Determinación de valores de corte de 17 hidroxiprogesterona ajustados por edad gestacional para la pesquisa neonatal de la hiperplasia suprarrenal congénita / Assessment of gestational age-adjusted 17-hydroxyprogesterone cut-off values for neonatal screening of congenital adrenal hyperplasia

La pesquisa neonatal de hiperplasia suprarrenal congénita se realiza mediante la determinación de 17 hidroxiprogesterona (17OHP) en gotas de sangre seca en papel de filtro. Los bebés prematuros presentan valores más elevados que los bebés de término, siendo de utilidad contar con límites de corte apropiados. Nuestro objetivo fue actualizar los valores de corte de 17OHP ajustados por edad gestacional para la metodología en uso a nivel nacional por las jurisdicciones asistidas por el "Programa Nacional de Fortalecimiento de la Detección Precoz de Enfermedades Congénitas". La 17OHP se determinó utilizando el kit comercial de enzimo-inmunoanálisis (ELISA competitivo), Elizen Neonatal 17OHP Screening (Zentech, Bélgica). Se obtuvieron límites de corte utilizando percentiles de la distribución de los valores de 17OHP para cada edad gestacional. La sensibilidad obtenida fue 100%, especificidad 98,76 %, tasa de falsos positivos 1,24 % y el valor predictivo positivo 1,12 %. Destacamos la importancia de disponer de límites de corte adecuados a la población. La armonización de los mismos permitirá resultados comparables entre los programas regionales de pesquisa neonatal (AU)

Newborn screening for congenital adrenal hyperplasia is performed by the measurement of 17-hydroxyprogesterone (17OHP) in dried blood spots on filter paper. Premature infants have higher values than full-term infants, and appropriate cutoff values are useful. Our aim was to update the cut-off values of 17OHP adjusted for gestational age for the methodology used at a national level in regions assisted by the "National Program for Strengthening the Early Detection of Congenital Diseases". 17OHP was determined using the commercial enzyme-linked immunosorbent assay (competitive ELISA) kit, Elizen Newborn 17OHP Screening (Zentech, Belgium). Cut-off values were obtained using percentiles of the distribution of 17OHP values for each gestational age. Sensitivity was 100%, specificity 98.76%, false positive rate 1.24%, and positive predictive value 1.12%. It is important to have cut-off values that are adjusted to the population. Harmonization will allow for the comparison of results among regional newborn screening programs (AU)

Polycystic ovary syndrome associated with increased adiposity interferes with serum levels of TNF-alpha and IL-6 differently from leptin and adiponectin

ABSTRACT Objective The aim of this study was to investigate polycystic ovary syndrome (PCOS) and to explore the relationship between body fat percentage and metabolic markers. Subjects and methods Sedentary women were assigned to PCOS (N = 60) and CONTROL (N = 60) groups. Each group was subdivided into three subgroups according to body fat percentage (22-27%, 27-32% and 32-37%). The protocol consisted of assessments of glucose, insulin, androgens, follicle stimulating hormone (FSH), luteinizing hormone (LH), 17-hydroxyprogesterone (17-OHP), leptin, adiponectin, tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). Results The PCOS subgroups showed higher concentrations of androgens, LH and 17-OHP. Leptin showed direct relationship with increased body fat percentage, whereas adiponectin showed the inverse effect. However, both were unaffected by PCOS. TNF-α and IL-6 were higher in PCOS women and showed a direct relationship with increased body fat percentage. Glucose showed direct relationship with body fat percentage, whereas insulin presented higher values in PCOS women and direct relationship with increased body fat percentage. Conclusions Our findings indicate that PCOS and body fat percentage directly influence concentrations of insulin, TNF-α and IL-6, whereas leptin and adiponectin are influenced only by the increase in body fat percentage in these women. Arch Endocrinol Metab. 2020;64(1):4-10

Clinical and molecular profile of newborns with confirmed or suspicious congenital adrenal hyperplasia detected after a public screening program implementation / Perfil clínico e molecular de recém-nascidos com suspeita ou confirmação de hiperplasia adrenal congênita após a implementação de um programa público de triagem neonatal

Abstract Objective: To describe the results obtained in a neonatal screening program after its implementation and to assess the clinical and molecular profiles of confirmed and suspicious congenital adrenal hyperplasia cases. Methods: A cross-sectional study was conducted. Newborns with suspected disease due to high 17-hydroxyprogesterone levels and adjusted for birth weight were selected. Classical congenital adrenal hyperplasia (salt-wasting and simple virilizing forms) was diagnosed by an increase in 17-hydroxyprogesterone levels as confirmed in the retest, clinical evaluation, and genotype determined by SNaPshot and multiplex ligation-dependent probe amplification. Results: After 24 months, 15 classic congenital adrenal hyperplasia cases were diagnosed in a total of 217,965 newborns, with an estimated incidence of 1:14,531. From 132 patients, seven non-classical and 14 heterozygous patients were screened for CYP21A2 mutations, and 96 patients presented false positives with wild type CYP21A2. On retest, increased 17-hydroxyprogesterone levels were found in classical congenital adrenal hyperplasia patients and showed significant correlation with genotype-related classical genital adrenal hyperplasia. The most frequent mutations were IVS2-13A/C>G followed by gene deletion or rearrangement events in the classical form. In non-classical and heterozygous diseases, p.Val282Leu was the most common mutation. Conclusions: The results underscore the effectiveness of congenital adrenal hyperplasia neonatal screening in the public health system and indicate that the adopted strategy was appropriate. The second sample collection along with genotyping of suspected cases helped to properly diagnose both severe and milder cases and delineate them from false positive patients.

Resumo Objetivo: Descrever os resultados obtidos em um programa de triagem neonatal após sua implementação e avaliar os perfis clínicos e moleculares de casos confirmados e suspeitos de hiperplasia adrenal congênita. Métodos: Foi feito um estudo transversal. Recém-nascidos com suspeita da doença devido aos altos níveis de 17-alfa-hidroxiprogesterona e ajustados pelo peso ao nascer foram selecionados. A hiperplasia adrenal congênita clássica (forma perdedora de sal e forma virilizante simples) foi diagnosticada por um aumento nos níveis de 17-alfa-hidroxiprogesterona confirmado no reteste, avaliação clínica e genótipo determinado com o uso do ensaio SNaPshot e amplificação multiplex de sondas dependente de ligação. Resultados: Após 24 meses, 15 casos clássicos de hiperplasia adrenal congênita foram diagnosticados em 217.965 recém-nascidos, com uma incidência estimada de 1:14.531. De 132 pacientes, sete não clássicos e 14 heterozigotos foram submetidos à triagem para mutações no gene CYP21A2 e 96 pacientes apresentaram resultados falso-positivos com CYP21A2 do tipo selvagem. No reteste, níveis aumentados de 17-alfa-hidroxiprogesterona foram encontrados em pacientes com hiperplasia adrenal congênita clássica e mostraram correlação significativa com HAC clássica relacionada ao genótipo. As mutações mais frequentes foram IVS2-13A/C>G, seguidas de deleção gênica ou eventos de rearranjo na forma clássica. Em casos de doenças não clássicas e heterozigose, a mutação p.Val282Leu foi a mais comum. Conclusões: Os resultados ressaltam a eficácia da triagem neonatal para a hiperplasia adrenal congênita no sistema público de saúde e indicam que a estratégia adotada foi adequada. A segunda coleta de amostras, juntamente com a genotipagem dos casos suspeitos, ajudou a diagnosticar adequadamente os casos graves e mais leves e diferenciá-los de pacientes com resultado falso-positivo.

17-hydroxiprogesterone values in healthy preterm infants / Valores de 17-hidroxiprogesterona en recién nacidos prematuros sanos

Abstract Introduction: In preterm newborn, problems with the interpretation of 17-OHP may occur. Objective: Evaluate 17-OHP values in healthy preterm newborns until they reach the corrected gestational age. Methods: Longitudinal study of 36 preterm infants with 17-OHP evaluation using ELISA from heel blood from 3 to 5 days and thereafter every 2 weeks until the corrected gestational age. Values adjusting multiple variables such as gestational age, birth weight and sex, among others were compared. The results were analyzed against 82 healthy full-term infants. Results: In the first week of life, early term infants born within less than 34 months of gestational age show 17-OHP values that are much higher than the full term neonates. After a week, the values decrease and stabilize, but are still higher than those of full term neonates and remain so even at the corrected gestational age. (average difference of 63.0%, CI 95%: 11.8%-115.5%). 33.6% (41 samples) of a total of 122 samples taken from preterm infants were higher than 30 ng/mL. Conclusions: 17-OHP values in early term infants are higher than those in full term neonates and can be related to postnatal adaptive processes. It is suggested that a second screening at the 37th week of corrected age be performed.

Resumen Introducción: En recién nacidos pretérmino se presentan problemas para interpretar la 17-OHP. Objetivo: Evaluar los valores de 17-OHP en recién nacidos sanos pretérmino hasta cuando alcanzan el término de edad gestacional corregida. Métodos: Estudio longitudinal de 36 prematuros con evaluación de la 17-OHP por ELISA en sangre de talón desde los 3-5 días de vida y luego cada dos semanas hasta la edad gestacional de término corregida. Se comparó los valores ajustando múltiples variables como edad gestacional, peso al nacer y sexo, entre otras. Se analizaron los resultados frente a los de 82 recién nacidos a término sanos. Resultados: En la primera semana de vida, los prematuros menores de 34 semanas de edad gestacional tienen valores de 17-OHP muy superiores a los neonatos de término. Al alcanzar la semana 34 de edad gestacional corregida, los valores descienden y se mantienen estables, siempre mayores a los de término, incluso al llegar a edad a término corregida (diferencia promedio de 63.0%, IC 95%: 11.8%-115.5%). El 33.6% (41 muestras) de un total de 122 muestras hechas en los prematuros eran mayores de 30 ng/mL. Conclusiones: Los valores de 17-OHP en recién nacidos pretérmino son más altos que en neonatos a término, pudiendo ser relacionado con los procesos adaptativos postnatales. Se sugiere realizar un segundo tamizaje al llegar a la semana 37 de edad corregida.

Puntos de corte de 17-hidroxiprogesterona en la detección de Hiperplasia Suprarrenal Congénita / Cut offs levels of 17-hydroxyprogesterone in screening of Congenital Adrenal Hyperplasia / Pontos de corte da 17-hidroxiprogesterona na detecção de Hiperplasia Adrenal Congênita

El presente estudio investiga la utilidad de determinar puntos de corte ajustados según la edad gestacional y el peso al nacer de neonatos (2-100 días) en la cuantificación de 17-hidroxiprogesterona en muestras de sangre seca en papel de filtro. Se analizaron los resultados de 6.266 determinaciones realizadas en el marco del Programa Nacional de Fortalecimiento de la Detección Precoz de Enfermedades Congénitas. Los datos se dividieron en cuatro grupos; Grupo 1: recién nacido pretérmino con bajo peso; Grupo 2: recién nacido pretérmino con peso normal; Grupo 3: recién nacido a término con bajo peso y Grupo 4: recién nacido a término con peso normal. Se establecieron puntos de corte diferentes a partir del cálculo del percentilo 99 de la distribución de frecuencias. Basado en este análisis se realizó la comparación de la tasa de resultados falsos positivos que se obtuvieron según el punto de corte establecido por el fabricante y los obtenidos en el estudio. Los nuevos puntos de corte obtenidos fueron: 217,72 nmol/L, 102,14 nmol/L, 61,62 nmol/L y 82,38 nmol/L para los grupos 1, 2, 3 y 4 respectivamente. Se evidenció una tasa total de falsos positivos del 1% con los nuevos puntos de corte, significativamente menor a la tasa del 6,2% obtenida al utilizar el punto de corte del fabricante. Esto puso en evidencia que el uso de puntos de corte adecuadamente establecidos para la población en estudio reduce significativamente las complicaciones derivadas de las repeticiones de análisis y eventualmente la tasa de recitaciones, lo cual es una importante contribución a la Salud Pública.

The present work studies the usefulness of determining adjusted cut-offs for the quantification of 17-hydroxyprogesterone in dried blood samples on filter paper, taking into account the gestational age and weight of the neonates. The results of 6266 determinations made within the framework of the National Program of Strengthening Early Detection of Congenital Disease were analysed. Data were divided into groups, Group 1: early established from the calculation of the 99 percentiles of the frequency distribution. New cutoff points were: 217.72 nmol/L, 102.14 nmol/L, 61.62 nmol/L and 82.38 nmol/L for groups 1, 2, 3 and 4 respectively. It showed a total rate of 1% false positives with the new cut-off points, which was significantly lower than the rate of 6.2% obtained using the manufacturer's cutoff. This revealed that the use of properly established cut-offs for the study of population reduces significantly the complications derived fromn analysis repetitions and eventually the recitation rate, which is an important contribution to Public Health.

O presente estudo investiga a utilidade de determinar pontos de corte estabelecidos conforme a idade gestacional e o peso ao nascer de neonatos (2-100 dias) na quantificação da 17-hidroxiprogesterona em amostras de sangue seco em papel filtro. Foram analisados os resultados de 6.266 determinações feitas no âmbito do Programa Nacional de Fortalecimento da Detecção Precoce de Doenças Congênitas. Os dados foram divididos em quatro grupos; Grupo 1: recém-nascido pré-termo com baixo peso, Grupo 2: recém-nascido pré-termo com peso normal, Grupo 3: recém-nascido a termo com baixo peso e Grupo 4: recém-nascido a termo com peso normal e foram estabelecidos pontos de corte diferentes a partir do cálculo do percentil 99 da distribuição de frequências. Com base nesta análise foi realizada a comparação da taxa de resultados falsos positivos obtidos conforme o ponto de corte estabelecido pelo fabricante e os obtidos no estudo. Os novos pontos de corte obtidos foram: 217,72 nmol/L, 102,14 nmol/L, 61,62 nmol/L e 82,38 nmol/L para os grupos 1, 2, 3 e 4, respectivamente. Tornou-se evidente uma taxa total de 1% de falsos positivos, com os novos pontos de corte significativamente menor do que a taxa de 6,2% obtida utilizando o ponto de corte do fabricante. Isto revelou que o uso de pontos de corte de forma adequada estabelecidos para a população em estudo reduz significativamente as complicações decorrentes das repetições de análises e eventualmente a taxa de repetição de novos encontros, o que é uma importante contribuição para a saúde pública.

Clinical Features of Congenital Adrenal Insufficiency Including Growth Patterns and Significance of ACTH Stimulation Test

Congenital adrenal insufficiency is caused by specific genetic mutations. Early suspicion and definite diagnosis are crucial because the disease can precipitate a life-threatening hypovolemic shock without prompt treatment. This study was designed to understand the clinical manifestations including growth patterns and to find the usefulness of ACTH stimulation test. Sixteen patients with confirmed genotyping were subdivided into three groups according to the genetic study results: congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH, n=11), congenital lipoid adrenal hyperplasia (n=3) and X-linked adrenal hypoplasia congenita (n=2). Bone age advancement was prominent in patients with CAH especially after 60 months of chronologic age (n=6, 67%). They were diagnosed in older ages in group with bone age advancement (P<0.05). Comorbid conditions such as obesity, mental retardation, and central precocious puberty were also prominent in this group. In conclusion, this study showed the importance of understanding the clinical symptoms as well as genetic analysis for early diagnosis and management of congenital adrenal insufficiency. ACTH stimulation test played an important role to support the diagnosis and serum 17-hydroxyprogesterone levels were significantly elevated in all of the CAH patients. The test will be important for monitoring growth and puberty during follow up of patients with congenital adrenal insufficiency.

A Case of Congenital Adrenal Hyperplasia Mimicking Cushing's Syndrome

Congenital adrenal hyperplasia (CAH) is characterized by decreased adrenal hormone production due to enzymatic defects and subsequent rise of adrenocorticotrophic hormone that stimulates the adrenal cortex to become hyperplastic, and sometimes tumorous. As the pathophysiology is basically a defect in the biosynthesis of cortisol, one may not consider CAH in patients with hypercortisolism. We report a case of a 41-yr-old man with a 4 cm-sized left adrenal tumorous lesion mimicking Cushing's syndrome who was diagnosed with CAH. He had central obesity and acanthosis nigricans involving the axillae together with elevated 24-hr urine cortisol level, supporting the diagnosis of Cushing's syndrome. However, the 24-hr urine cortisol was suppressed by 95% with the low dose dexamethasone suppression test. CAH was suspected based on the history of precocious puberty, short stature and a profound suppression of cortisol production by dexamethasone. CAH was confirmed by a remarkably increased level of serum 17-hydroxyprogesterone level. Gene mutation analysis revealed a compound heterozygote mutation of CYP21A2 (I173N and R357W).

Metformin therapy decreases hyperandrogenism and ovarian volume in women with polycystic ovary syndrome

It is well known that there is a close relationship between elevated androgen plasma levels and the ultrasound findings of stromal hypertrophy in polycystic ovary syndrome [PCOS]. The objective of this study was to investigate the effects metformin on the hyperandrogenism and ovarian volume in PCOS. The study is an unrandomized clinical trial with before-after design. Twenty eight patients with infertility [male or female factor] meeting the Rotterdam ESHRE/ASRM criteria for PCOS were studied during the 2008-2009. The anthropometric characteristics of the patients, mean bilateral ovarian volume, and morphology by trans vaginal sonography as well as the plasma levels of leutinizing hormone, follicle stimulating hormone, estradiol, testosterone, 17- alpha -hydroxyprogesterone, and dehydroepianderosterone sulfate were obtained before and after treatment with metformin [500 mg three times a day] for three months. Paired t, Pearson's Correlation Coefficient, or Partial Correlation test was used to analyze the findings. The patients had a mean age of 25.67 years. A significant reduction in mean ovarian volume [11.70 +/- 4.31 ml vs 8.27 +/- 3.71 ml P=0.001], body mass index [BMI, 28.11 +/- 4.55 kg/m[2] vs 26.84 +/- 4.55 kg/m[2] P=0.000] and serum androgen levels was seen after three months of treatment with metformin. There was positive correlations between the ovarian volume and serum testosterone level [r=0.589, P=0.001] or BMI [r=0.663, P=0.000]. Metformin therapy may lead to a reduction in ovarian volume. It is likely that the reduction of ovarian volume reflect a decrease in the mass of androgen producing tissues

Relationships of Basal Level of Serum 17-Hydroxyprogesterone with that of Serum Androstenedione and Their Stimulated Responses to a Low Dose of ACTH in Young Adult Patients with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

A single measurement of serum 17alpha-hydroxyprogesterone (17OHP) level can be unreliable because of its marked diurnal variation. We investigated the relationship of serum level of 17OHP 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 17OHP and AD levels were measured in 87 patients and a low-dose ACTH stimulation test was performed in 41 patients. The basal 17OHP 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, R2 = 0.75, P < 0.001). The area under the curve of 17OHP and AD correlated positively with their respective basal levels. The fold-change increase in 17OHP after ACTH injection correlated negatively with the basal 17OHP level, but that of AD did not correlate with the basal AD level. The random serum 17OHP 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.

frequency of 21-alpha hydroxylase enzyme deficiency and related sex hormones in Iraqi healthy male subjects versus patients with acne vulgaris

To find out the frequency of nonclassical congenital adrenal hyperplasia [CAH] due to 21-hydroxylase deficiency among Iraqi healthy male individuals versus male patients with acne vulgaris. This case-control study and single-center examination of hormone levels in a cohort of volunteers was conducted in the Department of Dermatology, Baghdad Teaching Hospital, and in the Physiological Chemistry Department of the College of Medicine, Baghdad University, Baghdad, Iraq, from September 2007 to February 2008. The frequency of 21-hydroxylase enzyme deficiency in healthy male subjects was 1:43 [2.3%], while in male patients with acne vulgaris, this was 6:43 [13.95%]. Serum 17-hydroxyprogesterone [OHP] levels were statistically and significantly elevated in male patients with acne vulgaris compared with healthy male controls [p=0.020]. The serum total cortisol level was significantly reduced in patients with acne vulgaris in comparison with that of healthy controls [p=0.022]. These results support the necessity of inclusion of the 21-alpha hydroxylase enzyme activity [serum 17-OHP level] screening test in acne patients

Monitoring congenital adrenal hyperplasia using blood spot 17-hydroxyprogesterone assay.

Blood spots taken by finger prick collected on filter paper cards can provide an option to venous blood extraction in monitoring 17-OHP levels in children with Congenital Adrenal Hyperplasia (CAH). This study was done to evaluate the usefulness of blood spot 17-OHP in monitoring disease control in pre-pubertal children with CAH, to correlate it with simultaneously extracted venous 17-OHP levels, and to compare blood spot levels of children with CAH with that of normal non-virilized children. Nine pre-pubertal children with CAH (1 male; 8 females) were enrolled in the study. Age, sex, growth velocity, height age and bone age were determined. Simultaneous venous and blood spot specimens were taken between 0800 and 0900 hours. Nine pre-pubertal, age- and sex-matched normal non-virilized children served as controls. COAT-A-COUNT was used to measure venous 17-OHP levels, and AutoDELFIA Neonatal 17alpha-OH-progesterone was employed for blood spot specimens. Mean age of patients with CAH was 42.78 months (SD= 21.45214). Four had simple virilizing form and five were salt-losers. Venous 17-OHP levels ranged from 7.5 to 800nmol/l. Blood spot 17-OHP levels ranged from < or =0.5000nmol/l to 355.5nmol/l. There was a strong positive correlation between the venous and blood spot determination, with a correlation coefficient gamma= 0.947 (p < 0.001). All of the children in the control group had a blood spot 17-OHP level < or =0.5000nmol/l. Taking blood spot 17-hydroxyprogesterone levels is a simple, acceptable, convenient, and less costly alternative to venous 17-OHP determination in monitoring treatment response of children with CAH. The decision to make treatment modification, however, should be made on random blood spot 17-OHP interpretation in conjunction with clinical history and evaluation of growth parameters.

Medición de 17-OH progesterona sanguínea en recién nacidos chilenos: antecedentes para implementar un programa de detección neonatal de hiperplasia suprarrenal congénita / 17 OH progesterone measurement in blood of chilean newborns: as a background to start a congenital adrenal hyperplasia screening program

Background: The early diagnosis and therapy of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency can prevent adrenal crises and erroneous gender assignment in affected newborns. To achieve this goal neonatal mass-screening programs have been developed, measuring blood 17 alpha-hydroxyprogesterone (17OHP). In Chile there is no experience with this type of screening. Aim: To develop a method for measuring 17OHP in filter paper blood specimens. To obtain reference ranges and determine neonatal 17OHP threshold levels according to gestational age and birth weight. To analyze factors affecting the cost-efficiency ratio and suggest recommendations for the organization of a neonatal screening program for CAH in Chile. Material and methods: Nine hundred twenty two newborns were studied. 17OHP was measured using double antibody radioimmunoassay in filter paper blood samples obtained 48 h after birth. Reference ranges were determined according to gestational age and birth weight and a cutoff point of 25 ng/ml was established. Results: Seventeen newborns had 17OHP over the cutoff value. They were assessed by a pediatric endocrinologist and in none of them, CAH was confirmed. Therefore the false positive rate of the determination was 1.8 percent. Among these newborns with elevated 17OHP, 66 percent had a birth weight below 1.5 kg and 5.8 percent, a birth weight between 1.5 and 2.5 kg. The cost per reported result was US $ l. Timing of the recall was between the 3 and 10 days of life. No newborn missed the follow-up. Discussion: To increase the cost-efficiency ratio of an eventual neonatal screening program, newborns with birth weights below 1.5 kg should be excluded and cutoff points should be defined according to birth weight

Screening and diagnosis of congenital adrenal hyperplasia in Basilicata (Italy).

Research of the frequency of 21-OH enzyme deficiency, autosomal recessive disease, caused by aberrations in the short arm of chromosome 6 was performed in order to prevent CAH (Congenital Adrenal Hyperplasia) manifested by: 1) possible cerebral damage 2) errors of sex attribution 3) behavioral hyperandrogenism 4) metabolic damage. Radioimmunoassay was used where there is competition between a radioactive and a non-radioactive antigens for a fixed number of antibody binding sites. In an 18 month period of screening 6,000 newborns we found one positive case of CAH which we confirmed by dosaging steroids such as, 4-androstenedione, testosterone, ACTH, PRA and electrolytic activity on the serum. We ascertained that an incidence of 1:6,000 in a 18 month period is high enough to deserve attention.

Newborn screening for congenital adrenal hyperplasia in Sapporo City: sixteen years experience.

A screening program for congenital adrenal hyperplasia (CAH) in Sapporo began in 1982, 7 years prior to the introduction of the national program. Since its inception, testing has involved the detection of 17-hydroxyprogesterone (17-OHP) in dried blood samples, using ELISA. Up to the end of March 1998, of 298,731 newborn screened, second samples were requested in 1,723 cases (0.6%). This number included 789 newborns who weighed less than 2,000 gm at birth. A total of 14 cases were diagnosed with 21-hydroxylase deficiency (21-OHD). "Salt-wasting type (SW)" outnumbered "simple virilizing type (SV)" by 11:3. The ratio of male to female was a converse. but unrelated, 3:11. Our study from 1982-1997 revealed that the incidence of 21-OHD in Sapporo City was 1:21.338, markedly similar to the worldwide incidence of 1:15,000. In order to improve the program, other type of analysis are also currently in use and under evaluation. These include highly sensitive HPLC analysis for 17-OHP and molecular analysis to identify some mutations associated with the 21-OHD gene (CYP21). These methodologies are very useful for the confirmation of information acquired from dried blood specimens.

Effect of gender, birth weight and gestational age on serum 17-hydroxyprogesterone concentration and distribution among neonates in Saudi Arabia.

Blood samples from 813 newborns were spotted on to filter paper and the 17-hydroxyprogesterone concentration was measured using the Delfia (R) fluorometric immunoassay. The median, mean, and standard deviation (SD) for the total population were 20, 21 and (11) nmol/L respectively. Males had significantly higher levels than females with median, mean and (SD) of 22, 22 and (12) nmol/L. Similarly, low birth weight babies were found to have significantly higher levels than normal birth weight babies with median, mean and (SD) of 21, 24 (12) nmol/L. Preterm babies were also found to have significantly higher levels than full term babies, with median, mean and (SD) of 25, 29 (16) nmol/L. As experienced elsewhere, those factors should be taken into consideration when considering a cut-off point in any neonatal screening program for congenital adrenal hyperplasia.