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1.
Cureus ; 16(6): e63152, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39055441

RESUMO

INTRODUCTION: Pituitary apoplexy (PA) is a rare neuroendocrinological emergency. The SARS-CoV-2 pandemic recommendations led to a shift in the management of patients with pituitary diseases, especially in the decision-making between conservative and surgical treatment of patients with PA. OBJECTIVE: This study aimed to describe the conservative and surgical treatment and the clinical, visual, and endocrinological outcomes in patients with PA at the Pituitary Center of Excellence (PTCEO) during the SARS-CoV-2 pandemic and within three years. METHODS: This is a cohort study. Patients with PA between April 2020 and September 2023 were followed up. Treatment decisions, clinical manifestations, hormonal profile, and tumor size with MRI were described at the onset, at three months, six months, one year, two years, and three years after diagnosis. RESULTS: A total of 27 patients with PA diagnosis were included in the study. Of these, 12 patients were conservatively treated, six (50%) had prolactinomas, five (41.6%) had non-functioning adenomas, and one (8.3%) had pituicytoma. Fifteen patients were surgically intervened during the first hospitalization, nine (60%) had non-functioning adenomas, four (26.6%) had prolactinomas, one (6.6%) had ACTH-producing adenoma, and one (6.6%) had gonadotropinoma. Two patients from the conservatively treated group (one non-functioning adenoma and one pituicytoma) were intervened surgically at years 2 and 3, respectively. During the initial assessment, there were no statistically significant differences between patients in visual acuity (9 [75%] vs 15 [100%]), visual field affection (8 [66.6%] vs 11 [73.3%]), and cranial nerve deficit (3 [25%] vs 6 [40%]). At six months follow-up, no statistically significant differences were found in the visual acuity improvement (8 [88%] vs 11 [100%]), visual field (8 [100%] vs 8 [72%]), and cranial nerve deficit between the two groups (3 [100%] vs 6 [100%]). Meanwhile, the average length of in-hospital stay was 1.5 vs 10 days (p = 0.019). The tumor size and largest diameter were smaller in the surgically treated group (6.2 vs. 0.5 cm3, p = 0.029 and 2.5 vs. 1.1 cm, p = 0.036, respectively). Visual acuity improved in nine (58.3%) patients at year 1: two (40%) conservative vs seven (100%) surgical (p = 0.039); six (85.7%) patients at year 2: two (66.6%) conservative vs. four (100%) surgical; and three (100%) patients on both groups at year 3. Fourteen patients needed hormonal substitution: 87.5% (eight [88.8%] conservative vs six [85.7%] surgical) at year 1, 85.7% (six patients in both groups) at year 2, and 80% (four conservative vs three [100%] surgical) at year 3. The thyrotropic axis was the most affected in both groups during the three years. During the first-year follow-up, six (85%) patients persisted with tumoral regression (2 [66.6%] conservative vs 4 [100%] surgical) and one (14.2%) patient from the medical group progressed. During the second and third years, 10 and three (100%) of the patients, respectively, showed the regression of the tumoral volume in both groups. CONCLUSIONS: The clinical, visual, and neuroendocrinological outcomes were similar in both groups of patients with PA during the SARS-CoV-2 pandemic. In cases where the Pituitary Apoplexy Score (PAS) score does not surpass three points without neurological deterioration, conservative management can be considered an adequate option for treatment.

2.
Cureus ; 16(4): e58850, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38784347

RESUMO

Cranial nerve palsy is common in pituitary disease and depends on the extension of the lesion into the cavernous sinuses. Bilateral cranial nerve palsy was described in pituitary adenomas with apoplexy and in only one case in hypophysitis. We present a case of a 32-year-old female manifesting with headache, diplopia, bilateral sixth nerve palsy, and hypopituitarism. Magnetic resonance imaging (MRI) revealed symmetric expansion of the pituitary gland, with bilateral cavernous sinus invasion and thickening of the pituitary stalk. Hypophysitis was suspected, and after treatment with IV methylprednisolone boluses, a decrease in the pituitary lesion was observed, with complete remission of sixth nerve palsy in the right eye and partial improvement in the left eye. In this case, we report an infrequent form of presentation of hypophysitis, and highlight that steroids are the first line of treatment.

3.
Cureus ; 15(6): e39869, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37404423

RESUMO

Background and objective Invasive prolactinoma accounts for 1-5% of all prolactinomas. Its mass and compromise of the diencephalon and frontal and temporal lobes may result in a range of neuropsychiatric symptoms that are often missed during initial evaluations. Cabergoline is a dopaminergic agonist used as the first-line treatment for these patients; however, its effect on neuropsychiatric symptoms in this particular setting remains unexplored. In this study, our primary objective was to describe the epidemiology of neuropsychiatric comorbidities in Mexican patients with invasive prolactinomas. The secondary aim of the study was to describe how these comorbidities are modified by treatment with cabergoline, through follow-up with standardized clinical scales. Methods This was a retrospective analytic study. Data were pulled from clinical records and evaluations of patients at baseline and at six-month follow-ups.  Results A total of 10 patients were included in the study. None of them had any prior psychiatric diagnosis. At the initial evaluation, 70% were diagnosed with depression or anxiety. During follow-up, two patients developed neuropsychiatric symptoms; there was a significant reduction in tumor size but no difference was found in clinimetric scores for neuropsychiatric comorbidities. Conclusions Patients with giant prolactinomas may present with several neuropsychiatric symptoms throughout the course of their disease. Although there are several mechanisms involved, it is important to keep in mind that cabergoline may interfere with the dopaminergic pathways involved. This study was underpowered to determine the association but can serve as a pilot for further research on this topic.

4.
Int J Mol Sci ; 23(9)2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35563252

RESUMO

Corticotroph cells give rise to aggressive and rare pituitary neoplasms comprising ACTH-producing adenomas resulting in Cushing disease (CD), clinically silent ACTH adenomas (SCA), Crooke cell adenomas (CCA) and ACTH-producing carcinomas (CA). The molecular pathogenesis of these tumors is still poorly understood. To better understand the genomic landscape of all the lesions of the corticotroph lineage, we sequenced the whole exome of three SCA, one CCA, four ACTH-secreting PA causing CD, one corticotrophinoma occurring in a CD patient who developed Nelson syndrome after adrenalectomy and one patient with an ACTH-producing CA. The ACTH-producing CA was the lesion with the highest number of single nucleotide variants (SNV) in genes such as USP8, TP53, AURKA, EGFR, HSD3B1 and CDKN1A. The USP8 variant was found only in the ACTH-CA and in the corticotrophinoma occurring in a patient with Nelson syndrome. In CCA, SNV in TP53, EGFR, HSD3B1 and CDKN1A SNV were present. HSD3B1 and CDKN1A SNVs were present in all three SCA, whereas in two of these tumors SNV in TP53, AURKA and EGFR were found. None of the analyzed tumors showed SNV in USP48, BRAF, BRG1 or CABLES1. The amplification of 17q12 was found in all tumors, except for the ACTH-producing carcinoma. The four clinically functioning ACTH adenomas and the ACTH-CA shared the amplification of 10q11.22 and showed more copy-number variation (CNV) gains and single-nucleotide variations than the nonfunctioning tumors.


Assuntos
Adenoma Hipofisário Secretor de ACT , Adenoma , Carcinoma , Genômica , Síndrome de Nelson , Neoplasias Hipofisárias , Adenoma Hipofisário Secretor de ACT/genética , Adenoma/genética , Adenoma/patologia , Hormônio Adrenocorticotrópico , Aurora Quinase A , Carcinoma/genética , Corticotrofos/patologia , Receptores ErbB , Humanos , Melanocortinas , Complexos Multienzimáticos , Nucleotídeos , Neoplasias Hipofisárias/genética
5.
BMC Med Genomics ; 15(1): 52, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35260162

RESUMO

BACKGROUND: Pituitary adenomas (PA) are the second most common intracranial tumors and are classified according to hormone they produce, and the transcription factors they express. The majority of PA occur sporadically, and their molecular pathogenesis is incompletely understood. METHODS: Here we performed transcriptome and proteome analysis of tumors derived from POU1F1 (GH-, TSH-, and PRL-tumors, N = 16), NR5A1 (gonadotropes and null cells adenomas, n = 17) and TBX19 (ACTH-tumors, n = 6) lineages as well as from silent ACTH-tumors (n = 3) to determine expression of kinases, cyclins, CDKs and CDK inhibitors. RESULTS: The expression profiles of genes encoding kinases were distinctive for each of the three PA lineage: NR5A1-derived tumors showed upregulation of ETNK2 and PIK3C2G and alterations in MAPK, ErbB and RAS signaling, POU1F1-derived adenomas showed upregulation of PIP5K1B and NEK10 and alterations in phosphatidylinositol, insulin and phospholipase D signaling pathways and TBX19-derived adenomas showed upregulation of MERTK and STK17B and alterations in VEGFA-VEGFR, EGF-EGFR and Insulin signaling pathways. In contrast, the expression of the different genes encoding cyclins, CDK and CDK inhibitors among NR5A1-, POU1F1- and TBX19-adenomas showed only subtle differences. CDK9 and CDK18 were upregulated in NR5A1-adenomas, whereas CDK4 and CDK7 were upregulated in POUF1-adenomas. CONCLUSIONS: The kinome of PA clusters these lesions into three distinct groups according to the transcription factor that drives their terminal differentiation. And these complexes could be harnessed as molecular therapy targets.


Assuntos
Adenoma , Neoplasias Hipofisárias , Adenoma/metabolismo , Hormônio Adrenocorticotrópico/genética , Proteínas Reguladoras de Apoptose/genética , Quinases Ciclina-Dependentes/genética , Quinases Ciclina-Dependentes/metabolismo , Ciclinas/genética , Ciclinas/metabolismo , Humanos , Insulina , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , Proteínas Serina-Treonina Quinases , Fatores de Transcrição/genética , Transcriptoma
6.
Endocrinol Diabetes Metab ; 4(2): e00229, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33855226

RESUMO

Objective: To study the impact of secondary mental disorders in patients affected with acromegaly and correlate them with quality of life (QoL) and disease status. Design: An observational transversal descriptive and comparative study that evaluates QoL's impact due to secondary mental disorders in affected Mexicans with acromegaly using AcroQoL and SF-36 instruments. Correlation of the results with the disease's biochemical status was performed. According to Beck's scales, anxiety and depression analyses evaluate QoL's impact, and its gender variability is described. Results: Eighty-five patients with diagnoses of acromegaly were included. The mean age was 43.18 years, 47 being women (55.29%). The mean age at diagnosis was 37.95 years, with no difference between men and women. AcroQoL and SF-36 global and sub-domain scores differed significantly between men and women, the latter having lower global and individual sub-domain scores. The mean score of QoL, according to AcroQoL, is 59.40. In women, the mean values are less (55.13) than men (64.68), p = 0.021. The sub-domain analyses' scores in physical, appearance and social relationships were less in women (53.21; 47.34; 62.32) than men (62.68; 56.76; 73.87) p = 0.044, 0.069 and 0.013, respectively. Higher Beck's Depression Inventory (BDI) and Beck's Anxiety Inventory (BAI) scores correlated with lower QoL as assessed by global and individual sub-domain scores. Women presented significantly higher BDI and BAI mean scores when compared to men regardless of their biochemical status. Anxiety (p = 0.027) and depression (p < 0.001) severity were higher in women compared to men. Conclusion: Correlations between female gender, depression/anxiety scores and QoL require further validation. There is much to be routinely done to improve secondary psychopathology in patients affected by this disease. The need for mental status screening at diagnosis should be emphasized to identify secondary mental illnesses to improve QoL with its treatment.


Assuntos
Acromegalia/complicações , Transtornos Mentais/etiologia , Qualidade de Vida , Adulto , Ansiedade , Depressão , Feminino , Humanos , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Fatores Sexuais
7.
J Clin Endocrinol Metab ; 105(12)2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32944780

RESUMO

CONTEXT: Acromegaly registries constitute a valuable source of therapeutic outcome information in real-life. OBJECTIVE: The objective of this work is to analyze surgical and pharmacological outcomes in the Mexican Acromegaly Registry (MAR). DESIGN AND METHODS: Data were extracted from the MAR informatic platform. Surgical remission was defined by a postoperative postglucose (GH) of less than 1 ng/mL and an insulin-like growth factor 1 (IGF-1) of less than 1.2 × upper limit of normal (ULN). Pharmacological remission was defined by a basal GH of less than 1 ng/mL and an IGF-1 of less than 1.2 × ULN. RESULTS: A total of 650 surgical outcomes were analyzed (94.6% transsphenoidal). Surgical remission was achieved in 40.15%, whereas 44.15% remained biochemically active. Persistently active disease after surgery was significantly associated with harboring an invasive macroadenoma, a basal GH of greater than 10 ng/mL, and/or an IGF-1 of greater than 2 × ULN at diagnosis on bivariate and multivariate analysis. The outcome of monotherapy with first-generation somatostatin analogs (SSAs) was evaluated in 267 patients (adjunctive in 65%), of whom 28.4% achieved remission. Persistently active disease was significantly associated with harboring an invasive macroadenoma as well as with pretreatment basal GH and IGF-1 levels of greater than 10 ng/mL and greater than 2 × ULN, respectively, on bivariate and multivariate analysis. Combined therapy with SSA and cabergoline was analyzed in 100 patients, of whom 19% achieved remission and 44% remained active; in this subset of patients, only a pretreatment IGF-1 of greater than 2 × ULN was significantly associated with persistent disease activity. CONCLUSION: Surgical and pharmacological outcomes in acromegaly are highly dependent on tumor size/invasiveness as well as on the degree of hypersomatotropinemia.


Assuntos
Acromegalia/tratamento farmacológico , Acromegalia/cirurgia , Acromegalia/diagnóstico , Acromegalia/epidemiologia , Adenoma/diagnóstico , Adenoma/tratamento farmacológico , Adenoma/epidemiologia , Adenoma/cirurgia , Adulto , Cabergolina/uso terapêutico , Terapia Combinada , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/epidemiologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Período Pós-Operatório , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Somatostatina/análogos & derivados , Resultado do Tratamento
8.
J Clin Endocrinol Metab ; 101(11): 3997-4004, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27428551

RESUMO

CONTEXT: Acromegaly is a systemic disorder caused by a GH-secreting pituitary adenoma. As with other rare diseases, acromegaly registries developed in various European countries have provided us with important information. OBJECTIVE: The objective of the study was to analyze the epidemiological, clinical, biochemical, and therapeutic data from the Mexican Acromegaly Registry (MAR). SETTING: The setting of the study was a nationwide patient registry. DESIGN AND METHODOLOGY: The MAR was created in 2009. It gathers data from 24 participating centers belonging to three different institutions using a specifically designed on-line platform. Only patients diagnosed after 1990 were included in the program. RESULTS: A total of 2057 patients (51% female, mean age at diagnosis 41.1 ± 24.5 y) have been registered for an estimated prevalence of 18 cases per 1 million inhabitants. Hypertension, glucose intolerance, diabetes, and dyslipidemia were present in 27%, 18.4%, 30%, and 24% of the patients, respectively. The IGF-1 level at diagnosis and the concomitant presence of hypertension were significantly associated with the development of diabetes. Transsphenoidal surgery was the primary treatment in 72% of the patients. Pharmacological treatment, mostly with somatostatin analogs, was administered primarily and adjunctively in 26% and 54% of the patients, respectively. Treatment choice varied among the three participating institutions, with the predominance of pharmacological therapy in two of them and of radiation therapy in the third. Therapeutic outcomes were similar to those reported in the European registries. CONCLUSIONS: The MAR is the largest and first non-European registry of the disease. Our findings highlight important within-country differences in treatment choice due to variations in the availability of resources.


Assuntos
Acromegalia/etiologia , Adenoma/diagnóstico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico , Hipófise/fisiopatologia , Acromegalia/prevenção & controle , Adenoma/epidemiologia , Adenoma/fisiopatologia , Adenoma/terapia , Adulto , Estudos de Coortes , Terapia Combinada , Feminino , Seguimentos , Adenoma Hipofisário Secretor de Hormônio do Crescimento/epidemiologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/fisiopatologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/terapia , Terapia de Reposição Hormonal/efeitos adversos , Hospitais Públicos , Humanos , Hipofisectomia/efeitos adversos , Masculino , México/epidemiologia , Hipófise/efeitos dos fármacos , Hipófise/efeitos da radiação , Hipófise/cirurgia , Padrões de Prática Médica , Prevalência , Radioterapia/efeitos adversos , Sistema de Registros , Estudos Retrospectivos , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Resultado do Tratamento
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