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PURPOSE: The separation between the inside and outside through the skin was fundamental for the evolution of prevertebrates, which grow through extrapituitary circuits, to vertebrates, which grow through the somatotrophic axis, namely pituitary growth hormone (GH). and circulating IGF1.Individuals with untreated isolated growth hormone (GH) deficiency (IGHD) due to a mutation in the GH-releasing hormone receptor (GHRH) gene, residing in Itabaianinha, Brazil, are vulnerable to skin cancer and have reduced sweating. However other aspects of their skin physiology are still unknown. Our objectives were to evaluate the number of skin cancers, skin aging, and functional aspects of the skin in this IGHD cohort. METHODS: Twenty-six IGHD individuals and 26 controls matched by age, sex, ethnicity, and occupation were submitted to a biochemical, dermatological and a functional skin assessment by the Multi Probe Adapter Cutometer® MPA 580. RESULTS: There was no difference in the number of skin cancers and in the degrees of photodamage between the groups. The melanin content in the forearm was similar between the groups but was lower in the buttocks (p = 0.005), as well as skin resistance (p < 0.0001) and elasticity (p = 0.003), lower in the IGHD. There was no difference in hydration and sebum content between the two groups. CONCLUSION: IGHD is apparently associated with a neutral profile in terms of skin cancer and photodamage, with similar melanin on the forearm and lower buttocks, lower skin resistance and elasticity, with hydration and sebum similar to controls.
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Hormônio do Crescimento Humano , Pele , Humanos , Masculino , Feminino , Adulto , Pele/metabolismo , Hormônio do Crescimento Humano/deficiência , Pessoa de Meia-Idade , Neoplasias Cutâneas , Envelhecimento da Pele/fisiologia , Adulto Jovem , Fenômenos Fisiológicos da Pele , Nanismo Hipofisário/epidemiologia , AdolescenteRESUMO
PURPOSE: Individuals with isolated GH deficiency (IGHD) due to a mutation in the GHRH receptor gene have a normal life expectancy and above 50 years of age, similar total cognitive performance, with better attention and executive function than controls. Our objectives were to evaluate their brain morphometry and brain aging using MRI. METHODS: Thirteen IGHD and 14 controls matched by age, sex, and education, were enrolled. Quantitative volumetric data and cortical thickness were obtained by automatic segmentation using Freesurfer software. The volume of each brain region was normalized by the intracranial volume. The difference between the predicted brain age estimated by MRI using a trained neuronal network, and the chronological age, was obtained. p < 0.005 was considered significant and 0.005 < p < 0.05 as a suggestive evidence of difference. RESULTS: In IGHD, most absolute values of cortical thickness and regional brain volumes were similar to controls, but normalized volumes were greater in the white matter in the frontal pole and in the insula bilaterally, and in the gray matter, in the right insula and in left Caudate (p < 0.005 for all comparisons) We also noticed suggestive evidence of a larger volume in IGHD in left thalamus (p = 0.006), right thalamus (p = 0.025), right caudate (p = 0.046) and right putamen (p = 0.013). Predicted brain ages were similar between groups. CONCLUSION: IGHD is primarily associated with similar absolute brain measurements, and a set of larger normalized volumes, and does not appear to alter the process of brain aging.
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Individuals with untreated isolated GH deficiency (IGHD) due to a mutation in the GHRH receptor gene from Itabaianinha Brazil have increased insulin sensitivity, normal life expectancy, and an extended health span, i.e. the period of life free from disabilities. We hypothesize that their prolonged health span is accompanied by a delayed cognitive decline in senescence. To test this hypothesis, we have administered the Literacy-Independent Cognitive Assessment (LICA) to 15 IGHD individuals aged over 50 years and 15 controls matched by age, sex, years of education, and percentage of illiteracy. All individuals were negative for HIV and syphilis serology, and there were no differences in serum levels of folate, vitamin B12 and TSH between the two groups, while free T4 was higher in the IGHD group. IGHD subjects had a higher total LICA score than controls, 215 (22.7) vs 204.2 (18.1), without reaching statistical significance. Scores of memory, visuoconstruction, language and calculation were similar between the two groups, with better attention (9.5 (1.4) vs 8.3 (1.1), P = 0.01) and executive function (38.3 (4.8) vs 35.1 (2.5), P = 0.03) scores in IGHD. MANCOVA revealed that group (but no age) had a significant effect on the LICA variables (partial eta squared of 0.455, power of 0.812, P = 0.02). This effect is verified on attention (partial eta squared 0.216, power of 0.749, P = 0.01) and executive function (partial eta squared 0.154, power of 0.570, P = 0.03. In conclusion, IGHD in senescence is associated with similar total cognitive performance but better attention and executive function than controls.
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This study evaluated the differences in vitamin D3 synthesis in two different latitudes throughout 1 year using an in vitro model, which simulates cutaneous vitamin D photoproduction. Borosilicate ampoules containing 7-dehydrocholesterol (7-DHC) were exposed to sunlight hourly throughout the daylight hours, 1 day per month for a year, in Fortaleza (latitude 03° 43' 01" S-LAT3° S) and Sao Paulo (latitude 23° 32' 53" S-LAT23° S). Later, vitamin D3 and photoisomers of 7-DHC (tachysterol and lumisterol) were measured by a high-performance liquid chromatography system (HPLC). Vitamin D synthesis weighted UV radiation (UVBVitD) and solar zenith angle (SZA) were calculated during the same periods for both latitudes. Vitamin D3 synthesis occurred throughout the year in both locations, as expected in latitudes lower than 35°. Median of photoconversion to vitamin D3 through the year was higher in LAT3°S [median (IQR): LAT 3°S 4.1% (6.0); LAT 23°S 2.9% (4.5); p value = 0.020]. Vitamin D3 production strongly correlated with UV-B (LAT3° S, r = 0.917; p < 0.0001 and at LAT23° S, r = 0.879; p < 0.0001) and SZA (LAT3° S, r = - 0.924; p < 0.0001 and in LAT23°S, r = - 0.808; p < 0.0001). Vitamin D3 production starts later in LAT23° S, especially in winter. Lowest percentages were observed in June in both cities, although, compared to LAT3° S, in LAT 23° S the conversion was over 50% lower in the winter period. Cloudiness impaired photoproduction of Vitamin D3 even in summer months in both latitudes. Our results provide data to help guide medical recommendations for sensible sun exposure to promote the cutaneous production of vitamin D3 at different latitudes, seasonality, time of day and cloudiness status in Brazil.
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Raios Ultravioleta , Vitamina D/química , Brasil , Colecalciferol/análise , Colecalciferol/química , Cromatografia Líquida de Alta Pressão , Desidrocolesteróis/análise , Desidrocolesteróis/química , Humanos , Estações do Ano , Vitamina D/análise , Vitamina D/efeitos da radiaçãoRESUMO
PURPOSE: A reciprocal relationship exists between the skin and the GH/IGF-I axis. Skin produces both IGF- I and vitamin D, and GH and IGF-I exert several actions in the skin. Reduced sweating and altered phosphor-calcium homeostasis are occasionally reported in subjects with GH deficiency (GHD), mostly in the setting of hypopituitarism, therefore associated to other hormonal deficiencies. It is unclear whether these findings are due to GHD. The aim of this study was to assess skin function in subjects with isolated GHD (IGHD) due to a mutation in the GHRH receptor gene. METHODS: In a cross-sectional study we enrolled 20 IGHD and 20 local controls. Sweating (volume, conductivity and chloride content) was assessed by a 30 min pilocarpine iontophoresis test, using the Macroduct® Sweat Collection System. IGF-I, Insulin, PTH, 25-hydroxyvitamin D, C-reactive protein (CRP), CPK, glucose, calcium, phosphate, alkaline phosphatase, total proteins and fractions, urinary calcium, and insulin were measured. HOMA-IR was calculated. RESULTS: IGHD presented lower sweating, but normal vitamin D and phosphor-calcium homeostasis. Additionally, IGHD subjects presented lower HOMA-IR, higher CRP and reduced CPK. CONCLUSION: Untreated IGHD cause reduction in sweating, but does not affect phosphor-calcium homeostasis.
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Hormônio do Crescimento Humano/deficiência , Sudorese , Deficiência de Vitamina D/sangue , Vitamina D/sangue , Adulto , Proteína C-Reativa/análise , Estudos de Coortes , Creatina Quinase/sangue , Estudos Transversais , Feminino , Homeostase , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Pele/fisiopatologia , Suor/química , Suor/metabolismo , Deficiência de Vitamina D/complicaçõesRESUMO
CONTEXT: GH and IGF-1 are crucial for attainment of normal body size and regulation of food intake, nutrient storage, and insulin sensitivity. Enteroendocrine connections exist between the GH-IGF-1 axis and insulin, ghrelin, and glucagon-like peptide 1 (GLP-1). The status of these connections in GH deficiency (GHD) is unknown. OBJECTIVE: To study the enteroendocrine connections before and after a standard meal test in a homogeneous population of adults with congenital untreated isolated GHD (IGHD) due to a mutation in the GHRH receptor gene. DESIGN: In a cross-sectional study of 20 individuals with IGHD and 20 control subjects, we measured glucose, insulin, ghrelin, and GLP-1 before and 30, 60, 120, and 180 minutes after a standardized test meal. Homeostasis model assessment index of insulin resistance (HOMA-IR) and homeostasis model assessment (HOMA)-ß were calculated. Participants scored feelings of hunger, fullness, and prospective food consumption on a visual analog scale. MAIN OUTCOME MEASURES: Area under the curve (AUC) values of glucose, insulin, ghrelin, GLP-1, hunger, fullness, and prospective food consumption. RESULTS: Fasting HOMA-IR and HOMA-ß were lower in individuals with IGHD than in control subjects (P = 0.002 and P = 0.023, respectively). AUC was higher for hunger (P < 0.0001), glucose (P = 0.0157), ghrelin (P < 0.0001), and GLP-1 (P < 0.0001) and smaller for fullness (P < 0.0001) in individuals with IGHD compared with control subjects. There was no difference in AUC for prospective food consumption or insulin. CONCLUSIONS: Untreated IGHD is associated with increased GLP-1 secretion and reduced postprandial ghrelin and hunger attenuation in response to a mixed meal. These enteroendocrine connections can result in a favorable outcome in terms of environmental adaptation and guaranteeing appropriate food intake and can confer metabolic benefits.
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Glicemia/metabolismo , Nanismo Hipofisário/metabolismo , Grelina/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Resistência à Insulina , Insulina/metabolismo , Período Pós-Prandial , Receptores LHRH/genética , Adulto , Área Sob a Curva , Estudos de Casos e Controles , Nanismo Hipofisário/genética , Ingestão de Alimentos , Feminino , Humanos , Fome , Masculino , Pessoa de Meia-Idade , Mutação , Resposta de SaciedadeRESUMO
Growth hormone (GH) and the insulin-like growth factor I (IGF-I) have cell proliferative and differentiation properties. Whether these hormones have a role in mutagenesis is unknown. Nevertheless, severe IGF-I deficiency seems to confer protection against the development of neoplasms. Here, we report five cases of adult patients with severe and congenital isolated GH deficiency (IGHD) due to the c.57+1G>A mutation in the GHRH receptor gene, who developed tumors. Four GH-naïve subjects presented skin tumors: a 42-year-old man with a fibroepithelial polyp, a 53-year-old woman and two men (59 and 56â¯years old) with epidermoid skin cancers. One of these died from it after three surgeries and radiotherapy. The fifth patient was a 25-year-old woman, who had intermittently received GH replacement therapy (GHRT) from age 11 to 18, who developed an ependymoma extending from the fourth ventricle to the end of the thoracic spine. She underwent three surgical procedures, without obvious evidence of tumor recurrence during the six years follow up. These observations suggest that severe IGHD does not protect completely from development of tumors.
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Biomarcadores/metabolismo , Nanismo Hipofisário/complicações , Hormônio do Crescimento Humano/deficiência , Mutação , Neoplasias/epidemiologia , Receptores de Neuropeptídeos/genética , Receptores de Hormônios Reguladores de Hormônio Hipofisário/genética , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/genética , Prognóstico , Índice de Gravidade de DoençaRESUMO
The GH/IGF-I axis has important interactions with the alimentary system and with the balance between energy intake (EI) and energy requirement (ER). Reduced EI has been described in adult-onset acquired GH deficiency (GHD). Individuals from the Brazilian Itabaianinha cohort, with isolated GHD (IGHD) due to a homozygous mutation (c.57+1GâA) in the GHRH receptor gene, are an ideal model to study the consequences of lifetime GHD. The purpose of this study is to evaluate EI and ER in this untreated IGHD cohort. Cross-sectional study of 24 adult IGHD patients and 23 controls from the same region, matched for age and gender. Estimated EI (EEI) was evaluated by dietary recall, and estimated ER (EER) by the equation of the Dietary Reference Intakes. Fat mass was assessed by DXA. Both EEI and EER were lower in IGHD than controls. However, when corrected by body weight, EEI was higher in IGHD (p = 0.005). IGHD individuals consume in percentage more proteins (p < 0.0001), less carbohydrates (p = 0.013), and equal amount of lipids in comparison to controls. The higher EEI per body weight suggests a possible increase of orexigenic mechanisms in untreated IGHD individuals, ensuring greater caloric intake, which would have adaptive advantages for small-sized individuals in environments with limited access to food. IGHD individuals seem to have a healthier dietary pattern than CO.