monitored by salivary androstenedione (A-dione) and 17α-hydroxyprogesterone (<em>17OHP</em>) levels. There are no objective criteria for setting relevant target values or data on changes of <em>17OHP</em> and A-dione during monitoring.

METHODS

We evaluated A-dione and <em>17OHP</em> levels in nearly 2000 salivary samples collected during long-term treatment of 84 paediatric patients with classic 21-hydroxylase deficiency.

RESULTS

A-dione and <em>17OHP</em> levels and its ratio <em>17OHP</em>/A-dione remained constant from 4 to 11 years with no sex-related differences. During puberty, A-dione and <em>17OHP</em> levels both increased, starting at earlier age in girls than in boys. The ratio <em>17OHP</em>/A-dione declined. Normalised A-dione concomitant with elevated <em>17OHP</em> [1.43 nmol/L (0.46-4.41) during prepuberty; 2.36 nmol/L (0.63-8.89) for boys and 1.99 nmol/L (0.32-6.98) for girls during puberty] could be obtained with overall median glucocorticoid doses of 11-15 mg/m2/day. A-dione levels above the upper reference limit (URL), suggesting undertreatment, coincided with <em>17OHP</em> levels ≥10 times URL. The percentage of A-dione levels above URL was 16% at ages 4-8 years, but increased to 31% for girls at 16 years and 46% for boys at 17 years.

CONCLUSIONS

Normalised A-dione consistent with <em>17OHP</em> three times URL during prepuberty and normalised A-dione consistent with 4-6 times URL during puberty could be obtained by moderate glucocorticoid dosages. A constant <em>17OHP</em>/A-dione ratio during prepuberty suggested absence of adrenarche. During puberty, a higher percentage of samples met the criteria for undertreatment, especially of boys.

Classic forms of 21-hydroxylase deficiency (21OHD) are usually diagnosed at birth by salt wasting or precocious puberty in male patients. Here we report the case of a 32-year-old male patient who presented with azoospermia and bilateral testicular tumors. He was referred to our endocrine unit after testicular surgery. His gonadotropins were undetectable. Liquid chromatography-tandem mass spectrometry revealed a high serum progesterone level, high 17-hydroxyprogesterone (<em>17OHP</em>) (255 ng/mL), and high levels of <em>17OHP</em> metabolites, suggesting a classic form of 21OHD. His blood pressure was normal. Molecular analysis showed a homozygous large 21-hydroxylase gene (CYP21A2) conversion. Furthermore, an adrenal CT scan revealed voluminous, heterogeneous bilateral and asymmetric adrenal masses containing calcifications. Our case report illustrates the fact that a classic form of 21OHD can be diagnosed in late adulthood, manifested by azoospermia and large adrenal tumors, associated with elevated <em>17OHP</em>.

Polycystic ovary syndrome is the most common cause of hyperandrogenism in young females. Other causes are congenital adrenal hyperplasia (CAH), androgen-producing tumours and drugs. The severity and tempo of virilisation help in distinguishing the tumoural from non-tumoural causes. We report a rare case of non-classic CAH and androgen-producing ovarian tumour in the same patient, causing hyperandrogenism. A 15-year-old female patient presented with secondary amenorrhea, excessive facial hair growth and clitoromegaly for 6 months. Due to severe virilisation, tumoural aetiology was considered. Investigations showed marked elevation of testosterone and mild elevation of 17 hydroxy progesterone (<em>17OHP</em>). Imaging confirmed right ovarian tumour. Adrenocorticotropic hormone stimulated <em>17OHP</em>, was elevated confirming the diagnosis of underlying non-classic CAH. Surgical removal of the tumour was followed by improvement in hyperandrogenism, but persistent elevation of <em>17OHP</em> confirmed the underlying presence of non-classic CAH.

OBJECTIVE

This study evaluated hormonal and skin effects in hyperandrogenic women of an oral estroprogestin (EP) association containing ethynilestradiol 30 mcg plus drospirenone 3 mg.

METHODS

Thirty two women with signs and symptoms of hyperandrogenism (seborrhea, acne, increased hair); hormonal assessment (follicle-stimulating hormone, [FSH]; luteinizing hormone, LH; 17-hydroxi-progesterone, <em>17OHP</em>; androstenedione, A, testosterone, T; dehydroepiandrosterone sulfate, DHEAS; sex hormone binding globulin, [SHBG]; Free Androgen Index [FAI, Tx100/SHBG] was performed before the start of treatment, and after 3 and 6 months of administration of EP. The impact on seborrhea, acne, and hair pattern (Ferriman-Gallwey score) was assessed, and, by non-invasive technique, hydration, water transpiration, and homogeneity of the skin were evaluated.

RESULTS

Treatment with this EP for 6 months decreased significantly circulating androgen levels (A, T, DHEAS) and FAI, and increased SHBG levels, also reducing seborrhea, acne and hirsutism. Moreover, EE/DRSP increased hydration and improved overall appearance of skin surface (homogeneity).

CONCLUSIONS

Treatment with EE 30 mcg+DRSP 3 mg improves hormonal pattern and skin appearance in hyperandrogenic patients, potentially with subsequent, beneficial effects on quality of life of these women.

<strong class="sub-title"> Purpose: </strong> To analyze the performance of basal 17OH-progesterone (<em>17OHP</em>) levels versus the basal <em>17OHP</em>/cortisol ratio in nonclassical congenital adrenal hyperplasia (NCAH) and polycystic ovary syndrome (PCOS) differential diagnosis. Basal <em>17OHP</em> levels >10 ng/mL have been used to confirm NCAH diagnosis without the adrenocorticotropic hormone (ACTH) test; however, the optimal cutoff value is a matter of debate.

<strong class="sub-title"> Methods: </strong> A cross-sectional study was performed at the endocrinology and gynecological endocrinology outpatient clinics of a tertiary hospital. A total of 361 patients with PCOS (age 25.0 ± 5.3 years) and 113 (age 19.0 ± 13.6 years) patients with NCAH were enrolled. Basal and ACTH-<em>17OHP</em> levels were measured by radioimmunoassay, and CYP21A2 molecular analysis was performed to confirm hormonal NCAH diagnosis. Receiver operating characteristic curve analysis compared basal <em>17OHP</em> levels and the <em>17OHP</em>/cortisol ratio between NCAH and PCOS patients.

<strong class="sub-title"> Results: </strong> Basal <em>17OHP</em> levels were higher in NCAH patients than in those with PCOS (8.85 [4.20-17.30] vs 1.00 [0.70-1.50] ng/mL; P < 0.0001), along with <em>17OHP</em>/cortisol ratio (0.86 [0.47-1.5]) vs 0.12 [0.07-0.19]; P < 0.0001, respectively). Basal <em>17OHP</em> levels and the <em>17OHP</em>/cortisol ratio were strongly correlated in both groups (rho = 0.82; P < 0.0001). Areas under the curves for basal <em>17OHP</em> levels (0.9528) and the <em>17OHP</em>/cortisol ratio (0.9455) were not different to discriminate NCAH and PCOS (P > 0.05). Basal <em>17OHP</em> level >5.4 ng/mL and <em>17OHP</em>/cortisol ratio >2.90 had 100% specificity to identify NCAH.

<strong class="sub-title"> Main conclusions: </strong> Basal <em>17OHP</em> levels >5.4 ng/mL can be used to perform differential diagnoses between NCAH and PCOS, dismissing the ACTH test. The basal <em>17OHP</em>/cortisol ratio was not superior to basal <em>17OHP</em> levels in this scenario.

Keywords: basal 17OH-progesterone levels; diagnosis screening; nonclassical congenital hyperplasia; polycystic ovary syndrome.

Obesity, the most frequent nutritional problem throughout the rich nations, can have a vast and significant influence on different aspects of endocrinology, in particular on ovulation disfunction, on hyperandrogenemia, on hormone-sensitive carcinomas. Our study proposes to value the response to adrenal cortex to stimulation with adrenocorticotropin (ACTH) hormone in obese patients, with particular attention to the behavior of adrenocortical androgens and their precursor. We recruited 30 female patients so divided: 12 obese, nonhirsute, eumenorrheic patients (group A); 10 normal weight, hirsute patients in situation of secondary amenorrhea (group B); 8 normal weight, nonhirsute, eumenorrheic patients (group C). Cortisol, progesterone, 17 OH progesterone, dehydroepiandrosterone sulfate, androstenedione, testosterone were measured at 60, 120, 180, 240, 300 min during continual infusion i.v., for 5 h, of ACTH 1-17 at 100 mcg dose, in physiological sodium chloride solution. All the women with monthly menstruation were studied between the IV and VIII day of their cycle. In the patients with secondary amenorrhea the value of basic progesterone was used to completely exclude an eventual luteal phase and the relationship LH/FSH was so as to logically exclude a diagnosis of polycystic ovary. This exclusion was also confirmed from the report of the ultrasonography. The basic concentration of hormone dosage is not significantly different between the patients of the three groups, except for T. This hormone is different because it is found to be significantly (p < 0.01) increase in the hirsute patients, in respect of the patients in group A and group C. Also P and <em>17OHP</em> have been found to be higher, if only in insignificant measure, in hirsute patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Progesterone was widely used in France during the 1980s and 1990s to prevent preterm birth until some published cases of cholestasis suddenly stopped its prescription. Since then, multiple randomized controlled trials have emerged and demonstrated the efficiency of the treatment but also its safety at low doses. In order to clarify its indications, we performed a current literature review. We analyzed literature data according to different categories of risk and different routes of administration. Results confirm that progesterone is an efficient treatment to prevent preterm birth in singleton gestation with short cervical length, and in singleton gestation with prior preterm birth with or without short cervical length. Apart from these indications, progesterone, especially 17-alpha-hydroxyprogesterone (<em>17OHP</em>), should not be used outside research protocols.