Congenital adrenal hyperplasia and early newborn screening: 17 alpha-hydroxyprogesterone (17 alpha-OHP) during the first days of life.

OBJECTIVE: Definition of upper limits for 17 alpha-hydroxyprogesterone (17 alpha-OHP) is important as its measurement is used in screening for congenital adrenal hyperplasia. This study aimed at investigating the cut off concentrations in relation to the day of sample collection. METHODS: 17 alpha-OHP concentration was determined in dried filter paper blood spots taken from cord blood and by heel pricking up to the sixth day of life. A sensitive fluoroimmunoassay (DELFIA) method was used. Samples from 1091 apparently health full term neonates were tested. Samples were separated according to the age of sampling. RESULTS: The 17 alpha-OHP (nmol/l blood) (median and 97.5th centile) concentrations according to the age of sampling were: cord blood (n = 126) 123.7, 265.6; first day 0-6 hours (n = 30) 49.4, 80.3; 6-12 hours (n = 57) 42.7, 79.8; 12-18 hours (n = 58) 38.1, 62.7; 18-24 hours (n = 67) 28.8, 49.7; second day 24-36 hours (n = 51) 23.6, 43.3; 36-48 hours (n = 63) 19.9, 35.4; third day (n = 200) 10.6, 23.5; fourth day (n = 197) 8.8, 20.8; fifth day (n = 76) 6.4, 18.3; sixth day (n = 166) 6.6, 19.4. CONCLUSION: Cord 17 alpha-OHP concentrations were very high as previously described, probably owing to steroid production by fetal adrenal glands. Therefore, cord blood is not useful for screening purposes. Thereafter there is a gradual decline in 17 alpha-OHP median concentrations. A cut off value of 30 nmol/l blood was useful in samples obtained after 48 hours of life. However, cut off values before 48 hours should be adjusted according to the sampling time.

Final height in long-term primary hypothyroid children.

OBJECTIVE: We studied retrospectively the statural growth and bone maturation of 32 children with primary hypothyroidism in order to relate their final heights to their chronological ages, height deficits and bone ages at the beginning of treatment. Patients were grouped according to age when treatment was started: Group 1 (G1) (n = 17): (15 girls, 1 boy) 3.09 +/- 0.8 yr; Group 2 (G2) (n = 9): (7 girls, 2 boys) 9.1 +/- 1.2 yr, and Group 3 (G3) (n = 6): (5 girls, 1 boy) 13.58 +/- 1.13 yr. At diagnosis G1 and G2 were prepubertal and G3 children were in puberty. In 10 patients of G1, 7 of G2 and 6 (all) of G3 final height was compared with target height. RESULTS: (SDS) Initial height: G1: -3.74 +/- 1.2; G2: -3.94 +/- 1.32; G3 -3.65 +/- 1. Height at onset of puberty: G1: -1.06 +/- 1.1; G2: -2.5 +/- 1.4. Height menarche stage 5: G1: -0.63 +/- 1.1; G2: -1.76 +/- 1.2; G3: -2.6 +/- 1.7. Final height: (whole group) G1: -0.85 +/- 0.91; G2: -1.6 +/- 1.3; G3: -2 +/- 1.5. Final height G1 (n = 10): -1.05 +/- 0.89; G2 (n = 7) 1.2 +/- 1. Target height G1 (n = 10): -1.22 +/- 0.78; G2 (n = 7): -0.8 +/- 1.2; G3 (n = 6): -1.07 +/- 1.5. Initial bone age: G1: -4.9 +/- 0.85; G2: -7.2 +/- 2.6; G3: -4.5 +/- 1.9. Bone age (onset of puberty) G1: -0.26 +/- 1.74; G2: -2 +/- 1.7; Bone age (menarche) G1: 0.09 +/- 0.6; G2: -0.5 +/- 0.6; G3: -0.76 +/- 0.82. CONCLUSION: G1 and G2, prepubertal at diagnosis, reached a normal adult height with respect to target height; G3 did not, the difference being statistically significant (p < 0.04). Puberty plays a decisive role in the incomplete catch-up growth of longstanding hypothyroid patients.

Growth follow-up in 100 children with congenital hypothyroidism before and during treatment.

In order to assess the influence of age at onset of treatment on subsequent growth, height, weight, head circumference (HC) and bone age as estimated by Greulich-Pyle and TW2-RUS methods, 100 children with congenital hypothyroidism (CH) were studied before and during adequate treatment up to 5 years of age. The patients were divided into five groups according to age at the start of treatment: Group 1: < 2 months (n = 26); Group 2: 2-3 months (n = 13); Group 3: 3-6 months (n = 21); Group 4: 6-12 months (n = 20); Group 5: 12-24 months (n = 20). Before treatment, groups 1 and 2 differed significantly from the others in height (p < 0.001). With hormone therapy, catch-up growth was observed in groups 3 to 5, but at age 5 years no differences were found between groups. In all groups, height at 5 years of age correlated significantly with children's midparental height (p < 0.002). Bone age was initially retarded in groups 3 to 5, but approximated the chronological age by age 5 years. Initially, HC was less affected than height and remained relatively larger up to age 5 years in all groups. These findings show that thyroid hormone replacement in CH as late as 24 months corrects the short stature and delayed bone age by age 5 years.

La determinación de PTH intraquirúrgica o posquirúrgica por quimioluminiscencia predice la hipocalcemia en el posoperatorio de la tiroidectomía en niños / Determination of PTH during or post surgery for quimioluminiscency can predict hypocalcemy in the post surgery children´s thyroidectomy

Objetivo: Evaluar la eficacia diagnóstica de la determinación de PTH en muestras de plasma tomadas durante la cirugía (intra) y posquirúrgica inmediata para predecir el riesgo de desarrollar hipocalcemia en el postoperatorio de la tiroidectomía total en pacientes pediátricos. Métodos: Se llevó a cabo un estudio de cohortes,prospectivo, longitudinal con 20 pacientes pediátricos en los que se practicó tiroidectomía total. Se determinaron los niveles de PTH preoperatorios, intraoperatorios y en el período posquirúrgico inmediato (basal, 5 y 60 minutos de la remoción de la glándula tiroides) utilizando un ensayo automatizado quimioluminiscente (IMMULITE, Siemens), límite de cuantificación 8 pg/mL, CV intra e interensayos < 5,4%. Para este estudio, la concentración de PTH de cada paciente no fue conocida por el equipo tratante hasta el final del mismo. Además se determinó la concentración en suero de Calcio total (Ca T) y/o Calcio iónico (Cai) regularmente durante las 48 hs posquirúrgicas y se controló la presencia de síntomas o signos de hipocalcemia. Se consideró hipocalcemia Ca T < 8 mg/dl y/o Cai < 0,8 nmol/L. Se realizó un análisis por curva ROC para determinar el nivel de PTH que fuera más eficaz en predecir la aparición de hipocalcemia según su sensibilidad (S), especificidad (E), eficiencia diagnóstica (ED) y Valor Predictivo Positivo (VPP). Resultados: Diez de los 20 pacientes (50%) desarrollaron hipocalcemia y 3 de ellos presentaron síntomas. La presentación de hipocalcemia sucedió: 40% en las primeras 6 hs y 40% a las 24 hs.vel de PTH en la muestra intraoperatoria < 14 pg/ml mostró S: 80%, E: 100%, ED: 90% (IC95%: 73-100) y VPP: 100% para predecir hipocalcemia posquirúrgica. En la muestra posquirúrgica inmediata, la concentración de PTH < 14 pg/ml presentó S: 80%, E: 90%, ED 82% (IC95% 63-100) y VPP 90% para predecir hipocalcemia posquirúrgica. Cuando la PTH intraquirúrgica o posquirúrgica es <14 pg/ml el riesgo relativo de presentar hipocalcemia postiroidectomía es de 9. Conclusiones: La medición de PTH intraquirúrgica y posquirúrgica es una herramienta eficiente para predecir hipocalcemia posquirúrgica por tiroidectomía total en la población pediátrica. Esta detección permite la inmediata decisión sobre el tratamiento suplementario con calcio en los pacientes de riesgo mejorando su evolución y evitando la presentación de tetania y otros síntomas de hipocalcemia. Además, permitiría disminuir los controles en los pacientes que evolucionarán con normocalcemia, reduciendo en ambos grupos de pacientes los costos de internación.