Abstract #810984: Discordant Serum 17-Hydroxyprogesterone and Androstenedione in the Management of Congenital Adrenal Hyperplasia: Are 11-Oxygenated-Androgens Useful?

Objective. To compare 17-hydroxyprogesterone (17-OHP) levels measured by quantitative serum radioimmunoassay (RIA), including an extraction step, and by screening fluoroimmnoassay (FIA) on blood spots in preterm infants. Methods. Subjects were 39 healthy infants born at less than 31 weeks' gestational age. Each infant had weekly blood sampling, and RIA and FIA were performed on each sample. Results. Two hundred twenty-seven samples were taken at 28 to 41 weeks' postconceptional age. Mean ± SD 17-OHP measured by RIA was 11.4 ± 11.1 nmol/L (0.4 ± 0.4 µg/dL), and decreased over time. Mean ± SD 17-OHP measured by FIA was 38.96 ± 37.3 nmol/L, greater than 17-OHP (RIA). Log(δFIA-RIA) was inversely related to postconceptional age (R2 = .39). Conclusion. Screening FIA of blood spots overestimates levels of 17-OHP in preterm infants and should not be used to determine the likelthood of congenital adrenal hyperplasia in this population. We have abandoned FIA screening for congenital adrenal hyperplasia in infants weiging less than 1500 g.

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Wisconsin’s Screening Algorithm for the Identification of Newborns with Congenital Adrenal Hyperplasia

International Journal of Neonatal Screening ◽

10.3390/ijns5030033 ◽

2019 ◽

Vol 5 (3) ◽

pp. 33 ◽

Cited By ~ 5

Author(s):

Eric R. Bialk ◽

Michael R. Lasarev ◽

Patrice K. Held

Keyword(s):

Birth Weight ◽

Congenital Adrenal Hyperplasia ◽

False Positive ◽

False Positive Rate ◽

Cross Reactivity ◽

Adrenal Hyperplasia ◽

Screening Assay ◽

Study Results ◽

Second Tier ◽

17 Hydroxyprogesterone

Newborn screening for congenital adrenal hyperplasia (CAH) has one of the highest false positive rates of any of the diseases on the Wisconsin panel. This is largely due to the first-tier immune assay cross-reactivity and physiological changes in the concentration of 17-hydroxyprogesterone during the first few days of life. To improve screening for CAH, Wisconsin developed a second-tier assay to quantify four different steroids (17-hydroxyprogesterone, 21-deoxycortisol, androstenedione, and cortisol) by liquid chromatography–tandem mass spectrometry (LC–MSMS) in dried blood spots. From validation studies which included the testing of confirmed CAH patients, Wisconsin established its own reporting algorithm that incorporates steroid concentrations as well as two different ratios—the birth weight and the collection time—to identify babies at risk for CAH. Using the newly developed method and algorithm, the false positive rate for the CAH screening was reduced by 95%. Patients with both classical forms of CAH, salt-wasting and simple virilizing, were identified. This study replicates and expands upon previous work to develop a second-tier LC–MSMS steroid profiling screening assay for CAH. The validation and prospective study results provide evidence for an extensive reporting algorithm that incorporates multiple steroids, birth weight, and collection times.

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ENERGY EXPENDITURE IN 21-HYDROXYLASE CONGENITAL ADRENAL HYPERPLASIA PATIENTS AND COMPARISON WITH PREDICTIVE EQUATIONS

Endocrine Practice ◽

10.4158/ep-2019-0390 ◽

2020 ◽

Vol 26 (4) ◽

pp. 388-398

Author(s):

Daniel Minutti de Oliveira ◽

Ana Carolina Junqueira Vasques ◽

Ezequiel Moreira Gonçalves ◽

Sofia Helena Valente de Lemos-Marini ◽

Gil Guerra-Junior ◽

...

Keyword(s):

Body Mass Index ◽

Body Weight ◽

Energy Expenditure ◽

Congenital Adrenal Hyperplasia ◽

Body Mass ◽

Indirect Calorimetry ◽

Resting Energy Expenditure ◽

Adrenal Hyperplasia ◽

Predictive Equations ◽

17 Hydroxyprogesterone

Objective: To characterize resting energy expenditure (REE) in patients with classic 21-hydroxylase congenital adrenal hyperplasia (21-OH CAH) using indirect calorimetry and compare it to the most commonly used REE predictive equations. Methods: This case-control study comprised 29 post-pubertal 21-OH CAH patients regularly followed at the University of Campinas. Elevated serum 17-hydroxyprogesterone and CYP21 gene molecular analysis confirmed the diagnosis. A healthy control group paired by age, gender, and body mass index was examined. Dual-energy X-ray absorptiometry (DEXA) measured body compositions. A bioimpedance analyzer determined fat-free mass, and indirect calorimetry using a metabolic cart measured REE. Results: Unlike our initial hypothesis, REE was similar between the groups (18.7 ± 3.1 kcal/kg/day in CAH vs. 20.3 ± 3.5 kcal/kg/day in controls; P = .728). No predictive equations reached the stipulated accuracy criteria, thus lacking validity in REE assessment in adults with the characteristics of the group studied. DEXA analysis revealed higher body fat and diminished nonbone lean mass in 21-OH CAH. Anthropometric and bioelectrical impedance parameters were not significantly different. Conclusion: Classic 21-OH CAH is generally followed in reference centers, which may facilitate indirect calorimetry use for REE measurement. Alternatively, considering our REE findings in adult 21-OH CAH patients, nutrition management based on 25 kcal/body weight/day (measured REE × activity factor 1.2 to 1.3) may be reasonable for current body weight maintenance in these patients. Abbreviations: 17-OHP = 17-hydroxyprogesterone; 21-OH CAH = classic 21-hydroxylase deficiency congenital adrenal hyperplasia; BMI = body mass index; REE = resting energy expenditure; VO2 = volume of oxygen; VCO2 = volume of carbon dioxide

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High frequency of non-classical congenital adrenal hyperplasia form among children with persistently elevated levels of 17-hydroxyprogesterone after newborn screening

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2018-0398 ◽

2019 ◽

Vol 32 (5) ◽

pp. 499-504

Author(s):

Patrícia S. Castro ◽

Tatiana O. Rassi ◽

Raquel F. Araujo ◽

Isabela L. Pezzuti ◽

Andresa S. Rodrigues ◽

...

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Newborn Screening ◽

Molecular Analysis ◽

High Frequency ◽

Clinical Status ◽

Confirmatory Test ◽

Adrenal Hyperplasia ◽

Asymptomatic Children ◽

17 Hydroxyprogesterone

Abstract Background Early diagnosis after newborn screening (NBS) for congenital adrenal hyperplasia (CAH) allows proper treatment, reducing mortality rates and preventing development of hyperandrogenic manifestations and incorrect sex assignment at birth. Despite the high NBS sensitivity to detect CAH classical forms, one of the main issues is identifying asymptomatic children who remained with increased 17-hydroxyprogesterone (17-OHP) levels. In this study, we aimed to contribute to understanding the diagnosis of these children. Methods Children with increased serum 17-OHP levels, and without disease-related clinical features during follow-up, underwent the entire CYP21A2 gene sequencing and multiplex ligation-dependent probe amplification (MLPA) analysis (SALSA MLPA P050B CAH). Patients’ genotypes were subsequently sorted as compatible with CAH disease, and children were evaluated to determine the clinical status. Results During the study period, 106,476 newborns underwent CAH NBS. During follow-up, 328 children (0.3%) were identified as having false-positive tests and 295 were discharged after presenting with 17-OHP levels within reference values. Thirty-three remained asymptomatic and with increased serum 17-OHP levels after a mean follow-up of 3.4 years, and were subjected to molecular analysis. Seventeen out of the 33 children carried mutations: seven in the heterozygous state, nine carried non-classical genotypes and the remaining child carried a classical genotype. Conclusions We found a high frequency of non-classical CAH (NCCAH) diagnosis among children with persistent elevation of 17-OHP levels. Our findings support molecular study as decisive for elucidating diagnosis in these asymptomatic children. Molecular analysis as a confirmatory test is relevant to guide their follow-up, allows genetic counseling and avoids over treating NCCAH form.

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