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1.
Eur J Endocrinol ; 183(2): 161-167, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32449698

RESUMO

Introduction: Intravenous etomidate infusion is effective to rapidly lower cortisol levels in severe Cushing's syndrome (CS) in the intensive care unit (ICU). Recently, etomidate treatment has also been proposed at lower doses in non-ICU wards, but it is not yet clear how this approach compares to ICU treatment. Methods: We compared data from patients with severe CS treated with high starting doses of etomidate (median: 0.30 mg/kg BW/day) in ICU or with lower starting doses (median: 0.025 mg/kg BW/day) in non-ICU medical wards. Results: Fourteen patients were included, among which ten were treated with low starting doses (LD) and four with high starting doses etomidate (HD). All patients had severe and complicated CS related to adrenal carcinoma (n = 8) or ectopic ACTH secretion (n = 6). Etomidate was effective in reducing cortisol levels below 500 nmol/L in a median of 1 day in the HD group compared to 3 days in the LD group (P = 0.013). However, all patients of the HD group had etomidate-induced cortisol insufficiency and needed frequent monitoring, while no patient from the LD group required hydrocortisone supplementation. No patient in either group died from complications of CS or etomidate treatment, but final outcome was poor as six patients in the LD group and all four patients in the HD group died from their cancer during follow-up. Conclusion: Our study suggests that, for patients with severe CS who do not require intensive organ-supporting therapy, the use of very low doses of etomidate in medical wards should be considered.


Assuntos
Síndrome de Cushing/tratamento farmacológico , Etomidato/administração & dosagem , Etomidato/efeitos adversos , Síndrome de ACTH Ectópico/complicações , Neoplasias das Glândulas Suprarrenais/complicações , Adulto , Idoso , Síndrome de Cushing/sangue , Síndrome de Cushing/complicações , Relação Dose-Resposta a Droga , Feminino , Unidades Hospitalares , Humanos , Hidrocortisona/sangue , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
3.
Monaldi Arch Chest Dis ; 89(3)2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31631643

RESUMO

Nocardia spp. is a genus of Gram-positive bacteria which can cause cutaneous, pleuropulmonary, or disseminated disease. The latter two forms are encountered in immunocompromised patients, with prolonged usage of corticosteroids being a well-recognized risk factor. However, endogenous Cushing's syndrome is less frequently associated with nocardiosis. We report on a 40-year-old woman who presented for further workup of abnormal findings in the chest computed tomography (three lung nodules, one of which being cavitary). She underwent trans-thoracic fine-needle lung aspiration of the cavitary nodule, which led to the diagnosis of lung nocardiosis. Moreover, the identification of cushingoid features from the history and clinical examination initiated further investigation with hormonal laboratory assessment and bilateral inferior petrosal sinus sampling which established the diagnosis of pituitary adrenocorticotropic hormone (ACTH) hypersecretion (Cushing's disease).  We conclude that pulmonary nocardiosis can be an opportunistic infection as well as a presenting manifestation of Cushing's disease.


Assuntos
Adenoma Hipofisário Secretor de ACT/complicações , Síndrome de Cushing/etiologia , Nocardiose/diagnóstico por imagem , Nocardiose/etiologia , Adenoma Hipofisário Secretor de ACT/sangue , Adenoma Hipofisário Secretor de ACT/patologia , Adenoma Hipofisário Secretor de ACT/cirurgia , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Síndrome de Cushing/sangue , Síndrome de Cushing/diagnóstico , Feminino , Humanos , Nocardiose/tratamento farmacológico , Nocardiose/microbiologia , Infecções Oportunistas/epidemiologia , Tomografia Computadorizada por Raios X/métodos , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
4.
Comput Methods Programs Biomed ; 178: 59-75, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31416563

RESUMO

BACKGROUND AND OBJECTIVE: In this study, a presentation is made for the automatic control of the hypothalamus-pituitary-adrenal axis which plays an important role in the immune stress responses and the circadian rhythms of mammalian organisms. METHODS: Control approaches are implemented on a novel second order nonlinear system which accepts adrenocorticotropin hormone as an input and models the variation of plasma concentrations of adrenocorticotropin and cortisol respectively. The control methods are based on back-stepping and input-output feedback linearization techniques. The controllers adjust the adrenocorticotropin injection to maintain the daily rhythm of the cortisol concentration. In accordance with the periodicity of biological clock mechanism, we provide a sinusoidally varying cortisol reference to the controllers. RESULTS: Numerical simulations are performed (on MATLAB) to demonstrate the closed loop performance of the controllers. Major concerns in the selection of the control gains are chattering and negative concentration in responses. The simulation results showed that one can successfully find gain levels which do not lead to those issues. However, the gains lie in different ranges for back-stepping and feedback linearization based controllers. CONCLUSION: The results showed that, both back-stepping and feedback linearization based controllers fulfilled their duty of synchronization of the cortisol concentration to a reference daily periodic rhythm. In addition to that, the risk of negative valued adrenocorticotropin injection can be eliminated by properly choosing the controller gains.


Assuntos
Hormônio Adrenocorticotrópico/sangue , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Algoritmos , Relógios Biológicos , Simulação por Computador , Síndrome de Cushing/sangue , Humanos , Modelos Teóricos
5.
J Steroid Biochem Mol Biol ; 192: 105410, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31201926

RESUMO

CONTEXT: Cushing's syndrome is caused by increased exposure to cortisol. Discrimination of different causes of endogenous hypercortisolism can make a diagnostic dilemma. PATIENTS AND METHODS: In serum samples from patients with Cushing's syndrome (47 with Cushing's disease, 6 with ectopic ACTH-dependent Cushing's syndrome, 16 with adrenal adenoma, 7 bilateral adrenal hyperplasia (BMAH) with overt Cushing's syndrome, 42 controls from the general population) using novel method based on gas chromatography-tandem mass spectrometry (GC-MS/MS) we measured 94 serum steroids to search for steroid fingerprint of each subtype. RESULTS: Patients with Cushing's disease and ectopic ACTH producing tumors showed elevated levels of androgens and their metabolites when compared with healthy controls. Mineralocorticoid precursors were also elevated in ectopic ACTH syndrome. The levels of androgens were decreased in adrenal adenomas and BMAH. ROC analysis showed 100% sensitivity and 93.6% specificity for 11ß-hydroxyepiandrosterone sulfate for discrimination of Cushing's disease from ectopic ACTH secretion. We didn't find any significant (p < 0.05) difference in steroids that would discriminate BMAH from unilateral adenomas causing Cushing's syndrome. CONCLUSION: Various causes of Cushing's syndrome show particular steroid fingerprints that can be used to discriminate and may help to achieve appropriate clinical diagnosis.


Assuntos
Síndrome de ACTH Ectópico/diagnóstico , Adenoma/diagnóstico , Hiperplasia Suprarrenal Congênita/diagnóstico , Hormônio Adrenocorticotrópico/sangue , Síndrome de Cushing/diagnóstico , Transtorno 46,XY do Desenvolvimento Sexual/diagnóstico , Hidrocortisona/sangue , Esteroides/sangue , Síndrome de ACTH Ectópico/sangue , Adenoma/sangue , Hiperplasia Suprarrenal Congênita/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Síndrome de Cushing/sangue , Transtorno 46,XY do Desenvolvimento Sexual/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
7.
J Endocrinol ; 242(2): 65-77, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31117053

RESUMO

Excessive and prolonged glucocorticoid (GC) exposure, resulting from either prescribed or endogenous hypercortisolism, is associated with a high cardiovascular and metabolic burden (Cushing's syndrome). Although previous studies in humans and mice have reported heterogeneous data about the persistence of metabolic syndrome features after remission of hypercortisolism, there is still controversy as to whether this is due to the deleterious changes induced by GCs during active disease or the result of various other factors interfering in the recovery period. In order to study metabolic effects after remission, we used a reversible mouse model of corticosterone (CORT) (100 µg/mL) administration in drinking water for 5 weeks, followed by a 10-week recovery period. We compared CORT-induced effects at these time points with a high-fat diet-treated group (HFD 45%) and a vehicle group (VEH). Plasma CORT, 11ß-HSD activity, food intake, glucose levels, interscapular brown adiposity, hepatic triglycerides and muscle mass were found altered during CORT treatment but normalized after recovery. Although hyperinsulinemia and insulin resistance were increased during CORT and HFD treatment, insulin homeostasis remained altered following the recovery period only in CORT-treated mice. Subcutaneous and visceral adipose tissues (SAT and VAT) were enlarged during HFD and CORT treatment as measured by MRI. However, increased muscle lipid content, adiposity and macrophage infiltration in VAT were only present in the CORT group following recovery. Taken together, CORT-induced insulin alterations were more potent than HFD-induced ones during the same period of treatment, and also more persistent long term. Moreover, we demonstrated that CORT treatment induces more long-lasting VAT enlargement than HFD.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Adiposidade/efeitos dos fármacos , Corticosterona/farmacologia , Dieta Hiperlipídica/efeitos adversos , Obesidade Abdominal/metabolismo , Tecido Adiposo/metabolismo , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/sangue , Anti-Inflamatórios/farmacologia , Peso Corporal/efeitos dos fármacos , Corticosterona/administração & dosagem , Corticosterona/sangue , Síndrome de Cushing/sangue , Modelos Animais de Doenças , Humanos , Resistência à Insulina , Masculino , Síndrome Metabólica/metabolismo , Camundongos , Obesidade Abdominal/etiologia
8.
Pituitary ; 22(5): 561-568, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31041631

RESUMO

Cushing's syndrome (CS) secondary to corticotropin releasing hormone (CRH) producing tumors is rare. In this paper we present an Iranian patient who was admitted to our hospital with classic signs and symptoms of CS. Laboratory evaluation revealed high serum and urine cortisol which could not be suppressed with dexamethasone. Abdominal CT scan revealed a mass in abdominal cavity. A percutaneous needle biopsy was performed and histopathologic evaluation revealed that the mass was a neuroendocrine tumor. A multi-disciplinary approach including resection of the mass, bilateral adrenalectomy somatostatin analogue and chemotherapy was applied for management of the disease. Extensive review of English literature focusing on the topic from 1971 to 2018 revealed that there have been only 75 similar cases. Clinical, laboratory, imaging, histopathologic characteristics and managements of these patients will also be discussed in this paper.


Assuntos
Hormônio Liberador da Corticotropina/sangue , Hormônio Liberador da Corticotropina/urina , Síndrome de Cushing/etiologia , Adrenalectomia , Síndrome de Cushing/sangue , Síndrome de Cushing/tratamento farmacológico , Síndrome de Cushing/cirurgia , Dexametasona/uso terapêutico , Humanos , Hidrocortisona/sangue , Hidrocortisona/urina , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico
9.
Horm Metab Res ; 51(5): 309-314, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31071735

RESUMO

Atherosclerotic cardiovascular events are one of the common causes of mortality in patients with Cushing's syndrome (CS). Atherogenic dyslipidemia is more common among South Asian Indians as compared to other ethnicities and is likely to worsen among patients with CS. This retrospective study was done over 5 years at a single institute to evaluate the pattern of lipid abnormalities in subjects with CS and the changes in lipid parameters after surgical control of hypercortisolemia. The study was done in two parts. In the first part, records of patients with CS diagnosed over 3 years were retrospectively reviewed. Hormonal and metabolic parameters including fasting plasma glucose (FPG), post prandial plasma glucose (PPPG), HbA1c, serum lipids, serum cortisol and plasma ACTH were recorded. In the second part, lipid parameters were rechecked among patients who underwent surgery and a median follow up of 4±2 months after remission. Out of the 126 patients diagnosed with endogenous CS over 3 years, 100 patients were eligible for inclusion in the study. At baseline, sixty five (65%) patients had dyslipidemia as defined by the NCEP-ATPIII criteria. 47 out of 63 (74.6%) subjects achieved remission after surgical management of CS. 32 (68.1%) of these patients had dyslipidemia prior to surgery. After excluding 1 death, 26 of 46 (56.5%) subjects had dyslipidemia after the follow up period. Lipid abnormalities are common among South Asian Indian subjects with endogenous CS and the pattern persists in most of them, 3 months after surgical correction of hypercortisolism.


Assuntos
Síndrome de Cushing/sangue , Síndrome de Cushing/cirurgia , Lipídeos/sangue , Adulto , Feminino , Seguimentos , Humanos , Índia , Masculino , Indução de Remissão , Fatores de Tempo
10.
Biomed Res Int ; 2019: 9721781, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31001560

RESUMO

Previous studies have linked systemic glucocorticoid use with intestinal perforation. However, the association between intestinal perforation and endogenous hypercortisolism has not been well described, with only 14 previously published case reports. In this study, we investigated if intestinal perforation occurred more frequently in patients with ectopic ACTH syndrome and in those with a greater than 10-fold elevation of 24-hour urinary free cortisol level. Of 110 patients with ACTH-dependent Cushing's syndrome followed in two clinics in Canada, six cases with intestinal perforation were identified over 15 years. Age of patients ranged from 52 to 72, five females and one male, four with Cushing's disease and two with ectopic ACTH production, one from a pancreatic neuroendocrine tumor and one from medullary carcinoma of the thyroid. Five had diverticular perforation and one had intestinal perforation from a stercoral ulcer. All cases had their lower intestinal perforation when the cortisol production was high, and one patient had diverticular perforation 15 months prior to the diagnosis of Cushing's disease. As in previously reported cases, most had hypokalemia and abdominal pain with minimal or no peritoneal symptoms and this occurred during the active phase of Cushing's syndrome. Whereas all previously reported cases occurred in patients with 24-hour urinary free cortisol levels greater than 10-fold the upper limit of normal when measured and 11 of 14 patients had ectopic ACTH production, only one of our patients had this degree of hypercortisolism and four of our six patients had Cushing's disease. Similar to exogenous steroid use, patients with endogenous hypercortisolism also have a higher risk of intestinal, in particular diverticular, perforation and should be monitored closely for its occurrence with a low threshold for investigation and surgical intervention. Elective colonoscopy probably should be deferred until Cushing's syndrome is under control.


Assuntos
Síndrome de ACTH Ectópico , Hormônio Adrenocorticotrópico/sangue , Síndrome de Cushing , Hidrocortisona/urina , Perfuração Intestinal , Síndrome de ACTH Ectópico/sangue , Síndrome de ACTH Ectópico/patologia , Síndrome de ACTH Ectópico/urina , Idoso , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/urina , Síndrome de Cushing/sangue , Síndrome de Cushing/fisiopatologia , Síndrome de Cushing/urina , Feminino , Humanos , Perfuração Intestinal/sangue , Perfuração Intestinal/patologia , Perfuração Intestinal/urina , Masculino , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/urina
11.
Diabetes Care ; 42(5): 938-945, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31010944

RESUMO

OBJECTIVE: To investigate the prevalence and causes of diabetes in patients with primary aldosteronism (PA) in a multi-institutional cohort study in Japan. RESEARCH DESIGN AND METHODS: The prevalence of diabetes was determined in 2,210 patients with PA (diagnosed or glycated hemoglobin [HbA1c] ≥6.5% [≥48 mmol/mol]; NGSP) and compared with that of the Japanese general population according to age and sex. In 1,386 patients with PA and clear laterality (unilateral or bilateral), the effects of plasma aldosterone concentration (PAC), hypokalemia (<3.5 mEq/L), suspected subclinical hypercortisolism (SH; serum cortisol ≥1.8 µg/dL after 1-mg dexamethasone suppression test), and PA laterality on the prevalence of diabetes or prediabetes (5.7% ≤ HbA1c <6.5% [39 mmol/mol ≤ HbA1c <48 mmol/mol]) were examined. RESULTS: Of the 2,210 patients with PA, 477 (21.6%) had diabetes. This prevalence is higher than that in the general population (12.1%) or in 10-year cohorts aged 30-69 years. Logistic regression or χ2 test revealed a significant contribution of suspected SH to diabetes. Despite more active PA profiles (e.g., higher PAC and lower potassium concentrations) in unilateral than bilateral PA, BMI and HbA1c values were significantly higher in bilateral PA. PA laterality had no effect on the prevalence of diabetes; however, the prevalence of prediabetes was significantly higher in bilateral than unilateral PA. CONCLUSIONS: Individuals with PA have a high prevalence of diabetes, which is associated mainly with SH. The prevalence of prediabetes is greater for bilateral than unilateral PA, suggesting a unique metabolic cause of bilateral PA.


Assuntos
Síndrome de Cushing/epidemiologia , Diabetes Mellitus/epidemiologia , Hiperaldosteronismo/epidemiologia , Estado Pré-Diabético/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aldosterona/sangue , Estudos de Coortes , Síndrome de Cushing/sangue , Síndrome de Cushing/complicações , Complicações do Diabetes/sangue , Complicações do Diabetes/complicações , Complicações do Diabetes/epidemiologia , Diabetes Mellitus/sangue , Feminino , Hemoglobina A Glicada/análise , Humanos , Hiperaldosteronismo/sangue , Hiperaldosteronismo/complicações , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Estado Pré-Diabético/complicações , Prevalência , Estudos Retrospectivos , Adulto Jovem
12.
Curr Opin Endocrinol Diabetes Obes ; 26(3): 160-165, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30893084

RESUMO

PURPOSE OF REVIEW: Liquid chromatography-tandem mass spectrometry (LC-MS/MS), allowing the reliable measurement of large panels of steroids, opened a new era in the characterization of adrenal diseases. This review summarizes the most recent findings on serum steroid profile in benign adrenocortical tumors and provides a focus on the most promising analytical developments. RECENT FINDINGS: Recently developed LC-MS/MS assays included challenging compounds, providing new knowledge on adrenal steroid secretion. Pioneering studies highlighted the potential of incoming technologies in increasing measurement selectivity and implementing the steroidomic approach. In primary aldosteronism, several studies highlighted the signature of aldosterone-producing adenomas, mainly characterized by secretion of hybrid steroids. The combination of steroid panel and radiological data reached an agreement with adrenal vein sampling-based classification in more than 80% of the cases. The serum steroid profiling in patients with Cushing's syndrome, mainly characterized by reduced androgens and increased 11-dexoycorticosterone in adrenal hypercortisolism, showed a good discriminant power for patients' subtyping (90% correct classification rate). Finally, a selected panel of steroids, including 11-deoxycortisol as the main discriminant compound, was able to achieve a good separation of patients with and without adrenocortical carcinomas. SUMMARY: The constantly evolving serum steroid profiling by MS may improve the diagnosis of different types of adrenocortical tumors.


Assuntos
Neoplasias do Córtex Suprarrenal/sangue , Neoplasias do Córtex Suprarrenal/diagnóstico , Análise Química do Sangue/métodos , Esteroides/sangue , Adenoma Adrenocortical/sangue , Adenoma Adrenocortical/diagnóstico , Carcinoma Adrenocortical/sangue , Carcinoma Adrenocortical/diagnóstico , Biomarcadores/sangue , Cromatografia Líquida , Síndrome de Cushing/sangue , Síndrome de Cushing/diagnóstico , Humanos , Hiperaldosteronismo/sangue , Hiperaldosteronismo/diagnóstico , Espectrometria de Massas em Tandem/métodos
13.
Endocrine ; 64(1): 1-13, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30847651

RESUMO

Adrenal incidentalomas (AI) are one of the most frequent reasons for consultation in Endocrinology, as they are present in 3-10% of the general population. Up to 20% of them may have autonomous cortisol secretion (ACS), a term that refers to AI carriers with biochemical evidence of excess cortisol, but without the "specific" clinical signs of Cushing's syndrome. As ACS is associated with an increased risk of diabetes, obesity, high blood pressure (HBP), osteoporosis, cardiovascular events, and global mortality; its correct identification is of great importance. There are different laboratory assays to detect ACS, but all of them have some limitations. The dexamethasone suppression test is the most accepted for screening. However, there is no consensus on the cutoff point that should be used. Low levels of ACTH and DHEA-S and high urinary free cortisol are also associated with ACS, but in isolation they are of little value to establish the diagnosis. Considering its clinical implications and the lack of consensus in the diagnosis and in which is the most appropriate management of these patients, this review offers a quick reference guide of ACS, presenting an exhaustive review of the topic: its definition, epidemiology, diagnosis, clinical implications, treatment, and follow-up.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Síndrome de Cushing/diagnóstico , Hidrocortisona/sangue , Neoplasias das Glândulas Suprarrenais/sangue , Síndrome de Cushing/sangue , Humanos , Achados Incidentais
14.
Osteoporos Int ; 30(5): 1059-1069, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30719548

RESUMO

Analyses using the largest Korean cohort of adrenal incidentaloma (AI) revealed that subtle cortisol excess in premenopausal women and reduced dehydroepiandrosterone-sulfate (DHEA-S) in postmenopausal women and men are associated with bone mineral density (BMD) reduction in Asian patients with subclinical hypercortisolism (SH). INTRODUCTION: Few studies evaluated bone metabolism in Asians with SH. We investigated associations of cortisol and DHEA-S, an adrenal androgen, with BMD in Asians with AI, with or without SH. METHODS: We used cross-sectional data of a prospective multicenter study from Korea. We measured BMD, bone turnover markers, cortisol levels after 1-mg dexamethasone suppression test (1-mg DST), DHEA-S, and baseline cortisol to DHEA-S ratio (cort/DHEA-S) in 109 AI patients with SH (18 premenopausal, 38 postmenopausal women, and 53 men) and 686 with non-functional AI (NFAI; 59 premenopausal, 199 postmenopausal women, and 428 men). RESULTS: Pre- and postmenopausal women, but not men, with SH had lower BMDs at lumbar spine (LS) than those with NFAI (P = 0.008~0.016). Premenopausal women with SH also had lower BMDs at the hip than those with NFAI (P = 0.009~0.012). After adjusting for confounders, cortisol levels after 1-mg DST demonstrated inverse associations with BMDs at all skeletal sites only in premenopausal women (ß = - 0.042~- 0.033, P = 0.019~0.040). DHEA-S had positive associations with LS BMD in postmenopausal women (ß = 0.096, P = 0.001) and men (ß = 0.029, P = 0.038). The cort/DHEA-S had inverse associations with LS BMD in postmenopausal women (ß = - 0.081, P = 0.004) and men (ß = - 0.029, P = 0.011). These inverse associations of cort/DHEA-S remained significant after adjusting for cortisol levels after 1-mg DST (ß = - 0.079~- 0.026, P = 0.006~0.029). In postmenopausal women, the odds ratios of lower BMD by DHEA-S and cort/DHEA-S was 0.26 (95% CI, 0.08-0.82) and 3.40 (95% CI, 1.12-10.33), respectively. CONCLUSION: Subtle cortisol excess in premenopausal women and reduced DHEA-S in postmenopausal women and men may contribute to BMD reduction in Asians with SH.


Assuntos
Neoplasias das Glândulas Suprarrenais/sangue , Densidade Óssea/fisiologia , Síndrome de Cushing/sangue , Sulfato de Desidroepiandrosterona/sangue , Hidrocortisona/sangue , Neoplasias das Glândulas Suprarrenais/fisiopatologia , Adulto , Idoso , Biomarcadores/sangue , Remodelação Óssea/fisiologia , Estudos Transversais , Síndrome de Cushing/fisiopatologia , Feminino , Colo do Fêmur/fisiopatologia , Humanos , Hidrocortisona/fisiologia , Achados Incidentais , Vértebras Lombares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Osteoporose/fisiopatologia , Pós-Menopausa/sangue , Pós-Menopausa/fisiologia , Pré-Menopausa/sangue , Pré-Menopausa/fisiologia
15.
Pituitary ; 22(2): 179-186, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30799512

RESUMO

BACKGROUND: Studies on the incidence of Cushing's disease (CD) are few and usually limited by a small number of patients. The aim of this study was to assess the annual incidence in a nationwide cohort of patients with presumed CD in Sweden. METHODS: Patients registered with a diagnostic code for Cushing's syndrome (CS) or CD, between 1987 and 2013 were identified in the Swedish National Patient Registry. The CD diagnosis was validated by reviewing clinical, biochemical, imaging, and histopathological data. RESULTS: Of 1317 patients identified, 534 (41%) had confirmed CD. One-hundred-and-fifty-six (12%) patients had other forms of CS, 41 (3%) had probable but unconfirmed CD, and 334 (25%) had diagnoses unrelated to CS. The mean (95% confidence interval) annual incidence between 1987 and 2013 of confirmed CD was 1.6 (1.4-1.8) cases per million. 1987-1995, 1996-2004, and 2005-2013, the mean annual incidence was 1.5 (1.1-1.8), 1.4 (1.0-1.7) and 2.0 (1.7-2.3) cases per million, respectively. During the last time period the incidence was higher than during the first and second time periods (P < 0.05). CONCLUSION: The incidence of CD in Sweden (1.6 cases per million) is in agreement with most previous reports. A higher incidence between 2005 and 2013 compared to 1987-2004 was noticed. Whether this reflects a truly increased incidence of the disease, or simply an increased awareness, earlier recognition, and earlier diagnosis can, however, not be answered. This study also illustrates the importance of validation of the diagnosis of CD in epidemiological research.


Assuntos
Síndrome de Cushing/epidemiologia , Hipersecreção Hipofisária de ACTH/epidemiologia , Hormônio Adrenocorticotrópico/sangue , Estudos de Coortes , Síndrome de Cushing/sangue , Humanos , Hidrocortisona/sangue , Incidência , Hipersecreção Hipofisária de ACTH/sangue , Suécia/epidemiologia
16.
Hormones (Athens) ; 18(1): 85-89, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30737657

RESUMO

OBJECTIVE: During follow-up in cancer patients, adrenal lesions are frequently found by computer tomography imaging. In these patients, the frequency of subclinical Cushing's syndrome (SCS) has not been fully explored. The aim of the present study was to investigate the presence of SCS in cancer patients with adrenal lesions in comparison to patients with true adrenal incidentalomas. DESIGN: We studied 95 patients with adrenal lesions: 57 patients (group A, 20 males and 37 females) had a history of extra-adrenal malignancy and adrenal lesions were discovered during staging of the primary cancer, and 38 patients (group B, 6 males and 32 females) had adrenal incidentalomas. The two groups had similar BMI. All patients had unenhanced HU < 10 in computed tomography to ensure low risk of adrenal metastatic disease. Patients' morning plasma cortisol levels and ACTH were measured. An overnight 1 mg dexamethasone suppression test (ODST) was performed in all participants; in case of abnormal results, 24-h urine cortisol and the low-dose dexamethasone suppression test were additionally conducted. The cutoffs of morning cortisol values used for ODST were 1.8 and 5 µg/dl. RESULTS: When the cutoff of 1.8 µg/dl for suppressed morning cortisol was used, 42.1% of group A and 39.5% of group B had abnormal results (p = 0.95). By using the threshold of 5 µg/dl after ODST, 5.3% of group A and 13.2% of group B did not have suppressed cortisol levels with the 1 mg ODST (p = 0.18). The main factors found to influence suppressed cortisol levels after ODST in both groups were BMI and size of the adrenal lesion. CONCLUSIONS: Patients with extra-adrenal malignancies and adrenal lesions had similar rates of subclinical hypercortisolemia compared to patients with true adrenal incidentalomas.


Assuntos
Doenças das Glândulas Suprarrenais/sangue , Neoplasias das Glândulas Suprarrenais/sangue , Síndrome de Cushing/sangue , Hidrocortisona/sangue , Neoplasias/sangue , Doenças das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idoso , Índice de Massa Corporal , Dexametasona/administração & dosagem , Feminino , Glucocorticoides/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia
17.
BMC Endocr Disord ; 19(1): 13, 2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30670014

RESUMO

BACKGROUND: Increased urinary free cortisol in response to the oral administration of dexamethasone is a paradoxical reaction mainly reported in patients with primary pigmented nodular adrenocortical disease. Here, we describe the first case of subclinical Cushing's syndrome represented by autonomous cortisol secretion and paradoxical response to oral dexamethasone administration, harboring an activating mutation in the α subunit of the stimulatory G protein (GNAS). CASE PRESENTATION: A 65-year-old woman was diagnosed with subclinical Cushing's syndrome during an evaluation for bilateral adrenal masses. Tumors of unknown origin were found in the heart, brain, thyroid gland, colon, pancreas, and both adrenal glands. Adenocarcinoma of the sigmoid colon and systemic brown-patchy skin pigmentation were also present. Her urinary cortisol levels increased in response to oral dexamethasone, while serum dehydroepiandrosterone-sulfate was not suppressed. After right adrenalectomy, genetic analysis of the resected tumor revealed the somatic GNAS activating mutation, p.R201H. Paradoxical urinary cortisol response persisted even after unilateral adrenal resection, although serum and urinary cortisol levels were attenuated. CONCLUSIONS: This patient harbored a GNAS activating mutation, and presented with a mild cortisol- and androgen-producing adrenal adenoma. Administration of oral dexamethasone paradoxically increased cortisol levels, possibly via the stimulation of the cyclic adenosine monophosphate-dependent protein kinase A signaling pathway, which is seen in patients with pigmented nodular adrenocortical disease or Carney complex. GNAS mutations may provide clues to the mechanisms of hyper-function and tumorigenesis in the adrenal cortex, especially in bilateral adrenal masses accompanied by multiple systemic tumors. Examining GNAS mutations could help physicians detect extra-adrenal malignancies, which may contribute to an improved prognosis for patients with this type of Cushing's syndrome.


Assuntos
Neoplasias das Glândulas Suprarrenais/complicações , Adenoma Adrenocortical/complicações , Cromograninas/genética , Síndrome de Cushing/sangue , Dexametasona/administração & dosagem , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Hidrocortisona/sangue , Mutação , Neoplasias das Glândulas Suprarrenais/patologia , Adenoma Adrenocortical/patologia , Idoso , Anti-Inflamatórios/administração & dosagem , Síndrome de Cushing/tratamento farmacológico , Síndrome de Cushing/etiologia , Feminino , Humanos , Prognóstico
18.
Endocr J ; 66(3): 207-214, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30674738

RESUMO

Adrenal Cushing's syndrome (CS) is caused by cortisol-producing adrenal adenoma and is frequently accompanied by glucose metabolism disorders, which are characterized by increased insulin resistance and insufficient ß-cell compensation. However, considering the rarity of CS, few studies have assessed whether the glucose metabolism disorders could be ameliorated by surgical treatment. In this case series, we evaluated glucose metabolism before and after surgery in 11 patients (10 women and 1 man) who underwent unilateral adrenalectomy for overt adrenal CS between 2005 and 2016. Patients with pre-diagnosed diabetes mellitus (DM) were excluded. Pre- and post-operative 75-g oral glucose tolerance tests were performed. Cortisol secretion decreased significantly after surgery (median 24-h urinary free cortisol: 582.0 µg/day [interquartile range: 321.0-743.0 µg/day] to 31.3 µg/day [23.6-40.6 µg/day], p = 0.001). The results of the OGTT generally improved after surgery (normal glucose tolerance/impaired glucose tolerance/DM: 2/8/1 to 8/3/0), with significant decreases in the immunoreactive insulin and glucose levels. We also found a decrease in the median homeostatic model assessment of insulin resistance (2.4 [1.4-2.8] to 1.0 [0.6-1.1], p = 0.002), and increases in the median Matsuda index (3.0 [2.3-4.5] to 8.2 [6.3-11.4], p < 0.001), median insulinogenic index (0.70 [0.22-1.51] to 1.22 [0.78-1.64], p = 0.08), and median disposition index (609.1 [237.8-1,095.2] to 1,286.0 [1,034.6-1,857.6], p = 0.002). These findings indicate that adrenalectomy for adrenal CS without overt DM may help ameliorate glucose metabolism disorders, and improve both insulin resistance and insulin secretion.


Assuntos
Glicemia/metabolismo , Síndrome de Cushing/sangue , Intolerância à Glucose/sangue , Hidrocortisona/metabolismo , Resistência à Insulina/fisiologia , Neoplasias do Córtex Suprarrenal/sangue , Neoplasias do Córtex Suprarrenal/complicações , Neoplasias do Córtex Suprarrenal/cirurgia , Adrenalectomia , Adenoma Adrenocortical/sangue , Adenoma Adrenocortical/complicações , Adenoma Adrenocortical/cirurgia , Adulto , Síndrome de Cushing/etiologia , Síndrome de Cushing/cirurgia , Feminino , Intolerância à Glucose/complicações , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
19.
Minerva Endocrinol ; 44(1): 33-42, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29963828

RESUMO

In current practice, an adrenal adenoma usually comes as an unexpected byproduct of an imaging study performed for unrelated reasons, without any prior suspect of adrenal disease. Therefore, these tumors currently represent a public health challenge because they are increasingly recognized due to the widespread use of high-resolution cross-sectional imaging for diagnostic purposes. In radiology series, the prevalence of adrenal adenomas increases steeply with age, from around 3% below the age of 50 years up to 10% in the ageing population. These tumors may have clinical relevance because they are able to secrete cortisol autonomously, independently from the pituitary control, in up to 20-30% of patients. In most of the cases the resulting cortisol excess is insufficient to produce a typical Cushing phenotype but may have clinical consequences, such as hypertension, diabetes, obesity, dyslipidemia and osteoporosis. Despite some controversy on the most effective diagnostic algorithm to define this subtle hypercortisolism, there is mounting evidence that a simple approach by using the 1-mg overnight dexamethasone suppression test (DST) may stratify patients for their cardiovascular risk. Cross-sectional, retrospective studies showed that patients with increasingly higher cortisol following DST have an adverse cardiovascular risk profile and are at increased risk of death. Therefore, also a subtle autonomous cortisol excess is associated with increased morbidity and mortality, mainly of cardiovascular origin.


Assuntos
Neoplasias das Glândulas Suprarrenais/terapia , Adenoma Adrenocortical/terapia , Síndrome de Cushing/terapia , Neoplasias das Glândulas Suprarrenais/sangue , Neoplasias das Glândulas Suprarrenais/patologia , Adenoma Adrenocortical/sangue , Adenoma Adrenocortical/patologia , Síndrome de Cushing/sangue , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/patologia , Humanos , Hidrocortisona/sangue
20.
World J Surg ; 43(2): 527-533, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30232569

RESUMO

BACKGROUND: Management of patients with bilateral adrenal masses and ACTH-independent Cushing's syndrome (AICS) is challenging, as bilateral adrenalectomy can lead to steroid dependence and lifelong risk of adrenal crisis. Adrenal venous sampling (AVS) has been previously reported to facilitate lateralization for guiding adrenalectomy. The aim of the current study was to investigate the utility of AVS using protocol from study by Young et al. in the management of patients with bilateral adrenal masses and AICS. METHODS AND DESIGN: A retrospective review of all patients with bilateral adrenal masses and AICS who underwent AVS from 2008 to 2016 was performed. AVS for cortisol and epinephrine was performed with dexamethasone suppression. The adrenal vein to peripheral vein cortisol ratios and side-to-side cortisol lateralization ratios were calculated. RESULTS: AVS was successful in 8 of 9 patients. All 8 patients had AVS results indicating bilateral cortisol hypersecretion. Six patients underwent adrenalectomy: 3 had unilateral adrenalectomy of the larger size mass, 2 had bilateral adrenalectomy (both sides >4 cm.) and 1 had stepwise bilateral adrenalectomy. Final pathology revealed macronodular adrenal hyperplasia in all 6 patients that underwent surgery. CONCLUSION: AVS was useful in excluding a unilateral adenoma as the source of AICS in this study of patients with bilateral adrenal masses and AICS. However, adrenal mass size influenced surgical decision making more than AVS results. More data are needed before AVS can be advocated as essential for management of patients with bilateral adrenal masses and AICS.


Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/métodos , Síndrome de Cushing/cirurgia , Epinefrina/sangue , Hidrocortisona/sangue , Neoplasias das Glândulas Suprarrenais/sangue , Glândulas Suprarrenais/irrigação sanguínea , Idoso , Síndrome de Cushing/sangue , Dexametasona/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Veias
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