Hepatitis tóxica por carbimazol / Carbimazole-induced toxic hepatitis

Las tionamidas son fármacos antitiroideos que poseen habitualmente una buena tolerancia. No obstante, pueden originar toxicidad hematológica y hepática potencialmente grave. Presentamos el caso de una paciente de 45 años con hipertiroidismo por enfermedad de Graves-Basedow que, 3 semanas después de iniciar tratamiento con carbimazol (30 mg/día), presentó clínica de prurito, ictericia mucocutánea, orinas colúricas y molestias abdominales. La clínica y la analítica realizada confirmaron la existencia de colestasis y hepatólisis y fue necesario interrumpir el tratamiento antitiroideo y administrar corticoides y N-acetil cisteína. Su recuperación fue lenta y casi completa al año de evolución. La ausencia de otras causas de afección hepática y la secuencia cronológica entre el inicio del tratamiento, el comienzo de la sintomatología y la mejora tras su retirada indican que la hepatotoxicidad se debió al carbimazol

Thyonamides are antythyroid drugs usually with a good tolerance. However, these drugs can produce a potencially serious hepatic and hematologic toxicity. A file case report of a 45-year-old-woman with severe hyperthyroidism caused by Graves-Basedow illness, which was treated with carbimazole (30 mg daily) is provided. Three weeks later, the patient presented itch, icterus, intense choluria and abdominal discomfort. Clinic and analysis confirm cholestasis and hepatolysis, making it neccesary to interrupt the antythyroid therapy and administer corticoids and n-acetyl-cisteine. The recovery of this patient was slow and almost complete within one year. The absense of other causes of hepatic injury, chronology at the beginning of therapy, appearance of symptons and improvement after discontinuing use, leads us to believe that this response is due to carbimazole

Síndrome de Cushing secundario a displasia adrenal micronodular familiar / Familial micronodular adrenal dysplasia originating Cushing's sindrome

Dos hermanas (14 y 18 años) estudiadas por hipercortisolismo en nuestro servicio en el último año presentaron datos analíticos y bioquímicos de síndrome de Cushing independiente del ACTH, aun cuando los estudios de localización realizados no pudieron poner de manifiesto un agrandamiento uni o bilateral de las glándulas adrenales. En sus antecedentes figuraba una tía materna con hallazgos "similares". La clínica de hipercortisolismo sólo fue evidente en la mayor de las hermanas, mientras que la hiperfunción adrenal fue demostrada tras un estudio de secreción espontánea en 24 h en la más pequeña. Fueron remitidas a cirugía siendo practicada en ambas una adrenalectomía bilateral. El estudio anatomopatológico reveló la presencia de múltiples nódulos entre 1 y 3 mm, de coloración oscura y atrofia perinodular confirmando la existencia de displasia micronodular pigmentaria. No se objetivaron datos de presencia de síndrome de Carney en ellas. Presentamos la clínica, los hallazgos analíticos e histológicos de nuestras pacientes afectadas de esta inusual enfermedad y una revisión de la bibliografía científica (AU)

Patrón secretorio y pulsatilidad de hormona de crecimiento en niños prepuberales de talla baja con normo o bajo peso al nacimiento / Secretory pattern and pulsatility of growth hormone (GH) in short stature prepuberal children with low or normal weight at birth

Antecedentes. Hemos querido investigar si el bajo peso al nacimiento se acompaña de alteraciones en la secreción y/o pulsatilidad de la hormona de crecimiento (GH). Métodos. Se han estudiado 17 niños prepuberales normosecretores de GH (EC: 10,98 ñ 1,13) seleccionados por no presentar diferencias en su patrón auxológico, IMC ajustado, edad gestacional y talla diana familiar, pero con diferencias importantes en su peso al nacimiento: grupo I n = 9, 2.178,3 ñ 120,1 ( P25), p < 0,0001. Hemos determinado tanto las concentraciones integradas de GH durante las 24 h (CI-24h), el día (CID) y la noche (CIN) como los parámetros de pulsatilidad (programa Pulsar): área bajo la curva (AUC-24) y el número de pulsos (NP) y área de los pulsos secretorios (AP). Los pulsos fueron clasificados como grandes (G) o pequeños (P) según fueran mayores o menores de 4 µg/l. Resultados. No encontramos diferencias significativas entre los valores de CI-24h, CIN ni de IGF-I entre ambos grupos. Los niños del grupo I presentaron una menor secreción de GID y un coeficiente CID/CIN significativamente diferente (0,37 ñ 0,26 frente a 0,72 ñ 0,47; p < 0,05). El AUC-24h y el NP fueron similares en los dos grupos. Sólo se observaron diferencias significativas en el área de los pulsos pequeños día (2,22 ñ 1,57 frente a 4,20 ñ 2,11; p < 0,05) y picos grandes día (15,40 ñ 4,79 frente a 22,21 ñ 13,09; p < 0,05), manteniéndose similar la pulsatilidad y secreción nocturna de los sujetos en ambos grupos. Conclusiones. Nuestros resultados demuestran que, aun en situación de normosecreción de GH, se pueden observar diferencias en la secreción de la misma en niños prepuberales nacidos con bajo peso (AU)

Nocturnal rise of leptin in normal prepubertal and pubertal children and in patients with perinatal stalk-transection syndrome.

We studied 24-h profiles of circulating leptin levels using a sensitive and specific radioimmunoassay in healthy pre- (Tanner 1) and pubertal boys and girls (Tanner 3-4) as well as in a group of patients with perinatal stalk-transection syndrome. Similar nyctohemeral rhythm in serum leptin levels were found in prepubertal (MESOR: 2.34 +/- 0.2 ng/ml; amplitude 0.32 +/- 0.1 ng/ml) and pubertal boys (MESOR 2.2 +/- 0.2 ng/ml; amplitude 0.38 +/- 0.07 ng/ml). Likewise, no differences were found between prepubertal (MESOR 6.6 +/- 1.07 ng/ml; amplitude 1.67 +/- 0.4 ng/ml) and pubertal girls (MESOR 4.05 +/- 0.5 ng/ml; amplitude 0.95 +/- 0.2 ng/ml). In contrast, higher MESOR (p < 0.002) and amplitude values (p < 0.005) were found in prepubertal and pubertal girls than in prepubertal and pubertal boys. Finally a significant nyctohemeral rhythm in serum leptin levels was found in patients with perinatal stalk-transection syndrome (MESOR: 9.3 +/- 2.3 ng/ml; amplitude 1.46 +/- 0.4 ng/ml). This data shows the existence of sexual dimorphism in the nyctohemeral rhythm in serum leptin levels that are not influenced by the pubertal stage or by pulsatile anterior pituitary hormone secretion.

Growth hormone secretion in normal prepubertal children: importance of relations between endogenous secretion, pulsatility and body mass.

OBJECTIVE: Although a negative relation between GH secretion and body mass has been described, few studies have been carried out in prepubertal subjects of normal weight and height. The aim of the present study was to examine the relations between GH secretion, pulsatility and body mass throughout the wide range of weights in normal prepubertal children. METHODS: We determined integrated GH concentrations during the day (IC-GHD), night (IC-GHN), and 24 hours (IC-GH24) in 46 prepubertal children (26 males, 20 females) of normal height and growth velocity and with a Z-score (BMI-SD) between +2 and -2 SD. In addition, in 28 of these patients randomized by their BMI-SD, the secretory profile was studied by the Pulsar program: area under curve (AUC), peak number (NP), high spontaneous peak of secretory profile (HSP), and area of pulses (AP) which were considered large (L) or small (S) if their amplitude was greater or less than 4 micrograms/l (8 mU/l). RESULTS: BMI-SD correlated negatively with IC-GH (IC-GHD, IC-GH24, r = -0.58, P < 0.001) and with Pulsar parameters r = -0.48, P < 0.001; IC-GHN, r = -0.45, P < 0.001; (AUC-24, r = -0.73, P < 0.0001; HSP, r = -0.65, P < 0.0001). The NP correlated negatively with BMI-SD (r = -0.51, P < 0.005) at the expense of NLP (r = -0.54, P < 0.003) without being significantly correlated with NSP. This inverse correlation between BMI-SD and NLP was greater during daytime (NLDP, r = -0.60, P < 0.001) and was not significant at night. NSP did not correlate with BMI-SD. A similar relation was observed with respect to pulse area (ALP, r = -0.38, P < 0.05; ALDP, r = -0.46, P < 0.02;) and was not significant for ALP during the night or for ASP in any period. CONCLUSIONS: We suggest that it should be necessary to relate GH secretion to body mass in prepubertal children before defining their secretion as normal or pathological.

[The effect of the follicle-stimulating hormone on testosterone liberation induced by lh in the isolated leydig cell (author's transl)]. / Efecto de la hormona folículo estimulante sobre la liberación de testosterona inducida por LH en la célula de Leydig aislada.

The effect of FSH on the liberation of testosterone induced by LH in the Leydig cell has been investigated. Leydig cells were obtained from adult male rats, and were incubated with LH in one group and with LH and FSH in another group. Incubation was kept at 37 degrees C, 120 cycles/min, in oxygen-carbon dioxide (95:5) atmosphere. Liberated testosterone was measured by RIA, at different periods of incubation. Other group of cells, in identical experimental conditions, were incubated for 120 min with LH and FSH, where the FSH had been previously incubated with anti-FSH antibody. The cells incubated with LH and FSH liberated more testosterone than those incubated with LH. However this effect disappeared when the added FSH had been previously incubated with its antibody. The results show clearly that FSH liberates testosterone by the action of LH, which must be specific since it disappears when the hormone is incubated with its antibody.

Loss of immunological and biological activity of insulin with a human muscle extract.

The isolation of a human muscle extract that degrades insulin to products incapable of any immunological or biological activity is reported. The extract Km value for human insulin is 0.79, and 1.43 for porcine proinsulin. It does not degrade Human Growth Hormone at the concentrations tested, it is inactivated by N-ethyl-maleimide, Trasylol, and heat, and it does not require glutathione for its action. Human muscle, therefore can contain an enzyme similar to "insulin-specific-protease" present in rat muscle.