Regulación de las concentraciones intratisulares y la producción de andrógenos en testículo humano y de rata

Objetivos del trabajo: - Establecer las concentraciones intratisulares de andrógenos y cinc en tejido testicular y epididimario humano y estudiar las modificaciones en el eje hipófiso-gonadal luego de la inducción de la. hipoprolactinemia. - Analizar la posible participación de la PRL en la función testicular durante la maduración sexual de la rata.Tesis digitalizada en SEDICI gracias a la Biblioteca Central de la Facultad de Ciencias Exactas (UNLP).Facultad de Ciencias Exacta

Thyrotropin and thyroid hormone levels in chronic renal patients under hemodyalisis

Las enfermedades críticas presentan cambios en el eje hipotálamo-hipófiso-tiroideo que dependen de la patología y de la gravedad de la misma. La Insuficiencia Renal Crónica es una patología grave con un alto índice de morbimortalidad. El objetivo del presente trabajo fue evaluar las hormonas del eje tiroideo en pacientes renales crónicos en hemodiálisis (HD) y su utilidad como pronosticadores de morbilidad. Se estudiaron pacientes renales crónicos de un Servicio de nefrología y hemodiálisis y se comparó con un grupo control (CT) sin enfermedad renal y/o tiroidea. Se monitoreó al enfermo pre (pre-DL) y posdiálisis (pos-DL), se realizó un seguimiento durante un año y se lo agrupó según el tiempo de permanencia bajo HD. Se evaluaron concentraciones de tirotrofina (TSH), triiodotironina (T3), tiroxina (T4) y tiroxina libre (T4L) y parámetros bioquímicos sensibles al estado del paciente: urea, creatinina, albúmina y proteínas totales. Las muestras pre-DL evidenciaron un aumento significativo en los niveles de TSH (p<0.05), con un descenso también significativo de T3 y de T4 y T4L aunque de menor magnitud (p<0.05) con respecto al CT. En el procedimiento de diálisis se observó una fluctuación transitoria de los niveles de las hormonas tiroideas (p<0.05), con una concentración máxima en la muestra pos-DL y mínima en la pre-DL, sin modificación en TSH. Durante el seguimiento de los pacientes detectamos una tendencia descendente de T3. Además, se constató un aumento de TSH y una disminución de T3 (p<0.05) en pacientes con mayor tiempo de permanencia en HD. Además, comprobamos una correlación directa entre TSH y urea e inversa entre TSH y albúmina, y correlaciones inversa entre T3 y urea y directa entre T3 y albúmina. Nuestro estudio muestra las modificaciones hormonales en el eje tiroideo debido a la enfermedad y al procedimiento de diálisis y la posible utilidad de T3 como otro indicador de morbilidad en estos pacientes.Severe illness induces various hormonal changes in the hypothalamic-pituitary-thyroid axis. Chronic renal failure is a serious condition showing a high mortality index. The aim of this work was to evaluate thyroid hormone level in chronic renal patients under hemodialysis in order to estimate its potential use as morbidity / mortality indicator. We studied chronic renal patients from Nephrology and Hemodialysis Units of our Hospital and compared them with a control group (CT) without renal or thyroid pathology. We evaluated patients before (pre-dialysis) and after dialysis (post-dialysis) during one year. We then classified patients according to the duration of their hemodialysis treatment. We assessed Thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4) and free thyroxine (T4L) levels and other biochemical indicators: urea, creatinine, albumin, and total protein. Pre-dialysis samples showed higher TSH levels (p<0.05), a significant decrease in T3, and a lower decrease in T4 and T4L than CT. During the dialysis procedure, we observed a fluctuation in thyroid hormone levels (p<0.05), higher in post-dialysis samples, and no changes in TSH levels. The one- year follow- up showed a low decrease in T3 levels in pre- and post-dialysis samples. An increase in TSH levels and a decrease in T3 levels (p<0.05) was observed in patients after long hemodialysis treatment. Renal patients showed a direct correlation between TSH and urea and inverse correlation between TSH and albumin. However, an inverse correlation between T3 and urea and a direct correlation between T3 and albumin was observed. This study shows that thyroid-hormonal changes are induced by pathology and dialysis treatment. We suggest T3 measurement as a useful morbidity indicator for chronic renal patients.Facultad de Ciencias ExactasInstituto Multidisciplinario de Biología Celula

Correlation between inhibin secretion and damage of seminiferous tubules in a model of experimental autoimmune orchitis

The aim of the present study was to evaluate inhibin secretion in rats with autoimmune orchitis. As we have previously described, experimental autoimmune orchitis (EAO) induced in rats by active immunization with testis homogenate and adjuvants is characterized by an interstitial mononuclear cell infiltrate and sloughing of the germinal epithelium. At 120 days after the first immunization 60% of the rats exhibited a severe orchitis with large areas of aspermatogenic seminiferous tubules in which only spermatogonia and Sertoli cells with cytoplasmic vacuolization remained attached to the tubular wall. None of the untreated (N) or control (C) rats revealed pathological alterations. Sixty percent decrease in testis weight was observed in rats with EAO compared with N or C groups. A 3-fold increase in serum FSH levels was observed in rats with EAO compared with N or C groups (19·8 ± 3·7 vs 5·6 ± 0·3 and 5·9 ± 0·1 ng/ml respectively). A significant decrease in inhibin B levels was observed in rats with EAO when compared with N or C groups (40 ± 4·6 vs 207 ± 38·8 and 221·4 ± 28·6 pg/ml respectively). An inverse correlation between inhibin B and FSH serum levels and a direct correlation between inhibin B and testis weight were found. Strong expression of the inhibin α-subunit in Sertoli cells of untreated and control rats was observed; this subunit was undetectable or poorly detectable in rats with orchitis. Positive staining for the inhibin α-subunit was also observed in Leydig cells of all groups studied. In conclusion, using a model of autoimmune orchitis our results show that circulating inhibin B levels and inhibin α-subunit expression in Sertoli cell cytoplasm closely correlate with the degree of damage of the germinal epithelium.Instituto Multidisciplinario de Biología CelularFacultad de Ciencias Exacta

Involvement of tumor necrosis factor-α in the pathogenesis of autoimmune orchitis in rats

We studied the testicular macrophages of rats with experimental autoimmune orchitis (EAO) and analyzed whether the tumor necrosis factor-α (TNFα) is involved in germ cell apoptosis and in Leydig cell steroidogenesis. The EAO was induced in adult male Sprague-Dawley rats by active immunization with testicular homogenate and adjuvants. In the experimental group, a severe orchitis was observed 80 days after the first immunization. ED1- and ED2-positive macrophages were quantified by immunohistochemistry. The TNFα concentration of conditioned media from testicular macrophages (TMCM) was determined by ELISA. The number of apoptotic TNF receptor 1 (TNFR1)-positive germ cells was identified by combining in situ end labeling of apoptotic DNA and immunohistochemical techniques. The effect of TNFα on Leydig cell testosterone production was determined by RIA. In rats with EAO, we observed a significant increase in the number of TNFα-positive testicular macrophages, the TNFα concentration in TMCM, and the number of TNFR1-positive germ cells. Sixty percent of TNFR1-positive germ cells were apoptotic. These results suggest that TNFα could be involved in the pathogenesis of EAO. Acting together with other local factors such as Fas-FasL, TNFα could trigger germ cell apoptosis. We also demonstrated that TNFα inhibited in vitro testosterone production in basal and hCG-stimulated Leydig cells from rats with orchitis.Facultad de Ciencias Exacta

Involvement of tumor necrosis factor-α in the pathogenesis of autoimmune orchitis in rats

We studied the testicular macrophages of rats with experimental autoimmune orchitis (EAO) and analyzed whether the tumor necrosis factor-α (TNFα) is involved in germ cell apoptosis and in Leydig cell steroidogenesis. The EAO was induced in adult male Sprague-Dawley rats by active immunization with testicular homogenate and adjuvants. In the experimental group, a severe orchitis was observed 80 days after the first immunization. ED1- and ED2-positive macrophages were quantified by immunohistochemistry. The TNFα concentration of conditioned media from testicular macrophages (TMCM) was determined by ELISA. The number of apoptotic TNF receptor 1 (TNFR1)-positive germ cells was identified by combining in situ end labeling of apoptotic DNA and immunohistochemical techniques. The effect of TNFα on Leydig cell testosterone production was determined by RIA. In rats with EAO, we observed a significant increase in the number of TNFα-positive testicular macrophages, the TNFα concentration in TMCM, and the number of TNFR1-positive germ cells. Sixty percent of TNFR1-positive germ cells were apoptotic. These results suggest that TNFα could be involved in the pathogenesis of EAO. Acting together with other local factors such as Fas-FasL, TNFα could trigger germ cell apoptosis. We also demonstrated that TNFα inhibited in vitro testosterone production in basal and hCG-stimulated Leydig cells from rats with orchitis.Facultad de Ciencias Exacta

Hipertensão gestacional e resistência à insulina: Estudo preliminar numa amostra do Município de La Plata

Las mujeres embarazadas con insulino-sensibilidad disminuida están en riesgo de desarrollar trastornos hipertensivos. Utilizando el corte HOMAIR en 2,64 la población en estudio fue dividida en dos grupos: (n=154 mujeres embarazadas), las que arrojaron un HOMA-IR basal (HOMA-0) 2,64 (insulinorresistentes, n=41). Se analizaron: a) las concentraciones circulantes de glucosa e insulina durante una prueba de tolerancia oral a 75 g de glucosa (PTOG), y b) las relaciones entre varios parámetros de insulino-sensibilidad y la predicción del desarrollo de trastornos hipertensivos. A las mujeres embarazadas (semana 24-28) se les cuantificaron las concentraciones plasmáticas de glucosa e insulina a ambos tiempos de la PTOG. Se calcularon los valores de HOMA-IR y las relaciones glucosa a insulina (G:I) y se registraron parámetros antropométricos y resultados del embarazo. Las mujeres con HOMA-0 >2,64, aunque con glucemias en ayunas normales, mostraron mayores niveles de insulinemia y de HOMA-IR, y menores valores G:I en ambos tiempos de la PTOG. Estas mujeres embarazadas fueron las que tuvieron un mayor riesgo de desarrollar trastornos hipertensivos y mayores parámetros de morbilidad durante el período estudiado al compararlas con aquellas cuyo HOMA-0 fue 2.64 (insulin resistant; n=41). Glucose and insulin circulating levels were analyzed throughout a 2-h oral 75 g glucose tolerance test (OGTT). The relationship between several parameters related to insulin resistance and the prevalence of pregnancy-induced hypertensive disorders was analyzed. Pregnant women (on week 24-28) were submitted to an OGTT, and glucose and insulin plasma concentrations were measured throughout the test. These peripheral metabolites levels and the values of the HOMA-IR and the glucose to insulin ratio (G:I) were analyzed. Anthropometric parameters and pregnancy outcome were recorded. Women with HOMA-0 >2.64 but normal fasting glycemia showed higher insulinemias, G:I values and HOMA-IR values at both times of the OGTT. The latter were at greater risk for developing late pregnancy-induced hypertension compared to women with HOMA-0 ≤2.64.As mulheres grávidas com diminuição da sensibilidade à insulina correm o risco de desenvolver distúrbios hipertensivos. Usando o corte HOMA-IR 2,64, a população em estudo foi dividida em dois grupos: (n=154 mulheres grávidas), que deram um HOMA-IR basal (HOMA-0) ≤2,64 (não resistentes à insulina; n=113) e aquelas com HOMA-0 >2,64 (resistentes à insulina, n=41). Foram analisadas: a) as concentrações circulantes de glicose e insulina durante uma prova de tolerância oral a 75 g. de glicose (PTOG), e b) as relações entre diversos parâmetros de sensibilidade à insulina e a predição de desenvolver distúrbios de hipertensão. Foram quantificadas nas mulheres grávidas (24-28 semanas) as concentrações plasmáticas de glicose e insulina a ambos os tempos da PTOG. Valores de HOMA-IR foram calculados e as relações glicose a insulina (G:I) e se registraram parâmetros antropométricos e os resultados da gravidez. Mulheres com HOMA-0 >2,64, mas com glicemias em jejuns normais, mostraram níveis mais elevados de insulinemia e de HOMA-IR, e menores valores G:I em ambos os tempos da PTOG. Essas mulheres grávidas foram aquelas que tiveram maior risco de desenvolver distúrbios de hipertensão e maiores parâmetros de morbidade durante o período estudado em comparação com as mulheres cujo HOMA-0 foi ≤2,64.Fil: Suárez Crivaro, Florencia. Laboratorio Central de la Secretaría de Salud de la Mul; ArgentinaFil: Romero, José. Clinica Perinat la Plata; ArgentinaFil: Castrogiovanni, Daniel Cayetano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Suescun, Maria Olga. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Spinedi, Eduardo Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentin

Correlation between inhibin secretion and damage of seminiferous tubules in a model of experimental autoimmune orchitis

The aim of the present study was to evaluate inhibin secretion in rats with autoimmune orchitis. As we have previously described, experimental autoimmune orchitis (EAO) induced in rats by active immunization with testis homogenate and adjuvants is characterized by an interstitial mononuclear cell infiltrate and sloughing of the germinal epithelium. At 120 days after the first immunization 60% of the rats exhibited a severe orchitis with large areas of aspermatogenic seminiferous tubules in which only spermatogonia and Sertoli cells with cytoplasmic vacuolization remained attached to the tubular wall. None of the untreated (N) or control (C) rats revealed pathological alterations. Sixty percent decrease in testis weight was observed in rats with EAO compared with N or C groups. A 3-fold increase in serum FSH levels was observed in rats with EAO compared with N or C groups (19·8 ± 3·7 vs 5·6 ± 0·3 and 5·9 ± 0·1 ng/ml respectively). A significant decrease in inhibin B levels was observed in rats with EAO when compared with N or C groups (40 ± 4·6 vs 207 ± 38·8 and 221·4 ± 28·6 pg/ml respectively). An inverse correlation between inhibin B and FSH serum levels and a direct correlation between inhibin B and testis weight were found. Strong expression of the inhibin α-subunit in Sertoli cells of untreated and control rats was observed; this subunit was undetectable or poorly detectable in rats with orchitis. Positive staining for the inhibin α-subunit was also observed in Leydig cells of all groups studied. In conclusion, using a model of autoimmune orchitis our results show that circulating inhibin B levels and inhibin α-subunit expression in Sertoli cell cytoplasm closely correlate with the degree of damage of the germinal epithelium.Instituto Multidisciplinario de Biología CelularFacultad de Ciencias Exacta

Thyrotropin levels and anti-thyroid peroxidase antibodies during first trimester of pregnancy associated with maternal and foetal complications in euthyroid women

Introducción: El embarazo es una situación fisiológica que presenta cambios endócrinos e inmunológicos. La tiroides modifica su economía para proveer suficientes hormonas a la madre y al feto. La autoinmunidad y las disfunciones tiroideas tienen alta prevalencia en mujeres en edad fértil y pueden afectar el curso de la gestación, con repercusiones clínicas adversas maternas y fetales. El objetivo de este estudio fue relacionar la proporción de gestantes eutiroideas con tirotrofina (TSH) en 2 niveles del rango de referencia (< 1,2 y entre 1,2 y 2,5 mUI/l) y anticuerpos antitiroperoxidasa (a-TPO) positivos y negativos, con la frecuencia de complicaciones en la gestación y evolución a disfunción tiroidea. Métodos: Se analizaron retrospectivamente los niveles de TSH, tiroxina libre (T4L), tiroxina total (T4) y a-TPO de mujeres eutiroideas que cursaban el primer trimestre de embarazo, 580 con a-TPO positivos (EP) y 533 a-TPO negativos (EN). Se subdividieron según sus niveles de TSH en: TSH < 1,2 mUI/l EP1-EN1 y TSH entre 1,2 y 2,5 mUI/l EP2-EN2. Se registraron complicaciones obstétrico-fetales: aborto espontáneo, muerte intraútero, parto pretérmino y disfunciones tiroideas durante la gestación y el posparto. Resultados: La TSH fue mayor en EP con respecto a EN (X¯ ± DS; 1,57 ± 0,82 vs. 1,16 ± 0,54 mUI/l, p = 0,001). Los niveles séricos de T4L y T4 fueron similares en ambos grupos. De la subpoblación EP, el 63% fue incluida en EP1 y el 37% en EP2, y en EN el 80% en EN1 y el 20% en EN2. Se observó un incremento significativo (p = 0,001) en las complicaciones en EP (22%) vs. EN (10%). En mujeres EP con y sin aborto espontáneo, la TSH (X¯ ± DS) fue 1,65 ± 0,67 vs. 0,99± 0,77 mUI/l (p = 0, 014). Las mujeres EP con y sin parto prematuro presentaron niveles de TSH (X¯ ± DS) 1,63 ± 0,70 vs. 1,15 ± 0,53 mUI/l (p = 0,012). En el grupo EN, el nivel de TSH (X¯ ± DS) para las mujeres con y sin aborto fue 1,45 ± 0,61 vs. 0,85± 0,66 mUI/l (p = 0,001), mientras que en mujeres con y sin parto prematuro la TSH (X¯ ± DS) fue 1,59 ± 0,71 vs. 0,83 ± 0,64 mUI/l (p = 0,001), respectivamente. Sin embargo, no hubo diferencias entre los niveles promedio de TSH encontrados en aborto vs. parto pretérmino en ambos grupos. En EP, 32 mujeres y 19 en EN desarrollaron hipotiroidismo en el curso del embarazo (ns) y 29 en EP y 10 en EN tiroiditis posparto (p = 0,005). Conclusión: La autoinmunidad tiroidea y los mayores niveles de TSH dentro del rango de referencia en mujeres en primer trimestre de embarazo estarían asociados a complicaciones en el transcurso de la gestación y desarrollo de disfunción tiroidea posparto.Introduction: Pregnancy is a physiological state presenting with endocrine and immunological changes. The thyroid gland modifies its output in order to provide enough hormones to the mother and foetus. Thyroid autoimmunity and thyroid dysfunction are prevalent in women of childbearing age and may affect the course of gestation and having maternal and foetal clinical consequences. The purpose of the present study was to establish the relationship between euthyroid pregnant women with thyrotropin (TSH) at two levels of the reference range (< 1.2 and between 1.2 and 2.5 mIU/L), and positive or negative anti-thyroid peroxidase autoantibodies (TPO Ab) with the frequency of pregnancy complications and the development of thyroid dysfunction. Methods: A retrospective study of euthyroid women in their first trimester of pregnancy was performed. TSH, free thyroxine (FT4), total thyroxine (T4), and TPOAb values were analysed. A total of 580 women had positive TPOAb (EP group), and 533 women had negative TPOAb (EN group). The EP and EN groups were subdivided according to TSH levels into EP1: positive TPOAb and TSH < 1.2, and EP2: positive TPOAb and TSH between 1.2 and 2.5 mIU/L. Maternal and foetal complications, such as miscarriage, intrauterine death, preterm delivery, and thyroid dysfunction during pregnancy and postpartum were taken into account. Results: TSH values were higher in EP group vs EN group (X¯ ± SD; 1.57 ± 0.82 vs 1.16 ± 0.54 mIU/L, P=.01). FT4 and T4 values were similar in both groups. Out of the pregnant women in the EP group, 63% were included in EP1, and 37% in EP2. In the EN group, 80% of women were included in EN1 and 20% in EN2. A significant (P=.001) increase in pregnancy complications in EP group (22%) vs EN (10%) was observed. In the EP group, TSH levels were: 1.65 ± 0.67 vs 0.99± 0.77 (X¯ ± SD) mIU/L (P=.014) respectively, in women with and without miscarriage. TSH levels were 1.63 ± 0.70 vs 1.15 ± 0.53 (X¯ ± SD) mIU/L (P=.012), respectively, in women with and without preterm delivery. In the EN group TSH levels were: 1.45 ± 0.61 vs 0.85± 0.66 (X¯ ± SD) mIU/L (P=.001), respectively, in women with and without miscarriage. TSH levels were 1.59 ± 0.71 vs 0.83 ± 0.64 (X¯ ± SD) mIU/L (P=.001), respectively, in women with and without preterm delivery. However, TSH levels in miscarriage and preterm delivery were similar. Thirty-two EP, and 19 EN women developed hypothyroidism in pregnancy (ns), and 29 EP and 10 EN women developed post-partum thyroiditis (P=.005). Conclusion: Thyroid autoimmunity and higher TSH levels within the reference range during the first trimester of pregnancy were associated with pregnancy complications and with the development of thyroid postpartum dysfunction.Facultad de Ciencias Exacta

Thyrotropin levels and anti-thyroid peroxidase antibodies during first trimester of pregnancy associated with maternal and foetal complications in euthyroid women

Introducción: El embarazo es una situación fisiológica que presenta cambios endócrinos e inmunológicos. La tiroides modifica su economía para proveer suficientes hormonas a la madre y al feto. La autoinmunidad y las disfunciones tiroideas tienen alta prevalencia en mujeres en edad fértil y pueden afectar el curso de la gestación, con repercusiones clínicas adversas maternas y fetales. El objetivo de este estudio fue relacionar la proporción de gestantes eutiroideas con tirotrofina (TSH) en 2 niveles del rango de referencia (< 1,2 y entre 1,2 y 2,5 mUI/l) y anticuerpos antitiroperoxidasa (a-TPO) positivos y negativos, con la frecuencia de complicaciones en la gestación y evolución a disfunción tiroidea. Métodos: Se analizaron retrospectivamente los niveles de TSH, tiroxina libre (T4L), tiroxina total (T4) y a-TPO de mujeres eutiroideas que cursaban el primer trimestre de embarazo, 580 con a-TPO positivos (EP) y 533 a-TPO negativos (EN). Se subdividieron según sus niveles de TSH en: TSH < 1,2 mUI/l EP1-EN1 y TSH entre 1,2 y 2,5 mUI/l EP2-EN2. Se registraron complicaciones obstétrico-fetales: aborto espontáneo, muerte intraútero, parto pretérmino y disfunciones tiroideas durante la gestación y el posparto. Resultados: La TSH fue mayor en EP con respecto a EN (X¯ ± DS; 1,57 ± 0,82 vs. 1,16 ± 0,54 mUI/l, p = 0,001). Los niveles séricos de T4L y T4 fueron similares en ambos grupos. De la subpoblación EP, el 63% fue incluida en EP1 y el 37% en EP2, y en EN el 80% en EN1 y el 20% en EN2. Se observó un incremento significativo (p = 0,001) en las complicaciones en EP (22%) vs. EN (10%). En mujeres EP con y sin aborto espontáneo, la TSH (X¯ ± DS) fue 1,65 ± 0,67 vs. 0,99± 0,77 mUI/l (p = 0, 014). Las mujeres EP con y sin parto prematuro presentaron niveles de TSH (X¯ ± DS) 1,63 ± 0,70 vs. 1,15 ± 0,53 mUI/l (p = 0,012). En el grupo EN, el nivel de TSH (X¯ ± DS) para las mujeres con y sin aborto fue 1,45 ± 0,61 vs. 0,85± 0,66 mUI/l (p = 0,001), mientras que en mujeres con y sin parto prematuro la TSH (X¯ ± DS) fue 1,59 ± 0,71 vs. 0,83 ± 0,64 mUI/l (p = 0,001), respectivamente. Sin embargo, no hubo diferencias entre los niveles promedio de TSH encontrados en aborto vs. parto pretérmino en ambos grupos. En EP, 32 mujeres y 19 en EN desarrollaron hipotiroidismo en el curso del embarazo (ns) y 29 en EP y 10 en EN tiroiditis posparto (p = 0,005). Conclusión: La autoinmunidad tiroidea y los mayores niveles de TSH dentro del rango de referencia en mujeres en primer trimestre de embarazo estarían asociados a complicaciones en el transcurso de la gestación y desarrollo de disfunción tiroidea posparto.Introduction: Pregnancy is a physiological state presenting with endocrine and immunological changes. The thyroid gland modifies its output in order to provide enough hormones to the mother and foetus. Thyroid autoimmunity and thyroid dysfunction are prevalent in women of childbearing age and may affect the course of gestation and having maternal and foetal clinical consequences. The purpose of the present study was to establish the relationship between euthyroid pregnant women with thyrotropin (TSH) at two levels of the reference range (< 1.2 and between 1.2 and 2.5 mIU/L), and positive or negative anti-thyroid peroxidase autoantibodies (TPO Ab) with the frequency of pregnancy complications and the development of thyroid dysfunction. Methods: A retrospective study of euthyroid women in their first trimester of pregnancy was performed. TSH, free thyroxine (FT4), total thyroxine (T4), and TPOAb values were analysed. A total of 580 women had positive TPOAb (EP group), and 533 women had negative TPOAb (EN group). The EP and EN groups were subdivided according to TSH levels into EP1: positive TPOAb and TSH < 1.2, and EP2: positive TPOAb and TSH between 1.2 and 2.5 mIU/L. Maternal and foetal complications, such as miscarriage, intrauterine death, preterm delivery, and thyroid dysfunction during pregnancy and postpartum were taken into account. Results: TSH values were higher in EP group vs EN group (X¯ ± SD; 1.57 ± 0.82 vs 1.16 ± 0.54 mIU/L, P=.01). FT4 and T4 values were similar in both groups. Out of the pregnant women in the EP group, 63% were included in EP1, and 37% in EP2. In the EN group, 80% of women were included in EN1 and 20% in EN2. A significant (P=.001) increase in pregnancy complications in EP group (22%) vs EN (10%) was observed. In the EP group, TSH levels were: 1.65 ± 0.67 vs 0.99± 0.77 (X¯ ± SD) mIU/L (P=.014) respectively, in women with and without miscarriage. TSH levels were 1.63 ± 0.70 vs 1.15 ± 0.53 (X¯ ± SD) mIU/L (P=.012), respectively, in women with and without preterm delivery. In the EN group TSH levels were: 1.45 ± 0.61 vs 0.85± 0.66 (X¯ ± SD) mIU/L (P=.001), respectively, in women with and without miscarriage. TSH levels were 1.59 ± 0.71 vs 0.83 ± 0.64 (X¯ ± SD) mIU/L (P=.001), respectively, in women with and without preterm delivery. However, TSH levels in miscarriage and preterm delivery were similar. Thirty-two EP, and 19 EN women developed hypothyroidism in pregnancy (ns), and 29 EP and 10 EN women developed post-partum thyroiditis (P=.005). Conclusion: Thyroid autoimmunity and higher TSH levels within the reference range during the first trimester of pregnancy were associated with pregnancy complications and with the development of thyroid postpartum dysfunction.Facultad de Ciencias Exacta

Thyrotropin levels and anti-thyroid peroxidase antibodies during first trimester of pregnancy associated with maternal and foetal complications in euthyroid women

Introducción: El embarazo es una situación fisiológica que presenta cambios endócrinos e inmunológicos. La tiroides modifica su economía para proveer suficientes hormonas a la madre y al feto. La autoinmunidad y las disfunciones tiroideas tienen alta prevalencia en mujeres en edad fértil y pueden afectar el curso de la gestación, con repercusiones clínicas adversas maternas y fetales. El objetivo de este estudio fue relacionar la proporción de gestantes eutiroideas con tirotrofina (TSH) en 2 niveles del rango de referencia (< 1,2 y entre 1,2 y 2,5 mUI/l) y anticuerpos antitiroperoxidasa (a-TPO) positivos y negativos, con la frecuencia de complicaciones en la gestación y evolución a disfunción tiroidea. Métodos: Se analizaron retrospectivamente los niveles de TSH, tiroxina libre (T4L), tiroxina total (T4) y a-TPO de mujeres eutiroideas que cursaban el primer trimestre de embarazo, 580 con a-TPO positivos (EP) y 533 a-TPO negativos (EN). Se subdividieron según sus niveles de TSH en: TSH < 1,2 mUI/l EP1-EN1 y TSH entre 1,2 y 2,5 mUI/l EP2-EN2. Se registraron complicaciones obstétrico-fetales: aborto espontáneo, muerte intraútero, parto pretérmino y disfunciones tiroideas durante la gestación y el posparto. Resultados: La TSH fue mayor en EP con respecto a EN (X¯ ± DS; 1,57 ± 0,82 vs. 1,16 ± 0,54 mUI/l, p = 0,001). Los niveles séricos de T4L y T4 fueron similares en ambos grupos. De la subpoblación EP, el 63% fue incluida en EP1 y el 37% en EP2, y en EN el 80% en EN1 y el 20% en EN2. Se observó un incremento significativo (p = 0,001) en las complicaciones en EP (22%) vs. EN (10%). En mujeres EP con y sin aborto espontáneo, la TSH (X¯ ± DS) fue 1,65 ± 0,67 vs. 0,99± 0,77 mUI/l (p = 0, 014). Las mujeres EP con y sin parto prematuro presentaron niveles de TSH (X¯ ± DS) 1,63 ± 0,70 vs. 1,15 ± 0,53 mUI/l (p = 0,012). En el grupo EN, el nivel de TSH (X¯ ± DS) para las mujeres con y sin aborto fue 1,45 ± 0,61 vs. 0,85± 0,66 mUI/l (p = 0,001), mientras que en mujeres con y sin parto prematuro la TSH (X¯ ± DS) fue 1,59 ± 0,71 vs. 0,83 ± 0,64 mUI/l (p = 0,001), respectivamente. Sin embargo, no hubo diferencias entre los niveles promedio de TSH encontrados en aborto vs. parto pretérmino en ambos grupos. En EP, 32 mujeres y 19 en EN desarrollaron hipotiroidismo en el curso del embarazo (ns) y 29 en EP y 10 en EN tiroiditis posparto (p = 0,005). Conclusión: La autoinmunidad tiroidea y los mayores niveles de TSH dentro del rango de referencia en mujeres en primer trimestre de embarazo estarían asociados a complicaciones en el transcurso de la gestación y desarrollo de disfunción tiroidea posparto.Introduction: Pregnancy is a physiological state presenting with endocrine and immunological changes. The thyroid gland modifies its output in order to provide enough hormones to the mother and foetus. Thyroid autoimmunity and thyroid dysfunction are prevalent in women of childbearing age and may affect the course of gestation and having maternal and foetal clinical consequences. The purpose of the present study was to establish the relationship between euthyroid pregnant women with thyrotropin (TSH) at two levels of the reference range (< 1.2 and between 1.2 and 2.5 mIU/L), and positive or negative anti-thyroid peroxidase autoantibodies (TPO Ab) with the frequency of pregnancy complications and the development of thyroid dysfunction. Methods: A retrospective study of euthyroid women in their first trimester of pregnancy was performed. TSH, free thyroxine (FT4), total thyroxine (T4), and TPOAb values were analysed. A total of 580 women had positive TPOAb (EP group), and 533 women had negative TPOAb (EN group). The EP and EN groups were subdivided according to TSH levels into EP1: positive TPOAb and TSH < 1.2, and EP2: positive TPOAb and TSH between 1.2 and 2.5 mIU/L. Maternal and foetal complications, such as miscarriage, intrauterine death, preterm delivery, and thyroid dysfunction during pregnancy and postpartum were taken into account. Results: TSH values were higher in EP group vs EN group (X¯ ± SD; 1.57 ± 0.82 vs 1.16 ± 0.54 mIU/L, P=.01). FT4 and T4 values were similar in both groups. Out of the pregnant women in the EP group, 63% were included in EP1, and 37% in EP2. In the EN group, 80% of women were included in EN1 and 20% in EN2. A significant (P=.001) increase in pregnancy complications in EP group (22%) vs EN (10%) was observed. In the EP group, TSH levels were: 1.65 ± 0.67 vs 0.99± 0.77 (X¯ ± SD) mIU/L (P=.014) respectively, in women with and without miscarriage. TSH levels were 1.63 ± 0.70 vs 1.15 ± 0.53 (X¯ ± SD) mIU/L (P=.012), respectively, in women with and without preterm delivery. In the EN group TSH levels were: 1.45 ± 0.61 vs 0.85± 0.66 (X¯ ± SD) mIU/L (P=.001), respectively, in women with and without miscarriage. TSH levels were 1.59 ± 0.71 vs 0.83 ± 0.64 (X¯ ± SD) mIU/L (P=.001), respectively, in women with and without preterm delivery. However, TSH levels in miscarriage and preterm delivery were similar. Thirty-two EP, and 19 EN women developed hypothyroidism in pregnancy (ns), and 29 EP and 10 EN women developed post-partum thyroiditis (P=.005). Conclusion: Thyroid autoimmunity and higher TSH levels within the reference range during the first trimester of pregnancy were associated with pregnancy complications and with the development of thyroid postpartum dysfunction.Facultad de Ciencias Exacta