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PURPOSE: Cabergoline (CAB) has shown to have benefic effects on the metabolism in different clinical settings but its metabolic role in acromegaly disease has not been studied yet. Aim of our study was to evaluate the impact of CAB on glucose metabolism and weight in patients with acromegaly. METHODS: All patients with acromegaly undergoing continuous treatment with CAB for at least 6 months were retrospectively screened. Exclusion criteria were discontinuation of CAB for more than one month, change of antidiabetic or other therapy for acromegaly, concomitant untreated hormonal deficiency, initiation of pregnancy and/or breastfeeding. All patients were evaluated in terms of biochemical disease control, glucose metabolism and weight at baseline (T0) and after the introduction of CAB therapy at 6 (T6) and 12 months (T12). RESULTS: Twenty-six patients (15 females and 11 males) were evaluated at T0 and T6 and 19 patients (12 females and 7 males) were also evaluated at T12. Insulin-like growth factor I (IGF-I) and prolactin (PRL) levels were significantly lower at T6 and T12 compared to baseline (p < 0.001 for IGF-I, p < 0.05 for PRL) even if no further differences were observed between T12 and T6. Considering the entire cohort, no differences were appreciated regarding the metabolic parameters but a significant reduction in weight and body mass index (BMI) was observed at both T6 (p = 0.009 for weight, p = 0.021 for BMI) and T12 (p = 0.014 for weight, p = 0.017 for BMI) compared to baseline. CONCLUSION: Our results confirm the efficacy of CAB in providing a significant improvement in the biochemical disease control but do not demonstrate a marked benefit on glucose metabolism of acromegaly patients. In such patients, CAB appears to have a rapid effect on weight and BMI, with significant changes noticeable as early as 6 months and persisting for at least 12 months.
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PURPOSE: The clinical features of adult GH deficiency (GHD) are nonspecific, and its diagnosis is established through GH stimulation testing, which is often complex, expensive, time-consuming and may be associated with adverse side effects. Moreover, diagnosing adult GHD can be challenging due to the influence of age, gender, and body mass index on GH peak at each test. The insulin tolerance test (ITT), GHRH + arginine test, glucagon stimulation test (GST), and, more recently, testing with macimorelin are all recognized as useful in diagnosing adult GHD. To date GST is still little used, but due to the unavailability of the GHRH all over the world and the high cost of macimorelin, in the next future it will probably become the most widely used test when ITT is contraindicated. The aim of the present review is to describe the current knowledge on GST. METHODS: Narrative review. RESULTS: In the last years several studies have suggested some changes in the original GST protocol and have questioned its diagnostic accuracy when the classic GH cut-point of 3 µg/L is used, suggesting to use a lower GH cut-point to improve its sensitivity and specificity in overweight/obese patients and in those with lower pretest GHD probability. CONCLUSION: This document provides an update on the utility of GST, summarizes how to perform the test, shows which cut-points should be used in interpreting the results, and discusses its drawbacks and caveats referring to the most recent studies.
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Glucagón , Hormona de Crecimiento Humana , Humanos , Hormona de Crecimiento Humana/deficiencia , AdultoRESUMEN
BACKGROUND: Patients with non-functioning pituitary adenoma (NFPA) often present with a variety of clinical manifestations and comorbidities, mainly determined by the local mass effect of the tumor and by hypopituitarism. Whether this has an impact on overall mortality, however, is still unclear. METHODS: PubMed/Medline, EMBASE, and Cochrane Library databases were systematically searched until May 2023 for studies reporting data either about standardized mortality ratios (SMRs) or about predictors of mortality in patients with NFPA. Effect sizes were pooled through a random-effect model. This systematic review and meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO, #CRD42023417782). RESULTS: Eleven studies were eligible for inclusion in the systematic review; among these, five studies reported data on SMRs, with a total follow-up time of approximately 130,000 person-years. Patients with NFPA showed an increased mortality risk compared to the general population (SMR = 1.57 [95%CI: 1.20-1.99], p < 0.01). Age and sex appeared to act as effect modifiers, with a trend towards higher SMRs in females (SMR = 1.57 [95%CI: 0.91-2.41], p = 0.10) than in males (SMR = 1.00 [95%CI: 0.89-1.11], p = 0.97), and in patients diagnosed at age 40 years or younger (SMR = 3.19 [95%CI: 2.50-3.97], p < 0.01) compared to those with later onset of the disease (SMR = 1.26 [95%CI: 0.93-1.65], p = 0.13). The trend towards excess mortality was similar in patients with normal (SMR = 1.22 [95%CI: 0.94-1.53], p = 0.13) or deficient (SMR = 1.26 [95%CI: 0.82-1.79], p = 0.27) pituitary function. CONCLUSIONS: Excess mortality is observed in patients with NFPA, regardless of pituitary function, especially in women and in patients with a younger age at diagnosis.
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PURPOSE: The precise effects of non-steroidal anti-inflammatory drugs on the neuroendocrine hydro-electrolytic regulation are not precisely understood. The aim of this pilot study was to evaluate, in healthy subjects, the neuroendocrine response of the antidiuretic system to intravenous diclofenac infusion. METHODS: For this single-blinded, cross-over study, we recruited 12 healthy subjects (50% women). Test sessions were divided into three observation times (pre-test; test; 48 h post-test), which were repeated equally on two different occasions, with the administration of diclofenac (75 mg in saline solution 0.9% 100 cc) on 1 day, or placebo (saline solution 0.9% 100 cc) on another day. The night before the test the subjects were asked to collect a salivary cortisol and cortisone sample, which was repeated on the night of the procedure session. Serial urine and blood samples were collected on the test day (for osmolality, electrolytes, ACTH, cortisol, copeptin, MR-proADM, MR-proANP; the last three represent more stable and analytically reliable molecules than their respective active peptides). Moreover, the subjects were evaluated with the bioimpedance vector analysis (BIVA) before and after the test. Forty-eight hours after the end of the procedure urine sodium, urine potassium, urine osmolality, serum sodium and copeptin were revaluated together with BIVA. RESULTS: No significant changes in circulating hormone levels were observed; anyway, 48 h after diclofenac, BIVA showed a significant water retention (p < 0.00001), especially in extracellular fluid (ECF) (16.47 ± 1.65 vs 15.67 ± 1.84, p < 0.001). Salivary cortisol and cortisone tended to increase only the night after placebo administration (p = 0.054 cortisol; p = 0.021 cortisone). CONCLUSION: Diclofenac resulted in an increased ECF at 48 h, but this phenomenon seems to be associated with a greater renal sensibility to the action of vasopressin rather than with an increase in its secretion. Moreover, a partial inhibitory effect on cortisol secretion can be hypothesized.
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Cortisona , Diclofenaco , Humanos , Femenino , Masculino , Proyectos Piloto , Voluntarios Sanos , Hidrocortisona/orina , Estudios Cruzados , Solución Salina , SodioRESUMEN
INTRODUCTION: The proportion of patients with low GH response to provocative tests increases with the number of other pituitary hormone deficiencies, reason why in panhypopituitary patients GH stimulation tests may be unnecessary to diagnose GH deficiency (GHD) PURPOSE: To re-evaluate the diagnostic cut-offs of GH response to GHRH + arginine (ARG) test related to BMI, considering the patients' pituitary function as the gold standard for the diagnosis of GHD. METHODS: The GH responses to GHRH + ARG were studied in 358 patients with history of hypothalamic-pituitary disease. GHD was defined by the presence of at least 3 other pituitary deficits (n = 223), while a preserved somatotropic function was defined by the lack of other pituitary deficits and an IGF-I SDS ≥ 0 (n = 135). The cut-off with the best sensitivity (SE) and specificity (SP), was identified for each BMI category using the ROC curve analysis. To avoid over-diagnosis of GHD we subsequently searched for the cut-offs with a SP ≥ 95%. RESULTS: The best GH cut-off was 8.0 µg/l (SE 95%, SP 100%) in lean, 7.0 µg/l (SE 97.3%, SP 82.8%) in overweight, and 2.8 µg/l (SE 84.3%, SP 91.7%) in obese subjects. The cut-off with a SP ≥ 95% was 2.6 µg/l (SE 68.5%, SP 96.6%) in overweight and 1.75 µg/l (SE 70.0%, SP 97.2%) in obese subjects. CONCLUSIONS: This is the first study that evaluates the diagnostic cut-offs of GH response to GHRH + ARG related to BMI using a clinical definition of GHD as gold standard. Our results suggest that with this new approach, the GHRH + ARG cut-offs should be revised to avoid GHD over-diagnosis.
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Enanismo Hipofisario , Hormona de Crecimiento Humana , Enfermedades de la Hipófisis , Humanos , Índice de Masa Corporal , Sobrepeso/complicaciones , Hormona Liberadora de Hormona del Crecimiento , ArgininaRESUMEN
BACKGROUND: When evaluating a patient for central adrenal insufficiency (CAI), there is a wide range of morning cortisol values for which no definite conclusion on hypothalamus-pituitary-adrenal (HPA) axis function can be drawn; in these cases, a stimulation test is required. Aim of this study was to develop an integrated model for CAI prediction when morning cortisol is in the grey zone, here defined as 40.0-160.0 µg/L. METHODS: Overall, 119 patients with history of sellar tumour which underwent insulin tolerance test (ITT) for the evaluation of HPA axis were enrolled. Supervised regression techniques were used for model development. RESULTS: An integrated predictive model was developed and internally validated, and showed a significantly better diagnostic performance than morning cortisol alone (AUC 0.811 vs 0.699, p = 0.003). A novel predictive score (CAI-score) was retrieved, on a 5.5-point scale, by considering morning cortisol (0 points if 130.1-160.0 µg/L, 1 point if 100.1-130.0 µg/L, 1.5 points if 70.1-100.0 µg/L, 2.5 points if 40.0-70.0 µg/L), other pituitary deficits (2 points if ≥ 3 deficits), and sex (1 point if male). A diagnostic algorithm integrating CAI-score and ITT was finally proposed, with an overall accuracy of 99%, and the possibility to avoid the execution of stimulation tests in 25% of patients. CONCLUSIONS: This was the first study that proposed an integrated score for the prediction of CAI when morning cortisol is in the grey zone. This score might be helpful to reduce the number of patients who need a stimulation test for the assessment of HPA axis function.
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Insuficiencia Suprarrenal , Hidrocortisona , Humanos , Masculino , Sistema Hipotálamo-Hipofisario , Sistema Hipófiso-Suprarrenal , Insuficiencia Suprarrenal/diagnóstico , HipófisisRESUMEN
PURPOSE: Patients with secondary adrenal insufficiency (SAI) have an increased morbidity and an impaired health-related quality of life (HRQoL), which seems to primarily depend on the sub-optimal replacement of hypoadrenalism with standard glucocorticoid (GC) therapy, and on the inadequate correction of other associated pituitary deficiencies. A dual-release hydrocortisone (DR-HC) formulation has shown to exert positive effects on morbidity and HRQoL, mainly in patients with primary adrenal insufficiency. We assessed the variations of anthropometric and metabolic parameters and HRQoL in patients with SAI after switching from cortisone acetate (CA) or hydrocortisone (HC) to DR-HC. METHODS: Twenty-one patients (17 M, 4 F) treated with CA (n = 16; 25 mg/day twice a day) or HC (n = 5; 20 mg/day three times a day), were evaluated for waist circumference, BMI, fasting glucose, HbA1c, insulin, HOMA-IR index, serum lipids, electrolytes, blood pressure and HRQoL at baseline, at 3, 6 and 12 months after switching from CA/HC to DR-HC. RESULTS: The study showed a significant reduction of waist circumference and BMI (p = 0.04, for both), after 3 and 6months of DR-HC treatment, respectively. No significant changes were observed for fasting glucose, insulin, HOMA-IR index, HbA1c, total cholesterol, triglycerides, LDL cholesterol, electrolytes, and blood pressure. However, HDL cholesterol significantly decreased (p = 0.003). An improvement of AddiQoL total score was observed during DR-HC treatment (p = 0.01), mainly for the category "emotions". No predictors resulted for these changes. CONCLUSION: DR-HC treatment provides some benefits in patients with SAI, reducing central adiposity and improving HRQoL; however, worsening of HDL cholesterol is observed during treatment with DR-HC.
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Insuficiencia Suprarrenal , Hidrocortisona , Humanos , Adiposidad , Hemoglobina Glucada , Calidad de Vida , HDL-Colesterol/metabolismo , Insuficiencia Suprarrenal/inducido químicamente , Obesidad , Obesidad Abdominal , Insulina , GlucosaRESUMEN
PURPOSE: This study aims to compare the accuracy of mean GH profile (GHP) < 2.5 ng/ml and single fasting GH (SGH) < 1 ng/ml in the evaluation of disease control in acromegaly patients during somatostatin receptor ligands (SRLs) therapy. METHODS: We retrospectively enrolled 100 acromegaly patients, 68 responder, and 32 partial responder to SRLs. Controlled disease has been defined as IGF-I levels within age-related normal limits, while partial response as pathological IGF-I values despite a reduction ≥ 50%. In all patients, GHP, SGH, IGF-I, and IGFBP-3 were evaluated. RESULTS: Median GHP levels (1.2 ng/ml, IQR 0.5-2.3 ng/ml) were lower (p = 0.001) than SGH (1.9 ng/ml, IQR 1.0-3.6 ng/ml). Accuracy of GHP was 81%, whereas that of SGH was 55%, with a Kappa index of 0.520 and 0.237, respectively. In multivariable analysis GHP (p = 0.002) and IGFBP-3 (p = 0.004), but not SGH, were independently associated with normal IGF-I levels. At receiver-operator characteristic curve (ROC) analysis GHP cut-off sensitivity and specificity were 94.1% and 50.0%, respectively, while SGH sensitivity and specificity were 35.3% and 93.7%, respectively. Finally, in obese patients the GH cut-off level (both as SGH and GHP) associated to good disease control was significantly different with respect to not obese ones. CONCLUSIONS: GHP associates with IGF-I (and therefore with appropriate control of disease) with higher accuracy than SGH. When GH evaluation is needed, the measurement of mean GHP should be preferred and use of BMI-related cut-offs is suggested.
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Acromegalia , Hormona de Crecimiento Humana , Acromegalia/tratamiento farmacológico , Ayuno , Hormona de Crecimiento Humana/metabolismo , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina , Factor I del Crecimiento Similar a la Insulina/metabolismo , Receptores de Somatostatina , Estudios RetrospectivosRESUMEN
BACKGROUND: In patients with suspected acromegaly, evaluation of IGF-I is recommended as first-line test, while the assessment of GH-nadir during oral glucose tolerance test (OGTT) is advised as confirmatory test. The procedure of this test generally involves GH measurement every 30 min (30') from baseline to +120' or +180'. However, the optimal timing of samplings for the distinction between patients with or without active acromegaly is still a matter of debate. METHODS: Sixty-seven healthy subjects and 46 acromegalic patients who achieved documented and persistent long-term cure were enrolled. A greedy algorithm was used to identify the minimal subset of time-points that sufficed to correctly detect GH suppression. RESULTS: The sampling at 90' was the one in which a GH level < 1 µg/L was most frequently achieved (i.e., in 91.3% of cured acromegalic patients and in 91.0% of healthy subjects). Considering the whole cohort, the best combination of 2 time-points was +90' and +150' and achieved 95.6% accuracy; the best combination of 3 time-points was +60', +90' and +150' and achieved 99.1% accuracy. The minimal subset of GH determinations that demonstrated perfect accuracy (100%) needed the inclusion of 4 time-points, namely +60', +90', +120' and +150'. CONCLUSION: A subset of 4 time-points (60' - 90' - 120' - 150') was identified as the most relevant to detect GH suppression at OGTT, with a perfect classification of 100% of subjects. This supports the possibility to restrict the blood samplings to these time-points when assessing disease cure, with possible advantages in terms of saving time and lowering costs.
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Acromegalia , Hormona de Crecimiento Humana , Acromegalia/diagnóstico , Recolección de Muestras de Sangre , Estudios de Cohortes , Prueba de Tolerancia a la Glucosa , Humanos , Factor I del Crecimiento Similar a la InsulinaRESUMEN
PURPOSE: Postoperative assessment of acromegaly activity is typically performed at least 3 months after neurosurgery (NS). Few studies have evaluated the use of early postoperative growth hormone (GH) levels as a test to predict short- and long-term remission of acromegaly. Our objective was to evaluate the diagnostic performance of serum random GH on a postoperative day one (D1-rGH) and two (D2-rGH), particularly in predicting long-term disease persistence. MATERIALS AND METHODS: Forty-one subjects with acromegaly who were undergoing NS were enrolled (mean age ± SD 47.4 ± 13.1 years at diagnosis; women 54%; macroadenomas 71%). The final assessment of disease activity was performed one year after NS. ROC curves were used to evaluate the diagnostic performance of D1-rGH and D2-rGH. RESULTS: After a 1-year follow-up, the overall remission rate was 55%. ROC analysis identified an optimal D1-rGH cut-off value of 2.1 ng/mL for diagnosing long-term disease persistence (55.6% SE; 90.9% SP). The cut-off point became 2.5 ng/mL after maximizing specificity for disease persistence (yielding a 100% positive predictive value) and 0.3 ng/mL after maximizing sensitivity for disease remission. The optimal D2-rGH cut-off value was 0.6 ng/mL (81.8% SE; 50% SP); the cut-off point became 2.9 ng/mL after maximizing specificity and 0.1 ng/mL after maximizing sensitivity, with no clinical utility. CONCLUSIONS: D1-rGH could be a highly specific test for the early diagnosis of long-term acromegaly persistence, which is predicted by a value > 2.5 ng/mL with a great degree of certainty. The diagnostic performance of D2-rGH was insufficient. Further research is required to validate these preliminary results prior to modifying the postoperative management of acromegaly.
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Acromegalia , Diagnóstico Precoz , Hormona de Crecimiento Humana/sangre , Efectos Adversos a Largo Plazo/diagnóstico , Procedimientos Neuroquirúrgicos/métodos , Cuidados Posoperatorios , Acromegalia/sangre , Acromegalia/diagnóstico , Acromegalia/cirugía , Femenino , Adenoma Hipofisario Secretor de Hormona del Crecimiento/cirugía , Humanos , Masculino , Persona de Mediana Edad , Gravedad del Paciente , Cuidados Posoperatorios/métodos , Cuidados Posoperatorios/normas , Valor Predictivo de las Pruebas , Pronóstico , Curva ROC , Inducción de Remisión/métodos , Sensibilidad y EspecificidadRESUMEN
PURPOSE: PATRO adults is an ongoing, multicenter, observational, post-marketing surveillance study aimed at investigating the long-term safety (primary endpoint) and effectiveness (secondary endpoint) of the recombinant human growth hormone (rhGH) Omnitrope® during routine clinical practice. This report describes data from Italian participants in PATRO Adults with growth hormone deficiency (GHD), up to August 2017. METHODS: Participants were adults (aged > 18 years) with GHD requiring rhGH therapy and were prescribed Omnitrope®, including those who had previously received another rhGH product. Adverse events (AEs) were evaluated in all study participants. Data were collected on insulin-like growth factor (IGF)-I levels and cardiovascular risk factors, including blood pressure, lipids, and anthropometric parameters. RESULTS: From September 2007 to August 2017, 88 patients (mean age 48.9 years, 58.0% male) were enrolled at 8 sites in Italy. The mean treatment duration with Omnitrope® was 51.5 ± 37 months. AEs occurred in 54 patients; the most common were asthenia (20.5%), headache (14.8%), and arthralgia (13.6%). Serious AEs occurred in 22 patients (25%), including pneumonia (n = 2) and renal failure (n = 2). Neoplasms (2 benign and 1 malignant) developed in three patients, but none were considered to be drug-related. There were no significant changes in fasting glucose or glycosylated hemoglobin (HbA1c) during the study period. Long-term Omnitrope® therapy showed slight positive effects on lipid profile, while no significant changes were observed in body weight and BMI during the study. CONCLUSION: This snapshot analysis of Italian participants in PATRO Adults confirmed the long-term safety and effectiveness of Omnitrope® in adults with GHD.
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Trastornos del Crecimiento/tratamiento farmacológico , Hormona de Crecimiento Humana/administración & dosificación , Hormona de Crecimiento Humana/deficiencia , Adulto , Anciano , Femenino , Estudios de Seguimiento , Trastornos del Crecimiento/epidemiología , Humanos , Italia/epidemiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
PURPOSE: Somatostatin receptor ligands (SRL) are the first-line medical treatment for acromegaly. Gallbladder alterations are one of most important SRL side effect, but according to some authors growth hormone hypersecretion itself is a risk factor for gallstones. This single center, longitudinal retrospective study evaluated the incidence and the predictors of biliary adverse events (BAE) in acromegaly during SRL therapy and their response to ursodeoxycholic acid (UDCA). METHODS: 91 acromegaly patients with indication to SRL were enrolled. Evaluations of acromegaly activity (GH, IGF-I, IGF-I/ULN) and metabolic profile were collected before starting treatment, yearly during follow-up and at BAE onset. In patients developing BAE we searched for predictors of UDCA effectiveness. RESULTS: 61.5% of patients developed BAE (58.9% cholelithiasis; 41.1% only sludge). IGF-I and IGF-I/ULN proved to be positive predictor of BAE, which occur about 5 years after SRL starting. None of metabolic markers proved to be associated with BAE. Only five patients (5.5%) underwent cholecystectomy for symptomatic cholelithiasis. 71% of patients started UDCA treatment, achieving regression of BAE in 60% of cases (88% in patients developing only sludge and 30% in patients affected by cholelithiasis, p < 0.001). BMI and obesity were negative predictors of UDCA efficacy. In 50% of the subjects BAE resolved after 36 months of therapy with a lower rate if cholelithiasis was present. CONCLUSION: Biliary stone disease is a frequent SRL adverse event, although it is often symptomless. Ultrasound follow-up mainly in the first 5 years of therapy, early UDCA starting and proper lifestyle represent a valid strategy in their detection and management.
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Acromegalia/tratamiento farmacológico , Receptores de Somatostatina/metabolismo , Acromegalia/sangre , Adulto , Femenino , Cálculos Biliares/sangre , Cálculos Biliares/tratamiento farmacológico , Hormona de Crecimiento Humana/sangre , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Octreótido/uso terapéutico , Péptidos Cíclicos/uso terapéutico , Estudios Retrospectivos , Somatostatina/análogos & derivados , Somatostatina/uso terapéutico , Ácido UrsodesoxicólicoRESUMEN
PURPOSE: The aim of the present study was to evaluate the rheumatic profile in acromegalic patients to better characterize joint pain. METHODS: The immunological pattern (rheumatoid factor; antinuclear antibodies-ANA, extractable nuclear antigens-ENA-Ab; anti-citrullinated protein antibodies; erythrocyte sedimentation rate) was evaluated in 20 acromegaly subjects (AS) and 20 control subjects (CS). Bilateral joint ultrasound of hands/wrists and nail capillaroscopy were also performed. RESULTS: Articular pain was more frequent in AS than in CS (p = 0.027). No difference was detected in immunological parameters. ANA and ENA-Ab were positive in only 10% of AS and in 5% of CS, while no difference was found in anti-citrullinated protein antibodies. No difference was detected between rheumatoid factor positivity, but threefold higher IgG were detected in AS compared to CS. The erythrocyte sedimentation rate was significantly higher in AS than CS (p = 0.040), while in AS, there was a trend in increased Power Doppler (PWD) articular uptake. The capillaroscopic evaluation showed a significant difference in almost each parameter (presence and number of tortuous capillaries, capillary enlargements, and hemorrhages), showing a moderate-to-severe microangiopathy in AS. CONCLUSION: The results of our study suggest that joint damage in acromegaly has not an autoimmune etiology. Increased erythrocyte sedimentation rate levels and PWD alteration in acromegalic population reflect a possible inflammatory nature, while the capillaroscopic findings suggest a moderate-to-severe microangiopathy that could help to identify patients with a greater macroangiopathic risk.
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Acromegalia/epidemiología , Adenoma/epidemiología , Artralgia/epidemiología , Adenoma Hipofisario Secretor de Hormona del Crecimiento/epidemiología , Enfermedades Reumáticas/epidemiología , Acromegalia/sangre , Acromegalia/etiología , Adenoma/sangre , Adenoma/complicaciones , Adulto , Anciano , Anticuerpos Antinucleares/sangre , Antígenos Nucleares/sangre , Artralgia/sangre , Artralgia/diagnóstico , Artralgia/etiología , Estudios de Casos y Controles , Estudios Transversales , Femenino , Adenoma Hipofisario Secretor de Hormona del Crecimiento/sangre , Adenoma Hipofisario Secretor de Hormona del Crecimiento/complicaciones , Humanos , Articulaciones/irrigación sanguínea , Articulaciones/patología , Masculino , Microcirculación/fisiología , Persona de Mediana Edad , Enfermedades Reumáticas/sangre , Enfermedades Reumáticas/diagnóstico , Enfermedades Reumáticas/etiologíaRESUMEN
PURPOSE: Uncertainties exist about the predictors of the severity of the clinical picture of GH deficiency (GHD) syndrome. Aim of the study was to evaluate, in adult patients with GHD, the predictors of the development of hypercholesterolemia, hypertension, diabetes mellitus, and osteoporosis. METHODS: We retrospectively studied 327 adult patients (age 47.1 ± 17.1 years) with untreated severe GHD (mean follow-up 110.9 ± 56.8 months). GHD was defined by GHRH + arginine test using BMI cut-offs. The possible development of hypercholesterolemia, hypertension, diabetes mellitus, and osteoporosis was investigated by Kaplan-Meier survival analysis. For each clinical outcome, either a univariate or multivariate analysis according to the Cox proportional-hazards model was performed to identify those factors that were associated with the development of the event. RESULTS: GH secretion parameters were not associated with the outcomes. Hypercholesterolemia was positively and negatively predicted by a BMI ≥ 30 kg/m2 (HR 2.50, p 0.00) and the dose of l-thyroxine possibly in place (HR 0.98, p 0.02), respectively. Hypertension was positively predicted by a BMI ≥ 30 kg/m2 (HR 2.64, p 0.00) and IGF-I SDS values (HR 2.26, p 0.00). Diabetes mellitus was positively predicted by hypertension (HR 11.76, p 0.01). Osteoporosis was positively and negatively predicted by hypercholesterolemia (HR 3.25, p 0.01) and hypertension (HR 0.21, p 0.00), respectively. CONCLUSIONS: The severity of the impairment of GH secretion does not predict the development of the clinical picture of GHD syndrome: untreated adult GHD does not increase the development of metabolic risk factors in hypopituitaric patients.
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Enanismo Hipofisario/sangre , Enanismo Hipofisario/diagnóstico , Hormona de Crecimiento Humana/sangre , Enfermedades Metabólicas/sangre , Enfermedades Metabólicas/diagnóstico , Adulto , Estudios de Cohortes , Diabetes Mellitus/sangre , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Enanismo Hipofisario/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/sangre , Hipertensión/diagnóstico , Hipertensión/epidemiología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Enfermedades Metabólicas/epidemiología , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
PURPOSE: To report the long-term effectiveness and safety of the recombinant human growth hormone Omnitrope®, a somatropin biosimilar to Genotropin®, in Italian patients with growth hormone deficiency (GHD) enrolled in the PATRO Adults study. METHODS: The PATRO Adults study is an ongoing observational, longitudinal, non-interventional global post-marketing surveillance study, conducted in several European countries. The primary endpoint is long-term safety; secondary endpoints include the effectiveness of Omnitrope®, which was assessed using serum insulin-like growth factor-1 levels, body composition, bone mineral density and lipid levels. Here we report the data from the Italian patients enrolled in the study. RESULTS: Sixty-seven patients (mean age 50.4 years, 61.2% male) have been enrolled and have received a mean 45.4 ± 24.3 months of Omnitrope®. A total of 55.2% of patients were reported to have experienced adverse events (AEs), including arthralgia, myalgia, abdominal distension and hypoaesthesia, and 4.5% had adverse drug reactions. Fourteen serious AEs have been recorded; none of these are considered related to the study drug. The effectiveness of Omnitrope® was similar to other available somatropin preparations. CONCLUSIONS: This study confirms the effectiveness and safety of Omnitrope® in adult patients with GHD in Italy. However, due to the limited size of the study population, these results need to be further confirmed by the global PATRO Adults study.
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Estatura/efectos de los fármacos , Densidad Ósea/efectos de los fármacos , Trastornos del Crecimiento/tratamiento farmacológico , Hormona de Crecimiento Humana/uso terapéutico , Adulto , Anciano , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , SeguridadRESUMEN
PURPOSE: To determine the validity of a self-administered questionnaire (Acro-CQ) developed to systematically assess the presence, type and time of onset of acromegaly comorbidities. METHODS: This is a cross-sectional study; 105 acromegaly patients and 147 controls with other types of pituitary adenoma, referred to a specialized Italian Center, autonomously compiled Acro-CQ in an outpatient clinical setting. To test its reliability in a different setting, Acro-CQ was administered via mail to 78 patients with acromegaly and 100 with other pituitary adenomas, referred to a specialized US Center. Data obtained from questionnaires in both settings were compared with medical records (gold standard). RESULTS: Demographics of patients and controls from both countries were similar. In both settings, >95 % of the questionnaires were completely filled; only one item was missed in the others. Concordance with medical record was excellent (k > 0.85) for most of the items, independently from the way of administration, patient age, gender and nationality, pituitary adenoma type and disease activity. CONCLUSIONS: Acro-CQ is an inexpensive, highly accepted from patients and reliable tool recommended to expedite systematic collection of relevant clinical data in acromegaly at diagnosis, to be replicated at follow-ups. This tool may guide a targeted, cost-effective management of complications. Moreover, it could be applied to retrieve data for survey studies in both acromegaly and other pituitary adenomas, as information is easily and rapidly accessible for statistical analysis.
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Acromegalia/epidemiología , Biomarcadores/análisis , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/prevención & control , Estudios de Casos y Controles , Comorbilidad , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
PURPOSE: The management of choice of non-functioning pituitary adenomas (NFPAs) remains debulking surgery when symptomatic. However, patient series systematically reporting the NFPAs outcome that were not treated either surgically, medically or with radiotherapy during long follow-up thereby giving an indication of their natural history are limited. Aim of the present study was to evaluate the natural course of presumed NFPAs, the outcome of confirmed NFPAs during a long follow-up period. METHODS: Between 1993 and 2013, 84 patients with presumed NFPA were studied retrospectively. Patients were enrolled based on the following criteria: imaging suggestive of pituitary adenoma, absence of any biochemical/clinical evidence of hormonal excess, exclusion of prolactinomas and at least one sequential imaging during the follow-up. Repeated assessment of the pituitary function, visual fields and imaging was performed at regular intervals. The follow-up duration was evaluated from the first and last imaging dates. RESULTS: In group F (follow-up without surgery, 33 patients), the macroadenomas showed a 15% probability of tumor growth and reduction. Similar tumor size alterations were observed also for the microadenomas. In group S (surgery, 51 patients), both residual tumors (>1 and <1 cm) following initial surgical resection remain mainly stable until the last imaging. CONCLUSIONS: Based on the given lack of approved medical treatment and the possible risks of surgical intervention in presence of significant comorbidities, our study proposes a conservative approach with a careful follow-up in patients with NFPAs without visual or neurological abnormalities.
Asunto(s)
Adenoma/patología , Progresión de la Enfermedad , Neoplasias Hipofisarias/patología , Adenoma/complicaciones , Adenoma/cirugía , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/cirugía , Estudios RetrospectivosRESUMEN
CONTEXT: Hepatotoxicity is one of the most serious adverse effects in acromegalic patients treated with pegvisomant (PEG-V). Recent studies have found an association between this adverse event and the UGT1A1 allele 28 polymorphism associated with Gilbert's syndrome. OBJECTIVE: To determine whether UGT1A1*28 and alcohol dehydrogenase (ADH) polymorphisms influence liver toxicity during PEG-V treatment. DESIGN AND SETTING: Multicenter observational retrospective study conducted in 13 tertiary care endocrinology units in Italy. PATIENTS: A total of 112 patients with active disease resistant to somatostatin analogs (SSTa) and 108 controls were enrolled. INTERVENTIONS: Clinical and biochemical data were recorded by electronic clinical reporting forms. Blood or DNA samples were sent to the coordinating center for genotyping. RESULTS: No differences in genotypes between patients and controls were found. During PEG-V therapy liver function tests (LFT), abnormalities and overt hepatotoxicity developed in 17 and 4.5% of patients respectively. Logistic and linear regression analyses showed an association between LFT abnormalities during the follow-up visit and prior events of LFT abnormalities in medical history (odds ratio=1.25; P=0.04) and the number of concomitant medications, other than SSTa (B=3.9; P=0.03). No correlation between LFT alterations and UGT1A1 allele 28 as well as ADH1C and B polymorphisms was found. CONCLUSIONS: UGT1A1 allele 28 and ADH1C and B polymorphisms do not predict increased risk of hepatotoxicity during PEG-V therapy. Conversely, patients with multi-therapies and with previous episodes of liver disease should be carefully managed, due to the observed association between these conditions and LFT abnormalities during PEG-V therapy.
Asunto(s)
Acromegalia/genética , Alcohol Deshidrogenasa/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Glucuronosiltransferasa/genética , Hormona de Crecimiento Humana/análogos & derivados , Acromegalia/complicaciones , Acromegalia/tratamiento farmacológico , Adulto , Femenino , Genotipo , Hormona de Crecimiento Humana/efectos adversos , Humanos , Italia , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Estudios RetrospectivosRESUMEN
OBJECTIVE: Hypopituitarism is associated with metabolic alterations but in TBI-induced hypopituitarism data are scanty. The aim of our study was to evaluate the prevalence of naïve hypertension, dyslipidemia, and altered glucose metabolism in TBI-induced hypopituitarism patients. DESIGN: Cross-sectional retrospective study in a tertiary care endocrinology center. 54 adult patients encountering a moderate or severe TBI were evaluated in the chronic phase (at least 12 months after injury) after-trauma. Presence of hypopituitarism, BMI, hypertension, fasting blood glucose and insulin levels, oral glucose tolerance test (if available) and a lipid profile were evaluated. RESULTS: The 27.8% of patients showed various degrees of hypopituitarism. In particular, 9.3% had total, 7.4% multiple and 11.1% isolated hypopituitarism. GHD was present in 22.2% of patients. BMI was similar between the two groups. Hypopituitaric patients presented a higher prevalence of dyslipidemia (p<0.01) and altered glucose metabolism (p<0.005) with respect to non hypopituitaric patients. In particular, triglycerides (p<0.05) and HOMA-IR (p<0.02) were higher in hypopituitaric TBI patients. CONCLUSIONS: We showed that long-lasting TBI patients who develop hypopituitarism frequently present metabolic alterations, in particular altered glucose levels, insulin resistance and hypertriglyceridemia. In view of the risk of premature cardiovascular death in hypopituitaric patients, major attention has to been paid in those who encountered a TBI, because they suffer from the same comorbidities and may present other deterioration factors due to complex pharmacological treatments and restriction in participation in life activities and healthy lifestyle.