RESUMO
BACKGROUND: The approach to acromegalic patients with persistent acromegaly after surgery and inadequate response to first-generation somatostatin receptor ligands (SRLs) should be strictly tailored. Current options include new pituitary surgery and/or radiosurgery, or alternative medical treatment with SRLs high dose regimens, pegvisomant (PEG) as monotherapy, or combined therapy with the addition of PEG or cabergoline to SRLs. A new pharmacological approach includes pasireotide, a second-generation SRL approved for patients who do not adequately respond to surgery and/or for whom surgery is not an option. No reports on efficacy and safety of combined therapy with pasireotide and pegvisomant (PEG) in acromegaly are available. CASE PRESENTATION: Here we report the case of a 41-year-old acromegalic man with a mixed GH/PRL pituitary adenoma post-surgical resistant to first-generation SRLs both alone and in combination with cabergoline and PEG who achieved biochemical and tumor control with the combined triple treatment with pasireotide, PEG and cabergoline without adverse events and with a good compliance to treatment. CONCLUSIONS: Twelve months of therapy with pasireotide, PEG and cabergoline proved to be safe and effective in this particular patient and the clinical improvement of disease resulted in an improved compliance to treatment.
Assuntos
Acromegalia/tratamento farmacológico , Ergolinas/uso terapêutico , Hormônio do Crescimento Humano/análogos & derivados , Terapia de Salvação , Somatostatina/análogos & derivados , Adulto , Antineoplásicos/uso terapêutico , Cabergolina , Quimioterapia Combinada , Hormônios/uso terapêutico , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Masculino , Prognóstico , Somatostatina/uso terapêuticoRESUMO
PURPOSE: In children, the plasma glucose value at 1 h (1hPG) during OGTT higher than 132.5 mg/dl is a predictor of alterations in glucose metabolism. We aimed to metabolically characterize GHD children according to 1hPG levels. METHODS: Fifty-one GHD children (35 M, 16 F; mean age 8.6 years), grouped according to 1hPG, were evaluated at diagnosis and after 12 months of GH treatment (GHT) and compared with 50 matched controls at baseline. Auxological parameters, insulin-like growth factor-1 (IGF-1), glucose and insulin during OGTT, lipid profile, the oral disposition index (DIo), the homeostasis model assessment estimate of insulin resistance (Homa-IR), and the insulin sensitivity index (ISI) were evaluated. RESULTS: At baseline, 31.4% of GHD children and 12% of controls (p = 0.016) showed 1hPG ≥ 132.5 mg/dl. The first ones showed higher mean 1hPG (p = 0.025) and LDL cholesterol (p = 0.029) and lower HDL cholesterol (p = 0.014) than controls. GHD with higher 1hPG showed a significant decrease in DIo (p < 0.001) without improvement in lipid profile after GHT, compared with children with lower 1hPG. After 12 months, the higher 1hPG group showed lower ISI Matsuda (p = 0.047) and DIo (p < 0.001) than the lower 1hPG group. 1hPG levels proved to be positively correlated with Homa-IR (p = 0.010) and LDL cholesterol (p = 0.032) and negatively with ISI Matsuda (p = 0.001) and DIo (p = 0.019). The 1hPG value at baseline was the only independent variable significantly associated with DIo at 12 months (p = 0.041). CONCLUSIONS: 1hPG level at baseline may be a useful tool to identify and properly follow up children with enhanced metabolic risk who probably need more surveillance during GHT.
Assuntos
Glicemia/metabolismo , Nanismo Hipofisário/sangue , Hormônio do Crescimento Humano/deficiência , Metaboloma , Estudos de Casos e Controles , Criança , Pré-Escolar , Nanismo Hipofisário/metabolismo , Feminino , Teste de Tolerância a Glucose/métodos , Humanos , Insulina/sangue , Insulina/metabolismo , Resistência à Insulina , Secreção de Insulina , Masculino , Fatores de TempoRESUMO
PURPOSE: To evaluate the effect of pasireotide on ß-cell and adipose function in patients with Cushing's disease (CD). METHODS: Clinical and hormonal parameters, insulin secretion evaluated by HOMA-ß and by the area under the curve (AUC2h) of C-peptide during a mixed meal tolerance test and insulin sensitivity, evaluated by the euglycaemic hyperinsulinaemic clamp, were evaluated in 12 patients with active CD, before and after 6 and 12 months of pasireotide. In addition, a panel of adipokines including leptin (Ob), leptin/leptin receptor ratio (Ob/Ob-R ratio), adiponectin, resistin, visfatin, adipocyte fatty acid binding protein (AFABP) and non-esterified fatty acids (NEFAs) was evaluated at baseline and after 12 months of pasireotide. RESULTS: During 12 months of pasireotide treatment, a significant decrease in weight (p = 0.004), BMI (p = 0.008), waist circumference (p = 0.009), urinary free cortisol (p = 0.007), fasting insulinaemia (p = 0.007), HOMA-ß (p = 0.015) and AUC2h c-peptide (p = 0.017), concomitance with an increase in fasting glycaemia (p = 0.015) and HbA1c (p = 0.030), was found. With regard to adipokines, a significant decrease in Ob (p = 0.039), Ob/Ob-R ratio (p = 0.017) and AFABP (p = 0.036) was observed concomitant with a significant increase in Ob-R (p = 0.028) after 12 months of pasireotide. CONCLUSIONS: 12 months of treatment with pasireotide in CD is associated with an impairment of insulin secretion and an improvement of adipose function without any interference in insulin sensitivity.
Assuntos
Adipocinas/sangue , Hormônios/administração & dosagem , Insulina/sangue , Hipersecreção Hipofisária de ACTH/sangue , Hipersecreção Hipofisária de ACTH/tratamento farmacológico , Somatostatina/análogos & derivados , Adulto , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Estudos de Coortes , Feminino , Humanos , Injeções Subcutâneas , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Somatostatina/administração & dosagem , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: Patients with growth hormone deficiency (GHD) demonstrate an increased cortisol/cortisone ratio which could potentially explain the metabolic features of GHD, while GH treatment (GHT) could increase the cortisol metabolism. METHODS: In 35 children (27 M, mean age 10.1 years) with idiopathic GHD at baseline and after 12 months of GHT and in 25 controls, in addition to metabolic parameters, we assessed adrenal function by morning serum cortisol, its peak, and its area under the curve (AUCCOR) during insulin tolerance test (ITT). RESULTS: A cortisol peak <18 µg/dl was shown in 22 and 31% of GHD children at baseline and after GHT, respectively. At baseline, GHD children had lower fasting glucose (p < 0.001) and ISI-Matsuda (p = 0.042), with concomitant higher Homa-IR (p = 0.006) and morning cortisol (p = 0.012) than controls. Morning cortisol was negatively correlated with GH (p < 0.001), fasting glucose (p < 0.001) and ISI-Matsuda (p < 0.001) and positively with Homa-IR (p = 0.010). Both cortisol peak and AUCCOR were negatively correlated with GH (all p < 0.001) and ISI-Matsuda (p = 0.016 and p = 0.001, respectively). After 12 months of GHT, a significant increase in fasting glucose (p < 0.001), and Homa-IR (p = 0.011) was documented, with a concomitant decrease in morning cortisol (p = 0.002), AUCCOR (p = 0.038), total (p = 0.003) and LDL-cholesterol (p = 0.016). No significant correlations were found among cortisol levels and all parameters were investigated. CONCLUSIONS: Cortisol levels correlate with GH secretion and with many metabolic parameters in GHD children, while the metabolic effects during GHT are mainly due to GHT per se and less to cortisol reduction.
Assuntos
Glândulas Suprarrenais/fisiologia , Nanismo Hipofisário/fisiopatologia , Hormônio do Crescimento Humano/metabolismo , Hidrocortisona/metabolismo , Resistência à Insulina , Testes de Função do Córtex Suprarrenal , Biomarcadores/metabolismo , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Seguimentos , Hormônio do Crescimento Humano/deficiência , Humanos , Masculino , Prognóstico , Estudos ProspectivosRESUMO
PURPOSE: The effect of growth hormone (GH) on adipose tissue and the role of adipokines in modulating metabolism are documented, but with discordant data. Our aim was to evaluate the impact of GH treatment on a series of selected adipokines known to have a metabolic role and poorly investigated in this setting. METHODS: This is a prospective study. Thirty-one prepubertal children (25 M, 6 F; aged 8.5 ± 1.6 years) with isolated GH deficiency treated with GH for at least 12 months and 30 matched controls were evaluated. Auxological and metabolic parameters, insulin sensitivity indexes, leptin, soluble leptin receptor, adiponectin, visfatin, resistin, omentin, adipocyte fatty acid-binding protein and retinol-binding protein-4 were evaluated before and after 12 months of treatment. RESULTS: At baseline, no significant difference in metabolic parameters was found between GHD children and controls, except for higher LDL cholesterol (p = 0.004) in the first group. At multivariate analysis, LDL cholesterol was independently associated with resistin (B 0.531; p = 0.002), while IGF-I was the only variable independently associated with visfatin (B 0.688; p < 0.001). After 12 months, a significant increase in fasting insulin (p = 0.008), Homa-IR (p = 0.007) and visfatin (p < 0.001) was found, with a concomitant decrease in LDL cholesterol (p = 0.015), QUICKI (p = 0.001), ISI Matsuda (p = 0.006), leptin (p = 0.015) and omentin (p = 0.003)]. At multivariate analysis, BMI was the only variable independently associated with leptin (B 0.485; p = 0.040). CONCLUSIONS: GH treatment modifies adipokine secretion and the perturbation of some adipokine levels could contribute to the clinical and metabolic changes observed during the follow-up.
Assuntos
Biomarcadores/sangue , Citocinas/sangue , Transtornos do Crescimento/metabolismo , Hormônios/sangue , Hormônio do Crescimento Humano/deficiência , Lectinas/sangue , Leptina/sangue , Nicotinamida Fosforribosiltransferase/sangue , Resistina/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Proteínas Ligadas por GPI/sangue , Humanos , Masculino , Estudos ProspectivosRESUMO
PURPOSE: This study aimed at evaluating the clinical and metabolic behavior of children with isolated growth hormone (GH)-deficiency (GHD), grouped according to the new AIFA criteria for the appropriateness of use and reimbursement of GH treatment in children. METHODS: The clinical and metabolic data of 310 prepubertal children (220 M, 90 F; mean age 10.8 years) grouped, according to new AIFA note 39, into Group A (No. 181 with a peak of GH <8 µg/l), Group B (No. 103 with a peak of GH ≥8 and <10 µg/l) and Group C (No. 26 with a peak of GH >10 µg/l) were retrospectively analyzed. Group A and B, diagnosed as having GHD, were treated with GH for at least 24 months, while Group C was analyzed only at baseline. RESULTS: At baseline, Group A showed higher waist circumference than B (p = 0.031) and C (p = 0.041), while no difference in metabolic parameters was found between the three groups. After 12 and 24 months of treatment, Group B showed lower height velocity (p < 0.001 and p = 0.049, respectively) than Group A. As regards the metabolic parameters, both after 12 and 24 months of treatment, in Group B we found higher fasting glucose (p < 0.001 and p = 0.020), insulin (p = 0.002 and p = 0.011), Homa-ß (p = 0.020 and p = 0.015) and Homa-IR (both p = 0.001) than Group A, with concomitant lower QUICKI (both p < 0.001) and HDL cholesterol (p = 0.020 and p = 0.011), without difference in other lipid parameters. The HbA1c levels, although always within the normal range, were found higher in Group B than Group A after 12 months (p = 0.015). CONCLUSIONS: According to the new AIFA criteria, the reduction of GH cut-off for GHD diagnosis can be supported by auxological and metabolic data. The real benefits from GH therapy in children with higher stimulated GH levels at diagnosis remains to be better understand.
Assuntos
Nanismo Hipofisário/sangue , Nanismo Hipofisário/tratamento farmacológico , Hormônio do Crescimento/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Guias de Prática Clínica como Assunto , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Órgãos Governamentais/normas , Hormônio do Crescimento/administração & dosagem , Humanos , Itália , MasculinoRESUMO
PURPOSE: To evaluate the performance of various indexes of insulin sensitivity and secretion and to identify the most useful indicator of deterioration of glucose metabolism in a cohort of children with growth hormone (GH) deficiency (GHD) during GH treatment. METHODS: In 73 GHD children (55 M, 18 F; mean age 10.5 years) at baseline and after 12 months of treatment, we evaluated a number of surrogate indexes of insulin secretion and sensitivity. In a subgroup of 11 children we also performed an euglycemic hyperinsulinemic clamp. RESULTS: After 12 months, a significant increase in fasting glucose (p < 0.001) and HbA1c levels (p < 0.001) was documented, despite all children remained with a normal glucose tolerance. With regard the insulin secretion, Homa-ß did not show any significant change (p = 0.073), while oral disposition index (DIo) showed a significant decrease (p = 0.031). With regard the insulin sensitivity, Homa-IR significantly increased (p < 0.001) with a concomitant decrease in QUICKI (p < 0.001). ISI Matsuda showed a decrease, although not statistically significant (p = 0.069). In the subgroup of 11 children, the M value derived from clamp showed a significant decrease (p = 0.011) and a significant positive correlation was found between M value and ISI Matsuda both at baseline (ρ 0.950; p = 0.001) and after 12 months (ρ 0.980; p = 0.001) but not with Homa-IR and QUICKI. CONCLUSIONS: 12 months of GH treatment lead to a decrease in insulin sensitivity and impairment in insulin secretion relative to insulin sensitivity even without evident changes in glucose tolerance. DIo has proven to be the most useful indicator of deterioration of glucose metabolism even in cases in which the overt glucose abnormalities have not yet appeared.
Assuntos
Glicemia/metabolismo , Nanismo Hipofisário/metabolismo , Hormônio do Crescimento Humano/uso terapêutico , Hipopituitarismo/tratamento farmacológico , Resistência à Insulina/fisiologia , Células Secretoras de Insulina/metabolismo , Adolescente , Criança , Pré-Escolar , Nanismo Hipofisário/tratamento farmacológico , Feminino , Teste de Tolerância a Glucose , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/deficiência , Humanos , Hipopituitarismo/metabolismo , Insulina/metabolismo , Masculino , Resultado do TratamentoRESUMO
PURPOSE: Insulin resistance and compensatory hyperinsulinism are the predominant metabolic defects in polycystic ovary syndrome (PCOS). However, hyperinsulinism, as well as being compensatory, can also express a condition of reduced insulin clearance. Our aim was to evaluate the differences in insulin action and metabolism between women with PCOS (with normal glucose tolerance) and age- and BMI-matched women with prediabetes (without hyperandrogenism and ovulatory disorders). METHODS: 22 women with PCOS and 21 age/BMI-matched women with prediabetes were subjected to a Hyperinsulinemic-euglycemic clamp and an Oral Glucose tolerance Test (OGTT). Insulin sensitivity was assessed by the glucose infusion rate during clamp (M value); insulin secretion by Insulinogenic index, Oral Disposition Index (DIo) and AUC(2h-insulin) during OGTT; and insulin clearance by the metabolic clearance rate of insulin (MCRI) during clamp. RESULTS: Women with PCOS showed significantly higher levels of AUC(2h-insulin) (p < 0.011), Insulinogenic Index (p < 0.001), DIo (p = 0.002) and significantly lower levels of AUC(2h-glucos)e (p = 0.001). No difference was found between the two groups regarding insulin sensitivity (M value). Lower levels of MCRI were found in women with PCOS [420 (IQR 227-588) vs. 743 (IQR 597-888) ml m(-2) min(-1): p < 0.001]. Furthermore, in the PCOS group, a strong independent inverse correlation was only observed between MCRI and AUC(2h-insulin) (PCOS: ß:-0.878; p < 0.001; Prediabetes: ß:-0.501; p = 0.019). CONCLUSIONS: Our study suggests that in normoglycemic women with PCOS there is peripheral insulin sensitivity similar to that of women with prediabetes. What sets PCOS apart is the hyperinsulinism, today still simplistically defined "compensatory"; actually this is mainly related to decreased insulin clearance whose specific causes and dynamics have yet to be clarified.
Assuntos
Hiperinsulinismo/sangue , Resistência à Insulina , Insulina/sangue , Síndrome do Ovário Policístico/sangue , Estado Pré-Diabético/sangue , Adolescente , Adulto , Feminino , Técnica Clamp de Glucose , Humanos , Adulto JovemRESUMO
BACKGROUND: Acromegaly is an insidious disorder caused by a pituitary growth hormone (GH)-secreting adenoma resulting in high circulating levels of GH and insulin-like growth factor I (IGF-I). Respiratory disorders are common complications in acromegaly, and can severely impact on quality of life, eventually affecting mortality. OBJECTIVES: The present study aimed to explore structural and functional lung alterations of acromegalic subjects. METHODS: We enrolled 10 consecutive patients (M/F: 5/5) affected by acromegaly. In all patients, magnetic resonance imaging (MRI) revealed the presence of pituitary tumor. All patients underwent clinical, lung functional, biological, and radiological assessments. Ten healthy age-matched subjects also served as controls. RESULTS: No statistically significant differences in lung function were detected between acromegalic and healthy subjects (p ≥ 0.05 for all analyses). However, the diffusing capacity for CO (TLCO) was significantly lower in the acromegalic group than in healthy subjects (TLCO% predicted: 78.1 ± 16 vs. 90 ± 6 %, respectively, p = 0.04; KCO% predicted: 77 ± 16 vs. 93 ± 5 %, p = 0.02, respectively). None of the lung function parameters correlated with duration of the disease, or with inflammatory marker of the airways. In acromegalics, biological (exhaled NO concentrations) and imaging (total lung volume, TLV, and mean lung density, MLD) evaluations were within normal values. The TLV measured by HRCT was 3540 ± 1555 ml in acromegalics, and the MLD was -711 ± 73 HU. None of the lung functional, radiological, and biological findings correlated with GH or IGF-I levels, and no correlation was found with duration of disease. CONCLUSIONS: In the current study, lung function evaluation allowed to detect early involvement of lung parenchyma, as assessed by TLCO and KCO, even in the absence of parenchymal density alterations of the lung by HRCT. These findings suggest to routinely include the carbon monoxide diffusing capacity in the lung function assessment for an early intervention in acromegaly.
Assuntos
Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Pneumopatias/etiologia , Pulmão/fisiopatologia , Adulto , Idoso , Estudos de Casos e Controles , Diagnóstico Precoce , Feminino , Volume Expiratório Forçado , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/fisiopatologia , Humanos , Pulmão/diagnóstico por imagem , Pneumopatias/diagnóstico , Pneumopatias/fisiopatologia , Medidas de Volume Pulmonar , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Capacidade de Difusão Pulmonar , Radiografia , Fatores de Tempo , Capacidade VitalRESUMO
PURPOSE: Although the correlation between vitamin D and growth hormone (GH)-insulin-like growth factor 1 (IGF1) axis is documented, as of date, few and conflicting studies have prospectively analyzed vitamin D before and after GH treatment. Our aim was to evaluate as to how the condition of GH deficiency (GHD) or GH treatment influences vitamin D in children. METHODS: Eighty Sicilian GHD children (M/F 58/22; mean age 10.3 years), grouped according to the season of evaluation in group A (June-September; 41 children) and group B (November-February; 39 children), were evaluated at baseline and after 12 months of GH treatment. RESULTS: Twenty-eight children (35 %) were vitamin D insufficient and 32 (40 %) deficient at baseline, and lower vitamin D levels were found in group B than in A (17.3 ± 5.3 vs. 31.1 ± 11.1 ng/ml; p < 0.001). A positive correlation between vitamin D and baseline GH levels (p < 0.001) was found. After 12 months, increased vitamin D was found both in all children (34.4 ± 16.4 vs. 24.5 ± 11.1 ng/ml; p = 0.002) and in group A (38.5 ± 14 vs. 31.1 ± 11.1 ng/ml; p < 0.001) and B (30 ± 17.7 vs. 17.3 ± 5.3 ng/ml; p < 0.001). Overall, only 25 (31 %) children remained insufficient and 15 (19 %) deficient, with an increase in prevalence of children with normal levels (p = 0.001). CONCLUSIONS: Our data demonstrated a very high prevalence of hypovitaminosis D in Sicilian GHD children, with an improvement after 12 months of GH treatment. Vitamin D assessment should therefore be considered routinely in GHD children both at diagnosis and during the follow-up.
Assuntos
Nanismo Hipofisário/epidemiologia , Hormônio do Crescimento Humano/uso terapêutico , Deficiência de Vitamina D/epidemiologia , Adolescente , Criança , Pré-Escolar , Comorbidade , Nanismo Hipofisário/tratamento farmacológico , Feminino , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/deficiência , Humanos , Lactente , Masculino , Prevalência , Resultado do Tratamento , Deficiência de Vitamina D/tratamento farmacológico , Adulto JovemRESUMO
BACKGROUND: Diabetes mellitus is frequently observed in patients with acromegaly. Current therapies for acromegaly may impact glucose regulation, influencing insulin sensitivity and secretion. The question whether these therapies modify control and progression of diabetes once present is still open. AIM: Aim of our study is to analyze glucose control in acromegalic patients with diabetes, evaluating the relation with treatments for GH excess and for diabetes. METHODS: Seventy patients with acromegaly and diabetes were studied. Duration and treatments of acromegaly and diabetes were recorded, together with clinical and metabolic parameters. RESULTS: Most patients (92.8%) were treated with somatostatin analogs (SSA), either alone or in combination with dopamine-agonists (20%) or pegvisomant (15.7%); 7.1% of patients had been treated by surgery alone. Metformin (65.7%), alone or in combination with other hypoglycemic drugs, was the most frequent treatment for diabetes, followed by insulin (21.5%). Only 15.7% were treated with diet alone. The whole cohort showed a very good control of diabetes and acromegaly. Median glycated hemoglobin was 6.4% (5.9-7). IGF-I was within normal range for age in most patients. No relation was observed between duration of acromegaly or diabetes and metabolic control. SSA had a negative effect on insulin secretion, but these effects did not influence glucose control. Finally, we observed a low prevalence of nephropathy (6%) and retinopathy (20%). CONCLUSIONS: Our study shows that a good control of hyperglycemia can be obtained with success in the majority of acromegalic patients with diabetes, independently of the type of treatment for GH excess.
Assuntos
Acromegalia/metabolismo , Acromegalia/terapia , Glicemia/metabolismo , Complicações do Diabetes/metabolismo , Diabetes Mellitus/metabolismo , Diabetes Mellitus/terapia , Acromegalia/sangue , Acromegalia/complicações , Idoso , Glicemia/efeitos dos fármacos , Estudos de Coortes , Complicações do Diabetes/sangue , Complicações do Diabetes/terapia , Diabetes Mellitus/sangue , Agonistas de Dopamina/uso terapêutico , Procedimentos Cirúrgicos Endócrinos , Hemoglobinas Glicadas/metabolismo , Hormônio do Crescimento Humano/sangue , Humanos , Hiperglicemia/sangue , Hiperglicemia/metabolismo , Hiperglicemia/terapia , Pessoa de Meia-Idade , Somatostatina/análogos & derivados , Somatostatina/uso terapêuticoRESUMO
BACKGROUND: GH exerts its effects on many organs and the eye also seems to be a target site, although few authors have investigated the corneal thickness in patients with acromegaly. AIM: To perform a detailed ophthalmological evaluation in acromegalic patients, in relation to disease activity. MATERIAL AND METHODS: Twenty-eight acromegalic patients (11 males, 17 females) and 22 voluntary healthy subjects underwent complete metabolic and ophthalmological evaluation, including retinal thickness (RT), central corneal thickness (CCT), and intraocular pressure values (IOP). RESULTS: Significantly greater CCT values were found in all acromegalic patients in comparison with controls (567 vs 528.5 µm; p<0.001), without concomitant greater corrected IOP. No difference was found for RT. Analyzing these data according to disease activity, uncontrolled patients showed greater CCT values (573.5 vs 559 µm; p=0.002) and corrected IOP (17.4 vs 16 mmHg; p=0.001) than the controlled ones. CCT also correlated with basal and nadir GH after oral glucose load levels, IGF-I levels, and duration of active disease. CONCLUSIONS: Acromegaly is characterized by greater CCT values, supporting the hypothesis that GH excess may have stimulatory effects on the cornea as well as on other target organs. Higher GH levels, disease control status and duration of active disease seem to be the main causes of increased corneal thickness. We suggest a careful and detailed corneal evaluation in acromegalic patients to prevent the potential risk of increased IOP, in addition to the already-known complications.
Assuntos
Acromegalia/patologia , Córnea/anatomia & histologia , Córnea/patologia , Hormônio do Crescimento Humano/metabolismo , Acromegalia/complicações , Acromegalia/fisiopatologia , Animais , Córnea/fisiologia , Feminino , Humanos , Pressão Intraocular , Masculino , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Hipertensão Ocular/etiologiaRESUMO
BACKGROUND: Dual-release hydrocortisone (DR-HC) improves metabolism in patients with adrenal insufficiency. The aims of this study were to compare the cardiovascular and metabolic effects of conventional glucocorticoids (GCs) vs. DR-HC and of high vs. low doses of GCs, after 48 months of observation. METHODS: We selected 27 patients on hydrocortisone (mean dose 17.5 ± 4.2 mg/day) and 20 patients on cortisone acetate (mean dose 37.5 ± 12.1 mg/day) who maintained this treatment (group A) and 53 patients switched to DR-HC (mean dose 22 ± 4.8 mg/day) (group B). At baseline and after 48 months, clinical and metabolic parameters and Framingham Risk Score (FRS) were obtained. RESULTS: After 48 months, patients in group A had a significant increase from baseline in BMI (P < 0.001), waist circumference (P = 0.001), systolic blood pressure (P = 0.001), LDL cholesterol (P = 0.018), HbA1c (P = 0.020) and FRS (P = 0.002). By contrast, patients in group B had a significant decrease in BMI (P = 0.002), waist circumference (P = 0.015), diastolic blood pressure (P = 0.031), total (P = 0.006) and LDL cholesterol (P = 0.005), HbA1c (P < 0.001) and FRS (P = 0.015) compared to baseline. No significant differences between high and low doses of both conventional GCs and DR-HC were observed. CONCLUSIONS: DR-HC is associated with an improvement of metabolic parameters and cardiovascular risk compared to conventional GCs, which are associated with a worsening of these parameters, regardless of the dose used.
RESUMO
PURPOSE: Patients with Cushing's disease (CD) experience metabolic alterations leading to increased cardiovascular mortality. Recently, the visceral adiposity index (VAI) has been proposed as a marker of visceral adipose tissue dysfunction (ATD) and of the related cardiometabolic risk. We aimed to evaluate the impact of 12-month pasireotide treatment on cardiometabolic risk in CD patients. METHODS: This is a multicentre, prospective, and observational study. Sixteen CD patients, referred to the Endocrine Units of the University Hospitals of Messina, Napoli, Padova, and Palermo (Italy), successfully treated with pasireotide for 12 month have been enrolled. In all patients, we assessed anthropometric, clinical, and biochemical parameters and calculated VAI, ATD severity, Framingham, and atherosclerotic cardiovascular disease (ASCVD) risk scores, before and after 6 and 12 months of treatment with pasireotide (1200-1800 mcg/daily). RESULTS: Before starting pasireotide treatment, ATD was present in 7/16 patients (mild in 2/16, moderate in 3/16, and severe 2/16). After 12 months of treatment: (i) 24h-urinary free cortisol levels (p = 0.003), BMI (p < 0.001), waist circumference (p = 0.001), LDL-cholesterol (p = 0.033), total-cholesterol (p = 0.032), triglycerides (p = 0.030), VAI (p = 0.015), and ATD severity (p = 0.026) were significantly decreased as compared to baseline; (ii) ATD was present in only 1/16 patients; (iii) prevalence of diabetes mellitus (p = 0.015) and HbA1c levels (p = 0.001) were significantly increased as compared to baseline; (iv) Framingham and ASCVD risk scores were not significantly different from pre-treatment values. CONCLUSIONS: Twelve-month pasireotide treatment significantly reduces VAI and ATD in CD patients. These positive effects on cardiometabolic risk occur despite no change in Framingham and ASCVD risk scores and the increase in the prevalence of diabetes mellitus.
Assuntos
Cardiopatias/prevenção & controle , Doenças Metabólicas/prevenção & controle , Hipersecreção Hipofisária de ACTH/tratamento farmacológico , Somatostatina/análogos & derivados , Adiposidade , Adulto , Aterosclerose/prevenção & controle , Feminino , Cardiopatias/etiologia , Humanos , Gordura Intra-Abdominal/fisiopatologia , Itália , Estudos Longitudinais , Masculino , Doenças Metabólicas/etiologia , Pessoa de Meia-Idade , Obesidade Abdominal/metabolismo , Hipersecreção Hipofisária de ACTH/complicações , Estudos Prospectivos , Fatores de Risco , Somatostatina/uso terapêuticoRESUMO
OBJECTIVE: GH replacement therapy in children with GH deficiency (GHD) mainly promotes linear growth. Not only have very few studies fully analyzed the metabolic consequences of GH therapy, but also the question as to whether GH may affect adipokine secretion has been insufficiently investigated. Our aim was to study the effects of GH replacement therapy on auxological data, lipid and glycemic profiles, insulin homeostasis (HOMA-IR) and serum adipokines in children. METHODS: This was a 1-year prospective study. Thirty-four GHD children (11.6 +/- 2.6 years) and thirty healthy matched controls were enrolled. Children affected by GHD were studied both before beginning continuous GH replacement therapy and again at 12 months. RESULTS: At the beginning of the study, total and LDL cholesterol were higher in GHD children than in controls (P<0.001), whereas HDL cholesterol, triglycerides, insulin, HOMA-IR, leptin, and adiponectin were similar. At 12 months of continuous GH replacement therapy in the GHD group, there was a significant increase in both auxological data and IGF-I (P<0.001); total cholesterol (P<0.001), LDL (P<0.001), triglycerides (P<0.005), and leptin (P<0.001) decreased significantly; HDL (P<0.003), insulin (P<0.001), HOMA-IR (P<0.001) increased while adiponectin was unmodified. Furthermore, IGF-IDelta showed an inverse correlation with leptin Delta (rho = -0.398, P = 0.02). CONCLUSIONS: In GHD children, the evaluation of metabolic parameters proves to be a useful tool for the evaluation of auxological parameters during GH replacement therapy. In our study, GH replacement therapy in GHD children improved final height, restored IGF-I levels, reduced leptin levels, and improved the lipid profile, without producing any unfavorable effects on glucose metabolism.
Assuntos
Transtornos do Crescimento/tratamento farmacológico , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Adiponectina/sangue , Adolescente , Estatura/efeitos dos fármacos , Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Criança , LDL-Colesterol/sangue , Feminino , Transtornos do Crescimento/sangue , Humanos , Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Leptina/sangue , Masculino , Fatores de Tempo , Resultado do Tratamento , Triglicerídeos/sangueRESUMO
The interplay between vitamin D and the growth hormone (GH)/insulin-like growth factor (IGF)-I system is very complex and to date it is not fully understood. GH directly regulates renal 1 alpha-hydroxylase activity, although the action of GH in modulating vitamin D metabolism may also be IGF-I mediated. On the other hand, vitamin D increases circulating IGF-I and the vitamin D deficiency should be normalized before measurement of IGF-I concentrations to obtain reliable and unbiased IGF-I values. Indeed, linear growth after treatment of nutritional vitamin D deficiency seems to be mediated through activation of the GH/IGF-I axis and it suggests an important role of vitamin D as a link between the proliferating cartilage cells of the growth plate and GH/IGF-I secretion. Vitamin D levels are commonly lower in patients with GH deficiency (GHD) than in controls, with a variable prevalence of insufficiency or deficiency, and this condition may worsen the already known cardiovascular and metabolic risk of GHD, although this finding is not common to all studies. In addition, data on the impact of GH treatment on vitamin D levels in GHD patients are quite conflicting. Conversely, in active acromegaly, a condition characterized by a chronic GH excess, both increased and decreased vitamin D levels have been highlighted, and the interplay between vitamin D and the GH/IGF-I axis becomes even more complicated when we consider the acromegaly treatment, both medical and surgical. The current review summarizes the available data on vitamin D in the main disorders of the GH/IGF-I axis, providing an overview of the current state of the art.
Assuntos
Acromegalia/metabolismo , Transtornos do Crescimento/fisiopatologia , Hormônio do Crescimento Humano/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Vitamina D/metabolismo , HumanosAssuntos
Adenoma , Antineoplásicos Hormonais/uso terapêutico , Gigantismo , Octreotida/uso terapêutico , Neoplasias Hipofisárias , Adenoma/complicações , Adenoma/tratamento farmacológico , Adenoma/patologia , Criança , Feminino , Gigantismo/tratamento farmacológico , Gigantismo/etiologia , Gigantismo/patologia , Humanos , Imageamento por Ressonância Magnética , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/patologia , Indução de Remissão , Resultado do TratamentoRESUMO
OBJECTIVE: The studies that have extensively evaluated the relation between adipokines and metabolic parameters in acromegaly treatment are quite discordant. We aimed to evaluate and correlate a set of selected adipokines, known to have a metabolic role, with the disease activity, metabolic status and treatment modalities. DESIGN: Data of 56 consecutive acromegalic patients (31 M and 25 F; aged 54 ± 12 years), admitted to the section of Endocrinology of the University of Palermo during the years 2005-2014, including 16 newly diagnosed untreated (ND), 21 during therapy with somatostatin analogues (SA), 12 with pegvisomant (PE) and 7 after surgical treatment (SU), grouped into uncontrolled (group A: No. 33) and controlled (group B: No. 23) were evaluated. Anthropometric and metabolic parameters, insulin sensitivity indexes, visceral adiposity index (VAI), leptin, soluble leptin receptor, adiponectin, visfatin, resistin, adipsin and non-esterified fatty acids (NEFAs) were assessed. In a subgroup of 21 subjects, the insulin sensitivity index (M value) derived from euglycemic clamp was calculated. RESULTS: Group A showed higher Homa-IR (p < 0.001), VAI (p < 0.001), triglycerides (p < 0.001), visfatin (p < 0.001), and NEFAs (p < 0.001) and lower ISI Matsuda (p < 0.001), M value (p < 0.001), HDL cholesterol (p < 0.001) and leptin (p < 0.001) than group B. ND patients showed higher VAI, triglycerides, Homa-IR, and visfatin and lower ISI Matsuda, M-value, and leptin compared to other groups (all p < 0.050), while no differences were found among SA, PE and SU patients. IGF-1 (p = 0.048), M-value (p = 0.0029) and VAI (p = 0.010) were independently associated with visfatin, while only ISI Matsuda (p = 0.019) was associated with leptin. CONCLUSIONS: In acromegaly visfatin could be considered a useful index of disease activity and metabolic alterations, such as insulin resistance and adipose dysfunction, regardless of the type of treatment.
Assuntos
Acromegalia/sangue , Citocinas/sangue , Nicotinamida Fosforribosiltransferase/sangue , Acromegalia/patologia , Acromegalia/terapia , Adipocinas/sangue , Adiposidade , Adulto , Idoso , Biomarcadores/sangue , HDL-Colesterol/sangue , Estudos Transversais , Ácidos Graxos não Esterificados/sangue , Feminino , Humanos , Resistência à Insulina , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangueRESUMO
BACKGROUND/AIM: The significance of changes in thyroid function in children during growth hormone (GH) treatment remains uncertain. We aimed to evaluate the impact of GH replacement on thyroid status in children with idiopathic GH deficiency (GHD). METHODS: Data of 105 GHD children (82 M, 23 F; aged 11.13 years) during a 36-month follow-up were analyzed. At diagnosis the areas under the curve of GH (AUCGH) were calculated during a GH-releasing hormone + arginine (GHRH-Arg) and insulin tolerance test. RESULTS: A significant ΔfT3 (p < 0.001) was documented at 12 months, without any further change at 24 and 36 months and without fT4 and TSH modifications. Grouping patients according to ΔfT3 at 12 months into those with lower (n = 80, 76%) or greater values than the 75th percentile (n = 25, 24%), the latter showed lower AUCGH and GH peak during a GHRH-Arg (p = 0.018 and 0.014, respectively) and insulin tolerance test (p = 0.023 and 0.020, respectively) at diagnosis. In addition, children with lower GH at diagnosis showed a greater ΔfT3 at 12 months (p = 0.030). CONCLUSIONS: In GHD children, GH treatment is associated with a significant increase in fT3 in the first 12 months, more pronounced in patients with more severe GHD, highlighting the strong correlation between severity of GHD and thyroid metabolism.
Assuntos
Hormônio do Crescimento Humano/deficiência , Glândula Tireoide/metabolismo , Adolescente , Arginina , Criança , Feminino , Hormônio Liberador de Hormônio do Crescimento , Humanos , Masculino , Estudos Retrospectivos , Tri-Iodotironina/metabolismoRESUMO
OBJECTIVE: The eye represents a target site for GH action, although few data are available in patients with GH deficiency (GHD). Our aim was to evaluate central corneal thickness (CCT) and intraocular pressure (IOP) values in GHD children to assess the role played by GHD or GH treatment on these parameters. DESIGN: In 74 prepubertal GHD children (51M, 23F, aged 10.4±2.4years) we measured CCT and IOP before and after 12months of treatment. A baseline evaluation was also made in 50 healthy children matched for age, gender and body mass index. The study outcome considered CCT and IOP during treatment and their correlations with biochemical and auxological data. RESULTS: No difference in CCT and IOP between GHD children at baseline and controls was found (all p>0.005). GHD children after 12months of therapy showed greater CCT (564.7±13.1µm) than both baseline values (535.7±17µm; p<0.001) and control subjects (536.2±12.5µm; p<0.001), with a concomitantly higher corrected mean IOP (15.6±0.7mmHg; p<0.001) than both baseline (12.5±0.8mmHg; p<0.001) and controls (12.3±0.5mmHg; p<0.001), without correlation with auxological and biochemical parameters. CONCLUSIONS: 12months of GH treatment in children with GHD, regardless of auxological and biochemical data, affect CCT and IOP. Our findings suggest careful ocular evaluation in these patients to prevent undesirable side effects during the follow-up.