Résumé
ABSTRACT Objective Investigate the therapeutic response of acromegaly patients to pegvisomant (PEGV) in a real-life, Brazilian multicenter study. Subjects and methods Characteristics of acromegaly patients treated with PEGV were reviewed at diagnosis, just before and during treatment. All patients with at least two IGF-I measurements on PEGV were included. Efficacy was defined as any normal IGF-I measurement during treatment. Safety data were reviewed. Predictors of response were determined by comparing controlled versus uncontrolled patients. Results 109 patients [61 women; median age at diagnosis 34 years; 95.3% macroadenomas] from 10 Brazilian centers were studied. Previous treatment included surgery (89%), radiotherapy (34%), somatostatin receptor ligands (99%), and cabergoline (67%). Before PEGV, median levels of GH, IGF-I and IGF-I % of upper limit of normal were 4.3 µg/L, 613 ng/mL, and 209%, respectively. Pre-diabetes/diabetes was present in 48.6% and tumor remnant in 71% of patients. Initial dose was 10 mg/day in all except 4 cases, maximum dose was 30 mg/day, and median exposure time was 30.5 months. PEGV was used as monotherapy in 11% of cases. Normal IGF-I levels was obtained in 74.1% of patients. Glycemic control improved in 56.6% of patients with pre-diabetes/diabetes. Exposure time, pre-treatment GH and IGF-I levels were predictors of response. Tumor enlargement occurred in 6.5% and elevation of liver enzymes in 9.2%. PEGV was discontinued in 6 patients and 3 deaths unrelated to the drug were reported. Conclusions In a real-life scenario, PEGV is a highly effective and safe treatment for acromegaly patients not controlled with other therapies.
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Humains , Mâle , Femelle , Enfant , Adolescent , Adulte , Adulte d'âge moyen , Sujet âgé , Sujet âgé de 80 ans ou plus , Jeune adulte , Acromégalie/traitement médicamenteux , Récepteur somatostatine/usage thérapeutique , Hormone de croissance humaine/analogues et dérivés , Cabergoline/usage thérapeutique , Glycémie/analyse , Brésil , Facteur de croissance IGF-I/analyse , Hormone de croissance/sang , Adénomes/traitement médicamenteux , Valeur prédictive des tests , Résultat thérapeutique , Association de médicaments , Cabergoline/administration et posologieRésumé
ABSTRACT Introduction Gigantism is a rare pediatric disease characterized by increased production of growth hormone (GH) before epiphyseal closure, that manifests clinically as tall stature, musculoskeletal abnormalities, and multiple comorbidities. Materials and methods Case series of 6 male patients with gigantism evaluated at the Endocrinology Service of Hospital de San José (Bogotá, Colombia) between 2010 and 2016. Results All patients had macroadenomas and their mean final height was 2.01 m. The mean age at diagnosis was 16 years, and the most common symptoms were headache (66%) and hyperhidrosis (66%). All patients had acral changes, and one had visual impairment secondary to compression of the optic chiasm. All patients underwent surgery, and 5 (83%) required additional therapy for biochemical control, including radiotherapy (n = 4, 66%), somatostatin analogues (n = 5, 83%), cabergoline (n = 3, 50%), and pegvisomant (n = 2, 33%). Three patients (50%) achieved complete biochemical control, while 2 patients showed IGF-1 normalization with pegvisomant. Two patients were genetically related and presented a mutation in the aryl hydrocarbon receptor-interacting protein (AIP) gene (pathogenic variant, c.504G>A in exon 4, p.Trp168*), fulfilling the diagnostic criteria of familial isolated pituitary adenoma. Conclusions This is the largest case series of patients with gigantism described to date in Colombia. Transsphenoidal surgery was the first-choice procedure, but additional pharmacological therapy was usually required. Mutations in the AIP gene should be considered in familial cases of GH-producing adenomas.
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Humains , Mâle , Adolescent , Jeune adulte , Tumeurs de l'hypophyse/thérapie , Adénomes/thérapie , Gigantisme/thérapie , Pedigree , Tumeurs de l'hypophyse/diagnostic , Facteur de croissance IGF-I/analyse , Hormone de croissance/sang , Adénomes/diagnostic , Études rétrospectives , Études de suivi , Résultat thérapeutique , Répartition par sexe , Colombie , Protéines et peptides de signalisation intracellulaire/génétique , Adénome hypophysaire à GH/génétique , Gigantisme/diagnostic , Mutation/génétiqueRésumé
OBJECTIVE: To evaluate the effectiveness of the treatment of acromegaly patients at the Federal University of Triangulo Mineiro. METHODS: Cross-sectional and retrospective study of thirty cases treated over a period of two decades. RESULTS: 17 men (56.7%) aged 14-67 years and 13 women aged 14-86 years were analyzed. Twenty-one patients underwent transphenoidal surgery, whichwas associated with somatostatin receptor ligands in 11 patients (39.3%), somatostatin receptor ligands + radiotherapyin 5 patients (17.8%), radiotherapy in 3 patients (10.7%), and radiotherapy + somatostatin receptorligands + cabergoline in 1 patient (3.6%). Additionally, 2 patients underwent radiotherapy and surgeryalone. Six patients received somatostatin receptor ligands before surgery, and 2 were not treated due to refusal and death. Nine patients have died, and 20 are being followed; 13 (65%) have growth hormonelevels o1 ng/mL, and 11 have normal insulin-like growth factor 1 levels. CONCLUSION: The current treatment options enable patients seen in regional reference centers to achieve strict control parameters, which allows them to be treated close to their homes.
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Humains , Mâle , Femelle , Adolescent , Adulte , Adulte d'âge moyen , Sujet âgé , Sujet âgé de 80 ans ou plus , Jeune adulte , Acromégalie/thérapie , Adénomes/chirurgie , Adénome hypophysaire à GH/chirurgie , Récepteur somatostatine/métabolisme , Acromégalie/sang , Adénomes/métabolisme , Glycémie/analyse , Brésil , Association thérapeutique , Études transversales , Gigantisme/sang , Gigantisme/thérapie , Hormone de croissance/sang , Facteur de croissance IGF-I/analyse , Ligands , Études rétrospectives , Résultat thérapeutiqueRésumé
ABSTRACT Objective To report the evolution of patients with a suggestive clinical scenario and elevated serum insulin-like growth factor-1 (IGF-1), but growth hormone (GH) suppression in the oral glucose tolerance test (OGTT), in whom acromegaly was not initially excluded. Subjects and methods Forty six patients with a suggestive clinical scenario, who had elevated IGF-1 (outside puberty and pregnancy) in two measurements, but GH < 0.4 µg/L in the OGTT, were selected. Five years after initial evaluation, the patients were submitted to clinical and laboratory (serum IGF-1) reassessment. Patients with persistently elevated IGF-1 were submitted to a new GH suppression test and magnetic resonance imaging (MRI) of the pituitary. Results Four patients were lost to follow-up. During reassessment, 42 patients continued to show no “typical phenotype” or changes in physiognomy. Fifteen of the 42 patients had normal IGF-1. Among the 27 patients with persistently elevated IGF-1 and who were submitted to a new OGTT, GH suppression was confirmed in all. Two patients exhibited a lesion suggestive of microadenoma on pituitary MRI. In our interpretation of the results, acromegaly was ruled out in 40 patients and considered “possible” in only 2. Conclusion Our results show that even in patients with a suggestive clinical scenario and elevated IGF-1, confirmed in a second measurement and without apparent cause, acromegaly is very unlikely in the case of GH suppression in the OGTT.
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Humains , Mâle , Femelle , Adulte , Adulte d'âge moyen , Acromégalie/sang , Facteur de croissance IGF-I/analyse , Hormone de croissance/sang , Phénotype , Hypophyse/imagerie diagnostique , Acromégalie/diagnostic , Imagerie par résonance magnétique , Études de suivi , Faux positifs , Hyperglycémie provoquée/méthodesRésumé
OBJECTIVES: To establish cut-off values for growth hormone concentrations using clonidine as a secretagogue and an immunochemiluminescent assay as the method of measurement and to analyze the response time as well as the influence of gender, nutritional status and pubertal stage. METHODS: A total of 225 tests were performed in 3 patient groups, categorized as group 1 (normal), group 2 (idiopathic short stature) and group 3 (growth hormone deficiency). Among the 199 disease-free individuals, 138 were prepubertal, and 61 were pubertal. Clonidine (0.1 mg/m2) was orally administered, and the growth hormone level was measured by immunochemiluminescent assay. The growth hormone peak and the difference between the growth hormone peak and the baseline level were then analyzed. Statistical analyses were performed using Student’s t-test or the Mann-Whitney test and Kruskal-Wallis test followed by Dunn’s post hoc test. Cut-off values were determined using a receiver operating characteristic curve. RESULTS: Group 1 and group 2 had no difference in growth hormone peak, gender, body mass index standard deviation score, or pubertal stage. Group 3 exhibited a significantly lower growth hormone peak than the other groups did. The receiver operating characteristic curve demonstrated that growth hormone concentrations ≥ 3.0 ng/mL defined responsiveness to clonidine. In total, 3.02% of individuals in group 1 and group 2 were considered false positive, i.e., these children lacked growth hormone deficiency and had a peak below 3.0 ng/mL. CONCLUSION: Clonidine-stimulated growth hormone concentrations ≥3 ng/mL, as measured by immunochemiluminescent assay, suggest responsiveness to the stimulus regardless of gender, body mass index standard deviation score or pubertal stage.
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Humains , Mâle , Femelle , Enfant d'âge préscolaire , Enfant , Adolescent , Agonistes des récepteurs alpha-2 adrénergiques/pharmacologie , Taille , Clonidine/pharmacologie , Troubles de la croissance/diagnostic , Hormone de croissance/déficit , Hormone de croissance humaine/sang , Études cas-témoins , Troubles de la croissance/sang , Troubles de la croissance/étiologie , Hormone de croissance/sang , Dosage immunologique/méthodes , Facteur de croissance IGF-I/analyse , Mesures de luminescence/méthodes , Études prospectives , Courbe ROCRésumé
A Síndrome de Proteus é uma rara associação de malformações que podem afetar vários tecidos e órgãos. É caracterizada por macrodactilia bilateral, hipertrofia craniana, anomalias ósseas, escoliose, hamartomas de tecidos moles, nevo verrucoso pigmentar, anormalidades viscerais e outras hipertrofias. Há pouco mais de 200 casos notificados em todo o mundo. O presente artigo relata a evolução clínica de um paciente pediátrico com essa síndrome. A criança apresentou desnutrição grave associada ao extremo gigantismo de membros inferiores. Além disso, apresentou repercussões psicossociais relacionadas à exclusão social. A doença tornou-se mais grave e progrediu como síndrome consumptiva. Finalmente, os pais concordaram com a amputação dos membros inferiores hipertróficos. Um ano após as amputações, a criança estava totalmente reabilitada, protetizada dos membros amputados, com melhora nutricional, além de apresentar notória recuperação psicológica e reinserção social, o que representou melhora significativa da qualidade de vida para o paciente.
Proteus syndrome is a rare combination of malformations that can affect several tissues and organs. It is characterized by bilateral macrodactyly, cranial hypertrophy, bone anomalies, scoliosis, soft-tissue hamartomas, verrucous pigmented nevus, visceral abnormalities and other forms of hypertrophy. Just over 200 cases have been reported worldwide. This article reports on the clinical course of a pediatric patient with this syndrome. The child had severe malnutrition associated with extreme gigantism of the lower limbs and also psychosocial problems related to social exclusion. As the disease progressed it exacerbated and evolved into a wasting syndrome. After several years, the parents agreed to amputation of the hypertrophic lower limbs. One year after the amputations the child had been rehabilitated and had adapted to prostheses, with nutritional improvement and notable psychological recovery and social reintegration, which represented a significant improvement in his quality of life.
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Humains , Mâle , Enfant , Malformations de l'appareil locomoteur/chirurgie , Membre inférieur/anatomopathologie , Membre inférieur , Gigantisme/diagnostic , Gigantisme/rééducation et réadaptation , Gigantisme , Amputation chirurgicale/rééducation et réadaptation , Hormone de croissance/sang , Spectroscopie par résonance magnétique , Tomodensitométrie , Échographie-dopplerRésumé
Objective To evaluate the association between objective short sleep duration in patients with insomnia and changes in blood parameters related to hypothalamic-pituitary-adrenal (HPA) axis activity.Method A cross-sectional pilot study was conducted in 30 middle-aged adults with chronic insomnia who were divided into 2 groups according to polysomnography (PSG) total sleep time (TST) (TST > 5h and < 5h). All patients underwent subjective analysis of sleep quality, anthropometric measurements, PSG, and determination off asting blood parameters.Results The results revealed lower sleep efficiency and higher sleep latency for those with a TST < 5h. The subjective sleep quality was worse in the TST < 5h. Significantly, higher glucose and cortisol levels were observed with a TST < 5h. Glucose, cortisol and ACTH levels were inversely correlated with the PSG total sleep time.Conclusion Patients with insomnia with objective short sleep duration had HPA-associated endocrine and metabolic imbalances chronically linked to increases in cardiovascular risk observed with this more severe insomnia phenotype.
Objetivo Avaliar a associação entre insônia com tempo de sono curto e alterações sanguíneas relacionados com a atividade do eixo hipotálamo-hipófise-adrenal (HPA).Método Estudo piloto transversal, com 30 adultos de meia-idade, distribuídos em 2 grupos de acordo com o tempo total de sono (TTS) pela polisonografia (PSG) (TTS > 5h e < 5h). Os pacientes foram submetidos a análise subjetiva da qualidade do sono, medidas antropométricas, PSG e parâmetros sanguíneos em jejum.Resultados Revelaram baixa eficiência do sono e maior latência do sono para aqueles com TTS < 5h. A qualidade subjetiva do sono foi pior no TTS < 5h. Significativamente, os níveis de glicose e cortisol mais elevados foram observados no grupo com TTS < 5h. Os níveis de glicose, cortisol e ACTH foram inversamente correlacionados com o TTS da PSG.Conclusão Pacientes com insônia com tempo de sono curto apresentaram desequilíbrios endócrinos e metabólicos associados a atividade do eixo HPA, correlacionados ao aumento do risco cardiovascular observado neste fenótipo mais grave de insônia.
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Adulte , Femelle , Humains , Mâle , Adulte d'âge moyen , Axe hypothalamohypophysaire/physiopathologie , Axe hypophyso-surrénalien/physiopathologie , Troubles de l'endormissement et du maintien du sommeil/sang , Troubles de l'endormissement et du maintien du sommeil/physiopathologie , Hormone corticotrope/sang , Indice de masse corporelle , Glycémie/analyse , Maladie chronique , Méthodes épidémiologiques , Jeûne , Hormone de croissance/sang , Hydrocortisone/sang , Polysomnographie , Valeurs de référence , Facteurs tempsRésumé
Objective To determine the value of acromegaly screening in adult patients not reporting enlargement of the extremities, but who present arterial hypertension associated with at least one other comorbidity of the disease. Subjects and methods Patients seen by general practitioners at primary health care units were evaluated. Among the patients without extremity enlargement, those with recently diagnosed arterial hypertension associated with at least one other comorbidity were selected. Results A total of 1,209 patients were submitted to laboratory investigation. Elevated IGF‐1 was observed in 22 patients. Eighteen patients had adequate suppression of growth hormone (GH). No GH suppression was observed in four women with confirmed elevated IGF‐1. In the latter, IGF‐1 and nadir GH were only slightly elevated, magnetic resonance showed a normal pituitary, and chest and abdominal computed tomography revealed no tumor, and no intervention was performed. Conclusion In patients with arterial hypertension without known pituitary disease, acromegaly is unlikely in the absence of enlargement of the extremities. .
Objetivo Determinar o valor do rastreamento de acromegalia em pacientes adultos sem aumento de extremidades, mas com hipertensão arterial associada a pelo menos uma outra comorbidade da doença. Sujeitos e métodos Pacientes vistos por clínicos em unidades primárias de saúde foram avaliados. Entre pacientes sem aumento de extremidades, aqueles com hipertensão arterial diagnosticada recentemente e associada a pelo menos uma outra comorbidade foram selecionados. Resultados Um total de 1.209 pacientes foi submetido à investigação laboratorial. IGF‐1 foi elevado em 22 pacientes. Dezoito pacientes apresentavam supressão adequada do hormônio do crescimento (GH). Ausência de supressão do GH foi vista em quatro mulheres com IGF‐1 repetidamente elevado. Nestas, IGF‐1 e nadir do GH foram apenas discretamente aumentados, ressonância magnética revelou hipófise normal, tomografia computadorizada de tórax e abdome não revelaram tumor, e nenhuma intervenção foi realizada. Conclusão Em pacientes com hipertensão arterial sem doença hipofisária conhecida, acromegalia é improvável na ausência de aumento de extremidades. .
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Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Jeune adulte , Acromégalie/diagnostic , Diabète/épidémiologie , Membres/anatomie et histologie , Céphalées/épidémiologie , Hypertension artérielle/diagnostic , Facteur de croissance IGF-I/analyse , Acromégalie/sang , Brésil , Marqueurs biologiques/sang , Comorbidité , Membres/physiologie , Hyperglycémie provoquée , Hormone de croissance/sang , Imagerie par résonance magnétique , Dépistage de masse , Soins de santé primaires , Hypophyse/physiologie , Enquêtes et questionnairesRésumé
Cows with different Insulin-like Growth Factor-I (IGF-I) concentrations showed comparable expression levels of hepatic growth hormone receptor (GHR). Suppressor of cytokine signaling 2 (SOCS2), could be responsible for additional inhibition of the GHR signal cascade. The aims were to monitor cows with high or low antepartal IGF-I concentrations (IGF-I(high) or IGF-I(low)), evaluate the interrelationships of endocrine endpoints, and measure hepatic SOCS2 expression. Dairy cows (n = 20) were selected (240 to 254 days after artificial insemination (AI)). Blood samples were drawn daily (day -17 until calving) and IGF-I, GH, insulin, thyroid hormones, estradiol, and progesterone concentrations were measured. Liver biopsies were taken (day 264 +/- 1 after AI and postpartum) to measure mRNA expression (IGF-I, IGFBP-2, IGFBP-3, IGFBP-4, acid labile subunit (ALS), SOCS2, deiodinase1, GHR1A). IGF-I concentrations in the two groups were different (p 0.05). Thyroxine levels and ALS expression were higher in the IGF-I(high) cows compared to IGF-I(low) cows. Estradiol concentration tended to be greater in the IGF-I(low) group (p = 0.06). It was hypothesized that low IGF-I levels are associated with enhanced SOCS2 expression although this could not be decisively confirmed by the present study.
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Animaux , Bovins , Femelle , Oestradiol/sang , Hormone de croissance/sang , Insuline/sang , Protéine-2 de liaison aux IGF/analyse , Protéine-3 de liaison aux IGF/analyse , Protéine-4 de liaison aux IGF/analyse , Facteur de croissance IGF-I/analyse , Foie/composition chimique , Grossesse/métabolisme , Gestation animale/métabolisme , Progestérone/sang , Protéines SOCS/analyse , Hormones thyroïdiennes/sangRésumé
OBJECTIVES: Acromegaly is frequently associated with thyroid diseases. In this study, we evaluated the frequency of thyroid disorders in a series of acromegalic patients. SUBJECTS AND METHODS: We evaluated 106 acromegalic patients using thyroid ultrasonography (US) and measurements of GH, IGF-I, free T4, TSH and anti-thyroperoxidase antibody levels. IGF-I was expressed in mass units and age-related standard deviation scores (SD-scores). Fine-needle aspiration biopsy (FNAB) was performed on thyroid nodules with a diameter greater than one centimeter or with suspicious characteristics. RESULTS: Thyroid disorders were found in 75 patients. Eleven patients had diffuse goiter, 42 patients had nodular goiter, and 22 patients had unspecific morphological abnormalities. Four patients (3.8%) had thyroid carcinoma. Considering the patients with diffuse or nodular goiter, thyroid volume was greater in patients with active acromegaly, and was positively correlated with GH, IGF-I, and IGF-I SD-score. CONCLUSIONS: Our study confirmed that benign thyroid diseases are frequent in acromegalic patients. The prevalence of thyroid cancer was higher than in the overall population. We suggest that thyroid US should be routinely performed in patients with acromegaly.
OBJETIVOS: Acromegalia está frequentemente associada a doenças tireoidianas. Neste estudo, avaliamos a presença de tireoidopatias em uma série de pacientes acromegálicos. SUJEITOS E MÉTODOS: Foram avaliados 106 pacientes por ultrassonografia (US) e dosagens de GH, IGF-1, T4 livre, TSH e anticorpo antitireoperoxidase. O IGF-I foi expresso em unidades de massa e desvio-padrão (DP-IGF-I). Punção aspirativa por agulha fina (PAAF) foi realizada quando os nódulos eram maiores que um centímetro ou tinham características suspeitas. RESULTADOS: Alterações tireoidianas foram encontradas em 75 pacientes. Onze apresentavam bócio difuso, 42, bócio nodular e 22, alterações morfológicas inespecíficas. Houve quatro casos (3,8%) de câncer diferenciado de tireoide. Considerando os pacientes com bócio difuso ou nodular, o volume tireoidiano foi maior naqueles com acromegalia em atividade e correlacionou-se positivamente com os níveis de GH, IGF-1 e DP-IGF-1. CONCLUSÕES: Nosso estudo confirmou que as doenças tireoidianas benignas são frequentes nos pacientes acromegálicos. A prevalência de câncer diferenciado de tireoide foi maior que na população geral. Sugerimos que US de tireoide seja realizado rotineiramente nos pacientes com acromegalia.
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Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Femelle , Humains , Mâle , Adulte d'âge moyen , Acromégalie/épidémiologie , Maladies de la thyroïde/épidémiologie , Acromégalie/complications , Cytoponction , Brésil/épidémiologie , Carcinomes/épidémiologie , Carcinomes/étiologie , Carcinomes/anatomopathologie , Hormone de croissance/sang , Facteur de croissance IGF-I/analyse , Iodide peroxidase/sang , Prévalence , Répartition par sexe , Tests de la fonction thyroïdienne , Maladies de la thyroïde/étiologie , Maladies de la thyroïde/anatomopathologie , Tumeurs de la thyroïde/épidémiologie , Tumeurs de la thyroïde/étiologie , Tumeurs de la thyroïde/anatomopathologie , Thyréostimuline/sangRésumé
Introduction Published data suggest that patients with acromegaly have an increased prevalence of prostate disorders. Objective To evaluate prostatic disorders in acromegalic patients comparing these results after one year of treatment of acromegaly and with a group of healthy men. Materials and Methods This study was composed of two parts: sectional study comparing patients with healthy controls (baseline) and prospective, longitudinal study (at baseline and after one year of treatment). Forty acromegalic patients were enrolled and evaluated at baseline and after one year with the application of international prostatic symptoms score (IPSS), digital rectal examination, measurements of growth hormone (GH), insulin-like growth factor-I (IGF-I), insulin-like growth factor-binding protein-3 (IGFBP-3), sex hormone-binding globulin (SHBG), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone, total and free prostate-specific antigen (PSA) levels and prostate ultrasonography (US). Thirty healthy men were selected as control group. Results We stratified patients and controls according to age, considering 40 years-old as cut off. Healthy controls under 40 had IPSS values lower than acromegalic patients. When considering only older patients and controls prostate hyperplasia and structural abnormalities were more frequent in acromegalics. After one year of treatment there was significant decrease in GH, IGF-I and prostate volume in acromegalics over 40 years-old. Conclusions Acromegalics under 40 have more urinary symptoms according to IPSS and above 40 years-old higher frequency of structural changes and increased prostate volume than healthy men. Significant reduction of GH and IGF-I levels during treatment of acromegaly leads to decrease in the prostate volume. .
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Adulte , Sujet âgé , Humains , Mâle , Adulte d'âge moyen , Acromégalie/physiopathologie , Acromégalie/thérapie , Maladies de la prostate/physiopathologie , Facteurs âges , Acromégalie/métabolisme , Brésil , Études cas-témoins , Toucher rectal , Gonadotrophines hypophysaires/sang , Hormone de croissance/sang , /sang , Facteur de croissance IGF-I/analyse , Antigène spécifique de la prostate/sang , Maladies de la prostate/métabolisme , Globuline de liaison aux hormones sexuelles/analyse , Résultat thérapeutique , Testostérone/sangRésumé
Osteoporosis is a major complication of chronic cholestatic liver disease (CCLD). We evaluated the efficacy of using disodium pamidronate (1.0 mg/kg body weight) for the prevention (Pr) or treatment (Tr) of cholestasis-induced osteoporosis in male Wistar rats: sham-operated (Sham = 12); bile duct-ligated (Bi = 15); bile duct-ligated animals previously treated with pamidronate before and 1 month after surgery (Pr = 9); bile duct-ligated animals treated with pamidronate 1 month after surgery (Tr = 9). Rats were sacrificed 8 weeks after surgery. Immunohistochemical expression of IGF-I and GH receptor was determined in the proximal growth plate cartilage of the left tibia. Histomorphometric analysis was performed in the right tibia and the right femur was used for biomechanical analysis. Bone material volume over tissue volume (BV/TV) was significantly affected by CCLD (Sham = 18.1 ± 3.2 vs Bi = 10.6 ± 2.2%) and pamidronate successfully increased bone volume. However, pamidronate administered in a preventive regimen presented no additional benefit on bone volume compared to secondary treatment (BV/TV: Pr = 39.4 ± 12.0; Tr = 41.2 ± 12.7%). Moreover, the force on the momentum of fracture was significantly reduced in Pr rats (Sham = 116.6 ± 23.0; Bi = 94.6 ± 33.8; Pr = 82.9 ± 22.8; Tr = 92.5 ± 29.5 N; P < 0.05, Sham vs Pr). Thus, CCLD had a significant impact on bone histomorphometric parameters and pamidronate was highly effective in increasing bone mass in CCLD; however, preventive therapy with pamidronate has no advantage regarding bone fragility.
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Animaux , Mâle , Agents de maintien de la densité osseuse/usage thérapeutique , Cholestase intrahépatique/complications , Diphosphonates/usage thérapeutique , Ostéoporose/prévention et contrôle , Densité osseuse/effets des médicaments et des substances chimiques , Maladie chronique , Hormone de croissance/sang , Immunohistochimie , Facteur de croissance IGF-I/analyse , Ostéoporose/étiologie , Rat WistarSujets)
Adulte , Femelle , Humains , Adénomes/traitement médicamenteux , Antinéoplasiques hormonaux/usage thérapeutique , Adénome hypophysaire à GH/traitement médicamenteux , Octréotide/usage thérapeutique , Tumeurs de l'hypophyse/traitement médicamenteux , Fosse crânienne postérieure , Hormone de croissance/sang , Imagerie par résonance magnétiqueRésumé
The physiological link between ghrelin and growth hormone [GH] has not yet been fully clarified. Furthermore, the existence of a negative feedback mechanism between growth hormone-insulin-like growth factor [GH-IGF]-I axis and ghrelin and the influence of amino acids on ghrelin secretion in children remain matters of debate. To understand the regulation of ghrelin secretion and clarify the relationship between ghrelin and GH secretion in GH-deficient [GHD] and GH-sufficient [GHS] children. Ten GHD [male/female [M/F], 6/4; age [mean +/- SEM], 10.7 +/- 0.9 years] and 10 GHS prepubertal children [M/F, 6/4; age [mean +/- SEM], 10.3 +/- 0.6 years], underwent an arginine [ARG] test [infusion, 0.5 g/kg, iv]. Levels of GH, total ghrelin, and acylated ghrelin [AG] were assayed every 30 min from 0 to +120 min. Peak GH values were lower in GHD subjects than in GHS subjects [P < 0.0001]. The baseline levels, peak levels, or area under the curves [AUC] for total ghrelin and AG were similar between GHD and GHS children. ARG infusion was followed by a slight to significant decrease in total ghrelin levels, but not AG levels, both in GHD and GHS subjects with a nadir at +30 min. No correlation was seen between GH, total ghrelin, or AG response and ARG infusion. Total ghrelin and AG levels seemed unaffected by GH status in prepubertal children. ARG infusion was unable to blunt ghrelin secretion irrespective of GH status in childhood. Moreover, since ARG influences GH secretion via modulation of somatostatin release, ghrelin secretion seems to be partially refractory to somatostatin action
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Humains , Mâle , Femelle , Enfant , Hormone de croissance/sang , Hormone de croissance/déficit , Arginine , SomatostatineRésumé
OBJECTIVES: To evaluate the presence of diabetes mellitus (DM) in a cohort of patients with acromegaly. METHODS: This was a cross sectional study. RESULTS: Fifty-eight acromegalic patients were assessed. Only 29 percent met the criteria for cure, and 27 percent had the disease controlled. Twenty-two had DM; HbA1c was equal to 7.34 ± 2.2 percent. Most of the diabetic patients (18 out of 22, 82 percent) did not meet criteria for cure. They were more often hypertensive [16/22 (73 percent) vs. 17/36 (46 percent), p = 0.04], and used statins more frequently [14/22 (64 percent) vs. 8/36 (21 percent), p = 0.004]. After regression analysis, hypertension was associated with diabetes [odds ratio (OR): 9.28 (95 percent CI: 1.59 - 54.00), p = 0.01], and cured/ controlled acromegaly was associated with protection against the presence of diabetes [OR: 0.17 (95 percent CI: 0.03 - 0.78), p = 0.02]. CONCLUSIONS: The presence of DM was associated with active acromegaly and presence of hypertension. However, absolute levels of GH and IGF-1 did not differ between patients with and without diabetes.
OBJETIVOS: Avaliar a presença de diabetes melito (DM) em uma coorte de acromegálicos. MÉTODOS: Este é um estudo transversal. RESULTADOS: Cinquenta e oito pacientes acromegálicos foram analisados. Apenas 29 por cento preencheram critérios de cura e 27 por cento estavam com a doença controlada. Vinte e dois pacientes (38 por cento) apresentaram DM, HbA1c 7,34 ± 2,2 por cento. Destes, 18 não preencheram critérios de cura. Pacientes com DM foram mais frequentemente hipertensos [16/22 (73 por cento) vs. 17/36 (46 por cento), p = 0,04] e usavam mais estatina [14/22 (64 por cento) vs.8/36 (21 por cento), p = 0,004]. Após regressão múltipla, hipertensão foi associada a DM [razão de chances (RC): 9,28 (95 por cento CI: 1,59 - 54,00), p = 0,01], e acromegalia curada/controlada foi fator protetor para presença de diabetes [OR: 0,17 (95 por cento CI: 0,03-0,78), p = 0,02]. CONCLUSÕES: A presença de DM esteve associada com acromegalia ativa e com a presença de hipertensão. No entanto, os níveis absolutos de GH e IGF-1 não diferiram entre aqueles com e sem diabetes.
Sujets)
Femelle , Humains , Mâle , Adulte d'âge moyen , Acromégalie/complications , Diabète/sang , Hormone de croissance/sang , Hypertension artérielle/complications , Facteur de croissance IGF-I/analyse , Acromégalie/sang , Études de cohortes , Études transversales , Hypertension artérielle/sang , Facteurs de risqueRésumé
Ten children aged 11 months to 10 years (means 5.7 years) with reflux nephropathy, vesicoureteric reflux (VUR) and normal or mildly impaired renal function having GFR more than 50 ml/min/1.72 m2, were included in the study. The hematological and biochemical parameters were within normal limits. Height standard deviation score (HZ score) was reduced at entry and, decreased further during follow-up (-2.2 and -2.6 at 0 and 12 months, respectively). Weight for height index (WHI) improved significantly (p=0.0004) during follow-up. The basal and stimulated peak growth hormone levels of these patients were found to be elevated, 18.53 ± 11.36 μg/L and 34.20 ± 5.86 μg/L, respectively. The IGF-1 levels were low ranging from 45.00 to 84.40 ng/dl (mean ± SD 61.54 ± 10.21 ng/dl) compared to 51.80 to 247.50 ng/dl (mean ± SD111.20 ± 70.24 ng/dl) in age and sex matched controls, indicating partial insensitivity to growth hormone.
Sujets)
Algorithmes , Marqueurs biologiques/sang , Taille , Poids , Études cas-témoins , Enfant , Enfant d'âge préscolaire , Femelle , Hormone de croissance/sang , Humains , Nourrisson , Facteur de croissance IGF-I/métabolisme , Maladies du rein/sang , Tests de la fonction rénale , Mâle , Reflux vésico-urétéral/sang , Reflux vésico-urétéral/diagnostic , Reflux vésico-urétéral/physiopathologieRésumé
Leptin, a protein with a cytokine-like helical structure and molecular weight of 16 KDa, regulates the body weight and homeostasis of the energy in the body. Adiponectin has protective and special metabolic effects as well as anti-inflammatory ones, and the adiponectin level in human blood has an inverse ratio relation with the insulin resistance. The purpose of this study was to compare levels of leptin and adiponectin, and related hormones in the serum of obese children and adolescents. Sixty obese subjects were divided into two groups of 30 children and 30 adolescents. Anthropometric characteristics were recorded and adiponectin and leptin testosterone, growth, insulin, and cortisol hormones were measured in a fasting state in all subjects. The serum levels of leptin [101%], adiponectin [98%] and cortisol hormone [38.62%] were significantly higher in children than in adolescents [p<0/05]. When leptin and adiponectin were adjusted to body fat mass, the same results were observed. Serum levels of testosterone [82.58%], insulin [34.47%] and growth hormone[36.36%] were significantly higher in adolescents than in children [p<0/05]. The ratio of leptin to adiponectin had no significant difference among children and adolescents. Levels of leptin and adiponectin are higher in children than in adolescents