Confirmation of neonatal screening: reference intervals and evaluation of methodological changes in TSH measurement.

Neonatal reference values for serum thyrotropin are scarce and comprise only small numbers of patients. During 2006, changes were made in IMMULITE kits for TSH measurement. To validate methodological changes, 80 serum samples from patients were evaluated and to establish reference intervals, 334 neonates and infants were analyzed (divided into 4 groups). Group 1 (G1) (48-72 h of life) (n=153), group 2A (G2A) (7-10 days of life) (n=65), group 2B (G2B) (11-14 days of life) (n=35), group 3 (G3) (28-40 days of life) (n=81). Current kits overestimate TSH results by 26 to 37%; TSH (mIU/L) reference intervals (percentile 2.5-97.5) were G1 (1.1-12.7), G2A (1.8-9.8), G2B (1.1-7.1) (p < 0.03 vs. G2A), G3 (1.2-6.9). We suggest that during the second week of life, reference values should be divided into an early stage and a late stage, at least, for there to be an adequate interpretation of borderline measurements in newborn thyroid screening.

Medium and long-term outcome of growth hormone therapy in growth hormone deficient adults.

We evaluated long-term replacement therapy outcomes in various subsets of patients with adult growth hormone (GH) deficiency (AGHD) as well as the patients' susceptibility to adverse events. Fifty-nine patients with AGHD were evaluated, 27 with childhood onset (CO) (18-44 years old, 12 females) and 32 with adult onset (AO) (27-70 years, 18 females). A significant improvement in HDL-cholesterol was observed in AGHD-AO males (basal: 41.3 +/- 12.9 mg/dl, intratreatment: 47.5 +/- 13.2 mg/dl, p = 0.009). However, individual analyses showed that total cholesterol decreased below 240 mg/dl in 33% of AGHD-CO patients and in 50% of AGHD-AO patients, and below 200 mg/dl in 67% of AGHD-CO patients and in 29% of AGHD-AO patients; in the AGHD-AO group, normalization of LDL-cholesterol (< or = 160 mg/dl) and triglycerides (< or = 200 mg/dl) was found in 100% and 50% of patients, respectively; the total cholesterol/HDL ratio decreased below 4.5 in 20% of AGHD-CO patients and in 25% of AGHD-AO patients. The cardiological evaluation showed a significant intra- and interindividual heterogeneity, but cardiac mass improved in patients with a baseline cardiac mass index below 60 g/m2. Markers of bone apposition increased significantly, while bone resorption markers were found to remain unchanged during treatment. A correlation was found between increased bone mineral content and lean body mass (p = 0.0009). Susceptibility to adverse events was not found to be dependent on gender or on the time of onset of the deficiency. Our findings would appear to confirm that a more severe metabolic impairment is correlated with a better therapeutic outcome.

Adult growth hormone deficiency. Metabolic alterations and evaluation of different risk groups.

Adult growth hormone deficiency (AGHD) is an heterogeneous clinical entity characterized by increased cardiovascular morbidity and mortality, alterations in body composition, osteoporosis and impaired quality of life. In order to characterize higher risk subpopulations we studied 77 patients with AGHD, 35 with childhood onset (AGHD-CO): CA 18-44 yr.; 13 females and 22 males, and 42 with adult onset (AGHD-AO): CA 25-70 yr.; 22 females and 20 males. IGF-I, lipid profile, glycemia and glycosylated hemoglobin were measured. Cardiological evaluation: blood pressure, electrocardiogram, ergometry and 2D echocardiogram with mitral Doppler, evaluation of diastolic function (A/E waves ratio and deceleration time), systolic function (ejection and shortening fractions) and Cardiac Mass Index (CMI). The Body Mass Index and waist circumference were recorded. Total body composition and bone mineral density were evaluated by densitometry, and the following bone markers were measured: osteocalcin, bone-specific alkaline phosphatase, carboxyterminal propeptide of type I procollagen, Pyridinoline and Deoxipyridinoline. The subset of females with AGHD-AO had higher levels of total cholesterol: 240 mg/dl (156-351) (p < 0.005), LDL: 140 mg/dl (62-262) (p < 0.04) and of total cholesterol/HDL: 4.04 (3.12-12.7) (p < 0.04); while females with AGHD-CO had a decreased CMI: 62 g/m2 (53-107) (p < 0.01), lower A/E waves ratio: 0.56 (0.39-0.72) (p < 0.01) and lower deceleration time: 164 msec. (135-210) (p < 0.01). The subset of males with AGHD-AO had a greater waist circumference: 98 cm (83-128) (p < 0.03) and males with AGHD-CO had a lower shortening fraction: 41% (30-49) (p < 0.006) and lower deceleration time: 153.5 msec. (127-230) (p < 0.03). In both genders, the bone mineral content was lower in patients with AGHD-CO (females p < 0.02, males: p < 0.0008). Our findings confirm the differences in impairment in AGHD patients, which are mainly dependent on gender and the time of onset of the deficiency, and thus demonstrate the heterogeneity of the syndrome.

Adult growth hormone deficiency. Metabolic alterations and evaluation of different risk groups.

Adult growth hormone deficiency (AGHD) is an heterogeneous clinical entity characterized by increased cardiovascular morbidity and mortality, alterations in body composition, osteoporosis and impaired quality of life. In order to characterize higher risk subpopulations we studied 77 patients with AGHD, 35 with childhood onset (AGHD-CO): CA 18-44 yr.; 13 females and 22 males, and 42 with adult onset (AGHD-AO): CA 25-70 yr.; 22 females and 20 males. IGF-I, lipid profile, glycemia and glycosylated hemoglobin were measured. Cardiological evaluation: blood pressure, electrocardiogram, ergometry and 2D echocardiogram with mitral Doppler, evaluation of diastolic function (A/E waves ratio and deceleration time), systolic function (ejection and shortening fractions) and Cardiac Mass Index (CMI). The Body Mass Index and waist circumference were recorded. Total body composition and bone mineral density were evaluated by densitometry, and the following bone markers were measured: osteocalcin, bone-specific alkaline phosphatase, carboxyterminal propeptide of type I procollagen, Pyridinoline and Deoxipyridinoline. The subset of females with AGHD-AO had higher levels of total cholesterol: 240 mg/dl (156-351) (p < 0.005), LDL: 140 mg/dl (62-262) (p < 0.04) and of total cholesterol/HDL: 4.04 (3.12-12.7) (p < 0.04); while females with AGHD-CO had a decreased CMI: 62 g/m2 (53-107) (p < 0.01), lower A/E waves ratio: 0.56 (0.39-0.72) (p < 0.01) and lower deceleration time: 164 msec. (135-210) (p < 0.01). The subset of males with AGHD-AO had a greater waist circumference: 98 cm (83-128) (p < 0.03) and males with AGHD-CO had a lower shortening fraction: 41

(30-49) (p < 0.006) and lower deceleration time: 153.5 msec. (127-230) (p < 0.03). In both genders, the bone mineral content was lower in patients with AGHD-CO (females p < 0.02, males: p < 0.0008). Our findings confirm the differences in impairment in AGHD patients, which are mainly dependent on gender and the time of onset of the deficiency, and thus demonstrate the heterogeneity of the syndrome.

Adult growth hormone deficiency metabolic alterations and evaluation of different risk groups

El déficit de hormona de crecimiento (GH) del Adulto (AGHD) es una entidad clínica heterogénea caracterizada por incremento de la morbimortalidad cardiovascular, cambios en la composición corporal, osteoporosis y deterioro de la calidad de vida. Para caracterizar subpoblaciones con mayor riesgo de afectación, estudiamos 77 pacientes AGHD, 35 de inicio en la infancia (AGHD-CO): EC 18-44 a; 13 mujeres y 22 varones, y 42 de inicio en la adultez (AGHD-AO): EC 25-70 a; 22 mujeres y 20 varones. Se midió IGF-I, perfil lipídico, glucemia y hemoglobina glicosilada. Evaluación cardiológica: tensión arterial, electrocardiograma, ergometría y ecocardiograma bidimensional con Doppler mitral, evaluando función diastólica (relación ondas A/E y tiempo de desaceleración), función sistólica (fracciones de eyección y acortamiento) e índice de masa cardíaca (IMC). Se registró el índice de masa corporal y la circunferencia de cintura. Se evaluó, mediante densitometría, la composición corporal total y la densidad mineral ósea y se dosaron marcadores óseos: osteocalcina, fosfatasa alcalina fracción ósea, propéptido tipo I carboxiterminal del procolágeno, Pyridinolina y Deoxipyridinolina. El subgrupo de mujeres AGHD-AO presentó mayores niveles de colesterol total: 240 mg/dl (156-351) (p< 0.005), LDL: 140 mg/dl (62-262) (p< 0.04) y de colesterol total / HDL: 4.04 (3.12-12.7) (p< 0.04); mientras que las mujeres AGHD-CO presentaron menor IMC: 62 g/m2 (53-107) (p< 0.01), menor relación A/E: 0.56 (0.39-0.72) (p< 0.01) y menor tiempo de desaceleración: 164 mseg (135-210) (p< 0.01). El subgrupo de varones AGHD-AO presentó mayor circunferencia de cintura: 98 cm (83-128) (p< 0.03) y los varones AGHD-CO, menor fracción de acortamiento: 41% (30-49) (p< 0.006) y menor tiempo de desaceleración: 153.5 mseg (127-230) (p< 0.03). En ambos sexos, el contenido mineral óseo fue menor en los pacientes AGHD-CO (mujeres p< 0.02, varones: p< 0.0008). Nuestros hallazgos confirman la diferente afectación de los pacientes AGHD, en particular en relación al sexo y al momento de inicio de la deficiencia, demostrando la heterogeneidad del síndrome.(AU)

Adult growth hormone deficiency metabolic alterations and evaluation of different risk groups

El déficit de hormona de crecimiento (GH) del Adulto (AGHD) es una entidad clínica heterogénea caracterizada por incremento de la morbimortalidad cardiovascular, cambios en la composición corporal, osteoporosis y deterioro de la calidad de vida. Para caracterizar subpoblaciones con mayor riesgo de afectación, estudiamos 77 pacientes AGHD, 35 de inicio en la infancia (AGHD-CO): EC 18-44 a; 13 mujeres y 22 varones, y 42 de inicio en la adultez (AGHD-AO): EC 25-70 a; 22 mujeres y 20 varones. Se midió IGF-I, perfil lipídico, glucemia y hemoglobina glicosilada. Evaluación cardiológica: tensión arterial, electrocardiograma, ergometría y ecocardiograma bidimensional con Doppler mitral, evaluando función diastólica (relación ondas A/E y tiempo de desaceleración), función sistólica (fracciones de eyección y acortamiento) e índice de masa cardíaca (IMC). Se registró el índice de masa corporal y la circunferencia de cintura. Se evaluó, mediante densitometría, la composición corporal total y la densidad mineral ósea y se dosaron marcadores óseos: osteocalcina, fosfatasa alcalina fracción ósea, propéptido tipo I carboxiterminal del procolágeno, Pyridinolina y Deoxipyridinolina. El subgrupo de mujeres AGHD-AO presentó mayores niveles de colesterol total: 240 mg/dl (156-351) (p< 0.005), LDL: 140 mg/dl (62-262) (p< 0.04) y de colesterol total / HDL: 4.04 (3.12-12.7) (p< 0.04); mientras que las mujeres AGHD-CO presentaron menor IMC: 62 g/m2 (53-107) (p< 0.01), menor relación A/E: 0.56 (0.39-0.72) (p< 0.01) y menor tiempo de desaceleración: 164 mseg (135-210) (p< 0.01). El subgrupo de varones AGHD-AO presentó mayor circunferencia de cintura: 98 cm (83-128) (p< 0.03) y los varones AGHD-CO, menor fracción de acortamiento: 41% (30-49) (p< 0.006) y menor tiempo de desaceleración: 153.5 mseg (127-230) (p< 0.03). En ambos sexos, el contenido mineral óseo fue menor en los pacientes AGHD-CO (mujeres p< 0.02, varones: p< 0.0008). Nuestros hallazgos confirman la diferente afectación de los pacientes AGHD, en particular en relación al sexo y al momento de inicio de la deficiencia, demostrando la heterogeneidad del síndrome.

Evaluation of diagnostic accuracy of insulin-like growth factor (IGF)-I and IGF-binding protein-3 in growth hormone-deficient children and adults using ROC plot analysis.

We critically evaluated the diagnostic value of IGF-I and IGF-binding protein-3 (IGFBP-3) in GH deficiency (GHD) in children and adults using receiver operating characteristic (ROC) plot analysis. Sixty-six children (chronological age, 1.3-15 yr) were studied: 34 GHD and 32 idiopathic short stature (ISS). Ninety-two adults (chronological age, 18-70 yr) were also evaluated: 72 GHD, 34 of childhood onset (AGHD-CO), and 38 of adult onset (AGHD-AO); and 20 healthy volunteers. The SD score (SDS) for IGF-I was calculated from 596 normal subjects (212 children and 384 adults), and the SDS for IGFBP-3 was calculated from 350 normal subjects (212 children and 138 adults). The ROC plot showed that the best IGF-I SDS cut-off line was -1.65 for children [sensitivity (S), 68%; specificity (Sp), 97%, diagnostic efficiency (DEf), 81%], the cut-off line for AGHD was -1.65 for AGHD-CO (S, 91%; Sp, 100%; DEf, 94%), and the cut-off line for AGHD-AO was -1.80 (S, 81%; Sp, 100%; DEf, 88%). For IGFBP-3 SDS, the best cut-off line was -1.80 for children (S, 90%; Sp, 60%; DEf, 78%); it was -1.45 for AGHD-CO (S, 90%; Sp, 75%; DEf, 82%) and -0.90 for AGHD-AO (S, 90%; Sp, 68%; DEf, 77%). An accurate diagnosis was obtained using IGF-I SDS alone in GHD children 65%; ISS, 97%; AGHD-CO, 92%; AGHD-AO, 86%, with IGFBP-3 SDS alone in GHD children 60%; ISS, 90%; AGHD-CO, 75%; AGHD-AO, 68%. Considering both, an accurate diagnosis was obtained in GHD children 60%; ISS, 87%; AGHD-CO, 71%; AGHD-AO, 64%. In conclusion, our findings support the need to use cut-off lines expressed in SDS obtained using an appropriate statistical methodology for better characterization of the various clinical presentations. IGF-I proved to be more useful because of its good diagnostic efficiency and accuracy in both children and adults, whereas IGFBP-3 did not significantly contribute to the diagnosis of GHD.

Alteraciones en la regulación de tirotrofina en el hipotiroidismo congénito / Thyrotropin regulation impairments in congenital hypothyroidism

La TSH constituye uno de los marcadores más importantes para el diagnóstico y control del tratamiento de pacientes con hipotiroidismo congénito (HC). Por otra parte, es conocido desde hace muchos años que algunos niños con HC presentan desde el nacimiento una alteración del umbral de sensibilidad de su unidad hipotálamo-hipofisaria, con niveles elevados de TSH a pesar de una sustitución apropiada. Sin embargo, no existen referencias sobre alteraciones de estas características desarrolladas tardíamente en la evolución del HC. En los últimos 20 años se evaluaron 8 pacientes (7 y 1 ) que presentaban esta situación clínica con diagnóstico etiológico de disenzimia (alteración de la organificación) en 4 casos, disgenesia en 4. La edad cronológica (EC) al diagnóstico e inicio del tratamiento fue de (x y rango): 3,25 (1-8) meses y los valores pretratamiento (mediana y rango) fueron: T4 (Ag/dl) = 1,28 (0,2-2,8); TSH = 50 (27-250) mUI/l. La dosis media de T4 utilizada a partir del primer año de vida fue 3,95 (3,03-6,30) Ag/kg/día. Bajo tratamiento sustitutivo los pacientes mantuvieron niveles normales para su EC de T3, T4 y TSH durante 7,1 (3,2-10,4) años, a partir del cual presentaron elevación de la TSH a pesar que sus hormonas tiroideas se encontraban en el rango normal: T3 (ng/dl) = 136 (105-180), T4 = 11,1 (8,4-12,0), T4l (ng/dl) = 1,9 (1,4-2,0), TSH basal = 23,5 (14-45,5), TSH post TRH = 55 (40-90). El seguimiento de los pacientes a partir de detectarse la secreción inapropiada de TSH fue de 6,3 (2,8-9,6) años, no constatándose normalización durante dicho período en ninguno de ellos. En todos los casos se incrementó la opoterapia alcanzando valores suprafisiológicos de T4: 13,38 (12,5-15,1) y T4l: 2,16 (2,1-2,3), con manifestaciones de sobredosificación en algunos, obteniéndose la normalización de la TSH basal y post TRH sólo en 2 de ellos. El diagnóstico por imágenes de la región selar no mostró alteraciones en ninguno. En 6 casos se asoció TRIAC al tratamiento con T4 en una dosis de 350 Ag (8,1-14,6 Ag/kg) con lo que se obtuvo normalización de los niveles de TSH en todos ellos; no constatándose ningún efecto indeseable. Se concluye: * Parecería existir un subgrupo de pacientes con HC quienes desarrollan tardíamente una alteración en la regulación de TSH. * Esto podría reflejar una alteración adquirida en el mecanismo de regulación de la TSH, posiblemente vinculada a una relativa insensibilidad a la T4... (AU)

Alteraciones en la regulación de tirotrofina en el hipotiroidismo congénito / Thyrotropin regulation impairments in congenital hypothyroidism

La TSH constituye uno de los marcadores más importantes para el diagnóstico y control del tratamiento de pacientes con hipotiroidismo congénito (HC). Por otra parte, es conocido desde hace muchos años que algunos niños con HC presentan desde el nacimiento una alteración del umbral de sensibilidad de su unidad hipotálamo-hipofisaria, con niveles elevados de TSH a pesar de una sustitución apropiada. Sin embargo, no existen referencias sobre alteraciones de estas características desarrolladas tardíamente en la evolución del HC. En los últimos 20 años se evaluaron 8 pacientes (7 y 1 ) que presentaban esta situación clínica con diagnóstico etiológico de disenzimia (alteración de la organificación) en 4 casos, disgenesia en 4. La edad cronológica (EC) al diagnóstico e inicio del tratamiento fue de (x y rango): 3,25 (1-8) meses y los valores pretratamiento (mediana y rango) fueron: T4 (µg/dl) = 1,28 (0,2-2,8); TSH = 50 (27-250) mUI/l. La dosis media de T4 utilizada a partir del primer año de vida fue 3,95 (3,03-6,30) µg/kg/día. Bajo tratamiento sustitutivo los pacientes mantuvieron niveles normales para su EC de T3, T4 y TSH durante 7,1 (3,2-10,4) años, a partir del cual presentaron elevación de la TSH a pesar que sus hormonas tiroideas se encontraban en el rango normal: T3 (ng/dl) = 136 (105-180), T4 = 11,1 (8,4-12,0), T4l (ng/dl) = 1,9 (1,4-2,0), TSH basal = 23,5 (14-45,5), TSH post TRH = 55 (40-90). El seguimiento de los pacientes a partir de detectarse la secreción inapropiada de TSH fue de 6,3 (2,8-9,6) años, no constatándose normalización durante dicho período en ninguno de ellos. En todos los casos se incrementó la opoterapia alcanzando valores suprafisiológicos de T4: 13,38 (12,5-15,1) y T4l: 2,16 (2,1-2,3), con manifestaciones de sobredosificación en algunos, obteniéndose la normalización de la TSH basal y post TRH sólo en 2 de ellos. El diagnóstico por imágenes de la región selar no mostró alteraciones en ninguno. En 6 casos se asoció TRIAC al tratamiento con T4 en una dosis de 350 µg (8,1-14,6 µg/kg) con lo que se obtuvo normalización de los niveles de TSH en todos ellos; no constatándose ningún efecto indeseable. Se concluye: * Parecería existir un subgrupo de pacientes con HC quienes desarrollan tardíamente una alteración en la regulación de TSH. * Esto podría reflejar una alteración adquirida en el mecanismo de regulación de la TSH, posiblemente vinculada a una relativa insensibilidad a la T4...

Reproducibility and variability of the arginine test in normal adults: comparison between sexes

The biochemical diagnosis of growth hormone deficiency in adults (AGHD) remains controversial, mainly as regards stimulation tests and suggested cut-off lines. The insulin tolerance test proved to be the most effective growth hormone (GH) secretagogue in normal males, but a poor intra-individual reproducibility has been reported. Given the safety of the arginine (AST), we decided to evaluate the incidence of false negatives (non responder normal subjects), its reproducibility and variability. Twenty five healthy non-obese volunteers (16 males, 9 females) with a chronological age range between 19 and 40 years, (mean: 29.8) were evaluated. AST was performed (0.5 g/kg IV infusion for 30 min), measuring GH (IRMA) at baseline (B), 30, 60 and 90 minutes, and it was repeated in the same subject 7 to 30 days later; in females both tests were performed in the early follicular phase. Results (median and range) were: 1st test B: 0.61 (0.35-22.60) mug/L; maximal response (Mx Resp) 10.00 (0.48-48.80 mug/L 2nd test B:0.50 (0.38-27.0) mug/L; Mx Resp 11.00 (0.50-47.70) mug/L. The statistical evaluation (Wilcoxon signed rank test) showed no differences between B vs. B and Mx Resp vs Mx Resp. Separated by Sex, males showed: 1st test: B 0.45 (0.35-4.30) mug/L; Mx Resp 6.30 (0.48-48.80) mug/L. 2nd test B 0.46 (0.38-8.80) mug/L; Mx Resp 10.90 (0.50-47.70) mug/L, while females showed 1st test: B 5.20 (0.50-22.60) mug/L; mx Resp 14.00 (3.50-36.70) mug/L 2nd test B 3.60 (0.75-27.00) mug/L; Mx Resp 13.00 (3.70-28.10) mug/L. The statistical comparison (Mann Whitney test) showed significant differences between both sexes in basal values of the first and second test (p<0.001), and in the naximal response of the first test (p<0.03). The statistical analysis did not show significant differences in delta increases between males and females, neither in the first AST nor in the second one. Considering GH values =3 mug/L as a positive response, 4 males exhibited insufficient responses in both tests and other 2 males showed discordant results between tests 1 and 2. All females evaluated produced responses above 3 mug/L in both tests. The results of the present study demonstrate that, particularly in men, AST has no clear limit of normality while it shows good intra-individual reproducibility. In conclusion, at present the biochemical diagnosis of AGHD requires a clear and precise standardization which includes all variables that can modify the GH response to the stimulus used. (AU)

Reproducibility and variability of the arginine test in normal adults: comparison between sexes

The biochemical diagnosis of growth hormone deficiency in adults (AGHD) remains controversial, mainly as regards stimulation tests and suggested cut-off lines. The insulin tolerance test proved to be the most effective growth hormone (GH) secretagogue in normal males, but a poor intra-individual reproducibility has been reported. Given the safety of the arginine (AST), we decided to evaluate the incidence of false negatives (non responder normal subjects), its reproducibility and variability. Twenty five healthy non-obese volunteers (16 males, 9 females) with a chronological age range between 19 and 40 years, (mean: 29.8) were evaluated. AST was performed (0.5 g/kg IV infusion for 30 min), measuring GH (IRMA) at baseline (B), 30, 60 and 90 minutes, and it was repeated in the same subject 7 to 30 days later; in females both tests were performed in the early follicular phase. Results (median and range) were: 1st test B: 0.61 (0.35-22.60) mug/L; maximal response (Mx Resp) 10.00 (0.48-48.80 mug/L 2nd test B:0.50 (0.38-27.0) mug/L; Mx Resp 11.00 (0.50-47.70) mug/L. The statistical evaluation (Wilcoxon signed rank test) showed no differences between B vs. B and Mx Resp vs Mx Resp. Separated by Sex, males showed: 1st test: B 0.45 (0.35-4.30) mug/L; Mx Resp 6.30 (0.48-48.80) mug/L. 2nd test B 0.46 (0.38-8.80) mug/L; Mx Resp 10.90 (0.50-47.70) mug/L, while females showed 1st test: B 5.20 (0.50-22.60) mug/L; mx Resp 14.00 (3.50-36.70) mug/L 2nd test B 3.60 (0.75-27.00) mug/L; Mx Resp 13.00 (3.70-28.10) mug/L. The statistical comparison (Mann Whitney test) showed significant differences between both sexes in basal values of the first and second test (p<0.001), and in the naximal response of the first test (p<0.03). The statistical analysis did not show significant differences in delta increases between males and females, neither in the first AST nor in the second one. Considering GH values =3 mug/L as a positive response, 4 males exhibited insufficient responses in both tests and other 2 males showed discordant results between tests 1 and 2. All females evaluated produced responses above 3 mug/L in both tests. The results of the present study demonstrate that, particularly in men, AST has no clear limit of normality while it shows good intra-individual reproducibility. In conclusion, at present the biochemical diagnosis of AGHD requires a clear and precise standardization which includes all variables that can modify the GH response to the stimulus used.

Infusión de hormona liberadora de gonadotrofinas y prueba de clorpromazina: evaluación en hipogonadismo hipogonadotrófico y retraso puberal femenino / Gonadotropin releasing hormone infusion and chlorpromazine test: evaluation in hypogonadotropic hypogonadism and famele delayed puberty

El objetivo del presente trabajo fue evaluar la infusión de LH-RH y Test de Clorpromazina para mejorar la eficacia diagnóstica diferencial entre Hipogonadismo Hipogonadotrófico (HH) y Retraso Puberal Femenino (RP). Se estudiaron 10 pacientes, 5 HH y 5 RP mediante infusión intravenosa de LH-RH (0,83 Ag/min) durante 120 min con dosaje de LH y FSH (IRMA) a los tiempos de 0, 15, 30, 45, 60 y 120 min. A los 7 días se realizó prueba de CPZ (0,33 mg/kg IM) midiendo PRL (IRMA) a los tiempos -15, 0, 30, 60, 90 y 120 min. Durante la infusión de LH-RH los HH mostraron una respuesta máxima de LH (15,56 ñ 4,57 m UI/ml) de menor magnitud que la de los RP (46,00 ñ 20,69 mUI/ml). Esta diferencia fue estadísticamente significativa (p < 0,01) según el test de Mann-Whitney. No se hallaron diferencias estadísticamente significativas en el basal de LH ni en ninguno de los valores de FSH ni de PRL en la prueba de CPZ entre ambos grupos. Conclusiones: * El aumento de LH en respuesta a la infusión de LH-RH permitió discriminar RP de HH. * Si bien no se encontró superposición de valores entre ambos grupos, esto debería confirmarse con un mayor número de casos. * La evaluación del eje prolactínico con CPZ no permitió discriminar los HH de los RP femeninos (AU)

Infusión de hormona liberadora de gonadotrofinas y prueba de clorpromazina: evaluación en hipogonadismo hipogonadotrófico y retraso puberal femenino / Gonadotropin releasing hormone infusion and chlorpromazine test: evaluation in hypogonadotropic hypogonadism and famele delayed puberty

El objetivo del presente trabajo fue evaluar la infusión de LH-RH y Test de Clorpromazina para mejorar la eficacia diagnóstica diferencial entre Hipogonadismo Hipogonadotrófico (HH) y Retraso Puberal Femenino (RP). Se estudiaron 10 pacientes, 5 HH y 5 RP mediante infusión intravenosa de LH-RH (0,83 µg/min) durante 120 min con dosaje de LH y FSH (IRMA) a los tiempos de 0, 15, 30, 45, 60 y 120 min. A los 7 días se realizó prueba de CPZ (0,33 mg/kg IM) midiendo PRL (IRMA) a los tiempos -15, 0, 30, 60, 90 y 120 min. Durante la infusión de LH-RH los HH mostraron una respuesta máxima de LH (15,56 ñ 4,57 m UI/ml) de menor magnitud que la de los RP (46,00 ñ 20,69 mUI/ml). Esta diferencia fue estadísticamente significativa (p < 0,01) según el test de Mann-Whitney. No se hallaron diferencias estadísticamente significativas en el basal de LH ni en ninguno de los valores de FSH ni de PRL en la prueba de CPZ entre ambos grupos. Conclusiones: * El aumento de LH en respuesta a la infusión de LH-RH permitió discriminar RP de HH. * Si bien no se encontró superposición de valores entre ambos grupos, esto debería confirmarse con un mayor número de casos. * La evaluación del eje prolactínico con CPZ no permitió discriminar los HH de los RP femeninos

Varicocele in prepubertal boys: evaluation of clinical, doppler and hormonal findings

Hormonal, clinical and scrotal Doppler findings were assessed in 16 prepubertal patients having unilateral varicocele. As already described in pubertal patients, Doppler studies made it possible to detect patterns of prolonged, intermittent or permanent reflux. An LH-RH test and an hCG test measuring LH, FSH and testosterone (T) were performed in all cases. patients with varicocele showed (median and range): LH B (mlU/ml): 0.40 (0.40-2.1); LH Mx.: 3.7 (1.1-15); FSH B (mlU/ml); 1.95 (0.40-4.5); FSH Mx.: 4.9 (3.1-10); T B (ng/ml): 0.2 (0.1-1.5): T Post.: 2.25 (0.82-11.5). The control group showed: LH B (mlU/ml): 0.40 (0.4-0.85); LH Mx.: 2.15 (0.63-12) FSH B (mlU/ml): 1.45 (0.4-3); FSH Mx.: 4.25 (2.6-5.9); T B (ng/ml): 0.1 (0.1-0.3); T Post.: 3.26 (1.0-5.6). No significant differences were found between the hormonal results of the different groups classifed according to the scrotal findings. Basal LH and FSH in grade 3 varicoceles were found to be significantly higher (p < 0.05) than those of the control group. Basal T, as well as the maximal response of both gonadotropins to LH-RH, and T response to hCG showed no significant differences with reference to the control group. Our findings provide indirect support to the notion that the gonadal damage would become detectable from puberty onwards.

Varicocele in prepubertal boys: evaluation of clinical, doppler and hormonal findings

Hormonal, clinical and scrotal Doppler findings were assessed in 16 prepubertal patients having unilateral varicocele. As already described in pubertal patients, Doppler studies made it possible to detect patterns of prolonged, intermittent or permanent reflux. An LH-RH test and an hCG test measuring LH, FSH and testosterone (T) were performed in all cases. patients with varicocele showed (median and range): LH B (mlU/ml): 0.40 (0.40-2.1); LH Mx.: 3.7 (1.1-15); FSH B (mlU/ml); 1.95 (0.40-4.5); FSH Mx.: 4.9 (3.1-10); T B (ng/ml): 0.2 (0.1-1.5): T Post.: 2.25 (0.82-11.5). The control group showed: LH B (mlU/ml): 0.40 (0.4-0.85); LH Mx.: 2.15 (0.63-12) FSH B (mlU/ml): 1.45 (0.4-3); FSH Mx.: 4.25 (2.6-5.9); T B (ng/ml): 0.1 (0.1-0.3); T Post.: 3.26 (1.0-5.6). No significant differences were found between the hormonal results of the different groups classifed according to the scrotal findings. Basal LH and FSH in grade 3 varicoceles were found to be significantly higher (p < 0.05) than those of the control group. Basal T, as well as the maximal response of both gonadotropins to LH-RH, and T response to hCG showed no significant differences with reference to the control group. Our findings provide indirect support to the notion that the gonadal damage would become detectable from puberty onwards. (AU)