Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 698
Filtrar
1.
Anticancer Res ; 41(5): 2669-2680, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952498

RESUMO

BACKGROUND/AIM: The histopathological variability of each type of pituitary adenoma (PA) that causes growth hormone (GH) excess influences the phenotype, radiological characteristics and therapy response of acromegaly patients. We correlated the immunohistochemical (IHC) features of GH-secreting PAs with their clinical, laboratory and imaging data. PATIENTS AND METHODS: We included 32 patients with documented acromegaly; tumour specimens were histologically and IHC examined: anterior pituitary hormones, pituitary-specific transcription factor-1 (PIT-1), Ki-67 labelling index were evaluated. RESULTS: Macroadenomas represented 93.75%. Post-surgery disease control negatively correlated with the maximum initial tumour diameter (p=0.04). Ki-67 did not predict remission. No correlation was found between GH serum levels and IHC expression (p=0.45). PIT-1 was positive in all specimens, two had a weak expression. Four were considered PIT-1 positive plurihormonal adenomas and several had unusual IHC combinations. CONCLUSION: PIT-1 accurately classifies GH-secreting PAs. The IHC classification as well as radiological dimensions and extent influence disease control, probably being the best prognosis factors.


Assuntos
Acromegalia/sangue , Hormônio do Crescimento/sangue , Neoplasias Hormônio-Dependentes/sangue , Neoplasias Hipofisárias/sangue , Acromegalia/complicações , Acromegalia/genética , Acromegalia/patologia , Adulto , Idoso , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Antígeno Ki-67/sangue , Masculino , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/genética , Neoplasias Hormônio-Dependentes/patologia , Hormônios Adeno-Hipofisários/sangue , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Período Pré-Operatório , Fator de Transcrição Pit-1/sangue
2.
J Clin Endocrinol Metab ; 106(9): 2690-2706, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-33871626

RESUMO

CONTEXT: Acromegaly can impair bone integrity, increasing the risk of vertebral fractures (VFs). OBJECTIVE: To evaluate the impact of isolated GH/IGF-I hypersecretion on bone turnover markers, Wnt inhibitors, bone mineral density (BMD), microarchitecture, bone strength and vertebral fractures in female patients with acromegaly (Acro), compared with healthy control group (HC). DESIGN, SETTING, AND PATIENTS: Cross-sectional study including 83 premenopausal women without any pituitary deficiency:18 acromegaly in remission (AcroR), 12 in group with active acromegaly (AcroA), and 53 HC. Serum procollagen type 1 N-terminal propeptide, ß-carboxy-terminal crosslinked telopeptide of type 1 collagen, osteocalcin, sclerostin, and DKK1 were measured in blood samples. dual-energy X-ray absorptiometry, high-resolution peripheral quantitative computed tomography (HR-pQCT) and vertebral fractures evaluation were also assessed simultaneously. MAIN OUTCOME AND RESULTS: AcroA showed significantly lower sclerostin and higher DKK1 compared with HC. On HR-pQCT of tibia and radius, Acro showed impairment of trabecular (area and trabecular number), increased cortical porosity, and increased cortical area and cortical thickness compared with HC. The only significant correlation found with HR-pQCT parameters was a positive correlation between cortical porosity and serum DKK1 (R = 0.45, P = 0.044). Mild VFs were present in approximately 30% of patients. CONCLUSIONS: Eugonadal women with acromegaly without any pituitary deficiency showed increased cortical BMD, impairment of trabecular bone microstructure, and increased VF. Sclerostin was not correlated with any HR-pQCT parameters; however, DKK1 was correlated with cortical porosity in tibia (P = 0.027). Additional studies are needed to clarify the role of Wnt inhibitors on bone microarchitecture impairment in acromegaly.


Assuntos
Acromegalia/patologia , Osso e Ossos/ultraestrutura , Via de Sinalização Wnt/fisiologia , Adulto , Densidade Óssea , Osso e Ossos/metabolismo , Estudos Transversais , Feminino , Análise de Elementos Finitos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Pessoa de Meia-Idade , Pré-Menopausa , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/etiologia
3.
BMC Endocr Disord ; 21(1): 50, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33736633

RESUMO

BACKGROUND: Pituitary adenomas are benign brain tumors that cause considerable morbidity and neurological symptoms. SOX9 as a regulatory transcriptional mediator affects normal and tumor cell growth with an undefined role in pituitary adenomas pathogenesis. Thus, in the present study, the expression pattern of SOX9 in GH-secreting pituitary tumors and normal pituitary tissues is investigated. METHODS: The SOX9 gene expression level was evaluated in 60 pituitary tissues including different types of GH-secreting adenomas and normal pituitary tissues through Real-Time PCR. The protein level of SOX9 was assessed using immunohistochemistry. The correlations of SOX9 gene and protein expression level with the patient's clinical and pathological features were considered. RESULTS: The SOX9 over-expression was detected in GH-secreting adenomas tumor tissues compared to normal pituitary tissues which were accompanied by overexpression of SOX9 protein in tumor tissues. The over-expression of SOX9 had a significant impact on GH-secreting adenomas tumor incidence with the odds ratio of 8.4 and the diagnostic value of SOX9 was considerable. The higher level of SOX9 expression was associated with invasive and macro tumors in GH-secreting pituitary adenoma patients. The positive correlation of SOX9 gene and protein level was observed and the tumor size and tumor invasive features were valuable in predicting SOX9 expression level in GH-producing pituitary tumors. CONCLUSION: The study provided the first shreds of evidence regarding the expression pattern of SOX9 in the GH- secreting pituitary adenomas at both gene and protein levels which may emphasize the possible involvement of SOX9 as a mediator in pituitary adenoma tumor formation also open up new intrinsic molecular mechanism regarding pituitary adenoma pathogenesis.


Assuntos
Adenoma/genética , Adenoma Hipofisário Secretor de Hormônio do Crescimento/genética , Fatores de Transcrição SOX9/genética , Acromegalia/genética , Acromegalia/metabolismo , Acromegalia/patologia , Adenoma/metabolismo , Adenoma/patologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição SOX9/metabolismo , Regulação para Cima/genética
4.
J Neurooncol ; 151(2): 313-324, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33394265

RESUMO

PURPOSE: Acromegaly is a rare neuroendocrine condition that can lead to significant morbidity. Despite China's vast population size, studies on acromegaly remain sparse. This study aimed to investigate the clinical characteristics and predictors of biochemical remission after surgery for acromegaly using the China Acromegaly Patient Association (CAPA) database. METHODS: A retrospective nationwide study was conducted using patient-reported data from CAPA database between 1998 and 2018. The principal component analysis (PCA) and logistic regression analysis were employed to determine independent predictors of biochemical remission at 3 months in patients after surgery. RESULTS: Of the 546 surgical cases (mean age: 36.8 years; 59.5% females), macroadenomas and invasive tumors (Knosp score 3-4) were 83.9% and 64.1%, respectively. Ninety-five percent of patients were treated with endonasal surgery and 36.8% exhibited biochemical remission at 3-months postoperatively. The following independent predictors of biochemical remission were identified: preoperative growth hormone (GH) levels between 12 and 28 µg/L [odds ratio (OR) = 0.58; 95% confidence interval (CI), 0.37-0.92; p = 0.021], preoperative GH levels > 28 µg/L (OR = 0.55; 95% CI, 0.34-0.88; p = 0.013), macroadenoma (OR = 0.56; 95% CI, 0.32-0.96; p = 0.034), giant adenomas (OR = 0.14; 95% CI, 0.05-0.38; p < 0.001), Knosp score 3-4 (OR = 0.37; 95% CI, 0.24-0.57; p < 0.001), and preoperative medication usage (OR = 2.32; 95% CI, 1.46-3.70; p < 0.001). CONCLUSIONS: In this nationwide study spanning over two decades, we highlight that higher preoperative GH levels, large tumor size, and greater extent of tumor invasiveness are associated with a lower likelihood of biochemical remission at 3-months after surgery, while preoperative medical therapy increases the chance of remission.


Assuntos
Acromegalia/cirurgia , Procedimentos Neurocirúrgicos/métodos , Acromegalia/patologia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Período Pós-Operatório , Prognóstico , Indução de Remissão , Estudos Retrospectivos
5.
Eur J Endocrinol ; 184(2): 231-241, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33112282

RESUMO

Background: Facial abnormality is the most significant feature in acromegaly patients. However, it is unclear whether and how patient facial appearance improves after treatment. This study aimed to identify 3D facial changes in acromegaly patients after surgical treatment. Methods: This study included 30 acromegaly patients who underwent resection of a pituitary GH adenoma. The location and extent of facial changes were identified by comparing baseline and 2-year follow-up 3D images of the face. Relationships between facial changes and GH and IGF-1 were evaluated with simple or multivariable linear regression models. Results: Significant soft tissue improvements were observed in acromegaly patients with complete remission, especially in the nose and lip region. Significant reductions in nasal width (3.46 mm, P < 0.001), tip protrusion (1.18 mm, P = 0.003), face curve length (3.89 mm, P = 0.004) and vermilion area (1.42 cm3, P = 0.001) were observed at the 2-year follow-up. Further, changes in nasal width were associated with decreases in GH (ß = 4.440, P = 0.017), the GH nadir (ß = 4.393, P = 0.011) and IGF-1 (ß = 5.263, P = 0.002). The associations were maintained after adjusting for confounders. Conclusions: Acromegaly patients achieved considerable facial improvements after surgical treatment. The change in nose width was associated with GH and IGF-1 decrease. Better control of patient hormone levels after surgery improves patient facial recovery.


Assuntos
Acromegalia/diagnóstico , Acromegalia/cirurgia , Face/patologia , Acromegalia/sangue , Acromegalia/patologia , Adenoma/sangue , Adenoma/diagnóstico , Adenoma/patologia , Adenoma/cirurgia , Adolescente , Adulto , Idoso , China , Estudos de Coortes , Feminino , Seguimentos , Hormônio do Crescimento Humano/análise , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Nariz/patologia , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Prognóstico , Indução de Remissão , Resultado do Tratamento , Adulto Jovem
6.
Eur J Endocrinol ; 184(2): 217-229, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33136550

RESUMO

Background: The treatment of acromegaly resistant to first-generation somatostatin receptor ligands (SRLs) is often difficult. Pegvisomant and Pasireotide LAR are mostly used in these subset of patients, as second line therapies. Choice of the type of second line therapies is difficult, since predictors of response are still unclear, impairing personalized therapy. We aimed to investigate predictors of response to Pegvisomant and Pasireotide LAR. Methods: Seventy-four acromegaly patients entered this observational, cross-sectional and retrospective study if (i) resistant to high dose first-generation SRLs and (ii) treated with Pegvisomant and Pasireotide LAR for at least 12 consecutive months. Patients treated with radiotherapy in the previous 10 years were excluded. Results: Fourty-one patients were treated with Pegvisomant and 33 with Pasireotide LAR. At the end of the study, acromegaly was controlled in 35 patients treated with Pegvisomant (85.4%) and in 23 treated with Pasireotide LAR (69.7%). In this cohort, a poor Pegvisomant response and a shorter progression free time were observed in cases with tumor extension to the third ventricle (P = 0.004, HR: 1.6, 95%CI: 1.2-4.6), with a Ki67-Li >4% (P = 0.004, HR: 3.49, 95%CI: 1.4-4.0) and with pre-treatment IGF-I >3.3×ULN (P=0.03, HR: 1.3, 95%CI: 1.1-6.0). A poor Pasireotide LAR response and a shorter progression free time were observed in cases with tumor extension to the third ventricle (P=0.025, HR: 1.6 95%CI: 1.4-3.4), pre-treatment IGF-I >2.3×ULN (P=0.049, HR: 2.4, 95%CI: 1.4-8.0), absent/low SST5 membranous expression (P=0.023 HR: 4.56 95%CI: 1.3-6.4) and in patients carried the d3-delated GHR isoform (P=0.005, HR: 11.37, 95%CI: 1.3-20.0). Conclusion: Molecular and clinical biomarkers can be useful in predicting the responsiveness to Pegvisomant and Pasireotide LAR.


Assuntos
Acromegalia/tratamento farmacológico , Hormônio do Crescimento Humano/análogos & derivados , Somatostatina/análogos & derivados , Acromegalia/metabolismo , Acromegalia/patologia , Adenoma/tratamento farmacológico , Adenoma/metabolismo , Adenoma/patologia , Adolescente , Adulto , Idoso , Quimioterapia Adjuvante , Estudos Transversais , Preparações de Ação Retardada , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Hormônio do Crescimento Humano/administração & dosagem , Humanos , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Somatostatina/administração & dosagem , Resultado do Tratamento , Adulto Jovem
7.
J Endocrinol Invest ; 44(3): 531-539, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32594452

RESUMO

PURPOSE: The aim of this study was to evaluate the somatotroph axis in a large series of patients with prolactinoma to verify the prevalence of silent acromegaly in this population. METHODS: A hundred and forty-four patients were enrolled in a multicenter study: 90 were already on cabergoline (CAB) and enrolled in a cross-sectional arm (group A) with random PRL, GH and IGF-I determination on treatment (≥ 3 months), whereas 54 untreated patients were enrolled at diagnosis in a prospective arm (group B) with PRL, GH and IGF-I measurement before and after 6 and 12 months of treatment. In the presence of high IGF-I, CAB was withdrawn for 3 months and GH, IGF-I, PRL and GH during an oral Glucose Tolerance Test (OGTT) were obtained. RESULTS: High IGF-I levels (ULN 1.01-1.56) were observed in 9 patients (6.25%, 5F). After CAB withdrawal, IGF-I levels normalized in 5/9 patients, GH was < 0.4 ng/ml after OGTT in 7/9 cases or at random GH determination in one case. After CAB re-introduction, IGF-I levels re-increased in a single case. Overall, a single young female patient harboring a macroadenoma in group A was diagnosed with silent acromegaly and underwent successful transsphenoidal removal of a GH/PRL-secreting adenoma. CONCLUSION: The prevalence of silent acromegaly in prolactinomas (0.7%) is lower than previously reported and OGTT is helpful to recognize silent acromegaly. We suggest that the somatotroph axis should be evaluated at diagnosis in all cases and not systematically during follow-up.


Assuntos
Acromegalia/epidemiologia , Prolactinoma/fisiopatologia , Acromegalia/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos Transversais , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Prospectivos , Adulto Jovem
8.
Front Endocrinol (Lausanne) ; 11: 577173, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33329385

RESUMO

Context: Hypertension is a major cardiovascular risk factor related to increased mortality in acromegaly. Surgical cure of acromegaly is associated with improvement in blood pressure levels, however little is known about the effect of pegvisomant (PEGV) treatment in patients with hypertension. This analysis evaluates outcomes in patients with hypertension and acromegaly included in ACROSTUDY. Methods: ACROSTUDY is a global non-interventional surveillance study of long-term treatment with PEGV, monitoring its safety and efficacy. The cohort was retrospectively divided in two subgroups: patients with and without hypertension. Stepwise logistic regression and Kaplan-Meyer analyses were performed for testing predictors of mortality. Results: The total cohort included 2,090 patients with acromegaly treated with PEGV who were followed for a median of 6.8 years (range up to 12.1 years). In ACROSTUDY there were 1,344 patients with hypertension (52.3% males). This subgroup was older, had a higher BMI, and higher prevalence of diabetes, hyperlipidemia, and cardiovascular disease (CVD) when compared to patients without hypertension. During ACROSTUDY, 68 deaths were reported in the hypertension cohort, vs 10 in the cohort without hypertension. Both CVD (p<0.0001) and anterior pituitary deficiencies (p=0.0105) at study entry independently predicted mortality in patients with acromegaly and hypertension; Kaplan-Meier analysis confirmed that CVD significantly impairs survival. Conclusions: Hypertension is common in patients with acromegaly and significantly increases mortality, especially when there is concomitant CVD. These data suggest that treatment goals should extend beyond IGF-I normalization, and include optimisation of substitution of pituitary deficiencies and scrutinous screening and treatment of CVD.


Assuntos
Acromegalia/complicações , Doenças Cardiovasculares/mortalidade , Hipertensão/mortalidade , Acromegalia/tratamento farmacológico , Acromegalia/patologia , Adulto , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/patologia , Estudos de Casos e Controles , Feminino , Seguimentos , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/análogos & derivados , Humanos , Hipertensão/etiologia , Hipertensão/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
9.
Growth Horm IGF Res ; 55: 101335, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33190108

RESUMO

Gamma knife radiosurgery (GKS) is a treatment option for recurrent or persistent disease in patients with acromegaly. OBJECTIVE: We aimed to retrospectively evaluate acromegaly patients who had undergone GKS in terms of pituitary hormone status, efficacy of GKS, and prognostic factors. METHOD: One-hundred and ten acromegaly patients who underwent GKS, and who were referred to our outpatient endocrinology clinic between 2007 and 2017, were included in the study. Anterior pituitary hormones and radiology imaging during follow-up were recorded. Remission for acromegaly was defined as a normal insulin-like growth factor 1 (IGF-1) level adjusted for age and gender, and a random growth hormone (GH) level < 1 ng/ml. Endocrine control was defined as normal GH and IGF-1 levels under medication. RESULTS: After a mean follow-up of 6.5 ±â€¯4.7 years; remission, endocrine control, and uncontrolled status was observed in 16.4%, 60%, and 23.6% of patients; respectively. Adenoma volume was decreased after GKS (P < .0001). Remnant adenoma diameter was higher in the uncontrolled group compared to the remission and endocrine control group. The presence of tumor extension was associated with disease status (P = .03) and higher initial GH and IGF-1 levels. The mean time after GKS to remission was 26.5 months. Six (5.4%) patients had new-onset pituitary deficiency after GKS. In the multivariate analysis, pre-GKS IGF-1 levels and patient's age were associated with disease status. CONCLUSION: GKS is an effective adjuvant treatment with minimal side effects to control GH and IGF-1 levels, increase remission rates, endocrine control, and reduce tumor diameter in persistent acromegaly patients after surgery.


Assuntos
Acromegalia/cirurgia , Biomarcadores/sangue , Hormônio do Crescimento Humano/sangue , Fator de Crescimento Insulin-Like I/análise , Acromegalia/sangue , Acromegalia/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Radiocirurgia , Estudos Retrospectivos
10.
Growth Horm IGF Res ; 55: 101356, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33010581

RESUMO

OBJECTIVE: To evaluate the prevalence of impulse control disorders (ICD) and psychiatric symptoms in patients with acromegaly receiving dopamine agonists (DA) in comparison with those with prolactinoma, nonfunctioning pituitary adenomas (NFA), and healthy controls (HC). DESIGN: Forty patients with acromegaly, 40 with prolactinoma, 38 with NFA, and 32 HCs were included. All patients and controls were evaluated using the revised version of the Minnesota Impulsive Disorders Interview (MIDI-R), Symptom Check List (SCL-90-R) questionnaire, Barratt Impulsiveness Scale (BIS-11), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). RESULTS: We detected ICD associated with DAs in two patients with acromegaly (5%) and three patients (7.5%) with prolactinoma. All patients' symptoms resolved after discontinuation of the drug. While the mean DA dose was higher in patients with acromegaly than prolactinomas (p < 0.05), no difference was detected in terms of ICD prevalence between two groups (p > 0.05). SCL-90 depression and interpersonal sensitivity subscale positivity was higher in patients with NFA than HCs. Patients with prolactinoma had higher obsession and interpersonal sensitivity positivity and those with NFA had higher somatization, interpersonal sensitivity, and depression positivity as compared to patients with acromegaly (p < 0.05 for all). CONCLUSIONS: Although DA dose was significantly higher in patients with acromegaly, there was no significant difference in the prevalence of DA-related ICD. The higher prevalence of positive screening in SCL-90 in patients with NFA in comparison to HCs supports the hypothesis that the presence of a pituitary adenoma per se might cause significant psychiatric symptoms.


Assuntos
Acromegalia/tratamento farmacológico , Adenoma/epidemiologia , Biomarcadores/sangue , Transtornos Disruptivos, de Controle do Impulso e da Conduta/epidemiologia , Agonistas de Dopamina/efeitos adversos , Neoplasias Hipofisárias/epidemiologia , Prolactinoma/epidemiologia , Acromegalia/patologia , Adenoma/sangue , Adenoma/induzido quimicamente , Adenoma/patologia , Adulto , Estudos de Casos e Controles , Estudos Transversais , Transtornos Disruptivos, de Controle do Impulso e da Conduta/sangue , Transtornos Disruptivos, de Controle do Impulso e da Conduta/induzido quimicamente , Transtornos Disruptivos, de Controle do Impulso e da Conduta/patologia , Feminino , Seguimentos , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/induzido quimicamente , Neoplasias Hipofisárias/patologia , Prevalência , Prognóstico , Prolactinoma/sangue , Prolactinoma/induzido quimicamente , Prolactinoma/patologia , Estudos Prospectivos , Turquia/epidemiologia
11.
Growth Horm IGF Res ; 55: 101354, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33011455

RESUMO

OBJECTIVE: To investigate the effectiveness and predictors of short-term somatostatin analog (SSA) presurgical therapy in a large cohort and to assess the correlation between clinical and pathological variables. DESIGN: 237 newly diagnosed patients with acromegaly received presurgical SSA treatment for three months were recruited. Clinical characteristics were collected, and response to SSA in hormone and tumor size was evaluated. The correlation between clinical information and pathological variables were analyzed. RESULTS: After 3 months presurgical SSA therapy, 51 (21.5%) patients were biochemically responsive with ≥50% decrease in IGF-1 while 126 (53.2%) patients showed at least 20% tumor size decrease. Biochemical responders were associated with a smaller maximum tumor diameter (MTD) and an older age (OR, 0.448; P = 0.003; OR, 1.050; P = 0.001). Tumor size responders were associated with a smaller MTD (OR, 0.435; P < 0.001). A combination of MTD < 2 cm and age ≥49 years predicted biochemical responders (PPV, 54.5%; NPV, 86.0%; P < 0.001), while MTD ≤2.2 cm (PPV, 67.1%; NPV, 67.0%; P < 0.001) predicted tumor size responders. Compared to patients with MTD < 2 cm, patients with MTD ≥ 2 cm showed higher percentage of sparsely granulated (SG) adenoma (62.1% vs. 31.3%, P = 0.005). In addition, the percentage of SG adenoma tended to be higher in patients < 49 years than ≥49 years (48.1% and 31.0% P = 0.089). CONCLUSIONS: The baseline MTD and age correlate with granulation patterns and may be used as easily acquired predictors of presurgical SSA treatment in acromegaly. Patients over their 50s with a tumor less than 2 cm in diameter are more likely to have a response to the short-term presurgical SSA therapy.


Assuntos
Acromegalia/tratamento farmacológico , Biomarcadores/sangue , Cuidados Pré-Operatórios , Somatostatina/administração & dosagem , Acromegalia/patologia , Adulto , Feminino , Seguimentos , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Somatostatina/análogos & derivados
12.
Growth Horm IGF Res ; 55: 101342, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32916586

RESUMO

AIM: The aim of this study was to clarify the prognostic values of various preoperative factors, including the surgeon's ability as well as the patient's age, gender, tumor size, cavernous sinus invasion, compression of the optic chiasm, hypopituitarism, immunohistochemical (IHC) staining pattern of the adenoma, and insulin-like growth factor-1 (IGF-1) level, in acromegalic patients who had undergone pituitary surgery. STUDY DESIGN: This single-center, retrospective study assessed the medical records of 108 patients who had undergone pituitary surgery with the same neurosurgical team. RESULTS: The mean total follow-up period after surgery was 44.8 (min: 24, max: 59) months. Remission was reported in 67 (62.0%) patients, and 57 (52.8%) patients did not experience recurrence. Initial tumor volume, IGF-1 level, and optic chiasm compression, but not patients' age, gender, cavernous sinus invasion, and IHC staining patterns of the adenoma, were prognostic of either remission or recurrence. An IGF-1 level of 860 ng/mLwas found to be a convenient cut-off point for determining remission. CONCLUSIONS: The experience of the surgical team suggests that the initial tumor volume, IGF-1 level, and optic chiasm compression have high prognostic values in relation to pituitary surgery for patients with acromegaly.


Assuntos
Acromegalia/patologia , Adenoma/fisiopatologia , Biomarcadores/sangue , Hormônio do Crescimento Humano/sangue , Fator de Crescimento Insulin-Like I/análise , Procedimentos Neurocirúrgicos/métodos , Neoplasias Hipofisárias/fisiopatologia , Acromegalia/sangue , Acromegalia/cirurgia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
13.
Nat Commun ; 11(1): 4752, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958754

RESUMO

Growth hormone (GH) is a key modulator of growth and GH over-secretion can lead to gigantism. One form is X-linked acrogigantism (X-LAG), in which infants develop GH-secreting pituitary tumors over-expressing the orphan G-protein coupled receptor, GPR101. The role of GPR101 in GH secretion remains obscure. We studied GPR101 signaling pathways and their effects in HEK293 and rat pituitary GH3 cell lines, human tumors and in transgenic mice with elevated somatotrope Gpr101 expression driven by the rat Ghrhr promoter (GhrhrGpr101). Here, we report that Gpr101 causes elevated GH/prolactin secretion in transgenic GhrhrGpr101 mice but without hyperplasia/tumorigenesis. We show that GPR101 constitutively activates not only Gs, but also Gq/11 and G12/13, which leads to GH secretion but not proliferation. These signatures of GPR101 signaling, notably PKC activation, are also present in human pituitary tumors with high GPR101 expression. These results underline a role for GPR101 in the regulation of somatotrope axis function.


Assuntos
Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Gigantismo/metabolismo , Hormônio do Crescimento/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Acromegalia/metabolismo , Acromegalia/patologia , Animais , Composição Corporal , Linhagem Celular , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Gigantismo/patologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/genética , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação , Hipófise/metabolismo , Proteína Quinase C/metabolismo , Ratos , Receptores Acoplados a Proteínas G/genética
14.
Artigo em Inglês | MEDLINE | ID: mdl-32733381

RESUMO

Background: Studies investigating the change in distance between the bilateral internal carotid arteries (ICAs) in acromegalic patients have provided ambiguous results. The influencing factors of these changes have not been well-identified. Objective: To further investigate the change in distance between bilateral ICAs in acromegaly patients and identify the influencing factors of the change. Method: Patients diagnosed as acromegaly from Jan 2016 to Sep 2019 in the Department of Neurosurgery of the First Affiliated Hospital of Fujian Medical University, were included in this study. Computed tomography angiography (CTA) or magnetic resonance angiography (MRA) data were obtained for all patients for three-dimensional reconstruction of the ICAs. Distance between bilateral ICAs was measured and recorded for assessment. Result: 172 patients including 86 cases with acromegaly in the study group and 86 cases with non-functional pituitary adenoma in the control group were enrolled in this study. The difference of adenoma sizes between two groups was not statistically significant. Patients in acromegaly group had significantly larger maximum distances between bilateral siphon carotid ectasias (25.5 ± 4.1 vs. 23.4 ± 3.5 mm, P = 0.001) and between bilateral lacerum segments (26.2 ± 3.2 vs. 24.1 ± 4.3 mm, P < 0.001) compared with those of patients with non-functional pituitary adenomas. Multivariate analysis showed that the increased bilateral ICAs distance was associated with disease duration (odds ratio = 1.01, 95% confidence interval = 1.01-1.02, P = 0.005) and refractory pituitary adenoma (odds ratio = 9.8, 95% confidence interval = 1.1-88.7, P = 0.043) but not with level of growth hormone (GH), insulin-like growth factor-1 (IGF-1) and adenoma size in acromegaly. Conclusion: Our study showed significant change in distance between the bilateral ICAs in acromegalic patients, comparing to patients with non-functional pituitary adenomas. The increased intercarotid artery distance is associated with disease duration but not with preoperative level of GH and IGF-1. Refractory pituitary adenoma and longer disease duration are the both risk factors of the increased ICAs distance in patient with acromegly.


Assuntos
Acromegalia/patologia , Adenoma/complicações , Artéria Carótida Interna/patologia , Neoplasias Hipofisárias/complicações , Acromegalia/diagnóstico por imagem , Acromegalia/etiologia , Adenoma/diagnóstico por imagem , Adulto , Artéria Carótida Interna/diagnóstico por imagem , Feminino , Hormônio do Crescimento Humano/metabolismo , Humanos , Masculino , Procedimentos Neurocirúrgicos , Neoplasias Hipofisárias/diagnóstico por imagem , Prognóstico , Fatores de Risco , Tomografia Computadorizada por Raios X
15.
Ann Endocrinol (Paris) ; 81(5): 482-486, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32822652

RESUMO

BACKGROUND: In acromegaly, chronic growth hormone (GH) and insulin-like growth factor-1 (IGF-1) exacerbate comorbidities in multiple organs. Differentiated thyroid carcinoma (DTC) has been reported as being a comorbid condition in acromegaly. Acromegaly is usuallysporadic, but 5% of cases may be genetic. The most frequent inheritable form of acromegaly is related to germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. Epidemiological data on the relationship between active acromegaly, its familial forms and DTC are sparse. We present the investigation of a FIPA family (familial isolated pituitary adenoma) with homogeneous acromegaly and 6 sporadic acromegaly patients with DTC. PATIENTS AND METHODS: A study of 59 acromegaly patients assessed thyroid nodules on ultrasound and fine-needle aspiration biopsy following the ATA 2015 criteria. We diagnosed 7 differentiated thyroid carcinomas. Resected thyroid carcinoma tissues were stained using an anti-AIP antibody. Analysis of germline and tumor-derived DNA for variants in the AIP and MEN1 genes were performed in the FIPA kindred. RESULTS: We describe one FIPA patient and 6 sporadic acromegaly cases with DTC. The FIPA family (AIP mutation negative) consisted of two sisters, one of whom had a DTC with intermediate risk and incomplete structural response to therapy. In our study, DTC in sporadic acromegaly had a low recurrence rate (6/6), and excellent response to therapy (6/6). Immunohistochemistry for AIP showed similar or increased staining intensity in DTC versus normal thyroid tissue. CONCLUSION: In our cohort of sporadic and familial forms of acromegaly with DTC, AIP did not appear to influence thyroid cancer progression.


Assuntos
Acromegalia/epidemiologia , Adenocarcinoma/epidemiologia , Adenoma/epidemiologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia , Acromegalia/diagnóstico por imagem , Acromegalia/etiologia , Acromegalia/patologia , Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adenoma/complicações , Adenoma/diagnóstico por imagem , Adenoma/patologia , Adulto , Idoso , Argentina/epidemiologia , Biópsia por Agulha Fina , Estudos de Coortes , Comorbidade , Progressão da Doença , Feminino , Mutação em Linhagem Germinativa , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico por imagem , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Ultrassonografia
16.
Hum Mol Genet ; 29(17): 2951-2961, 2020 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-32821937

RESUMO

Mutations of the regulatory subunit (PRKAR1A) of the cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA), leading to activation of the PKA pathway, are the genetic cause of Carney complex which is frequently accompanied by somatotroph tumors. Aryl hydrocarbon receptor-interacting protein (AIP) mutations lead to somatotroph tumorigenesis in mice and humans. The mechanisms of AIP-dependent pituitary tumorigenesis are still under investigation and evidence points to a connection between the AIP and PKA pathways. In this study, we explore the combined effects of Aip and Prkar1a deficiency on mouse phenotype and, specifically, pituitary histopathology. Aip+/- mice were compared with double heterozygous Aip+/-, Prkar1a+/- mice. The phenotype (including histopathology and serological studies) was recorded at 3, 6, 9 and 12 months of age. Detailed pituitary histological and immunohistochemical studies were performed at 12 months. Twelve-month old Aip+/- mice demonstrated phenotypic and biochemical evidence of GH excess including significantly elevated insulin-like growth factor 1 levels, larger weight and body length, higher hemoglobin and cholesterol levels and a higher frequency of growth plate thickening in comparison to Aip+/, Prkar1a+/- mice. Pituitary histopathology did not uncover any pituitary adenomas or somatotroph hyperplasia in either group. These results demonstrate a slow progression from elevated GH release to the formation of overt somatotropinomas in Aip+/- mice; the acromegalic phenotype of these mice is surprisingly ameliorated in Aip+/-, Prkar1a+/- mice. This highlights the complexities of interaction between the AIP and PKA pathway. Specifically targeting GH secretion rather than somatotroph proliferation may be an advantage in the medical treatment of AIP-dependent human acromegaly.


Assuntos
Acromegalia/genética , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/genética , Adenoma Hipofisário Secretor de Hormônio do Crescimento/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Acromegalia/patologia , Animais , AMP Cíclico/genética , AMP Cíclico/metabolismo , Modelos Animais de Doenças , Hormônio do Crescimento/genética , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Haploinsuficiência/genética , Humanos , Camundongos , Fenótipo
17.
Pituitary ; 23(5): 582-594, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32602066

RESUMO

PURPOSE: Biochemical control is the main determinant of survival, clinical manifestations and comorbidities in acromegaly. Transsphenoidal selective adenomectomy (TSA) is the initial treatment of choice with reported biochemical remission rates varying between 32 and 85%. Understanding the limiting factors is essential for identification of patients who require medical treatment. METHODS: We reviewed the English literature published in Medline/Pubmed until Dec 31, 2019 to identify eligible studies that described outcomes of TSA as primary therapy and performed analyses to determine the main predictors of remission. RESULTS: Most publications reported single-institution, retrospective studies. The following preoperative parameters were consistently associated with lower remission rates: cavernous sinus invasion by imaging, larger tumor size and higher GH levels. Young age and preoperative IGF-1 levels were predictive in some studies. When controlled for covariates, the best single preoperative predictor was cavernous sinus invasion, followed by preoperative GH levels. Conversely, low GH level in the first few days postoperatively was a robust predictor of durable remission. The influence of tumor histology (sparsely granular pattern, co-expression of prolactin and proliferation markers) on surgical remission remains to be established. Few studies developed predictive models that yielded much higher predictive values than individual parameters. CONCLUSION: Surgical outcome prognostication systems could be further generated by machine learning algorithms in order to support development and implementation of personalized care in patients with acromegaly.


Assuntos
Acromegalia/patologia , Acromegalia/cirurgia , Procedimentos Neurocirúrgicos/métodos , Acromegalia/sangue , Biomarcadores Tumorais/sangue , Hormônio do Crescimento Humano/sangue , Humanos , Prognóstico , Resultado do Tratamento
18.
Endocrinol Metab (Seoul) ; 35(2): 206-216, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32615705

RESUMO

Acromegaly presents with an enigmatic range of symptoms and comorbidities caused by chronic and progressive growth hormone elevations, commonly due to endocrinologic hypersecretion from a pituitary gland tumor. Comprehensive national acromegaly databases have been appearing over the years, allowing for international comparisons of data, although still presenting varying prevalence and incidence rates. Lack of large-scale analysis in geographical and ethnic differences in clinical presentation and management requires further research. Assessment of current and novel predictors of responsiveness to distinct therapy can lead to multilevel categorization of patients, allowing integration into new clinical guidelines and reduction of increased morbidity and mortality associated with acromegaly. This review compares current data from epidemiological studies and assesses the present-day application of prognostic factors in medical practice, the reality of precision therapy, as well as its future prospects in acromegaly, with a special focus on its relevance to the South Korean population.


Assuntos
Acromegalia/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Neoplasias Hipofisárias/complicações , Medicina de Precisão , Acromegalia/etiologia , Acromegalia/patologia , Humanos
19.
J Neurooncol ; 148(3): 401-418, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32506372

RESUMO

INTRODUCTION: We performed a systematic review and meta-analysis of clinical outcomes for patients with acromegaly treated with stereotactic radiosurgery (SRS). METHODS: Primary outcomes were 5- and 10-year endocrine remission (ER) and endocrine control (EC). Secondary outcomes were 10-year radiographic local control (LC), visual toxicity, and hypopituitarism rates. Weighted random effects meta-analyses using the DerSimonian and Laird methods were conducted to characterize and compare effect sizes. Mixed effects regression models were used to examine correlations between potential prognostic factors and primary and secondary outcomes. RESULTS: In total, 1533 patients across 20 published studies with acromegaly treated with SRS were included. At 5-years, estimated ER and EC rates were 43.2% (95% CI 31.7-54.6%) and 55.0% (95% CI 27.6-82.4%), respectively. At 10-years, estimated ER and EC rates were 56.9% (95% CI 47.5-66.4%) and 69.7% (95% CI 47.7-91.8%), respectively. The estimated 10-year LC rate was 92.8% (95% CI 83.0-100%). Visual toxicity and hypopituitarism following SRS were estimated to be 2.7% (95% CI 1.3-4.2%) and 26.8% (95% CI 16.9-36.7%), respectively. Every 1 Gy increase in margin prescription dose beyond 17 Gy was estimated to result in a 0.41% increased risk of visual toxicity (p = 0.03). No prognostic factors were associated with EC, ER, LC, or hypopituitarism. CONCLUSIONS: SRS was well-tolerated in the management of pituitary acromegaly resulting in gradually improving ER and EC rates over time that approached 60% and 70%. SRS-related visual loss is an uncommon treatment-related side effect, and patient-specific clinical decision making remains critical.


Assuntos
Acromegalia/cirurgia , Radiocirurgia/métodos , Acromegalia/patologia , Humanos , Agências Internacionais , Resultado do Tratamento
20.
Protein Pept Lett ; 27(12): 1260-1267, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32543356

RESUMO

Acromegaly and Growth Hormone Deficiency (GHD) are associated with skeletal fragility and with an increased prevalence of Vertebral Fractures (VFs). In the most recent years, several authors tried to investigate surrogate markers that may predict the risk of bone fragility in these endocrine disorders. The aim of this review is to evaluate the role of GH receptor polymorphisms in skeletal fragility in patients affected by GHD and acromegaly. In fact, until now, two different isoforms of the GH Receptor (GHR) were described, that differ for the presence or the absence of transcription of the exon 3 of the GHR gene. Both the isoforms produce a functioning receptor, but the exon 3-deleted isoforms (d3-GHR) has a higher sensitivity to endogenous and recombinant GH as compared to the full-length isoform (fl-GHR).


Assuntos
Acromegalia/metabolismo , Hormônio do Crescimento Humano , Receptores da Somatotropina/biossíntese , Fraturas da Coluna Vertebral/metabolismo , Coluna Vertebral/metabolismo , Transcrição Genética , Acromegalia/patologia , Éxons , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/metabolismo , Humanos , Isoformas de Proteínas/biossíntese , Fraturas da Coluna Vertebral/patologia , Coluna Vertebral/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...