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1.
Endocr J ; 70(3): 323-332, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-36464271

RESUMO

Immune checkpoint inhibitors (ICIs) frequently cause immune-related adverse events (irAEs) that often involve endocrine organs. Pembrolizumab and atezolizumab are currently administered in combination with chemotherapy for several malignancies. Although transient thyrotoxicosis within 6 weeks after the first ICI dose is the typical course of thyroid irAEs with ICI monotherapy, we encountered a unique course of a thyroid irAE in a patient who received combination therapy consisting of pembrolizumab plus pemetrexed and carboplatin. Delayed onset of thyrotoxicosis occurred at 22 weeks after the first dose of pembrolizumab. To understand more about this curious event, we conducted a retrospective cohort study of the following groups: pembrolizumab monotherapy (Pem-mono), pembrolizumab plus chemotherapy (Pem-combi), atezolizumab monotherapy (Atezo-mono), and atezolizumab plus chemotherapy (Atezo-combi). There were no differences in the incidence of overt thyroid irAEs: Pem-mono, 12 of 151 patients (7.9%) versus Pem-combi, 4 of 56 patients (7.1%) (p = 0.85) and Atezo-mono, 5 of 27 patients (18.5%) versus Atezo-combi, 5 of 57 patients (8.8%) (p = 0.20). Through detailed analyses of patients with thyrotoxicosis, we found some patients with delayed-onset thyroid irAE, defined as development at 16 weeks or more after the first ICI dose. Delayed-onset thyroid irAEs were only observed in the combination therapy groups: Pem-combi or Atezo-combi, 3 of 8 patients versus Pem-mono or Atezo-mono, 0 of 10 patients. Our observation that thyroid irAE development can be delayed with ICIs when used in combination with chemotherapy suggests longer monitoring of thyroid function is needed to avoid missing irAEs.


Assuntos
Antineoplásicos Imunológicos , Neoplasias , Tireotoxicose , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias/terapia , Tireotoxicose/induzido quimicamente
2.
Tohoku J Exp Med ; 239(2): 89-94, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27212224

RESUMO

Mitochondrial diabetes mellitus is a subtype of diabetes linked to mutations in mitochondrial DNA. In patients with mitochondrial diabetes mellitus, the effect of glycemic control on the serum concentrations of fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) has not been evaluated. FGF21 and GDF15 have been reported to be useful biomarkers for the diagnosis and severity assessment of mitochondrial diseases like mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Recent studies have shown FGF21 acts in an endocrine fashion to regulate glucose and lipid metabolism in type 2 diabetes mellitus, while the exact biological functions of GDF15 remain unknown. Although mitochondrial diabetes mellitus is commonly found in cases with mitochondrial diseases, the comparison of FGF21 and GDF15 levels between those with and without diabetes has not been performed. Here, we report a 24-year-old woman with mitochondrial diabetes mellitus, who showed a high level of serum FGF21, but not serum GDF15, at diagnosis. In our case, liraglutide, a glucagon-like peptide-1 receptor agonist, added to insulin glargine was effective for her glycemic control and showed no adverse effects, including gastrointestinal symptoms and hypoglycemia, during a 14-week observation. The successful glycemic control caused a decrease in the FGF21 level, without affecting the GDF15 level. Thus, we should consider patients' glycemic control levels in using FGF21 values for the diagnosis of mitochondrial diseases. In addition, sustained GDF15 levels during glycemic treatment in our case suggest the usefulness of GDF15 as a marker for clinical severity of muscle-manifested mitochondrial diseases.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Fatores de Crescimento de Fibroblastos/sangue , Fator 15 de Diferenciação de Crescimento/sangue , Hiperglicemia/sangue , Doenças Mitocondriais/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Hiperglicemia/complicações , Doenças Mitocondriais/complicações , Admissão do Paciente , Alta do Paciente , Adulto Jovem
3.
J Diabetes Investig ; 15(7): 874-881, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38426367

RESUMO

AIMS/INTRODUCTION: Diet directly affects glucose metabolism, and eating behavior is influenced by various daily life stressors. This study was conducted to investigate the relationship between common psychosomatic stressors on endocrine hormones and eating behavior in patients with type 2 diabetes. MATERIALS AND METHODS: This cross-sectional study was performed in 40 patients with type 2 diabetes. Resting hormone blood sampling and four self-reported questionnaires were employed. RESULTS: Patients who scored higher on the 'anger/hostility' (AH) subcategory of the profile of mood state (POMS) questionnaire had significantly higher serum cortisol (ß = 0.40, P = 0.01 by least squares adjusted for age and sex). In the eating behavior questionnaire, the subcategories of 'feeling of hunger/satiation' (ß = 0.49, P < 0.01) and 'eating as diversion' (ß = 0.39, P = 0.03) were associated with higher serum cortisol. Resting morning cortisol levels were higher in participants who rated high on the POMS-AH and in those who reported 'irritated when hungry' and 'tend to eat when irritated or anxious'. Sleep quality showed no association with eating behavior. CONCLUSIONS: Mood state is associated with eating behavior. Anger increases cortisol levels and may lead to compulsive eating. Various forms of hostility are important factors in appetite control and increased cortisol secretion, and can be an impediment to successful dietary self-management in patients with type 2 diabetes. Thus, assessment of mood state and control of negative mood are important therapeutic targets in diabetes management.


Assuntos
Diabetes Mellitus Tipo 2 , Comportamento Alimentar , Transtornos da Alimentação e da Ingestão de Alimentos , Autogestão , Humanos , Masculino , Feminino , Estudos Transversais , Diabetes Mellitus Tipo 2/psicologia , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/sangue , Pessoa de Meia-Idade , Japão , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Comportamento Alimentar/psicologia , Idoso , Hidrocortisona/sangue , Inquéritos e Questionários , Adulto
4.
J Diabetes Investig ; 13(1): 177-184, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34191406

RESUMO

AIMS/INTRODUCTION: An efficient screening strategy for identification of cognitive dysfunction remains a clinical issue in the management of elderly adults with diabetes. A magnetic resonance imaging voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) has been developed as an automated brain morphometry system that includes the hippocampus. We carried out a multicenter retrospective study to evaluate the utility of VSRAD for screening cognitive dysfunction in diabetes outpatient clinics. MATERIALS AND METHODS: We enrolled patients with diabetes aged >65 years who underwent brain magnetic resonance imaging scans for the purpose of a medical checkup between November 2018 and May 2019. Patients who were already suspected or diagnosed with mild cognitive impairment and/or dementia as well as those with a history of cerebrovascular disease were excluded. RESULTS: A total of 67 patients were enrolled. Five patients were diagnosed with mild cognitive impairment or dementia (clinical cognitive dysfunction). Patients with clinical cognitive dysfunction showed a significantly higher z-score in VSRAD analysis (2.57 ± 0.47 vs 1.15 ± 0.55, P < 0.01). The sensitivities and specificities for diagnosis of clinical cognitive dysfunction were 80 and 48% for the Mini-Mental State Examination, 100 and 89% for the z-score, and 100 and 90% for the combination of the Mini-Mental State Examination score and z-score, respectively. CONCLUSIONS: VSRAD analysis can distinguish patients with clinical cognitive dysfunction in the elderly with diabetes, and also shows reasonable sensitivity and specificity compared with the Mini-Mental State Examination alone. Thus, VSRAD analysis can be useful for early identification of clinical cognitive dysfunction in the elderly with diabetes.


Assuntos
Disfunção Cognitiva/diagnóstico , Diabetes Mellitus/diagnóstico por imagem , Avaliação Geriátrica/métodos , Imageamento por Ressonância Magnética , Programas de Rastreamento/métodos , Idoso , Idoso de 80 Anos ou mais , Instituições de Assistência Ambulatorial , Disfunção Cognitiva/etiologia , Diabetes Mellitus/psicologia , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Masculino , Estudos Retrospectivos , Sensibilidade e Especificidade
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