RESUMEN
During the last 40 year medical laboratory tests per hospital stay have increased 12-fold. This is due to an increase of traditional test as well as by newly introduced analyses. Traditional markers of liver, heart and kidney diseases as well as tumor markers, markers of endocrine and metabolic disorders are critically analysed for regarding their medical needs. Assays which are no longer needed (aspartate aminotransferase, lactate dehydrogenase in heart infarction, acid phosphatase) are assessed differently from those ordered at the wrong time and too often (tumor markers, lipids, HbA (1c), thyroid hormones) and those whose indication has to be continuously renewed because of rapidly changing conditions (autoantibodies, marker of iron status, natriuretic peptides and gene analysis). The rapidly proceeding scientific and technical development allows to conclude, that even under strong and critical control of the medical needs the reduction of tests will contribute little to the further development of total costs of the medical laboratory.
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Técnicas de Laboratorio Clínico/economía , Biomarcadores , Técnicas de Laboratorio Clínico/estadística & datos numéricos , Costos y Análisis de Costo , Técnicas y Procedimientos Diagnósticos/economía , Técnicas y Procedimientos Diagnósticos/estadística & datos numéricos , Alemania , Humanos , Garantía de la Calidad de Atención de Salud/economíaRESUMEN
The influence of press coverage is very important for the doctor-patient relationship. On the one hand nowadays the media provides the possibility to get informed by the media in advance. On the other hand it sometimes leads to grotesque over reactions on certain medical innovations. Often a simple solution is offered too fast. For example the side-effects of drugs are demonstrated in an absolutely exaggerated way. In this article examples for both, the positive and the negative effects of press coverage on medical issues, are presented.
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Medios de Comunicación de Masas , Relaciones Médico-Paciente , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , HumanosAsunto(s)
Hipotiroidismo/diagnóstico , Tiroiditis Autoinmune/diagnóstico , Adulto , Autoanticuerpos/análisis , Diagnóstico Diferencial , Femenino , Humanos , Hipotiroidismo/etiología , Hipotiroidismo/terapia , Miastenia Gravis/diagnóstico , Miastenia Gravis/cirugía , Púrpura Trombocitopénica Idiopática/complicaciones , Púrpura Trombocitopénica Idiopática/diagnóstico , Estómago/inmunología , Timo/cirugía , Tiroiditis Autoinmune/complicacionesAsunto(s)
Hipotiroidismo/diagnóstico , Factores de Edad , Anciano , Autoanticuerpos/sangre , Diabetes Mellitus Tipo 1/complicaciones , Diagnóstico Diferencial , Femenino , Enfermedad de Graves/diagnóstico , Humanos , Hipotiroidismo/sangre , Hipotiroidismo/epidemiología , Hipotiroidismo/etiología , Yoduro Peroxidasa/inmunología , Masculino , Persona de Mediana Edad , Prevalencia , Receptores de Tirotropina/inmunología , Glándula Tiroides/diagnóstico por imagen , Glándula Tiroides/enzimología , Tiroiditis Autoinmune/complicaciones , Tirotropina/sangre , Tiroxina/sangre , UltrasonografíaAsunto(s)
Terapia de Reemplazo de Hormonas , Hipotiroidismo/tratamiento farmacológico , Tiroxina/uso terapéutico , Autoanticuerpos/sangre , Análisis Costo-Beneficio , Femenino , Terapia de Reemplazo de Hormonas/economía , Humanos , Hipotiroidismo/economía , Yoduro Peroxidasa/inmunología , Embarazo , Complicaciones del Embarazo/tratamiento farmacológico , Tiroiditis Autoinmune/complicaciones , Tirotropina/sangre , Tiroxina/economíaAsunto(s)
Hipertiroidismo/diagnóstico , Yodo/deficiencia , Hormonas Tiroideas/sangre , Tirotropina/sangre , Factores de Edad , Diagnóstico Diferencial , Femenino , Humanos , Hipertiroidismo/inmunología , Inmunoglobulinas Estimulantes de la Tiroides/sangre , Yodo/uso terapéutico , Radioisótopos de Yodo/uso terapéutico , Persona de Mediana Edad , Tiroiditis Autoinmune/diagnósticoAsunto(s)
Hipertiroidismo/diagnóstico , Yodo/deficiencia , Tirotropina/sangre , Adolescente , Adulto , Factores de Edad , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Yodo/uso terapéutico , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Embarazo , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/prevención & control , Cintigrafía , Glándula Tiroides/diagnóstico por imagen , Tiroiditis Autoinmune/diagnóstico , UltrasonografíaAsunto(s)
Antitiroideos/uso terapéutico , Hipertiroidismo/terapia , Radioisótopos de Yodo/uso terapéutico , Hormonas Tiroideas/uso terapéutico , Factores de Edad , Antitiroideos/efectos adversos , Quimioterapia Combinada , Femenino , Humanos , Lactancia , Masculino , Embarazo , Complicaciones del Embarazo/terapia , Factores de TiempoRESUMEN
Eutopic corticotroph pituitary adenomas and adrenal cortisol-producing adenomas do not usually express somatostatin receptors. However, ectopic corticotropin (ACTH)-producing tumors often express somatostatin receptors. Thus, the octreoscan can detect and localize tumors in 80% of patients with ectopic ACTH syndrome, and so it can be used to differentiate between eutopic and ectopic ACTH-dependent bilateral adrenal hyperplasia. Octreotide therapy can produce a rapid and sustained reduction of ACTH and cortisol levels in patients with ectopic ACTH-dependent Cushing's syndrome and, in some, may be the only long-term therapy possible. Although no large series have been reported, a review of the literature reveals a large number of case reports that have demonstrated the effectiveness of octreotide.
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Síndrome de ACTH Ectópico/tratamiento farmacológico , Síndrome de ACTH Ectópico/metabolismo , Octreótido/uso terapéutico , Somatostatina/análogos & derivados , Síndrome de ACTH Ectópico/diagnóstico por imagen , Humanos , CintigrafíaRESUMEN
Repeated injection of GHRH leads to a decrease in the GH response in normal subjects. Arginine (Arg) stimulates GH secretion by suppression of hypothalamic somatostatin. To confirm these findings, eight normal men were examined in a series of five settings: test 1 (GHRH/GHRH-TRH), 100 micrograms GHRH injected iv, followed by 100 micrograms GHRH, iv, after 120 min and 200 micrograms TRH, iv, after 150 min; test 2 (GHRH/Arg-TRH), like test 1, but instead of the second GHRH injection, a 30 g Arg infusion over 30 min; test 3 (GHRH/GHRH-Arg-TRH), like test 1, but additionally a 30 g Arg infusion after 120 min; test 4 (GHRH-Arg-TRH), iv GHRH and Arg infusion initially, followed by iv TRH after 30 min; and test 5 (TRH), 200 micrograms TRH, iv, at 0 min. For statistical evaluation, the area under the GH curve (AUC) from 0-120 min was compared with the AUC from 120-240 min. The GH response to the second administration of GHRH was significantly lower (P < 0.02) than the first increase [AUC, 0.5 +/- 0.01 min.mg/L (mean +/- SE) vs. 1.2 +/- 0.3]. No significant differences were found between the GH responses to either GHRH or Arg alone (AUC, 0.9 +/- 0.2 min.mg/L vs. 0.9 +/- 0.2). A larger GH increase (P < 0.02) was seen after GHRH-Arg compared to GHRH alone (AUC, 1.9 +/- 0.4 min.mg/L vs. 1.2 +/- 0.3). The GH response (P < 0.02) to GHRH-Arg stimulation was lower after previous GHRH injection than after GHRH-Arg stimulation alone (AUC, 1.9 +/- 0.4 min.mg/L vs. 3.5 +/- 0.9). There was a statistically significant difference between the TRH-stimulated TSH response in test 4 compared to that in test 5. We could show that decreasing GH responses to repeated GHRH can be avoided by a combined stimulation with GHRH/Arg. These findings suggest that the decreased GH response to a second GHRH bolus may be partly due to an elevated hypothalamic somatostatin secretion, which can be suppressed by Arg. The lower GH response to GHRH-Arg stimulation after a previous GHRH bolus suggests, furthermore, that the readily available GH pool in the human pituitary may be limited.
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Hormona Liberadora de Hormona del Crecimiento/farmacología , Hormona del Crecimiento/metabolismo , Somatostatina/fisiología , Adulto , Arginina , Femenino , Hormona Liberadora de Hormona del Crecimiento/administración & dosificación , Humanos , Cinética , Masculino , Tirotropina/metabolismo , Hormona Liberadora de TirotropinaRESUMEN
The effects of 6 months of replacement therapy with recombinant human GH (hGH) on physical work capacity and cardiac structure and function were investigated in 20 patients with hGH deficiency of adult onset in a double blind, placebo-controlled trial. The GH dose of 12.5 micrograms/kg BW was self-administered daily sc. Oxygen consumption (VO2), CO2 production, and ventilatory volumes were measured during exercise on a bicycle spiroergometer. M-Mode echocardiography was performed using standard techniques. The VO2 max data, expressed per kg BW (mL/min.kg BW) showed a significant increase from 23.2 +/- 2.4 to 30.0 +/- 2.3 (P < 0.01) in the hGH-treated group, whereas the VO2 max data, expressed per lean body mass (milliliters per min/kg lean body mass) did not change significantly in either group. Maximal O2 pulse (milliliters per beat) increased significantly from 15.2 +/- 5.6 to 19.6 +/- 3.3 mL/beat (P < 0.01), but remained constant in the placebo group. The maximal power output (watts +/- SE) increased significantly (P < 0.01) from 192.5 +/- 13.5 to 227.5 +/- 11.5 in the hGH-treated group, but remained constant in the placebo group. Cardiac structure (left ventricular posterior wall, interventricular septum thickness, left ventricular mass, left ventricular end-systolic dimension, and left ventricular end-diastolic dimension) as well as echocardiographically assessed cardiac function did not change significantly after 6 months of treatment in either group. We conclude that hGH replacement in hGH-deficient adults improves oxygen uptake and exercise capacity. These improvements in pulmonary parameters might be due to an increase in respiratory muscle strength and partly to the changes in muscle volume per se observed during hGH replacement therapy. Furthermore, an increased cardiac output might contribute to the improvement in exercise performance during hGH treatment. According to our data, hGH replacement therapy leads to an improvement of exercise capacity and maximal oxygen uptake, but has no significant effect on cardiac structure.
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Hormona del Crecimiento/deficiencia , Hormona del Crecimiento/uso terapéutico , Corazón/fisiopatología , Pulmón/fisiopatología , Esfuerzo Físico , Adulto , Umbral Anaerobio/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Composición Corporal/efectos de los fármacos , Método Doble Ciego , Prueba de Esfuerzo , Ayuno , Femenino , Hormona del Crecimiento/efectos adversos , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Persona de Mediana Edad , Consumo de Oxígeno/efectos de los fármacos , PlacebosRESUMEN
OBJECTIVE: This study evaluated in male patients with idiopathic hypothalamic hypogonadism the effect of pulsatile GnRH therapy or testosterone replacement on the response of all anterior pituitary hormones to adequate dynamic stimuli. PATIENTS AND DESIGN: In nine patients with idiopathic hypothalamic hypogonadism--mean age 21 +/- 1 (mean +/- SE)--a combined pituitary stimulation (CPS) with 200 micrograms TRH, 100 micrograms GnRH, 100 micrograms CRH and 100 micrograms GRH and an insulin tolerance-test (ITT) with 0.1 U insulin/kg body weight were performed. Both tests were repeated during pulsatile GnRH therapy and thereafter on testosterone replacement. MEASUREMENTS: Hormone levels were measured by immunometric assays. For statistical analysis the area under the curve (AUC) was used as a measure for hormone response. RESULTS: Testosterone levels did not differ significantly during GnRH therapy (16.6 +/- 2.1 nmol/L) and testosterone replacement (18.5 +/- 1.7 nmol/L). No significant differences were observed before and during the two treatment modalities for TSH and ACTH. PRL increase was significantly higher during GnRH therapy (AUC: 73580 +/- 8940) compared to the rise before treatment (AUC: 36161 +/- 5853; p < 0.01) and on testosterone replacement (AUC: 49995 +/- 6158; p < 0.01). The GH response to CPS and ITT was higher under testosterone replacement (AUC: 1826 +/- 353 and 1423 +/- 125) compared with the pretreatment situation (AUC: 727 +/- 115; p < 0.05 and 541 +/- 110; p < 0.01) and also more pronounced than under GnRH therapy (AUC: 1148 +/- 180 and 798 +/- 129; p < 0.05). FSH and LH after CPS rose significantly more during GnRH therapy (AUC: 864 +/- 122 and 2215 +/- 219) than before (AUC: 418 +/- 61 and 1424 +/- 277; p < 0.01) and on testosterone treatment (342 +/- 83 and 1153 +/- 323; p < 0.05). CONCLUSION: These results show that GnRH exerts a stimulatory effect on PRL secretion and may modulate GH secretion independently from sex steroids.
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Hormona Liberadora de Gonadotropina/uso terapéutico , Hormona Liberadora de Hormona del Crecimiento/uso terapéutico , Hipogonadismo/tratamiento farmacológico , Hipogonadismo/metabolismo , Hormonas Adenohipofisarias/metabolismo , Testosterona/metabolismo , Adolescente , Adulto , Hormona Folículo Estimulante/metabolismo , Humanos , Hipogonadismo/etiología , Hormona Luteinizante/metabolismo , Masculino , Prolactina/metabolismo , Testosterona/análogos & derivados , Testosterona/uso terapéuticoRESUMEN
Ceruletide, a cholecystokinin-8-like peptide, was recently reported to stimulate ACTH secretion in man. The aim of this study was to investigate the effect of the mu-opiate agonist, loperamide, and the opiate antagonist, naloxone, on ceruletide-induced ACTH secretion in man. In 6 normal subjects, basal ACTH and cortisol plasma levels were significantly suppressed 3 h after loperamide administration (16 mg, orally) from 5 +/- 0 to 2 +/- 0 pmol/l and from 356 +/- 44 to 154 +/- 16 nmol/l. After stimulation with 8 ng ceruletide/kg body weight/min over a period of 5 min, the maximum ACTH levels (at 7.5 min) were significantly reduced by loperamide from 26 +/- 7 to 6 +/- 1 pmol/l and the maximum cortisol levels (at 30 min) were significantly reduced from 676 +/- 47 to 392 +/- 58 nmol/l. Furthermore, the ACTH peak (delta = 7.5 min) was significantly blunted by loperamide from 21 +/- 7 to 5 +/- 1 pmol/l and the integrated area under the curve from 0 to 120 min (delta AUC) of ACTH was significantly reduced from 40 +/- 11 to 14 +/- 4 pmol x 120 min/l. The cortisol peak (delta = 30 min) and the AUC of cortisol were not significantly diminished. The suppressive effect of loperamide on basal and ceruletide-induced ACTH and cortisol secretion was completely reversed by the administration of 0.8 mg naloxone, 20 min before and during infusion of ceruletide. The administration of naloxone itself had no significant effect on ACTH or cortisol levels. In conclusion, ACTH is released by peripherally administered ceruletide within a short period.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Hormona Adrenocorticotrópica/metabolismo , Ceruletida/farmacología , Loperamida/farmacología , Receptores Opioides mu/fisiología , Hormona Adrenocorticotrópica/sangre , Adulto , Interacciones Farmacológicas , Humanos , Hidrocortisona/sangre , Masculino , Naloxona/farmacología , Placebos , Receptores Opioides mu/efectos de los fármacosRESUMEN
The synthetic hexapeptide GH-releasing peptide (GHRP; His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) specifically stimulates GH secretion in humans in vivo and in animals in vitro and in vivo via a still unknown receptor and mechanism. To determine the effect of GHRP on human somatotroph cells in vitro, we stimulated cell cultures derived from 12 different human somatotroph adenomas with GHRP alone and in combination with GH-releasing hormone (GHRH), TRH, and the somatostatin analog octreotide. GH secretion of all 12 adenoma cultures could be stimulated with GHRP, whereas GHRH was active only in 6 adenoma cultures. In GHRH-responsive cell cultures, simultaneous application of GHRH and GHRP had an additive effect on GH secretion. TRH stimulated GH release in 4 of 7 adenoma cultures; in TRH-responsive cell cultures there was also an additive effect of GHRP and TRH on GH secretion. In 5 of 9 adenoma cultures investigated, octreotide inhibited basal GH secretion. In these cell cultures, GHRP-induced GH release was suppressed by octreotide. In 5 of 5 cases, the protein kinase-C inhibitor phloretin partly inhibited GHRP-stimulated GH release, but not basal GH secretion. In summary, GH secretion was stimulated by GHRP in all somatotroph adenomas investigated, indicating that its unknown receptor and signaling pathway are expressed more consistently in somatotroph adenoma cells than those for GHRH, TRH, and somatostatin. Our data give further evidence that GHRP-stimulated GH secretion is mediated by a receptor different from that for GHRH or TRH, respectively, and that protein kinase-C is involved in the signal transduction pathway. Because human somatotroph adenoma cell cultures respond differently to various neuropeptides (GHRH, TRH, somatostatin, and others), they provide a model for further investigation of the mechanism of action of GHRP-induced GH secretion.
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Adenoma/metabolismo , Hormona Liberadora de Hormona del Crecimiento/farmacología , Hormona del Crecimiento/metabolismo , Octreótido/farmacología , Oligopéptidos/farmacología , Neoplasias Hipofisarias/metabolismo , Hormona Liberadora de Tirotropina/farmacología , Adulto , Anciano , Células Cultivadas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Floretina/farmacologíaAsunto(s)
Hiperplasia Suprarrenal Congénita/genética , Adolescente , Hiperplasia Suprarrenal Congénita/diagnóstico , Hiperplasia Suprarrenal Congénita/tratamiento farmacológico , Niño , Femenino , Tamización de Portadores Genéticos , Humanos , Hidrocortisona/administración & dosificación , Masculino , Diagnóstico Prenatal , Pubertad Precoz/diagnóstico , Pubertad Precoz/tratamiento farmacológico , Pubertad Precoz/genética , Caracteres Sexuales , Maduración Sexual/efectos de los fármacosRESUMEN
We investigated the lymphocyte interleukin-2 (IL-2) system, which is critically involved in lymphocyte activation, in patients with disorders or the hypothalamic-pituitary-adrenal (HPA) axis. Patients with Cushing's syndrome (n = 9) showed a significant (p < 0.05) inhibition of phytohemagglutinin (PHA)-stimulated IL-2 secretion by peripheral lymphocytes and a decrease of sensitivity to cortisol inhibition in vitro compared to normal subjects (n = 9). Circulating soluble interleukin-2 receptor (sIL-2R) levels were significantly decreased (p < 0.05), whereas no significant difference was observed in PHA-induced sIL-2R release in vitro. In patients with hypocortisolism (n = 12), in vitro IL-2 synthesis was increased compared to normal subjects and to patients with Cushing's syndrome (p < 0.01). In vitro sIL-2R release was significantly higher (p < 0.01) compared to patients with Cushing's syndrome. In contrast to patients with secondary adrenal insufficiency (n = 7), patients with an adrenal origin of hypocortisolism (Addison's disease, bilateral adrenalectomy; n = 5) showed significantly elevated circulating sIL-2R levels compared to normal subjects and patients with Cushing's syndrome (p < 0.005). There was no significant difference between the study groups in mitogen-induced DNA synthesis. This is the first description of alterations of cytokine secretion in patients with HPA axis disorders. The contrary effects of long-term hypercortisolism and insufficient or absent adrenal glucocorticoid secretion on IL-2-mediated lymphocyte activation could account for the immune states previously observed in these patients.
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Síndrome de Cushing/inmunología , Hidrocortisona/deficiencia , Interleucina-2/fisiología , Activación de Linfocitos/fisiología , Adulto , Células Cultivadas , ADN/biosíntesis , Femenino , Humanos , Hidrocortisona/sangre , Hidrocortisona/farmacología , Interleucina-2/biosíntesis , Linfocitos/metabolismo , Masculino , Persona de Mediana EdadRESUMEN
The effect of the long-acting somatostatin analog octreotide (SMS 201-995) on adrenocorticotropin (ACTH) secretion was studied in five patients with untreated Cushing's disease in vivo and in six human corticotropic adenoma cell cultures in vitro. For the in vivo study, 100 micrograms of octreotide sc was given 30 and 180 min after cannulation of the cubital vein and 100 micrograms of corticotropin-releasing hormone (CRH) was injected iv at 210 min. Serum ACTH and cortisol levels were measured for 390 min. In vivo, octreotide had no significant effect either on basal or CRH-stimulated ACTH levels and did not influence cortisol levels. The in vitro studies were conducted with corticotropic adenoma cell cultures derived from adenoma tissue obtained from six patients with Cushing's disease. In four of six cell cultures, octreotide (1 nmol/l-1 mumol/l) inhibited basal ACTH secretion in a dose-dependent manner. The inhibition ranged from 70 to 92% for 1 nmol/l octreotide to 14-46% for 1 mumol/l octreotide as compared to controls (100%). In three of three octreotide-responsive adenoma cell cultures investigated. CRH-stimulated ACTH secretion was suppressed by octreotide. Hydrocortisone pretreatment in vitro abolished the inhibitory effect of octreotide on ACTH secretion in one octreotide-responsive corticotropic adenoma cell culture. In conclusion, we showed that octreotide in most cases could inhibit the ACTH release from human corticotropic adenoma cells in vitro but had no suppressive effect on ACTH levels of patients with Cushing's disease in vivo. This discrepancy could be due to a somatostatin receptor down-regulation by cortisol at the hypercortisolemic state in vivo.
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Síndrome de Cushing/tratamiento farmacológico , Octreótido/uso terapéutico , Neoplasias de la Corteza Suprarrenal/metabolismo , Neoplasias de la Corteza Suprarrenal/patología , Adenoma Corticosuprarrenal/metabolismo , Adenoma Corticosuprarrenal/patología , Hormona Adrenocorticotrópica/sangre , Hormona Adrenocorticotrópica/metabolismo , Hormona Liberadora de Corticotropina , Síndrome de Cushing/metabolismo , Regulación hacia Abajo , Femenino , Humanos , Hidrocortisona/sangre , Hidrocortisona/metabolismo , Masculino , Octreótido/farmacología , Receptores de Somatostatina/metabolismo , Células Tumorales CultivadasRESUMEN
The acute effects of experimentally elevated triiodothyronine (T3) serum levels were investigated in 14 healthy male subjects. After oral application of 100 micrograms triiodothyronine on 3 consecutive days a battery of neuropsychological tests and rating scales for mood and bodily complaints were administered. Results show slight mood disturbances but no cognitive impairment caused by T3 level changes. Time intervals were estimated as being longer than in euthyroid state, and word production showed a trend to accelerate. It is concluded that the immediate effects of elevated circulating T3 on cognition and mood are merely discrete. More severe cognitive impairments reported in hyperthyroid patients are probably due to long-term effects on the brain.