RESUMO
BACKGROUND: Bilateral adrenal infarction is rare and only a small number of cases have been reported so far. Adrenal infarction is usually caused by thrombophilia or a hypercoagulable state, such as antiphospholipid antibody syndrome, pregnancy, and coronavirus disease 2019. However, adrenal infarction with myelodysplastic/myeloproliferative neoplasm (MDS/MPN) has not been reported. CASE PRESENTATION: An 81-year-old man with a sudden severe bilateral backache presented to our hospital. Contrast-enhanced computed tomography (CT) led to the diagnosis of bilateral adrenal infarction. Previously reported causes of adrenal infarction were all excluded and a diagnosis of MDS/MPN-unclassifiable (MDS/MPN-U) was reached, which was considered to be attributed to adrenal infarction. He developed a relapse of bilateral adrenal infarction, and aspirin administration was initiated. Partial primary adrenal insufficiency was suspected as the serum adrenocorticotropic hormone level was persistently high after the second bilateral adrenal infarction. CONCLUSION: This is the first case of bilateral adrenal infarction with MDS/MPN-U encountered. MDS/MPN has the clinical characteristics of MPN. It is reasonable to assume that MDS/MPN-U may have influenced bilateral adrenal infarction development, considering the absence of thrombosis history and a current comorbid hypercoagulable disease. This is also the first case of recurrent bilateral adrenal infarction. It is important to carefully investigate the underlying cause of adrenal infarction once adrenal infarction is diagnosed, as well as to assess adrenocortical function.
Assuntos
COVID-19 , Doenças Mieloproliferativas-Mielodisplásicas , Neoplasias , Masculino , Humanos , Idoso de 80 Anos ou mais , Doenças Mieloproliferativas-Mielodisplásicas/diagnóstico , Recidiva , MutaçãoRESUMO
PURPOSE: To report our findings in a case of lens fragment-induced uveitis associated with supernormal flicker electroretinograms (ERGs) twenty months after the cataract surgery. METHODS: This is an observational case report. Full-field flicker ERGs were recorded with the RETeval system. Optical coherence tomography (OCT) and slit-lamp biomicroscopy were used to assess the uveitis during the follow-up period. RESULTS: A 70-year-old man, who had undergone cataract surgery 20 months earlier, visited our hospital with a complaint of decreased vision in his right eye. Slit-lamp biomicroscopy revealed corneal edema and a lens fragment was detected in the inferior part of the anterior chamber. OCT showed cystoid macular edema, and flicker ERGs showed a marked increase in the amplitude and a delay in the implicit time in the right eye. These abnormalities of the flicker ERGs improved gradually after the removal of lens fragment and application of topical anti-inflammatory medications. CONCLUSION: Our case of lens-induced uveitis had supernormal flicker ERG amplitudes. Clinicians should be aware that eyes with uveitis can have larger-than-normal ERG amplitudes.
Assuntos
Extração de Catarata , Catarata , Uveíte , Idoso , Eletrorretinografia , Humanos , Masculino , Tomografia de Coerência Óptica , Regulador Transcricional ERG , Uveíte/diagnóstico , Uveíte/etiologiaRESUMO
Ectopic ACTH syndrome (EAS) due to a prostate small cell carcinoma (SCC) is very rare with only 26 cases reported to date and has a poor prognosis. We here describe another case of this disorder that was clinically typical based on prior reports as it showed hypercortisolemia and severe hypokalemia with multiple metastasis. However, our current case of prostate SCC causing EAS is the first to display negative immunostaining for ACTH despite detectable POMC mRNA expression in the primary lesion. ACTH immunonegativity is thought to be associated with a more aggressive disease course and a poorer prognosis although there are few studies of the underlying mechanisms. We explored two possibilities for this finding in our current patient: aberrant POMC processing prevented immunodetection with an anti-ACTH antibody; and the ACTH content per cell was below the threshold for immunodetection due to its rapid secretion or low synthesis. The aberrant processing theory was thought to be less likely because of immunonegative findings even using anti-POMC/ACTH antibodies. As the plasma ACTH levels in our patient were comparable with those reported for previous immunopositive prostate EAS cases, we speculated that the depletion of ACTH may be caused not only by rapid secretion but also by low production levels as a sign of de-differentiation. De-differentiation may therefore explain the mechanism underlying the negative correlation between immunoreactivity for ACTH in EAS and disease aggressiveness. We believe that our present findings will be of use in future prospective studies aimed at confirming the mechanism of immunonegativity.
Assuntos
Síndrome de ACTH Ectópico/etiologia , Carcinoma de Células Pequenas/complicações , Próstata/metabolismo , Neoplasias da Próstata/complicações , Síndrome de ACTH Ectópico/metabolismo , Síndrome de ACTH Ectópico/patologia , Hormônio Adrenocorticotrópico/sangue , Idoso , Carcinoma de Células Pequenas/metabolismo , Carcinoma de Células Pequenas/patologia , Humanos , Masculino , Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologiaRESUMO
BACKGROUND/AIMS: Obesity and diabetes are intimately interrelated, and are independent risk factors for kidney disease. Overactivation of mineralocorticoid receptor (MR) is implicated in end organ damage of both pathologies. But the underlying mechanism of MR activation in kidney remains uncertain. We explored the involvement of Rac1, which we previously identified as a ligand-independent MR activator, in renal MR activation in vitro and in vivo. METHODS: We evaluated the MR activity and Rac1 activity under high-glucose stimulation using luciferase reporter system and glutathione S-transferase pull-down assay in cultured mesangial cells. To elucidate the role of Rac1 in vivo, we employed KKA(y), a mouse model of obesity-related type 2 diabetes, which spontaneously developed massive albuminuria and distinct glomerular lesions accompanied by increased plasma aldosterone concentration. RESULTS: High-glucose stimulation increased Rac1 activity and MR transcriptional activity in cultured mesangial cells. Overexpression of constitutively active Rac1 activated MR, and glucose-induced MR activation was suppressed by overexpression of dominant negative Rac1 or Rac inhibitor EHT1864. In KKA(y), renal Rac1 was activated, and nuclear MR was increased. EHT1864 treatment suppressed renal Rac1 and MR activity and mitigated renal pathology of KKA(y) without changing plasma aldosterone concentration. CONCLUSION: Our results suggest that MR activation plays an important role in the nephropathy of KKA(y) mice, and that glucose-induced Rac1 activation, in addition to hyperaldosteronemia, contributes to their renal MR activation. Along with MR blockade, Rac inhibition may potentially be a preferred option in the treatment of nephropathy in obesity-related diabetic patients.
Assuntos
Nefropatias Diabéticas/metabolismo , Obesidade/metabolismo , Receptores de Mineralocorticoides/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Albuminúria/metabolismo , Albuminúria/prevenção & controle , Animais , Western Blotting , Linhagem Celular , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/genética , Glucose/farmacologia , Humanos , Imuno-Histoquímica , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/complicações , Obesidade/genética , Tamanho do Órgão/efeitos dos fármacos , Pironas/farmacologia , Quinolinas/farmacologia , Receptores de Mineralocorticoides/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Proteínas rac1 de Ligação ao GTP/genéticaRESUMO
BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) plays pivotal roles in the pathogenesis of chronic kidney disease (CKD) progression. Aliskiren, a direct renin inhibitor, inhibits the rate-limiting step of the RAAS without any alternative pathway. It is proven to reduce albuminuria in CKD patients treated with angiotensin blockade. However, there are few reports which evaluate the advantage of aliskiren as the first-line drug against CKD progression in RAAS-activated hypertensive patients. METHODS: Tsukuba hypertensive mice (THM), double transgenic mice carrying both the human renin and human angiotensinogen genes, were fed a high-salt diet and treated with hydraladine, ramipril and aliskiren for 10 weeks. Blood pressure and urinary albumin excretion were measured every 2 weeks during the experimental period. We evaluated renal histological changes and gene expression. Plasma angiotensin concentration was measured to evaluate the RAAS inhibitory effect. RESULTS: High-salt-loaded THM showed severe hypertension and renal injury. All antihypertensive drugs suppressed blood pressure and prevented renal disease progression. RAAS blockade showed a higher renoprotective effect than hydraladine despite an equivalent blood pressure lowering effect. Aliskiren exhibited even stronger renoprotection than ramipril. Plasma angiotensin concentration was increased in THM fed both normal salt and high salt. Hydraladine did not alter the plasma angiotensin concentration. Ramipril significantly decreased angiotensin II concentration. Aliskiren treatment almost completely suppressed angiotensin I and resulted in lower angiotensin II concentration than ramipril treatment. CONCLUSION: Aliskiren prevents renal disease progression by suppressing both angiotensin I and II in RAAS-activated pathology. Our data suggest the application of a renin inhibitor for preventing kidney disease progression in CKD patients.
Assuntos
Amidas/farmacologia , Angiotensina II/sangue , Angiotensina I/sangue , Angiotensinogênio/metabolismo , Anti-Hipertensivos/farmacologia , Fumaratos/farmacologia , Hipertensão/tratamento farmacológico , Nefropatias/prevenção & controle , Rim/efeitos dos fármacos , Sistema Renina-Angiotensina/efeitos dos fármacos , Renina/antagonistas & inibidores , Cloreto de Sódio na Dieta , Albuminúria/tratamento farmacológico , Albuminúria/metabolismo , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Angiotensinogênio/genética , Animais , Pressão Sanguínea/efeitos dos fármacos , Citoproteção , Modelos Animais de Doenças , Progressão da Doença , Regulação para Baixo , Humanos , Hidralazina/farmacologia , Hipertensão/sangue , Hipertensão/genética , Hipertensão/patologia , Hipertensão/fisiopatologia , Rim/metabolismo , Rim/patologia , Rim/fisiopatologia , Nefropatias/sangue , Nefropatias/genética , Nefropatias/patologia , Nefropatias/fisiopatologia , Camundongos , Camundongos Transgênicos , Ramipril/farmacologia , Renina/genética , Renina/metabolismo , Sistema Renina-Angiotensina/genética , Fatores de TempoRESUMO
Purpose: To determine the characteristics of an eye that developed acute hydrops while being treated for infectious keratitis. Observation: A 35-year-old man presented with pain and blurred vision in his left eye. He had undergone cataract surgery seven years earlier and was being treated for poorly controlled atopic dermatitis. The decimal best-corrected visual acuity (BCVA) of the left eye was 0.01. Slit-lamp microscopy showed conjunctival injection, corneal opacification, and a corneal ulcer. The patient was diagnosed with infectious keratitis and was treated with topical and systemic antibiotics. During the hospitalization, the patient was noted to rub his eyes frequently and vigorously. Five days after the first visit, the cornea protruded markedly, and the stroma surrounding the ulcerated area was edematous. These findings led to a diagnosis of acute hydrops.Penetrating keratoplasty was performed to prevent corneal perforation. Histopathological study of the excised cornea showed stromal edema, infiltration of leukocytes, and a tear in Descemet's membrane. Unfortunately, the patient developed endophthalmitis the day after the surgery. The anterior chamber was irrigated with antibiotics, and antibiotics were also injected into the vitreous. The endophthalmitis gradually subsided, and two years after the surgery, the patient's decimal BCVA had improved to 0.6. Conclusion and importance: Vigorous eye rubbing in cases of infectious keratitis can induce acute hydrops, and timely surgical intervention is recommended.
RESUMO
Experiments with hyperaldosteronemic animals suggest that, despite lowering plasma aldosterone, salt worsens renal injury by paradoxical activation of the mineralocorticoid receptor (MR). Salt and aldosterone synergistically contribute to renal impairment through Rac1-mediated activation of the MR, but whether angiotensin II also promotes renal injury through this mechanism is unknown. Here, we placed angiotensin II-overproducing double transgenic Tsukuba hypertensive mice on a low- or high-salt intake for 6 weeks and treated some animals with adrenalectomy, the MR antagonist eplerenone, the Rac inhibitor EHT1864, or hydralazine. High-salt intake, but not low-salt intake, led to hypertension and prominent kidney injury. Adrenalectomy prevented angiotensin II/salt-induced nephropathy in mice receiving high-salt intake, which was recapitulated by aldosterone supplementation, suggesting the involvement of aldosterone/MR signaling. Plasma aldosterone levels, however, were lower in high- than low-salt conditions. Instead, angiotensin II/salt-evoked MR activation associated with Rac1 activation and was not dependent on plasma aldosterone level. Both EHT1864 and eplerenone repressed the augmented MR signaling and mitigated kidney injury with partial but significant reduction in BP with high-salt intake. Hydralazine similarly reduced BP, but it neither suppressed the Rac1-MR pathway nor ameliorated the nephropathy. Taken together, these results show that angiotensin II and salt accelerate kidney injury through Rac1-mediated MR activation. Rac inhibition may be a promising strategy for the treatment of CKD.
Assuntos
Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Aldosterona/metabolismo , Angiotensina II/efeitos adversos , Receptores de Mineralocorticoides/metabolismo , Cloreto de Sódio na Dieta/efeitos adversos , Injúria Renal Aguda/fisiopatologia , Adrenalectomia/métodos , Aldosterona/sangue , Análise de Variância , Angiotensina II/farmacologia , Animais , Western Blotting , Modelos Animais de Doenças , Eplerenona , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos , Distribuição Aleatória , Reação em Cadeia da Polimerase em Tempo Real/métodos , Transdução de Sinais , Cloreto de Sódio na Dieta/farmacologia , Espironolactona/análogos & derivados , Espironolactona/farmacologia , Estatísticas não Paramétricas , Proteínas rac1 de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/metabolismoRESUMO
PURPOSE: To report our findings in a case of pellucid marginal corneal degeneration (PMCD) in the left eye and keratoconus (KC) in the right eye, and to review earlier cases of PMCD and KC. OBSERVATIONS: A 45-year-old woman visited our hospital with a complaint of reduced vision in her right eye. She was predisposed to allergies since childhood and had a habit of rubbing her eyes. Based on the results of the corneal topographic study, we diagnosed her with KC in the right eye and PMCD in the left eye. We prescribed a rigid, gas permeable contact lens and treated her allergic conjunctivitis with ocular medications. Three years after her initial visit, she developed a corneal perforation in the left eye. The perforation was closed by conservative treatment consisting of therapeutic soft contact lens wear. One year after the cornea healed, the corneal astigmatism in the left eye was about one-half of what it was before the corneal perforation. Her corrected visual acuity improved to 1.0 with conventional spectacles. CONCLUSIONAND IMPORTANCE: We found a difference in the progression of KC and PMCD even when they occurred in same individual. We suggest that the atopic predisposition, which is considered a risk factor for acute hydrops in KC, to be a risk factor for acute hydrops and corneal perforation in eyes with PMCD.
RESUMO
CONTEXT: There are inconsistent results and insufficient evidence as to whether an association exists between the size and aldosterone-producing ability of aldosterone-producing adenomas. OBJECTIVE: We further investigated this possible association retrospectively. METHODS: A total of 142 cases of primary aldosteronism diagnosed as unilateral by adrenal venous sampling at 2 referral centers between 2009 and 2019 were included. We classified these individuals into small and large tumor groups using a diameter of 14â mm as a cutoff. This size was the median diameter of the tumor on the affected side of the adrenal gland. We compared plasma aldosterone concentration (PAC), plasma renin activity (PRA), PAC to PRA ratio, PAC from a saline infusion test (SIT), urinary aldosterone secretion (uAld), and serum potassium as indices of aldosterone-producing ability between the 2 groups. In some cases, we conducted histopathological evaluations and detection of the KCNJ5 mutation. RESULTS: PAC, PAC to PRA ratio, PAC from SIT, and uAld were higher and serum potassium was lower in the large tumor group. PAC, PAC from SIT, uAld, and serum potassium significantly correlated with tumor diameter. PRA was not associated with tumor diameter. Clear cell-dominant cases were more common in the large tumor group, while cases showing a strong expression of CYP11B2 were not significantly different between the groups. KCNJ5 mutations tended to be more common in the large tumor group. CONCLUSION: The higher aldosterone-producing ability in larger adenomas can be used to infer the responsible lesion and disease type.
Assuntos
Adenoma , Adenoma Adrenocortical , Hiperaldosteronismo , Humanos , Aldosterona , Hiperaldosteronismo/diagnóstico , Estudos Retrospectivos , Adenoma Adrenocortical/metabolismo , Adenoma/patologia , Potássio , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/genéticaRESUMO
PURPOSE: To report our findings in three cases of an inflamed conjunctival nevus whose size and degree of pigmentation were reduced by topical antiallergic and immunosuppressive ophthalmic solutions. METHODS: Observational case series. Three patients with inflamed conjunctival nevus were examined by slit-lamp biomicroscopy, and the findings before and after the treatments were compared. RESULTS: All three patients had a slightly pigmented and edematous conjunctival tumor at the corneal limbal area. The tumors were hyperemic, and papillae and follicles were present on the superior conjunctiva in all patients. All of the patients had an allergic predisposition. The antiallergic treatment not only resolved the hyperemia and edema of the palpebral conjunctiva, but also reduced the tumor size. In one case, the topical antiallergic agent alone led to a reduction of the tumor size. A combination of topical antiallergic agent and topical immunosuppressant was effective in reducing the tumor size and degree of pigmentation in the other two patients. CONCLUSION: The hyperemia and pigmentation in eyes with inflamed conjunctival nevus can be resolved by topical antiallergic agent and topical immunosuppressant without resection of the tumor.
RESUMO
Immune checkpoint inhibitors (ICIs) are potent therapeutic options for many types of advanced cancer. The expansion of ICIs use however has led to an increase in immune-related adverse events (irAEs). Secondary adrenal insufficiency (AI) can be life-threatening especially in patients with delayed diagnosis. We retrospectively investigated secondary AI in ICI-treated patients. A total of 373 cancer patients treated with ICIs were included and evaluated. An adrenocorticotropic hormone (ACTH) deficiency was described in 13 patients. Among 24 patients with a combination of nivolumab and ipilimumab therapy, 7 patients (29%) developed secondary AI in a median time of 8 weeks during the combination therapy and 2 of 15 patients (13%) developed isolated ACTH deficiency during maintenance nivolumab monotherapy following the combination therapy. More than half of the patients (4/7) with a combination therapy-induced multiple anterior hormone deficiencies was diagnosed as secondary AI based on regular ACTH and cortisol tests with slight subjective symptoms. Secondary AI can arise frequently and rapidly in cancer patients receiving a combination ICI therapy, and thus we speculate active surveillance of AI using regular ACTH and cortisol tests during the combination therapy might be useful for avoiding life-threatening conditions due to secondary AI.
Assuntos
Insuficiência Adrenal/diagnóstico , Inibidores de Checkpoint Imunológico/efeitos adversos , Ipilimumab/efeitos adversos , Neoplasias/tratamento farmacológico , Nivolumabe/efeitos adversos , Insuficiência Adrenal/sangue , Insuficiência Adrenal/induzido quimicamente , Insuficiência Adrenal/prevenção & controle , Hormônio Adrenocorticotrópico/sangue , Hormônio Adrenocorticotrópico/deficiência , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores/sangue , Diagnóstico Tardio , Feminino , Humanos , Hidrocortisona/sangue , Hidrocortisona/deficiência , Inibidores de Checkpoint Imunológico/administração & dosagem , Ipilimumab/administração & dosagem , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Neoplasias/sangue , Neoplasias/imunologia , Neoplasias/patologia , Nivolumabe/administração & dosagem , Estudos RetrospectivosRESUMO
To determine the parameters of the anterior segment of eyes that are significantly associated with the refractive error in healthy young Japanese university students. This was a cross-sectional observational study of 229 healthy Japanese university students (men: women,147:82) whose age ranged between 20 to 29 years. Univariate and multivariate linear regression analyses were performed to identify the factors that were significantly correlated with the refractive error. The independent variables included age, sex, axial length, anterior chamber depth, corneal diameter, curvature of anterior surface of cornea, and central corneal thickness. The mean refractive error (spherical equivalent) was -4.1 ± 2.7 diopters (D) with a range of -12.5 to +0.5 D, and the mean axial length was 25.4 ± 1.3 mm with a range of 22.4 to 29.0 mm. Pearson univariate correlation analysis found that the refractive error was significantly and negatively correlated with the axial length (R = -0.82, P < 0.001), deeper anterior chamber (R = -0.30, P < 0.001), and larger corneal diameter (R = -0.21, P = 0.001). Multiple regression analysis showed that the refractive error was significantly associated with a longer axial length (P < 0.001), a deeper anterior chamber (P < 0.001), and a flatter corneal curvature (P < 0.001).The biometric values of the anterior segment of the eyes should make the eye more hyperopic which would reduce the myopia-inducing lengthening of the axial length.
Assuntos
Câmara Anterior/patologia , Biometria , Erros de Refração/patologia , Estudantes , Universidades , Adulto , Comprimento Axial do Olho , Feminino , Humanos , Japão , Masculino , Análise Multivariada , Adulto JovemRESUMO
Hypertension is a leading contributor to cardiovascular mortality worldwide. Despite this, its underlying mechanism(s) and the role of excess salt in cardiorenal dysfunction are unclear. Previously, we have identified cross-talk between mineralocorticoid receptor (MR), a nuclear transcription factor regulated by the steroid aldosterone, and the small GTPase Rac1, which is implicated in proteinuric kidney disease. We here show that high-salt loading activates Rac1 in the kidneys in rodent models of salt-sensitive hypertension, leading to blood pressure elevation and renal injury via an MR-dependent pathway. We found that a high-salt diet caused renal Rac1 upregulation in salt-sensitive Dahl (Dahl-S) rats and downregulation in salt-insensitive Dahl (Dahl-R) rats. Despite a reduction of serum aldosterone levels, salt-loaded Dahl-S rats showed increased MR signaling in the kidneys, and Rac1 inhibition prevented hypertension and renal damage with MR repression. We further demonstrated in aldosterone-infused rats as well as adrenalectomized Dahl-S rats with aldosterone supplementation that salt-induced Rac1 and aldosterone acted interdependently to cause MR overactivity and hypertension. Finally, we confirmed the key role of Rac1 in modulating salt susceptibility in mice lacking Rho GDP-dissociation inhibitor α. Therefore, our data identify Rac1 as a determinant of salt sensitivity and provide insights into the mechanism of salt-induced hypertension and kidney injury.