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OBJECTIVE: Graves' ophthalmopathy (GO) is an inflammatory disease in the orbital region. The first-line medical treatment is glucocorticoids. An important potential side effect of glucocorticoid treatment is suppression of the hypothalamic-pituitary-adrenal (HPA) axis with impairment of endogenous cortisol production, implicating symptoms of adrenocortical insufficiency, especially in the period after cessation of therapy with possible risks in cases of intercurrent illness. The aim of this study was to evaluate HPA axis function before and after methylprednisolone pulse treatment of GO. STUDY DESIGN: HPA axis function was evaluated by measurements of plasma ACTH and an ACTH stimulation test with plasma cortisol measurements at 0 and 30 min after an intravenous bolus of synthetic ACTH (Synacthen® 250 µg). This was done in 12 patients with GO before and at cessation of methylprednisolone pulse treatment (500 mg i.v. per week for 6 weeks followed by 250 mg i.v. per week for an additional 6 weeks). RESULTS: All patients included fulfilled the criteria of intact HPA axis function before and at cessation of methylprednisolone pulse treatment. Data are given as medians (with ranges). Before glucocorticoid treatment basal plasma cortisol was 290 nM (196-579) and 786 nM (612-1,050) after ACTH stimulation. At cessation of therapy the corresponding values were 309 nM (88-718) and 852 nM (524-1,011), respectively. Thus, all patients passed a 30-min stimulated plasma cortisol of 500 nM. Before treatment plasma ACTH was 4.2 pmol/l (4-16) and at cessation of therapy the corresponding value was 4.8 pmol/l (2-9; p = 0.27). CONCLUSION: Transient suppression of the HPA axis with secondary adrenocortical insufficiency does not seem to be a common phenomenon after intravenous methylprednisolone pulse therapy for GO. Therefore, routine precautions are not necessary. However, our results do not exclude that transient secondary adrenocortical insufficiency might occur occasionally.
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OBJECTIVE: To investigate whether pegvisomant treatment in acromegaly induces gradual elevations in endogenous serum growth hormone (GH) levels and whether serum pegvisomant levels predict the therapeutic outcome. PATIENTS AND METHODS: Seventeen patients (6 women), mean age 46·3 years (range: 23·2-76·2), were studied. For each patient, four hospital visits were identified including 'active disease' (no treatment) and last follow-up. At each visit, 12 blood samples were drawn during 3 h including an oral glucose tolerance test (OGTT). Eight patients received a somatostatin analogue in addition to pegvisomant on the last visit. RESULTS: Median (range) pegvisomant doses (mg/day) were 10 (10-10), 15 (10-15) and 15 (10-15) at visits 2, 3 and 4, respectively, and the mean duration of pegvisomant treatment was 17·5 ± 3·2 (SEM) months. Serum IGF-I changed significantly during the treatment period with the highest level at baseline and lowest levels at visits 3 and 4. GH levels increased in a dose-dependent manner during pegvisomant treatment and decreased at visit 4. Changes in IGF-I levels correlated negatively with changes in serum pegvisomant levels between visits. Serum pegvisomant at each visit correlated with baseline growth hormone levels, whereas no associations between serum pegvisomant and either dose, gender, age or body weight were found. CONCLUSIONS: (1) Serum GH levels increased initially, but remained stable during prolonged pegvisomant treatment in patients with acromegaly, (2) serum pegvisomant levels predicted the reduction in serum IGF-I during treatment and (3) the interindividual variation in serum pegvisomant levels seems not predicted by either age, gender or body composition.
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Acromegalia/sangue , Acromegalia/tratamento farmacológico , Hormônio do Crescimento/sangue , Hormônio do Crescimento Humano/análogos & derivados , Adulto , Idoso , Esquema de Medicação , Feminino , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: High vasopressin levels and a correlation between vasopressin and cortisol has been observed in patients with depression. The aim was to assess copeptin, the c-terminal of provasopressin, and the association between cortisol, adrenocorticotropic hormone (ACTH) and copeptin in patients with depression. Secondly, to examine the copeptin response to acute exercise and aerobic training. METHODS: Copeptin, ACTH, and cortisol were measured in 111 patients with depression and 57 controls at rest. Copeptin was also measured during exercise. The depressed patients were subsequently randomized to an aerobic training intervention or an exercise control intervention. RESULTS: The plasma level of copeptin in depressed subjects was 5.14 pg/ml (IQR 3.4-8.4) and 4.82 pg/ml (IQR 2.8-7.5) in healthy controls (p=.66). The association between copeptin and cortisol was.02 (95% CI -.44 to.48; p=.93) and the association between copeptin and ACTH was -.06 (95% CI -.17 to.05; p=.27). All associations were independent of depression status (p=.15). Aerobic exercise training did not influence copeptin levels at rest (p=.09) or the response to acute exercise (p=.574). Copeptin decreased at rest in response to aerobic training in participants with high compliance to the exercise intervention (p=.04). LIMITATIONS: We did not measure plasma osmolality, which is a possible confounder in this study. CONCLUSIONS: Copeptin levels are not elevated or associated to ACTH or cortisol in depressed patients. Aerobic exercise training decreased copeptin levels in high attenders only. This study does not support a role of copeptin or vasopressin in depression.
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Transtorno Depressivo Maior/sangue , Glicopeptídeos/sangue , Adolescente , Hormônio Adrenocorticotrópico/sangue , Adulto , Transtorno Depressivo Maior/fisiopatologia , Exercício Físico , Feminino , Glicopeptídeos/fisiologia , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Descanso , Adulto JovemRESUMO
INTRODUCTION: The GH/IGF1 axis may modulate inflammatory processes. However, the relationship seems complicated as both pro- and anti-inflammatory effects have been demonstrated. METHODS/DESIGN: Twelve healthy volunteers (mean age 36, range 27-49 years) were treated in random order with increasing doses of GH for 3 weeks (first week 0.01â mg/kg per day, second week 0.02â mg/kg per day, and third week 0.03â mg/kg per day) or a GH receptor antagonist (pegvisomant; first week 10â mg/day and last two weeks 15 âmg/day), separated by 8 weeks of washout. Circulating levels of the pro-inflammatory cytokines tumor necrosis factor α (TNFα (TNFA)), interleukin 6 (IL6), and IL1ß (IL1B) and the acute phase proteins (APPs) C-reactive protein (CRP), haptoglobin, orosomucoid, YKL40 (CHI3L1), and fibrinogen were measured. RESULTS: During GH treatment, IGF1 (median 131 (Inter-quartile range (IQR) 112-166) vs 390 (322-524) µg/l, P=0.002) increased together with TNFα (0.87 (0.74-1.48) vs 1.27 (0.80-1.69) ng/l, P=0.003), IL6 (1.00 (0.83-1.55) vs 1.35 (0.80-4.28) ng/l, P=0.045), and fibrinogen (9.2 (8.8-9.6) vs 11.1 (9.4-12.4) µM, P=0.002). By contrast, orosomucoid decreased (18.0 (15.5-24.3) vs 15.0 (15.0-17.0) µM, P=0.018). CRP, YKL40, and haptoglobin were unchanged. During pegvisomant treatment, IGF1 decreased (139 (117-171) vs 91 (78-114) ng/ml, P=0.005). Orosomucoid (21.0 (16.3-23.8) vs 22.0 (17.0-29.3) µM, P=0.036) and CRP (1.00 (0.62-1.77) vs 1.43 (0.71-3.29) mg/l, P=0.074) increased without an increase in pro-inflammatory cytokines. CONCLUSIONS: GH/IGF1 action appears to modulate the initial stage of the inflammatory response as well as downstream processes elucidated by levels of APPs. The data suggest a complicated relationship not allowing any simple conclusions as to whether GH/IGF1 actions have mainly pro- or anti-inflammatory effects in vivo.
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Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/sangue , Mediadores da Inflamação/sangue , Receptores da Somatotropina/antagonistas & inibidores , Adulto , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/sangue , Anti-Inflamatórios não Esteroides/uso terapêutico , Biomarcadores/sangue , Estudos Cross-Over , Feminino , Hormônio do Crescimento Humano/efeitos adversos , Hormônio do Crescimento Humano/farmacologia , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Inflamação/sangue , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Receptores da Somatotropina/fisiologia , Resultado do TratamentoRESUMO
Assessed by conventional echocardiography the influence of growth hormone deficiency (GHD) and effects of replacement therapy on left ventricle (LV) function and mass (LVM) have shown inconsistent results. We aimed to evaluate cardiac function before and during replacement therapy employing the gold standard method cardiac magnetic resonance imaging (CMRI) and measurements of circulating levels of B-type natriuretic peptides. Sixteen patients (8 males and 8 females, mean age 49 years (range 18-75)) with severe GHD and 16 matched control subjects were included. CMRI was performed at baseline and after 1 year of GH replacement therapy. IGF-I, B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) were measured after 0, 1, 2, 3, 6 and 12 months of treatment. IGF-I Z-score increased from (median (IQR)) -2.3 (-3.8 to -1.4) to 0.5 (-0.3 to 1.7). LVM index (LVMI), ejection fraction (range 63-80%), cardiac output index and levels of BNP and NT-proBNP were similar at baseline in patients compared to controls (P-values from 0.09 to 0.37). The patients had significantly smaller LV end-diastolic volume index (P = 0.032) and end-systolic volume index (P = 0.038). No significant change in LV systolic function or LVM occurred during 1 year of GH treatment. BNP levels were unchanged (P = 0.88), whereas NT-proBNP tended to decrease (P = 0.052). Assessed by the highly sensitive and precise CMRI method, untreated GHD was not associated with impaired systolic function or reduced LVMI and 1 year of GH replacement using physiological doses did not influence cardiac mass or function.
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Nanismo Hipofisário/tratamento farmacológico , Nanismo Hipofisário/patologia , Terapia de Reposição Hormonal/métodos , Hormônio do Crescimento Humano/uso terapêutico , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Feminino , Coração/efeitos dos fármacos , Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Função Ventricular Esquerda/efeitos dos fármacos , Adulto JovemRESUMO
Long-term treatment of acromegaly prevents aggravation and reverses associated heart disease. A previous study has shown a temporary increase in serum levels of the N-terminal fraction of pro B-type natriuretic peptide (NT-proBNP) suggesting an initial decline in cardiac function when treatment of acromegaly is initiated. This was a three months prospective study investigating short-term cardiac effects of treatment in acromegalic patients. Cardiac function was evaluated by the gold standard method cardiac magnetic resonance imaging (CMRI) and circulating levels of B-type natriuretic peptides (BNP and NT-proBNP). CMRI was performed at baseline and after 3 months of treatment. Levels of IGF-I, BNP and NT-proBNP were measured after 0, 1, 2 and 3 months. Eight patients (5 males and 3 females, mean age 53 ± 12 years (range 30-70)) and 8 matched healthy control subjects were included. Median IGF-I Z-score decreased from 4.5 (range 2.5-6.4) to 2.3 (-0.1 to 3.3). At baseline the patients had increased left ventricle mass index (LVMI) compared to control subjects (ΔLVMI 35 g/m(2) (95% CI 8-63 g/m(2), P = 0.016). After 3 months of treatment there was an increase in end-diastolic volume index EDVI (ΔEDVI 9 mL/m(2) (95% CI 3-14), P = 0.007) and an increase in levels of BNP (median (ranges) 7 (0.58-286) vs. 20 (1-489) pg/mL, P = 0.033) and of NT-proBNP (63 (20-1004) vs. 80 (20-3391) pg/mL, P = 0.027). Assessed by the highly sensitive and precise CMRI method, 3 months treatment of acromegaly resulted in an increase in EDVI, and increased levels of BNP and NT-proBNP suggesting an initial decrease in cardiac function.
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Acromegalia/sangue , Acromegalia/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Coração/efeitos dos fármacos , Hormônio do Crescimento Humano/efeitos adversos , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Octreotida/efeitos adversos , Octreotida/uso terapêutico , Estudos Prospectivos , Somatostatina/efeitos adversos , Somatostatina/uso terapêuticoRESUMO
BACKGROUND AND OBJECTIVE: The objective of the present study was to test the hypothesis that circulating levels of insulin-like growth factor-I (IGF-I) are inversely associated with inflammatory processes in an elderly background population. PATIENTS AND DESIGN: We conducted a population-based study comprising 629 individuals, aged 50-89 years. Associations between plasma IGF-I versus interleukin 6 (IL-6) and the acute phase proteins high sensitive C-reactive protein (hsCRP) and YKL-40 were evaluated by linear regression analyses. Subsequently, the population was dichotomised at a CRP level of 3.0 mg/L and the associations were re-evaluated in the two subgroups. RESULTS: Adjusted for confounding variables, plasma IGF-I was inversely related to IL-6, hsCRP and YKL-40 (all P < 0.001). The strongest association was found for YKL-40 with a 34% reduction in YKL-40 per twofold increase in IGF-I. A significant inverse association between IGF-I and all markers of inflammation persisted in individuals with hsCRP below 3.0 mg/L whereas only YKL-40 was significantly associated with IGF-I in individuals with hsCRP above 3.0 mg/L. CONCLUSIONS: The data support the hypothesis of an inverse association between GH/IGF-I signalling and inflammation, and suggest that the relationship between the IGF-I and inflammation might be more predominant in healthy individuals with a low inflammatory activity.
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Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Glicoproteínas/sangue , Inflamação/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Interleucina-6/sangue , Lectinas/sangue , Grupos Populacionais , Adipocinas , Idoso , Idoso de 80 Anos ou mais , Proteína 1 Semelhante à Quitinase-3 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transdução de Sinais/fisiologiaRESUMO
BACKGROUND AND OBJECTIVE: Measurements of Insulin-Like Growth Factor-I (IGF-I) play a pivotal role in the evaluation of the growth hormone-IGF-I axis. Due to assay variation IGF-I reference ranges are assay specific. We provide serum IGF-I reference ranges for adult men and women obtained by a commercially available assay. METHOD: IGF-I was measured by an enzyme-linked immunosorbent assay (R&D Systems). Assay precision was evaluated in low, medium and high IGF-I pools and in single samples from outpatients. The reference ranges were obtained in 724 healthy Caucasians, mean age 48 years (range 19-91). RESULTS: IGF-I was measured higher in serum compared to plasma samples (p<0.001, R2=0.96). To convert EDTA plasma values to serum values a factor of 1.22 was calculated. The intraassay coefficients of variation (CV) for the low: 56.4+/-2.7 ng/mL, medium: 179.7+/-5.9 ng/mL and high pool: 445.61+/-3.2 ng/mL (mean 1 SD) were 5, 3 and 3%. Interassays CVs for the low, medium and high pool varied between 7-10, 5-7, and 6-9%. Reproducibility between 4 different lots showed a intraclass CV of 0.99 (95%CI 0.98-0.96). Logarithmically transformed IGF-I levels were linearly associated with age with a 13% reduction in IGF-I per decade in females and 11% in males. CONCLUSION: We have provided IGF-I reference ranges obtained by an assay that showed variations and reproducibility that was considered of sufficient high quality for clinical and scientific use.
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Saúde , Imunoensaio/métodos , Fator de Crescimento Insulin-Like I/metabolismo , Kit de Reagentes para Diagnóstico , População Branca , Adulto , Idoso , Idoso de 80 Anos ou mais , Coleta de Amostras Sanguíneas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Referência , Valores de Referência , Caracteres Sexuais , Adulto JovemRESUMO
OBJECTIVES: Insulin-like growth factor I (IGF-I) is an anabolic growth factor that seems to increase cardiac contractility. Reduced levels of IGF-I may be implicated in progression of CHF. The objective was to compare plasma IGF-I in CHF patients with healthy controls, and to examine the associations between baseline IGF-I levels, cardiac contractility and the prognosis as judged by all cause mortality and progression of CHF requiring admission to hospital. METHODS: A prospective study comprising 194 CHF outpatients, and 169 matched controls. All patients and controls underwent echocardiographic examination at baseline. Patients were followed for a median of 30 months. RESULTS: There was no difference in IGF-I levels between patients and controls (median and interquartile range), 78 (58-91) vs. 77 (57-94)ng/mL (P=0.92). Age-adjusted IGF-I levels were not related to left ventricular ejection fraction (LVEF) (P=0.58) or levels of N-terminal B-Type natriuretic peptide (NT-proBNP) (P=0.42). During follow-up 44 patients died and 94 were admitted to hospital due to worsening of CHF. Adjusted for cardiovascular risk factors (age, gender, NT-proBNP, lipids, diabetes mellitus, blood pressure, renal function and LVEF) IGF-I levels did not influence the overall mortality risk or the admission rate to hospital, hazard ratio (HR) (95% confidence intervals) 1.05 (0.75-1.47) (P=0.77) and 1.00 (0.80-1.26) (P=0.96), respectively per each SD increase in log IGF-I levels. CONCLUSIONS: IGF-I levels were not reduced in patients with CHF and did not influence cardiac status at baseline or the prognosis.
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Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Fator de Crescimento Insulin-Like I/biossíntese , Idoso , Estudos de Casos e Controles , Doença Crônica , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: IGF1 is believed to influence ageing and development of cardiovascular disease (CVD) through complex mechanisms. Reduced IGF1 levels might be causally associated with conditions accompanying ageing including development of CVD. However, in animal models reduced GH-IGF1 signalling increases lifespan. Reduced IGF1 activity might also be associated with longevity in humans. OBJECTIVE: The objective was to investigate if plasma IGF1 levels were associated with all cause mortality, and the development of chronic heart failure (CHF) and a major CV event. PATIENTS AND DESIGN: A population based study of 642 individuals, aged 50-89 years. Development of CHF was evaluated in 576 individuals with normal systolic function assessed by echocardiography and without the history of CHF or myocardial infarction. Development of the first major CV event was evaluated in 504 individuals with normal systolic function and without prevalent CVD. Outcomes were ascertained after 5 years using hospital discharge diagnoses. RESULTS: Adjustment for risk factors IGF1 values in the fourth quartile versus values below the fourth quartile was associated with increased mortality (n=103), hazard ratio (HR) 1.52 (95% confidence interval (CI) 1.01-2.28; P=0.044). IGF1 in the fourth quartile was also independently associated with risk of development of CHF (n=19), HR 5.02 (95% CI 2.00-12.64; P=0.001) but showed no association with the overall incidence of major CV events (n=58), HR 1.05 (95% CI 0.59-1.90; P=0.861). CONCLUSIONS: High IGF1 levels were independently associated with increased all cause mortality and risk of development of CHF, whereas no relation with the overall incidence of CVD was observed.
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Doenças Cardiovasculares/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/mortalidade , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Angiodysplasias account for 2-8% of GI-bleeding episodes. We describe a 75-year-old patient with a history of anaemia for 1 year before being diagnosed with multiple angiodysplasias in the GI-tract. The patient needed weekly blood transfusions until he started treatment with octreotide. After 4 months of treatment the need for transfusions had decreased dramatically and faeces was negative for blood. Treatment was switched to long-acting octreotide (Sandostatin Lar). The case illustrates the usefulness of somatostatin analogues in the treatment of bleeding GI-angiodysplasias.
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Angiodisplasia/complicações , Fármacos Gastrointestinais/uso terapêutico , Hemorragia Gastrointestinal/etiologia , Octreotida/uso terapêutico , Idoso , Anemia/etiologia , Transfusão de Sangue , Hemorragia Gastrointestinal/complicações , Humanos , MasculinoRESUMO
OBJECTIVE: To estimate morbidity in Denmark in all patients with GH deficiency (GHD). DESIGN: Morbidity was analyzed in 1794 GHD patients and 8014 controls matched on age and gender. All records in the GHD patients were studied and additional morbidity noted. Diagnoses and dates of admissions were identified in the National Patient Registry. Lag time until first admission was used as a measure of morbidity. Patients were divided into childhood onset (CO) and adult onset (AO), discriminated by an age cut-off of 18 years at onset of GHD. METHOD: Sex- and cause-specific hazard ratios (HRs) in CO and AO GHD compared with controls. RESULTS: Total morbidity was significantly increased in the GHD patients. HR for CO males: 3.1 (95% confidence interval (CI): 2.7-3.7), CO females: 3.2 (95% CI: 2.6-3.9), AO males: 2.9 (95% CI: 2.6-3.2), and AO females: 3.2 (95% CI: 2.8-3.6). In 18 out of 20 chapters from the International Classification of Diseases-10, a significantly increased morbidity was identified for at least one of the four subgroups of patients. Morbidity was significantly increased in all the four subgroups due to infectious, endocrine, pulmonary, urogenital, and neurological diseases; cancer; diseases of the eye, ear, and circulatory diseases; and traumas. Fractures were significantly increased in AO females, not in males. CONCLUSIONS: Morbidity was significantly increased in the GHD patients. The increased morbidity was due to a variety of disorders, some of which can readily be explained by GHD and other pituitary deficiencies, while others cannot be easily explained.
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Nanismo Hipofisário/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Causalidade , Criança , Pré-Escolar , Comorbidade , Dinamarca/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Morbidade , Sistema de RegistrosRESUMO
BACKGROUND: Acromegaly is accompanied by increased cardiovascular mortality and a cluster of proatherogenic risk factors. In the general population, ischaemic heart disease (IHD) is associated with elevated levels of inflammatory markers. The acute phase reactant (APR) C-reactive protein (CRP) has been reported to be reduced in acromegaly and increase after treatment, suggesting that excess of GH/IGF-I could have anti-inflammatory effects. This is in accordance with results obtained in patients with growth hormone deficiency (GHD), where increased levels of CRP have been reported. OBJECTIVE: To investigate the hypothesis that the GH/IGF-I system is a suppressive regulator of inflammatory processes. SUBJECTS AND METHODS: Twenty-one acromegalic patients and 19 GH-deficient patients were studied. The two APRs CRP and YKL-40 and the proinflammatory cytokine interleukin-6 (IL-6) were measured before and after treatment and in healthy matched controls. RESULTS: In acromegalic patients, serum concentrations of high-sensitive CRP (hsCRP) and YKL-40 were reduced compared to controls (P < 0.001) and increased (P < 0.001) after treatment, together with IL-6 (P = 0.021), to levels comparable with controls. Pretreatment serum YKL-40 and IL-6 showed a significant inverse correlation with IGF-I and GH. In GH-deficient patients, hsCRP and YKL-40 were elevated compared to controls (P = 0.001 and P = 0.048). During treatment, levels of both APRs showed a trend towards a decrease (P = 0.087 and P = 0.060), and after treatment, levels of YKL-40 no longer differed from that of controls. Serum IL-6 was not different from controls and did not change during GH treatment. CONCLUSION: The results point to the possibility of a relationship between GH disturbances and inflammatory processes.
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Acromegalia/sangue , Proteína C-Reativa/metabolismo , Nanismo Hipofisário/sangue , Interleucina-6/sangue , Acromegalia/tratamento farmacológico , Adipocinas/sangue , Adolescente , Adulto , Estudos de Casos e Controles , Proteína 1 Semelhante à Quitinase-3 , Nanismo Hipofisário/tratamento farmacológico , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Lectinas/sangue , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: To estimate the mortality in Denmark in patients suffering from GH deficiency (GHD). DESIGN: Mortality was analyzed in 1794 GHD patients and 8014 controls matched on age and gender. All records in GHD patients were studied and additional morbidity noted. Patients were divided into childhood onset (CO) and adult onset (AO), discriminated by an age cutoff below or above 18 years at onset of GHD. METHOD: Data on death were identified in national registries. Sex- and cause-specific mortalities were identified in CO and AO GHD when compared with controls. RESULTS: Mortality was increased in CO and AO GHD in both genders, when compared with controls. The hazard ratio (HR) for CO males was 8.3 (95% confidence interval (CI) 4.5-15.1) and for females 9.4 (CI 4.6-19.4). For AO males, HR was 1.9 (CI 1.7-2.2) and for females 3.4 (CI 2.9-4.0). We found a significantly higher HR in AO females versus AO males, both compared with controls (P < 0.001). In AO, mortality was increased due to cancer in all subgroups, due to circulatory diseases in all age groups for females and for males in the oldest age group. For CO, the increased mortality was due to cancer. CONCLUSIONS: We found a significantly increased mortality in GHD patients when compared with controls, possibly due to their hypopituitary status. Mortality was increased in AO female patients when compared with males. For CO and AO GHD, different causes of significantly increased mortality were identified.
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Nanismo Hipofisário/mortalidade , Adulto , Distribuição por Idade , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Caracteres SexuaisRESUMO
BACKGROUND: Acromegaly is associated with hypertrophic cardiomyopathy, hypertension and subsequent congestive heart failure. Impairment of cardiac function has also been associated with growth hormone deficiency (GHD). B-type natriuretic peptides (BNPs) have emerged as strong diagnostic and prognostic risk markers. They are cardioprotective hormones that compensate heart disease by promoting natriuresis and modulation of cardiac hypertrophy in response to volume expansion and ventricular wall stretch. OBJECTIVE: To investigate N-terminal pro-BNP (NT-proBNP) in patients with GH disturbances before and after treatment, and in healthy gender- and age-matched controls. SUBJECTS AND METHODS: Ten acromegalic patients (age 48 +/- 12 years) and 10 patients with GHD (age 41 +/- 14 years) were studied. None had symptoms or signs of cardiovascular disease except for hypertension. Serum NT-proBNP was measured before and 3, 6, 12 and 24 months after treatment. RESULTS: Baseline NT-proBNP was lower in acromegalic patients [median (interquartile range) 24.3 (17.8-33.0) pg/ml] than in 20 healthy matched controls [57.9 (35.4-92.2) pg/ml; P < 0.001]. NT-proBNP increased during treatment (P = 0.002), concomitant with a decrease in IGF-I (P < 0.001). After 3 months of treatment NT-proBNP peaked, with a fourfold increase to 96.4 (57.8-113.2) pg/ml. NT-proBNP did not differ in patients with GHD compared with controls (P = 0.19), and did not change during treatment (P = 0.39). CONCLUSION: Untreated patients with acromegaly had low NT-proBNP levels that increased fourfold after treatment. This is in contrast to other conditions with cardiac hypertrophy. Further studies are required to determine the significance of this novel finding in relation to acromegalic cardiac disease.
Assuntos
Acromegalia/sangue , Hormônio do Crescimento/deficiência , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Precursores de Proteínas/sangue , Acromegalia/tratamento farmacológico , Acromegalia/cirurgia , Adulto , Idoso , Análise de Variância , Antineoplásicos Hormonais/uso terapêutico , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Seguimentos , Hormônio do Crescimento/sangue , Hormônio do Crescimento/uso terapêutico , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Octreotida/uso terapêutico , Peptídeos Cíclicos/uso terapêutico , Estudos Retrospectivos , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Estatísticas não ParamétricasRESUMO
OBJECTIVE: To investigate the effect of Rosiglitazone in three patients treated with bilateral adrenalectomy followed by hyperpigmentation and hypersecretion of ACTH. PATIENTS AND METHODS: One patient had increasing ACTH after previous transsphenoidal surgery for Nelson's syndrome, and two patients without pituitary adenomas had recurrence of Cushing's disease after primary and repeated transsphenoidal surgery with need for bilateral adrenalectomy. The patients developed hyperpigmentation and increasing ACTH at nadir 2-4 h after morning hydrocortisone dose. ACTH during Rosiglitazone therapy (4 mg/day for 4 weeks and then 8 mg/day) was measured at regular intervals 24 h after the latest dose of hydrocortisone. RESULTS: In two patients there was a decrease in ACTH by 40% after 5 months. The first of these patients showed an escape with increasing ACTH to the initial value after 11 months. In the third patient no effect was observed. Tumour development or progression on magnetic resonance imaging was not observed. CONCLUSION: Rosiglitazone might represent an adjuvant therapy in patients with ACTH hypersecretion. Larger long-term studies are needed.
Assuntos
Adrenalectomia/efeitos adversos , Síndrome de Nelson/tratamento farmacológico , Síndrome de Nelson/prevenção & controle , Tiazolidinedionas/uso terapêutico , Hormônio Adrenocorticotrópico/sangue , Adulto , Idoso , Feminino , Humanos , Masculino , Síndrome de Nelson/sangue , Síndrome de Nelson/etiologia , Rosiglitazona , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: Surgical cure of Cushing's syndrome (CS) is followed by adrenocortical insufficiency, which may be long-lasting. The aim was to elucidate recovery of adrenocortical function, defined as a normal cortisol response to ACTH stimulation, and the relation to ACTH in patients cured for CS due to pituitary Cushing's disease (CD) or adrenal (AA) adenomas. DESIGN: A retrospective study including 32 patients considered surgically cured for CS (18 CD, 14 AA). RESULTS: Twelve (67%) patients with CD recovered within median 24 months (range 7 months-4(1)/(2) years) whereas six did not recover within 3-12 years. Plasma ACTH (p-ACTH) at time of recovery was not different from p-ACTH in patients not recovering (P = 0.9). Eleven (79%) patients with AA recovered within 24 months (10 months-4 years) whereas three did not recover within 4-10 years. p-ACTH at time of recovery was higher compared to patients not recovering (P < 0.04). No differences were observed comparing CD and AA patients concerning preoperative 24-h urinary free cortisol (UFC) excretion, postoperative unstimulated s-cortisol or recovery time. By contrast, p-ACTH measured at time of recovery was higher in AA compared to CD (median 12.3 vs. 4.6 pmol/l) (P < 0.001), whereas plasma dehydroepiandrosterone sulfate (p-DHEAS) was lower in AA compared to CD (median 300 vs. 1500 nmol/l) (P = 0.02). CONCLUSION: Recovery of secondary adrenal insufficiency is a slow process in both CD and AA. ACTH measured at time of recovery was significantly higher and DHEAS significantly lower in patients with AA compared to CD, which may suggest different mechanisms of the recovery process and different set points in the glucocorticoid feedback inhibition of ACTH secretion.