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1.
Artigo em Inglês | MEDLINE | ID: mdl-32898224

RESUMO

CONTEXT: More than half of patients diagnosed with unilateral primary aldosteronism (UPA) suffer from persisting hypertension after unilateral adrenalectomy. OBJECTIVE: To develop and validate a nomogram-based preoperative score (NBPS) to predict clinical outcomes after unilateral adrenalectomy for UPA. DESIGN AND SETTING: The NBPS was developed in an Asian cohort by incorporating predictors independently associated with remission of hypertension after unilateral adrenalectomy for UPA and validated in a Caucasian cohort. PARTICIPANTS: Patients with UPA achieving complete biochemical success after unilateral adrenalectomy. MAIN OUTCOME MEASURE: the predictive performance of NBPS compared with two previously developed outcome prediction scores: aldosteronoma resolution score (ARS) and primary aldosteronism surgical outcome (PASO) score. RESULTS: Ninety-seven of 150 (64.7%) patients achieved complete clinical success after unilateral adrenalectomy in the training cohort and 57 out of 165 (34.5%) in the validation cohort. A nomogram was established incorporating sex, duration of hypertension, aldosterone to renin ratio and target organ damage. The nomogram showed good concordance indices and calibration curves in both Asian and Caucasian cohorts. The area under the receiver operating characteristic curve (AUC) of NBPS for predicting hypertension remission in the training cohort was 0.853 (0.786-0.905), which was superior to ARS [0.745(0.667-0.812), p=0.019] and PASO score [0.747(0.670-0.815), p=0.012]. The AUC of NBPS in the validation cohort was 0.830 (0.764-0.884), which was higher than ARS [0.745 (95% CI 0.672-0.810), p=0.045], but not significantly different from PASO score [0.825 (95% CI 0.758-0.880), p=0.911]. CONCLUSION: The NBPS is useful in predicting clinical outcome for UPA patients, especially in the Asian population.

2.
J Hypertens ; 38(10): 1929-1936, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32890265

RESUMO

: Primary aldosteronism is a frequent cause of secondary hypertension requiring a specific pharmacological treatment with mineralocorticoid receptor antagonist or with unilateral adrenalectomy. These treatments have shown to reduce the excess of cardiovascular risk characteristically associated with this disease. In part I of this consensus, we discussed the procedures for the diagnosis of primary aldosteronism. In the present part II, we address the strategies for the differential diagnosis of primary aldosteronism subtypes and therapy. We also discuss the evaluation of outcomes and provide suggestions for follow-up as well as cardiovascular and metabolic complications specifically associated with primary aldosteronism. Finally, we analyse the principal gaps of knowledge and future challenges for research in this field.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32882010

RESUMO

CONTEXT: Glucocorticoid-induced myopathy is a characteristic symptom of endogenous Cushing's syndrome. Its long-term outcome is largely unknown. OBJECTIVE: To evaluate long-term muscle function following remission of endogenous Cushing's syndrome. STUDY DESIGN: Observational longitudinal cohort study. SETTING: Tertiary care hospitals and specialized outpatient clinic. PATIENTS: As part of the prospective multicenter German Cushing's Registry we assessed muscle strength in patients with overt endogenous Cushing's syndrome. We studied the patients at the time of diagnosis (n=88), after 6 months (n=69) and thereafter annually following surgical remission over a period of up to four years (1 year: n=55; 2 years: n=34; 3 years: n=29; 4 years: n=22). Muscle function was evaluated by hand grip strength and by chair rising test. RESULTS: Grip strength was decreased to 83 % of normal controls (100 %) at time of diagnosis. It further decreased to 71 % after 6 months in remission (p≤0.001) and showed no improvement during further follow-up compared to baseline. Chair rising test performance improved initially (8 seconds at baseline vs 7 seconds after 6 months, p=0.004) but remained at this reduced level thereafter (7 seconds after 3 years vs 5 seconds in controls, p=0.038). In multivariate analysis we identified as predictors for long-term muscle dysfunction age, waist-to-hip-ratio and HbA1c at baseline. Furthermore, muscle strength during follow-up was strongly correlated with quality of life. CONCLUSION: This study shows that Cushing's syndrome associated myopathy does not spontaneously resolve during remission. This calls for action to identify effective interventions to improve muscle dysfunction in this setting.

4.
Endocrine ; 2020 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-32743767

RESUMO

PURPOSE: Recurrence after pituitary surgery in Cushing's disease (CD) is a common problem ranging from 5% (minimum) to 50% (maximum) after initially successful surgery, respectively. In this review, we give an overview of the current literature regarding prevalence, diagnosis, and therapeutic options of recurrent CD. METHODS: We systematically screened the literature regarding recurrent and persistent Cushing's disease using the MESH term Cushing's disease and recurrence. Of 717 results in PubMed, all manuscripts in English and German published between 1980 and April 2020 were screened. Case reports, comments, publications focusing on pediatric CD or CD in veterinary disciplines or studies with very small sample size (patient number < 10) were excluded. Also, papers on CD in pregnancy were not included in this review. RESULTS AND CONCLUSIONS: Because of the high incidence of recurrence in CD, annual clinical and biochemical follow-up is paramount. 50% of recurrences occur during the first 50 months after first surgery. In case of recurrence, treatment options include second surgery, pituitary radiation, targeted medical therapy to control hypercortisolism, and bilateral adrenalectomy. Success rates of all these treatment options vary between 25 (some of the medical therapy) and 100% (bilateral adrenalectomy). All treatment options have specific advantages, limitations, and side effects. Therefore, treatment decisions have to be individualized according to the specific needs of the patient.

5.
PLoS One ; 15(8): e0237364, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764816

RESUMO

OBJECTIVES: Uromodulin has been associated with arterial hypertension in genome-wide association studies, but data from clinical and preclinical studies are inconsistent. We here analyzed the association of serum uromodulin (sUmod) with arterial hypertension and vasoactive hormones in a population-based study. METHODS: In 1108 participants of the KORA F4 study aged 62-81 years, sUmod was measured and the association of sUmod with arterial hypertension was assessed using logistic regression models. The associations of sUmod with renin and aldosterone and with the vasoconstrictive prohormone C-terminal pro-endothelin-1 (CT-proET-1) were analyzed in 1079 participants and in 618 participants, respectively, using linear regression models. RESULTS: After multivariable adjustment including sex, age, eGFR, BMI, fasting glucose, current smoking, previous stroke and myocardial infarction, sUmod was inversely associated with arterial hypertension (OR 0.78; 95% CI 0.68-0.91; p = 0.001). SUmod was not significantly associated with renin and aldosterone after adjustment for sex, age and eGFR. However, sUmod was inversely associated with CT-proET-1 (ß -0.19 ± 0.04; p < 0.001) after adjustment for sex, age, eGFR, BMI, arterial hypertension, fasting glucose, current smoking, previous stroke and myocardial infarction. The association with CT-proET-1 was stronger in participants with hypertension (ß -0.22 ± 0.04) than in normotensive participants (ß -0.13 ± 0.06; p for interaction hypertension = 0.003 in the model adjusted for hypertension). CONCLUSIONS: SUmod was inversely associated with arterial hypertension and the vasoconstrictive prohormone CT-proET-1, suggesting direct or indirect effects of sUmod on blood pressure regulation.

6.
J Psychiatr Res ; 130: 82-88, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32798773

RESUMO

High levels of aldosterone appear to be related to depressive and anxiety related behavior as demonstrated in therapy refractory depression and primary aldosteronism (PA). We analyzed data from a large register of patients with PA in order to clarify mediators and moderators of this influence. Up to 624 subjects were analyzed, however not all subjects had a complete dataset. Due to the known gender differences in subjects with PA we performed the analyses adjusted for gender. We compared subjects with (PHQ-9 ≥ 5) vs. no depressive symptomatology. 56% of men and 61% of women met this depression criterion. In women aldosterone concentration was significantly higher in depressed patients and renin levels were significantly increased with higher anxiety scores. This was not found in men. Depressive symptoms in men and women were significantly associated to BMI (men: dep vs non-dep: 29.6 vs. 28.4, p < 0.05; women: 26.9 vs. 24.5) and body weight (p < 0.05). Neither blood pressure nor electrolytes were different between depression groups. The relationship of these parameters to anxiety was less pronounced and partially unexpected: only in men higher anxiety (GAD ≥ 5) was related to lower systolic blood pressure. In conclusion, higher aldosterone appears to be associated with depressive symptoms in women, but less so in men with PA. BMI appears to be strongly and independently associated with depressive symptoms in patients with PA, independent of gender. Further studies are required to clarify the causal relationship.

7.
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
8.
J Clin Endocrinol Metab ; 105(9)2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32609829

RESUMO

CONTEXT: Catecholamines and adrenocortical steroids are important regulators of blood pressure. Bidirectional relationships between adrenal steroids and catecholamines have been established but whether this is relevant to patients with pheochromocytoma is unclear. OBJECTIVE: This study addresses the hypothesis that patients with pheochromocytoma and paraganglioma (PPGL) have altered steroid production compared with patients with primary hypertension. DESIGN: Multicenter cross-sectional study. SETTING: Twelve European referral centers. PATIENTS: Subjects included 182 patients with pheochromocytoma, 36 with paraganglioma and 270 patients with primary hypertension. Patients with primary aldosteronism (n = 461) and Cushing syndrome (n = 124) were included for additional comparisons. INTERVENTION: In patients with PPGLs, surgical resection of tumors. OUTCOME MEASURES: Differences in mass spectrometry-based profiles of 15 adrenal steroids between groups and after surgical resection of PPGLs. Relationships of steroids to plasma and urinary metanephrines and urinary catecholamines. RESULTS: Patients with pheochromocytoma had higher (P < .05) circulating concentrations of cortisol, 11-deoxycortisol, 11-deoxycorticosterone, and corticosterone than patients with primary hypertension. Concentrations of cortisol, 11-deoxycortisol, and corticosterone were also higher (P < .05) in patients with pheochromocytoma than with paraganglioma. These steroids correlated positively with plasma and urinary metanephrines and catecholamines in patients with pheochromocytoma, but not paraganglioma. After adrenalectomy, there were significant decreases in cortisol, 11-deoxycortisol, corticosterone, 11-deoxycorticosterone, aldosterone, and 18-oxocortisol. CONCLUSIONS: This is the first large study in patients with PPGLs that supports in a clinical setting the concept of adrenal cortical-medullary interactions involving an influence of catecholamines on adrenal steroids. These findings could have implications for the cardiovascular complications of PPGLs and the clinical management of patients with the tumors.

9.
J Hypertens ; 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32618890

RESUMO

: Primary aldosteronism is a frequent cause of secondary hypertension requiring a specific pharmacological treatment with mineralocorticoid receptor antagonist or with unilateral adrenalectomy. These treatments have shown to reduce the excess of cardiovascular risk characteristically associated with this disease. In part I of this consensus, we discussed the procedures for the diagnosis of primary aldosteronism. In the present part II, we address the strategies for the differential diagnosis of primary aldosteronism subtypes and therapy. We also discuss the evaluation of outcomes and provide suggestions for follow-up as well as cardiovascular and metabolic complications specifically associated with primary aldosteronism. Finally, we analyse the principal gaps of knowledge and future challenges for research in this field.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32717746

RESUMO

OBJECTIVE: Develop a consensus for the nomenclature and definition of adrenal histopathologic features in unilateral primary aldosteronism (PA). CONTEXT: Unilateral PA is the most common surgically-treated form of hypertension. Morphologic examination combined with CYP11B2 (aldosterone synthase) immunostaining reveals diverse histopathologic features of lesions in the resected adrenals. PATIENTS AND METHODS: Surgically removed adrenals (n= 37) from 90 patients operated from 2015 to 2018 in Munich, Germany, were selected to represent the broad histologic spectrum of unilateral PA. Five pathologists (Group 1 from Germany, Italy and Japan) evaluated the histopathology of haematoxylin-eosin and CYP11B2 immunostained sections and a consensus was established to define the identifiable features. The consensus was subsequently used by six additional pathologists (Group 2 from Australia, Brazil, Canada, Japan, UK, USA) for the assessment of all adrenals with disagreement for histopathologic diagnoses among group 1 pathologists. RESULTS: Consensus was achieved to define histopathologic features associated with PA. Use of CYP11B2 immunostaining resulted in a change of the original haematoxylin-eosin morphology-driven diagnosis in 5 (14%) of 37 cases. Using the consensus criteria, group 2 pathologists agreed for the evaluation of 11 of the 12 cases of disagreement among group 1 pathologists. CONCLUSION: The HISTALDO (histopathology of primary aldosteronism) consensus is useful to standardize nomenclature and achieve consistency among pathologists for the histopathologic diagnosis of unilateral PA. CYP11B2 immunohistochemistry should be incorporated into the routine clinical diagnostic workup to localize the likely source of aldosterone production.

11.
Endocrine ; 69(3): 625-633, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32594379

RESUMO

CONTEXT: Primary aldosteronism (PA) is the most frequent form of endocrine hypertension. Besides its deleterious impact on cardiovascular target organ damage, PA is considered to cause osteoporosis. PATIENTS AND METHODS: We assessed bone turnover in a subset of 36 postmenopausal women with PA. 18 patients had unilateral PA and were treated by adrenalectomy, whereas 18 patients had bilateral PA and received mineralocorticoid receptor antagonist (MRA) therapy respectively. 18 age- and BMI-matched females served as controls. To estimate bone remodeling, we measured the bone turnover markers intact procollagen 1 N-terminal propeptide, bone alkaline phosphatase, osteocalcin and tartrate resistant acid phosphatase 5b in plasma by chemiluminescent immunoassays at time of diagnosis and one year after initiation of treatment. STUDY DESIGN: Observational longitudinal cohort study. SETTING: Tertiary care hospital. RESULTS: Compared with controls, patients with PA had mildly elevated osteocalcin at baseline (p = 0.013), while the other bone markers were comparable between both groups. There were no differences between the unilateral and the bilateral PA subgroup. One year after initiation of MRA treatment with spironolactone bone resorption and bone formation markers had significantly decreased in patients with bilateral PA. In contrast, patients adrenalectomized because of unilateral PA showed no significant change of bone turnover markers. CONCLUSION: This study shows that aldosterone excess in postmenopausal women with PA is not associated with a relevant increase of bone turnover markers at baseline. However, we observed a significant decrease of bone markers in patients treated with spironolactone, but not in patients treated by adrenalectomy.

12.
J Clin Endocrinol Metab ; 105(10)2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32561919

RESUMO

CONTEXT: Primary aldosteronism (PA) comprises unilateral (lateralized [LPA]) and bilateral disease (BPA). The identification of LPA is important to recommend potentially curative adrenalectomy. Adrenal venous sampling (AVS) is considered the gold standard for PA subtyping, but the procedure is available in few referral centers. OBJECTIVE: To develop prediction models for subtype diagnosis of PA using patient clinical and biochemical characteristics. DESIGN, PATIENTS AND SETTING: Patients referred to a tertiary hypertension unit. Diagnostic algorithms were built and tested in a training (N = 150) and in an internal validation cohort (N = 65), respectively. The models were validated in an external independent cohort (N = 118). MAIN OUTCOME MEASURE: Regression analyses and supervised machine learning algorithms were used to develop and validate 2 diagnostic models and a 20-point score to classify patients with PA according to subtype diagnosis. RESULTS: Six parameters were associated with a diagnosis of LPA (aldosterone at screening and after confirmatory testing, lowest potassium value, presence/absence of nodules, nodule diameter, and computed tomography results) and were included in the diagnostic models. Machine learning algorithms displayed high accuracy at training and internal validation (79.1%-93%), whereas a 20-point score reached an area under the curve of 0.896, and a sensitivity/specificity of 91.7/79.3%. An integrated flowchart correctly addressed 96.3% of patients to surgery and would have avoided AVS in 43.7% of patients. The external validation on an independent cohort confirmed a similar diagnostic performance. CONCLUSIONS: Diagnostic modelling techniques can be used for subtype diagnosis and guide surgical decision in patients with PA in centers where AVS is unavailable.

13.
Horm Metab Res ; 52(6): 345-346, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32544975

RESUMO

Primary aldosteronism (PA) is characterized by hypertension caused by inappropriately high adrenal aldosterone secretion, consecutively low plasma renin, and an elevated aldosterone to renin ratio. It is nowadays the universally accepted main cause of endocrine hypertension. According to the most recent epidemiological data, PA is present in 5.8% of unselected hypertensives in primary care, 6-12% of hypertensives treated in hypertension centers, and up to 30% in subjects with resistant hypertension 1. Despite this high prevalence, a recent survey demonstrated that screening for PA is not universally followed. Renin and aldosterone measurements, the basis for PA screening, are currently performed by only 7% of general practitioners in Italy and 8% in Germany 2. Accordingly, the prevalence of PA was low with 1% among hypertensives in Italy and 2% in Germany. In a retrospective cohort study of 4660 patients with resistant hypertension in California the screening rate for PA was 2.1% 3. Based on these data, it is clear that we still miss the majority of PA cases, despite advances in diagnosis and therapy.

14.
Dtsch Med Wochenschr ; 145(11): 716-721, 2020 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-32492739

RESUMO

Primary aldosteronism (PA) represents the leading cause of endocrine hypertension, accounting for 4-13 % of all cases. Simultaneously, it is the most common endocrine form of hypertension that can be cured by surgery. Estimates suggest that 2.5 million people in Germany are affected, yet only 8 % of hypertensive patients undergo the proper diagnostic screening for PA. The diagnosis of PA is evidently not taken into account sufficiently when it comes to the everyday management of hypertension. Since PA patients carry an increased risk of cardio- and cerebrovascular events as well as metabolic comorbidities, early screening and diagnosis is crucial.This manuscript highlights the current guidelines of screening and diagnosing PA and addresses some currently published findings regarding this area. The aim is to raise awareness when it comes to diagnosing and screening for PA in the everyday management of hypertensive patients.

15.
Eur J Endocrinol ; 183(1): G1-G7, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: covidwho-256412

RESUMO

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


Assuntos
Infecções por Coronavirus/prevenção & controle , Síndrome de Cushing/terapia , Inibidores Enzimáticos/uso terapêutico , Glucocorticoides/uso terapêutico , Controle de Infecções/métodos , Procedimentos Neurocirúrgicos/métodos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Telemedicina , Inibidores de 14-alfa Desmetilase/uso terapêutico , Adenoma Hipofisário Secretor de ACT/complicações , Adenoma Hipofisário Secretor de ACT/diagnóstico , Adenoma Hipofisário Secretor de ACT/terapia , Adenoma/complicações , Adenoma/diagnóstico , Adenoma/terapia , Infecções por Coronavirus/transmissão , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiologia , Síndrome de Cushing/imunologia , Gerenciamento Clínico , Humanos , Hidrocortisona/sangue , Hospedeiro Imunocomprometido , Cetoconazol/uso terapêutico , Metirapona/uso terapêutico , Educação de Pacientes como Assunto , Pneumonia Viral/transmissão , Guias de Prática Clínica como Assunto , Índice de Gravidade de Doença , Fatores de Tempo
16.
Eur J Endocrinol ; 183(2): 191-201, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32460235

RESUMO

Objective: Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) has become state of the art for the quantitative analysis of steroid hormones. Although method comparisons show that aldosterone measurement using LC-MS/MS yields considerably lower levels than immunoassays (IAs), method-specific cutoff values for primary aldosteronism (PA) are largely missing. Objective of this study was to analyze the diagnostic accuracy of proposed LC-MS/MS-specific cutoff values for the saline infusion test (SIT). Design and methods: From 2016 to 2019, 104 consecutive patients suspected of PA underwent the SIT and captopril challenge test in the tertiary medical center at the University Hospital of Leipzig, Germany. Patients with positive case confirmation underwent adrenal imaging and adrenal venous sampling for subtype classification. Results: Overall, proposed assay-specific PACLC-MS/MS cutoff values for the SIT achieved higher diagnostic accuracy than established PACIA values with a sensitivity and specificity of 87.5% (95% CI: 71.0-96.5) and 97% (95% CI: 89.6-99.6) for a cutoff of 120 pmol/L and 93.8% (95% CI: 79.2-99.2) and 92.5% (95% CI: 83.4-97.5) for a cutoff of 94 pmol/L. The most accurate post-SIT PACLC-MS/MS cutoff value in this study was 83 pmol/L, yielding a sensitivity and specificity of 96.9% (95% CI: 83.8-99.9) and 92.5% (95% CI: 83.4-97.5), respectively. Conclusions: The present data confirm the need for the implication of lower method-specific aldosterone cutoff values for the diagnosis of PA with LC-MS/MS based aldosterone measurement.


Assuntos
Aldosterona/sangue , Hiperaldosteronismo/sangue , Hiperaldosteronismo/diagnóstico , Solução Salina/farmacologia , Glândulas Suprarrenais/diagnóstico por imagem , Adulto , Idoso , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Captopril/farmacologia , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Valores de Referência , Reprodutibilidade dos Testes , Solução Salina/administração & dosagem , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem , Adulto Jovem
17.
Eur J Endocrinol ; 183(1): G1-G7, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32380475

RESUMO

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


Assuntos
Infecções por Coronavirus/prevenção & controle , Síndrome de Cushing/terapia , Inibidores Enzimáticos/uso terapêutico , Glucocorticoides/uso terapêutico , Controle de Infecções/métodos , Procedimentos Neurocirúrgicos/métodos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Telemedicina , Inibidores de 14-alfa Desmetilase/uso terapêutico , Adenoma Hipofisário Secretor de ACT/complicações , Adenoma Hipofisário Secretor de ACT/diagnóstico , Adenoma Hipofisário Secretor de ACT/terapia , Adenoma/complicações , Adenoma/diagnóstico , Adenoma/terapia , Infecções por Coronavirus/transmissão , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiologia , Síndrome de Cushing/imunologia , Gerenciamento Clínico , Humanos , Hidrocortisona/sangue , Hospedeiro Imunocomprometido , Cetoconazol/uso terapêutico , Metirapona/uso terapêutico , Educação de Pacientes como Assunto , Pneumonia Viral/transmissão , Guias de Prática Clínica como Assunto , Índice de Gravidade de Doença , Fatores de Tempo
18.
Horm Metab Res ; 52(6): 404-411, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32403151

RESUMO

Excess aldosterone is associated with the increased risk of cardio-/cerebrovascular events as well as metabolic comorbidities not only due to its hypertensive effect but also due to its proinflammatory action. Autonomous cortisol secretion (ACS) in the setting of primary aldosteronism (PA) is known to worsen cardiovascular outcome and potentially exhibit immunosuppressive effects. The aim of this study was to determine the impact of ACS status in patients with PA on kinetics of thyroid autoantibodies (anti-TPO, anti-TG) pre and post therapy initiation. Ninety-seven PA patients (43 unilateral, 54 with bilateral PA) from the database of the German Conn's Registry were included. Anti-TPO and anti-TG levels were measured pre and 6-12 months post therapeutic intervention. Patients were assessed for ACS according to their 24- hour urinary cortisol excretion, late night salivary cortisol and low-dose dexamethasone suppression test. Abnormal test results in line with ACS were identified in 74.2% of patients with PA. Following adrenalectomy, significant increases in anti-TPO levels were observed in patients with at least one abnormal test (p = 0.049), adrenalectomized patients with at least two pathological ACS tests (p = 0.015) and adrenalectomized patients with pathologic dexamethasone suppression tests (p = 0.018). No antibody increases were observed in unilateral PA patients without ACS and in patients with bilateral PA receiving mineralocorticoid antagonist therapy (MRA). Our data are in line with an immunosuppressive effect of mild glucocorticoid excess in PA on thyroid autoantibody titers. This effect is uncovered by adrenalectomy, but not by MRA treatment.

20.
Endocr Relat Cancer ; 27(7): 403-413, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32348959

RESUMO

Biochemical characterization of primary bilateral macronodular adrenocortical hyperplasia (PBMAH) by distinct plasma steroid profiles and its putative correlation to disease has not been previously studied. LC-MS/MS-based steroid profiling of 16 plasma steroids was applied to 36 subjects (22 females, 14 males) with PBMAH, 19 subjects (16 females, 3 males) with other forms of adrenal Cushing's syndrome (ACS), and an age and sex-matched control group. Germline ARMC5 sequencing was performed in all PBMAH cases. Compared to controls, PBMAH showed increased plasma 11-deoxycortisol, corticosterone, 11-deoxycorticosterone, 18-hydroxycortisol, and aldosterone, but lower progesterone, DHEA, and DHEA-S with distinct differences in subjects with and without pathogenic variants in ARMC5. Steroids that showed isolated differences included cortisol and 18-oxocortisol with higher (P < 0.05) concentrations in ACS than in controls and aldosterone with higher concentrations in PBMAH when compared to controls. Larger differences in PBMAH than with ACS were most clear for corticosterone, but there were also trends in this direction for 18-hydroxycortisol and aldosterone. Logistic regression analysis indicated four steroids - DHEA, 11-deoxycortisol, 18-oxocortisol, and corticosterone - with the most power for distinguishing the groups. Discriminant analyses with step-wise variable selection indicated correct classification of 95.2% of all subjects of the four groups using a panel of nine steroids; correct classification of subjects with and without germline variants in ARMC5 was achieved in 91.7% of subjects with PBMAH. Subjects with PBMAH show distinctive plasma steroid profiles that may offer a supplementary single-test alternative for screening purposes.

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