RESUMEN
BACKGROUND: Conflicting data exist on the effects of GH replacement therapy (GHRT) on thyroid function and thyroid volume (TV) in GH-deficient (GHD) patients. AIM: The aim of this study was to assess the effects of GHRT on thyroid function and TV in adults with congenital lifetime isolated GHD (IGHD). SUBJECTS AND METHODS: We studied 20 GH-naïve adults with IGHD due to a homozygous mutation of the GHRH-receptor gene at baseline, after 6-month depot- GH replacement therapy (pGH), and 6-month washout (6mo). Total T(3), free T(4) (FT(4)), reverse T(3) (rT(3)), TSH, IGF-I, SHBG, and TV were measured; body surface area-corrected TV (CTV) was calculated. RESULTS: IGF-I and T(3) increased pGH. T(3) levels remained elevated at 6mo. GHRT did not significantly change FT(4), rT(3), TSH, and SHBG. TV and CTV increased pGH and remained elevated at 6mo. CONCLUSIONS: GHRT in IGHD adults caused an increase in serum T(3) levels and TV, suggesting an important role of the GH-IGF-I axis in thyroid function.
Asunto(s)
Terapia de Reemplazo de Hormonas/métodos , Hormona de Crecimiento Humana/deficiencia , Hormona de Crecimiento Humana/uso terapéutico , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/fisiología , Adulto , Femenino , Homocigoto , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Persona de Mediana Edad , Receptores de Neuropéptido/genética , Receptores de Hormona Reguladora de Hormona Hipofisaria/genética , Globulina de Unión a Hormona Sexual/metabolismo , Glándula Tiroides/anatomía & histología , Tirotropina/sangre , Tiroxina/sangre , Resultado del Tratamiento , Triyodotironina/sangreRESUMEN
BACKGROUND/OBJECTIVES: Vitamin A deficiency (VAD) is a major public health problem. The supplementation of lactating women could be an effective strategy to combat it. The objective of this study was to assess the impact of maternal vitamin A supplementation on the mother-infant pair. SUBJECTS/METHODS: This was a double blind, placebo-controlled randomized clinical assay in which 33 women received 200 000 IU of vitamin A and 33 women received soy oil between 20th and 30th postpartum days. Maternal blood and milk samples were collected immediately before supplementation and 3 months after delivery, when blood was also collected from the babies. Retinol concentrations îº0.70 µmol/l in serum and 1.05 µmol/l in milk were considered to indicate VAD. RESULTS: Increase in serum retinol level was observed in the supplemented group compared with the pre-supplementation levels (1.05 and 1.17 µmol/l, respectively; P=0.026) and to the post-supplementation levels of the control group (1.02 µmol/l; P=0.032). Reduction in breast milk retinol was observed in the control group compared with the pre-supplementation levels (1.93 and 1.34 µmol/l, respectively; P<0.0001) and to the post-supplementation levels of the supplemented group (1.56 µmol/l; P=0.0003). There was significant difference in the prevalence of VAD in breast milk after supplementation, 55.6% (15/27) in the control group and 16.1% (5/31) in the supplemented group (P=0.002). VAD was present in 66.1% (39/59) of infants, with mean serum retinol levels of 0.64±0.30 µmol/l in the control group and of 0.69±0.26 µmol/l in the supplemented group. CONCLUSIONS: Supplementation had a positive impact on maternal vitamin A status. No effect on infant status was detectable 2 months after supplementation with a single dose.
Asunto(s)
Suplementos Dietéticos , Leche Humana/química , Deficiencia de Vitamina A/tratamiento farmacológico , Vitamina A/uso terapéutico , Adulto , Brasil/epidemiología , Método Doble Ciego , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Aceite de Soja/administración & dosificación , Vitamina A/análisis , Vitamina A/sangre , Deficiencia de Vitamina A/sangre , Deficiencia de Vitamina A/epidemiología , Adulto JovenRESUMEN
PURPOSE: Corticoids have been an option for phimosis treatment since 1993. However, long-term use or repeated cycles pose a concern regarding drug absorption and consequent systemic effects. The aim of this study was to investigate the effect of topical corticoids used in treating phimosis on the hypothalamus-pituitary-adrenal axis in children. MATERIALS AND METHODS: A total of 31 children were included in the study. Cortisol secretion was evaluated by the measurement of salivary cortisol in saliva samples collected at 9:00 a.m. before starting treatment and after 8 weeks of topical treatment with 0.05% clobetasol propionate. Salivary cortisol was determined by radioimmunoassay. To confirm that use of clobetasol propionate was not detected by the assay, the presence of cortisol circadian rhythm was checked by an extra saliva sample obtained at 11:00 p.m. from 10 children, and was observed to be maintained in all of them. RESULTS: No significant difference in salivary cortisol levels was observed between samples obtained at 9:00 a.m. before starting treatment and after completing treatment when the entire group was analyzed. However, in 2 children the salivary cortisol levels after treatment were lower than the cutoff value (358 ng/dl) assumed to be suggestive of hypothalamus-pituitary-adrenal axis suppression. CONCLUSIONS: Topical clobetasol propionate used twice daily for clinical treatment of phimosis does not affect the hypothalamus-pituitary-adrenal axis in most patients. However, salivary cortisol level should be considered as a laboratory marker in long-term treatment or during repeated cycles to detect possible hypothalamus-pituitary-adrenal axis suppression.
Asunto(s)
Clobetasol/uso terapéutico , Glucocorticoides/uso terapéutico , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Fimosis/tratamiento farmacológico , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Adolescente , Niño , Preescolar , Clobetasol/farmacología , Glucocorticoides/farmacología , Humanos , Hidrocortisona/análisis , Masculino , Saliva/químicaRESUMEN
BACKGROUND/OBJECTIVES: Vitamin A deficiency (VAD) is a world public health problem contributing to the increase in childhood morbidity and mortality in developing countries and severe deficiency of vitamin A may lead to xerophthalmia and blindness. The objective of this study was to determine the prevalence of VAD among Brazilian school-aged children attended at a primary health unit and to verify if some considered risk factor was associated with VAD in this group. SUBJECTS/METHODS: A descriptive prospective transverse study was conducted on 103 randomly selected children. A total of 54 boys and 49 girls aged 5.5-11 years had the relative dose-response (RDR) test performed on. Possible ocular alterations related to vitamin A and the status of anemia, serum zinc, some acute-phase proteins, and anthropometric situation were determinate by an analytic design. RESULTS: No child presented xerophthalmia. Serum retinol values lower than 1.05 and 0.7 micromol l(-1), respectively were found in 26.2 and 5.8% of the children. The prevalence of hypovitaminosis detected by RDR test was 20.4%. The following variables and their relationship with VAD were evaluated: sex (P=0.33; 95% confidence interval 0.61-4.34), weight and height (P> or =0.5), hemoglobin (P=0.15), C-reactive protein (P=0.56; 95% confidence interval 0.75-18.26), alpha-1-acid-glycoprotein (P=0.56; 95% confidence interval 0.15-15.42) and serum zinc (P=0.31). None of these variables was related to VAD. CONCLUSIONS: In this population, the prevalence of VAD detected could be considered a public health problem. School-aged children can be considered at risk for VAD mainly of a subclinical level, even without some associated risk factors.
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Deficiencia de Vitamina A/epidemiología , Vitamina A/sangre , Vitaminas/sangre , Brasil/epidemiología , Niño , Preescolar , Femenino , Humanos , Masculino , Prevalencia , Deficiencia de Vitamina A/sangre , Xeroftalmia/epidemiologíaRESUMEN
BACKGROUND: Vitamin A deficiency (VAD) is endemic in Brazil and health professionals have difficulty in recognizing its subclinical form. In addition, serum retinol concentrations do not always represent vitamin A status in the organism. OBJECTIVE: To identify VAD in preschool children by the serum 30-day dose-response test (+S30DR) and to examine its potential as a tool for the assessment of vitamin A status in the community. DESIGN: A prospective transverse study in which blood samples were obtained from 188 preschool children for the determination of serum retinol concentrations and the children were submitted to ocular inspection and anthropometric measurements. Information about the presence of diarrhea and/or fever during the 15 days preceding the study was also obtained. The children received an oral dose of 200,000 IU vitamin A immediately after the first blood collection. A second blood sample was obtained 30-45 days after supplementation in order to determine the +S30DR. RESULTS: In all, 74.5% (140/188; 95% confidence interval: 68.3-80.7%) of the children presented +S30DR values indicative of low hepatic reserves. The mean serum retinol concentration was significantly lower before supplementation (0.92 and 1.65 micromol/l, respectively; P < 0.0001). No child presented xerophthalmia; 3.7% (7/188) of the children were malnourished. The presence of fever and/or diarrhea during the 15 days preceding the first blood collection did not affect the +S30DR value. CONCLUSIONS: The prevalence of VAD in the study group was elevated. +S30DR proved to be a good indicator of subclinical VAD in children from an underdeveloped country.
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Trastornos de la Nutrición del Niño/diagnóstico , Deficiencia de Vitamina A/diagnóstico , Vitamina A/administración & dosificación , Vitamina A/sangre , Antropometría , Brasil/epidemiología , Trastornos de la Nutrición del Niño/sangre , Trastornos de la Nutrición del Niño/epidemiología , Preescolar , Suplementos Dietéticos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Evaluación Nutricional , Estado Nutricional , Estudios Prospectivos , Estudios Seroepidemiológicos , Deficiencia de Vitamina A/sangre , Deficiencia de Vitamina A/epidemiologíaRESUMEN
Salivary cortisol is an index of plasma free cortisol and is obtained by a noninvasive procedure. We have been using salivary cortisol as a tool for physiological and diagnostic studies, among them the emergence of circadian rhythm in preterm and term infants. The salivary cortisol circadian rhythm in term and premature infants was established between 8 and 12 postnatal weeks. In the preterm infants the emergence of circadian rhythm was parallel to the onset of sleep rhythm. We also studied the use of salivary cortisol for screening for Cushing's syndrome (CS) in control and obese outpatients based on circadian rhythm and the overnight 1 mg dexamethasone (DEX) suppression test. Salivary cortisol was suppressed to less than 100 ng/dl after 1 mg DEX in control and obese patients. A single salivary cortisol measurement at 23:00 h and again after 1 mg DEX above the 90th percentile of the obese group values had sensitivity and specificity of 93 and 93% (23:00 h), and 91 and 94% (after DEX), respectively. The sensitivity improved to 100% when we combined both parameters. We also studied 11 CS children and 21 age-matched primary obese children for whom salivary cortisol sensitivity and specificity were 100/95% (23:00 h), and 100/95% (1 mg DEX), respectively. Similar to adults, sensitivity and specificity of 100% were obtained by combining 23:00 h and 1 mg DEX. The measurement of salivary cortisol is a useful tool for physiological studies and for the diagnosis of CS in children and adults on an outpatient basis.
Asunto(s)
Ritmo Circadiano , Síndrome de Cushing/diagnóstico , Hidrocortisona/análisis , Saliva/química , Adolescente , Adulto , Biomarcadores/análisis , Biomarcadores/sangre , Síndrome de Cushing/metabolismo , Dexametasona/administración & dosificación , Femenino , Glucocorticoides/administración & dosificación , Humanos , Hidrocortisona/sangre , Lactante , Recién Nacido , Obesidad/metabolismoRESUMEN
Measurement of the insulin-like growth factors (IGFs) and their binding proteins has become commonplace in the indirect assessment of the integrity of the GH axis. However, the relative effect of GH deficiency (GHD) on each component of the IGF axis and the merit of any one parameter as a diagnostic test have not been defined in a homogeneous population across all ages. We therefore measured IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), IGFBP-2, IGFBP-3, and acid labile subunit (ALS) in 27 GHD subjects (aged 5-82 yr) from an extended kindred in Northeast Brazil with an identical GHRH receptor mutation and in 55 indigenous controls (aged 5-80 yr). The effect of GHD on the theoretical distribution of IGFs between the IGFBPs and the ternary complex was also examined. All components of the IGF axis, measured and theoretical, showed complete separation between GHD and control subjects, except IGFBP-1 and IGFBP-2 concentrations, which did not differ. The most profound effects of GHD were on total IGF-I, IGF-I in the ternary complex, and ALS. The proportion of IGF-I associated with IGFBP-3 remained constant throughout life, but was significantly lower in GHD due to an increase in IGF-I/IGFBP-2 complexes. IGF-I in the ternary complex was determined principally by concentrations of ALS in GHD and IGFBP-3 in controls, implying that ALS has greater GH dependency. In the controls, IGF-II was associated primarily with IGFBP-3 and to a lesser extent with IGFBP-2, whereas in GHD the reverse was found. There was also a dramatic decline in the proportion of free ALS in GHD adults that was not evident in controls. As diagnostic tests, IGF-I in the ternary complex and total IGF-I provided the greatest separation between GHD and controls in childhood. Similarly, in older adults the best separation was achieved with IGF-I in the ternary complex, with free ALS being optimal in younger adults. Severe GHD not only reduces the amounts of IGFs, IGFBP-3, and ALS, but also modifies the distribution of the IGFs bound to each IGFBP. Diagnostic tests used in the investigation of GHD should be tailored to the age of the individual. In particular, measurement of IGF-I in the ternary complex may prove useful in the diagnosis of GHD in children and older adults, whereas free ALS may be more relevant to younger adults.
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Hormona de Crecimiento Humana/deficiencia , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor II del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Mutación , Receptores de Neuropéptido/genética , Receptores de Hormona Reguladora de Hormona Hipofisaria/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: A positive correlation between 24-h spontaneous growth hormone (GH) and cortisol secretion was previously reported in children. This observation prompted us to examine the relationship between physiological diurnal cortisol variation and the levels of insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) under physiological conditions. DESIGN AND PATIENTS: Starting at 0800 h, blood was sampled every 20 minutes over 24 h for measurement of GH and cortisol concentration in nine non-GH- deficient boys as part of a protocol for the investigation of short stature. MEASUREMENTS: IGFBP-1 and insulin were measured in samples drawn every 4 h over the 24-h period while IGF-I, IGF-II, IGFBP-2 and IGFBP-3 were determined in samples collected at the end of the study. RESULTS: No correlation was observed between IGF-I or IGF-II and mean cortisol levels. IGFBP-1 concentrations showed a marked circadian variation that was superimposed on the circadian rhythm for cortisol while a significant positive correlation was found for single point measurements between IGFBP-1 concentrations and cortisol levels measured in the same sample (r = 0.53) or at the preceding 20 minutes (r = 0.43), 40 minutes (r = 0.47) and 2 h (r = 0.38), suggesting an interplay between cortisol and IGFBP-1. A negative correlation (r = - 0.54) was found between IGFBP-1 and insulin levels determined in the same sample. A negative correlation (r = - 0.93) was also found between IGFBP-2 levels and mean cortisol concentrations during the preceding 12 h. No correlation was observed between plasma IGFBP-3 measured by IRMA and mean cortisol levels. CONCLUSION: Our data indicate a clear correlation between cortisol and IGFBP-1 and IGFBP-2 levels. Thus, the interplay of spontaneous GH and cortisol secretion in children may involve changes in IGFBP-1 and IGFBP-2 levels.
Asunto(s)
Ritmo Circadiano , Trastornos del Crecimiento/sangre , Hidrocortisona/sangre , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Adolescente , Área Bajo la Curva , Niño , Hormona del Crecimiento/sangre , Humanos , Insulina/sangre , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Factor II del Crecimiento Similar a la Insulina/análisis , Modelos Lineales , MasculinoRESUMEN
OBJECTIVE: Cushing's syndrome (CS) is characterized by changes in diurnal cortisol variation and total or partial resistance to cortisol suppression by dexamethasone (DEX). Diagnosing CS is a challenge especially in childhood and requires differentiation from primary obesity. The aim was verify the efficacy of salivary cortisol in differentiating primary obesity from CS in children. SUBJECTS AND METHODS: We studied 11 patients with CS confirmed by standard laboratory investigation and surgical findings aged 1-16 years, and 21 age-matched primary obese controls. Salivary samples were collected at 0900 h, 2300 h, and after an overnight DEX suppression test (20 microg/kg up to 1 mg). Salivary cortisol was measured by RIA. RESULTS: Diurnal variation of salivary cortisol levels was observed in all controls, as opposed to only 5 of 11 patients with CS. Suppression of salivary cortisol was detected in all controls but in no CS patient after the overnight DEX test. Mean salivary cortisol levels were higher in the CS than in the control group both at 2300 hours and at 0900 hours after DEX but no difference was observed at 0900 hours of the first day. The sensitivity and specificity of salivary cortisol at 0900 h, 2300 hours and after-DEX in diagnosing CS were 27% and 95.2%, 100% and 95. 2%, and 100% and 95.2%, respectively. Sensitivity and specificity of 100% were obtained by combining the data for 2300 hours and after-DEX. CONCLUSION: The combination of salivary cortisol determination at 2300 hours and after-Dexamethasone is an easily performed and noninvasive method with high specificity and sensitivity for diagnosing Cushing's syndrome in children.
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Síndrome de Cushing/diagnóstico , Hidrocortisona/análisis , Saliva/química , Adolescente , Biomarcadores/análisis , Niño , Preescolar , Ritmo Circadiano , Dexametasona , Diagnóstico Diferencial , Femenino , Glucocorticoides , Humanos , Lactante , Masculino , Obesidad/diagnóstico , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Estadísticas no ParamétricasRESUMEN
OBJECTIVE: Dual effects of corticoids upon GH release in man have been described: a rapid, potentiating effect and a delayed suppressive one. Many investigators have used pharmacological doses of glucocorticoids in an attempt to detect this interaction of corticoids and GH. The aim of the present study was to determine the relationship between GH and cortisol spontaneous secretion in children under physiological conditions. DESIGN AND PATIENTS: Nine children aged 7.5-13.5 years with different growth rates were evaluated over a 24-hour period. Four were of normal stature (+/- 2 SD) and five were below 2 SD (familial or constitutional short stature). Blood samples were obtained at 20-minute intervals over a 24-hour period. MEASUREMENTS: GH and cortisol concentrations were measured by radioimmunoassay in each of the 73 samples collected. RESULTS: A significant correlation was obtained between mean 24-hour cortisol concentration and mean 24-hour GH concentration (r = 0.83; P < 0.01), the sum of 24-hour GH pulse amplitudes (r = 0.85; P < 0.01) and the highest 24-hour GH concentration (r = 0.88; P < 0.01). A significant positive correlation was also detected between mean 24-hour cortisol concentration and the number of GH pulses over a 24-hour period (r = 0.70; P < 0.05). However, there was no significant correlation between mean 24-hour GH concentration and number of cortisol pulses over a 24-hour period. The correlation between number of cortisol pulses and number of GH pulses was also non-significant. CONCLUSION: These data suggest an interplay of spontaneous GH and cortisol secretion in children. Physiological plasma cortisol levels may play a role in brain-pituitary regulatory mechanisms of GH secretion.