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1.
Endocrine ; 2020 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-32533509

RESUMO

PURPOSE: Differentiated thyroid cancer (DTC) has an increasing incidence in childhood and adolescence but long-term outcome data are limited. We aimed to identify possible risk factors associated with disease persistence, with special focus on the usefulness of ATA risk stratification system and pre-ablation stimulated thyroglobulin (Tg) levels. METHODS: We retrospectively studied 103 patients, 79 females (76.7%), aged 15.6 ± 3.2 years (range 5-21 years) who underwent total thyroidectomy for DTC. Patients were classified by ATA risk stratification criteria as low, intermediate, and high risk for recurrence. All, except five with papillary microcarcinoma, received radioactive iodine (RAI) treatment. RESULTS: At diagnosis, 44.7% of patients had cervical lymph node and 7.8% pulmonary metastases. Amongst the 72 patients with long-term follow-up data, 31.9% had persistent disease. Lymph node as well as pulmonary metastases and increased pre-ablation stimulated thyroglobulin (Tg) levels were associated with persistent disease. The risk of persistent disease was significantly higher in both the intermediate- (OR 17.95; 95% CI 2.66-120.94, p < 0.01) and high-risk (OR 17.65; 95% CI 4.47-69.74, p < 0.001) groups. ROC curve analysis showed that a pre-ablation Tg level higher than 14 ng/ml had a sensitivity of 94.7% to predict persistence, corresponding to a positive (PPV) and negative predictive values (NPV) of 66.7% and 93.8%, respectively. CONCLUSIONS: ATA risk stratification was validated in our population of children and young adults with DTC. Moreover, pre-ablation stimulated Tg levels of <14 ng/ml were associated with a low risk of long-term persistence and may therefore serve as a marker to identify patients who may need less intensive surveillance.

2.
J Clin Endocrinol Metab ; 105(7)2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32170323

RESUMO

CONTEXT: Patients with adrenal insufficiency require increased hydrocortisone cover during major stress to avoid a life-threatening adrenal crisis. However, current treatment recommendations are not evidence-based. OBJECTIVE: To identify the most appropriate mode of hydrocortisone delivery in patients with adrenal insufficiency who are exposed to major stress. DESIGN AND PARTICIPANTS: Cross-sectional study: 122 unstressed healthy subjects and 288 subjects exposed to different stressors (major trauma [N = 83], sepsis [N = 100], and combat stress [N = 105]). Longitudinal study: 22 patients with preserved adrenal function undergoing elective surgery. Pharmacokinetic study: 10 patients with primary adrenal insufficiency undergoing administration of 200 mg hydrocortisone over 24 hours in 4 different delivery modes (continuous intravenous infusion; 6-hourly oral, intramuscular or intravenous bolus administration). MAIN OUTCOME MEASURE: We measured total serum cortisol and cortisone, free serum cortisol, and urinary glucocorticoid metabolite excretion by mass spectrometry. Linear pharmacokinetic modeling was used to determine the most appropriate mode and dose of hydrocortisone administration in patients with adrenal insufficiency exposed to major stress. RESULTS: Serum cortisol was increased in all stress conditions, with the highest values observed in surgery and sepsis. Continuous intravenous hydrocortisone was the only administration mode persistently achieving median cortisol concentrations in the range observed during major stress. Linear pharmacokinetic modeling identified continuous intravenous infusion of 200 mg hydrocortisone over 24 hours, preceded by an initial bolus of 50-100 mg hydrocortisone, as best suited for maintaining cortisol concentrations in the required range. CONCLUSIONS: Continuous intravenous hydrocortisone infusion should be favored over intermittent bolus administration in the prevention and treatment of adrenal crisis during major stress.

3.
Hormones (Athens) ; 19(2): 245-251, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32124257

RESUMO

PURPOSE: Nonfunctioning pituitary adenomas (NFPAs) are among the commonest benign tumors of the pituitary. Hypopituitarism is frequently present at the time of diagnosis, and this has been attributed to stalk portal vessel compression and/or destruction of normal anterior pituitary cells. The aim of our study was to examine possible factors at diagnosis associated with the presence of hypopituitarism. METHODS: We retrospectively evaluated the records of patients with nonfunctioning pituitary macroadenomas from the database of our department. The inclusion criterion was the availability of imaging data regarding the extension of the lesion. RESULTS: A total of 148 patients (89 men, 60.1%) with nonfunctioning macroadenomas and available imaging data were identified. Mean age at diagnosis was 56.0 ± 14.5 years, and hypopituitarism was found in 66.2%. The maximum diameter of the adenoma, the patient's age at diagnosis, and compression of the optic chiasm were significant factors predicting the presence of hypopituitarism (OR 1.077, p = 0.006; OR 1.025, p = 0.045; and OR 2.893, p = 0.042, respectively). Suprasellar adenomas with extension to adjacent sinuses, although larger than those with only suprasellar extension, did not differ as to the degree of hypopituitarism. Moreover, in suprasellar adenomas, prolactin levels, albeit not independently, were also related to hypopituitarism (OR 1.035, p = 0.045). CONCLUSIONS: In patients with NFPAs, prognostic factors related to increased risk of hypopituitarism are age at diagnosis, size of the adenoma, and most importantly the presence of suprasellar extension. These data accentuate the necessity for surgical decompression in case of suprasellar extension, in order, apart from saving visual acuity, to possibly avoid or reverse hypopituitarism.

4.
Curr Opin Endocrinol Diabetes Obes ; 27(3): 125-131, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32209820

RESUMO

PURPOSE OF REVIEW: The current review provides a summary on the most recent developments regarding the cause, work-up and management of bilateral adrenal incidentalomas (BAI). RECENT FINDINGS: The recent ENS@T/ESE guidelines provide comprehensive directions on the evaluation and management of patients with adrenal incidentalomas with special focus on those with bilateral tumours. Intraadrenal ACTH synthesis that may locally stimulate cortisol secretion challenging the traditionally used term 'ACTH-independent'. Inactivating mutations of a new tumour suppressor gene, armadillo repeat containing 5 (ARMC5), are implicated in a number of patients, especially those with multiple macronodules (bilateral macronodular hyperplasia) and evidence of hypercortisolism. Loss-of-function mutations of the glucocorticoid receptor gene (NR3C1) consist a new possible genetic cause of BAIs. Regarding management an increasing number of studies provide data on the benefits and safety of unilateral rather than bilateral adrenalectomy. There is also emerging data on the beneficial use of steroidogenesis inhibitors in a dosing schedule that aims to mimic the normal cortisol rhythm with promising short-term results, but the long-term clinical benefits of this approach remain to be demonstrated. SUMMARY: The diagnostic approach consists of imaging and hormonal evaluation. Imaging characterization should be done separately for each lesion. Hormonal evaluation includes testing for primary aldosteronism, pheochromocytoma and evaluation for autonomous cortisol secretion, using the 1-mg overnight dexamethasone suppression test. Midnight cortisol or 24-h urinary-free cortisol may aid in establishing the degree of cortisol excess. In patients with hypercortisolism ACTH levels should be measured to establish ACTH-independency. The appropriate management of BAI associated with cortisol excess remains controversial. Bilateral adrenalectomy results in lifetime steroid dependency and is better reserved only for patients with overt and severe hypercortisolism. Unilateral adrenalectomy might be considered in selected patients. Medical therapy is not an established approach yet but it may be considered when control of hypercortisolism is desired, but surgery is not an option.

5.
J Clin Endocrinol Metab ; 105(3)2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31665449

RESUMO

CONTEXT: Urine steroid metabolomics, combining mass spectrometry-based steroid profiling and machine learning, has been described as a novel diagnostic tool for detection of adrenocortical carcinoma (ACC). OBJECTIVE, DESIGN, SETTING: This proof-of-concept study evaluated the performance of urine steroid metabolomics as a tool for postoperative recurrence detection after microscopically complete (R0) resection of ACC. PATIENTS AND METHODS: 135 patients from 14 clinical centers provided postoperative urine samples, which were analyzed by gas chromatography-mass spectrometry. We assessed the utility of these urine steroid profiles in detecting ACC recurrence, either when interpreted by expert clinicians or when analyzed by random forest, a machine learning-based classifier. Radiological recurrence detection served as the reference standard. RESULTS: Imaging detected recurrent disease in 42 of 135 patients; 32 had provided pre- and post-recurrence urine samples. 39 patients remained disease-free for ≥3 years. The urine "steroid fingerprint" at recurrence resembled that observed before R0 resection in the majority of cases. Review of longitudinally collected urine steroid profiles by 3 blinded experts detected recurrence by the time of radiological diagnosis in 50% to 72% of cases, improving to 69% to 92%, if a preoperative urine steroid result was available. Recurrence detection by steroid profiling preceded detection by imaging by more than 2 months in 22% to 39% of patients. Specificities varied considerably, ranging from 61% to 97%. The computational classifier detected ACC recurrence with superior accuracy (sensitivity = specificity = 81%). CONCLUSION: Urine steroid metabolomics is a promising tool for postoperative recurrence detection in ACC; availability of a preoperative urine considerably improves the ability to detect ACC recurrence.

6.
Mol Cell Endocrinol ; 501: 110656, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-31756425

RESUMO

PURPOSE: Glucocorticoid actions are mediated by the glucocorticoid receptor (GCR) whose dysfunction leads to glucocorticoid tissue resistance. Our objective was to evaluate GCR-α and GCR-ß expression and key steps in the GCR signalling cascade in critical illness. METHODS: Expression of GCR and major GCR-target genes, cortisol, adrenocorticotropin (ACTH) and cytokines was measured in 42 patients on ICU admission and on days 4, 8, and 13. Twenty-five age- and sex-matched subjects were used as controls. RESULTS: Acutely, mRNA expression of GCR-α was 10-fold and of GCR-ß 3-fold the expression of controls, while during the sub-acute phase expression of both isoforms was lower compared to controls. Expression of FKBP5 and GILZ decreased significantly. Cortisol levels remained elevated and ACTH increased during the 13-day period. CONCLUSIONS: GCR expression and hypothalamic-pituitary-adrenal axis function undergo a biphasic response during critical illness. The dissociation between low GCR expression and high cortisol implies an abnormal stress response.

7.
Endocrinol Metab Clin North Am ; 48(4): 667-680, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31655769

RESUMO

Hypertension is one of the commonest chronic diseases contributing to cardiovascular disease. Idiopathic (primary) hypertension accounts for approximately 85% of the diagnosed cases, and 15% of hypertensive patients have other contributing conditions leading to elevated blood pressure (secondary hypertension). Endocrine hypertension is a common secondary cause of hypertension. The most common causes of endocrine hypertension are excess production of mineralocorticoids (ie, primary hyperaldosteronism), glucocorticoids (Cushing syndrome), and catecholamines (pheochromocytoma). After biochemical confirmation of hormonal excess, appropriate use of imaging modalities, both functional and anatomic, should occur for the diagnostic workup of these patients and for location of the source of hormonal excess.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Síndrome de Cushing/diagnóstico por imagem , Hiperaldosteronismo/diagnóstico por imagem , Hipertensão/diagnóstico , Hipertensão/etiologia , Imagem por Ressonância Magnética , Feocromocitoma/diagnóstico por imagem , Cintilografia , Neoplasias das Glândulas Suprarrenais/complicações , Síndrome de Cushing/complicações , Humanos , Hiperaldosteronismo/complicações , Feocromocitoma/complicações
8.
Eur J Clin Invest ; 49(4): e13073, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30703253

RESUMO

INTRODUCTION: In critically ill patients, the hypothalamic-pituitary-adrenal axis is activated, resulting in increased serum cortisol concentrations. However, in some patients, especially those with sepsis, cortisol levels are relatively low for the degree of illness severity. Therefore, in the present project, we aim to characterize the time course of glucocorticoid receptor (GCR) alpha and beta expression in peripheral polymorphonuclear cells of critically ill septic or nonseptic patients using real-time PCR. DESIGN: A prospective observational study conducted on 32 critically ill adults not receiving steroids, in a university-affiliated, multidisciplinary intensive care unit (ICU). Blood samples were collected for measurement of glucocorticoid receptor expression within 24-48 hours of admission to the ICU and at days 4, 8 and 13 after admission, reflecting the acute and chronic phase of the illness. RESULTS: During ICU stay, patients expressed over time reduced levels of both GCR-α and GCR-ß mRNA. More specifically, GCR-α mRNA expression was decreased fourfold 4 days after admission (P < 0.0001) and remained low up to 2 weeks after admission (P < 0.001). On the other hand, GCR-ß mRNA levels remained stable shortly after admission, but approx. one week after admission, its levels decreased threefold (P < 0.01) and remained reduced up to 2 weeks after admission (P < 0.001). DISCUSSION: Our results suggest that critically ill patients have highly variable expression of alpha and beta GCR, and moreover, the levels of both receptors decrease during ICU stay. Taken together, these might explain the differential responsiveness of patients to exogenous steroid administration or to endogenous cortisol secretion.


Assuntos
Receptores de Glucocorticoides/metabolismo , Sepse/sangue , Cuidados Críticos , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Estudos Prospectivos , RNA Mensageiro/metabolismo , Sepse/terapia , Choque Séptico/sangue , Choque Séptico/terapia
9.
J Endocrinol ; 240(1): 27-39, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30452386

RESUMO

Corticosteroid-binding globulin (CBG) transports glucocorticoids in blood and is a serine protease inhibitor family member. Human CBG has a reactive center loop (RCL) which, when cleaved by neutrophil elastase (NE), disrupts its steroid-binding activity. Measurements of CBG levels are typically based on steroid-binding capacity or immunoassays. Discrepancies in ELISAs using monoclonal antibodies that discriminate between intact vs RCL-cleaved CBG have been interpreted as evidence that CBG with a cleaved RCL and low affinity for cortisol exists in the circulation. We examined the biochemical properties of plasma CBG in samples with discordant ELISA measurements and sought to identify RCL-cleaved CBG in human blood samples. Plasma CBG-binding capacity and ELISA values were consistent in arterial and venous blood draining skeletal muscle, liver and brain, as well as from a tissue (adipose) expected to contain activated neutrophils in obese individuals. Moreover, RCL-cleaved CBG was undetectable in plasma from critically ill patients, irrespective of whether their ELISA measurements were concordant or discordant. We found no evidence of RCL-cleaved CBG in plasma using a heat-dependent polymerization assay, and CBG that resists immunoprecipitation with a monoclonal antibody designed to specifically recognize an intact RCL, bound steroids with a high affinity. In addition, mass spectrometry confirmed the absence of NE-cleaved CBG in plasma in which ELISA values were highly discordant. Human CBG with a NE-cleaved RCL and low affinity for steroids is absent in blood samples, and CBG ELISA discrepancies likely reflect structural differences that alter epitopes recognized by specific monoclonal antibodies.


Assuntos
Hidrocortisona/metabolismo , Elastase de Leucócito/metabolismo , Esteroides/metabolismo , Transcortina/metabolismo , Adulto , Idoso , Animais , Anticorpos Monoclonais/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Ligação Proteica , Proteólise , Esteroides/sangue , Transcortina/química , Transcortina/imunologia
10.
Hormones (Athens) ; 18(2): 117-126, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30368687

RESUMO

Non-functioning pituitary adenomas (NFPAs) are the second most common variant of pituitary tumors. When symptomatic, primary therapy is surgery. Recurrence rates are high. Since many NFPAs express dopamine and somatostatin receptors, medical therapy has been used after surgery in order to prevent recurrence. So far, dopamine agonists have been more widely tested with some promise when introduced immediately after surgery but with less efficacy when introduced later upon tumor regrowth. Currently, the role of medical therapy to prevent tumor regrowth in NFPAs is limited by imprecisions as to final outcome and uncertainties concerning on patient selection, dosing, duration, and side effects.


Assuntos
Adenoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Adenoma/complicações , Adenoma/patologia , Adenoma/cirurgia , Quimioterapia Adjuvante/métodos , Terapia Combinada , Agonistas de Dopamina/uso terapêutico , Humanos , Hipopituitarismo/tratamento farmacológico , Hipopituitarismo/etiologia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Receptores de Somatostatina/antagonistas & inibidores
11.
Endocr Relat Cancer ; 26(10): R567-R581, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32053747

RESUMO

Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a highly heterogeneous entity. The incidental identification of an increasing number of cases has shifted its clinical expression from the rarely encountered severe forms, regarding both cortisol excess and adrenal enlargement, to mild forms of asymptomatic or oligosymptomatic cases with less impressive imaging phenotypes. Activation of cAMP/PKA pathway, either due to alterations of the different downstream signaling pathways or through aberrantly expressed G-protein-coupled receptors, relates to both cortisol secretion and adrenal growth. Germline ARMC5 mutations are a frequent genetic defect. The diagnostic approach consists of both imaging and hormonal characterization. Imaging characterization should be done separately for each lesion. Endocrine evaluation in cases with clinically overt Cushing's syndrome (CS) is similar to that applied for all forms of CS. In incidentally detected PBMAH, hormonal evaluation includes testing for primary aldosteronism, pheochromocytoma and evaluation for autonomous cortisol secretion, using the 1 mg overnight dexamethasone suppression test. Midnight cortisol or 24-h urinary free cortisol may aid in establishing the degree of cortisol excess. In patients with hypercortisolism, ACTH levels should be measured in order to establish ACTH independency. At variance with other forms of CS, PBMAH may be characterized by a distinct pattern of inefficient steroidogenesis. The appropriate management of PBMAH remains controversial. Bilateral adrenalectomy results in lifetime steroid dependency and is better reserved only for patients with severe CS. Unilateral adrenalectomy might be considered in selected patients. In cases where the regulation of cortisol secretion is mediated by aberrant receptors there is some potential for medical therapy.


Assuntos
Glândulas Suprarrenais/patologia , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/terapia , Glândulas Suprarrenais/metabolismo , Glândulas Suprarrenais/cirurgia , Adrenalectomia/efeitos adversos , Adrenalectomia/métodos , Hormônio Adrenocorticotrópico/metabolismo , Proteínas do Domínio Armadillo/genética , Síndrome de Cushing/genética , Síndrome de Cushing/patologia , Humanos , Hidrocortisona/metabolismo , Hidrocortisona/urina , Hiperplasia , Fenótipo , Receptores Acoplados a Proteínas-G/metabolismo
12.
Maturitas ; 116: 1-7, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30244768

RESUMO

OBJECTIVE: Visceral adiposity index (VAI), initially developed for the assessment of cardiometabolic risk, has been also proposed for the detection of nonalcoholic fatty liver disease (NAFLD); however, its diagnostic performance for NAFLD is still under investigation. We evaluated VAI as a marker of NAFLD and compared its diagnostic performance with that of three other NAFLD indices - fatty liver index (FLI), lipid accumulation product (LAP) and hepatic steatosis index (HSI) - in premenopausal women with and without polycystic ovary syndrome (PCOS) assessed for NAFLD by ultrasonography. DESIGN: Cross-sectional case-control study. METHODS: Anthropometric measurements, biochemical testing and abdominal ultrasonography after excluding causes of secondary liver disease were performed in 145 premenopausal women with PCOS (Rotterdam criteria) and 145 healthy control women within the same age range and matched for body mass index (BMI). The diagnostic performance of the four indices was assessed with receiver operating characteristic (ROC) analysis. RESULTS: NAFLD by ultrasonography was detected in 132 of the total sample of 290 women (45.5%). VAI, FLI, LAP and HSI values were significantly higher in women with NAFLD than those without. The areas under the curve (AUROCs) for VAI, FLI, LAP and HSI were 0.77 ±â€¯0.03, 0.87 ±â€¯0.02, 0.84 ±â€¯0.02 and 0.83 ±â€¯0.02, respectively, in the whole group, showing an adequate discriminatory ability for NAFLD of the four indices. AUROCs of the four indices calculated separately for PCOS and control women showed a similar performance of all indices in the two groups. CONCLUSIONS: These data show that VAI is useful for detecting NAFLD in premenopausal women with and without PCOS. However, VAI had a lower diagnostic performance in this cohort than FLI, LAP and HSI.


Assuntos
Adiposidade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Obesidade Abdominal/diagnóstico , Síndrome do Ovário Policístico/diagnóstico , Adolescente , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Pré-Menopausa , Ultrassonografia , Adulto Jovem
13.
Metabolites ; 8(2)2018 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-29690538

RESUMO

No study has directly measured tissue lactate clearance in patients with sepsis during the post-resuscitation period. In this study we aimed to assess in ICU patients with sepsis (n = 32) or septic shock (n = 79)—during the post-resuscitation phase—the relative kinetics of blood/tissue lactate clearances and to examine whether these are associated with outcome. We measured serially—over a 48-h period—blood and adipose tissue interstitial fluid lactate levels (with microdialysis) and we calculated lactate clearance. Statistics included mixed model analysis, Friedman’s analysis of variance, Wilcoxon’s test, Mann-Whitney’s test, receiver operating characteristics curves and logistic regression. Forty patients died (28-day mortality rate = 28%). Tissue lactate clearance was higher compared to blood lactate clearance at 0⁻8, 0⁻12, 0⁻16, 0⁻20 and 0⁻24 h (all p < 0.05). Tissue lactate clearance was higher in survivors compared to non-survivors at 0⁻12, 0⁻20 and 0⁻24 h (all p = 0.02). APACHE II along with tissue lactate clearance <30% at 0⁻12, 0⁻20 and 0⁻24 h were independent outcome predictors. We did not find blood lactate clearance to be related to survival. Thus, in critically ill septic patients, elevated tissue (but not blood) lactate clearance, was associated with a favorable clinical outcome.

14.
Eur J Endocrinol ; 178(5): R201-R214, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29472379

RESUMO

Desmopressin is a vasopressin analogue selective for type 2 vasopressin receptors that mediate renal water retention. In contrast to the native hormone arginine vasopressin, a well-known ACTH secretagogue, desmopressin, exerts minimal or no activity on ACTH excretion. However, in a substantial proportion of patients with ACTH-dependent Cushing's syndrome (CS), desmopressin elicits an ACTH and cortisol response, which contrasts with the minimal responses obtained in healthy subjects. The mechanism underlying this paradoxical response involves upregulation of vasopressin type 3 and/or the aberrant expression of type 2 receptors by neoplastic ACTH-producing cells. This makes desmopressin administration a suitable test enabling the distinction between neoplastic from functional (formerly termed 'pseudo-Cushing syndrome') ACTH-dependent cortisol excess. Several studies have now established an adjunctive role of desmopressin in the initial diagnostic workup of CS. Despite some early data indicating that this test may also have a role in distinguishing between Cushing's disease (CD) and ectopic ACTH secretion, subsequent studies failed to confirm this observation. The ability of the paradoxical response to desmopressin to depict the presence of neoplastic ACTH-secreting cells was also exploited in the follow-up of patients with CD undergoing surgery. Loss of the desmopressin response, performed in the early postoperative period, was a good predictor for a favorable long-term outcome. Moreover, during follow-up, reappearance of desmopressin paradoxical response was an early indicator for recurrence. In conclusion, the desmopressin test is a valid tool in both the diagnosis and follow-up of patients with CD and should be more widely applied in the workup of these patients.


Assuntos
Antidiuréticos/uso terapêutico , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/tratamento farmacológico , Desamino Arginina Vasopressina/uso terapêutico , Hormônio Adrenocorticotrópico/sangue , Hormônio Adrenocorticotrópico/metabolismo , Síndrome de Cushing/sangue , Testes Diagnósticos de Rotina/métodos , Seguimentos , Humanos
15.
In Vivo ; 29(4): 497-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26130795

RESUMO

BACKGROUND/AIM: Cortisol is involved in in many aspects of adipose tissue metabolism. A positive association between plasma cortisol and lipolysis has been observed. Critically ill patients exhibit 'lipemia of sepsis'. The aim of the present study was to study, in septic ICU patients, adipose tissue lipolysis in relation to tissue cortisol using microdialysis (MD). PATIENTS AND METHODS: We studied 17 mechanically-ventilated patients (9 men; mean±SD age=63±19 years) with a diagnosis of severe sepsis. Upon ICU admission, an MD catheter was inserted under sterile conditions into the subcutaneous adipose tissue of the upper thigh. On days 2, 3 and 4, MD samples were collected six times per day for glycerol (used as an index of lipolysis) and tissue cortisol determinations. The mean of these six collections was used for analysis (normal values for adipose tissue glycerol <200 µmol/l). Statistics were carried-out with analysis of covariance (ANCOVA) and linear regression. RESULTS: More than half of the samplings (19/31) indicated accentuated lipolysis with above-normal MD glycerol levels. By ANCOVA, MD glycerol (log values) was associated with MD cortisol (log values) (p=0.012) and was not associated with age or day of sampling. Furthermore, MD glycerol (log values) was positively correlated to MD cortisol (log values) (r=0.490, p=0.012). DISCUSSION: Changes in interstitial/tissue cortisol may not be reflected in (total) plasma cortisol concentration. Thus, it is interesting that we observed, albeit weak, an association between tissue lipolysis (via MD glycerol levels) and MD cortisol, verifying (although modestly so) the well-known association between lipolysis and cortisol.


Assuntos
Estado Terminal , Hidrocortisona/metabolismo , Lipólise , Gordura Subcutânea/metabolismo , Gordura Subcutânea/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hidrocortisona/sangue , Unidades de Terapia Intensiva , Masculino , Microdiálise/métodos , Pessoa de Meia-Idade , Respiração Artificial , Sepse/sangue , Sepse/metabolismo
16.
J Crit Care ; 30(2): 276-81, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25457114

RESUMO

PURPOSE: Cytomegalovirus (CMV) reactivation, a significant cause of morbidity and mortality in immunosuppression, may affect "immunocompetent" seropositive critically ill patients. The aim of this prospective, observational study was to define the incidence, risk factors, and the association with morbidity and mortality of CMV reactivation in a general population of critically ill immunocompetent patients. We also studied the relationship between reactivation and patients' inflammatory response, as expressed by cytokine levels and stress up-regulation by salivary cortisol. METHODS: This study included mechanically ventilated CMV-seropositive patients. A quantitative real-time polymerase chain reaction (PCR) was performed for CMV plasma DNAemia determination, upon intensive care unit (ICU) admission and weekly thereafter until day 28. Cytomegalovirus reactivation was defined as CMV plasma DNAemia greater than or equal to 500 copies/mL. Upon ICU admission, interferon γ, interleukin (IL) 10, IL-17A, IL-2, IL-6, and tumor necrosis factor α were quantified in plasma, and morning saliva was obtained to measure cortisol. Disease severity was assessed by Acute Physiology and Chronic Health Evaluation II score, whereas the degree of organ dysfunction was quantified by Sequential Organ Failure Assessment score. Mortality, duration of mechanical ventilation, and ICU length of stay were recorded. RESULTS: During the study period, 80 (51 men) patients with a median age of 63 years fulfilled the inclusion criteria. Reactivation of CMV occurred in 11 patients (13.75%). Median day of reactivation was day 7 post ICU admission. Total number of red blood cell units transfused (odds ratio [OR], 1.50; confidence interval [CI], 1.06-2.13; P = .02) and C-reactive protein levels upon ICU admission (OR, 1.01; CI, 1.00-1.02; P = .02) were independently associated with CMV reactivation. High IL-10 was marginally related to reactivation (P = .06). Sequential Organ Failure Assessment scores were higher in the group with CMV reactivation compared with patients without reactivation during the entire 28-day observation period (P < .006). Salivary cortisol, mortality, length of ICU stay, and duration of mechanical ventilation were similar in the 2 groups. CONCLUSIONS: Cytomegalovirus reactivation occurred in 13.75% of critically ill, immunocompetent patients. The degree of inflammation and the total number of transfused red blood cells units constituted risk factors. Cytomegalovirus reactivation was associated with more severe of organ dysfunction, but not with a worse clinical outcome.


Assuntos
Citocinas/imunologia , Infecções por Citomegalovirus/epidemiologia , Citomegalovirus/fisiologia , DNA Viral/sangue , Ativação Viral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Estado Terminal , Citomegalovirus/genética , Infecções por Citomegalovirus/imunologia , Feminino , Humanos , Imunocompetência , Incidência , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/epidemiologia , Insuficiência de Múltiplos Órgãos/imunologia , Escores de Disfunção Orgânica , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Respiração Artificial , Fatores de Risco , Saliva/química , Adulto Jovem , Cimento de Óxido de Zinco e Eugenol/análise
17.
J Clin Endocrinol Metab ; 99(12): 4471-80, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25148237

RESUMO

CONTEXT: Adrenal dysfunction remains a controversial issue in critical care. The long-stay intensive care unit (ICU) population may be at increased risk of adrenal insufficiency. OBJECTIVE: We aimed to determine whether adrenal dysfunction develops during the course of sepsis. DESIGN: This is a prospective observational longitudinal study. SETTING: The study was conducted in the ICU of a secondary/tertiary care hospital. PATIENTS: We studied 51 consecutive mechanically ventilated patients with sepsis. INTERVENTION: We measured cortisol, ACTH, cortisol-binding globulin, cytokines, and cortisol 30 minutes after 1 µg ACTH(1-24), upon sepsis diagnosis and every 3 to 4 days, until Day 30 or until recovery or death. MAIN OUTCOME MEASURES: We looked for changes in baseline and stimulated cortisol levels and its relationship to ACTH levels, sepsis severity or survival. RESULTS: Baseline and stimulated cortisol levels did not vary significantly. Septic patients with shock had higher baseline (20 ± 6 vs 17 ± 5 µg/dL, P = .03) and stimulated cortisol levels (26 ± 5 vs 23 ± 6 µg/dL, P = .04), compared with those without shock. On Day 1, ACTH levels could not predict cortisol levels (R(2) = 0.06, P = .08). ACTH levels increased significantly after Day 10 and, at this time point, they related to cortisol levels (R(2) = 0.35, P < .001). Development of septic shock, or resolution from it, was not associated with changes in baseline, stimulated cortisol levels, or the cortisol increment. There was much inpatient variability in the diagnosis of adrenal dysfunction at different time points. CONCLUSIONS: Total cortisol levels relate both to the severity and outcome of sepsis and remain fairly unchanged during the course of illness. Initially, cortisol levels are largely ACTH independent, whereas ACTH increases and correlates with cortisol levels later on. Adrenal dysfunction does not seem to be a major problem during the prolonged phase of sepsis. Although not significant, the variation in cortisol levels may be such that classification of patients varies, questioning the utility of arbitrary cut-offs to define adrenal dysfunction in septic patients.


Assuntos
Glândulas Suprarrenais/fisiopatologia , Citocinas/sangue , Sepse/fisiopatologia , Hormônio Adrenocorticotrópico/sangue , Adulto , Idoso , Estado Terminal , Feminino , Hormônios/sangue , Humanos , Hidrocortisona/sangue , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Respiração Artificial , Análise de Sobrevida , Resultado do Tratamento
18.
Intensive Care Med ; 39(10): 1752-9, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23881209

RESUMO

PURPOSE: Endothelial protein C receptor (EPCR) is expressed mainly in endothelial cells and is involved in regulation of the cytoprotective and anticoagulant pathways of protein C. We assessed whether haplotypes in the EPCR gene modify the risk of severe sepsis and/or septic shock (SS/SS) development in critically ill patients. METHODS: Three polymorphisms in the EPCR gene were genotyped in 389 Caucasian critically ill patients, hospitalized in the intensive care units of two major hospitals in Athens, Greece. Multivariate logistic regression analysis controlling for age, acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores, sex, and diagnosis was performed to determine the effect of haplotypes H1 and H3 in the EPCR gene on the development of SS/SS. RESULTS: H2 carriers versus all other genotypes combined had a nonsignificant excess of SS/SS (p = 0.087). SS/SS occurred in 38.8% of critically ill patients carrying minor alleles belonging to both H1 and H3 haplotypes, in 58.0% of H1 carriers, 64.3% of H3 carriers, and 65.2% of patients carrying all common alleles (H2). Compared with H2 carriers, the odds ratios (OR) for developing SS/SS were 0.34 [95% confidence interval (CI) 0.16-0.76, p = 0.008] for simultaneous H1 and H3 carriers, 0.65 (95% CI 0.37-1.13, p = 0.123) for H1 carriers, and 0.82 (95 % CI 0.39-1.70, p = 0.590) for H3 carriers. CONCLUSIONS: Our results indicate that simultaneous carriers of minor alleles belonging to both the H1 and H3 haplotypes may be at reduced risk of developing SS/SS in this cohort of critically ill patients.


Assuntos
Antígenos CD/genética , Estado Terminal , Proteína C/genética , Receptores de Superfície Celular/genética , Choque Séptico/genética , APACHE , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/fisiologia , Receptor de Proteína C Endotelial , Feminino , Frequência do Gene , Predisposição Genética para Doença , Grécia , Haplótipos , Humanos , Unidades de Terapia Intensiva , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Proteína C/fisiologia , Receptores de Superfície Celular/fisiologia , Medição de Risco , Sepse/genética , Adulto Jovem
19.
J Crit Care ; 28(2): 158-65, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22981531

RESUMO

PURPOSE: The aim of this study was to measure subcutaneous tissue cortisol obtained by microdialysis (MD) in 35 mechanically ventilated septic patients. MATERIALS AND METHODS: Upon intensive care unit admission, an MD catheter was inserted into the subcutaneous tissue of the thigh. Cortisol (CORT) was determined in a 5:00 to 9:00 am microdialysate sample collected within 72 hours. Concurrently, serum total (T-CORT) and free CORT (F-CORT) were measured. The Acute Physiology and Chronic Health Evaluation (APACHE II) and Sequential Organ Failure Assessment scores were calculated. Both T-CORT less than 10 µg/dL and F-CORT less than 0.8 µg/dL were considered as indicating critical illness-related corticosteroid insufficiency. Adrenal adequacy was defined as T-CORT greater than 20 µg/dL or F-CORT greater than 2.0 µg/dL. RESULTS: Total CORT correlated significantly with F-CORT (rs = +0.8, P < .0001). Microdialysis CORT had a lower correlation with T-CORT (rs = +0.6, P < .0001) and F-CORT (rs = +0.7, P < .0001) and a weak correlation with APACHE II score (rs = +0.4, P < .01). On the basis of MD-CORT, the patients were divided in quartiles. Although the median F-CORT and T-CORT levels were significantly different (P < .001) among the MD-CORT quartiles, there was a considerable overlap between the subgroups. All patients with T-CORT less than 10 µg/dL and all but 3 patients with F-CORT less than 0.8 µg/dL had tissue CORT in the lower quartile. However, only 50% and 58% of patients with adequate T-CORT and F-CORT levels, respectively, had concordant MD-CORT in the highest quartile. CONCLUSIONS: Microdialysis CORT levels correlate moderately with circulating T-CORT and F-CORT. Of note, several patients presented with discrepant measurements between interstitial and circulating CORT concentrations. Thus, interstitial CORT measurements represent an additional tool to investigate the tissue CORT availability in critically ill patients.


Assuntos
Hidrocortisona/análise , Unidades de Terapia Intensiva , Respiração Artificial , Sepse/fisiopatologia , APACHE , Idoso , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Microdiálise , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Prognóstico , Estudos Prospectivos
20.
J Crit Care ; 27(6): 742.e9-18, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23089678

RESUMO

PURPOSE: The aim of the study was to study the interrelationship between blood and tissue lactate in critically ill patients with or without shock admitted in a general intensive care unit. MATERIALS AND METHODS: We studied 162 mechanically ventilated patients: 106 with shock (septic shock, 97; cardiogenic shock, 9) and 56 without shock (severe sepsis, 38; systemic inflammatory response syndrome, 18). A microdialysis catheter was inserted in the subcutaneous adipose tissue of the upper thigh, and interstitial fluid was collected every 4 hours for a maximum of 6 days. We assessed the relationship between tissue and blood lactate using cross-approximate entropy and cross-correlation analysis. RESULTS: Patients with shock had higher area under the curve for blood (261 vs 175 mmol/L*hours, P < .0001) and tissue lactate (386 vs 281 mmol/L*hours, P < .0001) compared with patients without shock. The interrelationship of tissue-blood lactate, as assessed with cross-approximate entropy, was more regular in patients with shock compared with patients without shock. Cross-correlation of tissue vs blood lactate yielded higher correlation coefficients in patients with shock compared with those without shock, being higher when tissue lactate preceded blood lactate by 4 hours compared with tissue vs blood lactate with no lag time. CONCLUSIONS: In critical illness, the detailed dynamics between blood and tissue lactate are affected by the presence of shock. In patients with shock, microdialysis-assessed tissue lactate is higher compared with those without shock and may detect metabolic disturbances before these become evident in the systemic circulation.


Assuntos
Tecido Adiposo/química , Unidades de Terapia Intensiva/estatística & dados numéricos , Ácido Láctico/análise , Choque/metabolismo , Idoso , Líquido Extracelular/química , Feminino , Indicadores Básicos de Saúde , Humanos , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sepse/metabolismo , Choque/sangue , Choque Cardiogênico/metabolismo , Choque Séptico/metabolismo , Síndrome de Resposta Inflamatória Sistêmica/metabolismo
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