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BACKGROUND: Recurrence of acromegaly after successful surgery is a rare event, but no clear data are reported in the literature about its recurrence rates. This study aimed to evaluate the recurrence rate in a series of acromegalic patients treated by transsphenoidal surgery (TSS) with a long follow-up. METHODS: We retrospectively analyzed data from 283 acromegalic patients who underwent TSS at two pituitary units in Milan (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and IRCCS Humanitas Research Hospital). The diagnosis and recurrence of acromegaly were defined by both elevated IGF-1 levels and a lack of GH suppression based on appropriate criteria for the assay used at the time of diagnosis. RESULTS: After surgery, 143 patients (50%) were defined as not cured, 132 (47%) as cured and 8 (3%) as partially cured because of normalization of only one parameter, either IGF1 or GH. In the cured group, at the last follow-up (median time 86.8 months after surgery), only 1 patient (0.7%) showed full recurrence (IGF-1 + 5.61 SDS, GH nadir 1.27 µg/l), while 4 patients (3%) showed only increased IGF1. In the partially cured group at the last follow-up, 2/8 (25%) patients showed active acromegaly (IGF-1 SDS + 2.75 and + 3.62; GH nadir 0.6 and 0.5 µg/l, respectively). CONCLUSIONS: In the literature, recurrence rates range widely, from 0 to 18%. In our series, recurrence occurred in 3.7% of patients, and in fewer than 1%, recurrence occurred with elevation of both IGF-1 and the GH nadir. More frequently (25%), recurrence came in the form of incomplete normalization of either IGF-1 or GH after surgery.
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OBJECTIVE: This study aimed to assess the long-term outcome of patients with acromegaly. DESIGN: This is a multicenter, retrospective, observational study which extends the mean observation period of a previously reported cohort of Italian patients with acromegaly to 15 years of follow-up. METHODS: Only patients from the centers that provided information on the life status of at least 95% of their original cohorts were included. Life status information was collected either from clinical records or from the municipal registry offices. Standardized mortality ratios (SMRs) were computed comparing data with those of the general Italian population. RESULTS: A total of 811 patients were included. There were 153 deaths, with 90 expected and an SMR of 1.7 (95% CI 1.4-2.0, p < 0.001). Death occurred after a median of 15 (women) or 16 (men) years from the diagnosis, without gender differences. Mortality remained elevated in the patients with control of disease (SMR 1.3, 95% CI 1.1-1.6). In the multivariable analysis, only older age and high IGF1 concentrations at last available follow-up visit were predictors of mortality. The oncological causes of death outweighed the cardiovascular ones, bordering on statistical significance with respect to the general population. CONCLUSIONS: Mortality remains significantly high in patients with acromegaly, irrespectively of disease status, as long as the follow-up is sufficiently long with a low rate of patients lost to follow-up. Therapy strategy including radiotherapy does not have an impact on mortality. Oncological causes of death currently outweigh the cardiovascular causes.
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Acromegalia , Humanos , Masculino , Feminino , Acromegalia/mortalidade , Acromegalia/terapia , Itália/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Seguimentos , Idoso , Taxa de Sobrevida , PrognósticoRESUMO
OBJECTIVES: To report epidemiological and virological results of an outbreak investigation of influenza-like illness (ILI) among refugees in Northern Italy. STUDY DESIGN: Outbreak investigation of ILI cases observed among nearly 100 refugees in Northern Italy unvaccinated for influenza. METHODS: An epidemiological investigation matched with a differential diagnosis was carried out for each sample collected from ILI cases to identify 10 viral pathogens (SARS-CoV-2, influenza virus type A and B, respiratory syncytial virus, metapneumovirus, parainfluenza viruses, rhinovirus, enterovirus, parechovirus, and adenovirus) by using specific real-time PCR assays according to the Centers for Disease Control and Prevention (CDC) protocols. In cases where the influenza virus type was identified, complete hemagglutinin (HA) gene sequencing and the related phylogenetic analysis were conducted. RESULTS: The outbreak was caused by influenza A(H3N2): the attack rate was 83.3% in children aged 9-14 years, 84.6% in those aged 15-24 years, and 28.6% in adults ≥25 years. Phylogenetic analyses uncovered that A(H3N2) strains were closely related since they segregated in the same cluster, showing both a high mean nucleotide identity (100%), all belonging to the genetic sub-group 3C.2a1b.2a.2, as those mainly circulating into the general population in the same period. CONCLUSIONS: The fact that influenza outbreak strains as well as the community strains were genetically related to the seasonal vaccine strain suggests that if an influenza prevention by vaccination strategy had been implemented, a lower attack rate of A(H3N2) and ILI cases might have been achieved.
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Vírus da Influenza A , Vacinas contra Influenza , Influenza Humana , Refugiados , Viroses , Adulto , Criança , Humanos , Influenza Humana/epidemiologia , Vírus da Influenza A Subtipo H3N2/genética , Filogenia , Surtos de DoençasRESUMO
PURPOSE: Dynamic testing represents the mainstay in the differential diagnosis of ACTH-dependent Cushing's syndrome. However, in case of undetectable or detectable lesion < 6 mm on MRI, bilateral inferior petrosal sinus sampling (BIPSS) is suggested by current guidelines. Aim of this study was to analyze the performance of CRH, desmopressin and high-dose dexamethasone suppression test (HDDST) in the differential diagnosis of ACTH-dependent Cushing's syndrome as well as the impact of invasive and noninvasive tests on surgical outcome in patients affected by Cushing's disease (CD). METHODS: Retrospective analysis on 148 patients with CD and 26 patients with ectopic ACTH syndrome. RESULTS: Among CD patients, negative MRI/lesion < 6 mm was detected in 97 patients (Group A); 29 had a 6-10 mm lesion (Group B) and 22 a macroadenoma (Group C). A positive response to CRH test, HDSST and desmopressin test was recorded in 89.4%, 91·4% and 70.1% of cases, respectively. Concordant positive response to both CRH/HDDST and CRH/desmopressin tests showed a positive predictive value of 100% for the diagnosis of CD. Among Group A patients with concordant CRH test and HDDST, no difference in surgical outcome was found between patients who performed BIPSS and those who did not (66.6% vs 70.4%, p = 0.78). CONCLUSIONS: CRH, desmopressin test and HDDST have high accuracy in the differential diagnosis of ACTH-dependent CS. In patients with microadenoma < 6 mm or non-visible lesion, a concordant positive response to noninvasive tests seems sufficient to diagnose CD, irrespective of MRI finding. In these patients, BIPSS should be reserved to discordant tests.
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Hormônio Adrenocorticotrópico/sangue , Síndrome de Cushing/diagnóstico , Imageamento por Ressonância Magnética/métodos , Amostragem do Seio Petroso/métodos , Hipersecreção Hipofisária de ACTH , Testes de Função Hipofisária/métodos , Neoplasias Hipofisárias , Adulto , Síndrome de Cushing/epidemiologia , Diagnóstico Diferencial , Técnicas de Diagnóstico Endócrino , Feminino , Humanos , Hipofisectomia/métodos , Hipofisectomia/estatística & dados numéricos , Itália/epidemiologia , Masculino , Hipersecreção Hipofisária de ACTH/sangue , Hipersecreção Hipofisária de ACTH/diagnóstico , Hipersecreção Hipofisária de ACTH/epidemiologia , Hipersecreção Hipofisária de ACTH/cirurgia , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Estudos RetrospectivosRESUMO
OBJECTIVE: Patients with Cushing's syndrome (CS) are at high risk of venous thromboembolism related to a hypercoagulability due to procoagulant imbalance. However, whether these alterations are reversible after disease remission is still unclear. The endogenous thrombin potential (ETP) measured with and without the addition of thrombomodulin provides a global representation of coagulation and previous data confirmed hypercoagulable profile in patients with active hypercortisolism. Aim of this study was to assess the short- and long-term modification of ETP in patients with CS after disease remission. DESIGN AND METHODS: Nineteen patients with CS for whom surgical remission was achieved, were prospectively evaluated for clinical characteristics, cortisol secretion profile and ETP at different time points: (i) before surgical intervention; (ii) after 6 months and (iii) 5 years from the time of persistent remission. Nineteen healthy subjects matched for age and gender were also evaluated as control group. RESULTS: Before surgery, patients showed higher ETP-ratio (with/without thrombomodulin) than controls (0.62 ± 0.09-vs-0.56 ± 0.09, p = 0.034). No significant correlation between ETP-ratio and cortisol secretion was found. 6 months after remission, ETP-ratio was still significantly increased compared to controls (0.64 ± 0.09-vs-0.56 ± 0.09, p = 0.01), but was similar to baseline (0.64 ± 0.09-vs-0.62 ± 0.09, p = 0.87). At 5 years, ETP-ratio showed a significant decrease (0.55 ± 0.14-vs-0.62 ± 0.09, p = 0.02) and was comparable to controls (0.55 ± 0.14-vs-0.56 ± 0.09, p = 0.7). CONCLUSIONS: Plasma hypercoagulability detected in patients with active hypercortisolism persists at short-term evaluation and seems to be completely reversible after long-term remission of disease. These data, as part of a whole evaluation of thrombotic risk, can contribute to make appropriate therapeutic choice in these patients.
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Testes de Coagulação Sanguínea/métodos , Síndrome de Cushing , Hidrocortisona/sangue , Trombina/análise , Trombofilia , Tromboembolia Venosa , Adrenalectomia/métodos , Adulto , Coagulação Sanguínea , Síndrome de Cushing/sangue , Síndrome de Cushing/complicações , Síndrome de Cushing/cirurgia , Feminino , Humanos , Hipofisectomia/métodos , Masculino , Período Pós-Operatório , Indução de Remissão , Medição de Risco/métodos , Trombofilia/sangue , Trombofilia/etiologia , Tempo , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controleRESUMO
PURPOSE: A long-lasting remission of acromegaly after somatostatin analogues (SAs) withdrawal has been described in some series. Our aim was to update the disease evolution after SAs withdrawal in a cohort of acromegalic patients. METHODS: We retrospectively evaluated 21 acromegalic patients previously included in a multicentre study (Ronchi et al. 2008), updating data at the last follow-up. We added further 8 patients selected for SAs withdrawal between 2008-2018. Pituitary irradiation represented an exclusion criterion. The withdrawal was suggested after at least 9 months of clinical and hormonal disease control. Clinical and biochemical data prior and after SAs withdrawal were analysed. RESULTS: In the whole cohort (29 patients) mean age was 50 ± 14.9 years and 72.4% were females. In 69% pituitary surgery was previously performed. Overall, the median time of treatment before SAs withdrawal was 53 months (IQR = 24-84). At the last follow up in 2019, 23/29 patients (79.3%) had a disease relapse after a median time of 6 months (interquartile range or IQR = 3-12) from the drug suspension, while 6/29 (20.7%) were still on remission after 120 months (IQR = 66-150). IGF-1 levels were significantly lower before withdrawal in patients with persistent remission compared to relapsing ones (IGF-1 SDS: -1.5 ± 0.6 vs -0.11 ± 1, p = 0.01). We did not observe any other difference between patients with and without relapse, including SAs formulation, dosage and treatment duration. CONCLUSION: A successful withdrawal of SAs is possible in a subset of well-controlled acromegalic patients and it challenges the concept that medical therapy is a lifelong requirement.
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Acromegalia , Fator de Crescimento Insulin-Like I/análise , Prevenção Secundária , Somatostatina , Suspensão de Tratamento/estatística & dados numéricos , Acromegalia/sangue , Acromegalia/diagnóstico , Acromegalia/tratamento farmacológico , Duração da Terapia , Feminino , Hormônios/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Indução de Remissão/métodos , Prevenção Secundária/métodos , Prevenção Secundária/estatística & dados numéricos , Somatostatina/análogos & derivados , Somatostatina/farmacologia , Tempo , Resultado do TratamentoRESUMO
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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Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/deficiência , Adulto , Idoso , Feminino , Seguimentos , Transtornos do Crescimento/epidemiologia , Humanos , Itália/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
BACKGROUND: First-line therapy of Cushing disease (CD) is transsphenoidal surgery (TSS) aimed to obtain a complete removal of the pituitary adenoma and remission of disease. PURPOSE: To analyse the surgical outcome of patients with CD who underwent TSS in our Centre. METHODS: Retrospective analysis on patients with CD who underwent TSS between 1990 and 2016. RESULTS: We analysed 102 TSS that included: 84 first TSS and 18 second and third TSS. The overall remission rate after surgery was 76.5%, with a significant higher percentage of remitted patients after the first TSS compared to the subsequent TSS (82% vs 50%, p = 0.014). The remission after the first TSS was significantly higher when performed by a dedicated surgical team (DST) (89.8% vs 71% p = 0.04) and when the immunohistochemical examination confirmed the adrenocorticotropic adenoma (87% vs 55%, p = 0.04). Neuroradiological findings influenced the surgical outcome in a non-significant manner. Post-TSS complications were reported in 32 patients, with no significant variation when TSS was performed by DST. In case of reintervention, remission of disease was obtained in 72.7% of microadenoma, while no remitted patients were observed in case of macroadenomas. The DST did not significantly improve the outcome. CONCLUSION: Cushing disease is characterized by a broad spectrum of neuroradiological presentation. Despite the availability of a DST make the TSS a safe and effective first-line treatment among all these patients, a precise pre-treatment evaluation is needed in order to define the aim of neurosurgery and to schedule the management of recurrent disease.
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Adenoma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Hipersecreção Hipofisária de ACTH/cirurgia , Neoplasias Hipofisárias/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Patients with cystic fibrosis awaiting lung transplantation for end-stage respiratory failure have high prevalence of reduced bone mineral density and fragility fracture. Suboptimal 25-hydroxyvitamin D levels could significantly contribute to the development of cystic fibrosis-related bone disease. INTRODUCTION: The assessment of the prevalence of cystic fibrosis-related bone disease (CFBD) and its associated risk factors in young adults with cystic fibrosis (CF) awaiting lung transplantation for end-stage respiratory failure. METHODS: Clinical characteristics, bone mineral density (BMD), the parameters of calcium metabolism, including vitamin D (25OHVitD) levels, and the presence of fragility fractures were evaluated in 42 CF patients (24 females, age 34.0 ± 8.4 years) consecutively referred as lung transplant candidates. RESULTS: Mean 25OHVitD levels (54.9 ± 26.2 nmol/L) were below the reference range and hypovitaminosis D (25OHVitD < 75 nmol/L) was found in 34 patients (81%) and daily calcium intakes (median 550 mg/day) were lower than recommended. A BMD below the expected range for age (Z-score of - 2.0 or lower) and at least one prevalent fragility fracture were found in 22 patients (52.4%) and 18 patients (45.2%), respectively. The coexistence of low BMD and the presence of fracture was observed in 13 patients (31.0%). In these patients, the prevalence of nephrolithiasis was higher than in the remaining ones (p = 0.046). The presence of kidney stones was associated with a worse bone status and with severe vitamin D deficiency. In the whole sample, femoral BMD Z-scores were directly correlated with albumin-adjusted calcium (p < 0.05) and 25OHVitD levels (p < 0.01). CONCLUSIONS: Despite the improvement of CF care, CFBD is still highly prevalent in young adults awaiting lung transplantation for end-stage CF. Suboptimal 25OHVitD levels could significantly contribute to the development of CFBD. The presence of nephrolithiasis could be an additional warning about the need for a careful evaluation of bone health in CF patients.
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Fibrose Cística/complicações , Transplante de Pulmão , Osteoporose/etiologia , Insuficiência Respiratória/etiologia , Adulto , Densidade Óssea/fisiologia , Estudos Transversais , Fibrose Cística/sangue , Fibrose Cística/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefrolitíase/etiologia , Osteoporose/sangue , Osteoporose/fisiopatologia , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/fisiopatologia , Insuficiência Respiratória/sangue , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/cirurgia , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/etiologia , Deficiência de Vitamina D/fisiopatologia , Adulto JovemRESUMO
PURPOSE: Arthropathy is a common and disabling complication of acromegaly. Since in this condition radiological findings rarely correspond to functional impairment, we elected to quantify in a large cohort of acromegalic patients: the degree of motor disability compared with data from general population, the impact of joint involvement on quality of life and work productivity, and to look for associated factors. METHODS: In 211 acromegalic patients, 131 with controlled disease and 80 with active disease, eight validated scales were used to evaluate the (i) prevalence and distribution of arthropathy, (ii) degree of motor disability and joint symptoms (VAS, AIMS symptoms and WOMAC), (iii) quality of life (AcroQoL and PASQ) and work capability (WPAI:GH) as consequences of joint complications. RESULTS: Using the WOMAC questionnaire, for which population based normative values are available, a significantly higher prevalence and severity of motor disability was detected in acromegalics compared to the general population from literature. The results provided by the different questionnaires turned out to be highly concordant. All measures of motor disability correlated both with impaired quality of life and motor disability and were worse in females and in patients with higher BMI. CONCLUSIONS: The questionnaires VAS, AIMS symptoms, and WOMAC (this latter both as a whole and with its functionality subscale), with their scores, proved to be the most adequate tools to evaluate motor disability and its consequences on both quality of life and work productivity in acromegaly. Female gender and higher BMI are associated with worse articular symptoms.
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Acromegalia/fisiopatologia , Artropatias/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Inquéritos e Questionários , Adulto JovemRESUMO
The pharmacological therapy of GH-secreting pituitary tumors is based on somatostatin (SS) analogs that reduce GH secretion and cell proliferation by binding mainly SS receptors type 2 (SST2). Antimigratory effects of SS have been demonstrated in different cell models, but no data on pituitary tumors are available. Aims of our study were to evaluate SST2 effects on migration and invasion of human and rat tumoral somatotrophs, and to elucidate the molecular mechanism involved focusing on the role of cofilin and filamin A (FLNA). Our data revealed that SST2 agonist BIM23120 significantly reduced GH3 cells migration (-22% ± 3.6%, p < 0.001) and invasion on collagen IV (-31.3% ± 12.2%, p < 0.01), both these effects being reproduced by octreotide and pasireotide. Similar results were obtained in primary cultured cells from human GH-secreting tumors. These inhibitory actions were accompanied by a marked increase in RhoA/ROCK-dependent cofilin phosphorylation (about 2.7-fold in GH3 and 2.1-fold in human primary cells). Accordingly, the anti-invasive effect of the SS analog was mimicked by the overexpression in GH3 cells of the S3D phosphomimetic cofilin mutant, and abolished by both phosphodeficient S3A cofilin and a specific ROCK inhibitor that prevented cofilin phosphorylation. Moreover, FLNA silencing and FLNA dominant-negative mutants FLNA19-20 and FLNA21-24 transfection demonstrated that FLNA plays a scaffold function for SST2-mediated cofilin phosphorylation. Accordingly, cofilin recruitment to agonist-activated SST2 was completely lost in FLNA silenced cells. In conclusion, we demonstrated that SST2 inhibits rat and human tumoral somatotrophs migration and invasion through a molecular mechanism that involves FLNA-dependent cofilin recruitment and phosphorylation.
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Citoesqueleto/metabolismo , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/metabolismo , Receptores de Somatostatina/agonistas , Receptores de Somatostatina/metabolismo , Somatostatina/análogos & derivados , Fatores de Despolimerização de Actina/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Citoesqueleto/efeitos dos fármacos , Filaminas/metabolismo , Humanos , Invasividade Neoplásica , Fosforilação , Neoplasias Hipofisárias/patologia , Ratos , Transdução de Sinais/efeitos dos fármacos , Somatostatina/farmacologia , Proteína rhoA de Ligação ao GTP/metabolismoRESUMO
OBJECTIVE: To evaluate if the parameters of hypothalamic-pituitary-adrenal (HPA) axis activity could predict the occurrence and duration of post-surgical hypocortisolism (PSH) in patients with Cushing's syndrome (CS) and with adrenal incidentaloma (AI). METHODS: We studied 80 patients (54 females, age 53.3 ± 11 years), who underwent adrenalectomy for CS (17 patients) or for AI (53 patients). Before surgery, we measured adrenocorticotroph hormone (ACTH), urinary free cortisol (UFC) and serum cortisol after 1 mg dexamethasone suppression test (1 mg-DST) levels. After surgery, all patients were given a steroid replacement therapy, and PSH was searched after 2 months by a low-dose (1 µg, iv) corticotropin stimulation test, that was repeated every 6 months in PSH patients for at least 4 years. RESULTS: The PSH occurred in 82.4 and 46% of CS and AI patients, respectively. In the whole sample and in AI patients separately considered, the PSH was independently predicted by the preoperative cortisol levels after 1 mg-DST, however, with a low (< 70%) accuracy. In AI patients the PSH occurrence was not ruled out even by the cortisol levels after 1 mg-DST lower than 1.8 µg/dL (50 nmol/L). In the 50% of CS patients and in 31% of AI patients the PSH lasted more than 18 months and in 35.7% of CS patients it persisted for more than 36 months. In AI patients, the PSH duration was not predictable by any parameter. However, a PSH duration of at least 12 months was significantly predicted before adrenalectomy (sensitivity 91.7%, specificity 41.2%, positive predictive value 52.4%, negative predictive value 87.5%, p = 0.05) by the presence of at least 2 out of low ACTH levels, increased UFC levels and cortisol levels after 1 mg-DST ≥ 3.0 µg/dL (83 nmol/L). CONCLUSION: The PSH occurrence and its duration are hardly predictable before surgery. All patients undergoing unilateral adrenalectomy should receive a steroid substitutive therapy.
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Doença de Addison/diagnóstico , Doença de Addison/epidemiologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/efeitos adversos , Hormônio Adrenocorticotrópico/sangue , Síndrome de Cushing/cirurgia , Complicações Pós-Operatórias , Doença de Addison/sangue , Doença de Addison/etiologia , Adulto , Idoso , Feminino , Humanos , Sistema Hipotálamo-Hipofisário , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-SuprarrenalRESUMO
PURPOSE: To compare the response to denosumab (DMAb) therapy with that of oral bisphosphonate (BISPH) treatment in postmenopausal women with primary osteoporosis (PO). METHODS: In this retrospective study, we compared data of 75 PO female patients treated for 24 months with DMab (DMAb Group, age 72.6 ± 8.9 years) with those of 75 PO patients treated with oral bisphosphonates (BISPH Group), matched for age, body mass index, femoral bone mineral density (BMD), prevalent fragility fractures and familiar history of hip fracture. In all subjects at baseline and after 24 months we assessed the calcium-phosphorous metabolism parameters, BMD at lumbar spine (LS-BMD) and femoral neck (FN-BMD) by dual X-ray absorptiometry and the morphometric vertebral fractures by radiograph. The patients were considered inadequate responders in the presence of ≥ 2 incident fragility fractures and/or a decrease in BMD greater than the least significant change (LS 2.8%, FN 5.9%). RESULTS: After 24 months, the DMab Group showed a greater ALP decrease (- 22.8 ± 18.2%), a higher LS-BMD and FN-BMD increase (6.6 ± 6.9 and 4.4 ± 8.2%, respectively) and a lower number of patients with an incident fracture (8%) and with an inadequate response (6.7%) than BISPH Group (- 14.9 ± 15.3, 2.5 ± 4.3, 1.9 ± 4.5, 21.3 and 22.7%, respectively, p < 0.05 for all comparisons). The inadequate response was 4.5-fold more likely in BISPH Group than in DMab one (p = 0.027), regardless of possible confounders. CONCLUSIONS: In postmenopausal PO females, denosumab was more effective than oral bisphosphonates in increasing BMD and reducing bone turnover and the number of inadequate responder patients.
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Conservadores da Densidade Óssea/uso terapêutico , Denosumab/uso terapêutico , Difosfonatos/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
Recently, the European Society of Endocrinology (ESE) published new guidelines on the management of adrenal incidentalomas. At the same time Lopez and coworkers published on the Annals of Internal Medicine an important study showing that even patients with non-functioning adrenal tumors have an increased risk of incident diabetes. In consideration of previous data and of the results of the study of Lopez and coworkers, some points emerge from the ESE Guidelines that deserve attention. Firstly, it must be observed that the term "autonomous cortisol secretion," introduced by the ESE Panel in the place of the commonly used "subclinical hypercortisolism," seems questionable, since the guidelines do not suggest determining the adrenocorticotroph hormone levels that could give the certain proof of a truly autonomous cortisol secretion. Secondly, the ESE Guidelines suggest against repeated hormonal workup in AI patients with a normal hormonal secretion at initial evaluation, but also in those with a "possible autonomous cortisol secretion," if in the absence of comorbidities potentially related to hypercortisolism. Thirdly, the ESE Guidelines suggest against further imaging during follow-up in patients with an adrenal mass below 4 cm in size with clear benign features on imaging studies. Considering the available literature data that are briefly summarized in this comment, we believe that no sufficient evidence is available to date for giving sharp-cutting recommendations about the uselessness of a biochemical and morphological follow-up in AI patients, even in those with initially benign and not hypersecreting adrenal adenomas. However, if a recommendation has to be given on the basis of the present evidences, we should suggest to biochemically and morphologically follow-up AI patients for at least 5 years.
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Neoplasias das Glândulas Suprarrenais/patologia , Endocrinologia/normas , Guias de Prática Clínica como Assunto/normas , Neoplasias das Glândulas Suprarrenais/terapia , Seguimentos , Humanos , Achados IncidentaisAssuntos
COVID-19/diagnóstico , COVID-19/epidemiologia , Hipersecreção Hipofisária de ACTH/diagnóstico , Hipersecreção Hipofisária de ACTH/epidemiologia , Centros de Atenção Terciária/tendências , Adulto , Idoso , COVID-19/terapia , Estudos de Coortes , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Hipersecreção Hipofisária de ACTH/terapiaAssuntos
Biomarcadores/metabolismo , Diabetes Insípido/diagnóstico , Glicopeptídeos/metabolismo , Procedimentos Neurocirúrgicos/efeitos adversos , Doenças da Hipófise/cirurgia , Complicações Pós-Operatórias/diagnóstico , Diabetes Insípido/etiologia , Diabetes Insípido/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/patologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/metabolismo , Prognóstico , Estudos ProspectivosAssuntos
Endocrinologia/normas , Hiponatremia/terapia , Oncologia/normas , Nefrologia/normas , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Consenso , Endocrinologia/métodos , Endocrinologia/organização & administração , Humanos , Hiponatremia/diagnóstico , Hiponatremia/epidemiologia , Hiponatremia/etiologia , Itália , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/terapia , Oncologia/métodos , Oncologia/organização & administração , Nefrologia/métodos , Nefrologia/organização & administração , Neurologia/métodos , Neurologia/normas , Procedimentos Neurocirúrgicos/métodos , Procedimentos Neurocirúrgicos/normas , Prevalência , Sociedades Médicas/organização & administração , Sociedades Médicas/normasRESUMO
PURPOSE: The aim of this study was to assess the performance measurements of the new PET/CT system Discovery-600 (D-600, GEMS, Milwaukee, WI). METHODS: Performance measures were obtained with the National Electrical Manufacturers Association (NEMA) NU 2-2007 procedures. RESULTS: The transverse (axial) spatial resolution FWHMs were 4.9 (5.6) mm and 5.6 (6.4) mm at 1 and 10 cm off axis, respectively. The sensitivity (average at 0 and 10 cm) was 9.6 cps/kBq. The scatter fraction was 36.6% (low energy threshold: 425 keV). The NEC peak rate (k=1) was 75.2 kcps at 12.9 kBq/cc. The hot contrasts for 10, 13, 17, and 22 mm spheres were 41%, 51%, 62%, and 73% and the cold contrasts for 28 and 37 mm spheres were 68% and 72%. CONCLUSIONS: The Discovery-600 has good performance for the NEMA NU 2-2007 parameters, particularly in improved sensitivity compared to the scanners of the same Discovery family, D-ST and D-STE.
Assuntos
Eletricidade , Tomografia por Emissão de Pósitrons/normas , Tomografia Computadorizada por Raios X/normas , Padrões de Referência , Estados UnidosRESUMO
Isolated growth hormone deficiency (IGHD) is the most frequent endocrinological disorder in children with short stature, however the diagnosis is still controversial due to the scarcity of reliable diagnostic criteria and pre-treatment predictive factors of long term-response. To evaluate recombinant growth hormone (rGH) long-term response and retesting results in three different groups of children divided in accordance with the biochemical criteria of initial diagnosis. Height gain (∆HT) at adult height (AH) and retesting results were evaluated in 57 rGH treated children (M = 34, 59.6%) divided into 3 groups according to initial diagnosis: Group A (n = 25) with max GH peak at stimulation test < 8 µg/L, Group B (n = 19) between 8 and 10 µg/L and Group C (n = 13) with mean overnight GH < 3 µg/L (neurosecretory dysfunction, NSD). Retesting was carried out in all patients after at least one month off therapy upon reaching the AH. 40/57 (70.2%) patients were pre-pubertal at diagnosis and showed ∆HT of 1.37 ± 1.00 SDS, with no significant differences between groups (P = 0.08). Nonetheless, 46% patients in Group B showed ∆HT < 1SDS (vs 13% and 12% in Group A and C, respectively) and 25% children failed to reach mid-parental height (vs 6% and 0% in Group A and C, respectively). At AH attainment, IGHD was reconfirmed in 28% (7/25) and 10% (2/19) in Group A and B, respectively. A reduction of diagnostic cut-off at GH stimulation tests could better discriminate between "good" and "poor responders" and predict the persistence of IGHD through transition. Group C response and the predictive value of baseline IGF-I SDS bring back to light NSD: should we consider an underlying hypothalamic derangement when the clinical presentation is strongly consistent with IGHD but pharmacological stimulation test is normal?
Assuntos
Estatura , Nanismo Hipofisário/diagnóstico , Nanismo Hipofisário/tratamento farmacológico , Hormônio do Crescimento/uso terapêutico , Adolescente , Estatura/efeitos dos fármacos , Criança , Pré-Escolar , Feminino , Hormônio do Crescimento Humano/sangue , Hormônio do Crescimento Humano/deficiência , Humanos , Lactente , Fator de Crescimento Insulin-Like I/análise , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
CONTEXT: Acromegalic patients have an increased vertebral fracture (VFx) risk due to bone quality reduction, independently of bone mineral density (BMD). OBJECTIVE: The aim of the study is to describe bone quality in acromegaly, measured by trabecular bone score (TBS), a noninvasive index for assessing bone microarchitecture. METHODS: We collected data from 18 patients (13 female, age 56.2â ±â 15 years) newly diagnosed with acromegaly. Thirty-six age- and sex-matched healthy controls were also recruited. Pituitary function, bone and calcium-phosphorous metabolism, and BMD at spine and femur and TBS (by dual-energy x-ray absorptiometry) were assessed in acromegalic patients at diagnosis and 12 months after the achievement of insulin-like growth factor 1 (IGF-1) normalization. RESULTS: At diagnosis, BMD and the VFx prevalence were comparable between patients and controls (28.3â ±â 5.9 vs 27.6â ±â 3.7 and 11% vs 8.3%), whereas TBS was significantly lower in acromegalic patients (1.20â ±â 0.13 vs 1.30â ±â 0.06; Pâ <â .001) and carboxyterminal telopeptide (CTX) and osteocalcin were significantly higher compared to controls (707â ±â 365.7 vs 371â ±â 104.1 pg/mL; Pâ =â .001 and 31.6â ±â 15.4 vs 17.0â ±â 5.7 ng/mL; Pâ =â .001, respectively). One year after IGF-1 normalization, a significant reduction of bone turnover indexes was observed in the group of acromegalic patients surgically cured (osteocalcin decrease of 61.2%, CTX decrease of 60.3%) compared to the ones controlled by medical therapy (osteocalcin decrease of 39%, CTX decrease of 40.7%; Pâ =â .01 and Pâ =â .001, respectively). Despite these findings, no TBS or BMD variations were observed. CONCLUSION: Acromegalic patients have impaired bone quality despite normal density. Achieving normal growth hormone secretion rapidly leads to the normalization of bone turnover.