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1.
J Clin Endocrinol Metab ; 92(1): 160-5, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17062774

RESUMEN

CONTEXT: Low birth weight might increase risk of diabetes mellitus type 2 and metabolic syndrome (MS). GH has insulin-antagonistic properties. Therefore, long-term follow-up of GH-treated children born small for gestational age (SGA) is important. OBJECTIVE AND PATIENTS: The objective of the study was to evaluate insulin sensitivity (Si) and disposition index (DI), all components of the MS and IGF-I and IGF binding protein (IGFBP)-3 levels in 37 previously GH-treated young SGA adults in comparison with 25 untreated short SGA controls. RESULTS: GH-treated subjects were 22.3 (1.7) yr old. Mean duration of GH treatment had been 7.3 (1.3) yr. Mean period after discontinuation was 6.5 (1.4) yr. Si and DI were comparable for GH-treated and untreated SGA subjects. Fasting glucose and insulin levels increased during GH treatment but recovered after discontinuation. Body mass index, waist circumference, high-density lipoprotein cholesterol levels, and triglycerides were equivalent. Systolic and diastolic blood pressure and cholesterol were significantly lower in GH-treated subjects. Thirty-two percent of untreated controls vs. none of the GH-treated subjects had an increased blood pressure. GH-induced rises in IGF-I and IGFBP-3 levels had completely recovered after GH stop. CONCLUSION: At 6.5 yr after discontinuation of long-term GH treatment, Si, DI, fasting levels of glucose and insulin, body mass index, waist circumference, and IGF-I and IGFBP-3 levels were equivalent for GH-treated and untreated young SGA adults. Systolic and diastolic blood pressure and serum cholesterol were even lower in GH-treated subjects. These data are reassuring because they suggest that long-term GH treatment does not increase the risk for diabetes mellitus type 2 and MS in young adults.


Asunto(s)
Diabetes Mellitus Tipo 2/etiología , Hormona del Crecimiento/uso terapéutico , Recién Nacido Pequeño para la Edad Gestacional , Síndrome Metabólico/etiología , Adolescente , Adulto , Presión Sanguínea , Índice de Masa Corporal , Niño , Método Doble Ciego , Femenino , Glucosa/metabolismo , Humanos , Recién Nacido , Resistencia a la Insulina , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Lípidos/sangre , Masculino , Factores de Riesgo , Relación Cintura-Cadera
2.
Horm Res ; 64(4): 166-74, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16205095

RESUMEN

BACKGROUND/AIMS: To evaluate quality of life (QoL) in adolescents born SGA without spontaneous catch-up growth, treated with and without long-term growth hormone (GH) therapy. Additionally, to assess whether GH treatment has a positive effect on QoL, besides improving adult height and height SDS during childhood. METHODS: Two groups of adolescents born SGA without spontaneous catch-up growth participated in the QoL evaluation; a GH-treated group (n = 44, mean GH duration: 8.8 (1.7) years) and an untreated group (n = 28), both mean age 15.8 (2.1) years. QoL was measured by self-reports of the TACQOL-S, a disorder-specific questionnaire, and the CHQ, a generic questionnaire. RESULTS: The GH group scored significantly better health status and health-related QoL on several scales of the TACQOL-S. On all TACQOL-S scales the GH group scored better QoL than the untreated group, with effect sizes of moderate to large, not all differences reaching statistical significance. The generic CHQ did not reveal significant differences in QoL between the GH group and the untreated group. CONCLUSIONS: Firstly, adolescents born SGA, with a GH-induced improved height, had in many aspects a better QoL than untreated adolescents born SGA, according to the disorder-specific questionnaire. Secondly, we advise to use, in addition to a generic questionnaire, a disorder-specific questionnaire for measuring QoL in children treated for short stature, as the generic CHQ did not reveal such differences.


Asunto(s)
Hormona de Crecimiento Humana/uso terapéutico , Recién Nacido Pequeño para la Edad Gestacional/fisiología , Calidad de Vida , Adolescente , Estatura , Imagen Corporal , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Crecimiento , Hormona de Crecimiento Humana/administración & dosificación , Humanos , Recién Nacido , Calidad de Vida/psicología , Encuestas y Cuestionarios , Factores de Tiempo
3.
Horm Res ; 63(5): 238-44, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15900109

RESUMEN

It is common practice in the case of Turner syndrome (TS) to treat short stature with GH treatment and to induce puberty with estrogens at an age as close to normal puberty as possible. This approach in most cases leads to a height in the normal range in childhood, adolescence, and adulthood in TS. Little data is available, however, on its effect on psychosocial functioning. In the present study, we evaluated psychosocial functioning in a group of 50 women with TS, after reaching final height in two multicenter GH trials. Thirty-six girls participated in a randomized dose-response study from mean (SEM) age 6.8 (0.4) years, and 14 girls participated in a frequency-response study from age 13.2 (0.4) years. After discontinuation of long-term GH treatment, these 50 girls were evaluated for psychosocial functioning at a mean age of 18.8 (0.3) years. GH was given in a dosage of 4 IU/m2/day (approximately 0.045 mg/kg/day), 6 IU/m2/day, or 8 IU/m2/day. After a mean GH treatment duration of 7.1 (0.4) years, mean final height (ref. normal girls) was FH1.2 (0.2) SD score. Behavioral problem scores (Achenbach) of the TS women were comparable to normal Dutch peers. Although self-perception (Harter total scale: p < 0.01), and bodily attitude (Baardman: p < 0.05) was significantly less positive than for their normal Dutch peers, we found no evidence of depression. TS women rated their family functioning higher than their Dutch peers (p < 0.0001), and had a slightly different coping pattern. These results show that even after reaching a height in most cases within the normal range and puberty induction at a pubertal age, some women with TS still experience psychosocial problems. It is likely, however, that GH and estrogen treatment improved psychosocial functioning. Long-term follow-up of these GH-treated patients will allow an evaluation of their life achievements.


Asunto(s)
Hormona de Crecimiento Humana/uso terapéutico , Síndrome de Turner/tratamiento farmacológico , Síndrome de Turner/psicología , Adaptación Psicológica , Imagen Corporal , Niño , Preescolar , Depresión , Femenino , Humanos , Modelos Logísticos , Autoimagen , Conducta Social
4.
Horm Res ; 64 Suppl 3: 95-9, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16439851

RESUMEN

Short stature is not the only problem faced by children born small for gestational age (SGA). Being born SGA has also been associated with lowered intelligence, poor academic performance, low social competence and behavioural problems. This paper summarizes the results of a randomized, double-blind, growth hormone (GH) dose-response study (1 or 2 mg/m2/day [ approximately 0.035 or 0.07 mg/kg/day]) on growth, intelligence quotient (IQ) and psychosocial functioning in 79 children born SGA at the start, and after 2 and 8 years of GH therapy, and addresses the associations with head circumference. Mean age at start of therapy was 7.4 years; mean duration of GH treatment was 8.0 years. In 2001, 91% of children born SGA had reached a normal height (> -2.0 standard deviation score [SDS]). Block-design s-score (Performal IQ) and Total IQ score increased (p < 0.001 for both indices) from scores significantly lower than those of Dutch peers at the start of therapy (p < 0.001) to scores that were comparable to those of Dutch peers in 2001. Vocabulary s-score (Verbal IQ) was normal at the start of therapy and remained so over time. Externalizing Problem Behaviour SDS and Total Problem Behaviour SDS improved during GH therapy (p < 0.01-0.05) to scores comparable to those of Dutch peers. Internalizing Problem Behaviour SDS was comparable to that of Dutch peers at the start of therapy and remained so, whereas Self-Perception improved from the start of GH therapy until 2001 (p < 0.001), when it reached normal scores. Head circumference SDS at the start of GH therapy and head growth during GH therapy were positively related to all IQ scores (p < 0.01), whereas neither were related to height SDS at the start of, or to its improvement during, GH therapy. A significant improvement in height and head circumference in children born SGA was seen after only 3 years of GH therapy, in contrast to randomized SGA controls. In conclusion, most children born SGA showed a normalization of height during GH therapy and, in parallel to this, a significant improvement in Performal IQ and Total IQ. In addition, problem behaviour and self-perception improved significantly. Interestingly, Performal, Verbal and Total IQ scores were positively related to head circumference, both at the start of, and during, GH therapy; head circumference increased in GH-treated children born SGA, but not in untreated SGA controls. These results are encouraging but also warrant confirmational studies and further investigations into the effects of GH on the central nervous system.


Asunto(s)
Cognición/efectos de los fármacos , Cabeza , Hormona de Crecimiento Humana/administración & dosificación , Recién Nacido Pequeño para la Edad Gestacional , Solución de Problemas/efectos de los fármacos , Inteligibilidad del Habla/efectos de los fármacos , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Cabeza/crecimiento & desarrollo , Humanos , Lactante , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional/crecimiento & desarrollo , Masculino , Estudios Retrospectivos , Autoimagen
5.
Horm Res ; 62 Suppl 3: 149-54, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-15539818

RESUMEN

Twelve years of growth hormone (GH) therapy of short children born small for gestational age (SGA) have demonstrated that GH is an effective and well-tolerated therapy. Most children will reach a normal adult height (AH). AH of 55 SGA adolescents was comparable for those treated with a GH dose of 1 or 2 mg/m2 (approximately 0.033 or 0.066 mg/kg) per day, mean (SD) AH SDS being -1.2 (0.7) and -0.8 (0.7), respectively. GH therapy had no influence on the age at onset, the progression of puberty, duration of puberty and pubertal height gain. GH therapy induced higher fasting and glucose-stimulated insulin levels after 1 and 6 years, but 6 months after GH stop, all levels returned to normal. At baseline mean systolic blood pressure was significantly increased, but both systolic and diastolic blood pressure decreased significantly during 6 years of GH and remained so after GH stop. GH therapy demonstrated a beneficial effect on serum lipid profiles, body composition, bone mineral density and head growth. Treatment with 2 mg GH/m2 per day induced mean serum IGF-I levels of +2 SDS, whereas IGF-I levels remained within the normal range with 1 mg GH/m2 per day. In conclusion, long-term GH therapy of short SGA children with 1 mg/m2 per day appears to be effective and safe. Since the future consequences of high serum IGF-I levels during long-term GH therapy with 2 mg/m2 per day are as yet unknown, it seems safer to treat short prepubertal SGA children with a GH dose of 1 mg/m2 per day when children are to be treated continuously for many years.


Asunto(s)
Trastornos del Crecimiento/tratamiento farmacológico , Hormona del Crecimiento/administración & dosificación , Recién Nacido Pequeño para la Edad Gestacional/crecimiento & desarrollo , Esquema de Medicación , Hormona del Crecimiento/efectos adversos , Hormona del Crecimiento/uso terapéutico , Humanos , Recién Nacido , Resultado del Tratamiento
6.
J Clin Endocrinol Metab ; 89(11): 5295-302, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15531473

RESUMEN

Short stature is not the only problem faced by small for gestational age (SGA) children. Being born SGA has also been associated with lowered intelligence, poor academic performance, low social competence, and behavioral problems. Although GH treatment in short children born SGA can result in a normalization of height during childhood, the effect of GH treatment on intelligence and psychosocial functioning remains to be investigated. We show the longitudinal results of a randomized, double-blind, GH-dose response study initiated in 1991 to follow growth, intelligence quotient (IQ), and psychosocial functioning in SGA children during long-term GH treatment. Patients were assigned to one of two treatment groups (1 or 2 mg GH/m(2) body surface.d, or approximately 0.035 or 0.07 mg/kg.d). Intelligence and psychosocial functioning were evaluated at start of GH treatment (n = 74), after 2 yr of GH treatment (n = 76), and in 2001 (n = 53). IQ was assessed by a short-form Wechsler Intelligence Scale for Children-Revised or Wechsler Adult Intelligence Scale (Block-design and Vocabulary subtests). Behavioral problems were measured by the Achenbach Child Behavior Checklist or Young Adult Behavior Checklist, and self-perception was measured by the Harter Self-Perception Profile. Mean (sem) birth length sd score was -3.6 (0.2), mean age and height at start was 7.4 (0.2) yr and -3.0 (0.1) sd score, respectively, mean duration of GH treatment was 8.0 (0.2) yr, and mean age in 2001 was 16.5 (0.3) yr. After 2 yr of GH treatment, 96% of both GH groups showed a height gain sd score of 1 sd from the start of treatment or more, resulting in a normal height (i.e. height >/= -2.0 sd for age and sex) in 70% of the children. In 2001, 48 (91%) of the 53 children participating in this study had reached a normal height. Block-design s-score and the estimated total IQ significantly increased (P < 0.001 and P < 0.001, respectively) from scores significantly lower than Dutch peers at start (P < 0.001 and P < 0.001, respectively) to comparable scores in 2001. The increase over time for the Vocabulary s-score was not significant. Internalizing Behavior sd scores remained comparable to Dutch peers, whereas Externalizing Behavior sd scores and Total Problem Behavior sd scores improved significantly during GH therapy (P < 0.01 and P < 0.05, respectively) to scores comparable to Dutch peers. Self-perception sd scores improved from start of GH treatment until 2001 (P < 0.001) to scores significantly higher than Dutch peers (P < 0.05). No significant differences between the two GH dosage groups were found. Improvement in Externalizing and Total Problem Behavior sd scores over time was significantly related to change in height sd score (P < 0.05 and P < 0.01, respectively), whereas scores over time for Vocabulary, Block-design, Internalizing, or total Harter Self-Perception score were not related to change in height sd scores. In conclusion, parallel to a GH-induced catch-up growth in adolescents born SGA, IQ, behavior, and self-perception showed a significant improvement over time from scores below average to scores comparable to Dutch peers. In addition, children whose height over time became closer to that of their peers showed less problem behavior.


Asunto(s)
Conducta Infantil , Hormona de Crecimiento Humana/uso terapéutico , Recién Nacido Pequeño para la Edad Gestacional/crecimiento & desarrollo , Inteligencia , Estatura , Niño , Método Doble Ciego , Femenino , Cabeza/anatomía & histología , Humanos , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional/psicología , Masculino , Autoimagen
7.
J Clin Endocrinol Metab ; 88(12): 5753-8, 2003 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-14671164

RESUMEN

Seventy-five small for gestational age (SGA) children were studied in a randomized, double-blind, dose-response GH trial with either 1 or 2 mg GH/m(2).d. Mean (SD) age at the start of GH therapy was 7.3 (2.2) yr. Data were compared with Dutch reference data. In SGA boys, mean (SD) age at onset of puberty was 12.0 (1.0) and 11.6 (0.7) yr, and in SGA girls it was 10.9 (1.1) and 10.6 (1.2) yr when treated with 1 and 2 mg GH/m(2).d, respectively. SGA boys treated with the lower GH dose started puberty later than the appropriate for gestational age (AGA) controls; for the other GH-dosage groups there was no significant difference in age at onset of puberty compared to AGA controls. The age at menarche and the interval between breast stage M2 and menarche were not significantly different for GH-treated SGA girls compared to their peers. The duration of puberty and pubertal height gain of GH-treated SGA boys and girls were not significantly different between the two GH-dosage groups and were comparable with untreated short children born SGA. In conclusion, long-term GH therapy in short SGA children has no influence on the age at onset and progression of puberty compared to AGA controls, regardless of treatment with a dose of 1 or 2 mg GH/m(2).d. Duration of puberty and pubertal height gain were not significantly different between the GH-dosage groups.


Asunto(s)
Hormona del Crecimiento/uso terapéutico , Hormona de Crecimiento Humana/deficiencia , Recién Nacido Pequeño para la Edad Gestacional , Pubertad , Envejecimiento , Estatura , Niño , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Hormona del Crecimiento/administración & dosificación , Humanos , Recién Nacido , Masculino , Menarquia , Factores de Tiempo
8.
J Clin Endocrinol Metab ; 88(8): 3584-90, 2003 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-12915640

RESUMEN

The GH dose-response effect of long-term continuous GH treatment on adult height (AH) was evaluated in 54 short children born small for gestational age (SGA) who were participating in a randomized, double-blind, dose-response trial. Patients were randomly and blindly assigned to treatment with either 3 IU (group A) or 6 IU (group B) GH/m(2).d ( approximately 0.033 or 0.067 mg/kg.d, respectively). The mean (+/-SD) birth length was -3.6 (1.4), the age at the start of the study was 8.1 (1.9) yr, and the height SD score (SDS) at the start of the study -3.0 (0.7). Seventeen of the 54 children were partially GH deficient (stimulated GH peak, 10-20 mU/liter). Fifteen non-GH-treated, non-GH-deficient, short children born SGA, with similar inclusion criteria, served as controls [mean (+/-SD) birth length, -3.3 (1.2); age at start, 7.8 (1.7) yr; height SDS at start, -2.6 (0.5)]. GH treatment resulted in an AH above -2 SDS in 85% of the children after a mean (+/-SD) GH treatment period of 7.8 (1.7) yr. The mean (SD) AH SDS was -1.1 (0.7) for group A and -0.9 (0.8) for group B, resulting from a mean (+/-SD) gain in height SDS of 1.8 (0.7) for group A and 2.1 (0.8) for group B. No significant differences between groups A and B were found for AH SDS (mean difference, 0.3 SDS; 95% confidence interval, -0.2, 0.6; P > 0.2) and gain in height SDS (mean difference, 0.3 SDS; 95% confidence interval, -0.1, 0.7; P > 0.1). When corrected for target height, the mean corrected AH SDS was -0.2 (0.8) for group A and -0.4 (0.9) for group B. The mean (+/-SD) AH SDS of the control group [-2.3 (0.7)] was significantly lower than that of the GH-treated group (P < 0.001). Multiple regression analysis indicated the following predictive variables for AH SDS: target height SDS, height SDS, and chronological age minus bone age (years) at the start of the study. GH dose had no significant effect. In conclusion, long-term continuous GH treatment in short children born SGA without signs of persistent catch-up growth leads to a normalization of AH, even with a GH dose of 3 IU/m(2).d ( approximately 0.033 mg/kg.d).


Asunto(s)
Estatura/efectos de los fármacos , Hormona del Crecimiento/uso terapéutico , Recién Nacido Pequeño para la Edad Gestacional , Adulto , Desarrollo Óseo/efectos de los fármacos , Preescolar , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Hormona del Crecimiento/efectos adversos , Hormonas/sangre , Hormona de Crecimiento Humana/sangre , Humanos , Recién Nacido , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Pronóstico , Pubertad/efectos de los fármacos , Análisis de Regresión
9.
J Clin Endocrinol Metab ; 88(3): 1119-25, 2003 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-12629094

RESUMEN

Although GH treatment for short stature in Turner syndrome is an accepted treatment in many countries, which GH dosage to use and which age to start puberty induction are issues of debate. This study shows final height (FH) in 60 girls with Turner syndrome treated in a randomized dose-response trial, combining GH treatment with low dose estrogens at a relatively young age. Girls were randomly assigned to group A (4 IU/m(2).d; approximately 0.045 mg/kg/d), group B (first year, 4 IU/m(2).d; thereafter 6 IU/m(2).d), or group C (first year, 4 IU/m(2).d; second year, 6 IU/m(2).d; thereafter, 8 IU/m(2).d). After a minimum of 4 yr of GH treatment, at a mean age of 12.7 +/- 0.7 yr, low dose micronized 17beta-estradiol was given orally. After a mean duration of GH treatment of 8.6 +/- 1.9 yr, FH was reached at a mean age of 15.8 +/- 0.9 yr. FH, expressed in centimeters or SD score, was 157.6 +/- 6.5 or -1.6 +/- 1.0 in group A, 162.9 +/- 6.1 or -0.7 +/- 1.0 in group B, and 163.6 +/- 6.0 or -0.6 +/- 1.0 in group C. The difference in FH in centimeters, corrected for height SD score and age at start of treatment, was significant between groups A and B [regression coefficient, 4.1; 95% confidence interval (CI), 1.4, 6.9; P < 0.01], and groups A and C (coefficient, 5.0; 95% CI, 2.3, 7.7; P < 0.001), but not between groups B and C (coefficient, 0.9; 95% CI, -1.8, 3.6). Fifty of the 60 girls (83%) had reached a normal FH (FH SD score, more than -2). After starting estrogen treatment, the decrease in height velocity (HV) changed significantly to a stable HV, without affecting bone maturation (change in bone age/change in chronological age). The following variables contributed significantly to predicting FH SD score: GH dose, height SD score (ref. normal girls), chronological age at start of treatment, and HV in the first year of GH treatment. GH treatment was well tolerated. In conclusion, GH treatment leads to a normalization of FH in most girls, even when puberty is induced at a normal pubertal age. The optimal GH dosage depends on height and age at the start of treatment and first year HV.


Asunto(s)
Estatura/efectos de los fármacos , Estradiol/administración & dosificación , Hormona de Crecimiento Humana/administración & dosificación , Síndrome de Turner/tratamiento farmacológico , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Estradiol/efectos adversos , Femenino , Hormona de Crecimiento Humana/efectos adversos , Humanos , Factor I del Crecimiento Similar a la Insulina/análisis , Síndrome de Turner/fisiopatología
10.
J Clin Endocrinol Metab ; 88(1): 347-53, 2003 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-12519875

RESUMEN

Hyperlipidemia, diabetes mellitus type 2, and coronary heart disease have been associated with being born small for gestational age (SGA). It has been reported that GH treatment induced higher insulin levels, which has led to concern regarding the long-term effect of GH treatment in predisposed individuals such as children born SGA. In this study, we assessed the effect of discontinuation of long-term GH treatment in 47 adolescents born SGA on oral glucose tolerance tests, blood pressure (BP), and serum lipid levels for two GH dosage groups (3 vs. 6 IU/m2 x d). At 6 months after discontinuation of GH treatment mean (SD) age was 16.0 (2.1) yr. Mean duration of GH treatment had been 6.9 (1.5) yr. Fasting glucose levels and 120-min area under the curve for glucose 6 months after discontinuation of GH treatment showed no difference from pretreatment levels for both GH dosage groups. After discontinuation of GH treatment, fasting insulin levels returned to pretreatment levels (8.4 mU/liter), whereas the 120-min area under the curve for insulin decreased, compared with 6-yr levels (P < 0.01), regardless of GH dosage group. No significant difference was found when levels were compared with a control group. In addition, for both GH dosage groups, no significant changes in systolic and diastolic BP SD score, total cholesterol, and atherogenic index (total cholesterol/high-density lipoprotein cholesterol) were seen from 6 yr of GH until 6 months after discontinuation of GH treatment. In conclusion, in children born SGA, the GH-induced insulin insensitivity disappeared after discontinuation of GH, even after long-term GH treatment. Furthermore, the beneficial effect of GH on BP was not changed after discontinuation of GH, and most children had normal lipid levels.


Asunto(s)
Enfermedades Cardiovasculares/etiología , Hormona del Crecimiento/administración & dosificación , Recién Nacido Pequeño para la Edad Gestacional , Adolescente , Presión Sanguínea/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Prueba de Tolerancia a la Glucosa , Hormona del Crecimiento/uso terapéutico , Humanos , Recién Nacido , Insulina/sangre , Lípidos/sangre , Masculino , Factores de Riesgo
11.
J Clin Endocrinol Metab ; 87(12): 5442-8, 2002 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-12466334

RESUMEN

GH treatment increases insulin levels in girls with Turner syndrome (TS), who are already predisposed to develop diabetes mellitus and other risk factors for developing cardiovascular disease. Therefore, in the present study, we investigated carbohydrate metabolism and several other risk factors that may predict development of cardiovascular disease in girls with TS after discontinuation of long-term GH treatment. Fifty-six girls, participating in a randomized dose-response study, were examined before, during, and 6 months after discontinuing long-term GH treatment with doses of 4 IU/m(2).d ( approximately 0.045 mg/kg.d), 6 IU/m(2).d, or 8 IU/m(2).d. After a minimum of 4 yr of GH treatment, low-dose micronized 17beta-estradiol was given orally. Mean (SD) age at 6 months after discontinuation of GH treatment was 15.8 (0.9) yr. Mean duration of GH treatment was 8.8 (1.7) yr. Six months after discontinuation of GH treatment, fasting glucose levels decreased and returned to pretreatment levels. The area under the curve for glucose decreased to levels even lower than pretreatment level (P < 0.001). Fasting insulin levels and the area under the curve for insulin decreased to levels just above pretreatment level (P < 0.001 for both), although being not significantly different from the control group. No dose-dependent differences among GH dosage groups were found. At 6 months after discontinuation, impaired glucose tolerance was present in 1 of 53 girls (2%), and none of the girls developed diabetes mellitus type 1 or 2. Compared with pretreatment, the body mass index SD-score had increased (P < 0.001), and the systolic and diastolic blood pressure SD-score had decreased significantly at 6 months after discontinuation of GH treatment (P < 0.001 for both) although remaining above zero (P < 0.001, P < 0.05, and P < 0.005, respectively). Compared with pretreatment, total cholesterol (TC) did not change after discontinuation of GH treatment, whereas the atherogenic index [AI = TC/high-density lipoprotein cholesterol (TC/HDL-c)] and low-density lipoprotein cholesterol (LDL-c) had decreased; and both HDL-c and triglyceride levels increased (P < 0.001 for AI, LDL-c, and HDL-c; P < 0.05 for triglyceride). Compared with the control group, AI, serum TC, and LDL-c levels were significantly lower (P < 0.001 for all), whereas HDL-c levels were significantly higher (P < 0.05). In conclusion, after discontinuation of long-term GH treatment in girls with TS, the GH-induced insulin resistance disappeared, blood pressure decreased but remained higher than in the normal population, and lipid levels and the AI changed to more cardio-protective values.


Asunto(s)
Metabolismo de los Hidratos de Carbono , Enfermedades Cardiovasculares/etiología , Hormona del Crecimiento/administración & dosificación , Síndrome de Turner/metabolismo , Síndrome de Turner/fisiopatología , Presión Sanguínea , Índice de Masa Corporal , Niño , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Hormona del Crecimiento/uso terapéutico , Humanos , Resistencia a la Insulina/fisiología , Lípidos/sangre , Masculino , Factores de Riesgo , Síndrome de Turner/patología
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