17-hydroxyprogesterone Concentrations Research Articles

Neonatal reference intervals for serum steroid hormone concentrations measured by LC-MS/MS.

Congenital adrenal hyperplasia (CAH) is a rare, inherited disorder of adrenal steroid synthesis. In many countries it is part of the neonatal screening program enabling early diagnosis and treatment. In case of an abnormal neonatal screening result or when other differences of sexual development (DSD) are suspected, measurement of serum steroid hormones using liquid chromatography coupled to mass spectrometry (LC-MS/MS) is needed for further diagnosis. However, reliable age- and sex-specific reference intervals (RIs) for serum steroid hormones during the neonatal period are missing. We therefore aimed to establish LC-MS/MS based RIs for serum steroid hormones in neonates. Serum was obtained from healthy term neonates at two time points: 130 samples at day 3-8 (T1, time of the neonatal screening) and 126 samples at day 13-15 (T2,two weeks old). Concentrations of cortisol, cortisone, corticosterone, 11-deoxycortisol, 21-deoxycortisol, 11-deoxycorticosterone, testosterone, androstenedione, and 17-hydroxyprogesterone (17-OHP) were measured using LC-MS/MS. RIs (in nmol/L) were established for T1 and T2: cortisone (19.3-215;18.0-212), cortisol (10.0-407;8.4-446), corticosterone (<31;<50), 11-deoxycortisol (0.73-4.6;0.70-3.6), 17-OHP (<4.9;<5.1), androstenedione (0.3-1.8;0.3-2.7), 11-deoxycorticosterone (<0.2;<0.2), and 21-deoxycortisol (<1;<1), respectively. Testosterone differed between boys and girls: RIs at T1 and T2 for boys were 0.27-4.3 and 0.63-13.9, and for girls<0.30 and <0.47, respectively. We established LC-MS/MS based RIs for cortisol, cortisone, corticosterone, 11-deoxycortisol, 21-deoxycortisol, 11-deoxycorticosterone, testosterone, androstenedione, and 17-OHP in neonates in the first and second week of life.

A-070 Evaluation of Plain and Serum-Separator Blood Collection Tubes for the Measurement of Steroid Hormones by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

Abstract Background Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) is the preferred method for quantifying steroids. Commonly measured steroids 11-deoxycortisol, androstenedione, testosterone, 17-hydroxyprogesterone and dehydroepiandrosterone (DHEA). Although serum separator blood collection tubes may not be recommended but their frequent use is attributed to the ease of serum separation. Moreover, the serum separator tube may be the only available option for analysis, without the need for additional sample collection. Under such conditions, from certain serum separator tubes, we observed occasional interference in LC-MS/MS steroid method. We pursued to evaluate the performance of blood collection tubes without and those with serum separators, for the quantification of specified steroids by LC-MS/MS. Methods Blood samples were collected from 10 volunteers using both plain and serum separator blood collection tubes procured from two major suppliers (Greiner and BD). The specified steroids were measured by LC-MS/MS method. The procedure involved addition of labeled internal standards to the samples and extraction of steroids in methyl tert-butyl ether. Subsequently, the extract dried under a stream of nitrogen, and the residue was reconstituted in the mobile phase. LC-MS/MS analysis involved multiple reaction monitoring (MRM) for the specified steroids and their internal standards. Results The figure shows a sample chromatogram from a subject with blood samples collected in a plain (A) and serum separator tubes from Greiner (B) and BD (C1 and C2, a zoomed of C1). In this sample, from the plain tube, the concentrations of 11-deoxycortisol, androstenedione, testosterone, 17-hydroxyprogesterone and DHEA were 27, 55, 690, 99 and 283 ng/mL respectively. No significant interference was observed in Greiner serum separator tube. Whereas BD serum separator tube exhibited several erroneous peaks making the quantitation of several steroids challenging or inaccurate. Conclusions In the described LC-MS/MS method, BD serum-separator tubes exhibited erroneous peaks. These peaks were not seen in Greiner serum-separator tubes.

A-062 Determination Neonatal 17-Hydroxyprogesterone Cutoff Levels for Congenital Adrenal Hyperplasia in Korea: 3 years' experience

Abstract Background Newborn screening for congenital adrenal hyperplasia (CAH) is a crucial practice with significant global adoption. While it offers substantial benefits, it also presents challenges due to high false positive rates, which can lead to mental strain for families and unnecessary hospital visits. Our research delved into the impact of birth weight (BW), gestational age (GA), and GA combined with sampling time on 17-hydroxyprogesterone (17-OHP) concentration. Specifically, we aimed to establish appropriate 17-OHP cutoff values for preterm, low birth weight weight (LBW), and sick newborns. Methods A total of 2,429 newborns born between October 2020 and January 2024 were screened for CAH. Samples were collected from neonates on a filter paper with a heel prick method. The 17-OHP concentration was measured by AutoDELFIA Neonatal 17-hydroxyprogesterone kit (PerkinElmer, Turku, Finland). This assay is a solid phase, time-resolved fluoroimmunoassay based on the competitive reaction between europium labeled 17-OHP and sample 17-OHP for a limited amount of binding sites on 17-OHP specific polyclonal antibodies. The 99.5 percentile was applied to the cutoff of 17-OHP for CAH. Results 17-OHP concentrations in newborns with lower BW and GA were significantly higher than those in normal BW and term newborns. 17-OHP concentration showed a statistically significant negative correlation with BW (r = -0.512, p &amp;lt; 0.001) and GA (r = -0.578, p &amp;lt; 0.001). Not only the full-term subgroup, but also preterm subgroups had a same tendency of 17-OHP concentration decrease with increasing sampling time. Application of newly establishing 99.5 percentile cutoff criteria significantly reduced recall rates to 1.02%, 0.81%, and 1.45% according to each criterion of BW, GA, and GA with sampling time, respectively. Conclusions This research introduces novel 17-OHP cutoff values for preterm, low birth weight (LBW), and sick newborns in the context of congenital adrenal hyperplasia (CAH). We analyzed the distribution of these cutoff values, considering factors such as birth weight, gestational age, and the timing of sample collection. Notably, applying the newly established cutoff criteria led to a significant reduction in false positive rates. Our laboratory’s data can serve as a valuable reference for other institutions aiming to set appropriate cutoffs, thereby minimizing unnecessary follow-up tests and enhancing the efficiency of CAH screening. As we continue to accumulate additional data, further reserch in this field remains promising.

Genetics of 21-OH Deficiency and Genotype-Phenotype Correlation: Experience of the Hellenic National Referral Center.

21-hydroxylase deficiency (21-OHD) represents the most common form of congenital adrenal hyperplasia (CAH) due to CYP21A2 gene pathogenic variants. Τhe aim of this study was the identification of CYP21A2 variants in 500 subjects of Greek origin with a suspicion of 21-OHD and, by using the existing hormonal assessment and genotypes of the 500 subjects tested, to identify a biomarker that could differentiate between the heterozygotes and the cases with no pathogenic variants identified. Five hundred subjects with clinical suspicion of 21-OHD underwent CYP21A2 gene sequencing and Multiplex Ligation Dependent Probe Amplification (MLPA). Genetic diagnosis was achieved in 27.4% of the subjects tested, most of which presented with the non-classic form (NC) of 21-OHD. Heterozygotes accounted for 42.6% of cases, whereas no pathogenic variants were identified in 27% of cases. De novo aberrations, duplications, and five novel variants were also identified. Statistical analysis revealed that the difference between the basal and 60' post-ACTH stimulation 17-hydroxyprogesterone concentrations (Δ17-OHP60-0) could be a potential biomarker (p < 0.05) distinguishing the heterozygotes from the cases with no pathogenic variants identified, although no clear cut-off value could be set. Further analysis revealed overlapping clinical manifestations among all the subjects tested. The presented phenotypic traits of the subjects tested and the inability to identify a discriminative biochemical marker highlight the importance of comprehensive CYP21A2 genotyping to ascertain the correct genetic diagnosis and proper genetic counselling.

The effect of the steroid profile on the severity and the outcome of treatment of newborns with congenital malformations

Introduction. Adrenal insufficiency is often found in critical conditions of the neonatal period and has nonspecific symptoms, which greatly complicates its diagnosis. The objective was to study the hormonal status of newborns with congenital malformations (CM according to the outcome of treatment in the intensive care unit.Materials and methods. Study design – observational, dynamic retrospective comparative study. 60 newborns were examined: 26 healthy and 34 with CM. Depending on the severity of the condition, children with CM were divided into two groups. Group I included patients in an extremely severe condition, and in group II – in a stable condition. We studied the concentration of 17-hydroxypregnenolone, aldosterone, dehydroepiandrosterone, cortisol, cortisone, corticosterone, progesterone, testosterone, estradiol and 17-hydroxyprogesterone upon admission to the ICU, immediately after surgery and on the first day after it.Results. In all children with CM, the concentration of 17-hydroxypregnenolone, 17-hydroxyprogesterone, progesterone and dehydroepiandrosterone before surgery was significantly lower compared to healthy newborns, while in group I, it was minimal. After surgery, the concentration of cortisol precursors remained low, but its level increased significantly, especially in children of group I. A risk factor for lethal outcome in newborns with CM needing treatment in the ICU is the 17-OH-pregnenolone/dehydroepiandrosterone ratio, both at the time of admission to the ICU (AUC = 0.821; sensitivity = 68.97; specificity = 100; p = 0.0002; cut-off &lt; 1,52); and on the first day after surgery (AUC = 0.807; sensitivity = 79.3; specificity = 80; р = 0.025; cut-off = 0).Conclusion. The increase in the concentration of cortisol against the background of low level of hormone precursors and the reduction of the 17-OH-pregnenolone/dehydroepiandrosterone ratio in the first day after surgery is a marker of an adverse course of the postoperative period and outcome.

Minipuberty in Daughters of Women with Hypothyroidism during Pregnancy.

Minipuberty is a term describing transient postnatal activation of the hypothalamic-pituitary-gonadal axis, likely playing an important role in the postnatal growth of female genital organs and breasts. Unlike infant boys, there are no data concerning the impact of gestational hypothyroidism on the course of minipuberty in infant girls. Therefore, the aim of the current study was to investigate the reproductive axis and genital organs in daughters of women with thyroid hypofunction during pregnancy. The study population included three matched groups of infant girls: offspring of women with thyroid hypofunction non-substituted or inadequately treated during gestation (group 1), descendants of women adequately substituted throughout pregnancy (group 2), and daughters of healthy women (group 3). Salivary concentrations of estradiol, progesterone, 17-hydroxyprogesterone, and androgens (testosterone, androstenedione, and dehydroepiandrosterone sulfate) and urine levels of gonadotropins were measured monthly from month 1 to month 6, once every two months between postnatal months 6 and 12, and once every three months between postnatal months 12 and 18. During each visit, we also determined ovarian volume, uterine length, and breast diameter. Concentrations of FSH, LH, and estradiol were lowest in group 1, and this group was also characterized by the shortest detection period for gonadotropins and estradiol. These differences were paralleled by differences in ovarian volume, uterine length, and breast diameter. There were no differences between groups 2 and 3 in levels of both hormones and in the size of the measured structures. The obtained results seem to indicate that non-substituted or inadequately substituted hypothyroidism during pregnancy may impair the course of minipuberty in the female offspring.

The Course of Minipuberty in Daughters of Women with Low Gestational Vitamin D Status.

Minipuberty is a term describing temporary, sex-specific activation of the hypothalamic-pituitary-gonadal axis, which is implicated in the development of male and female genital organs. Sons of women with low vitamin D during gestation were found to be characterized by increased activity of the reproductive axis and faster postnatal growth of genital organs. The current study assesses for the first time the course of minipuberty in female descendants of women with a vitamin D deficit. The study population included three matched groups of infant girls: children born to women with vitamin D deficiency (25OHD concentration below 50 nmol/L), offspring of women with vitamin D insufficiency (25OHD concentration between 50 and 75 nmol/L), and daughters of healthy females (25OHD concentration between 75 and 150 nmol/L). Salivary concentrations of estradiol, progesterone, 17-hydroxyprogesterone and androgens, as well as urine concentrations of FSH and LH, were assayed during the first 18 months of life (once a month in the first 6 months, bimonthly between months 6 and 12, and then every three months). At each visit, beyond hormone measurements, the investigators assessed the size of reproductive organs: ovaries, uterus and breasts. In daughters of mothers with vitamin D deficiency, concentrations of FSH, LH and estradiol were higher and detectable for a longer period of time, while ovarian volume, uterine length and breast diameter were greater than in the remaining groups. Children born to women with vitamin D insufficiency were characterized by higher FSH levels than daughters of healthy females, though the detection period was the same, and both groups differed in breast diameter. These findings suggest that low vitamin D status during gestation leads to more pronounced and longer-lasting activation of the reproductive axis, and is associated with increased dimensions of sexual organs, the magnitude of which depends on the degree of vitamin D deficit.

Severe adrenal insufficiency in six neonates with normal newborn screening for CAH.

Newborn screening (NBS) reduces the risk of mortality in congenital adrenal hyperplasia (CAH), mainly due to the salt-wasting form of 21-hydroxylase deficiency. There is limited knowledge regarding the results of NBS in non-CAH primary adrenal insufficiency (non-CAH PAI). Clinical and NBS for CAH data of neonates who were diagnosed with non-CAH PAI between January and December 2022 were examined. Patients (n = 6, 4 females) were presented with severe hyperpigmentation (n = 6), hypoglycemia (n = 4), hyponatremia (n = 3), hyperkalemia (n = 1), respiratory distress syndrome (n = 1) between 3rd hour to 2 months of life. All had normal NBS results. The median first-tier 17-hydroxyprogesterone (17OHP) concentration in NBS for CAH was 0.14 ng/mL (range; 0.05-0.85). Molecular studies revealed biallelic mutations in the MC2R (n = 4; 3 homozygous, 1 compound heterozygous), MRAP (n = 1) and STAR (n = 1) genes. Glucocorticoid with or without mineralocorticoid replacement was initiated once the diagnosis ofnon-CAH PAI was established. Neonates with non-CAH PAI have always normal NBS due to persistently low 17OHP, even when these newborn infants are severely symptomatic for adrenal insufficiency. Clinicians should be alert for signs of adrenal insufficiency in neonates, even if the patient has a 'normal' screening for CAH, so as not to delay diagnosis and treatment. This fact should be kept in mind particularly in countries where these conditions are more common than elsewhere.

Serum steroid and thyroid hormone concentrations in healthy domestic male and female alpacas.

Alpacas are high quality fiber producing animals, kept for production purpose and as pets. Endocrine imbalances from adrenal glands, gonads, or thyroid gland may result in coat abnormalities in domestic animals and affect reproduction. Contrary to many domesticated animals, information on hormone concentrations in alpacas is scarce. The purpose of this study was to provide steroid and thyroid hormone values in domestic alpacas. Blood was collected from healthy male (35 intact, 2 castrated) and female (48 non-pregnant, 3 pregnant) alpacas from local farms in Tennessee. Adrenal, reproductive, and thyroid hormones were analyzed. There were no significant differences in median concentrations of progesterone, estradiol, thyroxine (T4), and triiodothyronine (T3) between intact male and female non-pregnant alpacas. Median concentrations of testosterone, androstenedione, 17-hydroxyprogesterone, and cortisol were significantly higher in intact male alpacas compared to female non-pregnant alpacas. This information provides adrenal, gonadal, and thyroid hormone concentrations in alpacas to help with diagnosis of endocrine disorders.

Minipuberty in Sons of Women with Low Vitamin D Status during Pregnancy.

Minipuberty is a transient phase of reproductive axis activation during the first several months of life, playing an important role in the development of reproductive organs in boys. Low 25-hydroxyvitamin D levels during pregnancy are associated with an increased risk of neonatal complications. An inadequate gestational vitamin D status is hypothesized to affect the postnatal activation of the hypothalamic-pituitary-gonadal axis. The purpose of our study was to assess whether a low vitamin D status during pregnancy determines the course of minipuberty in boys. The study included three groups of male infants born to women with different vitamin D statuses: sons of women with vitamin D deficiency (group 1), sons of women with vitamin D insufficiency (group 2), and male offspring of females with normal 25-hydroxyvitamin D levels (group 3 (the reference group)). Concentrations of testosterone, androstenedione, dehydroepiandrosterone sulfate, estradiol, progesterone, and 17-hydroxyprogesterone in saliva, as well as concentrations of gonadotropins in urine, were assayed monthly from postnatal months 1 to 6, and once every 2 months in the second half of the first year of life. Additionally, at each visit, penile length and testicular volume were assessed. Concentrations of testosterone, FSH, and LH, as well as penile length and testicular volume, were greater in group 1 than in groups 2 and 3. In turn, group 2 was characterized by higher FSH levels and a greater testicular volume than group 3. Peak concentrations of LH and testosterone were observed earlier in group 1 than in the remaining groups. The obtained results suggest that a low vitamin D status during pregnancy may have a stimulatory impact on reproductive axis activity and on the early postnatal development of male genital organs, correlating with the severity of hypovitaminosis D.

Crinecerfont, a CRF1 Receptor Antagonist, Lowers Adrenal Androgens in Adolescents With Congenital Adrenal Hyperplasia.

Crinecerfont, a corticotropin-releasing factor type 1 receptor antagonist, has been shown to reduce elevated adrenal androgens and precursors in adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD), a rare autosomal recessive disorder characterized by cortisol deficiency and androgen excess due to elevated adrenocorticotropin. To evaluate the safety, tolerability, and efficacy of crinecerfont in adolescents with 21OHD CAH. This was an open-label, phase 2 study (NCT04045145) at 4 centers in the United States. Participants were males and females, 14 to 17 years of age, with classic 21OHD CAH. Crinecerfont was administered orally (50 mg twice daily) for 14 consecutive days with morning and evening meals. The main outcomes were change from baseline to day 14 in circulating concentrations of ACTH, 17-hydroxyprogesterone (17OHP), androstenedione, and testosterone. 8 participants (3 males, 5 females) were enrolled; median age was 15 years and 88% were Caucasian/White. After 14 days of crinecerfont, median percent reductions from baseline to day 14 were as follows: ACTH, -57%; 17OHP, -69%; and androstenedione, -58%. In female participants, 60% (3/5) had ≥50% reduction from baseline in testosterone. Adolescents with classic 21OHD CAH had substantial reductions in adrenal androgens and androgen precursors after 14 days of oral crinecerfont administration. These results are consistent with a study of crinecerfont in adults with classic 21OHD CAH.

A novel p.Leu197Pro homozygous variant in HSD3B2 as a cause of 46,XY DSD with hyperpigmentation in an infant

We report a novel missense variant of the HSD3B2 gene in a 46,XY child born to third degree consanguineous parents presenting with undervirilization and progressive hyperpigmentation. The steroid profile showed elevated concentrations of 17-hydroxyprogesterone, but normal androstenedione and testosterone. The adrenocorticotropic hormone was elevated. The direct DNA sequencing of the child revealed a new homozygous missense variant in the HSD3B2 gene, resulting in the amino acid substitution of proline for leucine at codon 197. We have described a hitherto novel HSD3B2 gene variant in an undervirilized male infant causing 3β-hydroxysteroid dehydrogenase 2 deficiency.

Metabotypes of congenital adrenal hyperplasia in infants determined by gas chromatography-mass spectrometry in spot urine

Biochemical monitoring of treatment in infants with classic congenital adrenal hyperplasia (CAH) is not yet well defined. The aim of this study was to perform a cluster analysis of the urinary steroid metabolome for treatment monitoring of infants with classic salt-wasting CAH. We analyzed spot urine samples obtained from 60 young children ≤ 4 years of age (29 females) with classic CAH due to 21-hydroxylase deficiency treated with hydrocortisone and fludrocortisone by targeted gas chromatography-mass spectrometry (GC-MS). Patients were classified into different groups according to their metabolic patterns (metabotypes) using unsupervised k-means clustering algorithms. Three metabotypes could be discovered. Metabotype #1 (N = 15 (25%)) showed high concentrations of androgen and 17-hydroxyprogesterone (17OHP) precursor steroids, metabotype #2 (N = 28 (47%)) revealed balanced metabolic control, and metabotype #3 (N = 17; 28%) demonstrated severe adrenal suppression with low concentrations of androgen and 17OHP precursor steroids. Daily hydrocortisone doses and urinary concentrations of cortisol and cortisone metabolites did not differ between all three metabotypes. Metabotype #2 had highest daily dose of fludrocortisone (p = 0.006). Receiver operating characteristic curve analysis showed that 11-ketopregnanetriol (area under the curve [AUC] 0.967) and pregnanetriol (AUC 0.936) were most suitable of separating metabotype #1 from #2. For separation between metabotypes #2 vs. #3, the 11-oxygenated androgen metabolite 11-hydroxyandrosterone (AUC 0.983) and the ratio of 11-hydroxyandrosterone to tetrahydrocortisone (AUC 0.970) were most suitable. In conclusion, GC-MS-based urinary steroid metabotyping is a new method to help monitor the treatment of infants with CAH. This method allows classification of under-, over- and adequately treated young children.

Establishing 17-Hydroxyprogesterone Cutoff Values for Congenital Adrenal Hyperplasia in Preterm, Low Birth Weight, and Sick Newborns.

Newborn screening for congenital adrenal hyperplasia (CAH) has benefits with a high adoption rate worldwide. It also has problems of high false positives, which can cause stress to the patient's family with economic losses and unnecessary visits of newborns to hospitals. Therefore, we investigated the influence of birth weight (BW), gestational age (GA), and GA with sampling time on 17-hydroxyprogesterone (17-OHP) concentration and attempted to establish the 17-OHP cutoff values in preterm, low birth weight (LBW), and sick newborns. Newborns (n=1,071) born between October 2020 and January 2022 were screened for CAH. Samples from neonates were collected on filter paper with the heel prick method. 17-OHP concentration was measured by time-resolved immunofluorescence with an AutoDELFIA Neonatal 17-hydroxyprogesteron kit and grouped in relation to BW, GA, and GA with sampling time. The median age of newborns at neonatal sample collection was 6 days. 17-OHP concentration showed a statistically significant negative correlation with BW (r=-0.488, p<0.001) and GA (r=-0.560, p<0.001). Full-term and preterm subgroups had a similar decreasing tendency of 17-OHP concentration with increasing sampling time. Application of newly establishing cutoff criteria significantly reduced recall rates to 1.16%, 0.9%, and 1.75% according to each criterion of BW, GA, and GA with sampling time, respectively. This study presents new 17-OHP cutoff values for preterm, LBW, and sick newborns. These data in our laboratory can be used as a reference by other laboratories for establishing new cutoff criteria to help lower the high recall rate and reduce unnecessary follow-up tests.

Neklasičan oblik kongenitalne adrenalne hiperplazije

Introduction: Congenital adrenal hyperplasia is an autosomal recessive disease caused by gene mutation resulting in 21a-hydroxylase deficiency and a consequent reduction in adrenal steroidogenesis. The disease could present as classic and non-classic form. The frequency of non-classic form is 0.1% in general population, the most common clinical presentation is premature adrenarche, and the diagnosis is made by determining the concentration of 17-hydroxyprogesterone. The recommended treatment is hydrocortisone with close growth monitoring. Case report: A 7.5-year-old girl was admitted due to premature puberty, accelerated bone maturation and tall stature. The clinical exam revealed hypertrichosis, normal blood pressure and normal ultrasound of internal reproductive organs. The karyotype was 46 XX, the basal and stimulated levels of 17-hydroxyprogesterone were elevated. Clinical and laboratory regression with stagnation of bone and body growth after starting treatment with hydrocortisone confirmed the diagnosis of non-classic congenital adrenal hyperplasia. Conclusion: Early diagnosis and therapy provide a better quality of life, reaching the target height in adulthood and avoiding the development of complications.

PSAT028 Congenital Adrenal Hyperplasia with Adrenal Myelolipoma: Gender Identity and Choice of Therapy

Abstract Background Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder characterized by impaired glucocorticoid and mineralocorticoid synthesis with excessive adrenal androgen production. In affected females, most forms of CAH lead to virilization. Persons with CAH have a higher prevalence of adrenal myelolipomas compared with the general population. Clinical case A 38-year-old Spanish speaking individual who identified as male presented with headache and chest pain. Imaging revealed diffuse nodular thickening and enlargement of the right adrenal gland consistent with hyperplasia as well as 11 cm multilobulated left adrenal lesion containing macroscopic fat and soft tissue consistent with myelolipoma. A small uterus posterior to the bladder and presumed ovaries were also visualized with no visualization of prostate, spermatic cord or testicles. He reported a brother with a childhood hormone condition leading to an attempt to raise as female, resulting in subjective distress and unhappiness. Our patient never had breast development, menstrual cycles, or recurrent abdominal pain. There was no history of adrenal crisis, lightheadedness, or syncope and no hyperpigmentation on exam. He recalled salt craving as a child. Genital exam was refused by the patient. Labs demonstrated plasma cortisol 4.5 mcg/dl (6-18.4), ACTH 123 pg/ml (7-63), serum aldosterone 30 ng/dl (&amp;lt;=21), plasma renin activity 3.0 ng/ml/h (&amp;lt;=0.6-4.3), sodium 139 mEq/l (135-145) and potassium 4.2 mEq/l (3.5-5). The 17-hydroxyprogesterone concentration was 16,713 ng/dl (&amp;lt;=138), androstenedione was 36.52 ng/ml (0.33-1.34), and total testosterone was 621 ng/dl (male reference range 249-836). Based on the above findings and clinical history, his biologic sex was strongly felt to be female. A decision had to made regarding the need for glucocorticoid therapy and for possible adrenalectomy for the large myelolipoma. Because he had no symptoms of adrenal insufficiency and quite content with his gender identity, neither hormone therapy nor surgical intervention were performed. As of 8 months after presentation, he reported on going health and well-being. We recommended follow-up adrenal imaging and discussed glucocorticoid coverage for possible future stress conditions and educated him for this potential need. Discussion This case is unusual in that he was asymptomatic for adrenal insufficiency yet maintained male gender identity into adulthood. His adrenal myelolipoma likely developed from untreated CAH. We felt that treating with steroids and/or resecting his adrenal gland might well suppress ACTH and adrenal androgen production which would be detrimental to his gender identity and quality of life. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Serum concentrations of 17-hydroxyprogesterone and dehydroepiandrosterone sulfate in women with polycystic ovary syndrome and their relation to the parameters of glucose metabolism

Serum concentrations of 17-hydroxyprogesterone and dehydroepiandrosterone sulfate in women with polycystic ovary syndrome and their relation to the parameters of glucose metabolism

Twenty Years of Neonatal Screening for Congenital Adrenal Hyperplasia in North-Eastern Italy: Role of Liquid Chromatography-Tandem Mass Spectrometry as a Second-Tier Test

Background: Newborn screening for congenital adrenal hyperplasia (CAH) based on 17-hydroxyprogesterone (17-OHP) concentration in dried blood spots has been taking place in North-Eastern Italy since 2001. Since 2017, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been introduced, for the first time in Italy, as a second-tier test. Aims: Our study aims to evaluate, on the one hand, the effectiveness of the newborn screening for CAH after 20 years of testing and, on the other, the impact that the introduction of the second-tier test had on the diagnostic accuracy of the screening program. Methods: Since 2001 dried blood spots taken from newborns have been screened with a time-resolved fluoroimmunoassay for 17-OHP determination. Over the years, the cut-off levels of 17-OHP were adjusted according to gestational age. Since 2017, a second-tier test in LC-MS/MS was introduced for samples displaying fluoroimmunoassay 17-OHP exceeding the cut-off. Results: In total, 862,521 newborns have been screened over a period of 20 years. The total incidence of 21-hydroxylase deficiency (21-OHD) was 1:25,368, moreover, a case of 11-β-hydroxylase deficiency was identified. All these diagnoses were genetically confirmed. The sensitivity and specificity of the screening program were 97% and 99.4%, respectively. The use of LC-MS/MS as a second-tier test significantly reduced the recall rate and increased the positive predictive value. Conclusions: Screening for CAH is useful in the neonatal diagnosis of a classic form of 21-OHD, allowing a precocious treatment of affected children. The introduction of an LC-MS/MS second-tier reduced the recall rate, avoiding unnecessary blood withdrawal and medical evaluations and preventing stress to families. Furthermore, it helped identify rarer forms of CAH.

Abnormal Newborn Screen During a Pandemic.

Abnormal Newborn Screen During a Pandemic.

Plasma Steroid Profiling in Patients With Adrenal Incidentaloma.

Most patients with adrenal incidentaloma have nonfunctional lesions that do not require treatment, while others have functional or malignant tumors that require intervention. The plasma steroid metabolome may be useful to assess therapeutic need. This work aimed to establish the utility of plasma steroid profiling combined with metanephrines and adrenal tumor size for the differential diagnosis of patients with adrenal incidentaloma. This retrospective cross-sectional study, which took place at 7 European tertiary-care centers, comprised 577 patients with adrenal incidentaloma, including 19, 77, 65, 104 and 312 respective patients with adrenocortical carcinoma (ACC), pheochromocytoma (PHEO), primary aldosteronism (PA), autonomous cortisol secretion (ACS), and nonfunctional adrenal incidentaloma (NFAI). Mesaures of diagnostic performance were assessed (with [95% CIs]) for discriminating different subgroups of patients with adrenal incidentaloma. Patients with ACC were characterized by elevated plasma concentrations of 11-deoxycortisol, 11-deoxycorticosterone, 17-hydroxyprogesterone, androstenedione, and dehydroepiandrosterone-sulfate, whereas patients with PA had elevations of aldosterone, 18-oxocortisol, and 18-hydroxycortisol. A selection of those 8 steroids, combined with 3 others (cortisol, corticosterone, and dehydroepiandrosterone) and plasma metanephrines, proved optimal for identifying patients with ACC, PA, and PHEO at respective sensitivities of 83.3% (66.1%-100%), 90.8% (83.7%-97.8%), and 94.8% (89.8%-99.8%); and specificities of 98.0% (96.9%-99.2%), 92.0% (89.6%-94.3%), and 98.6% (97.6%-99.6%). With the addition of tumor size, discrimination improved further, particularly for ACC (100% [100%-100%] sensitivity, 99.5% [98.9%-100%] specificity). In contrast, discrimination of ACS and NFAI remained suboptimal (70%-71% sensitivity, 89%-90% specificity). Among patients with adrenal incidentaloma, the combination of plasma steroid metabolomics with routinely available plasma free metanephrines and data from imaging studies may facilitate the identification of almost all clinically relevant adrenal tumors.