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In this real-world pilot study, we evaluated the metabolic and endocrinological effects in patients with adult growth hormone deficiency (AGHD) who switched from daily growth hormone (GH) replacement therapy to weekly GH replacement therapy using somapacitan. Eleven patients with AGHD, whose medical treatment aside from GH replacement therapy did not change, were enrolled. We investigated the metabolic and endocrinological parameters between at switching and 6 months after switching from daily GH formulation to somapacitan. The results showed that body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), fasting plasma glucose (FPG), and liver functions were significantly improved 6 months after switching compared to those at switching (each P < .05). Besides, the improvement in HOMA-IR was significantly associated with the period of daily GH replacement therapy before switching (P = .048), while age, sex, improvement in BMI or liver functions, presence of any hormonal deficiency, and the existence of any hormonal replacement therapy significantly associated (P > .05). In addition, switching to GH replacement therapy did not affect endocrinological parameters. In conclusion, this study might indicate that weekly GH replacement therapy with somapacitan could have more beneficial points than daily GH replacement therapy. Considering the cohort of this study was small, future studies with larger cohorts should be necessary to confirm the results of this study.
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Endocrinología , Hormona de Crecimiento Humana , Humanos , Adulto , Proyectos Piloto , Terapia de Reemplazo de Hormonas , Hormona de Crecimiento Humana/uso terapéuticoRESUMEN
Combination strategies of KRAS inhibition with immunotherapy in treating advanced or recurrent colorectal carcinoma (CRC) may need to be assessed in circulating tumour cells (CTCs) to achieve better clinical outcomes. This study aimed to investigate the genomic variations of KRAS in CTCs and matched CRC tissues and compared mRNA expression of KRAS and CTLA-4 between wild-type and KRAS-mutated CTCs and CRC tissues. Clinicopathological correlations were also compared. Six known mutations of KRAS were identified at both codon 12 and codon 13 (c.35G>T/G12V, c.35G>A7/G12D, c.35G>C/G12A, c.34G>A/G12S, c.38G>C/G13A, and c.38G>A/G13D). Three CTC samples harboured the identified mutations (16.7%; 3/18), while fifteen matched primary tumour tissues (65.2%, 15/23) showed the mutations. CTCs harbouring the KRAS variant were different from matched CRC tissue. All the mutations were heterozygous. Though insignificant, CTLA-4 mRNA expression was higher in patients carrying KRAS mutations. Patients harbouring KRAS mutations in CTCs were more likely to have poorly differentiated tumours (p = 0.039) and with lymph node metastasis (p = 0.027) and perineural invasion (p = 0.014). KRAS mutations in CTCs were also significantly correlated with overall pathological stages (p = 0.027). These findings imply the genetic basis of KRAS with immunotherapeutic target molecules based on a real-time platform. This study also suggests the highly heterogeneous nature of cancer cells, which may facilitate the assessment of clonal dynamics across a single patient's disease.
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Neoplasias Colorrectales , Células Neoplásicas Circulantes , Humanos , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Antígeno CTLA-4/genética , Recurrencia Local de Neoplasia/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Mutación , Codón , ARN Mensajero/genéticaRESUMEN
Pituitary apoplexy is an uncommon syndrome that often results in spontaneous hemorrhage or infarction of pituitary tumors or glands. We previously reported pituitary apoplexy occurred most frequently in nonfunctional pituitary adenomas among all types of pituitary incidentalomas. In the present study, we aimed to investigate the characteristics of pituitary apoplexy in patients with incidental nonfunctional pituitary adenomas. 65 patients with pituitary incidentaloma were enrolled. All patients underwent clinical/endocrinological/pathological investigations. As a result, 33 patients were diagnosed with nonfunctional pituitary adenomas. Of these, 12.1% of patients had pituitary apoplexy. There was no difference in tumor diameter, age, or sex between the apoplexy and the non-apoplexy groups. However, the liver enzymes aspartate transaminase and alanine aminotransferase were significantly higher, and plasma sodium and chloride levels were significantly lower in the apoplexy group than in the non-apoplexy group (each Pâ <â .05). In addition, low-density lipoprotein-cholesterol was significantly higher in the apoplexy group than in the non-apoplexy group (Pâ <â .05). Besides, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, and prolactin deficiencies were significantly more frequent in the apoplexy group than in the non-apoplexy group (each Pâ <â .05), and growth hormone and adrenocorticotropic hormone deficiencies were more frequent in the apoplexy group than in the non-apoplexy group (Pâ =â .09 and.08, respectively). Furthermore, tumor diameter was not associated with pituitary apoplexy, whereas thyroid-stimulating hormone, luteinizing hormone, and follicle-stimulating hormone deficiencies were significantly associated with the apoplexy group (each Pâ <â .05). Hence, the present study indicated that pituitary apoplexy could not be related to tumor diameter. Moreover, hormonal deficiencies, hepatic dysfunction, hyponatremia or hypochloremia, and dyslipidemia might be indicators of pituitary apoplexy. There could be the possibility the treatment for dyslipidemia prevents pituitary apoplexy.
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Adenoma , Apoplejia Hipofisaria , Neoplasias Hipofisarias , Humanos , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/patología , Adenoma/complicaciones , Adenoma/patología , Hormona Folículo Estimulante , Hormona Luteinizante , Tirotropina , Apoplejia Hipofisaria/etiología , Apoplejia Hipofisaria/diagnósticoRESUMEN
Hypothalamic adrenal insufficiency (AI) is a rare but distinct type of AI. The leading cause of hypothalamic AI is a secondary side-effect of exogenous steroid intake, particularly in large amounts and/or long-term periods. The next cause would be the effect of the tumor in the hypothalamic lesions. We show here 9 cases of hypothalamic AI without any disorder on imagings and a history of steroid administration. All patients had general fatigue; 7 patients (77.8%) had a history of hypoglycemia; 5 patients (55.6%) had a history of hypotension. None of the patients had hyponatremia, hyperkalemia, or eosinophilia. Their morning plasma adrenocorticotropic hormone (ACTH) value was low at 8.5 ± 4.2 pg/mL, and serum cortisol value was low at 4.5 ± 1.3 µg/dL. All patients demonstrated normal responses during the corticotropin-releasing hormone loading (CRH) test but inadequate responses during the insulin tolerance test (ITT). After hydrocortisone replacement therapy, their morning plasma ACTH and serum cortisol values were significantly recovered (P < .05). Moreover, more than half of the patients were fine after discontinuing hydrocortisone replacement therapy. These results indicate that this unique type of hypothalamic AI has a curable clinical course making hydrocortisone replacement therapy a novel therapeutic option.
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Insuficiencia Suprarrenal , Hidrocortisona , Insuficiencia Suprarrenal/tratamiento farmacológico , Insuficiencia Suprarrenal/etiología , Hormona Adrenocorticotrópica , Hormona Liberadora de Corticotropina , Humanos , InsulinaRESUMEN
Ultrasound examination of the thyroid is useful for preoperative assessment of thyroid nodules including papillary thyroid carcinoma. The examination mainly is to determine the malignant potential of thyroid nodule(s). There are different systems to predict malignant potential in the thyroid nodules and cervical lymph nodes by ultrasound. Ultrasound is used in conjunction with fine-needle aspiration to diagnosis papillary thyroid carcinoma. It is used as guidance to locate the sites to obtain the samples for diagnosis and research in papillary thyroid carcinoma.
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Carcinoma Papilar , Neoplasias de la Tiroides , Nódulo Tiroideo , Carcinoma Papilar/diagnóstico por imagen , Carcinoma Papilar/patología , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Cáncer Papilar Tiroideo/diagnóstico por imagen , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/patologíaRESUMEN
Fine-needle aspiration biopsy is the most common method for preoperative diagnosis of thyroid carcinomas including papillary carcinoma. The procedure is best performed with ultrasound by operator with professional skill and knowledge. Several guidelines recommend the indication of fine-needle aspiration concerning the pattern of ultrasound and size of nodules. Besides, fine-needle aspiration biopsy of lymph nodes should be performed if malignancies are suspected. Fine-needle aspiration biopsy of thyroid gland is mostly safe, but complications such as blood extravasation-related complications, acute thyroid enlargement, infection in thyroid gland, and pneumothorax could occur. The most frequent complications are blood extravasation-related complications, which could be fatal. Similarly, acute thyroid enlargement could also be severe. To conclude, fine-needle aspiration biopsy is useful and should be performed under the precise indication and the updated knowledge of complications including the way of handling if they occur.
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Carcinoma Papilar , Neoplasias de la Tiroides , Nódulo Tiroideo , Biopsia con Aguja Fina/métodos , Carcinoma Papilar/patología , Humanos , Neoplasias de la Tiroides/patología , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/patologíaRESUMEN
Context: Mutations in the NR0B1 gene, also well-known as the DAX1 gene, are known to cause congenital adrenal hypoplasia associated with hypogonadotropic hypogonadism. The abnormal NR0B1 protein fails to suppress the transcription of promoters of steroidogenic enzymes, which are also targets of NR5A1 protein, also well-known as Ad4BP/SF-1 protein. Since NR5A1 and NR0B1 have antagonistic effects on steroidogenesis, the loss of function due to NR0B1 mutations may be compensated by inducing loss of function of NR5A1 protein. Patient: A middle-aged man was diagnosed with congenital adrenal hypoplasia associated with hypogonadotropic hypogonadism and genetic analysis revealed him to have a novel NR0B1 mutation, c.1222C>T(p.Gln408Ter). Methods: NR0B1 activity was evaluated in CLK1/4 inhibitor-treated 293T cells via immunoblotting and luciferase assays of the STAR promoter. Results: TG003 treatment suppressed NR5A1 protein function to compensate for the mutant NR0B1 showing inhibited suppression of transcription. Immunoblotting analyses showed that the phosphorylation status of NR5A1 at Ser203 was attenuated by the CLK1/4 inhibitor. Conclusion: The specific reduction of NR5A1 phosphorylation by a CLK1/4 inhibitor may alleviate developmental defects in patients with NR0B1 mutations.
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Neoplasias de las Glándulas Suprarrenales , Endocrinología/tendencias , Feocromocitoma , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Neoplasias de las Glándulas Suprarrenales/genética , Neoplasias de las Glándulas Suprarrenales/terapia , Carcinogénesis/metabolismo , Carcinogénesis/patología , Terapia Combinada/métodos , Terapia Combinada/tendencias , Endocrinología/métodos , Humanos , Terapia Molecular Dirigida/métodos , Terapia Molecular Dirigida/tendencias , Mutación , Feocromocitoma/diagnóstico , Feocromocitoma/genética , Feocromocitoma/terapia , Cuidados Preoperatorios/métodos , Cuidados Preoperatorios/tendencias , Pronóstico , Receptores Acoplados a Proteínas G/genética , Medición de Riesgo , Succinato Deshidrogenasa/genética , Hipoxia Tumoral/genética , Hipoxia Tumoral/fisiologíaRESUMEN
Vascular endothelial growth factor (VEGF) is important in pathogenesis of different cancers. The aim of this study is to investigate the relationships between different VEGFs and clinicopathological factors in patients with phaeochromocytomas. Twenty patients (10 men; 10 women) with non-hereditary, non-metastatic phaeochromocytomas were examined for VEGF mRNA expressions by polymerase chain reaction. The expressions were correlated with the clinical and pathological factors of the patients. In addition, mouse double minute 2 (MDM2) expression in these tumours were studied by immunohistochemistry. High expressions of VEGF-A, VEGF-B, and VEGF-C mRNA were detected in 11 (55%), 9 (45%), and 9 (45%) of the tumours respectively. High expression of VEGF-A in phaeochromocytomas was significantly correlated with the tumour size (p=0.025) but did not correlate with patients' age, gender, and tumour laterality. Besides, there was a trend of VEGF-A expression correlated with MDM2 expression (p=0.064). On the other hand, expressions of VEGF-B and VEGF-C were not significantly correlated with tumour size, patients' age, gender, tumour laterality, and MDM2 expression. In addition, high expressions of VEGF-B and VEGF-A were associated with increase of tumour size (p=0.042). Co-expression of different VEGFs did not correlate with MDM2 expression. To conclude, there is a role for VEGF-A/VEGF-B/VEGF-C in the pathogenesis of non-hereditary, non-metastatic phaeochromocytomas.
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Feocromocitoma/metabolismo , Factores de Crecimiento Endotelial Vascular/metabolismo , Neoplasias de las Glándulas Suprarrenales/metabolismo , Neoplasias de las Glándulas Suprarrenales/patología , Adulto , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neovascularización Patológica/metabolismo , Feocromocitoma/patología , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , ARN Mensajero/análisis , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor B de Crecimiento Endotelial Vascular/metabolismo , Factor C de Crecimiento Endotelial Vascular/metabolismoRESUMEN
PURPOSE OF REVIEW: Anaplastic thyroid carcinoma is a type of thyroid carcinoma with the most aggressive biological behaviour amongst thyroid cancer. Here, we review the current genomic and the impacts of advances in therapies to improve the management of patients with the cancer. RECENT FINDINGS: Common mutations being identified in anaplastic thyroid carcinoma are p53 and TERT promoter mutations. Other common mutated genes included BRAF, RAS, EIF1AX, PIK3CA, PTEN and AKT1, SWI/SNF, ALK and CDKN2A. Changes in expression of different microRNAs are also involved in the pathogenesis of anaplastic thyroid carcinoma. Curative resection combined with radiotherapy and combination chemotherapies (such as anthracyclines, platins and taxanes) has been shown to have effects in the treatment of some patients with anaplastic thyroid carcinoma. Newer molecular targeted therapies in clinical trials target mostly the cell membrane kinase and downstream proteins. These include targeting the EGFR, FGFR, VEGFR, c-kit, PDGFR and RET on the cell membrane as well as VEGF itself and the downstream targets such as BRAF, MEK and mTOR. Immunotherapy is also being tested in the cancer. Updated knowledge of genomic as well as clinical trials on novel therapies is needed to improve the management of the patients with this aggressive cancer.
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Terapia Molecular Dirigida/métodos , Carcinoma Anaplásico de Tiroides/genética , Carcinoma Anaplásico de Tiroides/terapia , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/terapia , Genómica , Humanos , Carcinoma Anaplásico de Tiroides/patología , Neoplasias de la Tiroides/patologíaRESUMEN
INTRODUCTION: Cinacalcet is a calcimimetic that modulates the functions of calcium-sensing receptor and is currently used to treat patients with primary hyperparathyroidism (PHPT). Although it was reported that cinacalcet treatment reduced the size of hyperplastic parathyroid glands in patients with secondary hyperparathyroidism, whether or not cinacalcet treatment can reduce the size of parathyroid adenomas in patients with PHPT has been unknown. MATERIALS AND METHODS: We recruited nine (male: one, female: eight) patients with PHPT due to parathyroid adenomas who did not undergo parathyroidectomy. Cinacalcet was administered at a dose of 50 mg/day, and we evaluated the size of parathyroid adenomas (width × thickness) (mm2) using ultrasonography before and after 6 months of cinacalcet treatment. RESULTS: The mean age of the subjects was 58.1 ± 7.2 years old, and the mean serum intact parathyroid hormone (PTH) concentration was 134.8 ± 8.7 pg/ml. All participants showed hypercalcemia and osteopenia. After 6 months, the mean size of parathyroid adenomas was significantly decreased (baseline: 73.8 ± 33.4 mm2 vs. after 6 months: 52.5 ± 25.0 mm2, p = 0.045). Thus, 6-month cinacalcet treatment induced a 29% size reduction in parathyroid adenomas. Furthermore, the serum intact PTH concentration before cinacalcet treatment was positively correlated with the reduction in the size of parathyroid adenomas. CONCLUSION: The present study revealed that cinacalcet treatment reduces the size of parathyroid adenomas in patients with PHPT. The accumulation of more PHPT cases with cinacalcet therapy is required to confirm this finding.
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Adenoma/complicaciones , Adenoma/tratamiento farmacológico , Cinacalcet/uso terapéutico , Hiperparatiroidismo Primario/complicaciones , Neoplasias de las Paratiroides/complicaciones , Neoplasias de las Paratiroides/tratamiento farmacológico , Adenoma/sangre , Adenoma/diagnóstico por imagen , Calcio/sangre , Cinacalcet/efectos adversos , Femenino , Humanos , Hiperparatiroidismo Primario/sangre , Hiperparatiroidismo Primario/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Neoplasias de las Paratiroides/sangre , Neoplasias de las Paratiroides/diagnóstico por imagen , Paratiroidectomía , Carga Tumoral , UltrasonografíaRESUMEN
Due to its rarity, adrenal hemorrhage is difficult to diagnose, and its precise etiology has remained unknown. One of the pivotal mechanisms of adrenal hemorrhage is the thrombosis of the adrenal vein, which could be due to thrombophilia. However, detailed pathological evaluation of resected adrenal glands is usually required for definitive diagnosis. Here, we report a case of a cortisol-secreting adenoma with concomitant foci of hemorrhage due to antiphospholipid syndrome diagnosed both clinically and pathologically. In addition, the tumor in this case was pathologically diagnosed as cortisol-secreting adenoma, although the patient did not necessarily fulfill the clinical diagnostic criteria of full-blown Cushing or sub-clinical Cushing syndrome during the clinical course, which also did highlight the importance of detailed histopathological investigations of resected adrenocortical lesions.
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Adenoma , Síndrome Antifosfolípido , Síndrome de Cushing , Adenoma/complicaciones , Adenoma/diagnóstico , Adenoma/cirugía , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Síndrome de Cushing/complicaciones , Síndrome de Cushing/etiología , Hemorragia/complicaciones , Hemorragia/etiología , Humanos , HidrocortisonaRESUMEN
Anaplastic thyroid carcinoma is an uncommon carcinoma representing 1 to 4% of all thyroid cancers. The carcinoma is most common in females of the eight decades. It is a locally advanced cancer with frequent infiltration of surrounding organs, blood vessels and skin of neck. Paraneoplastic manifestations could occur. Approximately half of the patients with anaplastic thyroid carcinoma had distant metastasis with lung and brain as the most frequent sites of metastasis. The median survival of patients with anaplastic thyroid carcinoma reported was from 1 to 6 months. The terminology of the cancer in World Health Organization is "anaplastic thyroid carcinoma" rather than "undifferentiated thyroid carcinoma". In the latest American Joint Committee on Cancer (AJCC) TNM staging system for anaplastic thyroid carcinoma, there are updates on T and N categories. To conclude, updated knowledge of clinicopathological features, classification, pathological staging will improve our understanding of the cancer and will help in the management of the patients with this aggressive cancer.
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Estadificación de Neoplasias , Carcinoma Anaplásico de Tiroides/patología , Neoplasias de la Tiroides/patología , Biopsia , Humanos , Valor Predictivo de las Pruebas , Carcinoma Anaplásico de Tiroides/clasificación , Carcinoma Anaplásico de Tiroides/epidemiología , Carcinoma Anaplásico de Tiroides/terapia , Neoplasias de la Tiroides/clasificación , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/terapia , Resultado del Tratamiento , Organización Mundial de la SaludRESUMEN
Half of the patients with phaeochromocytoma have glucose intolerance which could be life-threatening as well as causing postoperative hypoglycemia. Glucose intolerance is due to impaired insulin secretion and/or increased insulin resistance. Impaired insulin secretion is caused by stimulating adrenergic α2 receptors of pancreatic ß-cells and increased insulin resistance is caused by stimulating adrenergic α1 and ß3 receptors in adipocytes, α1 and ß2 receptors of pancreatic α-cells and skeletal muscle. Furthermore, different affinities to respective adrenergic receptors exist between epinephrine and norepinephrine. Clinical studies revealed patients with phaeochromocytoma had impaired insulin secretion as well as increased insulin resistance. Furthermore, excess of epinephrine could affect glucose intolerance mainly by impaired insulin secretion and excess of norepinephrine could affect glucose intolerance mainly by increased insulin resistance. Glucose intolerance on paraganglioma could be caused by increased insulin resistance mainly considering paraganglioma produces more norepinephrine than epinephrine. To conclude, the difference of actions between excess of epinephrine and norepinephrine could lead to improve understanding and management of glucose intolerance on phaeochromocytoma.
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Neoplasias de las Glándulas Suprarrenales/complicaciones , Intolerancia a la Glucosa/etiología , Paraganglioma/complicaciones , Feocromocitoma/complicaciones , Animales , Intolerancia a la Glucosa/patología , HumanosRESUMEN
PURPOSE: In this retrospective study, we investigated the status and validity of endoscopic transsphenoidal surgery (eTSS) for pituitary incidentalomas (PIs) as well as the value of basing the indication for surgery on the PI guidelines. METHODS: Patients who underwent eTSS at Fukuoka University Chikushi Hospital between 2012 and 2018 were divided into the PI group and the non-PI group in accordance with the PI guideline of the Endocrine Society and their clinicopathological characteristics and outcomes were compared and analyzed. RESULTS: A total of 59 patients were enrolled, with 35 patients in the PI group and 24 patients in the non-PI group. The diagnoses in the PI group were of non-functioning pituitary adenoma (NFPA) (nâ=â12, 34%), gonadotropin-producing pituitary adenoma (nâ=â8, 23%), Rathke cleft cyst (nâ=â7, 20%), meningioma (nâ=â4, 11%), and growth hormone-producing pituitary adenoma (nâ=â3, 9%); those in the non-PI group were of NFPA (nâ=â6, 25%), gonadotropin-producing pituitary adenoma (nâ=â3, 13%), Rathke cleft cyst (nâ=â3, 13%), growth hormone-producing pituitary adenoma (nâ=â3, 13%), and prolactin producing pituitary adenoma (nâ=â3, 13%). Regarding the preoperative factors, 1 patient in the PI group with panhypopituitarism was diagnosed with pituitary apoplexy (pure infarction) of an NFPA. The rates of postoperative anterior pituitary hormonal deficiencies (14% vs 46%, Pâ=â.015), residual tumor size (2â±â5 vs 6â±â7âmm, Pâ=â.008), and reoperation (nâ=â0, 0% vs nâ=â5, 21%, Pâ=â.005) were significantly different between the PI and non-PI groups. CONCLUSIONS: This study showed that, postoperatively, the incidence of anterior pituitary hormonal deficiencies was lower in the PI than in the non-PI group, although it was comparable between the 2 groups before the operation. The patients in the PI group also had smaller residual tumors and a lower risk of reoperation than those in non-PI group. PIs could have a better postoperative clinical outcome than non-PIs when the indication for eTSS is based on preoperative scrutiny according to the PI guidelines and eTSS is performed by an experienced pituitary surgeon. Hence, more aggressive scrutiny and treatment for PIs might be desirable.
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Endocrinología/normas , Endoscopía/métodos , Neoplasias Hipofisarias/cirugía , Guías de Práctica Clínica como Asunto , Adulto , Anciano , Femenino , Humanos , Hallazgos Incidentales , Masculino , Persona de Mediana Edad , Selección de Paciente , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/patología , Hueso Esfenoides/cirugía , Resultado del TratamientoRESUMEN
Anaplastic thyroid cancer (ATC) remains as one of the most aggressive human carcinomas with poor survival rates in patients with the cancer despite therapeutic interventions. Novel targeted and personalized therapies could solve the puzzle of poor survival rates of patients with ATC. In this review, we discuss the role of non-coding RNAs in the regulation of gene expression in ATC as well as how the changes in their expression could potentially reshape the characteristics of ATCs. A broad range of miRNA, such as miR-205, miR-19a, miR-17-3p and miR-17-5p, miR-618, miR-20a, miR-155, etc., have abnormal expressions in ATC tissues and cells when compared to those of non-neoplastic thyroid tissues and cells. Moreover, lncRNAs, such as H19, Human leukocyte antigen (HLA) complex P5 (HCP5), Urothelial carcinoma-associated 1 (UCA1), Nuclear paraspeckle assembly transcript 1 (NEAT1), etc., participate in transcription and post-transcriptional regulation of gene expression in ATC cells. Dysregulations of these non-coding RNAs were associated with development and progression of ATC by modulating the functions of oncogenes during tumour progression. Thus, restoration of the abnormal expression of these miRNAs and lncRNAs may serve as promising ways to treat the patients with ATC. In addition, siRNA mediated inhibition of several oncogenes may act as a potential option against ATC. Thus, non-coding RNAs can be useful as prognostic biomarkers and potential therapeutic targets for the better management of patients with ATC.
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Osteoporosis is a complication of type 2 diabetes mellitus (T2DM). Blockade of receptor activator of nuclear factor kappa-B ligand (RANKL) improves osteoporosis, but might also improve glucose tolerance through reduction of hepatic insulin resistance. However, the effect of denosumab (a human monoclonal antibody of RANKL) upon glycemic and metabolic parameters is controversial. We revealed the effect of denosumab upon glycemic and metabolic parameters for 52 weeks. We evaluated 20 individuals diagnosed with both osteoporosis (male and female: postmenopausal) and T2DM. We measured glycemic and metabolic parameters before and 26/52 weeks after administration of denosumab (60âmg per 26 weeks) without changing any other medication each patient was taking. All patients completed the study without complications and the T-score (lumbar spine and femoral neck) improved significantly from baseline to 52 weeks after denosumab administration (Pâ<â.001, .001, respectively). None of the glycemic parameters changed significantly from baseline to 26 weeks after denosumab administration, but levels of glycated hemoglobin and homeostasis model assessment of insulin resistance improved significantly from baseline to 52 weeks after administration (Pâ=â.019, .008, respectively). The levels of liver enzymes did not change significantly from baseline to 26 weeks after denosumab administration, but levels of aspartate transaminase and alanine aminotransferase improved significantly from baseline to 52 weeks after administration (Pâ=â.014, .004, respectively). None of the markers of lipid metabolism and body mass index changed significantly from baseline to 26/52 weeks after denosumab administration. These data demonstrated that denosumab is useful for T2DM patients with osteoporosis for glycemic control via improvement of insulin resistance. Also, the effect of denosumab might be due to improvement of hepatic function.
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Glucemia/efectos de los fármacos , Conservadores de la Densidad Ósea/farmacología , Conservadores de la Densidad Ósea/uso terapéutico , Denosumab/farmacología , Denosumab/uso terapéutico , Complicaciones de la Diabetes/tratamiento farmacológico , Complicaciones de la Diabetes/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Osteoporosis/metabolismo , Anciano , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Masculino , Osteoporosis/etiología , Ligando RANK/inmunologíaRESUMEN
Pituitary incidentaloma (PI) is a generic term for pituitary tumors that are identified on images acquired for non-malignant conditions. Acromegaly is an extremely rare form of PI. Occasionally, a functional pituitary adenoma (PA) may be misdiagnosed as PI, which may result in a poor clinical outcome. Here we report the first case, to the best of our knowledge, of PI diagnosed as trauma-triggered acromegaly. A 42-year-old man with a chief complaint of head trauma was referred to our hospital after computed tomography (CT) revealed a pituitary tumor. His appearance was suggestive of acromegaly. Mild hypertrophy of the extremities was also observed. Preoperative blood tests, magnetic resonance imaging (MRI), and endocrine tolerance test findings indicated acromegaly. Accordingly, we suspected a growth hormone (GH)-producing PA, and we performed endoscopic transsphenoidal surgery (eTSS). Histopathology showed a densely granulated GH-producing PA, which was also confirmed via immunohistochemistry. Two months after surgery, blood tests showed decreased levels of GH and insulin-like growth factor-1. In addition, a postoperative endocrine tolerance test revealed no abnormalities. There was no recurrence at 24 months after surgery. The findings from this case suggest that PIs can also present as functional adenomas, which can be diagnosed using initial hormone examinations and endocrine tolerance tests. Therefore, thorough endocrine examination is necessary for early diagnosis and treatment and improved patient outcomes.
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There are few reports of pituitary adenomas (PA) mimicking dementia. Delay in disease diagnosis and treatment may result in poor clinical outcome. We experienced a rare case where endoscopic transsphenoidal surgery (eTSS) effectively treated a gonadotroph adenoma mimicking dementia and report on literature considerations. We report the case of a 72-year-old man with chief complaints of cognitive decline, bradykinesia, anorexia, dressing apraxia, and vigor decline over several months. He was admitted to our hospital for scrutiny in a disoriented state. Blood tests showed hyponatremia and thyroid hormone depression. Magnetic resonance imaging showed a pituitary tumor, and preoperative endocrine stress tests showed reduced reactivities of growth hormone, adrenocorticotropic hormone/cortisol, and luteinizing hormone/follicle-stimulating hormone. Symptomatic pituitary adenoma was suspected, and eTSS was performed. The permanent pathological diagnosis was of gonadotroph adenoma. Postoperatively, the hyponatremia, cognitive decline, movement retardation, loss of appetite, dressing apraxia, and limb edema markedly improved. The patient was discharged under hydrocortisone 15 mg/day administration without complications. The endocrine stress test performed 2 months postoperatively showed secondary hypoadrenocorticism, while the other endocrine functions had normalized. No recurrence had occurred by 30 months postoperatively; the medication of hydrocortisone was gradually discontinued and the patient at the time was still being followed as an outpatient with modified Rankin Scale score 0. Secondary hypothyroidism and secondary hypoadrenocorticism due to the pituitary tumor primarily caused the condition. It is important to consider PA in the differential diagnosis of dementia, and early diagnosis and treatment can contribute to a patient's good clinical outcome.
RESUMEN
We present a case of a patient with drug-induced hypersensitivity syndrome (DIHS) caused by salazosulfapyridine combined with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) caused by interstitial pneumonia (IP). A 67-year-old man with a past history of rheumatism (RA) presented with right hemiparalysis and aphasia as the chief complaints. A diagnosis of left embolic cerebral infarction following trial therapy for RA based on computed tomography findings was made, and external decompression was performed. Salazosulfapyridine was newly started on day 7. Dabigatran was started on day 37. On day 41, the patient developed fever. On day 42, edema and erythema appeared on his face, and erythema and rash appeared on his trunk and extremities, with gradual transition to erythroderma. The drug eruption was initially attributed to the dabigatran. Various symptoms of organ dysfunction (enteritis, myocarditis, interstitial pneumonia, hepatic disorder, stomatitis, and others) then appeared and persisted; hence, a diagnosis of DIHS associated with human herpes virus 6 and cytomegalovirus infection induced by salazosulfapyridine was suggested, and the oral administration of salazosulfapyridine was discontinued on day 53. Hyponatremia was observed in association with exacerbation of IP. Due to low serum osmotic pressure and prompt improvement of the serum sodium level by fluid restriction, the SIADH was attributed to IP. In this case, steroid pulse therapy followed by gradual decrease therapy prevented worsening of the condition.