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1.
JCEM Case Rep ; 1(3): luad033, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37908586

RESUMEN

We present the case of a 27-year-old female who had a history of recurrent headaches and visual disturbances. Magnetic resonance imaging of the brain showed a lesion that suggested pituitary adenoma, with indications of a recent bleeding or cystic degeneration. Nonhormonal deficiencies were documented, restricted to nontumoral hyperprolactinemia. Transsphenoidal approach surgery was performed and the purulent material was drained, confirming the diagnosis of pituitary abscess. Sinusitis was considered to be the only possible cause of this condition. Empirical treatment to Gram-positive anaerobic cocci was administrated, with a satisfactory response.

2.
Cancers (Basel) ; 15(5)2023 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-36900229

RESUMEN

OBJECTIVE: To analyze, in a cohort of acromegalic patients, the results of the efficiency and safety of radiosurgery (CyberKnife), as well as the prognostic factors associated with disease remission. MATERIAL AND METHODS: Observational, retrospective, longitudinal, and analytical study that included acromegalic patients with persistent biochemical activity after initial medical-surgical treatment, who received treatment with CyberKnife radiosurgery. GH and IGF-1 levels at baseline after one year and at the end of follow-up were evaluated. RESULTS: 57 patients were included, with a median follow-up of four years (IQR, 2-7.2 years). The biochemical remission rate was 45.6%, 33.33% achieved biochemical control, and 12.28% attained biochemical cure at the end of follow-up. A progressive and statistically significant decrease was observed in the comparison of the concentrations of IGF-1, IFG-1 x ULN, and baseline GH at one year and at the end of follow-up. Both cavernous sinus invasion and elevated baseline IGF-1 x ULN concentrations were associated with an increased risk of biochemical non-remission. CONCLUSION: Radiosurgery (CyberKnife) is a safe and effective technique in the adjuvant treatment of GH-producing tumors. Elevated levels of IGF x ULN before radiosurgery and invasion of the cavernous sinus by the tumor could be predictors of biochemical non-remission of acromegaly.

3.
Biomedicines ; 11(3)2023 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-36979787

RESUMEN

BACKGROUND: Fatigue is a common symptom in hypothyroidism; however, the effect of levothyroxine on fatigue has been little studied. The aim of this study was to evaluate the effect of levothyroxine on fatigue in Latino patients with primary hypothyroidism, as well as the association of TSH and free T4 (FT4) with the severity and persistence of fatigue. METHODS: A prospective study was performed in 92 patients with primary hypothyroidism. Fatigue severity scale (FSS) scores and clinical and biochemical characteristics before and at 6 months of levothyroxine were evaluated. RESULTS: After 6 months of levothyroxine, a reduction in FSS (53 (47-57) vs. 36 (16-38); p = 0.001) and fatigue frequency (45.7% vs. 26.1%; p = 0.008) was evident. Both before and after 6 months of levothyroxine, there was a positive correlation of the FSS score with TSH and a negative correlation with FT4. Persistent fatigue was associated with a pretreatment FSS score (r = 0.75; p = 0.001) and diabetes (r = 0.40; p = 0.001). An FSS > 34 (RR 3.9 (95% CI 1.43-10.73; p = 0.008)), an FSS > 36 (RR 3.23 (95% CI 1.21-8.6; p = 0.019)), and diabetes (RR 5.7 (95% CI 1.25-9.6; p = 0.024)) before treatment were risk factors for persistent fatigue. CONCLUSIONS: Levothyroxine improved fatigue in most patients. Diabetes and an FSS score >34 or >36 before treatment were risk factors for persistent fatigue.

4.
J. bras. nefrol ; 45(1): 77-83, Jan.-Mar. 2023. tab
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1430651

RESUMEN

Abstract Objective: To evaluate hypothalamic-pi- tuitary-gonadal (HPG) axis alterations at 1 and 12 months after kidney transplan- tation (KT) and their association with in- sulin resistance. Methods: A retrospective clinical study was conducted in a tertiary care center in kidney transplantation recipients (KTRs) aged 18- 50 years with primary kidney disease and stable renal graft function. LH, FSH, E2/T, and HOMA-IR were assessed at 1 and 12 months after KT. Results: Twenty-five KTRs were included; 53% were men, and the mean age was 30.6±7.7 years. BMI was 22.3 (20.4-24.6) kg/m2, and 36% had hypogonadism at 1 month vs 8% at 12 months (p=0.001). Re- mission of hypogonadism was observed in all men, while in women, hypogonadotropic hypogonadism persisted in two KTRs at 12 months. A positive correlation between go- nadotrophins and age at 1 and 12 months was evident. Fifty-six percent of patients had insulin resistance (IR) at 1 month and 36% at 12 months (p=0.256). HOMA-IR showed a negative correlation with E2 (r=- 0.60; p=0.050) and T (r=-0.709; p=0.049) at 1 month, with no correlation at 12 months. HOMA-IR at 12 months after KT correlated positively with BMI (r=0.52; p=0.011) and tacrolimus dose (r=0.53; p=0.016). Conclusion: Successful KT restores the HPG axis in the first year. Hypogonadism had a negative correlation with IR in the early pe- riod after KT, but it was not significant at 12 months.


Resumo Objetivo: Avaliar as alterações do eixo hipotálamo-hipófise-gonadal (HHG) em 1 e 12 meses após transplante renal (TR) e sua associação com a resistência à insulina. Métodos: Foi realizado um estudo clínico retrospectivo em um centro de cuidados terciários em receptores de transplante renal (RTR) com idade entre 18-50 anos com doença renal primária e função do enxerto renal estável. LH, FSH, E2/T e HOMA-IR foram avaliados em 1 e 12 meses após o TR. Resultados: foram incluídos 25 RTR; 53% eram homens e a média de idade foi de 30,6±7,7 anos. O IMC foi de 22,3 (20,4-24,6) kg/m2 e 36% apresentaram hipogonadismo em 1 mês vs 8% aos 12 meses (p=0,001). A remissão do hipogonadismo foi observada em todos os homens, enquanto nas mulheres, o hipogonadismo hipogonadotrófico persistiu em dois RTR aos 12 meses. Ficou evidente uma correlação positiva entre gonadotrofinas e idade em 1 e 12 meses. Cinquenta e seis por cento dos pacientes apresentaram resistência à insulina (RI) em 1 mês e 36% aos 12 meses (p=0,256). O HOMA-IR mostrou uma correlação negativa com E2 (r=-0,60; p=0,050) e T (r=-0,709; p=0,049) em 1 mês, sem correlação em 12 meses. O HOMA-IR aos 12 meses após TR correlacionou-se positivamente com o IMC (r=0,52; p=0,011) e a dose de tacrolimus (r=0,53; p=0,016). Conclusão: O TR bem-sucedido restaura o eixo HHG no primeiro ano. O hipogonadismo apresentou uma correlação negativa com a RI no período inicial após o TR, mas essa correlação não foi significativa aos 12 meses.

5.
J Bras Nefrol ; 45(1): 77-83, 2023.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-35608374

RESUMEN

OBJECTIVE: To evaluate hypothalamic-pi- tuitary-gonadal (HPG) axis alterations at 1 and 12 months after kidney transplan- tation (KT) and their association with in- sulin resistance. METHODS: A retrospective clinical study was conducted in a tertiary care center in kidney transplantation recipients (KTRs) aged 18- 50 years with primary kidney disease and stable renal graft function. LH, FSH, E2/T, and HOMA-IR were assessed at 1 and 12 months after KT. RESULTS: Twenty-five KTRs were included; 53% were men, and the mean age was 30.6±7.7 years. BMI was 22.3 (20.4-24.6) kg/m2, and 36% had hypogonadism at 1 month vs 8% at 12 months (p=0.001). Re- mission of hypogonadism was observed in all men, while in women, hypogonadotropic hypogonadism persisted in two KTRs at 12 months. A positive correlation between go- nadotrophins and age at 1 and 12 months was evident. Fifty-six percent of patients had insulin resistance (IR) at 1 month and 36% at 12 months (p=0.256). HOMA-IR showed a negative correlation with E2 (r=- 0.60; p=0.050) and T (r=-0.709; p=0.049) at 1 month, with no correlation at 12 months. HOMA-IR at 12 months after KT correlated positively with BMI (r=0.52; p=0.011) and tacrolimus dose (r=0.53; p=0.016). CONCLUSION: Successful KT restores the HPG axis in the first year. Hypogonadism had a negative correlation with IR in the early pe- riod after KT, but it was not significant at 12 months.


Asunto(s)
Hipogonadismo , Resistencia a la Insulina , Trasplante de Riñón , Masculino , Humanos , Femenino , Adulto Joven , Adulto , Eje Hipotálamico-Pituitario-Gonadal , Estudios Retrospectivos
6.
Arch. endocrinol. metab. (Online) ; 66(4): 506-511, July-Aug. 2022. tab
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1403232

RESUMEN

ABSTRACT Objective: To evaluate the response to cabergoline (CBG) treatment in patients with non-functioning pituitary adenomas (NFPA). Subjects and methods: Retrospective, single tertiary care center study. A total of 44 patients were treated with 3 mg/week of CBG, 32 after surgical treatment (transsphenoidal surgery [TSS] in 27 and TC in 5 patients) and 12 as primary therapy. Mean age was 59.2 ± 12 years and 23 (52.2%) were women. Response to therapy was ascertained by serial magnetic resonance imaging. The median duration of CBG therapy was 30 months (IQR 24-48). Response to CBG therapy was defined as a greater than 20% reduction in tumor size and volume. Results: A significant reduction in tumor size was documented in 29 patients (66%), whereas in 11 patients (25%) the tumor increased in size and in 4 (9%), it remained stable. Significant tumor shrinkage was documented in 4 (33.3%) of 12 patients treated primarily and in 23 (71.8%) of those treated secondarily. The three-year progression-free survival was 0.61. Conclusion: Cabergoline therapy is effective in reducing tumor growth in over two thirds of patients with NFPA, however 16% of patients will escape to this beneficial effect and will require alternative forms of treatment to halt tumor progression.

7.
Arch Endocrinol Metab ; 66(4): 506-511, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35758837

RESUMEN

Introduction: To evaluate the response to cabergoline (CBG) treatment in patients with non-functioning pituitary adenomas (NFPA). Subjects and methods: Retrospective, single tertiary care center study. A total of 44 patients were treated with 3 mg/week of CBG, 32 after surgical treatment (transsphenoidal surgery [TSS] in 27 and TC in 5 patients) and 12 as primary therapy. Mean age was 59.2 ± 12 years and 23 (52.2%) were women. Response to therapy was ascertained by serial magnetic resonance imaging. The median duration of CBG therapy was 30 months (IQR 24-48). Response to CBG therapy was defined as a greater than 20% reduction in tumor size and volume. Results: A significant reduction in tumor size was documented in 29 patients (66%), whereas in 11 patients (25%) the tumor increased in size and in 4 (9%), it remained stable. Significant tumor shrinkage was documented in 4 (33.3%) of 12 patients treated primarily and in 23 (71.8%) of those treated secondarily. The three-year progression-free survival was 0.61. Conclusion: Cabergoline therapy is effective in reducing tumor growth in over two thirds of patients with NFPA, however 16% of patients will escape to this beneficial effect and will require alternative forms of treatment to halt tumor progression.


Asunto(s)
Adenoma , Neoplasias Hipofisarias , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adenoma/tratamiento farmacológico , Adenoma/patología , Cabergolina/uso terapéutico , Ergolinas/uso terapéutico , Neoplasias Hipofisarias/tratamiento farmacológico , Estudios Retrospectivos
8.
J Clin Med ; 11(10)2022 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-35628907

RESUMEN

The presence of cardio-metabolic and respiratory comorbidities, immunosuppression, and chronic kidney disease have been associated with an increase in mortality from COVID-19. The objective of this study is to establish the risk factors associated with 30-day mortality in a cohort of hospitalized patients with COVID-19. This paper conducts a retrospective and analytical study of patients hospitalized for COVID-19 in a tertiary care center. A Cox proportional hazard analysis was performed to estimate the association of comorbidities with 30-day mortality. A total of 1215 patients with a median age of 59 years were included. In the adjusted Cox proportional hazards regression model, hypothyroidism, D-dimer ≥ 0.8 µg/mL, LHD ≥ 430 IU/L, CRP ≥ 4.83 ng/mL, and triglycerides ≥ 214 mg/dL were associated with an increased risk of death. The presence of a history of hypothyroidism and biomarkers (D-dimer, lactic dehydrogenase, CRP, and triglycerides) were associated with an increase in mortality in the studied cohort.

9.
BMC Med Genomics ; 15(1): 52, 2022 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-35260162

RESUMEN

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.


Asunto(s)
Adenoma , Neoplasias Hipofisarias , Adenoma/metabolismo , Hormona Adrenocorticotrópica/genética , Proteínas Reguladoras de la Apoptosis/genética , Quinasas Ciclina-Dependientes/genética , Quinasas Ciclina-Dependientes/metabolismo , Ciclinas/genética , Ciclinas/metabolismo , Humanos , Insulina , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/metabolismo , Neoplasias Hipofisarias/patología , Proteínas Serina-Treonina Quinasas , Factores de Transcripción/genética , Transcriptoma
10.
Growth Horm IGF Res ; 60-61: 101431, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34740022

RESUMEN

INTRODUCTION: Goiter is very common in patients with acromegaly; its development is correlated to the duration of the disease. Thyroid cells express the IGF-1 receptor and the TSH/IGF-1 interaction has been demonstrated to have a synergistic effect in thyroid cell growth. There is a correlation between IGF-1 levels and the thyroid volume of patients with acromegaly. The aim of this study was to evaluate, in a retrospective case-cohort study of patients with acromegaly, the associated risk factors for thyroid nodules disease in this population. METHODS: This was a case-cohort study matched by age, gender, and growth hormone at diagnosis. Cases consisted of acromegalic patients that developed thyroid nodules during the follow up, and controls consisted in acromegalic patients without thyroid nodules. A Cox proportional hazard estimation was carried out for measure the associated risk factors for thyroid nodules disease in acromegalic patients. A nodular thyroid disease-free survival analysis was estimated using the Kaplan-Meier analysis. RESULTS: We recruited 49 cases and 56 controls. In a multivariate Cox proportional hazard analysis age and IGF-1 ≥ 2.2 x ULN were significantly related with the presence of thyroid nodules [HR of 2.21 (95% CI; 1.15-4.25, p = 0.01)]. Nodularity-free survival rates in patients who had an IGF-1 X ULN ≥ 2.2 was found to be lower in comparison to those who had IGF-1 X ULN < 2.2, according to a Kaplan-Meier survival analysis. CONCLUSIONS: Our findings support that exist more probability to develop thyroid nodular disease in patients with acromegaly that present IGF-1 X ULN ≥ 2.2, suggesting a possible direct effect between the time of exposure to the IGF-1 axis hyperactivity and the genesis of thyroid nodules.


Asunto(s)
Acromegalia/complicaciones , Biomarcadores/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Centros de Atención Terciaria/estadística & datos numéricos , Nódulo Tiroideo/patología , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Nódulo Tiroideo/etiología , Nódulo Tiroideo/metabolismo
11.
Case Rep Endocrinol ; 2021: 5556977, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33981462

RESUMEN

INTRODUCTION: Parathyroidectomy is the curative treatment option in primary hyperparathyroidism (PHPT). The decrease of parathormone (PTH) by 50% or more from levels prior to surgery after excision predicts successful parathyroidectomy. Serum calcium is expected to return to normal within 24-72 hours after the surgery; however, nearly 10% have transient, persistent postoperative hypercalcemia. We present a case report of delayed calcium normalization after successful parathyroidectomy in a 38-year-old patient with PHPT. METHODS: Parathyroidectomy was performed, with evidence of a decrease in PTH levels of more than 50% in the first 24 hours postoperatively compared to presurgical PTH; however, despite curative parathyroidectomy, a delayed calcium normalization was evidenced, with hypercalcemia persistence up to 120 hours postoperatively. RESULTS: After the first month postoperatively, serum calcium remained normal. In conclusion, approximately 10% of patients with curative parathyroidectomy have transient, persistent postoperative hypercalcemia, which is more likely to occur in patients with higher preoperative serum calcium and PTH levels. CONCLUSION: Persistent hypercalcemia after the first month postoperatively is related with persistent PHPT, highlighting the importance of calcium monitoring after parathyroidectomy to predict short-term, medium-term, and long-term outcomes and prognosis.

12.
BMC Infect Dis ; 21(1): 255, 2021 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-33706707

RESUMEN

BACKGROUND: The SARS-CoV-2 pandemic continues to be a priority health problem; According to the World Health Organization data from October 13, 2020, 37,704,153 confirmed COVID-19 cases have been reported, including 1,079,029 deaths, since the outbreak. The identification of potential symptoms has been reported to be a useful tool for clinical decision-making in emergency departments to avoid overload and improve the quality of care. The aim of this study was to evaluate the performances of symptoms as a diagnostic tool for SARS -CoV-2 infection. METHODS: An observational, cross-sectional, prospective and analytical study was carried out, during the period of time from April 14 to July 21, 2020. Data (demographic variables, medical history, respiratory and non-respiratory symptoms) were collected by emergency physicians. The diagnosis of COVID-19 was made using SARS-CoV-2 RT-PCR. The diagnostic accuracy of these characteristics for COVID-19 was evaluated by calculating the positive and negative likelihood ratios. A Mantel-Haenszel and multivariate logistic regression analysis was performed to assess the association of symptoms with COVID-19. RESULTS: A prevalence of 53.72% of SARS-CoV-2 infection was observed. The symptom with the highest sensitivity was cough 71%, and a specificity of 52.68%. The symptomatological scale, constructed from 6 symptoms, obtained a sensitivity of 83.45% and a specificity of 32.86%, taking ≥2 symptoms as a cut-off point. The symptoms with the greatest association with SARS-CoV-2 were: anosmia odds ratio (OR) 3.2 (95% CI; 2.52-4.17), fever OR 2.98 (95% CI; 2.47-3.58), dyspnea OR 2.9 (95% CI; 2.39-3.51]) and cough OR 2.73 (95% CI: 2.27-3.28). CONCLUSION: The combination of ≥2 symptoms / signs (fever, cough, anosmia, dyspnea and oxygen saturation < 93%, and headache) results in a highly sensitivity model for a quick and accurate diagnosis of COVID-19, and should be used in the absence of ancillary diagnostic studies. Symptomatology, alone and in combination, may be an appropriate strategy to use in the emergency department to guide the behaviors to respond to the disease. TRIAL REGISTRATION: Institutional registration R-2020-3601-145, Federal Commission for the Protection against Sanitary Risks 17 CI-09-015-034, National Bioethics Commission: 09 CEI-023-2017082 .


Asunto(s)
COVID-19/diagnóstico , Evaluación de Síntomas , Adulto , Anosmia/virología , Tos/virología , Estudios Transversales , Disnea/virología , Femenino , Fiebre/virología , Cefalea/virología , Humanos , Masculino , México , Persona de Mediana Edad , Pandemias , Estudios Prospectivos
13.
Genes (Basel) ; 11(12)2020 11 27.
Artículo en Inglés | MEDLINE | ID: mdl-33261069

RESUMEN

BACKGROUND: Pituitary adenomas (PA) are the second most common tumor in the central nervous system and have low counts of mutated genes. Splicing occurs in 95% of the coding RNA. There is scarce information about the spliceosome and mRNA-isoforms in PA, and therefore we carried out proteomic and transcriptomic analysis to identify spliceosome components and mRNA isoforms in PA. METHODS: Proteomic profile analysis was carried out by nano-HPLC and mass spectrometry with a quadrupole time-of-flight mass spectrometer. The mRNA isoforms and transcriptomic profiles were carried out by microarray technology. With proteins and mRNA information we carried out Gene Ontology and exon level analysis to identify splicing-related events. RESULTS: Approximately 2000 proteins were identified in pituitary tumors. Spliceosome proteins such as SRSF1, U2AF1 and RBM42 among others were found in PA. These results were validated at mRNA level, which showed up-regulation of spliceosome genes in PA. Spliceosome-related genes segregate and categorize PA tumor subtypes. The PA showed alterations in CDK18 and THY1 mRNA isoforms which could be tumor specific. CONCLUSIONS: Spliceosome components are significant constituents of the PA molecular machinery and could be used as molecular markers and therapeutic targets. Splicing-related genes and mRNA-isoforms profiles characterize tumor subtypes.


Asunto(s)
Adenoma/metabolismo , Neoplasias Hipofisarias/metabolismo , Proteoma , Empalmosomas , Factor Esteroidogénico 1/genética , Factor de Transcripción Pit-1/genética , Transcriptoma , Adenoma/genética , Adenoma/patología , Empalme Alternativo , Biomarcadores de Tumor , Linaje de la Célula , Cromatografía Líquida de Alta Presión , Exones/genética , Ontología de Genes , Hormonas/análisis , Humanos , Nanotecnología , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/patología , Análisis de Componente Principal , Isoformas de Proteínas/biosíntesis , Isoformas de Proteínas/genética , ARN Mensajero/biosíntesis , ARN Neoplásico/biosíntesis , Espectrometría de Masas en Tándem , Factores de Transcripción/análisis
14.
Sci Rep ; 10(1): 19373, 2020 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-33168897

RESUMEN

Pituitary adenomas (PA) are the second most common intracranial tumors. These neoplasms are classified according to the hormone they produce. The majority of PA occur sporadically, and their molecular pathogenesis is incompletely understood. The present transcriptomic and methylomic analysis of PA revealed that they segregate into three molecular clusters according to the transcription factor driving their terminal differentiation. First cluster, driven by NR5A1, consists of clinically non-functioning PA (CNFPA), comprising gonadotrophinomas and null cell; the second cluster consists of clinically evident ACTH adenomas and silent corticotroph adenomas, driven by TBX19; and the third, POU1F1-driven TSH-, PRL- and GH-adenomas, segregated together. Genes such as CACNA2D4, EPHA4 and SLIT1, were upregulated in each of these three clusters, respectively. Pathway enrichment analysis revealed specific alterations of these clusters: calcium signaling pathway in CNFPA; renin-angiotensin system for ACTH-adenomas and fatty acid metabolism for the TSH-, PRL-, GH-cluster. Non-tumoral pituitary scRNAseq data confirmed that this clustering also occurs in normal cytodifferentiation. Deconvolution analysis identify potential mononuclear cell infiltrate in PA consists of dendritic, NK and mast cells. Our results are consistent with a divergent origin of PA, which segregate into three clusters that depend on the specific transcription factors driving late pituitary cytodifferentiation.


Asunto(s)
Epigenoma , Regulación Neoplásica de la Expresión Génica , Proteínas de Neoplasias , Neoplasias Hipofisarias , Transcriptoma , Células Dendríticas/metabolismo , Células Dendríticas/patología , Femenino , Humanos , Células Asesinas Naturales/metabolismo , Células Asesinas Naturales/patología , Masculino , Mastocitos/metabolismo , Mastocitos/patología , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/metabolismo , Neoplasias Hipofisarias/patología
15.
Int J Endocrinol ; 2020: 6913506, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32256576

RESUMEN

Bone mineral metabolism disease, which included persistent hyperparathyroidism, is common after successful kidney transplantation (KT) and is related with negative outcomes in kidney transplant recipients. There is a lack of information about bone mineral metabolism, persistent hyperparathyroidism, and its risk factors in Latin kidney transplant recipients (KTRs). Material and Methods: A retrospective study was conducted in 74 patients aged 18-50 years with evolution of 12 months after KT and estimated glomerular filtration rate (eGFR) >60 ml/min; biochemical data of bone mineral metabolism before and at 1, 3, 6, and 12 months of KT were registered. Results. Age was 33 (IQR 27-37) years; 54% (n = 40) were men. Before KT, all patients had hyperparathyroidism, 40% (n = 30) hypocalcemia, 86% (n = 64) hyperphosphatemia, and 42% (n = 31) hyperphosphatasemia. After KT, an increase of calcium and a diminution of PTH, phosphorus, and alkaline phosphatase were corroborated (p=0.001). All patients had hypovitaminosis D (deficiency: 91% (n = 67); insufficiency: 9% (n = 7)); 40% (n = 30) had persistent hyperparathyroidism at 12 months. Hyperphosphatasemia before KT (OR = 4.17 (95% CI: 1.21-14.44); p=0.04), hyperparathyroidism at 6 months (OR = 1.84 (95% CI; 1.67-2.06); p=0.02), hypovitaminosis D at 6 months (OR = 3.94 (95% CI: 1.86-17.9); p=0.01), and hyperphosphatasemia at 6 months (OR = 1.47 (95% CI: 1.07-2.86); p=0.03) were risk factors for persistent hyperparathyroidism at 12 months after KT. Conclusion. Persistent hyperparathyroidism at 6 months, hypovitaminosis D, and hyperphosphatasemia are risk factors for persistent hyperparathyroidism at 1 year of KT in Latin population.

16.
Int J Endocrinol ; 2019: 2356580, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31781206

RESUMEN

OBJECTIVE: To evaluate cardiovascular risk, metabolic profile, low urinary tract symptoms (LUTS), and sexual function in patients with nonfunctional pituitary macroadenoma (NFPMA) and hypogonadotropic hypogonadism with testosterone therapy (TTh). METHODS: A retrospective clinical study at a tertiary care center was performed in 101 men with NFPMA, HH, and TTh; metabolic profile, cardiovascular risk, International Prostate Symptoms Score (IPSS), and International Index of Erectile Function 5 (IIEF-5) scores were evaluated before initiation of TTh and at the last checkup with TTh. RESULTS: Age was 49.3 ± 8.8 years; T before TTh was 195 ng/mL (101-259) vs. 574 (423-774) at the last checkup. The time of TTh administration was 34 months (12-72). An increase in triglyceride levels (200 (153-294) vs. 174 (134-233) mg/dL; p=0.03), dyslipidemia (40% vs. 52%; p=0.03), and MetS (25% vs. 34%; p=0.05) was corroborated. A statistical difference in the Globorisk score and cardiovascular (CV) risk stratification was not found. IIEF-5 score was 15.5 ± 6.5 vs. 17.8 ± 5.3 (p=0.11). An improvement in penetration quality (2.0 ± 1.5 vs. 2.6 ± 1.3; p=0.05), erection after penetration (1.8 ± 1.2 vs. 2.5 ± 1.6; p=0.02), completion of intercourse (1.8 ± 1.2 vs. 2.4 ± 1.3; p=0.03), and satisfaction of sexual intercourse (1.8 ± 1.3 vs. 2.5 ± 1.5; p=0.01) was evidenced. IPSS score was 6 (IQR 2-10) vs. 7 (IQR 4-12); p=0.30. A lower rate of intermittency (14% vs. 3%; p=0.02), urgency (39% vs. 16%; p=0.01), and episodes of nocturia (18% vs. 4%; p=0.02) was found. An increase of hematocrit (44.1 ± 4.4 vs. 47.3 ± 4.4%; p=0.001), hemoglobin (14.9 ± 1.4 vs. 15.9 ± 1.4 g/dL; p=0.001), and prostatic specific antigen (0.59 (0.43-1.19) vs. 0.82 (0.45-1.4) ng/mL; p=0.02) was evidenced during TTh. CONCLUSION: TTh in young men with NFPMA improves LUTS, sexual function, and some metabolic parameters, and it is relatively safe in the prostatic context.

17.
Endocrine ; 65(2): 386-392, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31098940

RESUMEN

BACKGROUND AND PURPOSE: Conformal, fractionated radiation therapy (XRT) is variably used as a treatment alternative for active acromegaly patients, usually, after failed pituitary surgery. Our objective was to evaluate the long-term efficacy and safety of XRT using strict criteria of biochemical control. SETTING, DESIGN, PATIENTS, AND METHODS: Retrospective cohort study of 94 patients (73 women, mean age at radiation 53.16 ± 12.9 years) attending a specialized multidisciplinary clinic between 1998 and 2014 with a mean duration of follow-up of 12.9 ± 7.3 years. RESULTS: A basal growth hormone < 1 ng/mL and an IGF-1 < 1.2 × the upper limit of normal was achieved by 41% and 50.8%, respectively, at 5 years of follow-up, and by 44% and 66%, respectively, 10 years after XRT. Median tumor volume decreased significantly from 904 mm3 at baseline to 424 mm3 upon last follow-up (p = 0.01). The prevalence of central hypogonadism, central hypocortisolism, and central hypothyroidism increased from 18%, 35%, and 35% at baseline, to 38%, 53%, and 64%, respectively, after 10 years of follow-up. One patient was diagnosed with a meningioma and another one developed optic neuritis. No cerebrovascular events were recorded, and all patients are currently alive. CONCLUSION: XRT is an effective and reasonably safe means of controlling acromegalic activity. Its main disadvantages are the time required to achieve biochemical control and the development of anterior pituitary hormone deficiencies.


Asunto(s)
Acromegalia/radioterapia , Radioterapia Conformacional/métodos , Acromegalia/sangre , Adulto , Anciano , Femenino , Estudios de Seguimiento , Hormonas/sangre , Humanos , Masculino , Persona de Mediana Edad , Radioterapia Conformacional/efectos adversos , Resultado del Tratamiento
18.
Rev Med Inst Mex Seguro Soc ; 57(1): 48-55, 2019 Apr 01.
Artículo en Inglés, Español | MEDLINE | ID: mdl-31071255

RESUMEN

Background: Non-functional pituitary adenomas (NFPAs) present low growth rates; however, some are aggressive and invasive. In 2017 the World Health Organization recognized clinically aggressive adenomas as "high-risk pituitary adenomas". These include the sparsely granulated somatotroph adenoma, the Crooke's cell adenoma, the silent corticotroph adenoma and the plurihormonal Pit-1-positive adenoma (subtype 3). Clinical case: 25-year-old woman who presented oligomenorrhea, increased weight, decreased visual acuity and chronic headache. Biochemical and imaging evaluation showed a NFPA. Transsphenoidal surgery was performed with complete resection of lesion, and during short-term follow-up it was observed recurrence, which is why the patient needed two more interventions. The immunohistochemistry reported: ACTH ++ 90%, prolactin ++ 20%, GH ++ 5%, CKAE1-AE3 +++ 90%, Ki-67 10%. The final diagnosis was plurihormonal adenoma, since the immunohistochemical analysis was positive for more than one pituitary hormone and suggested two distinct cell lineages: Pit-1 and Tpit, both recognized as aggressive adenomas. Conclusions: This case report highlights the significance of a comprehensive immunohistochemical study, which includes transcriptional factors to classify cell lineage, in order to predict aggressiveness and provide personalized treatment.


Introducción: los adenomas hipofisarios no funcionantes (AHNF) presentan una baja tasa de crecimiento; sin embargo, algunos son agresivos e invasivos. En 2017 la Organización Mundial de la Salud denominó los adenomas de comportamiento clínico agresivo como "tumores hipofisarios de alto riesgo", incluyendo los adenomas del somatotropo escasamente granulados, los adenomas de células de Crooke, los silentes de corticotropo y los adenomas plurihormonal Pit-1 positivo (subtipo 3). Caso clínico: mujer de 25 años de edad con oligoamenorrea, aumento de peso, disminución del campo visual y cefalea crónica. La evaluación bioquímica y de imagen correspondió a un AHNF. Se realizó cirugía transesfenoidal con resección completa de la lesión y durante el seguimiento a corto plazo se observó recurrencia tumoral, por lo que ameritó dos intervenciones más. La inmunohistoquímica reportó: ACTH ++ 90%, prolactina ++ 20%, GH ++ 5%, CKAE1-AE3 +++ 90%, Ki-67 10%. El diagnóstico definitivo correspondió a un adenoma plurihormonal, debido a que la inmunohistoquímica fue positiva para la expresión de más de una hormona hipofisaria, con sugerencia de contenido celular con dos linajes distintos, tanto de Pit-1 como de Tpit, ambos reportados como adenomas agresivos. Conclusiones: este caso resalta la importancia de una inmunohistoquímica completa que incluya factores de transcripción que permitan clasificar el linaje celular para predecir agresividad y proporcionar un tratamiento individualizado.


Asunto(s)
Adenoma/diagnóstico , Biomarcadores de Tumor/metabolismo , Adenoma Hipofisario Secretor de Hormona del Crecimiento/diagnóstico , Adenoma/metabolismo , Adulto , Femenino , Adenoma Hipofisario Secretor de Hormona del Crecimiento/metabolismo , Humanos , Inmunohistoquímica
19.
J Thyroid Res ; 2018: 9461079, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30581552

RESUMEN

BACKGROUND: The primary hyperparathyroidism (PHPT) is a common disease for the endocrinologist. The concomitant thyroid disease and differentiated thyroid cancer (DTC) appear to be more frequent in patients with PHPT than in the general population. The aim of this study was to characterize patients with symptomatic PHPT with and without DTC and analyze frequency and risk factors. METHODS: We consecutively studied patients with symptomatic PHPT diagnosed and treated at our center between 2013 and 2015. Patients with subclinical and syndromic forms of PHPT were excluded. Clinical and biochemical characteristics of patients with and without DTC were compared and risk factors were determined. All patients were studied with thyroid ultrasound and thyroid gammagraphy with TC-MIBI. Two expert surgeons performed all the surgical procedures. RESULTS: In 59 patients included, we found 12 cases of PTC (20.3%). The final histopathological report of the PTC was 7 cases of follicular variant, 2 cases of oncocytic variant, 2 cases of classic variant, and 1 case of columnar cells variant of PTC. Patients with thyroid cancer were older than patients without thyroid cancer (62 ± 9.5 versus 52 ± 15.8, p = 0.03). Higher preoperative levels of iPTH were associated with PTC (p=0.03) [OR 5.16 (95% CI: 1.08-24.7)]. CONCLUSION: PTC is frequent in patients with symptomatic PHPT. Thyroid nodules in patients with symptomatic PHPT must be studied before parathyroidectomy. In symptomatic PHPT, higher level concentration of parathormone (PTH) was associated with higher risk of DTC.

20.
Int J Endocrinol ; 2018: 2852710, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30224919

RESUMEN

CONTEXT: An elevated incidence of type 2 diabetes and cardiovascular disease (CVD) has been reported in patients with nonfunctional pituitary macroadenoma (NFPMA). There is no information about metabolic syndrome and cardiovascular risk in patients with NFPMA in our population. OBJECTIVE: Analyze the metabolic syndrome (MetS) components and estimate cardiovascular risk in patients with NFPMA. DESIGN AND SETTING: Retrospective study, at the tertiary care center. PATIENTS AND METHODS: 71 patients with NFPMA treated according to a preestablished multimodal protocol. MAIN OUTCOME MEASURES: Prevalence of diabetes, hypertension, high cholesterol, obesity, and cardiovascular risk and its relationship with the clinical and biochemical characteristics. RESULTS: The prevalence of diabetes, hypertension, high cholesterol, and obesity at diagnosis was 30%, 27%, 48%, and 85% and did not change upon the last visit. The prevalence of MetS changes from 54 to 48% (p = 0.001). NFPMA patients showed a significant increase risk for high total cholesterol (SMR 1.68, 95% CI 1.28-2.17, p = 0.001) and diabetes (SMR 3.19, 95% CI 2.19-4.49, p = 0.01). According to Globorisk, the male gender was an evidence of high CVD before (81% versus 18%, p = 0.01) and after (72% versus 28%, p = 0.01) multimodal treatment. CONCLUSION: A high prevalence of cardiovascular and metabolic disease and a high cardiovascular risk were evidenced in patients with NFPMA, especially in men. Risk factors such as the personal history of hypertension and dyslipidemia could explain the foregoing, so the control and treatment of metabolic parameters and cardiovascular risk should be an integral part of the follow-up of these patients.

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