RESUMEN
An important defect in insulin-dependent diabetes mellitus (IDDM) is that the liver does not meet its full fuel-processing function, because many of the enzymes involved depend on high insulin concentrations in the portal vein. We tried to reactivate the liver by long-term treatment of IDDM patients with intravenous insulin in pulses, with the aim of achieving high portal-vein concentrations during and after a glucose meal. We studied 20 IDDM patients with brittle disease; despite use of a four-injection regimen with manipulation of insulin doses, diet, and physical activity, and frequent clinic visits for at least a year, these patients still had wide swings in blood glucose and frequent hypoglycaemic reactions. The intermittent therapy consisted of 7-10 pulses of intravenous insulin, infused while the patient was ingesting carbohydrate, primarily glucose, during the first hour of a 3 h treatment; three treatments were given in a day. After 2 consecutive days' treatment, patients were treated for 1 day per week. No patient was withdrawn from the study. At the time of this analysis the duration of intermittent treatment ranged from 7 to 71 months (mean 41 [SE 5] months). Haemoglobin A1C concentrations declined from 8.5 (0.4)% at the end of the stabilisation phase to 7.0 (0.2)% at the analysis point (p = 0.0003). During the same time the frequencies of major and minor hypoglycaemic events also fell significantly (major 3.0 [1.1] to 0.1 [0], minor 13.0 [2.6] to 2.4 [0.8] per month; both p < 0.0001). Because the use of saline rather than insulin pulses would have led to unacceptable hyperglycaemia we opted for a historical control design. The absence of a true control group limits the interpretation of these preliminary results, but we believe further studies of hepatic and muscle metabolism before and after long-term intermittent intravenous insulin therapy would be worth while.
Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Sistemas de Infusión de Insulina , Insulina/administración & dosificación , Adolescente , Adulto , Anciano , Algoritmos , Niño , Preescolar , Diabetes Mellitus Tipo 1/sangre , Femenino , Hemoglobina Glucada/análisis , Humanos , Hipoglucemia/prevención & control , Infusiones Intravenosas , Insulina/farmacología , Insulina/uso terapéutico , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Persona de Mediana Edad , Flujo Pulsátil , Resultado del TratamientoRESUMEN
The natural course of Graves' disease results in hypothyroidism in up to 20% of patients previously treated with antithyroid drugs. The precise mechanisms are not known, although autoimmune destruction of thyroid tissue has been proposed. We studied sequentially obtained serum samples from three patients with hyperthyroid Graves' disease previously treated with an antithyroid drug who became hypothyroid to determine possible causes of their hypothyroidism. Antithyroglobulin and antithyroid microsomal autoantibodies, TSH binding inhibitory immunoglobulin (TBII), thyroid-stimulating antibody (TSAb), and thyroid stimulation-blocking activity were measured. Autoantibodies were markedly elevated throughout the clinical course in all three patients. Patient 1 had no TBII and blocking activity and extremely high TSAb when she was euthyroid as well as hypothyroid. Hypothyroidism was probably the result of autoimmune thyroid destruction. In patient 2, TSAb disappeared, and TBII and blocking activity increased markedly when she developed hypothyroidism, which thus appeared to result from blocking antibodies. Patient 3 had intermittent periods of hyper- and hypothyroidism before becoming and remaining euthyroid. While initially hypothyroid, TBII was weakly positive, and TSAb was strongly positive; subsequently, when hyperthyroidism recurred, TBII and TSAb were strongly positive. Hypothyroidism appeared to result from focal autoimmune thyroiditis. Patients with hyperthyroid Graves' disease may develop hypothyroidism later by different means. Autoimmune thyroiditis, diffuse or focal, with thyroid destruction is one mechanism. The appearance of antibodies that block TSH stimulation may be another.
Asunto(s)
Autoanticuerpos/análisis , Enfermedad de Graves/tratamiento farmacológico , Hipotiroidismo/etiología , Inmunoglobulina G/análisis , Adulto , Antitiroideos/uso terapéutico , Femenino , Enfermedad de Graves/complicaciones , Humanos , Hipotiroidismo/inmunología , Inmunoglobulinas Estimulantes de la Tiroides , Microsomas/inmunología , Tiroglobulina/inmunología , Glándula Tiroides/inmunología , Hormonas Tiroideas/sangre , Tirotropina/antagonistas & inhibidoresRESUMEN
Human growth hormone (hGH) responses to thyrotropin-releasing hormone (TRH) were investigated in normal subjects under psychological stress. Fifteen subjects (4 men and 11 women), whose ages ranged from 19 to 22 years, were studied. The mirror-drawing test (MDT) was performed to induce psychological stress. Plasma hGH and prolactin (PRL) were determined serially before, during and after the following tests: TRH alone (500 micrograms synthetic TRH i.v. bolus), MDT alone, and TRH with MDT. The changes in hGH concentrations with MDT alone were not significant. The hGH response to TRH alone also showed no remarkable change; however, hGH responses to TRH combined with MDT were significantly higher than the responses to TRH alone. PRL did not respond with MDT alone but responded significantly with the other two tests. Thus there was a divergence in hGH and PRL secretion to TRH and psychological stress. Significant increases in hGH secretion were observed only when TRH and psychological stress were combined as stimuli.
Asunto(s)
Hormona del Crecimiento/sangre , Estrés Psicológico/sangre , Hormona Liberadora de Tirotropina , Adulto , Nivel de Alerta/fisiología , Femenino , Humanos , Masculino , Prolactina/sangre , Desempeño Psicomotor/fisiologíaRESUMEN
There are clinical similarities between anorexia nervosa and hypothyroidism. Circulating levels of T4 and particularly T3 have been reported to be low in this eating disorder. Previous reports have, however, shown normal basal levels of serum TSH with normal or delayed responses to TRH. To assess thyroid function and the hypothalamic-pituitary axis in 21 women with anorexia nervosa, serum levels of free and total thyroid hormones, binding proteins, and TSH employing an extremely sensitive assay (detection limit = 0.02 microU/ml) were measured. Serum T4, free T4, T3, free T3, TSH, TBG and TBPA concentrations were significantly lower and rT3 levels were significantly higher in anorexia nervosa patients than in normal controls. A delayed TSH response to TRH was noted in 66% of patients, hyporesponsiveness was seen in another 24%, and a normal response in only 10%. In 10 anorexia nervosa patients studied after weight gain, T4, T3, free T3, TSH, TBG and TBPA were significantly increased, and rT3 was significantly decreased. No change in mean free T4 levels with weight gain was noted. Other parameters of hypothalamic dysfunction in anorexia nervosa have been reported and the present data suggest that apparent hypothalamic hypothyroidism occurs perhaps as an adaptation to prolonged starvation.
Asunto(s)
Anorexia Nerviosa/sangre , Hormonas Tiroideas/sangre , Hormona Liberadora de Tirotropina , Adolescente , Adulto , Anorexia Nerviosa/diagnóstico , Peso Corporal , Femenino , Humanos , Tirotropina/sangre , Proteínas de Unión a Tiroxina/sangreRESUMEN
Abnormalities of hypothalamic-pituitary function in patients with anorexia nervosa (AN) have been reported previously. Since atypical responses to thyrotropin-releasing hormone (TRH) and luteinizing-hormone-releasing hormone (LHRH) have been observed in other disease states, hormonal responses to these hypothalamic peptides in 60 otherwise unstressed young women with anorexia nervosa were studied. Sixteen patients demonstrated a growth hormone (GH) response to TRH and 10 showed an increase in GH after LHRH. Five patients had an increase in cortisol after TRH, 2 of whom showed GH response, and 2 patients demonstrated a cortisol response to LHRH, 1 of whom had a GH response. Variable TSH responses to TRH were observed in the study but there was no correlation with the occurrence of GH or cortisol responses. GH responses to TRH and LHRH were typically not seen in the same patients, nor were they predictive of a cortisol response to the same stimulus. These data add to the evidence for an abnormal hypothalamic-pituitary regulation in AN.