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1.
PLoS One ; 15(11): e0242679, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33237923

RESUMO

PURPOSE: Ectopic Cushing Syndrome (EAS) is a rare condition responsible for about 5-20% of all Cushing syndrome cases. It increases the mortality of affected patients thus finding and removal of the ACTH-producing source allows for curing or reduction of symptoms and serum cortisol levels. The aim of this study is to present a 20-year experience in the diagnosis and clinical course of patients with EAS in a single Clinical Centre in Southern Poland as well as a comparison of clinical course and outcomes depending on the source of ectopic ACTH production-especially neuroendocrine tumors with other neoplasms. METHODS: Twenty-four patients were involved in the clinical study with EAS diagnosed at the Department of Endocrinology between years 2000 and 2018. The diagnosis of EAS was based on the clinical presentation, hypercortisolemia with high ACTH levels, high dose dexamethasone suppression test and/or corticotropin-releasing hormone tests. To find the source of ACTH various imaging studies were performed. RESULTS: Half of the patients were diagnosed with neuroendocrine tumors, whereby muscle weakness was the leading symptom. Typical cushingoid appearance was seen in merely a few patients, and weight loss was more common than weight gain. Patients with neuroendocrine tumors had significantly higher midnight cortisol levels than the rest of the group. Among patients with infections, we observed a significantly higher concentrations of cortisol 2400 levels in gastroenteropancreatic neuroendocrine tumors. Chromogranin A correlated significantly with potassium in patients with neuroendocrine tumors and there was a significant correlation between ACTH level and severity of hypokalemia. CONCLUSION: EAS is not common, but if it occurs it increases the mortality of patients; therefore, it should be taken into consideration in the case of coexistence of severe hypokalemia with hypertension and muscle weakness, especially when weight loss occurs. Because the diagnosis of gastroenteropancreatic neuroendocrine tumor worsens the prognosis-special attention should be paid to these patients.


Assuntos
Síndrome de ACTH Ectópico , Síndrome de ACTH Ectópico/sangue , Síndrome de ACTH Ectópico/diagnóstico , Síndrome de ACTH Ectópico/fisiopatologia , Adolescente , Hormônio Adrenocorticotrópico/sangue , Adulto , Idoso , Síndrome de Cushing/sangue , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/fisiopatologia , Feminino , Humanos , Hidrocortisona/sangue , Hipertensão/sangue , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Hipopotassemia/sangue , Hipopotassemia/diagnóstico , Hipopotassemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/sangue , Debilidade Muscular/diagnóstico , Debilidade Muscular/fisiopatologia , Polônia , Estudos Retrospectivos
2.
Zhonghua Yi Xue Za Zhi ; 100(36): 2822-2827, 2020 Sep 29.
Artigo em Chinês | MEDLINE | ID: mdl-32988141

RESUMO

Objective: To evaluate the changes and diagnostic value of serum dehydroepiandrosterone sulfate (DHEAS) in Cushing's syndrome (CS) with different etiologies. Methods: The study retrospectively recruited patients diagnosed as CS in Drum Tower Hospital affiliated to Nanjing University Medical School between January 2012 and June 2019, including 36 patients (8 males, 28 females, with an average age of 44 years) with Cushing disease (CD) and 64 patients (6 males, 58 females, with an average age of 39 years) with adrenal CS (ACS). Meanwhile, 97 patients diagnosed as nonfunctional adrenal adenoma (NFA) were also included as controls. Clinical characteristics, laboratory data, adrenocorticotropic hormone (ACTH), serum DHEAS level and sex-and age-adjusted DHEAS ratio of the three groups were collected. The sensitivity and specificity of DHEAS and its ratio in differential etiology diagnosis of CS were compared using receiver operating characteristic (ROC) curve analysis. Results: Compared to NFA group, ACS patients had lower DHEAS levels [0.39 (0.39, 0.63) µmol/L vs 2.96 (1.92, 4.60) µmol/L, P<0.01] and lower DHEAS ratio [0.58 (0.27, 0.98) vs 3.95 (3.08, 6.83), P<0.01]. DHEAS [6.49 (4.32, 11.63) µmol/L] and DHEAS ratio [9.17 (4.49, 15.41)] in CD patients were significantly higher compared to those in NFA and ACS patients (all P<0.01). There were 53 ACS patients (82.8%) with suppressed ACTH level (<2.2 pmol/L) and 11 patients (17.2%) with normal/high ACTH level (≥2.2 pmol/L). The level of 24 hour urine free cortisol in normal/high ACTH level group was lower than the suppressed ACTH group [(1 299±511) nmol/24 h vs (1 972±876) nmol/24 h, P=0.04]. No significant differences were found in the DHEAS and DHEAS ratio between the two groups. ROC analysis showed that the area under the curve of serum DHEAS and DHEAS ratio in diagnosing ACS from CD was 0.997 and 0.990, respectively. The optimal cut-off values for DHEAS and its ratio were 2.06 µmol/L and 2.10, respectively. The diagnostic sensitivity and specificity of DHEAS were 97.5% and 100%, and those of DHEAS ratio were 95.0% and 100%, respectively. Conclusion: There are significant differences in serum DHEAS level and DHEAS ratio between ACS and CD patients, which might be used as indicators for the identification of the two main CS etiologies, especially in the identification of ACS patients without plasma ACTH suppression from CD patients.


Assuntos
Síndrome de Cushing/diagnóstico , Adulto , Sulfato de Desidroepiandrosterona , Diagnóstico Diferencial , Feminino , Humanos , Hidrocortisona , Masculino , Estudos Retrospectivos
4.
Klin Lab Diagn ; 65(7): 418-423, 2020 Jun 04.
Artigo em Russo | MEDLINE | ID: mdl-32762179

RESUMO

Immunochemical methods of analysis are traditionally used for diagnosis of various forms of Cushing's syndrome (CS). In the presence of boundary values of hormonal parameters, doubtful situations, a combination of changes both in pituitary and in adrenal glands, it is useful to determine additional differential diagnostic criteria for the diagnosis of various forms of CS. Urinary steroid profiles (USP) were analyzed by gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) for 38 females with adrenal Cushing's syndrome (CSA), 42 females with pituitary CS (CSP) and 25 healthy females (control group). An increase of free cortisol/free cortisone ratio in the urine (UFF/UFE) for CSP patients in comparison of CSA was obtained by HPLC method. Decreased urinary excretion of UFF and UFE by more than 60% after the 8 mg dexamethasone suppression test had 100% sensitivity and specificity of more than 90% for the diagnosis of CSP. GC-MS method in patients with CSA and CSG revealed the peculiarities of androgens, progestins and glucocorticoids metabolism which leaded to obtain specific USP for CS of different genesis. Increased urinary excretions of dehydroepiandrosterone and its metabolites, metabolites of androstenedione, the ratio of sum of cortisol and cortisone tetrahydrometabolites to tetrahydro-11-deoxycortisol (more then 36) in CSP patients compared with CSA are additional signs for differential diagnosis of these diseases. The combination of classical tests and USP obtained by HPLC and GC-MS methods increased the sensitivity and specificity of differential diagnosis of CSA and CSP.


Assuntos
Cromatografia Líquida de Alta Pressão , Cortisona , Síndrome de Cushing , Cortisona/análise , Síndrome de Cushing/diagnóstico , Dexametasona , Diagnóstico Diferencial , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Hidrocortisona
5.
Arch. argent. pediatr ; 118(3): e278-e283, jun. 2020. ilus, tab
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1116944

RESUMO

El incremento de la expectativa de vida con el advenimiento de la terapia antirretroviral de alta eficacia plantea desafíos en cuanto a la toxicidad e interacciones medicamentosas. El síndrome de Cushing exógeno por interacción entre ritonavir y fluticasona inhalada en niños con diagnóstico de infección por virus de la inmunodeficiencia humana y patología pulmonar crónica es infrecuente. Hasta el momento, hay 20 casos reportados. Se describen 3 casos pediátricos con diagnóstico de infección por virus de la inmunodeficiencia humana y patología pulmonar crónica que presentaron síndrome de Cushing exógeno con fluticasona inhalada en dosis habituales por la interacción medicamentosa entre esta y ritonavir. Los pacientes resolvieron el cuadro clínico luego de 2-4 meses de suspensión de la fluticasona y permanecieron asintomáticos en el seguimiento


The increase in life expectancy with the advent of highly effective antiretroviral therapy poses challenges in terms of toxicity and drug interactions. Exogenous Cushing syndrome by interaction between ritonavir and inhaled fluticasone in children diagnosed with human immunodeficiency virus infection and chronic pulmonary pathology is rare. So far, there are 20 cases reported. Three pediatric cases are reported, with a diagnosis of human immunodeficiency virus infection and chronic pulmonary pathology who presented exogenous Cushing syndrome with inhaled fluticasone at usual doses due to drug interaction between it and ritonavir. The patients resolved the clinical Síndrome de Cushing exógeno por interacción medicamentosa de ritonavir y fluticasona inhalada. Reporte de tres casos pediátricos Exogenous Cushing syndrome due to drug interaction of ritonavir and inhaled fluticasone. Report of three pediatric cases picture after 2-4 months of fluticasone suspension and remain asymptomatic in the follow-up.


Assuntos
Humanos , Masculino , Criança , Adolescente , Síndrome de Cushing/diagnóstico , HIV , Ritonavir/uso terapêutico , Síndrome de Cushing/terapia , Fluticasona/efeitos adversos , Fluticasona/uso terapêutico , Pneumopatias
6.
Eur J Endocrinol ; 183(1): G1-G7, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: covidwho-256412

RESUMO

Clinical evaluation should guide those needing immediate investigation. Strict adherence to COVID-19 protection measures is necessary. Alternative ways of consultations (telephone, video) should be used. Early discussion with regional/national experts about investigation and management of potential and existing patients is strongly encouraged. Patients with moderate or severe clinical features need urgent investigation and management. Patients with active Cushing's syndrome, especially when severe, are immunocompromised and vigorous adherence to the principles of social isolation is recommended. In patients with mild features or in whom a diagnosis is less likely, clinical re-evaluation should be repeated at 3 and 6 months or deferred until the prevalence of SARS-CoV-2 has significantly decreased; however, those individuals should be encouraged to maintain social distancing. Diagnostic pathways may need to be very different from usual recommendations in order to reduce possible exposure to SARS-CoV-2. When extensive differential diagnostic testing and/or surgery is not feasible, it should be deferred and medical treatment should be initiated. Transsphenoidal pituitary surgery should be delayed during high SARS-CoV-2 viral prevalence. Medical management rather than surgery will be the used for most patients, since the short- to mid-term prognosis depends in most cases on hypercortisolism rather than its cause; it should be initiated promptly to minimize the risk of infection in these immunosuppressed patients. The risk/benefit ratio of these recommendations will need re-evaluation every 2-3 months from April 2020 in each country (and possibly local areas) and will depend on the local health care structure and phase of pandemic.


Assuntos
Infecções por Coronavirus/prevenção & controle , Síndrome de Cushing/terapia , Inibidores Enzimáticos/uso terapêutico , Glucocorticoides/uso terapêutico , Controle de Infecções/métodos , Procedimentos Neurocirúrgicos/métodos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Telemedicina , Inibidores de 14-alfa Desmetilase/uso terapêutico , Adenoma Hipofisário Secretor de ACT/complicações , Adenoma Hipofisário Secretor de ACT/diagnóstico , Adenoma Hipofisário Secretor de ACT/terapia , Adenoma/complicações , Adenoma/diagnóstico , Adenoma/terapia , Infecções por Coronavirus/transmissão , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiologia , Síndrome de Cushing/imunologia , Gerenciamento Clínico , Humanos , Hidrocortisona/sangue , Hospedeiro Imunocomprometido , Cetoconazol/uso terapêutico , Metirapona/uso terapêutico , Educação de Pacientes como Assunto , Pneumonia Viral/transmissão , Guias de Prática Clínica como Assunto , Índice de Gravidade de Doença , Fatores de Tempo
7.
Praxis (Bern 1994) ; 109(7): 531-538, 2020.
Artigo em Alemão | MEDLINE | ID: mdl-32456577

RESUMO

CME: Endogenous Hypercortisolism (Endogenous Cushing's Syndrome) Abstract. Endogenous Cushing's syndrome (eCS) represents a rare disease entity. At the beginning symptoms and signs often are non-specific. However, untreated eCS is associated with a substantial morbidity and mortality rate. This article provides an actual overview about the etiology, clinical presentation and diagnosis of eCS with special focus on specific screening tests.


Assuntos
Síndrome de Cushing , Síndrome de Cushing/diagnóstico , Humanos , Hidrocortisona
10.
Eur J Endocrinol ; 183(1): G1-G7, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32380475

RESUMO

Clinical evaluation should guide those needing immediate investigation. Strict adherence to COVID-19 protection measures is necessary. Alternative ways of consultations (telephone, video) should be used. Early discussion with regional/national experts about investigation and management of potential and existing patients is strongly encouraged. Patients with moderate or severe clinical features need urgent investigation and management. Patients with active Cushing's syndrome, especially when severe, are immunocompromised and vigorous adherence to the principles of social isolation is recommended. In patients with mild features or in whom a diagnosis is less likely, clinical re-evaluation should be repeated at 3 and 6 months or deferred until the prevalence of SARS-CoV-2 has significantly decreased; however, those individuals should be encouraged to maintain social distancing. Diagnostic pathways may need to be very different from usual recommendations in order to reduce possible exposure to SARS-CoV-2. When extensive differential diagnostic testing and/or surgery is not feasible, it should be deferred and medical treatment should be initiated. Transsphenoidal pituitary surgery should be delayed during high SARS-CoV-2 viral prevalence. Medical management rather than surgery will be the used for most patients, since the short- to mid-term prognosis depends in most cases on hypercortisolism rather than its cause; it should be initiated promptly to minimize the risk of infection in these immunosuppressed patients. The risk/benefit ratio of these recommendations will need re-evaluation every 2-3 months from April 2020 in each country (and possibly local areas) and will depend on the local health care structure and phase of pandemic.


Assuntos
Infecções por Coronavirus/prevenção & controle , Síndrome de Cushing/terapia , Inibidores Enzimáticos/uso terapêutico , Glucocorticoides/uso terapêutico , Controle de Infecções/métodos , Procedimentos Neurocirúrgicos/métodos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Telemedicina , Inibidores de 14-alfa Desmetilase/uso terapêutico , Adenoma Hipofisário Secretor de ACT/complicações , Adenoma Hipofisário Secretor de ACT/diagnóstico , Adenoma Hipofisário Secretor de ACT/terapia , Adenoma/complicações , Adenoma/diagnóstico , Adenoma/terapia , Infecções por Coronavirus/transmissão , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiologia , Síndrome de Cushing/imunologia , Gerenciamento Clínico , Humanos , Hidrocortisona/sangue , Hospedeiro Imunocomprometido , Cetoconazol/uso terapêutico , Metirapona/uso terapêutico , Educação de Pacientes como Assunto , Pneumonia Viral/transmissão , Guias de Prática Clínica como Assunto , Índice de Gravidade de Doença , Fatores de Tempo
12.
Best Pract Res Clin Endocrinol Metab ; 34(2): 101382, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32139169

RESUMO

Pituitary surgery is the first-line treatment for patients with Cushing's disease. For patients who are not considered candidates for pituitary surgery, pituitary radiation and bilateral adrenalectomy are further treatment alternatives. Not all patients are cured with pituitary surgery, and a substantial number of patients develop recurrence, sometimes many years after an apparently successful treatment. The same applies to patients treated with radiotherapy. Far from all patients are cured, and in many cases the disease recurs. Bilateral adrenalectomy, although always curative, causes chronic adrenal insufficiency and the remaining pituitary tumour can continue to grow and cause symptoms due to pressure on adjacent tissues, a phenomenon called Nelson's syndrome. In this paper the rate of recurrence of hypercortisolism, as well as the rate of development of Nelson's syndrome, following treatment of patients with Cushing's syndrome, will be reviewed. The aim of the paper is also to summarize clinical and biochemical factors that are associated with recurrence of hypercortisolism and how the patients should be monitored following treatment.


Assuntos
Biomarcadores/análise , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/terapia , Diagnóstico por Imagem/métodos , Técnicas de Diagnóstico Endócrino , Monitorização Fisiológica/métodos , Doença de Addison/diagnóstico , Doença de Addison/epidemiologia , Doença de Addison/etiologia , Doença de Addison/terapia , Adenoma/complicações , Adenoma/diagnóstico , Adenoma/epidemiologia , Adenoma/terapia , Adrenalectomia/efeitos adversos , Síndrome de Cushing/epidemiologia , Síndrome de Cushing/patologia , Humanos , Síndrome de Nelson/diagnóstico , Síndrome de Nelson/epidemiologia , Síndrome de Nelson/etiologia , Síndrome de Nelson/cirurgia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/terapia , Recidiva
13.
Eur J Endocrinol ; 182(6): 569-582, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32213657

RESUMO

Objective: The challenge of diagnosing Cushing's syndrome (CS) calls for high precision biochemical screening. This study aimed to establish robust reference intervals for, and compare the diagnostic accuracy of, salivary cortisol and cortisone in late-night samples and after a low-dose (1 mg) dexamethasone suppression test (DST). Design and methods: Saliva samples were collected at 08:00 and 23:00 h, and at 08:00 h, after a DST, from 22 patients with CS and from 155 adult reference subjects. We also collected samples at 20:00 and 22:00 h from 78 of the reference subjects. Salivary cortisol and cortisone were analysed with liquid chromatography-tandem mass spectrometry. The reference intervals were calculated as the 2.5th and 97.5th percentiles of the reference population measurements. Diagnostic accuracies of different tests were compared, based on areas under the receiver-operating characteristic curves. Results: The upper reference limits of salivary cortisol and cortisone at 23:00 h were 3.6 nmol/L and 13.5 nmol/L, respectively. Using these reference limits, CS was detected with a sensitivity (95% CI) of 90% (70-99%) and specificity of 96% (91-98%) for cortisol, and a 100% (84-100%) sensitivity and 95% (90-98%) specificity for cortisone. After DST, cortisol and cortisone upper reference limits were 0.79 nmol/L and 3.5 nmol/L, respectively. CS was detected with 95% (75-100%) sensitivity and 96% (92-99%) specificity with cortisol, and 100% (83-100%) sensitivity and 94% (89-97%) specificity with cortisone. No differences in salivary cortisol or cortisone levels were found between samples collected at 22:00 and 23:00 h. Conclusion: Salivary cortisol and cortisone in late-night samples and after DST showed high accuracy for diagnosing CS, salivary cortisone being slightly, but significantly better.


Assuntos
Cortisona/análise , Síndrome de Cushing/diagnóstico , Hidrocortisona/análise , Programas de Rastreamento/estatística & dados numéricos , Saliva/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Ritmo Circadiano , Dexametasona , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Curva ROC , Valores de Referência , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem , Fatores de Tempo , Adulto Jovem
14.
Best Pract Res Clin Endocrinol Metab ; 34(2): 101380, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32165101

RESUMO

Cushing's syndrome (CS) is a severe condition that results from chronic exposure to elevated circulating cortisol levels; it is a rare but potentially life-threating condition, especially when not timely diagnosed and treated. Even though the diagnosis can be straightforward in florid cases due to their typical phenotype, milder forms can be missed. Despite the availability of different screening tests, the diagnosis remains challenging as none of the available tools proved to be fully accurate. Due to the ubiquitous effect of cortisol, it is easy understandable that its excess leads to a variety of systemic complications including hypertension, metabolic syndrome, bone damages and neurocognitive impairment. This article discusses clinical presentation of CS with an eye on the most frequent cortisol-related comorbidities and discuss the main pitfalls of first- and second-line tests in endogenous hypercortisolism diagnostic workup.


Assuntos
Síndrome de Cushing/complicações , Síndrome de Cushing/diagnóstico , Técnicas de Diagnóstico Endócrino , Comorbidade , Síndrome de Cushing/epidemiologia , Diagnóstico Diferencial , Técnicas de Diagnóstico Endócrino/tendências , Humanos , Hidrocortisona/metabolismo , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/etiologia , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia
15.
Best Pract Res Clin Endocrinol Metab ; 34(3): 101386, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32115357

RESUMO

Adrenocortical hyperplasia may develop in different contexts. Primary adrenal hyperplasia may be secondary to primary bilateral macronodular adrenocortical hyperplasia (PBMAH) or micronodular bilateral adrenal hyperplasia (MiBAH) which may be divided in primary pigmented nodular adrenocortical disease (PPNAD) and isolated micronodular adrenocortical disease (i-MAD). Both lead to oversecretion of cortisol and potentially to Cushing's syndrome. Moreover, adrenocortical hyperplasia may be secondary to longstanding ACTH stimulation in ACTH oversecretion as in Cushing's disease, ectopic ACTH secretion or glucocorticoid resistance syndrome and congenital adrenal hyperplasia secondary to various enzymatic defects within the cortex. Finally, idiopathic bilateral adrenal hyperplasia is the most common cause of primary aldosteronism. We will discuss recent findings on the multifaceted forms of adrenocortical hyperplasia.


Assuntos
Doenças do Córtex Suprarrenal , Glândulas Suprarrenais/patologia , Doenças do Córtex Suprarrenal/classificação , Doenças do Córtex Suprarrenal/diagnóstico , Doenças do Córtex Suprarrenal/etiologia , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/etiologia , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiologia , Humanos , Hidrocortisona/metabolismo , Hiperaldosteronismo/complicações , Hiperaldosteronismo/diagnóstico , Hiperplasia/diagnóstico , Hiperplasia/etiologia , Erros Inatos do Metabolismo/complicações , Erros Inatos do Metabolismo/diagnóstico , Receptores de Glucocorticoides/deficiência
16.
Best Pract Res Clin Endocrinol Metab ; 34(2): 101381, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32035797

RESUMO

Overt Cushing's syndrome is a severe condition responsible for multiple comorbidities and increased mortality. Effective treatment is essential to reduce mortality, improve comorbidities and long-term quality of life. Surgical resection of the causal lesion(s) is generally the first-line and most effective treatment to normalize cortisol secretion. Adjunctive symptomatic treatments of co-morbidities are often necessary both during the active phase of the disease and for persisting co-morbidities after cessation of hypercortisolism. Second-line treatments include various pharmacological treatments, bilateral adrenalectomy, and radiotherapy of corticotroph tumors. The choice of these treatments is complex, must be performed in a multidisciplinary expert team to be individualized for each patient, and use a shared decision-making approach.


Assuntos
Síndrome de Cushing/terapia , Terapias em Estudo , Adrenalectomia/efeitos adversos , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/epidemiologia , Síndrome de Cushing/etiologia , Técnicas de Diagnóstico Endócrino , Humanos , Qualidade de Vida , Terapias em Estudo/métodos , Terapias em Estudo/tendências , Resultado do Tratamento
17.
Biosens Bioelectron ; 154: 112071, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32056965

RESUMO

In the neuroendocrine system, corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) play important roles in the regulation of the hypothalamic-pituitary-adrenal (HPA) system. Disorders of the HPA system lead to physiological problems, such as Addison's disease and Cushing's syndrome. Therefore, detection of CRH and ACTH is essential for diagnosing disorders related to the HPA system. Herein, receptors of the HPA axis were used to construct a bioelectronic sensor system for the detection of CRH and ACTH. The CRH receptor, corticotropin-releasing hormone receptor 1 (CRHR1), and the ACTH receptor, melanocortin 2 receptor (MC2R), were produced using an Escherichia coli expression system, and were reconstituted using nanodisc (ND) technology. The receptor-embedded NDs were immobilized on a floating electrode of a carbon nanotube field-effect transistor (CNT-FET). The constructed sensors sensitively detected CRH and ACTH to a concentration of 1 fM with high selectivity in real time. Furthermore, the reliable detection of CRH and ACTH in human plasma by the developed sensors demonstrated their potential in clinical and practical applications. These results indicate that CRHR1 and MC2R-based bioelectronic sensors can be applied for rapid and efficient detection of CRH and ACTH.


Assuntos
Hormônio Adrenocorticotrópico/isolamento & purificação , Técnicas Biossensoriais , Hormônio Liberador da Corticotropina/isolamento & purificação , Sistema Hipotálamo-Hipofisário/metabolismo , Doença de Addison/diagnóstico , Doença de Addison/genética , Hormônio Adrenocorticotrópico/química , Hormônio Liberador da Corticotropina/química , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/genética , Humanos , Hidrocortisona/química , Hidrocortisona/genética , Sistema Hipófise-Suprarrenal/metabolismo , Receptor Tipo 2 de Melanocortina/química , Receptor Tipo 2 de Melanocortina/genética , Receptores da Corticotropina/química , Receptores da Corticotropina/genética , Receptores de Hormônio Liberador da Corticotropina/química , Receptores de Hormônio Liberador da Corticotropina/genética
18.
Medicina (Kaunas) ; 56(2)2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32050625

RESUMO

Due to the growing availability of imaging examinations the percentage of patients with incidentally diagnosed adrenal tumors has increased. The vast majority of these lesions are benign, non-functioning adenomas, although according to various estimates even up to 30%-50% of patients with adrenal incidentaloma may present biochemical hypercortisolemia, without typical clinical features of Cushing's syndrome. Adrenal adenomas secreting small amounts of glucocorticoids may cause morphological and functional changes in the myocardium and blood vessels. Early stages of cardiovascular remodeling may be observed among asymptomatic patients with adrenal adenoma. Vascular changes precede the development of cardiovascular diseases and can increase morbidity and mortality in patients with adrenal incidentaloma. This risk may result not only from the traditional risk factors. Seemingly hormonally inactive adrenal tumors can indeed produce small amounts of glucocorticoids that have metabolic implications. Therefore, evaluation of patients with incidental adrenal findings presenting with subclinical cardiovascular disease seems of particular importance.


Assuntos
Adenoma/complicações , Neoplasias das Glândulas Suprarrenais/complicações , Doenças Cardiovasculares/etiologia , Neoplasias das Glândulas Suprarrenais/sangue , Doenças Cardiovasculares/sangue , Espessura Intima-Media Carotídea , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiologia , Ecocardiografia , Endotélio Vascular/fisiopatologia , Humanos , Hidrocortisona/sangue , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Rigidez Vascular
19.
BMC Vet Res ; 16(1): 35, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32014021

RESUMO

BACKGROUND: Ectopic Cushing's syndrome (ECS) associated with malignant tumors, such as small cell lung carcinoma, bronchial carcinoids, and pheochromocytoma, has been reported in human medicine. However, ECS related to pheochromocytoma has not been reported in dogs. CASE PRESENTATION: An 11-year-old castrated, male Scottish terrier was diagnosed with a left adrenal mass. Cushing's syndrome was suspected based on clinical signs, including pot belly, polyuria, polydipsia, bilateral alopecia, recurrent pyoderma, and calcinosis cutis. Cushing's syndrome was diagnosed on the basis of consistent clinical signs and repeated adrenocorticotropic hormone (ACTH) stimulation tests. In addition, tests for fractionated plasma metanephrine/normetanephrine suggested a pheochromocytoma. Unilateral adrenalectomy was performed after medical management with trilostane and phenoxybenzamine. Histopathology confirmed a diagnosis of pheochromocytoma without cortical lesions. After surgery, fractionated metanephrine/normetanephrine and the findings of low-dose dexamethasone suppression and ACTH stimulation tests were within the normal ranges without any medication. There were no clinical signs or evidence of recurrence and metastasis on thoracic and abdominal X-rays and ultrasonography up to 8 months after surgery. CONCLUSIONS: Pheochromocytoma should be considered a differential diagnosis for dogs with Cushing's syndrome with an adrenal tumor. A good prognosis can be expected with prompt diagnosis and surgical intervention.


Assuntos
Neoplasias das Glândulas Suprarrenais/veterinária , Síndrome de Cushing/veterinária , Doenças do Cão/diagnóstico , Feocromocitoma/veterinária , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/veterinária , Animais , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiologia , Di-Hidrotestosterona/análogos & derivados , Di-Hidrotestosterona/uso terapêutico , Doenças do Cão/etiologia , Doenças do Cão/terapia , Cães , Masculino , Fenoxibenzamina/uso terapêutico , Feocromocitoma/complicações , Feocromocitoma/diagnóstico
20.
Ann Lab Med ; 40(4): 285-296, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32067427

RESUMO

Determination of cortisol levels in the urine (24 hours urine free cortisol), saliva (late-night), or serum (total cortisol after dexamethasone suppression) is recommended to screen for Cushing's syndrome (CS). This review focuses on the differences between the frequently used cortisol-antibody immunoassay-based methods and the highly specific mass-spectrometry-based methods that are progressively being employed in clinical laboratories for CS screening. The particular characteristics of cortisol metabolism and the lack of specificity of the immunoassays cause marked differences between both methods that are in turn highly dependent on the biological matrix, in which the cortisol is measured. Understanding the origin of these differences is essential for the interpretation of these results. Although cross-reactivity with endogenous steroids leads to grossly inaccurate results of immunoassay measurements of cortisol in the saliva and urine, preliminary evidence suggests that the clinical sensitivity of CS screening using immunoassays may be similar to CS screening using mass spectrometry. However, mass spectrometry offers more accurate results and considerably reduced variation across laboratories, while avoiding false-positive results. Moreover, mass spectrometry can overcome some common diagnostic challenges, such as identification of exogenous corticosteroids or simultaneous assessment of appropriate dexamethasone levels in suppression tests. Further, comprehensive mass spectrometry-based profiling of several steroid metabolites may be useful for discriminating among different subtypes of CS. Finally, this review discusses the main preanalytical factors that could cause variations in cortisol measurements and their influence on the reliability of the results.


Assuntos
Síndrome de Cushing/diagnóstico , Hidrocortisona/análise , Imunoensaio , Espectrometria de Massas em Tandem , Biomarcadores/análise , Biomarcadores/sangue , Biomarcadores/urina , Cromatografia Líquida de Alta Pressão , Humanos , Hidrocortisona/sangue , Hidrocortisona/urina , Reprodutibilidade dos Testes , Saliva/metabolismo , Sensibilidade e Especificidade
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