RESUMO
ABSTRACT Objective To evaluate melatonin secretion in adult hypopituitary patients with Growth Hormone deficiency (AGHD) on and off replacement therapy. Subjects and methods We studied 48 subjects: 12 (6 males) untreated AGHD (AGHDnt), 20 (10 males) treated AGHD (AGHDt) and 16 healthy subjects (8 males) as control group (CG). We measured urinary 6-sulfatoxymelatonin (6-SM) in total (24 h samples), nocturnal (6-SMn): 1800-0800 and diurnal samples (6-SMd): 0800-1800. Results Significant differences were observed among the 3 groups of male subjects, in total 6-SM (p < 0.05), nocturnal 6-SM (p < 0.02) and nighttime-daytime delta values (p < 0.003). CG had significantly higher values than the AGHDnt in total 6-SM (p < 0.01), nocturnal 6-SM (p < 0.05) and nighttime-daytime delta values (p < 0.01). AGHDt patients showed significantly higher levels in nighttime-daytime delta values than AGHDnt patients (p < 0.05). In females, no significant differences were found among the 3 groups studied in total, nocturnal, diurnal or nighttime-daytime delta values. In males, significant correlations were found among total 6-SM (r = 0.58; p = 0.029), nocturnal 6-SM (r = 0.70; p = 0.006) and nighttime-daytime delta values (r = 0.71; p = 0.004) vs. serum IGF-1 levels in subjects evaluated. In females, significant correlations were found among total 6-SM (r = 0.57; p = 0.02) vs. serum IGF-1 levels in subjects evaluated. A tendency towards a significant correlation was found in diurnal 6-SM (r = 0.48; p = 0.07). Conclusions Our findings show a sexual dimorphism in 6-SM excretion in AGHD patients and provide an interesting approach to a further understanding of some chronobiological disorders involved in GH deficiency.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Fatores Sexuais , Ritmo Circadiano/fisiologia , Hormônio do Crescimento Humano/deficiência , Melatonina/análogos & derivados , Hipófise/fisiologia , Fator de Crescimento Insulin-Like I , Estudos de Casos e Controles , Estudos Prospectivos , Hipopituitarismo/fisiopatologia , Melatonina/metabolismo , Melatonina/urinaRESUMO
Longitudinal growth results from multifactorial and complex processes that take place in the context of different genetic traits and environmental influences. Thus, in view of the difficulties in comprehension of the physiological mechanisms involved in the achievement of normal height, our ability to make a definitive diagnosis of GH impairment still remains limited. There is a myriad of controversial aspects in relation to GH deficiency, mainly related to diagnostic controversies and advances in molecular biology. This might explain the diversity in therapeutic responses and may also serve as a rationale for new "nonclassical" treatment indications for GH. It is necessary to acquire more effective tools to reach an adequate evaluation, particularly while considering the long-term implications of a correct diagnosis, the cost, and safety of treatments. On the other hand, overgrowth constitutes a heterogeneous group of different pathophysiological situations including excessive somatic and visceral growth. There are overlaps in clinical and molecular features among overgrowth syndromes, which constitute the real burden for an accurate diagnosis. In conclusion, both GH deficiency and overgrowth are a great dilemma, still not completely solved. In this chapter, we review the most burdensome aspects related to short stature, GH deficiency, and excess in children, avoiding any details about well-known issues that have been extensively discussed in the literature.
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Hormônio do Crescimento/deficiência , Hormônio do Crescimento/metabolismo , Criança , Transtornos do Crescimento/etiologia , HumanosRESUMO
OBJECTIVE: To evaluate melatonin secretion in adult hypopituitary patients with Growth Hormone deficiency (AGHD) on and off replacement therapy. SUBJECTS AND METHODS: We studied 48 subjects: 12 (6 males) untreated AGHD (AGHDnt), 20 (10 males) treated AGHD (AGHDt) and 16 healthy subjects (8 males) as control group (CG). We measured urinary 6-sulfatoxymelatonin (6-SM) in total (24 h samples), nocturnal (6-SMn): 1800-0800 and diurnal samples (6-SMd): 0800-1800. RESULTS: Significant differences were observed among the 3 groups of male subjects, in total 6-SM (p < 0.05), nocturnal 6-SM (p < 0.02) and nighttime-daytime delta values (p < 0.003). CG had significantly higher values than the AGHDnt in total 6-SM (p < 0.01), nocturnal 6-SM (p < 0.05) and nighttime-daytime delta values (p < 0.01). AGHDt patients showed significantly higher levels in nighttime-daytime delta values than AGHDnt patients (p < 0.05). In females, no significant differences were found among the 3 groups studied in total, nocturnal, diurnal or nighttime-daytime delta values. In males, significant correlations were found among total 6-SM (r = 0.58; p = 0.029), nocturnal 6-SM (r = 0.70; p = 0.006) and nighttime-daytime delta values (r = 0.71; p = 0.004) vs. serum IGF-1 levels in subjects evaluated. In females, significant correlations were found among total 6-SM (r = 0.57; p = 0.02) vs. serum IGF-1 levels in subjects evaluated. A tendency towards a significant correlation was found in diurnal 6-SM (r = 0.48; p = 0.07). CONCLUSIONS: Our findings show a sexual dimorphism in 6-SM excretion in AGHD patients and provide an interesting approach to a further understanding of some chronobiological disorders involved in GH deficiency.
Assuntos
Ritmo Circadiano/fisiologia , Hormônio do Crescimento Humano/deficiência , Hipopituitarismo/fisiopatologia , Melatonina/análogos & derivados , Fatores Sexuais , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Fator de Crescimento Insulin-Like I , Masculino , Melatonina/metabolismo , Melatonina/urina , Pessoa de Meia-Idade , Hipófise/fisiologia , Estudos Prospectivos , Adulto JovemRESUMO
AIM: To evaluate melatonin secretion in a group of untreated and treated male growth hormone (GH)-deficient children and adolescents. METHODS: We studied 44 male subjects: 8 untreated GH-deficient patients (GHDnt), 16 treated GH-deficient patients (GHDt) and 20 healthy children and adolescents as control group (CG). We measured urinary 6-sulfatoxymelatonin (6-SM) in total (24-hour samples), nocturnal (18.00-8.00 h) and diurnal samples (8.00-18.00 h). Levels of 6-SM were expressed as micrograms excreted per time interval and x0394; values (difference between nighttime and daytime values). RESULTS: Significant differences were observed among the 3 groups of pediatric subjects studied for total 6-SM (p < 0.0001), nocturnal 6-SM (p < 0.0001) and x0394; values (p < 0.0001). Subsequent analysis showed significantly higher levels for total 6-SM, nocturnal 6-SM and nighttime-daytime x0394; in the CG versus the GHDnt (p < 0.01) and in the CG versus the GHDt group (p < 0.01). No significant correlations were found between 6-SM excretion and insulin-like growth factor-1 values in the children and adolescents studied. CONCLUSIONS: GH-deficient patients showed lower levels of 6-SM. Our findings provide a different insight to a further understanding of some chronobiological disorders involved in GH deficiency in children.
Assuntos
Hormônio do Crescimento Humano/deficiência , Melatonina/análogos & derivados , Adolescente , Estatura/efeitos dos fármacos , Criança , Pré-Escolar , Ritmo Circadiano , Transtornos do Crescimento/tratamento farmacológico , Transtornos do Crescimento/urina , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/urina , Masculino , Melatonina/urina , Proteínas Recombinantes/uso terapêuticoRESUMO
BACKGROUND: It is possible that genes on the X chromosome are expressed differently depending of its parental origin. The objective of this study was to determine the influence of the parental origin of the X-chromosome on phenotypic variability, response to rhGH and on the biochemical profile of TS patients. METHODS: This was a cross-sectional multicenter correlational study carried out over three years in six Latin-American university hospitals. Unrelated 45,X TS patients (n = 93; 18.3 ± 8.5 years )) were evaluated. A subgroup (n = 34) of the patients were prospectively treated with rhGH over two years. DNA profiles of patients and their mothers were compared to determine the parental origin of the retained X-chromosome through 10 polymorphic X-chromosome-STRs. The association with clinical features, biochemical profiles and anthropometric data at the beginning and after two years of rhGH treatment was determined. RESULTS: Seventy two percent of patients retained the maternal X chromosome (Xm). A trend towards significance between maternal height and patients final height (p ≤ 0.07) in 45,Xm subjects was observed. There was no correlation between paternal height and patient height. No differences were detected between both groups in regard to dysmorphic features, classical malformations or increase in the height-SDS after rhGH. There were higher levels of triglycerides, total and LDL cholesterol in patients >20 years who retained the Xm. CONCLUSIONS: The parental origin of the retained X chromosome may influence lipid metabolism in TS patients, but its effect on growth seems to be minimal. No parental-origin-effect on the phenotypic features, associated anomalies and on the growth response to rhGH was found in 45,X TS individuals.
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On behalf of the Global Pediatric Endocrinology and Diabetes group, the authors provide a perspective on the rights of a child as enshrined in the United Nations Convention on the Rights of the Child (1989) concerning the care of pediatric endocrine disorders and diabetes mellitus, throughout the world, with particular reference to care in resource-constrained settings. In this article, we define the spectrum of health care needs of the child with an endocrine disorder and how they may be addressed, in terms of education, research, and development of sustainable programs for improved health outcomes. We emphasize the responsibilities of medical communities, the pharmaceutical industry, and relevant governments in promoting and supporting such concepts.
Assuntos
Defesa da Criança e do Adolescente , Países em Desenvolvimento , Diabetes Mellitus/terapia , Doenças do Sistema Endócrino/terapia , Promoção da Saúde/organização & administração , Garantia da Qualidade dos Cuidados de Saúde/organização & administração , Adolescente , Criança , Pré-Escolar , Comportamento Cooperativo , Estudos Transversais , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Doenças do Sistema Endócrino/diagnóstico , Doenças do Sistema Endócrino/epidemiologia , Feminino , Acessibilidade aos Serviços de Saúde/organização & administração , Necessidades e Demandas de Serviços de Saúde/organização & administração , Humanos , Lactente , Recém-Nascido , Comunicação Interdisciplinar , Masculino , Triagem Neonatal/organização & administração , Equipe de Assistência ao Paciente/organização & administração , Gravidez , Responsabilidade Social , Sociedades Médicas , Resultado do Tratamento , Nações Unidas , Organização Mundial da SaúdeRESUMO
OBJECTIVE: To study two subsets of patients with GH deficiency (GHD) during the transition period: childhood onset GHD (CO-GHD) and patients who develop GHD during the transition phase (TO-GHD) before and after GH replacement. PATIENTS AND MEASUREMENTS: In 1340 GHD subjects from KIMS (Pfizer International Metabolic Database), CO (n=586) or TO (n=754), background characteristics, anthropometric measurements, IGF-1, lipids and quality of life (QoL) were evaluated at baseline and after 3 years of GH replacement. RESULTS: Both groups responded similarly to GH treatment. Changes of clinical outcomes were mainly determined by their value at baseline. Onset of the disease in childhood or transition period did not appear to be a significant predictor of response in any of the clinical outcomes. CONCLUSIONS: Age at GHD diagnosis was a significant predictor for many outcomes at baseline, but disease onset did not appear as an independent predictor concerning changes after 3 years of GH treatment. The results suggest that GH replacement during the transition period should be considered independently of the onset of the deficiency.
Assuntos
Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/deficiência , Adolescente , Adulto , Idade de Início , Feminino , Humanos , Masculino , Qualidade de Vida , Análise de RegressãoRESUMO
Neonatal reference values for serum thyrotropin are scarce and comprise only small numbers of patients. During 2006, changes were made in IMMULITE kits for TSH measurement. To validate methodological changes, 80 serum samples from patients were evaluated and to establish reference intervals, 334 neonates and infants were analyzed (divided into 4 groups). Group 1 (G1) (48-72 h of life) (n=153), group 2A (G2A) (7-10 days of life) (n=65), group 2B (G2B) (11-14 days of life) (n=35), group 3 (G3) (28-40 days of life) (n=81). Current kits overestimate TSH results by 26 to 37%; TSH (mIU/L) reference intervals (percentile 2.5-97.5) were G1 (1.1-12.7), G2A (1.8-9.8), G2B (1.1-7.1) (p < 0.03 vs. G2A), G3 (1.2-6.9). We suggest that during the second week of life, reference values should be divided into an early stage and a late stage, at least, for there to be an adequate interpretation of borderline measurements in newborn thyroid screening.
Assuntos
Triagem Neonatal/métodos , Kit de Reagentes para Diagnóstico , Tireotropina/sangue , Testes de Química Clínica/métodos , Testes de Química Clínica/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Valores de Referência , Hormônios Tireóideos/sangueAssuntos
Hormônio do Crescimento/uso terapêutico , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/deficiência , Puberdade , Adolescente , Fatores Etários , Idade de Início , Densidade Óssea/efeitos dos fármacos , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/prevenção & controle , Criança , Monitoramento de Medicamentos , Nanismo Hipofisário/diagnóstico , Nanismo Hipofisário/tratamento farmacológico , Nanismo Hipofisário/genética , Nanismo Hipofisário/metabolismo , Hormônio do Crescimento/farmacologia , Hormônio do Crescimento Humano/genética , Hormônio do Crescimento Humano/fisiologia , Humanos , América Latina , Desenvolvimento Muscular/efeitos dos fármacos , Adulto JovemRESUMO
OBJECTIVE: GH deficiency (GHD) in adults is characterized by elevated body mass index (BMI), increased waist girth (WG) and increased fat mass (FM). Information about how these indicators of obesity affect the lipid profile and quality of life (QoL) of GHD subjects is scarce. It is also unclear how changes in these indicators brought about by GH replacement influence lipids and QoL. DESIGN AND METHODS: Adult GHD subjects from the Pfizer International Metabolic Database were grouped according to BMI (n=291 with BMI <25 kg/m(2), n=372 with BMI 25-30 kg/m(2), n=279 with BMI >30 kg/m(2)), WG (n=508 with normal WG, n=434 with increased WG) and FM (n=357) and according to changes in these variables after 1 year of GH replacement. Serum IGF-I concentrations, lipid concentrations and QoL using the QoL Assessment of GHD in Adults questionnaire were assessed at baseline and after 1 year of treatment. RESULTS: At baseline, total and low-density lipoprotein (LDL) cholesterol were similarly elevated in the BMI and WG groups, but high-density lipoprotein (HDL) cholesterol decreased and triglycerides increased with increasing BMI and WG. QoL was progressively poorer with increasing BMI and WG. After 1 year of GH replacement, total and LDL cholesterol and QoL improved in all BMI, WG and FM groups. CONCLUSIONS: Variables of obesity adversely affect the already unfavourable lipid profile in GHD subjects by decreasing HDL cholesterol, but do not counteract the positive effect of GH replacement on LDL cholesterol. Similarly, QoL is influenced by obesity, but responds equally well to GH treatment independent of BMI, WG and FM.
Assuntos
Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/uso terapêutico , Hipopituitarismo/sangue , Lipídeos/sangue , Obesidade/sangue , Qualidade de Vida , Adulto , Feminino , Terapia de Reposição Hormonal/métodos , Humanos , Hipopituitarismo/tratamento farmacológico , Hipopituitarismo/psicologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/tratamento farmacológico , Obesidade/psicologia , Qualidade de Vida/psicologiaAssuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Puberdade Tardia/diagnóstico , Puberdade Tardia/etiologiaRESUMO
We evaluated long-term replacement therapy outcomes in various subsets of patients with adult growth hormone (GH) deficiency (AGHD) as well as the patients' susceptibility to adverse events. Fifty-nine patients with AGHD were evaluated, 27 with childhood onset (CO) (18-44 years old, 12 females) and 32 with adult onset (AO) (27-70 years, 18 females). A significant improvement in HDL-cholesterol was observed in AGHD-AO males (basal: 41.3 +/- 12.9 mg/dl, intratreatment: 47.5 +/- 13.2 mg/dl, p = 0.009). However, individual analyses showed that total cholesterol decreased below 240 mg/dl in 33% of AGHD-CO patients and in 50% of AGHD-AO patients, and below 200 mg/dl in 67% of AGHD-CO patients and in 29% of AGHD-AO patients; in the AGHD-AO group, normalization of LDL-cholesterol (< or = 160 mg/dl) and triglycerides (< or = 200 mg/dl) was found in 100% and 50% of patients, respectively; the total cholesterol/HDL ratio decreased below 4.5 in 20% of AGHD-CO patients and in 25% of AGHD-AO patients. The cardiological evaluation showed a significant intra- and interindividual heterogeneity, but cardiac mass improved in patients with a baseline cardiac mass index below 60 g/m2. Markers of bone apposition increased significantly, while bone resorption markers were found to remain unchanged during treatment. A correlation was found between increased bone mineral content and lean body mass (p = 0.0009). Susceptibility to adverse events was not found to be dependent on gender or on the time of onset of the deficiency. Our findings would appear to confirm that a more severe metabolic impairment is correlated with a better therapeutic outcome.
Assuntos
Terapia de Reposição Hormonal/efeitos adversos , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Adolescente , Adulto , Idade de Início , Idoso , Biomarcadores/sangue , Composição Corporal , Índice de Massa Corporal , HDL-Colesterol/sangue , Métodos Epidemiológicos , Feminino , Hormônio do Crescimento Humano/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento , Relação Cintura-QuadrilRESUMO
In June 2005, an ad hoc Expert Committee formed by the Pituitary Society convened during the 9th International Pituitary Congress in San Diego, California. Members of this committee consisted of invited international experts in the field, and included endocrinologists and neurosurgeons with recognized expertise in the management of prolactinomas. Discussions were held that included all interested participants to the Congress and resulted in formulation of these guidelines, which represent the current recommendations on the diagnosis and management of prolactinomas based upon comprehensive analysis and synthesis of all available data.
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Algoritmos , Neoplasias Hipofisárias , Complicações Neoplásicas na Gravidez , Prolactinoma , Adenoma/diagnóstico , Adenoma/terapia , Adulto , Criança , Agonistas de Dopamina/uso terapêutico , Feminino , Seguimentos , Humanos , Hiperprolactinemia/diagnóstico , Hiperprolactinemia/etiologia , Hiperprolactinemia/terapia , Masculino , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/terapia , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico , Complicações Neoplásicas na Gravidez/terapia , Prolactinoma/diagnóstico , Prolactinoma/terapiaRESUMO
The objective of this study was to measure the urinary excretion of the main melatonin metabolite 6-sulfatoxymelatonin in obese and normal weight (wt) boys and girls. The study included 94 subjects, aged 4-15.7 yr (50 obese and 44 normal wt; 48 boys) classified as: mid-childhood (4-7.99 yr), late-childhood (8-12 yr) and pubertal (10.1-15.7 yr, Tanner II-IV). Normal wt subjects were children with a body mass index (BMI) between the 25th and 75th percentiles, and the group of obese subjects included children whose BMI was above the 97th percentile. A 24-hr urine sample was collected during two intervals: (i) 18:00-08:00 hr, and (ii) 08:00-18:00 hr. Analysis of urinary 6-sulfatoxymelatonin levels was performed by radioimmunoassay. Excretion of 6-sulfatoxymelatonin was expressed as: (i) total amount excreted (microg); (ii) mug excreted per time interval, nocturnal or diurnal; and (iii) the difference between nocturnal and diurnal samples (microg, estimated amplitude). A factorial analysis of variance indicated that nocturnal 6-sulfatoxymelatonin excretion and amplitude were significantly higher in the obese individuals. A significant interaction 'BMI x age' was detected, i.e. the effect of BMI was significant in the pubertal group only. Total, nocturnal and diurnal 6-sulfatoxymelatonin excretion was significantly higher in girls. The increase in 6-sulfatoxymelatonin excretion found in obesity occurred only in boys and at the pubertal age. To what extent this increase in melatonin production contributes to a delayed puberty in some pubertal obese males remains to be established.
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Melatonina/análogos & derivados , Obesidade/urina , Puberdade/urina , Adolescente , Criança , Pré-Escolar , Ritmo Circadiano , Feminino , Humanos , Masculino , Melatonina/urina , Puberdade Tardia/etiologia , Caracteres SexuaisAssuntos
Humanos , Feminino , Criança , Adolescente , Hiperprolactinemia , Agonistas de Dopamina , HiperprolactinemiaRESUMO
Adult growth hormone deficiency (AGHD) is an heterogeneous clinical entity characterized by increased cardiovascular morbidity and mortality, alterations in body composition, osteoporosis and impaired quality of life. In order to characterize higher risk subpopulations we studied 77 patients with AGHD, 35 with childhood onset (AGHD-CO): CA 18-44 yr.; 13 females and 22 males, and 42 with adult onset (AGHD-AO): CA 25-70 yr.; 22 females and 20 males. IGF-I, lipid profile, glycemia and glycosylated hemoglobin were measured. Cardiological evaluation: blood pressure, electrocardiogram, ergometry and 2D echocardiogram with mitral Doppler, evaluation of diastolic function (A/E waves ratio and deceleration time), systolic function (ejection and shortening fractions) and Cardiac Mass Index (CMI). The Body Mass Index and waist circumference were recorded. Total body composition and bone mineral density were evaluated by densitometry, and the following bone markers were measured: osteocalcin, bone-specific alkaline phosphatase, carboxyterminal propeptide of type I procollagen, Pyridinoline and Deoxipyridinoline. The subset of females with AGHD-AO had higher levels of total cholesterol: 240 mg/dl (156-351) (p < 0.005), LDL: 140 mg/dl (62-262) (p < 0.04) and of total cholesterol/HDL: 4.04 (3.12-12.7) (p < 0.04); while females with AGHD-CO had a decreased CMI: 62 g/m2 (53-107) (p < 0.01), lower A/E waves ratio: 0.56 (0.39-0.72) (p < 0.01) and lower deceleration time: 164 msec. (135-210) (p < 0.01). The subset of males with AGHD-AO had a greater waist circumference: 98 cm (83-128) (p < 0.03) and males with AGHD-CO had a lower shortening fraction: 41% (30-49) (p < 0.006) and lower deceleration time: 153.5 msec. (127-230) (p < 0.03). In both genders, the bone mineral content was lower in patients with AGHD-CO (females p < 0.02, males: p < 0.0008). Our findings confirm the differences in impairment in AGHD patients, which are mainly dependent on gender and the time of onset of the deficiency, and thus demonstrate the heterogeneity of the syndrome.