RESUMEN
OBJECTIVE: To measure a profile of hormones in a group of elite athletes. Increasing awareness of the widespread use of hormones as performance-enhancing agents focusses attention on what may be considered as normal in this unusual group. DESIGN: Blood samples were obtained from 813 volunteer elite athletes from a cross-section of 15 sporting categories. An endocrine profile was measured on a subset of 693. PARTICIPANTS: Volunteer elite athletes. Samples were drawn within two hours of an event at a major national or international competition. MEASUREMENTS: Demographics and hormone profiles were obtained on 454 male and 239 female elite athletes. RESULTS: Hormone profiles showed significant differences in 19 of the 24 measured variables between sexes and between all of the 15 sporting disciplines in men and 11 out of 24 in women. 16.5% of men had low testosterone levels, whereas 13.7% of women had high levels with complete overlap between the sexes. Women had a lean body mass 85% that of men - sufficient to account for sex differences in performance. There were highly significant correlations between many of the measured hormones. CONCLUSIONS: Hormone profiles from elite athletes differ from usual reference ranges. Individual results are dependent on a number of factors including age, gender and physique. Differences in profiles between sports suggest that an individual's profile may contribute to his/her proficiency in a particular sport. The IOC definition of a woman as one who has a 'normal' testosterone level is untenable.
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Atletas , Sistema Endocrino/metabolismo , Hormonas/sangre , Deportes/fisiología , Adulto , Estudios Transversales , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Hidrocortisona/sangre , Hormona Luteinizante/sangre , Masculino , Prolactina/sangre , Receptores de Superficie Celular/sangre , Testosterona/sangre , Tirotropina/sangre , Triyodotironina/sangre , Adulto JovenRESUMEN
BACKGROUND: Although the social communicative domain is recognized as being at risk in young children with visual impairment (VI), few tools are available for identifying those most at risk or the aspects that are most vulnerable. METHODS: A standard parent interview - Social Communication Interview for young children with visual impairment (SOCI-VI), was developed and tested with 55 parents of 17 profoundly, 15 severely VI and 23 normally sighted children; mean age 22 months (range 10-40 months). The 35-item SOCI-VI 35 showed adequate inter-rater and test-retest reliability (P < 0.001). RESULTS: Thirteen of 35 items discriminated within and between the vision groups (anova P 0.008). The group with profound VI scored significantly lower than the Sighted group on the reduced 13 item SOCI-VI 13 (t-test P 0.002), the disparity being greatest for items exploring joint attention. The reduced SOCI-VI 13 showed adequate internal consistency (Cronbach alpha > 0.75) and concurrent validity with the Vineland adaptation questionnaire within a randomized VI subgroup (r 0.8, P < 0.01). CONCLUSIONS: The study reveals trends in early social communicative development in the young VI population and provides preliminary reliability and validity testing for future research within a clinical context.
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Trastornos de la Comunicación/psicología , Conducta Social , Trastornos de la Visión/psicología , Análisis de Varianza , Atención , Preescolar , Trastornos de la Comunicación/epidemiología , Femenino , Humanos , Lactante , Masculino , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Trastornos de la Visión/complicaciones , Trastornos de la Visión/epidemiologíaRESUMEN
There is widespread anecdotal evidence that growth hormone (GH) is used by athletes for its anabolic and lipolytic properties. Although there is little evidence that GH improves performance in young healthy adults, randomized controlled studies carried out so far are inadequately designed to demonstrate this, not least because GH is often abused in combination with anabolic steroids and insulin. Some of the anabolic actions of GH are mediated through the generation of insulin-like growth factor-I (IGF-I), and it is believed that this is also being abused. Athletes are exposing themselves to potential harm by self-administering large doses of GH, IGF-I and insulin. The effects of excess GH are exemplified by acromegaly. IGF-I may mediate and cause some of these changes, but in addition, IGF-I may lead to profound hypoglycaemia, as indeed can insulin. Although GH is on the World Anti-doping Agency list of banned substances, the detection of abuse with GH is challenging. Two approaches have been developed to detect GH abuse. The first is based on an assessment of the effect of exogenous recombinant human GH on pituitary GH isoforms and the second is based on the measurement of markers of GH action. As a result, GH abuse can be detected with reasonable sensitivity and specificity. Testing for IGF-I and insulin is in its infancy, but the measurement of markers of GH action may also detect IGF-I usage, while urine mass spectroscopy has begun to identify the use of insulin analogues.
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Doping en los Deportes , Hormona de Crecimiento Humana/farmacología , Factor I del Crecimiento Similar a la Insulina/farmacología , Insulina/farmacología , Rendimiento Atlético/fisiología , Hormona de Crecimiento Humana/efectos adversos , Humanos , Insulina/efectos adversos , Factor I del Crecimiento Similar a la Insulina/efectos adversos , Detección de Abuso de Sustancias/métodosRESUMEN
OBJECTIVE: To develop a test for GH abuse in sport. DESIGN: A double blind placebo controlled study of one month's GH administration to 102 healthy non-competing but trained subjects. Blood levels of nine markers of GH action were measured throughout the study and for 56 days after cessation of GH administration. Blood samples were also taken from 813 elite athletes both in and out of competition. RESULTS: GH caused a significant change in the nine measured blood markers. Men were more sensitive to the effects of GH than women. IGF-I and N-terminal extension peptide of procollagen type III were selected to construct formulae which gave optimal discrimination between the GH and placebo groups. Adjustments were made to account for the fall in IGF-I and P-III-P with age and the altered distribution seen in elite athletes. Using a cut-off specificity of 1:10,000 these formulae would allow the detection of up to 86% of men and 60% of women abusing GH at the doses used in this study. CONCLUSIONS: We report a methodology that will allow the detection of GH abuse. This will provide the basis of a robust and enforceable test identifying those who are already cheating and provide a deterrent to those who may be tempted to do so.
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Doping en los Deportes , Hormona del Crecimiento/administración & dosificación , Factor I del Crecimiento Similar a la Insulina/análisis , Fragmentos de Péptidos/sangre , Procolágeno/sangre , Trastornos Relacionados con Sustancias/diagnóstico , Adolescente , Adulto , Biomarcadores/sangre , Método Doble Ciego , Femenino , Humanos , Masculino , PlacebosRESUMEN
CONTEXT: Recombinant human-GH (r-hGH), in supraphysiological doses, is self-administered by athletes in the belief that it is performance enhancing. OBJECTIVE: The objective of this study was to determine whether r-hGH alters whole-body glucose and glycerol metabolism in endurance-trained athletes at rest and during and after exercise. DESIGN: This was a 4-wk double-blind placebo-controlled trial. SETTING: This study was conducted at St. Thomas Hospital (London, UK). PARTICIPANTS: Twelve endurance-trained male athletes were recruited and randomized to r-hGH (0.2 U/kg.d) (n = 6) or identical placebo (n = 6) for 4 wk. One (placebo group) withdrew after randomization. INTERVENTION: Intervention was conducted by randomization to r-hGH (0.2 U/kg x d) or identical placebo for 4 wk. MAIN OUTCOME MEASURES: Whole-body rates of appearance (Ra) of glucose and glycerol (an index of lipolysis) and rate of disappearance of glucose were measured using infusions of d-[6-6-2H2]glucose and 2H5-glycerol. RESULTS: Plasma levels of glycerol and free fatty acids and glycerol Ra at rest and during and after exercise increased during r-hGH treatment (P < 0.05 vs. placebo). Glucose Ra and glucose rate of disappearance were greater after exercise during r-hGH treatment (P < 0.05 vs. placebo). Resting energy expenditure and fat oxidation were greater under resting conditions during r-hGH treatment (P < 0.05 vs. placebo). CONCLUSIONS: r-hGH in endurance-trained athletes increased lipolysis and fatty acid availability at rest and during and after exercise. r-hGH increased glucose production and uptake rates after exercise. The relevance of these effects for athletic performance is not known.
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Glucemia/metabolismo , Ejercicio Físico/fisiología , Glicerol/metabolismo , Hormona del Crecimiento/farmacología , Resistencia Física/fisiología , Aptitud Física/fisiología , Descanso/fisiología , Adulto , Calorimetría Indirecta , Estudios Cruzados , Carbohidratos de la Dieta/metabolismo , Método Doble Ciego , Metabolismo Energético/efectos de los fármacos , Prueba de Esfuerzo , Ácidos Grasos/metabolismo , Ácidos Grasos no Esterificados/sangre , Hormona de Crecimiento Humana/sangre , Humanos , Lipólisis/efectos de los fármacos , Masculino , Oxidación-ReducciónRESUMEN
OBJECTIVES: Exercise is a potent physiological stimulus of GH secretion. We hypothesized that exogenous recombinant human growth hormone (rhGH) administration through an increase in GH and IGF-I levels would blunt the GH response to exercise. The aim of the study was to examine and compare the impact of rhGH on the exercise-induced GH response in healthy normal men and women. DESIGN AND MEASUREMENTS: Sixty-nine subjects (36 men, 33 women) were randomized to receive low-dose rhGH (0.1 U/kg/day), high dose rhGH (0.2 U/kg/day), or placebo. Subjects were matched for age (24 +/- 3.1), and body mass index (BMI). rhGH was given as a single subcutaneous (s.c.) injection for the first 28 days. All subjects exercised to exhaustion (maximal oxygen consumption--VO2max) before rhGH treatment (Test 1), and on day 28 (Test 2). GH was measured before exercise (time 0), immediately after exercise (time 0') and at 15, 30, 60, 90 and 120 min postexercise. Baseline IGF-I levels were measured before exercise on days 0 and 28. RESULTS: Baseline IGF-I levels showed no gender differences (42.3 women vs. 38.8 nmol/l men) but basal GH values were higher in women (9.9 vs. 1.8 mU/l, P < 0.001). The areas under the GH response curve, for Test 1 were similar in men and women. Peak GH values were higher in women than men (37.9 vs. 23.5 mU/l, but this did not quite reach statistical significance (P = 0.055). In men, administration of rhGH resulted in a significant increase in IGF-I levels over the basal state in both the LD and HD groups (P < 0.0001). In women, the increase in lGF-I levels reached significance only in the HD group (P < 0.0001). On day 28, GH secretion in response to exercise was calculated from the areas under the GH response curve correcting for an exogenous rhGH component (delta AUC). In men, the delta AUC, for Test 2 were similar in all three groups. In women, the delta AUC was higher in the placebo group, than in the HD group (P < 0.02). Free T4 levels decreased significantly in men, and free T3 increased in both men and women, in HD group after the rhGH administration. TSH levels were suppressed only in women. No changes in sex hormones were found in men or women in any of the treatment groups. Conclusions In terms of IGF-I, men are more responsive to rhGH treatment than women. In addition, as men, but not women, were able to overcome the negative feedback control of the elevated IGF-I levels, it seems that exercise may be a more robust stimulus to GH release in men compared to women.
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Ejercicio Físico/fisiología , Hormona de Crecimiento Humana/metabolismo , Caracteres Sexuales , Adulto , Antropometría , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Hormonas Gonadales/sangre , Hormona de Crecimiento Humana/sangre , Hormona de Crecimiento Humana/farmacología , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Hormonas Hipofisarias/sangre , Proteínas Recombinantes/farmacologíaRESUMEN
This paper investigates the construction of age-related standards for ordinal outcome data. Asymmetric logistic models are used to describe the age-related changes in the cumulative probabilities for each ordinal level. Maximum likelihood estimation of model parameters allows the use of likelihood ratio tests to ascertain the appropriate model complexity. In contrast to methodologies for constructing age-related standards where the outcome is continuous, we show how the methodology leads directly to centile estimation for individuals. The method is illustrated using visual acuity measurements collected from 2968 children between 2 and 9 years of age made on a 30-point ordinal scale. We show how, in this instance, smoothing of parameters across ordinal categories leads to reduced validity of the centiles, justifying the need for specialized methodology for non-continuous outcomes.
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Modelos Estadísticos , Agudeza Visual , Factores de Edad , Biometría , Niño , Preescolar , Estudios Transversales , Humanos , Funciones de Verosimilitud , Probabilidad , Valores de Referencia , Reino UnidoRESUMEN
GH replacement therapy has been shown to improve the dyslipidemic condition in a substantial proportion of patients with adult GH deficiency. The mechanisms are not yet fully elucidated. Low-density lipoprotein (LDL) apolipoprotein B100 (apoB) formation and catabolism are important determinants of plasma cholesterol concentrations. This study examined the effect of GH replacement therapy on LDL apoB metabolism using a stable isotope turnover technique. LDL apoB kinetics was determined in 13 adult patients with GH deficiency before and after 3 months GH/placebo treatment in a randomized, double-blind, placebo-controlled study. LDL apoB (13)C-leucine enrichment was determined by isotope-ratio mass spectrometry. Plasma volume was assessed by standardized radionuclide dilution technique. GH replacement therapy significantly decreased LDL cholesterol, LDL apoB concentrations, and LDL apoB pool size compared with placebo. Compared with baseline, GH replacement therapy resulted in a significant increase in plasma volume and fractional catabolic rate, whereas LDL formation rate remained unchanged. LDL lipid content did not significantly change after GH and placebo. This study suggests that short-term GH replacement therapy decreases the LDL apoB pool by increasing removal of LDL particles without changing LDL composition or LDL apoB production rate. In addition, it is possible that the beneficial effects of GH on the cardiovascular system contribute to these findings.
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Apolipoproteínas B/sangre , Hormona del Crecimiento/uso terapéutico , Terapia de Reemplazo de Hormonas , Hormona de Crecimiento Humana/sangre , Hormona de Crecimiento Humana/deficiencia , Lipoproteínas LDL/sangre , Apolipoproteína B-100 , Composición Corporal , Isótopos de Carbono , Método Doble Ciego , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Cinética , Lípidos/sangre , Masculino , Errores Innatos del Metabolismo/sangre , Errores Innatos del Metabolismo/tratamiento farmacológicoRESUMEN
We report a randomised double blind controlled trial investigating the short-term biochemical and adverse clinical responses to recombinant human growth hormone (r-hGH) after surgery for hip fracture. Hip fractures are common, dangerous and expensive, typically affecting frail women with osteoporosis and reduced muscle mass and strength, factors also associated with poor clinical outcomes. Growth hormone therapy increases IGF-I levels, promotes anabolism and increases muscle strength in well older people and selected patient groups and therefore has therapeutic potential to assist recovery of frail patients.Thirty-one women, mean age 86 years, received 14 nightly subcutaneous injections of r-hGH 0.05 mg/kg/day (high dose) or 0.025 mg/kg/day (low dose), or placebo from the 4th post-operative day. There were several serious adverse clinical events but no excess number of adverse events in the r-hGH treatment groups. The r-hGH treatment groups had similar serum IGF-I and IGFBP-3 responses, both significantly different from placebo. The large inter-individual variation of IGF-I responses were inversely correlated with pre-treatment indicators of frailty (body composition and functional abilities).
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Anciano Frágil , Fracturas de Cadera/cirugía , Hormona de Crecimiento Humana/administración & dosificación , Proteínas Recombinantes/administración & dosificación , Anciano , Anciano de 80 o más Años , Densidad Ósea , Método Doble Ciego , Fijación de Fractura/métodos , Humanos , Inyecciones Subcutáneas , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/crecimiento & desarrollo , PlacebosRESUMEN
The anabolic actions of GH in GH-deficient adults and children are well documented. Replacement with GH in such individuals promotes protein synthesis and reduces irreversible loss of protein through oxidation. Although GH is known to be self-administered by athletes, its protein metabolic effects in this context are unknown. This study was designed to determine whether 4 wk of high dose recombinant human GH (r-hGH) administration altered whole body leucine kinetics in endurance-trained athletes at rest and during and after 30 min of exercise at 60% of maximal oxygen uptake. Eleven endurance-trained male athletes were studied, six randomized to receive r-hGH (0.067 mg/kg.d), and five to receive placebo. Whole body leucine turnover was measured at rest and during and after exercise, using a 5-h primed constant infusion of 1-[(13)C]leucine, from which rates of leucine appearance (an index of protein breakdown), leucine oxidation, and nonoxidative leucine disposal (an index of protein synthesis) were estimated. Under resting conditions, r-hGH administration increased rate of leucine appearance and nonoxidative leucine disposal, and reduced leucine oxidation (P < 0.01). This effect was apparent after 1 wk, and was accentuated after 4 wk, of r-hGH administration (P < 0.05). During and after exercise, GH attenuated the exercise-induced increase in leucine oxidation (P < 0.05). There were no changes observed in placebo-treated subjects compared with the baseline study. We conclude that GH administration to endurance-trained male athletes has a net anabolic effect on whole body protein metabolism at rest and during and after exercise.
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Hormona de Crecimiento Humana/administración & dosificación , Consumo de Oxígeno/efectos de los fármacos , Esfuerzo Físico/efectos de los fármacos , Adulto , Isótopos de Carbono , Doping en los Deportes , Hormona de Crecimiento Humana/efectos adversos , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Leucina/farmacocinética , Masculino , Consumo de Oxígeno/fisiología , Resistencia Física , Esfuerzo Físico/fisiología , Descanso/fisiología , Deportes , Hormonas Tiroideas/sangreRESUMEN
OBJECTIVE: Growth hormone (GH) is known to be required for physical well-being. Although it is also widely believed to be important for quality of life (QoL) and psychological health, there is less supportive evidence. The objective of this study was to investigate the psychological effects of discontinuation of GH replacement from adults with severe GH deficiency (GHD). DESIGN: A double-blind, placebo-controlled trial in which GH replacement therapy was discontinued for 3 months from 12 of 21 GH-deficient adults, where nine continued with GH replacement. PATIENTS: GH-treated adults (10 men, 11 women), all with severe GHD (peak GH < 7.7 mU/l on provocative testing), mean age 44.9 years (range 25-68 years). MEASUREMENTS: Semi-structured interviews were given at baseline and end-point plus questionnaires that included a new hormone-deficiency specific, individualized, QoL questionnaire (HDQoL), the General Well-being Index (GWBI), the Well-being Questionnaire (W-BQ12), the Short-Form 36 health status questionnaire (SF-36), the Nottingham Health Profile (NHP) and the General Health Questionnaire (GHQ). RESULTS: Three months after baseline the serum total IGF-I of placebo-treated patients fell from normal, age-related levels (mean 26.6 +/- 13.2 nmol/l) to levels indicative of severe GHD (11.6 +/- 6.6 nmol/l) (P<0.001). Psychological symptoms of GH withdrawal, reported in interviews at end-point by placebo-treated patients, included decreased energy, and increased tiredness, pain, irritability and depression. Patients who believed they knew which treatment they had received correctly identified the treatment (GH or placebo) at end-point (chi2=11.25, P<0.01). Significant between-treatment-group differences in change scores were found for SF-36 General Health (P<0.01), W-BQ12 Energy (P<0.01) and HDQoL do physically (P<0.05), indicating reduced general health, reduced energy and greater perceived impact of hormone deficiency on physical capabilities in the placebo-treated group at end-point relative to GH-treated patients. CONCLUSION: Withdrawal of GH treatment from adults with severe GH deficiency has detrimental psychological effects.
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Terapia de Reemplazo de Hormonas/psicología , Hormona de Crecimiento Humana/deficiencia , Calidad de Vida , Síndrome de Abstinencia a Sustancias/psicología , Adulto , Anciano , Depresión/psicología , Método Doble Ciego , Femenino , Hormona de Crecimiento Humana/efectos adversos , Humanos , Factor I del Crecimiento Similar a la Insulina/análisis , Entrevista Psicológica , Masculino , Fatiga Mental/psicología , Persona de Mediana Edad , Dolor/etiología , Esfuerzo Físico , Factores Sexuales , Encuestas y CuestionariosRESUMEN
GH is an important regulator of fat metabolism at rest, but it is not known whether it regulates fat metabolism during exercise. To determine whether physiologic concentrations of GH influence fat metabolism during exercise, we randomized 16 GH-deficient adults, receiving long-term (mean duration, 5 yr) GH replacement, to either continue GH (n = 8) or receive identical placebo (n = 8) for a 3-month period. Metabolic studies, at rest, during and following exhaustive exercise were carried out at baseline and at the end of the 3 months. The rate of appearance of glycerol (glycerol Ra, an index of lipolysis) and free fatty acids (FFA, FFA Ra) and the rate of disappearance of FFA (FFA Rd) in the plasma were measured using infusions of (2)H(5)-glycerol and 1-(13)C-palmitic acid. Changes in body composition were assessed using dual-energy x-ray absorptiometry scanning and anthropometric measurements. In the baseline studies, exercise resulted in an increase in plasma glycerol and FFA concentrations, glycerol Ra, FFA Ra, and FFA Rd (P < 0.001). Three months of GH withdrawal resulted in reductions in plasma glycerol and FFA, glycerol Ra, FFA Ra, and FFA Rd at rest (P < 0.05 vs. baseline) and during exercise (P < 0.05 vs. baseline and vs. GH treated). Lean body mass decreased after 3 months of GH withdrawal, but total body fat, trunk fat, waist circumference, and the sum of skinfold thicknesses increased after 3 months of GH withdrawal (P < 0.05 vs. baseline and vs. GH treated). Fasting insulin and homeostasis model assessment of insulin resistance decreased after 3 months of GH withdrawal (P < 0.05 vs. baseline and vs. GH treated). In summary, GH withdrawal for 3 months resulted in reductions in release of glycerol and FFA into the circulation and uptake of FFA into the tissues during intense exercise. These changes were accompanied by reduced lean body mass and increased total body and trunk fat. Further studies are required to determine whether reduced mobilization of fat during exercise contributes to reduced exercise capacity and increased body fat in GH-deficient adults.
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Ejercicio Físico/fisiología , Ácidos Grasos no Esterificados/sangre , Glicerol/sangre , Hormona de Crecimiento Humana/administración & dosificación , Hormona de Crecimiento Humana/deficiencia , Absorciometría de Fotón , Tejido Adiposo , Adulto , Aerobiosis , Anciano , Composición Corporal , Constitución Corporal , Isótopos de Carbono , Deuterio , Método Doble Ciego , Ayuno , Femenino , Homeostasis , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Insulina/sangre , Resistencia a la Insulina , Factor I del Crecimiento Similar a la Insulina/análisis , Cinética , Lipólisis , Masculino , Persona de Mediana Edad , Placebos , Grosor de los Pliegues CutáneosRESUMEN
OBJECTIVES: Specific problems in patients with insulin-dependent diabetes mellitus (IDDM) and GH deficiency are hypoglycaemic attacks, increased insulin sensitivity and loss of energy. These problems may be related to GH deficiency. PATIENTS: GH replacement was initiated in five patients with type 1 diabetes mellitus and GH deficiency for 6 months [four males and one female, mean age 41.6 +/- 3.8 years, mean +/- standard error of the mean (SEM); body mass index (BMI) 22.3 +/- 1.2 kg/m2]. METHODS: Body composition (bioimpedance), metabolic control [haemoglobin A1C (HbA1C)], insulin requirement and frequency of hypoglycaemia were measured, and quality of life was assessed using validated questionnaires. Monthly eye photographs were taken. RESULTS: IGF-I concentrations were below the age-adjusted range at baseline and increased significantly following GH replacement therapy [analysis of variance (ANOVA), P < 0.05]. Diabetes control as assessed by HbA1C remained stable (8.2 +/- 0.2 vs. 8.0 +/- 0.4), but needed a 1.75-fold increase in insulin dose/day. Lean body mass tended to increase (P = 0.07) and body fat mass decreased significantly (P > 0.01). Number of severe hypoglycaemic (< 3 mmol/l) attacks decreased significantly (P < 0.04) and quality of life assessed by validated questionnaires improved significantly in all patients [Psychological and General Well-Being Schedule (PGWBS), P < 0.04; Nottingham Health Profile (NHP), P < 0.05]. Monthly eye photographs revealed no changes in the retina in any patients. CONCLUSION: GH replacement therapy has a beneficial effect at the dose used. It restores body composition and decreases frequency and severity of hypoglycaemic episodes, thus improving quality of life. Long-term trials are needed to determine the safety of GH replacement therapy in these patients.
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Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hormona del Crecimiento/deficiencia , Hormona del Crecimiento/uso terapéutico , Adulto , Análisis de Varianza , Glucemia/análisis , Composición Corporal , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/psicología , Femenino , Hemoglobina Glucada/análisis , Humanos , Hipopituitarismo/sangre , Hipopituitarismo/tratamiento farmacológico , Hipopituitarismo/psicología , Insulina/sangre , Insulina/uso terapéutico , Factor I del Crecimiento Similar a la Insulina/análisis , Masculino , Calidad de VidaRESUMEN
OBJECTIVE: To evaluate the psychometric properties of two health status measures for adults with growth hormone deficiency (GHD): Nottingham Health Profile (NHP) and Short-Form Health Survey (SF-36). DESIGN: (1) A cross-sectional survey of adults with treated or untreated GHD to assess reliability and validity of the questionnaires. (2) A randomized, placebo-controlled study of 3 months' GH withdrawal from GH-treated adults to assess the sensitivity of the questionnaires to change. PATIENTS: (1) A cross-sectional survey of 157 patients with severe GHD (peak GH < 10 mU/l on provocative testing), mean age 48.9 years (range 23-70 years), who had either received GH replacement therapy for at least 6 months immediately prior to the study or had not received GH treatment in the previous 6 months. (2) GH treatment was withdrawn from 12 of 21 GH-treated adults, all with severe GHD (peak GH < 7.7 mU/l on provocative testing), mean age 44.9 years (range 25-68 years). MEASUREMENTS: The NHP and SF-36 were used once in the cross-sectional survey, but twice in the GH-withdrawal study, at baseline and end-point (after 3 months). RESULTS: (1) Cross-sectional survey. Both questionnaires had high internal consistency reliability with subscale Cronbach's alphas of > 0.73 (NHP) and > 0.78 (SF-36). Calculation of an NHP Total Score, occasionally reported in the literature, was shown to be inadvisable. Overall, patients with GHD were found to have significantly worse perceived functioning than the UK general population in SF-36 subscales of General Health, Bodily Pain, Social Functioning, Physical Functioning, Role-Emotional, Role-Physical, and Vitality. Although neither questionnaire found significant differences between GH-treated and non-GH-treated patients, there were correlations with duration of GH treatment (P < 0.01) for GH-treated patients in SF-36 Mental Health (r = 0.29, N = 87) and SF-36 Vitality (r = 0.33, N = 88), indicating improvement with increasing treatment duration. The SF-36 was also more sensitive than the NHP to sex differences: men had significantly better health status compared with women (P < 0.05) in all SF-36 subscales but Mental Health, but only in one NHP subscale (Physical Mobility). (2) GH-withdrawal study. Significant between-group differences in change were found in SF-36 General Health [t(17) = 2.76, P = 0.013, two-tailed] and SF-36 Mental Health [t(17) = 2.41, P = 0.027, two-tailed]: patients withdrawn from GH reported reduced general health and mental health at end-point. The NHP found no significant change. CONCLUSIONS: The SF-36 is a better measure than the NHP of health status of people with GH deficiency because of its greater discriminatory power, with ability to detect lesser degrees of disability. It also has superior sensitivity to some subgroup differences and superior sensitivity to change compared with the NHP. The SF-36 is highly acceptable to respondents, and has very good internal consistency reliability. The SF-36 is recommended to measure the health status of adults with GH deficiency.
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Hormona del Crecimiento/deficiencia , Indicadores de Salud , Adulto , Anciano , Estudios Transversales , Femenino , Hormona del Crecimiento/uso terapéutico , Terapia de Reemplazo de Hormonas , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estadísticas no ParamétricasRESUMEN
Homeostatic mechanisms normally maintain the plasma glucose concentration within narrow limits despite major fluctuations in supply and demand. There is increasing evidence that the growth hormone (GH)-insulin-like growth factor (IGF) axis may play an important role in glucose metabolism. GH has potent effects on intermediary metabolism, some of which antagonize the actions of insulin. In contrast, IGF-I has insulin-like actions, which are, in the case of glucose metabolism, opposite to those of GH. There is often deranged glucose metabolism in situations where GH is deficient or in excess. The clinical administration of GH or IGF-I results in altered glucose metabolism and changes in insulin resistance. Despite these observations, the precise role of GH and IGF-I and their interactions with insulin in controlling normal glucose homeostasis are unknown. In diabetes, GH secretion is abnormally increased as a result of reduced portal insulin resulting in impaired hepatic IGF-I generation. Evidence suggests that this may contribute to the development of diabetic microvascular complications. IGF-I 'replacement' in diabetes is under investigation and new methods of delivering IGF-I as a complex with IGFBP-3 offer exciting new prospects.
Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus/metabolismo , Hormona del Crecimiento/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Animales , Animales Modificados Genéticamente , Diabetes Mellitus/tratamiento farmacológico , Angiopatías Diabéticas/etiología , Hormona del Crecimiento/deficiencia , Hormona del Crecimiento/uso terapéutico , Homeostasis , Humanos , Resistencia a la Insulina , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/uso terapéuticoRESUMEN
OBJECTIVE: Hypopituitary GH-deficient patients have an increased cardiovascular mortality and GH replacement in this population has resulted in considerable therapeutic benefit. GH replacement involves administration of a potentially mitogenic substance to patients with a previous or residual pituitary tumour. Our objective was to evaluate whether GH replacement results in an increase in the size of pituitary tumours. METHODS: This was a non-randomised observational study on patients recruited from the endocrine clinic. All subjects had GH deficiency, proven on an insulin tolerance test and were divided into those who were or were not receiving long-term GH replacement. Comparison of change in pituitary size was made with interval radiological imaging of the pituitary. RESULTS: Seventy-five patients (40 men and 35 women) were in the study, 47 were on long-term GH replacement and there were 28 controls. The average length of treatment for the treated group was 3.6 patient years. Thirty-nine patients in the treated group had at least 2 years of GH treatment between imaging studies of the pituitary. Two patients in the treated group had an increase in pituitary size (non-functioning adenomas) and two in the control group (one functioning and one non-functioning adenoma adenoma). None of these four patients required further treatment. There was no statistically significant difference between the two groups. CONCLUSION: Using a representative cohort of hypopituitary patients attending an endocrine clinic, GH replacement was not associated with an increased pituitary tumour recurrence rate. Although the results are not conclusive, in the period of observation GH had little adverse effect but longer studies are required to be certain.
Asunto(s)
Hormona de Crecimiento Humana/efectos adversos , Hormona de Crecimiento Humana/deficiencia , Hipopituitarismo/tratamiento farmacológico , Recurrencia Local de Neoplasia/inducido químicamente , Neoplasias Hipofisarias/cirugía , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Hipopituitarismo/sangre , Hipopituitarismo/etiología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Neoplasias Hipofisarias/sangre , Método Simple CiegoRESUMEN
Exercise is a potent stimulus for GH secretion. Aging and obesity are associated with a diminution of GH secretion. We wanted to determine whether age or fat mass is more important in regulating the GH response to exercise. Four groups of healthy men were studied: seven lean young men [age, <40 yr; body mass index (BMI), <25 kg/m(2)], six overweight young men (age, <40 yr; BMI, >27.5), seven lean older men (age, >60 yr; BMI, <25), and 6 overweight older men (age, 60 yr; BMI, >27.5). The men performed a maximal exercise test. GH secretion was higher in the younger men than in the older men. Peak GH was higher in the older lean men than in the older overweight men. There was no difference between the young groups. Fitness correlated negatively with age and positively with peak GH. In young men, there was no relation between BMI, bioimpedance, or leptin and GH secretion. In contrast, in older men there was an inverse correlation between measures of fat mass and GH secretion. Age and physical fitness are more important than body fat in regulating exercise-induced GH secretion. These findings have important clinical implications if we are to prevent the frailty and morbidity associated with aging.
Asunto(s)
Envejecimiento/fisiología , Ejercicio Físico/fisiología , Hormona de Crecimiento Humana/biosíntesis , Obesidad/metabolismo , Aptitud Física/fisiología , Adulto , Composición Corporal/fisiología , Prueba de Esfuerzo , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Persona de Mediana EdadRESUMEN
The development and long term progression of diabetic peripheral neuropathy was studied using vibration perception threshold (VPT) as a validated measure. Three hundred and ninety-two patients had a normal age corrected VPT (12.1 +/- 3.7 volts) at baseline, with an age corrected logarithmic VPTscore < 12. 19.9% developed an abnormal VPT over a 12 year period, increasing from 14.2 +/- 3.7 volts (VPTscore 10.4 +/- 0.6) at baseline to 35.9 +/- 9.5 volts (VPTscore 12.6 +/- 0.45) at follow up (P = 0.0001), and from 10.1 +/- 3.7volts (VPTscore 9.4 +/- 0.8) to 14.2 +/- 4.7 (VPTscore 9.8 +/- 0.8) in the rest. Over 80% thus retained a "normal" VPT after a mean diabetes duration of 16 years despite only average glycaemic control, suggesting that non-ideal long term glycaemic control leads to neuropathy in a subset of predisposed patients. VPT was correlated in 123 diabetic patients with definitive criteria for neuropathy and a range of quantitative sensory and autonomic tests. 62/63 patients with abnormal VPT fulfilled neuropathy criteria; of patients with normal VPT who fulfilled neuropathy criteria, all had at least one abnormal thermal threshold test result. We conclude that a combination of log-transformed VPT values (VPTscore > 10.1) and thermal thresholds can identify diabetic patients at risk of developing peripheral neuropathy and select patients likely to benefit from prophylaxis in clinical trials.
Asunto(s)
Neuropatías Diabéticas , Umbral Sensorial , Adulto , Articulación del Tobillo , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/epidemiología , Neuropatías Diabéticas/fisiopatología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reflejo , Factores de Riesgo , VibraciónRESUMEN
OBJECTIVES: Computers are a part of everyday life and offer an exciting way of learning. The aim of our study was to determine the effectiveness of teaching undergraduate endocrinology using a Computer Assisted Learning (CAL) programme. DESIGN AND SUBJECTS: One hundred and eighty-five first year clinical medical students were randomly assigned either to attend a series of conventional lectures (n = 77) or to have the same material available through a CAL programme. MEASUREMENTS: A multiple choice question examination was performed before and after the course. Lecture attendance and individual usage of the computer system were recorded. Students were asked to fill in an evaluation form at the end of the study. RESULTS: There was no significant difference in the first examination scores between the groups. Both groups improved their scores after the course. Students spent longer performing CAL than attending lectures. Those who scored lowest in the first examination spent the most time on the CAL course. Those who spent the most time on the CAL course showed the largest improvement in examination score. Thirty-six out of the 42 students, who completed an evaluation of the CAL programme, rated it better than the standard lectures. CONCLUSIONS: Computer assisted learning is an effective way of increasing knowledge in teaching undergraduate endocrinology. The course was easy to run and was valued more highly than conventional lectures. The module is now running routinely in the year 3 clinical firms at St Thomas' and has resulted in an increase in knowledge in the end of firm assessment.
Asunto(s)
Instrucción por Computador , Educación de Pregrado en Medicina/métodos , Endocrinología/educación , Comportamiento del Consumidor , Evaluación Educacional , HumanosRESUMEN
This review examines some interesting 'new' histories of insulin and reviews our current understanding of its physiological actions and synergy with GH in the regulation of metabolism and body composition. It reviews the history of GH abuse that antedates by many years the awareness of endocrinologists to its potent anabolic actions. Promising methods for detection of GH abuse have been developed but have yet to be sufficiently well validated to be ready for introduction into competitive sport. So far, there are two promising avenues for detecting GH abuse. The first uses immunoassays that can distinguish the isomers of pituitary-derived GH from the monomer of recombinant human GH. The second works through demonstrating circulating concentrations of one or more GH-sensitive substances that exceed the extremes of normal physiological variability. Both methods require blood rather than urine samples. The first method has a window of opportunity lasting about 24 h after an injection and is most suitable for 'out of competition' testing. The second method has reasonable sensitivity for as long as 2 weeks after the last injection of GH and is uninfluenced by extreme exercise and suitable for post-competition samples. This method has a greater sensitivity in men than in women. The specificity of both methods seems acceptably high but lawyers need to decide what level of scientific probability is needed to obtain a conviction. Both methods need further validation before implementation. Research work carried out as part of the fight against doping in sport has opened up a new and exciting area of endocrinology.