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.

Supervisión del déficit de yodo en Salta Capital / Surveillance of iodine deficiency in Salta Capital

El déficit de yodo (IDD) es un problema de Salud Pública que afecta a millones de personas en todo el mundo causando alteraciones en la neuromaduración que pueden ser evitados si se realiza una yodoprofilaxis adecuada. Objetivo: Realizar un monitoreo de IDD en la localidad de Salta Capital, por su ubicación geográfica y hábitos alimentarios con posible consumo regional de sal no iodada. Material y métodos: En 442 escolares (221 mujeres) de 5 a 14 años de edad, se evaluaron: peso, SDS talla y, SDS BMI. Se realizó la palpación tiroidea y el volumen glandular fue clasificado según los criterios de la OMS. En 97 niños se determinó la yoduria en muestras casuales de orina por el método de Sandell y Kolthof modificado. Se analizó la distribución de los niveles de TSH de la pesquisa neonatal (IFMA-DELFIA) realizada en la región de los 18 meses previos al estudio Se aplicaron los criterios de suficiencia iodada establecidos por la OMS/ ICCDD Resultados: La prevalencia de bocio fue de 6.3 %. Los niveles de yoduria fueron: mediana de 127.5 ug/l con 20 % < 50 ug/l. Sólo el 1.6 % de las muestras de TSH neonatal fueron > 5 uU/ml. Cuando se aplicaron los criterios de la OMS la prevalencia de bocio superaba levemente lo esperado para una zona suficiente y los niveles de ioduria correspondían con un aporte iodado adecuado pero marginal en su distribución. La distribución de TSH fue la esperada para una zona suficiente. Conclusión: Si bien el aumento de la prevalencia de bocio podría explicarse por factores ambientales la distribución marginal de la ioduria señala un aporte de yodo suficiente pero con necesidad de supervisión estrecha.

The iodide deficit disorder (IDD) is a worldwide Public Health problem that affects more than a million subjects causing neuromadurative disorders that could be avoided with adequate iodide supply. Objective: To monitor IDD in Salta Capital, due to its geographic location and possible utilization of non iodated salt. Population and methods:. SDSHeight , SDS BMI and weight were assessed in 442 scholars (221 girls) aged 5 to 14. Thyroid volume was evaluated and classified according to WHO criteria. In 97 children iodide urinary concentration was measured in casual urine samples by the modified Sandell and Kolthof method.TSH level's distribution of the neonatal screening performed in the region 18 months prior to this study (n 310) was evaluated. Criteria suggested by WHO to indicate iodide deficiency were applied. Results: Goitre prevalence was 6.3%, Iodide urine median levels were 127.5 ug/l with 20% < 50 ug/l. Only 1.6% of the 310 TSH samples were > 5 μU/ml. Applying WHO criteria goiter prevalence was higher that expected for a iodide sufficient area and urine iodide content was normal but marginal in its distribution. Neonatal TSH levels were the expected for a sufficient area. Conclusion: Although high goiter prevalence could be explained by environmental factors the distribut-ion of urinary iodide points out an adequate but marginal iodide supply underscoring the need of close monitoring.

Neonatal screening program for congenital adrenal hyperplasia: adjustments to the recall protocol.

OBJECTIVE: To evaluate the influence of gestational age (GA) and birth weight (BW) on 17 alpha-OH-progesterone (17-OHP) levels with respect to their impact on the recall rate of neonatal screening programs for congenital adrenal hyperplasia (CAH). PATIENTS AND METHODS: In June 1997 we began a pilot screening program for CAH measuring 17-OHP using a fluoroimmunoassay method (DELFIA) on dried blood spots. Until September 1999, 24,153 babies were screened. Among them, we analyzed the levels of 17-OHP in 1,313 samples from healthy preterm babies (23-36 weeks) and 1,500 term babies (>37 weeks), grouped according to GA and BW. All preterm babies underwent another sampling in their 2nd week of life. RESULTS: 5 CAHs were detected. The 30-nmol/l cutoff limit for 17-OHP in blood corresponded to the calculated 99th percentile in term newborns, while in preterm babies higher levels were found. GA and BW correlated inversely with 17-OHP levels. CONCLUSION: GA and BW were useful tools to adjust cutoff levels, obtaining a significant reduction in follow-up testing and psychological stress for families. The high false-positive recall rate in preterm babies can be substantially lowered with adjusted GA and/or BW criteria.

Usefulness of thyroxine and free thyroxine filter paper measurements in neonatal screening for congenital hypothyroidism of preterm babies.

INTRODUCTION: Low thyroxine (T4) with normal thyroid stimulating hormone (TSH) is a well known condition in preterm (PT) infants. The establishment of T4 and freeT4 (FT4) values in filter paper dried blood spots in PT could provide useful information in the neonatal period. OBJECTIVE: To study T4 and FT4 levels in dried blood filter paper samples of PT and full term (FT) babies. METHODS: We measured T4 by fluoroimmunoassay (FIA) DELFIA and TSH by IFMA DELFIA (Wallac Inc Turku, Finland) in 193 PT (26 to 37 weeks of gestational age (GA)) in samples from the first and second week of life and in 153 FT babies in the first week of life. In 131 PT and 31 FT we determined FT4 in filter paper blood spots using FIA (Alonso Fernandez J). Infants were grouped according to GA. RESULTS: There was a significant difference in T4 between PT and FT (p < 0.001). The lowest T4 levels were at 26 to 29 weeks GA. T4 values were lower in the second week. FT4 in PT up to 35 weeks GA, during the first week, was significantly different with FT infants (G1 to G3 p < 0.01, G4 p < 0.05). FT4 values in the first and second weeks of life did not vary. CONCLUSIONS: T4 values were significantly lower in PT than in FT neonates, increasing with GA. PT infants had low T4 with normal FT4 values. This could suggest a decreased thyroxine binding globulin (TBG) or decreased protein binding and/or an adaptative mechanism that would not require therapeutical intervention.

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.

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.

Nocturnal TSH surge and TRH test response in the evaluation of thyroid axis in hypothalamic pituitary disorders in childhood.

We studied, by means of TSH nocturnal secretion and TRH test, 42 children (4.2-19.9 years) with hypothalamic pituitary disorders and 24 healthy euthyroid children (5.7-15.4 years) as control group. Patients were divided according to their serum values of FT4 in group 1 (n = 27) with FT4 >/=10.3 pmol/l and group 2 (n = 15) with FT4 <10.3 pmol/l. TSH was measured by immunoradiometric assay. TSH nadir, TSH peak and TSH surge were calculated. Both groups differed significantly from control group in TSH surge values: group 1 (p < 0. 05), group 2 (p < 0.01). TRH test was abnormal in 11/27 patients of group 1 and 10/15 patients of group 2. In group 1, 7 patients had normal tests, 2 had abnormalities in both tests, 9 had only TSH nocturnal surge altered and 9 showed only TRH alterations. All patients of group 2 presented thyroid axis abnormalities. In conclusion, in patients with hypothalamic pituitary disorders with low FT4, no further investigation is required to demonstrate thyroid axis alterations, however in patients with normal FT4, nocturnal TSH secretion and TRH test may be required to evidence thyroid abnormalities.

A new point mutation (M313T) in the thyroid hormone receptor beta gene in a patient with resistance to thyroid hormone.

Sequence analysis of the TR beta gene from a patient with the syndrome of resistance to thyroid hormone revealed a novel missense mutation in exon 9, changing thymidine in position 1123 to cytosine. The corresponding amino acid alteration is a substitution of a methionine (ATG) for a threonine (ACG) at codon 313 being the patient heterozygous for the mutation. In contrast, his parents had only the wild-type sequence, suggesting a de novo mutational event.

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.