Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 10 de 10
Filtrar
Mais filtros











Intervalo de ano de publicação
1.
Int J Mol Sci ; 24(3)2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36769196

RESUMO

Acromegaly is a chronic systemic disease caused in the vast majority of cases by growth hormone (GH)-secreting adenoma, with surgery being the first-line treatment. When a cure is not attained with surgery, first-generation somatostatin receptor ligands (fg-SRLs) are the most common medication prescribed. Predictors of response to fg-SRLs have been studied; however, they cannot fully predict the response to fg-SRL. MicroRNAs are small RNAs, the main role of which is messenger RNA (mRNA) post-transcriptional regulation. This study aimed to identify the microRNAs involved in resistance to treatment with fg-SRLs in acromegaly. Ten patients with acromegaly undergoing treatment with fg-SRLs were selected to undergo miRNA sequencing: five controlled and five uncontrolled with treatment. Bioinformatic analysis was performed to detect differentially expressed miRNAs. Then, the same 10 samples were used for validation by qPCR and an additional 22 samples were analyzed, totaling 32 samples. e We found 59 differentially expressed miRNAs in the first analysis. miR-181a-5p and miR-181b-5p were downregulated, and miR-383-5p was upregulated in the uncontrolled group. Receiver operating characteristic (ROC) curve analysis of miR-383-5p showed an NPV of 84.3% and a PPV of 84.5%. In summary, miR-181a-5p, miR-181b-5p, and miR-383-5p are biomarkers of response to fg-SRLs, and they can be used individually or included in prediction models as tools to guide clinical decisions.


Assuntos
Acromegalia , MicroRNAs , Humanos , Acromegalia/genética , Receptores de Somatostatina/genética , MicroRNAs/genética , MicroRNAs/uso terapêutico
2.
Int J Mol Sci ; 23(15)2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35955787

RESUMO

Acromegaly is a chronic and systemic disease due to excessive growth hormone and insulin-like growth factor type I caused, in the vast majority of cases, by a GH-secreting pituitary adenoma. About 40% of these tumors have somatic mutations in the stimulatory G protein alpha-subunit 1 gene. The pathogenesis of the remaining tumors, however, is still not fully comprehended. Surgery is the first-line therapy for these tumors, and first-generation somatostatin receptor ligands (fg-SRL) are the most prescribed medications in patients who are not cured by surgery. MicroRNAs are small, non-coding RNAs that control the translation of many mRNAs, and are involved in the post-transcriptional regulation of gene expression. Differentially expressed miRNAs can explain differences in the pathogenesis of acromegaly and tumor resistance. In this review, we focus on the most validated miRNAs, which are mainly involved in acromegaly's tumorigenesis and fg-SRL resistance, as well as in circulating miRNAs in acromegaly.


Assuntos
Acromegalia , Adenoma , Hormônio do Crescimento Humano , MicroRNAs , Acromegalia/genética , Adenoma/metabolismo , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , MicroRNAs/genética , MicroRNAs/uso terapêutico , Receptores de Somatostatina/genética , Receptores de Somatostatina/metabolismo , Somatostatina/genética , Somatostatina/uso terapêutico
3.
Expert Rev Endocrinol Metab ; 16(6): 309-320, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34678108

RESUMO

INTRODUCTION: Non-functioning pituitary adenomas (NFPAs) are clinically silent tumors and the second most common pituitary adenoma. Surgery is the mainstay of treatment as there is, as yet, no effective medical treatment. AREAS COVERED: We present current knowledge on the clinical diagnosis, histopathological classification, molecular data, and management strategies in NFPA. EXPERT OPINION: NFPA is a heterogeneous group of tumors, in respect to their origin and clinical course. In recent years, research on pathology and molecular biology have advanced our knowledge of NFPA pathogenesis. NFPA exhibit, in the majority of cases, an indolent behavior, with satisfactory response to treatment. In aggressive cases, multimodal management is needed; however, even this approach may be insufficient, so the development of new treatments is warranted for better management. In this setting, the understanding of the mechanisms involved in the genesis and progression of NFPA is crucial for the identification and development of directed treatments with higher chances of response.


Assuntos
Adenoma , Neoplasias Hipofisárias , Adenoma/diagnóstico , Adenoma/terapia , Humanos , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/terapia , Resultado do Tratamento
4.
Arch Endocrinol Metab ; 65(5): 648-663, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34591404

RESUMO

Acromegaly caused by ectopic growth hormone-releasing hormone (GHRH)-secreting tumor is exceedingly rare. We report a case of acromegaly secondary to GHRH secretion by an incidentally diagnosed pulmonary neuroendocrine tumor (NET) and review 47 similar cases in literature. A 22-year-old male patient presented with symptoms of pituitary apoplexy. Magnetic resonance imaging (MRI) showed apoplexy of a pituitary adenoma. Routinely prior to surgery, a chest radiography was performed which revealed a mass in the left lung. During investigation, the patient was diagnosed with metastatic GHRH-secreting pulmonary NET. In retrospect, it was noted that the patient had pituitary hyperplasia 20 months prior to the MRI which showed the presence of a pituitary adenoma. The histological findings confirmed somatotroph hyperplasia adjacent to somatotropinoma. This case suggests that GHRH secretion can be associated with pituitary hyperplasia, which may be followed by pituitary adenoma formation.


Assuntos
Acromegalia , Adenoma , Carcinoma Neuroendócrino , Neoplasias Hipofisárias , Adenoma/complicações , Adenoma/diagnóstico por imagem , Adulto , Hormônio Liberador de Hormônio do Crescimento , Humanos , Hiperplasia , Masculino , Adulto Jovem
5.
Arch. endocrinol. metab. (Online) ; 65(4): 512-516, July-Aug. 2021. graf
Artigo em Inglês | LILACS | ID: biblio-1339101

RESUMO

SUMMARY Cyclic Cushing's syndrome (CS) due to thymic carcinoid is a rare disorder. We report a case of cyclic CS due to ectopic adrenocorticotropic hormone (ACTH)-secreting atypical thymic carcinoid tumor and reviewed similar cases published in the literature. Our patient had hypercortisolemia lasting approximately one month, followed by normal cortisol secretion, with relapse one year later. Histopathology revealed an atypical ACTH-positive thymic carcinoid. Ectopic CS can be derived from atypical thymic carcinoids, which can be aggressive tumors with early relapse, suggesting that this type of tumor probably needs aggressive treatment.


Assuntos
Humanos , Neoplasias do Timo/diagnóstico por imagem , Síndrome de ACTH Ectópico , Tumor Carcinoide , Síndrome de Cushing/etiologia , Hormônio Adrenocorticotrópico , Recidiva Local de Neoplasia
6.
Arch Endocrinol Metab ; 65(4): 512-516, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33844892

RESUMO

Cyclic Cushing's syndrome (CS) due to thymic carcinoid is a rare disorder. We report a case of cyclic CS due to ectopic adrenocorticotropic hormone (ACTH)-secreting atypical thymic carcinoid tumor and reviewed similar cases published in the literature. Our patient had hypercortisolemia lasting approximately one month, followed by normal cortisol secretion, with relapse one year later. Histopathology revealed an atypical ACTH-positive thymic carcinoid. Ectopic CS can be derived from atypical thymic carcinoids, which can be aggressive tumors with early relapse, suggesting that this type of tumor probably needs aggressive treatment.


Assuntos
Síndrome de ACTH Ectópico , Tumor Carcinoide , Síndrome de Cushing , Neoplasias do Timo , Hormônio Adrenocorticotrópico , Síndrome de Cushing/etiologia , Humanos , Recidiva Local de Neoplasia , Neoplasias do Timo/diagnóstico por imagem
7.
Clin Endocrinol (Oxf) ; 94(4): 590-597, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33147364

RESUMO

OBJECTIVE: Growth hormone deficiency (GHD) is usually treated with recombinant human GH (rhGH), and this has been rarely associated with hip disorders. We analysed the clinical data of patients with congenital GHD receiving rhGH who had associated hip dysplasia or Legg-Calve-Perthes disease (LCPD), with a view to determining whether the hip dysplasia was associated with the underlying disease or with rhGH treatment. DESIGN: We performed a retrospective analysis of paediatric and adolescent patients seen between 1992-2018 with congenital GHD and hip disorders. Data were collected through a review of the patients' medical records and included demographics, clinical and imaging data, and the time frame between the onset of the symptoms related to the hip disorders and the onset of GH treatment. RESULTS: Of the 13 patients with hip disorders, hip dysplasia was present in ten patients and LCPD in three. Hip dysplasia was diagnosed before rhGH was initiated in 50% of cases. These patients had bilateral hip dysplasia and isolated GHD. LCPD was diagnosed in one patient before rhGH was commenced and did not progress. In two patients, LCPD was diagnosed after rhGH was started and did temporarily progress in one of them, but rhGH was not discontinued because LCPD did not seem to be related to rhGH treatment. CONCLUSIONS: This study suggests that hip dysplasia could be a manifestation of an underlying GHD. Additionally, rhGH treatment may not necessarily be causative of LCPD.


Assuntos
Nanismo Hipofisário , Luxação do Quadril , Hormônio do Crescimento Humano , Doença de Legg-Calve-Perthes , Adolescente , Criança , Hormônio do Crescimento Humano/deficiência , Humanos , Estudos Retrospectivos
8.
Arch. endocrinol. metab. (Online) ; 65(5): 648-663, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1345192

RESUMO

SUMMARY Acromegaly caused by ectopic growth hormone-releasing hormone (GHRH)-secreting tumor is exceedingly rare. We report a case of acromegaly secondary to GHRH secretion by an incidentally diagnosed pulmonary neuroendocrine tumor (NET) and review 47 similar cases in literature. A 22-year-old male patient presented with symptoms of pituitary apoplexy. Magnetic resonance imaging (MRI) showed apoplexy of a pituitary adenoma. Routinely prior to surgery, a chest radiography was performed which revealed a mass in the left lung. During investigation, the patient was diagnosed with metastatic GHRH-secreting pulmonary NET. In retrospect, it was noted that the patient had pituitary hyperplasia 20 months prior to the MRI which showed the presence of a pituitary adenoma. The histological findings confirmed somatotroph hyperplasia adjacent to somatotropinoma. This case suggests that GHRH secretion can be associated with pituitary hyperplasia, which may be followed by pituitary adenoma formation.


Assuntos
Humanos , Masculino , Adulto , Adulto Jovem , Neoplasias Hipofisárias , Acromegalia , Adenoma/complicações , Adenoma/diagnóstico por imagem , Carcinoma Neuroendócrino , Hormônio Liberador de Hormônio do Crescimento , Hiperplasia
9.
Endocrine ; 70(2): 380-387, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32621052

RESUMO

PURPOSE: Assess cyclin A in nonfunctioning pituitary adenomas (NFPA) and compare its expression in non-invasive and non-proliferative tumors with invasive and proliferative tumors (12× higher risk of recurrence). METHODS: Quantitative real time polymerase chain reaction to analyze cyclin A using normal pituitary gland as reference. Fold change (FC) > 1 was considered as increased. Tumor invasion was based on Knosp criteria (grades 3-4 considered invasive) and proliferation on the presence of at least two of three criteria: Ki-67 ≥ 3%; mitoses > 2/10; positive p53. Both groups were compared with Mann-Whitney test considering p value < 0.05 as statistically significant. RESULTS: Thirty-one patients with NFPA were included. Tumors were mainly of gonadotrophic origin (74.2%), followed by corticotrophic (19.4%) and lactotrophic (3.2%) origins and null-cell adenomas (3.2%). Median tumor diameter was 3.5 cm (1.8-8.0) and Ki-67 was 3.0% (0.3-11%). Sixteen patients had tumors classified as non-invasive and non-proliferative and 15 as invasive and proliferative. Median FC was 0.31 in all tumors (0.13-1.94). Cyclin A was not related to invasion or proliferation (FC 0.41 in non-invasive and non-proliferative tumors and FC 0.30 in invasive and proliferative tumors; p = 0.968). Four (12.9%) patients had tumors that exhibited increased cyclin A [median FC of 1.04 (1.02-1.94)]-three of gonadotrophic origin and one null-cell adenoma, with two tumors classified as non-invasive and non-proliferative and two tumors classified as invasive and proliferative. Median tumor diameter in these samples was 3.4 cm (2.4-3.6) and Ki-67 was 5.1% (2-11%). CONCLUSIONS: Cyclin A was increased in a minority of NFPA and does not seem to be related to invasion or proliferation.


Assuntos
Adenoma , Neoplasias Hipofisárias , Biomarcadores Tumorais , Ciclina A , Humanos , Antígeno Ki-67 , Recidiva Local de Neoplasia , Neoplasias Hipofisárias/genética
10.
J Clin Endocrinol Metab ; 103(6): 2079-2082, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29618062

RESUMO

Context: 45,X/46,XY mosaicism is a disorder of sex development leading to abnormal gonadal development and to unpredictable genital phenotype, growth, and pubertal development. Case Description: A 2-year-old male presented with a right impalpable testis. Blood karyotype was 46,XY. A laparoscopy performed for right orchidopexy revealed a right streak gonad with Mullerian structures, whereas on the left side, a normal descended testis was present. The karyotype of the removed gonad was 45,X/46,XY. The child grew along the second centile, within the midparental height (MPH) range, until the time of puberty, when linear growth worsened due to a lack of a pubertal growth spurt, and growth hormone (GH) therapy was initiated. He developed spontaneous puberty (13 years of age) and showed normal pubertal progression. However, from the age of 15 years, he had low normal testosterone, raised follicle-stimulating hormone, and reduction of inhibin B, possibly suggestive of declining testicular function. His final height was -2.24 standard deviation score (SDS) (-2.4 SDS at GH start; MPH -1.6 SDS). Conclusions: Our case describes a mild male phenotype associated with 45,X/46,XY mosaicism characterized by unilateral cryptorchidism, spontaneous onset of puberty, and normal blood karyotype. The case illustrates the difficulties inherent in making a diagnosis of 45,X/46,XY mosaicism when there is no genital ambiguity and makes the point that growth and testicular impairment may occur, mostly manifesting during adolescence. An early diagnosis is crucial to initiate careful monitoring for growth and pubertal disorders, increased tumor risk, and fertility issues commonly seen in these children.


Assuntos
Criptorquidismo/genética , Transtornos do Desenvolvimento Sexual/genética , Disgenesia Gonadal 46 XY/genética , Adolescente , Criança , Pré-Escolar , Criptorquidismo/patologia , Transtornos do Desenvolvimento Sexual/patologia , Disgenesia Gonadal 46 XY/patologia , Humanos , Cariótipo , Cariotipagem , Masculino , Mosaicismo , Puberdade/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA