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1.
Endocr Connect ; 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35560299

RESUMO

INTRODUCTION: Most studies reporting posterior pituitary tumors (PPTs) are small case series or single cases. METHODS: Patients with a histological diagnosis of PPT from January 2010 to December 2021 in a tertiary center were identified. We reported clinical symptoms, endocrine assessments, radiological and pathological features, and surgical outcomes of PPTs. RESULTS: A total of 51 patients (23 males, 51.3 ± 10.3 years old) with PPT were included in this study. Major symptoms were visual defects, headache, and hypopituitarism, while diabetes insipidus was uncommon (9.8%). The typical radiological feature was homogeneous enhancement (84.3%) of a regular-shaped mass on T1 contrast imaging without cystic change, calcification, or cavernous sinus invasion. We achieved gross total resection in 38/51 patients (74.5%). Pathologically, all tumors showed TTF-1 immunoreactivity. Among 29 patients with suprasellar PPTs, postoperative hemorrhage due to tumor residue was encountered in 2/15 cases in the transcranial group and 0/14 in the endoscopy group. Patients with spindle cell oncocytoma (SCO) were more likely to be surgically treated (25% vs. 0%, P = 0.018), harbor a higher Ki-67 index (16.7% vs. 0% > 5% P = 0.050), and present a lower 2-year recurrence-free survival rate (67.5% vs. 90.9%) compared with patients with pituicytoma or granular cell tumor. CONCLUSION: PPTs should be considered in the differential diagnosis of patients with sellar and suprasellar masses with a regular lesion with homogeneous enhancement. SCOs had high proliferation activity and risk of recurrence.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35521682

RESUMO

BACKGROUND: The pathogenesis of Cushing's disease (CD) is still not adequately understood despite the identification of somatic driver mutations in USP8, BRAF and USP48. In this multiomics study, we combined RNA sequencing (RNA-seq) with Sanger sequencing to depict transcriptional dysregulation under different gene mutation backgrounds. Furthermore, we evaluated the potential of achaete-scute complex homolog 1 (ASCL1), a pioneer transcription factor, as a novel therapeutic target for treatment of CD and its possible downstream pathway. METHODS: RNA-seq was adopted to investigate the gene expression profile of CD, and Sanger sequencing was adopted to detect gene mutations. Bioinformatics analysis was used to depict transcriptional dysregulation under different gene mutation backgrounds. The function of ASCL1 in hormone secretion, cell proliferation and apoptosis were studied in vitro. The effectiveness of a ASCL1 inhibitor was evaluated in primary CD cells, and the clinical relevance of ASCL1 was examined in 68 patients with CD. RNA-seq in AtT-20 cells upon Ascl1 knockdown combined with published ChIp-seq data and dual luciferase assays were used to explore downstream pathways. RESULTS: ASCL1 was exclusively overexpressed in USP8-mutant and wild type tumors. Ascl1 promoted adrenocorticotrophin hormone overproduction and tumorigenesis and directly regulated Pomc in AtT-20 cells. A ASCL1 inhibitor presented promising efficacy in both AtT-20 and primary CD cells. ASCL1 overexpression was associated with a larger tumor volume and higher adrenocorticotrophin secretion in patients with CD. CONCLUSION: Our findings help to clarify the pathogenesis of CD and suggest that ASCL1 is a potential therapeutic target for treatment of CD.

3.
Mol Cell ; 82(9): 1660-1677.e10, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35320754

RESUMO

Tumor-infiltrating myeloid cells (TIMs) are crucial cell populations involved in tumor immune escape, and their functions are regulated by multiple epigenetic mechanisms. The precise regulation mode of RNA N6-methyladenosine (m6A) modification in controlling TIM function is still poorly understood. Our study revealed that the increased expression of methyltransferase-like 3 (METTL3) in TIMs was correlated with the poor prognosis of colon cancer patients, and myeloid deficiency of METTL3 attenuated tumor growth in mice. METTL3 mediated m6A modification on Jak1 mRNA in TIMs, the m6A-YTHDF1 axis enhanced JAK1 protein translation efficiency and subsequent phosphorylation of STAT3. Lactate accumulated in tumor microenvironment potently induced METTL3 upregulation in TIMs via H3K18 lactylation. Interestingly, we identified two lactylation modification sites in the zinc-finger domain of METTL3, which was essential for METTL3 to capture target RNA. Our results emphasize the importance of lactylation-driven METTL3-mediated RNA m6A modification for promoting the immunosuppressive capacity of TIMs.


Assuntos
Metiltransferases , Neoplasias , Adenosina/metabolismo , Animais , Humanos , Metiltransferases/genética , Metiltransferases/metabolismo , Camundongos , Células Mieloides/metabolismo , RNA , Microambiente Tumoral
4.
J Pers Med ; 12(2)2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35207641

RESUMO

INTRODUCTION: This study aims to develop a machine learning-based model integrating clinical and ophthalmic features to predict visual outcomes after transsphenoidal resection of sellar region tumors. METHODS: Adult patients with optic chiasm compression by a sellar region tumor were examined to develop a model, and an independent retrospective cohort and a prospective cohort were used to validate our model. Predictors included demographic information, and ophthalmic and laboratory test results. We defined "recovery" as more than 5% for a p-value in mean deviation compared with the general population in the follow-up. Seven machine learning classifiers were employed, and the best-performing algorithm was selected. A decision curve analysis was used to assess the clinical usefulness of our model by estimating net benefit. We developed a nomogram based on essential features ranked by the SHAP score. RESULTS: We included 159 patients (57.2% male), and the mean age was 42.3 years old. Among them, 96 patients were craniopharyngiomas and 63 patients were pituitary adenomas. Larger tumors (3.3 cm vs. 2.8 cm in tumor height) and craniopharyngiomas (73.6%) were associated with a worse prognosis (p < 0.001). Eyes with better outcomes were those with better visual field and thicker ganglion cell layer before operation. The ensemble model yielded the highest AUC of 0.911 [95% CI, 0.885-0.938], and the corresponding accuracy was 84.3%, with 0.863 in sensitivity and 0.820 in specificity. The model yielded AUCs of 0.861 and 0.843 in the two validation cohorts. Our model provided greater net benefit than the competing extremes of intervening in all or no patients in the decision curve analysis. A model explanation using SHAP score demonstrated that visual field, ganglion cell layer, tumor height, total thyroxine, and diagnosis were the most important features in predicting visual outcome. CONCLUSION: SHAP score can be a valuable resource for healthcare professionals in identifying patients with a higher risk of persistent visual deficit. The large-scale and prospective application of the proposed model would strengthen its clinical utility and universal applicability in practice.

5.
Horm Metab Res ; 54(1): 25-32, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34986497

RESUMO

The short-term effects of long-acting somatostatin analogues (SSAs) on lipid profiles in patients with acromegaly are not well studied. We retrospectively analyzed the effects of SSAs on lipid profiles and associated cardiovascular risk factors in a cohort of 120 newly diagnosed acromegaly patients. In this study, 69 females and 51 males were included. These patients were treated with either octreotide LAR (OCT) or lanreotide SR (LAN) for 3 months. After SSAs treatment, both GH and IGF-1 significantly decreased (p<0.001). Triglyceride (TG), total to high-density lipoprotein cholesterol (HDL-C) ratio, and lipoprotein (a) [Lp(a)] levels were significantly decreased, while HDL-C levels were increased (p<0.05). The reduction of mean serum GH (GHm) was positively associated with the decrease of TG (r=0.305, p=0.001) and Lp(a) (r=0.257, p=0.005), as well as the increase of HDL-C (r=-0.355, p<0.001). The changes of lipid profiles were observed only in OCT group, but not in LAN group. In addition, systolic blood pressure (SBP) had significantly declined after SSAs treatment, with an average reduction of 4.4 mmHg (126.7±1.28 vs. 122.3±1.44 mmHg, p=0.003), while no change was observed regarding diastolic blood pressure (DBP) (p>0.05). Fasting insulin, fasting C-peptide, and HOMA-IR were significantly decreased after SSAs treatment. In conclusion, our current study revealed that short-term SSAs treatment improves lipid profiles and other cardiovascular risk factors in patients with acromegaly.


Assuntos
Acromegalia/tratamento farmacológico , Acromegalia/metabolismo , Metabolismo dos Lipídeos , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Acromegalia/sangue , Acromegalia/diagnóstico , Adulto , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Feminino , Glucose/metabolismo , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Lipídeos/sangue , Masculino , Estudos Retrospectivos , Carga Tumoral/efeitos dos fármacos
6.
J Genet Genomics ; 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35032691

RESUMO

Aging is a slow and progressive natural process that compromises the normal functions of cells, tissues, organs, and systems. The aging of the hypothalamic median eminence (ME), a structural gate linking neural and endocrine systems, may impair hormone release, energy homeostasis, and central sensing of circulating molecules, leading to systemic and reproductive aging. However, the molecular and cellular features of ME aging remain largely unknown. Here, we describe the transcriptional landscape of young and middle-aged mouse ME at single-cell resolution, revealing the common and cell type-specific transcriptional changes with age. The transcriptional changes in cell-intrinsic programs, cell-cell crosstalk, and cell-extrinsic factors highlight five molecular features of ME aging and also implicate several potentially druggable targets at cellular, signaling, and molecular levels. Importantly, our results suggest that vascular and leptomeningeal cells may lead the asynchronized aging process among diverse cell types and drive local inflammation and cellular senescence via a unique secretome. Together, our study uncovers how intrinsic and extrinsic features of each cell type in the hypothalamic ME are changed by the aging process, which will facilitate our understanding of brain aging and provide clues for efficient anti-aging intervention at the middle-aged stage.

7.
Microbiol Spectr ; 10(1): e0042521, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35019688

RESUMO

Prior study has demonstrated that gut microbiota at the genus level is significantly altered in patients with growth hormone (GH)-secreting pituitary adenoma (GHPA). Yet, no studies exist describing the state of gut microbiota at species level in GHPA. We performed a study using 16S rRNA amplicon sequencing in a cohort of patients with GH-secreting pituitary adenoma (GHPA, n = 28) and healthy controls (n = 67). Among them, 9 patients and 10 healthy controls were randomly chosen and enrolled in metagenomics shotgun sequencing, generating 280,426,512 reads after aligning to NCBI GenBank DataBase to acquire taxa information at the species level. Weighted UniFrac analysis revealed that microbial diversity was notably decreased in patients with GHPA, consistent with a previous study. With 16S rRNA sequencing, after correction for false-discovery rate (FDR), rank-sum test at the genus level revealed that the relative abundance of Oscillibacter and Enterobacter was remarkably increased in patients and Blautia and Romboutsia genera predominated in the controls, augmented by additional LEfSe (linear discriminant analysis effect size) analysis. As for further comparison at the species level with metagenomics sequencing, rank-sum test together with LEfSe analysis confirmed the enrichment of Alistipes shahii and Odoribacter splanchnicus in the patient group. Notably, LEfSe analysis with metagenomics also demonstrated that Enterobacter sp. DC1 and Enterobacter sp. 940 PEND, derived from Enterobacter, were both significantly enriched in patients. Functional analysis showed that amino acid metabolism pathway was remarkably enriched in GHPA, while carbohydrate metabolism pathway was notably enriched in controls. Further, significant positive correlations were observed between Enterobacter and baseline insulin-like growth factor 1 (IGF-1), indicating that Enterobacter may be strongly associated with GH/IGF-1 axis in GHPA. Our data extend our insight into the GHPA microbiome, which may shed further light on GHPA pathogenesis and facilitate the exploration of novel therapeutic targets based on microbiota manipulation. IMPORTANCE Dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extraintestinal diseases. Growth hormone-secreting pituitary adenoma (GHPA) is an insidious disease with persistent hypersecretion of GH and IGF-1, causing increased morbidity and mortality. Researches have reported that the GH/IGF-1 axis exerts its own influence on the intestinal microflora. Here, the results showed that compared with healthy controls, GHPA patients not only decreased the alpha diversity of the intestinal flora but also significantly changed their beta diversity. Further, metagenomics shotgun sequencing in the present study exhibited that Enterobacter sp. DC1 and Enterobacter sp. 940 PEND were enriched in patients. Also, we were pleasantly surprised to find that the Enterobacter genus was strongly positively correlated with baseline IGF-1 levels. Collectively, our work provides the first glimpse of the dysbiosis of the gut microbiota at species level, providing a better understanding of the pathophysiological process of GHPA.


Assuntos
Bactérias/isolamento & purificação , Microbioma Gastrointestinal , Adenoma Hipofisário Secretor de Hormônio do Crescimento/microbiologia , Adulto , Bactérias/classificação , Bactérias/genética , Estudos de Casos e Controles , DNA Bacteriano/genética , Disbiose/microbiologia , Fezes/microbiologia , Feminino , Hormônio do Crescimento/metabolismo , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Metagenômica , Pessoa de Meia-Idade , Filogenia , RNA Ribossômico 16S/genética
8.
Eur Radiol ; 32(3): 1570-1578, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34837512

RESUMO

OBJECTIVE: To predict silent corticotroph adenomas (SCAs) among non-functioning pituitary adenomas preoperatively using noninvasive radiomics. METHODS: A total of 302 patients including 146 patients diagnosed with SCAs and 156 patients with non-SCAs were enrolled (training set: n = 242; test set: n = 60). Tumor segmentation was manually generated using ITK-SNAP. From T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and contrast-enhanced T1WI, 2550 radiomics features were extracted using Pyradiomics. Pearson's correlation coefficient values were calculated to exclude redundant features. Several machine learning algorithms were developed to predict SCAs incorporating the radiomics and semantic features including clinical, laboratory, and radiology-associated features. The performance of models was evaluated by AUC. RESULTS: Patients in the SCA group were younger (49.5 vs 55.2 years old) and more female (85.6% vs 37.2%) than those in the non-SCA group (p < 0.001). More invasiveness (p = 0.011) and cystic and microcystic change (p < 0.001) were observed in patients with SCAs. The ensemble algorithm presented the largest AUC of 0.927 among all the algorithms trained in the test set, and the accuracy, specificity, and sensitivity of predicting SCAs were all 0.867 (at cut-off 0.5). The overall model performed better than that only using semantic features available in the clinic. Radiomics prediction was the most important feature, with gender ranking second and age ranking third. Radiomics features on T2WI were superior to those on other MR modalities in SCA prediction. CONCLUSION: Our ensemble learning model outperformed current clinical practice in differentiating patients with SCAs and non-SCAs using radiomics, which might help make appropriate treatment strategies. KEY POINTS: • Radiomics might improve the preoperative diagnosis of SCAs by MR images. • T2WI was superior to T1WI and CE-T1WI in the preoperative diagnosis of SCAs. • The ensemble machine learning model outperformed current clinical practice in SCAs diagnosis and treatment decision-making could be more individualised using the nomogram.


Assuntos
Adenoma Hipofisário Secretor de ACT , Adenoma , Neoplasias Hipofisárias , Adenoma/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Nomogramas , Neoplasias Hipofisárias/diagnóstico por imagem , Estudos Retrospectivos
9.
Clin Endocrinol (Oxf) ; 96(4): 578-588, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34323314

RESUMO

OBJECTIVE: Cushing disease is a potentially fatal endocrine disorder caused by adrenocorticotropin (ACTH)-secreting microadenomas in the pituitary gland. Accurate detection and localization of the adenomas is the key to clinical treatment. This study analysed the value of contrast-enhanced Sampling Perfection with Application-optimized Contrasts using different flip angle Evolutions (SPACE) sequence in magnetic resonance imaging (MRI) assessment of ACTH-secreting pituitary microadenomas. DESIGN AND PATIENTS: We carried out a retrospective study in which 45 patients with ACTH-secreting pituitary microadenomas were enrolled. Dynamic contrast-enhanced (DCE) coronal T1-SE sequence was performed. A contrast-enhanced coronal SPACE sequence was added immediately after DCE MRI finished. Two independent observers assessed the tumour existence and location, then the results were compared with surgical findings. RESULTS: Twenty-four lesions (53.3%) were detected by the DCE T1-SE sequence alone, while 35 lesions (80.0%) were detected with the addition of contrast-enhanced SPACE sequence. The sensitivity (58.5% vs. 85.3%; p < .05) and best diagnostic accuracy (62.0% vs. 84.4%; p < .05) were significantly better for addition with SPACE sequence than DCE-SE images alone in detection of ACTH-secreting pituitary microadenomas. For lesions <5 mm, the detected numbers were 4 (16.6%) versus 10 (27.8%) by DCE T1-SE sequence and combined DCE T1-SE with SPACE sequence. CONCLUSIONS: A combination of contrast-enhanced SPACE with DCE T1-SE sequence could improve the detection of ACTH-secreting pituitary microadenomas. Contrast-enhanced SPACE sequence could be a supplementary sequence for imaging of ACTH-secreting pituitary adenomas when T1-SE sequence provides negative or equivocal findings.


Assuntos
Adenoma , Neoplasias Hipofisárias , Adenoma/diagnóstico por imagem , Adenoma/patologia , Hormônio Adrenocorticotrópico , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias Hipofisárias/cirurgia , Estudos Retrospectivos
10.
Artigo em Inglês | MEDLINE | ID: mdl-34948680

RESUMO

Efficient risk communication is aimed at improving the supply of risk information to meet the information needs of individuals, thus reducing their vulnerability when facing the risk of emergency. There is little information available in the literature regarding information preference from an individual's need perspective, and there is a lack of differentiation in evaluation between information need and supply. Under the guidance of the crisis stage analysis theory, using multiple response analysis and weighted analysis methods, this study explores earthquake disaster information content and communication channel preferences, and develops an information deviation index (IDI) to evaluate the efficiency of risk communication before, during, and after an earthquake. A questionnaire-based survey of 918 valid respondents in Songyuan, China, which had been hit by a small earthquake swarm, was conducted to provide practical evidence for this study. The results indicated the following. Firstly, the information needs of individuals are highly differentiated in the different stages of an earthquake. From pre-disaster to post-disaster, individuals show a shift in information need from "preparedness and response knowledge" to "disaster information", then to "disaster information and disaster relief information" in parallel, to "reconstruction and reflection information". Based on the above analysis, a composition of the main earthquake disaster information is proposed for different stages. Secondly, by measuring the values of the IDI, we found that most individuals' information needs were met for the earthquake. Thirdly, the TV and the internet were the two preferred commutation channels for acquiring disaster information from among all the effective channels in all the stages.


Assuntos
Planejamento em Desastres , Desastres , Terremotos , China , Humanos , Inquéritos e Questionários
11.
FEBS J ; 2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34839588

RESUMO

ß cell number is maintained mainly by cell proliferation and cell apoptosis. Protein kinase A (PKA) pathway is an important intracellular signalling-mediating ß cell proliferation. However, the precise roles of PKA isoforms are not well-defined. We found that the RIIB subunit of PKA is expressed specifically by ß cells of mouse and human islets. Sixty percent pancreatectomy caused increased ß cell proliferation. Deletion of type IIB PKA by disruption of RIIB expression further promoted ß cell proliferation, leading to enhanced ß cell mass expansion. RIIB KO mice also showed increased insulin levels and improved glucose tolerance. Mechanistically, activation of type IIB PKA decreased Cyclin D1 levels and inhibition of RIIB expression increased Cyclin D1 levels. Consistently, activation of type IIB PKA inhibited cell cycle entry. These results suggest that type IIB PKA plays a pivotal role in ß cell proliferation via regulating Cyclin D1 expression.

12.
Front Neurol ; 12: 753944, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803890

RESUMO

Objective: To investigate the factors associated with recurrence/progression after endoscopic endonasal resection of suprasellar craniopharyngiomas. Special attention was paid to assess the impact of pituitary stalk preservation on tumor recurrence/progression and endocrinological outcomes. Methods: We retrospectively recruited 73 patients with suprasellar craniopharyngiomas undergone endoscopic endonasal approach (EEA) surgery from September 2014 to May 2019 and assessed their clinical characteristics, surgical outcomes, and recurrence/progression. Stalk preservation or sacrifice was determined by reviewing operative records, videos, and post-operative magnetic resonance imaging. Results: Gross total resection (GTR) was achieved in 51 cases (69.9%). Tumor recurrence was seen in 5 cases (9.8%) and progression was seen in 8 cases (36.4%), respectively. GTR (OR = 0.248 CI 0.081-0.759; p = 0.015) was the only independent factor influencing recurrence/progression. Kaplan-Meier survival analysis showed that the mean recurrence/progression-free survival were 53 (95% CI 48-59) and 39 (95% CI 28-50) months, respectively, in patients with and without GTR (p = 0.011). Pituitary stalk preservation was more common in cases with peripheral type tumors (83% vs. 30%, p < 0.01). Preserving the pituitary stalk does not appear to decrease the percentage of GTR (75.5% vs. 55.0%, p = 0.089), or increase the rate of tumor recurrence (12.5% vs. 0%, p = 0.508) or progression (46.2% vs. 22.2%, p = 0.486). However, surgically induced hypothyroidism (60.5% vs. 100%, p = 0.041) and diabetes insipidus (35.1% vs. 81.8%, p = 0.017) were significantly lower in patients with stalk preservation. For patients who had hypopituitarism before EEA, there was no difference between those with and without stalk preservation regarding post-operative hypopituitarism (p > 0.05). Conclusion: GTR is the only independent predictor of recurrence/progression after EEA surgery for suprasellar craniopharyngiomas. Preserving the pituitary stalk does not appear to increase the risk of non-GTR and tumor recurrence/progression and might help reduce the risk of surgically induced hypothyroidism and diabetes insipidus. We recommend preserving the pituitary stalk in peripheral type suprasellar craniopharyngiomas with normal pituitary function, especially in cases without hypothyroidism or diabetes insipidus. On the other hand, stalk sacrifice could be considered in central type tumors with severe pre-operative endocrinopathy.

13.
BMC Endocr Disord ; 21(1): 197, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620143

RESUMO

BACKGROUND: Macroprolactin is responsible for pseudohyperprolactinemia and is a common pitfall of the prolactin immunoassay. We aimed to determine the frequency of macroprolactinemia in Chinese hyperprolactinemic patients using monomeric prolactin discriminated by precipitation with polyethylene glycol (PEG). METHODS: Post-PEG monomeric prolactin gender-specific reference intervals were established for the Elecsys immunoassay method (Roche Diagnostics) using sera from healthy female (n = 120) and male (n = 120) donors. The reference intervals were validated using 20 macroprolactinemic (as assessed by gel filtration chromatography (GFC)) sera samples, and presence of monomeric prolactin was discriminated by GFC. Patients with high total prolactin were then screened by PEG precipitation to analyze macroprolactin. The demographic and biochemical details of patients with true hyperprolactinemia and macroprolactinemia were compared. RESULTS: Reference intervals for monomeric prolactin in females and males were 3.4-18.5 and 2.7-13.1 ng/mL, respectively. Among 1140 hyperprolactinemic patients, macroprolactinemia was identified in 261 (22.9 %) patients while the other 879 (77.1 %) patients were diagnosed with true hyperprolactinemia. Menstrual disturbances were the most common clinical feature in both groups. Galactorrhea, amenorrhea, and visual disturbances occurred more frequently in true hyperprolactinemic patients (P < 0.05). CONCLUSIONS: The prevalence of macroprolactin in Chinese patients with hyperprolactinemia was described for the first time. Monomeric prolactin concentration, along with a reference interval screening with PEG precipitation, provides a diagnostic approach for hyperprolactinemia with improved accuracy.


Assuntos
Técnicas de Diagnóstico Endócrino/normas , Hiperprolactinemia/diagnóstico , Prolactina/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , China/epidemiologia , Estudos Transversais , Diagnóstico Diferencial , Feminino , Humanos , Hiperprolactinemia/sangue , Hiperprolactinemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prolactina/análise , Valores de Referência , Adulto Jovem
14.
Front Endocrinol (Lausanne) ; 12: 693669, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603197

RESUMO

Background: Solitary intracranial hypothalamic mass occurs rarely. The etiological diagnosis of solitary hypothalamus lesion is challenging and often unachievable. Although previous studies indicated that lesions affecting the hypothalamus often cause significant metabolic disorders, few reports about the metabolic disturbances of patients with solitary hypothalamic mass have been reported. Method: Twenty-five patients with solitary hypothalamus lesions who had been evaluated and treated in Huashan Hospital from January 2010 to December 2020 were retrospectively enrolled. The clinical manifestations, radiological features, endocrine and metabolic disorders, and pathology were analyzed. Results: The male to female ratio was 5/20. The median age of onset was 22 (19, 35) years old. The most common initial symptom was polydipsia/polyuria (19/25, 76.0%) and amenorrhea (9/20, 45.0%). A high prevalence of hypopituitarism of different axes was found, with almost all no less than 80%. Central hypogonadism (21/22, 95.5%) and central diabetes insipidus (19/21, 90.5%) were the top two pituitary dysfunctions. Conclusive diagnoses were achieved by intracranial surgical biopsy/resection or stereotactic biopsy in 16 cases and by examining extracranial lesions in 3 cases. The pathological results were various, and the most common diagnoses were Langerhans cell histiocytosis (7/19) and hypothalamitis (5/19). The mean timespan from onset to diagnosis in the 19 cases was 34 ± 26 months. Metabolic evaluations revealed remarkable metabolic disorders, including hyperlipidemia (13/16, 81.3%), hyperglycemia (10/16, 62.5%), hyperuricemia (12/20, 60%), overweight/obesity (13/20, 65.0%), and hepatic adipose infiltration (10/13, 76.6%). Conclusion: Either surgical or stereotactic biopsy will be a reliable and relatively safe procedure to help to confirm the pathological diagnosis of solitary hypothalamic mass. Metabolic disorders were severe in patients with solitary hypothalamic mass. The management of such cases should cover both the treatment of the primary disease, as well as the endocrine and metabolic disorders.


Assuntos
Doenças Hipotalâmicas/diagnóstico , Doenças Metabólicas/diagnóstico , Adolescente , Adulto , Idoso , Biópsia , Glicemia , Índice de Massa Corporal , Feminino , Hormônios/sangue , Humanos , Doenças Hipotalâmicas/sangue , Doenças Hipotalâmicas/patologia , Doenças Hipotalâmicas/cirurgia , Hipotálamo/diagnóstico por imagem , Hipotálamo/patologia , Hipotálamo/cirurgia , Imageamento por Ressonância Magnética , Masculino , Doenças Metabólicas/sangue , Doenças Metabólicas/patologia , Doenças Metabólicas/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
15.
Ann Palliat Med ; 10(9): 9415-9426, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34628867

RESUMO

BACKGROUND: Exercise is generally recognized as beneficial to prevent obesity; however, it is not clear which indicator can better reflect the benefits, especially in adolescents. The aim of this study was to describe the effects of exercise on body mass and fat indexes and to clarify the significance of different indexes in clinical use. METHODS: We conducted a prospective cohort study involving 1,941 freshmen from 2014, followed-up biennially until 2018. Various body mass and fat indexes, including weight, height, waist and hip circumference and body fat percentage (BFP), were measured. Physical activity and other variables were collected by questionnaire. All study participants were divided into two groups according to the frequency and intensity of exercise. RESULTS: Compared with the low frequency and intensity exercise group, the high frequency and intensity exercise group had a lower increase in BFP during the 4-year follow-up, and no significant differences were observed in the changes of other indexes between the groups. Even after adjusting, the high frequency and intensity exercise group still exhibited a higher likelihood of reducing BFP. CONCLUSIONS: High frequency and intensity exercise provides benefits for reducing BFP. No other body mass or fat indexes showed any association. BFP could be a much more sensitive indicator to detect and control obesity in adolescents.


Assuntos
Adiposidade , Exercício Físico , Tecido Adiposo , Adolescente , Índice de Massa Corporal , Seguimentos , Humanos , Obesidade , Estudos Prospectivos
16.
iScience ; 24(9): 102983, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34485865

RESUMO

Rosiglitazone, a synthetic peroxisome proliferator-activated receptor γ (PPARγ) ligand, has been reported to reduce growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in 10 patients with acromegaly. However, the mechanisms remain unknown. Here, we reveal that PPARγ directly enhances 15-hydroxyprostaglandin dehydrogenase (15-PGDH) expression, whose expression is decreased and negatively correlates with tumor size in acromegaly. Rosiglitazone decreases GH production and promotes apoptosis and autophagy in GH3 and primary somatotroph adenoma cells and suppresses hepatic GH receptor (GHR) expression and IGF-1 secretion in HepG2 cells. Activating the PGE2/cAMP/PKA pathway directly increases GHR expression. Rosiglitazone suppresses tumor growth and decreases GH and IGF-1 levels in mice inoculated subcutaneously with GH3 cells. The above effects are all dependent on 15-PGDH expression. Rosiglitazone as monotherapy effectively decreases GH and IGF-1 levels in all nineteen patients with active acromegaly. Evidence suggests that rosiglitazone may be an alternative pharmacological approach for acromegaly by targeting both pituitary adenomas and liver.

17.
Front Endocrinol (Lausanne) ; 12: 694213, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394000

RESUMO

Context: Hypothalamic obesity (HO) is a severe complication following craniopharyngioma, but studies regarding the sequelae in adult-onset patients with craniopharyngioma are sparse. Objective: The objective of the study was to describe weight changes after surgical treatment in adult-onset craniopharyngioma patients and to analyze risk factors for postoperative weight gain and HO. Subjects and Method: A retrospective analysis was conducted of 120 adult-onset patients who underwent surgery for craniopharyngioma and follow-up at the institution of the authors between January 2018 and September 2020. Clinical characteristics, anthropometric data, image features, treatment modalities, and endocrine indices were collected. Multivariable logistic regression analysis was used to identify independent risk factors for postoperative weight gain and HO. Results: Forty-nine (40.8%) patients had clinically meaningful weight gain (≥5%) in a median follow-up time of 12.0 months (range 1.0-41.0 months) after surgery. The mean postoperative weight gain in this subgroup was 17.59 ± 12.28 (%). Weight gain continued in the first year following surgery. Patients with lower preoperative BMI [OR 0.78, 95% CI (0.67-0.90), P = 0.001] and the adamantinomatous subtype [OR 3.46, 95% CI (1.02-11.76), P = 0.047] were more likely to experience postoperative weight gain ≥5%. The prevalence of HO was 19.2% preoperatively and increased to 29.2% at last follow-up postoperatively. Only preoperative BMI [OR 2.51, 95% CI (1.64-3.85), P < 0.001] was identified as an independent risk factor for postoperative HO. Conclusions: HO is a common complication in patients with adult-onset craniopharyngioma. Patients with higher preoperative BMI had a greater risk for developing HO postoperatively.


Assuntos
Craniofaringioma/complicações , Doenças Hipotalâmicas/etiologia , Obesidade/etiologia , Neoplasias Hipofisárias/complicações , Adulto , Idade de Início , Índice de Massa Corporal , China/epidemiologia , Estudos de Coortes , Craniofaringioma/epidemiologia , Craniofaringioma/cirurgia , Feminino , Seguimentos , Humanos , Doenças Hipotalâmicas/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Ganho de Peso/fisiologia , Adulto Jovem
18.
Clin Neurol Neurosurg ; 207: 106781, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34246994

RESUMO

INTRODUCTION: Previous studies failed to show the benefit of endoscopic surgery over microscopic surgery in terms of early endocrine remission. This study was to investigate whether early endocrine outcomes in patients with GH-secreting pituitary adenoma underwent endoscopic transsphenoidal surgery would be better than those operated by microscopic surgery. METHODS: An acromegaly database collected from 2010 to 2019 in a single institution was used to emulate a randomized trial. Adult patients operated by a transsphenoidal approach using either endoscope or microscope were included. The primary outcome was endocrine remission based on insulin-like growth factor-1 (IGF-1) at six-month follow-up after surgery. We used inverse probability weighting to construct a pseudo population from which the treatment effect was estimated. RESULTS: In the original cohort, 1118 patients underwent transsphenoidal surgery (424 with an endoscopic approach and 694 with a microscopic approach). Patients treated with endoscopic surgery were more likely to be previously surgical treated and to have an invasive tumor than patients who underwent microscopic surgery. In the pseudo population, the proportion of endocrine remission was 54.9% in the endoscopic group and 42.0% in the microscopic group (odds ratio, 1.68; 95% CI, 1.27-2.23). This finding was consistent and robust across several sensitivity analyses. CONCLUSIONS: Among patients with growth hormone secreting pituitary adenoma who underwent transsphenoidal surgery, endoscopic surgery was associated with higher early endocrine remission than microscopic surgery.


Assuntos
Adenoma/cirurgia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Neuroendoscopia/métodos , Procedimentos Neurocirúrgicos/métodos , Resultado do Tratamento , Acromegalia/etiologia , Adenoma/complicações , Adulto , Idoso , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Humanos , Masculino , Microcirurgia/métodos , Pessoa de Meia-Idade
19.
Front Endocrinol (Lausanne) ; 12: 694162, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305816

RESUMO

Introduction: Brown adipose tissue (BAT) becomes the favorite target for preventing and treating metabolic diseases because the activated BAT can produce heat and consume energy. The brain, especially the hypothalamus, which secretes Neuropeptide Y (NPY), is speculated to regulate BAT activity. However, whether NPY is involved in BAT activity's central regulation in humans remains unclear. Thus, it's essential to explore the relationship between brain glucose metabolism and human BAT activity. Methods: A controlled study with a large sample of healthy adults used Positron emission tomography/computed tomography (PET/CT) to noninvasively investigate BAT's activity and brain glucose metabolism in vivo. Eighty healthy adults with activated BAT according to the PET/CT scan volunteered to be the BAT positive group, while 80 healthy adults without activated BAT but with the same gender, similar age, and BMI, scanning on the same day, were recruited as the control (BAT negative). We use Statistical parametric mapping (SPM) to analyze the brain image data, Picture Archiving & Communication System (PACS), and PET/CT Viewer software to calculate the semi-quantitative values of brain glucose metabolism and BAT activity. ELISA tested the levels of fasting plasma NPY. The multiple linear regression models were used to analyze the correlation between brain glucose metabolism, the level of NPY, and the BAT activity in the BAT positive group. Results: (1) Compared with controls, BAT positive group showed significant metabolic decreases mainly in the right Insula (BA13a, BA13b) and the right claustrum (uncorrected P <0.01, adjusted BMI). (2) The three brain regions' semi-quantitative values in the BAT positive group were significantly lower than the negative group (all P values < 0.05). (3) After adjusting for age, gender, BMI, and outside temperature, there was a negative correlation between brain metabolic values and BAT activity (all P values < 0.05). However, after further adjusting for NPY level, there were no significant differences between the BA13b metabolic values and BAT activity (P>0.05), while the correlation between the BA13a metabolic values and BAT activity still was significant (P< 0.05). Conclusions: Regional brain glucose metabolism is closely related to healthy adults' BAT activity, which may be mediated by NPY.


Assuntos
Tecido Adiposo Marrom/fisiologia , Encéfalo/metabolismo , Glucose/metabolismo , Neuropeptídeo Y/fisiologia , Tecido Adiposo Marrom/diagnóstico por imagem , Adulto , Encéfalo/diagnóstico por imagem , Metabolismo dos Carboidratos , China , Feminino , Fluordesoxiglucose F18/farmacocinética , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Neuropeptídeo Y/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto Jovem
20.
J Neuroendocrinol ; 33(5): e12958, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33998086

RESUMO

The present study investigated the factors associated with recurrence during long-term follow-up in acromegaly and compared the recurrence rate between patients in remission with 2010 vs 2000 consensus criteria. We retrospectively recruited 133 adult acromegalic patients who had undergone transsphenoidal surgery (TSS) from January 2013 to December 2014 and assessed their clinical characteristics, surgical outcomes and recurrence. Surgical remission was defined as normalised insulin-like growth factor 1 (IGF-1) with nadir growth hormone (GH) during an oral glucose tolerance test (OGTT) < 1 µg/ L no less than 3 months after TSS without adjuvant therapy. Recurrence was defined as persistently reelevated IGF-1 after surgical remission. Cox regression analysis and Kaplan-Meier survival analysis were performed to evaluate the factors associated with recurrence. Remission was achieved in 77 cases (57.9%) after TSS alone. Recurrence was seen in five cases (6.5%) at 12, 12, 12, 36 and 54 months, respectively, after surgery. Cox regression analysis showed that a nadir GH < 0.4 µg /L (vs 0.4-1.0 µg /L) at surgical remission (odds ratio [OR] = 0.106; 95% confidence interval [CI] = 0.017-0.645; P = 0.015) and Ki-67 index (OR = 2.636; 95% CI = 1.023-6.791; P = 0.045) were independent factors influencing recurrence. Kaplan-Meier survival analysis showed that the median recurrence-free survival was 36 months (95% CI = 20-52) for patients with nadir GH 0.4-1.0 µg /L at surgical remission. The median recurrence-free survival for patients with nadir GH < 0.4 µg /L at surgical remission was much longer (ie, required further follow-up to estimate). A failure of GH suppression under 0.4 µg /L during an OGTT in patients with normalised IGF-1 and a higher Ki-67 index are independent predictors of recurrence after surgical remission in GH-secreting pituitary adenomas. Compared to patients with nadir GH < 0.4 µg /L, those with nadir GH 0.4-1.0 µg /L appear to have a significantly higher risk of recurrence.


Assuntos
Acromegalia/cirurgia , Fator de Crescimento Insulin-Like I/metabolismo , Procedimentos Neurocirúrgicos/métodos , Acromegalia/sangue , Adulto , Consenso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Recidiva , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento
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