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1.
Expert Rev Endocrinol Metab ; : 1-14, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32967470

RESUMO

INTRODUCTION: Pituitary gland is vulnerable to traumatic brain injury (TBI). As a result a series of neuroendocrine changes appear after head injury; in many occasions they reverse with time, while occasionally new late onset changes may develop. AREAS COVERED: In this review, we focus on the prevalence of anterior and posterior pituitary hormonal changes in the acute and chronic post-TBI period in both children and adults. Moreover, we present evidence supporting the need for evaluating pituitary function along with the current suggestions for the most appropriate screening strategies. We attempted to identify all published literature and we conducted an online search of PubMed, from January 1970 to June 2020. EXPERT OPINION: Adrenal insufficiency and water metabolism disorders are medical emergencies and should be promptly recognized. Awareness for long-term hormonal derangements is necessary, as they may lead to a series of chronic health issues and compromise quality of life. There is a need for well-designed prospective long-term studies that will estimate pituitary function during the acute and chronic phase after head injury.

2.
Lancet Diabetes Endocrinol ; 8(9): 773-781, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32711725

RESUMO

BACKGROUND: Cross-sectional imaging regularly results in incidental discovery of adrenal tumours, requiring exclusion of adrenocortical carcinoma (ACC). However, differentiation is hampered by poor specificity of imaging characteristics. We aimed to validate a urine steroid metabolomics approach, using steroid profiling as the diagnostic basis for ACC. METHODS: We did a prospective multicentre study in adult participants (age ≥18 years) with newly diagnosed adrenal masses. We assessed the accuracy of diagnostic imaging strategies based on maximum tumour diameter (≥4 cm vs <4 cm), imaging characteristics (positive vs negative), and urine steroid metabolomics (low, medium, or high risk of ACC), separately and in combination, using a reference standard of histopathology and follow-up investigations. With respect to imaging characteristics, we also assessed the diagnostic utility of increasing the unenhanced CT tumour attenuation threshold from the recommended 10 Hounsfield units (HU) to 20 HU. FINDINGS: Of 2169 participants recruited between Jan 17, 2011, and July 15, 2016, we included 2017 from 14 specialist centres in 11 countries in the final analysis. 98 (4·9%) had histopathologically or clinically and biochemically confirmed ACC. Tumours with diameters of 4 cm or larger were identified in 488 participants (24·2%), including 96 of the 98 with ACC (positive predictive value [PPV] 19·7%, 95% CI 16·2-23·5). For imaging characteristics, increasing the unenhanced CT tumour attenuation threshold to 20 HU from the recommended 10 HU increased specificity for ACC (80·0% [95% CI 77·9-82·0] vs 64·0% [61·4-66.4]) while maintaining sensitivity (99·0% [94·4-100·0] vs 100·0% [96·3-100·0]; PPV 19·7%, 16·3-23·5). A urine steroid metabolomics result indicating high risk of ACC had a PPV of 34·6% (95% CI 28·6-41·0). When the three tests were combined, in the order of tumour diameter, positive imaging characteristics, and urine steroid metabolomics, 106 (5·3%) participants had the result maximum tumour diameter of 4 cm or larger, positive imaging characteristics (with the 20 HU cutoff), and urine steroid metabolomics indicating high risk of ACC, for which the PPV was 76·4% (95% CI 67·2-84·1). 70 (3·5%) were classified as being at moderate risk of ACC and 1841 (91·3%) at low risk (negative predictive value 99·7%, 99·4-100·0). INTERPRETATION: An unenhanced CT tumour attenuation cutoff of 20 HU should replace that of 10 HU for exclusion of ACC. A triple test strategy of tumour diameter, imaging characteristics, and urine steroid metabolomics improves detection of ACC, which could shorten time to surgery for patients with ACC and help to avoid unnecessary surgery in patients with benign tumours. FUNDING: European Commission, UK Medical Research Council, Wellcome Trust, and UK National Institute for Health Research, US National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.


Assuntos
Neoplasias das Glândulas Suprarrenais/epidemiologia , Neoplasias das Glândulas Suprarrenais/urina , Metabolômica/métodos , Esteroides/urina , Neoplasias das Glândulas Suprarrenais/diagnóstico , Adulto , Idoso , Diagnóstico Diferencial , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
3.
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.

4.
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.

5.
Curr Opin Endocrinol Diabetes Obes ; 27(3): 125-131, 2020 06.
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.

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.
J Clin Endocrinol Metab ; 105(4)2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31606735

RESUMO

OBJECTIVE: The aim of the Acromegaly Consensus Group was to revise and update the consensus on diagnosis and treatment of acromegaly comorbidities last published in 2013. PARTICIPANTS: The Consensus Group, convened by 11 Steering Committee members, consisted of 45 experts in the medical and surgical management of acromegaly. The authors received no corporate funding or remuneration. EVIDENCE: This evidence-based consensus was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence following critical discussion of the current literature on the diagnosis and treatment of acromegaly comorbidities. CONSENSUS PROCESS: Acromegaly Consensus Group participants conducted comprehensive literature searches for English-language papers on selected topics, reviewed brief presentations on each topic, and discussed current practice and recommendations in breakout groups. Consensus recommendations were developed based on all presentations and discussions. Members of the Scientific Committee graded the quality of the supporting evidence and the consensus recommendations using the GRADE system. CONCLUSIONS: Evidence-based approach consensus recommendations address important clinical issues regarding multidisciplinary management of acromegaly-related cardiovascular, endocrine, metabolic, and oncologic comorbidities, sleep apnea, and bone and joint disorders and their sequelae, as well as their effects on quality of life and mortality.

8.
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
9.
Eur J Endocrinol ; 181(5): 461-472, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31480014

RESUMO

Objective: Patients with Cushing's syndrome (CS) have increased mortality. The aim of this study was to evaluate the causes and time of death in a large cohort of patients with CS and to establish factors associated with increased mortality. Methods: In this cohort study, we analyzed 1564 patients included in the European Registry on CS (ERCUSYN); 1045 (67%) had pituitary-dependent CS, 385 (25%) adrenal-dependent CS, 89 (5%) had an ectopic source and 45 (3%) other causes. The median (IQR) overall follow-up time in ERCUSYN was 2.7 (1.2-5.5) years. Results: Forty-nine patients had died at the time of the analysis; 23 (47%) with pituitary-dependent CS, 6 (12%) with adrenal-dependent CS, 18 (37%) with ectopic CS and two (4%) with CS due to other causes. Of 42 patients whose cause of death was known, 15 (36%) died due to progression of the underlying disease, 13 (31%) due to infections, 7 (17%) due to cardiovascular or cerebrovascular disease and 2 due to pulmonary embolism. The commonest cause of death in patients with pituitary-dependent CS and adrenal-dependent CS were infectious diseases (n = 8) and progression of the underlying tumor (n = 10) in patients with ectopic CS. Patients who had died were older and more often males, and had more frequently muscle weakness, diabetes mellitus and ectopic CS, compared to survivors. Of 49 deceased patients, 22 (45%) died within 90 days from start of treatment and 5 (10%) before any treatment was given. The commonest cause of deaths in these 27 patients were infections (n = 10; 37%). In a regression analysis, age, ectopic CS and active disease were independently associated with overall death before and within 90 days from the start of treatment. Conclusion: Mortality rate was highest in patients with ectopic CS. Infectious diseases were the commonest cause of death soon after diagnosis, emphasizing the need for careful clinical vigilance at that time, especially in patients presenting with concomitant diabetes mellitus.


Assuntos
Síndrome de Cushing/mortalidade , Doenças das Glândulas Suprarrenais/etiologia , Doenças das Glândulas Suprarrenais/mortalidade , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Estudos de Coortes , Comorbidade , Síndrome de Cushing/complicações , Complicações do Diabetes/mortalidade , Europa (Continente)/epidemiologia , Feminino , França/epidemiologia , Humanos , Infecções/complicações , Infecções/mortalidade , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/etiologia , Doenças da Hipófise/mortalidade , Sistema de Registros , Fatores Sexuais , Adulto Jovem
10.
Artigo em Inglês | MEDLINE | ID: mdl-30802917

RESUMO

BACKGROUND: The purpose of the present study was to determine whether patients with DM1 have shown improvement, stabilization or deterioration of their urine albumin excretion levels during a close follow-up. PATIENTS AND METHODS: A cohort of 84 patients, 18-76 years of age, a median duration of diabetes of 24 years (1-50 years) and a median follow-up duration of 12 years (1-37 years) were included in the study. RESULTS: Among the 84 patients for whom we had UAE levels at the beginning and by the end of the study, mean glycosylated hemoglobin was statistically significantly decreased during the follow-up period, from 8.02±2.04-7.06±1.05% (p=0.036). Normoalbuminuria was present in 66 patients and remained so in 56 patients while 9 patients progressed to microalbuminuria and one patient to macroalbuminuria by the end of the study. Microalbuminuria was present in 15 patients: regression was observed in 8 patients, and progression in one patient. Regression of macroalbuminuria to microalbuminuria was noted in one patient and to normoalbuminuria was noted in one participant, too. CONCLUSIONS: Improvement of glycemic control with close monitoring of DM1 patients together with the appropriate use ACE or AT2 inhibitors and statins, seems to exert nephron-protective potential and to delay or even reverse the presence of micro/macroalbuminuria. This long term follow-up study has demonstrated a statistically significant increase in serum HDLcholesterol levels. The study also revealed that intensively treated diabetes patients may show reductions in serum ALP levels. Whether this finding is related to diabetic nephropathy, NAFLD, or diabetic hepatosclerosis remains to be assessed in future trials.

11.
Hormones (Athens) ; 18(2): 141-144, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30719628

RESUMO

The ratio of human to bacterial cells in the human body (microbiota) is around 1:1. As a result of co-evolution of the host mucosal immune system and the microbiota, both have developed multiple mechanisms to maintain homeostasis. However, dissociations between the composition of the gut microbiota and the human host may play a crucial role in the development of type 2 diabetes. Metformin, the most frequently administered medication to treat patients with type 2 diabetes, has only recently been suggested to alter gut microbiota composition through the increase in mucin-degrading Akkermansia muciniphila, as well as several SCFA-producing (short-chain fatty acid) microbiota. The gut microbiota of participants on metformin has exerted alterations in gut metabolomics with increased ability to produce butyrate and propionate, substances involved in glucose homeostasis. Thus, metformin appears to affect the microbiome, and an individual's metformin tolerance or intolerance may be influenced by their microbiome. In this review, we will focus on the effects of metformin in gut microbiota among patients with T2DM.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Metformina/uso terapêutico , Diabetes Mellitus Tipo 2/sangue , Homeostase/efeitos dos fármacos , Humanos , Metformina/farmacologia , Resultado do Tratamento
12.
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
13.
Pituitary ; 22(3): 283-295, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30746590

RESUMO

PURPOSE: It is estimated that approximately 69 million individuals worldwide will sustain a TBI each year, which accounts for substantial morbidity and mortality in both children and adults. TBI may lead to significant neuroendocrine changes, if the delicate pituitary is ruptured. In this review, we focus on the anterior pituitary hormonal changes in the acute post-TBI period and we present the evidence supporting the need for screening of anterior pituitary function in the early post-TBI time along with current suggestions regarding the endocrine assessment and management of these patients. METHODS: Original systematic articles with prospective and/or retrospective design studies of acute TBI were included, as were review articles and case series. RESULTS: Although TBI may motivate an acute increase of stress hormones, it may also generate a wide spectrum of anterior pituitary hormonal deficiencies. The frequency of post-traumatic anterior hypopituitarism (PTHP) varies according to the severity, the type of trauma, the time elapsed since injury, the study population, and the methodology used to diagnose pituitary hormone deficiency. Early neuroendocrine abnormalities may be transient, but additional late ones may also appear during the course of rehabilitation. CONCLUSIONS: Acute hypocortisolism should be diagnosed and managed promptly, as it can be life-threatening, but currently there is no evidence to support treatment of acute GH, thyroid hormones or gonadotropins deficiencies. However, a more comprehensive assessment of anterior pituitary function should be undertaken both in the early and in the post-acute phase, since ongoing hormone deficiencies may adversely affect the recovery and quality of life of these patients.


Assuntos
Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/patologia , Animais , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Humanos , Hipopituitarismo/metabolismo , Hipopituitarismo/patologia , Doenças da Hipófise/metabolismo , Doenças da Hipófise/patologia , Qualidade de Vida
14.
Diabetes Metab Syndr ; 13(1): 608-611, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30641774

RESUMO

AIMS: In type 1 diabetes mellitus and autoimmune thyroiditis, there seems to be common genetic loci. The purpose of the present study was to determine whether patients with type 1 diabetes had increased prevalence of autoimmune thyroiditis, and which factors were influencing the co-existence of these two clinical entities. PATIENTS AND METHODS: A cohort of 256 patients, 18-79 years of age, a median duration of diabetes of 20 years and a mean follow-up duration of 13 years were included in the study. RESULTS: Of the 256 patients with type 1 diabetes, 150 participants (58.6%) were women and 106 (41.4%) were men. One hundred and fifty-nine patients (64.6%) did not have autoimmune thyroiditis, whereas 97 (35.4%) had autoimmune thyroiditis, as was documented by the presence of anti-thyroid antibodies (anti-TPO and/or anti-TG). Of the 97 patients with both diabetes type 1 and autoimmune thyroiditis, 64 (66%) were women and 33 (34%) were men. Among the 97 patients who had both diabetes type 1 and autoimmune thyroiditis, 87 had abnormal levels of both anti-TPO and anti-TG, while 7 patients had subnormal levels of solely anti-TPO and only 3 patients had abnormal levels of only anti-TG. CONCLUSIONS: There was a slightly higher prevalence of autoimmune thyroiditis among our patients with type 1 diabetes mellitus. Also, female sex was predominant, when compared to male sex, among the adult participants of this study. Therefore, regular screening of thyroid function and thyroid autoantibodies may be suggested for all patients with type 1 diabetes.


Assuntos
Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiologia , Tireoidite Autoimune/diagnóstico , Tireoidite Autoimune/epidemiologia , Adolescente , Adulto , Idoso , Estudos de Coortes , Diabetes Mellitus Tipo 1/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tireoidite Autoimune/sangue , Fatores de Tempo , Adulto Jovem
15.
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
16.
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
17.
Diabetes Res Clin Pract ; 146: 111-118, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30342053

RESUMO

Alterations in the diversity or structure of gut microbiota known as dysbiosis, may affect metabolic activities, resulting in metabolic disorders, such as obesity and diabetes. The development of more sophisticated methods, such as metagenomics sequencing, PCR-denaturing gradient gel electrophoresis, microarrays and fluorescence in situ hybridization, has expanded our knowledge on gut microbiome. Dysbiosis has been related to increased plasma concentrations of gut microbiota-derived lipopolysaccharide (LPS), which triggers the production of a variety of cytokines and the recruitment of inflammatory cells. Metabolomics have demonstrated that butyrate and propionate suppress weight gain in mice with high fat diet-induced obesity, and acetate has been proven to reduce food intake in healthy mice. The role of prebiotics, probiotics, genetically modified bacteria and fecal microbiota transplantation, as potential therapeutic challenges for type 2 diabetes will be discussed in this review.


Assuntos
Diabetes Mellitus Tipo 2/microbiologia , Disbiose/microbiologia , Transplante de Microbiota Fecal/métodos , Microbioma Gastrointestinal/genética , Prebióticos/microbiologia , Probióticos/metabolismo , Animais , Humanos , Camundongos
18.
Eur J Endocrinol ; 178(4): 399-409, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29440375

RESUMO

BACKGROUND: Surgery is the definitive treatment of Cushing's syndrome (CS) but medications may also be used as a first-line therapy. Whether preoperative medical treatment (PMT) affects postoperative outcome remains controversial. OBJECTIVE: (1) Evaluate how frequently PMT is given to CS patients across Europe; (2) examine differences in preoperative characteristics of patients who receive PMT and those who undergo primary surgery and (3) determine if PMT influences postoperative outcome in pituitary-dependent CS (PIT-CS). PATIENTS AND METHODS: 1143 CS patients entered into the ERCUSYN database from 57 centers in 26 countries. Sixty-nine percent had PIT-CS, 25% adrenal-dependent CS (ADR-CS), 5% CS from an ectopic source (ECT-CS) and 1% were classified as having CS from other causes (OTH-CS). RESULTS: Twenty per cent of patients took PMT. ECT-CS and PIT-CS were more likely to receive PMT compared to ADR-CS (P < 0.001). Most commonly used drugs were ketoconazole (62%), metyrapone (16%) and a combination of both (12%). Median (interquartile range) duration of PMT was 109 (98) days. PIT-CS patients treated with PMT had more severe clinical features at diagnosis and poorer quality of life compared to those undergoing primary surgery (SX) (P < 0.05). Within 7 days of surgery, PIT-CS patients treated with PMT were more likely to have normal cortisol (P < 0.01) and a lower remission rate (P < 0.01). Within 6 months of surgery, no differences in morbidity or remission rates were observed between SX and PMT groups. CONCLUSIONS: PMT may confound the interpretation of immediate postoperative outcome. Follow-up is recommended to definitely evaluate surgical results.


Assuntos
Síndrome de Cushing/tratamento farmacológico , Síndrome de Cushing/cirurgia , Glândulas Suprarrenais/fisiopatologia , Adulto , Idoso , Síndrome de Cushing/fisiopatologia , Bases de Dados Factuais , Europa (Continente) , Feminino , Humanos , Cetoconazol/uso terapêutico , Masculino , Metirapona/uso terapêutico , Pessoa de Meia-Idade , Síndromes Endócrinas Paraneoplásicas , Hipófise/fisiopatologia , Cuidados Pós-Operatórios , Período Pós-Operatório , Qualidade de Vida , Resultado do Tratamento
19.
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
20.
Eur J Endocrinol ; 176(5): 613-624, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28377460

RESUMO

OBJECTIVE: To evaluate which tests are performed to diagnose hypercortisolism in patients included in the European Registry on Cushing's syndrome (ERCUSYN), and to examine if their use differs from the current guidelines. PATIENTS AND METHODS: We analyzed data on the diagnostic tests performed in 1341 patients with Cushing's syndrome (CS) who have been entered into the ERCUSYN database between January 1, 2000 and January 31, 2016 from 57 centers in 26 European countries. Sixty-seven percent had pituitary-dependent CS (PIT-CS), 24% had adrenal-dependent CS (ADR-CS), 6% had CS from an ectopic source (ECT-CS) and 3% were classified as having CS from other causes (OTH-CS). RESULTS: Of the first-line tests, urinary free cortisol (UFC) test was performed in 78% of patients, overnight 1 mg dexamethasone suppression test (DST) in 60% and late-night salivary cortisol (LSaC) in 25%. Use of LSaC increased in the last five years as compared with previous years (P < 0.01). Use of HDDST was slightly more frequent in the last 5 years as compared with previous years (P < 0.05). Of the additional tests, late-night serum cortisol (LSeC) was measured in 62% and 48-h 2 mg/day low-dose dexamethasone suppression test (LDDST) in 33% of cases. ACTH was performed in 78% of patients. LSeC and overnight 1 mg DST supported the diagnosis of both PIT-CS and ADR-CS more frequently than UFC (P < 0.05). CONCLUSIONS: Use of diagnostic tests for CS varies across Europe and partly differs from the currently available guidelines. It would seem pertinent that a European consensus be established to determine the best diagnostic approach to CS, taking into account specific inter-country differences with regard to the availability of diagnostic tools.


Assuntos
Síndrome de Cushing/diagnóstico , Síndrome de Cushing/metabolismo , Testes Diagnósticos de Rotina/normas , Guias de Prática Clínica como Assunto/normas , Sistema de Registros , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Idoso , Síndrome de Cushing/epidemiologia , Testes Diagnósticos de Rotina/estatística & dados numéricos , Europa (Continente)/epidemiologia , Feminino , Humanos , Hidrocortisona/metabolismo , Masculino , Pessoa de Meia-Idade , Estatística como Assunto/métodos
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