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BACKGROUND: The incidence of cardiovascular complications may be higher in unilateral than in bilateral primary aldosteronism (PA). We compared non-invasive hemodynamics before and after targeted therapy of bilateral versus unilateral PA. METHODS: Adrenal vein sampling was performed, and cardiovascular variables were recorded using radial artery pulse wave analysis and whole-body impedance cardiography (n=114). In a subset of 40 patients (adrenalectomy n=20, spironolactone-based treatment n=20), hemodynamic recordings were again performed after 33 months of targeted PA treatment. RESULTS: In initial cross-sectional analysis, 51 patients had bilateral and 63 had unilateral PA. The mean ages were 50.6 and 54.3 years (p=0.081), and body mass indexes were 30.3 and 30.6 kg/m2 (p=0.724), respectively. Aortic blood pressure and cardiac output did not significantly differ between the groups, but evaluated left cardiac work was ~10% higher in unilateral PA (p=0.022). In the followup study, initial and final blood pressure levels in the aorta were not significantly different, while initial cardiac output (+13%, p=0.015) and left cardiac work (+17%, p=0.009) were higher in unilateral than in bilateral PA. After a median treatment time of 33 months, the differences in cardiac load were abolished, and extracellular water volume was reduced by 1.3 and 1.4 liters in bilateral versus unilateral PA, respectively (p=0.814). CONCLUSIONS: These results suggest that unilateral PA burdens the heart more than bilateral PA, providing a possible explanation for the higher incidence of cardiac complications in unilateral disease. A similar reduction in aldosterone-induced volume excess was obtained with targeted surgical and medical treatment of PA.
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OBJECTIVE: Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries. METHODS: A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert-type scale. RESULTS: Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists. CONCLUSION: This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
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Acromegalia , Técnica Delphi , Somatostatina , Acromegalia/terapia , Humanos , Somatostatina/análogos & derivados , Somatostatina/uso terapéutico , Países Escandinavos y Nórdicos/epidemiología , Consenso , Hormona de Crecimiento Humana/uso terapéutico , Hormona de Crecimiento Humana/análogos & derivados , Encuestas y CuestionariosRESUMEN
AIMS: To identify individuals with incidental fatty liver disease (FLD), and to evaluate its prevalence, metabolic co-morbidities and impact on follow-up. METHODS: We leveraged the data-lake of Helsinki Uusimaa Hospital district (Finland) with a population of 1.7 million (specialist and primary care). A phrase recognition script on abdominal imaging reports (2008-2020) identified/excluded FLD or cirrhosis; we extracted ICD-codes, laboratory and BMI data. RESULTS: Excluding those with other liver diseases, the prevalence of FLD was 29% (steatosis yes/no, N=61,271/155,521; cirrhosis, N=3502). The false positive and negative rates were 5-6%. Only 1.6% of the FLD cases had the ICD code recorded and 32% had undergone full clinical evaluation for associated co-morbidities. Of the 35-65-year-old individuals with FLD, 20% had diabetes, 42% prediabetes and 28% a high liver fibrosis index. FLD was independently predicted by diabetes (OR 1.56, CI 1.46-1.66, p = 2.3 * 10^-41), BMI (1.46, 1.42-1.50, p = 1.7 * 10^-154) and plasma triglyceride level (1.5, 1.43-1.57, p = 3.5 * 10^-68). Alanine aminotransferase level mildly increased (1.12, 1.08-1.16, p = 2.2 * 10^-9) and high age decreased the risk (0.92, 0.89-0.94, p = 4.65*10^-09). Half of the cases had normal ALT. CONCLUSIONS: The incidental radiological finding of FLD is reliable and associated with metabolic risks but largely ignored, although it should lead to metabolic and hepatic follow-up.
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Diabetes Mellitus , Enfermedad del Hígado Graso no Alcohólico , Humanos , Adulto , Persona de Mediana Edad , Anciano , Estudios de Cohortes , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Comorbilidad , Cirrosis Hepática/epidemiología , Diabetes Mellitus/epidemiologíaRESUMEN
OBJECTIVES: We examined haemodynamics, focusing on volume balance and forward and backward wave amplitudes, before and after 2.8âyears of targeted treatment of primary aldosteronism. Patients with essential hypertension and normotensive individuals were examined for comparison ( n â=â40 in each group). METHODS: Recordings were performed using radial artery pulse wave analysis and whole-body impedance cardiography. Unilateral aldosteronism was treated with adrenalectomy ( n â=â20), bilateral aldosteronism with spironolactone-based medication ( n â=â20), and essential hypertension with standard antihypertensive agents. RESULTS: Aortic SBP and DBP, forward and backward wave amplitudes, and systemic vascular resistance were equally elevated in primary aldosteronism and essential hypertension. All these haemodynamic variables were similarly reduced by the treatments. Primary aldosteronism presented with 1âlitre (â¼10%) extracellular water excess ( P â<â0.001) versus the other groups, and this excess was normalized by treatment. Initial pulse wave velocity (PWV) was similarly increased in primary aldosteronism and essential hypertension, but final values remained higher in primary aldosteronism ( P â<â0.001). In regression analyses, significant explanatory factors for treatment-induced forward wave amplitude reduction were decreased systemic vascular resistance ( ß â=â0.380) and reduced extracellular water volume ( ß â=â0.183). Explanatory factors for backward wave amplitude reduction were changes in forward wave amplitude ( ß â=â0.599), heart rate ( ß â=â-0.427), and PWV ( ß â=â0.252). CONCLUSION: Compared with essential hypertension, the principal haemodynamic difference in primary aldosteronism was higher volume load. Volume excess elevated forward wave amplitude, which was subsequently reduced by targeted treatment of primary aldosteronism, along with normalization of volume load. We propose that incorporating extracellular water evaluation alongside routine diagnostics could enhance the identification and diagnosis of primary aldosteronism.
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Hiperaldosteronismo , Análisis de la Onda del Pulso , Humanos , Hiperaldosteronismo/fisiopatología , Hiperaldosteronismo/complicaciones , Persona de Mediana Edad , Masculino , Femenino , Estudios de Seguimiento , Adulto , Hipertensión/fisiopatología , Hipertensión/tratamiento farmacológico , Hemodinámica , Adrenalectomía , Espironolactona/uso terapéutico , Presión Sanguínea , Antihipertensivos/uso terapéuticoRESUMEN
Objective: The associations between adrenal histopathology, lateralization studies, and surgical outcomes in primary aldosteronism remain poorly characterized. We examined the value of immunohistochemical analysis of CYP11B2 for evaluation of adrenalectomy outcomes after anatomical versus functional subtyping. Design: A retrospective multicenter study of 277 patients operated for primary aldosteronism who had an adrenalectomy sample available in the Finnish biobanks from 1 January 2000 to 31 December 2019. Adrenal slides from biobanks were analyzed centrally after CYP11B2 and CYP11B1 staining. Clinical data were obtained from patient registries. Histopathological diagnosis and cure after surgery were assessed as outcome measures. Results: Re-evaluation with CYP11B2 staining changed the histopathological diagnosis in 91 patients (33%). The presence of a CYP11B2-positive adenoma and the use of functional subtyping independently predicted clinical cure of primary aldosteronism. CYP11B2-positive <7 mm nodules were more frequent in patients without clinical cure, whereas CYP11B2-positive micronodules were common in all patients and had no impact on adrenalectomy outcomes. Small CYP11B2-positive nodules and micronodules were equally prevalent regardless of the subtyping method applied. Clinical cure rates were lower and CYP11B2-negative adenomas more common after adrenalectomy based on anatomical imaging than functional studies. Conclusions: Incorporating CYP11B2 staining in histopathological diagnosis enhances the prediction of surgical outcomes in primary aldosteronism. A finding of CYP11B2-positive adenoma is indicative of cure of primary aldosteronism, whereas smaller CYP11B2-positive nodules associate with poorer results at postoperative evaluation. Functional subtyping methods decrease the operations of CYP11B2-negative adenomas and are superior to anatomical imaging in identifying unilateral primary aldosteronism.
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OBJECTIVE: We sought to characterise the clinical picture of Martorell hypertensive ischaemic leg ulcer (HYTILU) by describing the ulcer borders with three clinical features: 'the red lipstick sign'; purple border; and livedo racemosa. We also aimed to characterise comorbidities and determinants of healing time. METHOD: A single-centre, retrospective cohort study was conducted between 2015-2020. We scrutinised ulcer photographs for relevant clinical signs. Data on comorbidities, medication and ulcer treatments, as well as method of diagnosis and healing time, were collected from patients' electronic medical records. RESULTS: In total, 38 female patients and 31 male patients (mean age 73 years) were assessed, with a mean follow-up time of 174 days. The 'red lipstick-like' margin covered 0-50% of the ulcer margin in 56.5% of the ulcers, and 51-100% of the ulcer margin in 43.5% of the ulcers. Purple border or livedo racemosa was observed in 70.5% of the ulcers. All patients had hypertension and 52.2% of patients had type 2 diabetes. A heavy cardiovascular disease burden and frequent concomitant vascular pathologies were found. Infections requiring systemic antibiotics, ulcer size and duration of symptoms before diagnosis were strongly associated with healing time. We also found that use of systemic corticosteroids and severity of hypertension (measured by the number of antihypertensive medications used) delayed healing. CONCLUSION: Our data suggest that 'the red lipstick sign' could be a novel diagnostic feature in HYTILUs alongside purple border, livedo racemosa and necrotic/fibrinous ulcer bed. The results also elucidated HYTILU comorbidities, and showed that infections and delay in diagnosis impeded healing.
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Diabetes Mellitus Tipo 2 , Hipertensión , Úlcera de la Pierna , Livedo Reticularis , Úlcera Varicosa , Humanos , Masculino , Femenino , Anciano , Úlcera , Estudios Retrospectivos , Diabetes Mellitus Tipo 2/complicaciones , Livedo Reticularis/complicaciones , Úlcera de la Pierna/terapia , Hipertensión/complicaciones , Hipertensión/epidemiología , Isquemia/complicaciones , Úlcera Varicosa/complicacionesRESUMEN
AIMS/HYPOTHESIS: This study explored the hypothesis that significant abnormalities in the metabolism of intestinally derived lipoproteins are present in individuals with type 2 diabetes on statin therapy. These abnormalities may contribute to residual CVD risk. METHODS: To investigate the kinetics of ApoB-48- and ApoB-100-containing lipoproteins, we performed a secondary analysis of 11 overweight/obese individuals with type 2 diabetes who were treated with lifestyle counselling and on a stable dose of metformin who were from an earlier clinical study, and compared these with 11 control participants frequency-matched for age, BMI and sex. Participants in both groups were on a similar statin regimen during the study. Stable isotope tracers were used to determine the kinetics of the following in response to a standard fat-rich meal: (1) apolipoprotein (Apo)B-48 in chylomicrons and VLDL; (2) ApoB-100 in VLDL, intermediate-density lipoprotein (IDL) and LDL; and (3) triglyceride (TG) in VLDL. RESULTS: The fasting lipid profile did not differ significantly between the two groups. Compared with control participants, in individuals with type 2 diabetes, chylomicron TG and ApoB-48 levels exhibited an approximately twofold higher response to the fat-rich meal, and a twofold higher increment was observed in ApoB-48 particles in the VLDL1 and VLDL2 density ranges (all p < 0.05). Again comparing control participants with individuals with type 2 diabetes, in the latter, total ApoB-48 production was 25% higher (556 ± 57 vs 446 ± 57 mg/day; p < 0.001), conversion (fractional transfer rate) of chylomicrons to VLDL was around 40% lower (35 ± 25 vs 82 ± 58 pools/day; p=0.034) and direct clearance of chylomicrons was 5.6-fold higher (5.6 ± 2.2 vs 1.0 ± 1.8 pools/day; p < 0.001). During the postprandial period, ApoB-48 particles accounted for a higher proportion of total VLDL in individuals with type 2 diabetes (44%) compared with control participants (25%), and these ApoB-48 VLDL particles exhibited a fivefold longer residence time in the circulation (p < 0.01). No between-group differences were seen in the kinetics of ApoB-100 and TG in VLDL, or in LDL ApoB-100 production, pool size and clearance rate. As compared with control participants, the IDL ApoB-100 pool in individuals with type 2 diabetes was higher due to increased conversion from VLDL2. CONCLUSIONS/INTERPRETATION: Abnormalities in the metabolism of intestinally derived ApoB-48-containing lipoproteins in individuals with type 2 diabetes on statins may help to explain the residual risk of CVD and may be suitable targets for interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT02948777.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Apolipoproteína B-100/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Apolipoproteína B-48 , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/complicaciones , Lipoproteínas VLDL/metabolismo , Apolipoproteínas B/metabolismo , Apolipoproteínas B/uso terapéutico , Lipoproteínas , Triglicéridos , Lipoproteínas IDL , QuilomicronesRESUMEN
BACKGROUND: Screening for primary aldosteronism is based on measuring aldosterone-to-renin ratio. Non-suppressed renin may cause false negative screening results, and such patients may miss focused, potentially curable treatment. We investigated the association between renal cysts and non-suppressed plasma renin. METHODS: Altogether, 114 consecutive patients with confirmed primary aldosteronism undergoing adrenal vein sampling were prospectively recruited between October 7, 2020 and December 30, 2021. During the procedure, plasma samples for renin analyses were collected from the right and left renal veins and the inferior vena cava. Renal cysts were identified using contrast-enhanced computed tomography. RESULTS: Renal cysts were found in 58.2% of the 114 patients. Neither screening nor renal vein renin concentrations were significantly different in patients with and without cysts, or when the kidneys with and without cysts were evaluated. However, cysts were significantly more prevalent in the "high-normal renin" group (cut point 23.0â mU/L) than in the "low to low-normal renin" group (90.9%, n = 11 vs. 56.0%, n = 102, P = .027, respectively). All patients ≤50 years of age in the "high-normal renin" group had renal cysts. Strong correlations were found between renin concentrations in the right and left renal veins (r = .984), and between renin concentration and renin activity in the inferior vena cava (r = .817). CONCLUSION: Renal cysts are found in the majority of patients with primary aldosteronism, and they may interfere with diagnostics, especially in patients aged 50 years or less. In patients with non-suppressed renin due to renal cysts, aldosterone-to-renin ratio below the diagnostic threshold does not always exclude the diagnosis of primary aldosteronism.
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Quistes , Hiperaldosteronismo , Hipertensión , Enfermedades Renales Quísticas , Humanos , Persona de Mediana Edad , Aldosterona/metabolismo , Quistes/complicaciones , Hipertensión/etiología , Enfermedades Renales Quísticas/diagnóstico por imagen , Enfermedades Renales Quísticas/complicaciones , Renina/metabolismo , Estudios Prospectivos , Masculino , Femenino , Adulto , AncianoRESUMEN
OBJECTIVE: Pancreatic neuroendocrine tumors (panNETs) are the leading cause of death in patients with multiple endocrine neoplasia type 1 (MEN1). The role of somatostatin receptor positron emission tomography/computed tomography (SSTR PET/CT) in MEN1 has not been established. The aim was to assess pancreatic imaging in MEN1 in a real-life setting. DESIGN: Fifty-eight patients with MEN1 [median age 40 (range 16-72) years] underwent SSTR PET/CT imaging; either as a screening tool regardless of disease stage (n = 47) or to further characterize known panNETs (n = 11). SSTR PET/CT and matched conventional imaging were blindly analyzed. We assessed the findings and the impact of SSTR PET/CT during a median follow-up of 47 months. RESULTS: SSTR PET/CT detected three times as many panNETs as conventional imaging (P < .001). SSTR PET/CT altered the management of 27 patients (47%). Seven patients (12%) were referred for surgery, and five (9%) received systemic treatment. In 15/25 (60%) patients with no previous panNET (n = 22) or in remission after surgery (n = 3), SSTR PET/CT identified a panNET (n = 14) or recurrence (n = 1). In eight patients, SSTR PET/CT revealed a panNET not immediately visible on conventional imaging. During a median follow-up of 47 months, three became visible on conventional imaging, but none required intervention. When SSTR PET/CT was negative, no panNETs were identified on conventional imaging during 38 months of follow-up. CONCLUSIONS: SSTR PET/CT demonstrates high accuracy in the detection of panNETs and alters the clinical management in nearly half of the MEN1-patients. SSTR PET/CT enables timely diagnosis and staging of MEN1-related panNETs.
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Neoplasia Endocrina Múltiple Tipo 1 , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Receptores de Somatostatina , Neoplasias Pancreáticas/diagnóstico , Páncreas/patología , Tumores Neuroendocrinos/patologíaRESUMEN
INTRODUCTION: Subtype classification method is essential when considering adrenalectomy as a possible treatment for primary aldosteronism. We aimed to retrospectively evaluate surgical outcomes of primary aldosteronism in patients who had undergone 11 C-metomidate positron emission tomography (11 C-MTO-PET) for subtype classification. METHODS: Postoperative clinical and biochemical cure and histopathological diagnosis from biobank samples were retrospectively evaluated in 44 patients who had all undergone preoperative 11 C-MTO-PET with or without adrenal venous sampling (AVS). We compared those operated based on 11 C-MTO-PET alone and those with concordant or discordant lateralization in 11 C-MTO-PET and AVS studies according to postoperative immunohistochemical findings and biochemical and clinical cure. RESULTS: Adrenalectomy side was based on 11 C-MTO-PET alone in 14 cases and on AVS in 30 cases of whom 42 achieved complete and two partial biochemical cures. Among those who underwent AVS and were operated according to it, the two lateralization methods were concordant in 22 cases and discordant in 8 cases. Similar immunohistochemical profiles and cure rates were seen after 11 C-MTO-PET alone or AVS-based operations. Respectively, those with concordant or discordant 11 C-MTO-PET and AVS lateralization did not differ in surgical outcome. Together, we found errors of lateralization diagnostics with 11 C-MTO-PET in 18% and with AVS in 3% among those eligible for adrenal surgery. CONCLUSIONS: Outcomes of adrenalectomy based on clinically significant lateralization in 11 C-MTO-PET alone correspond to those based on 11 C-MTO-PET with concordant AVS lateralization. However, our results suggest that diagnosis of unilateral PA should be performed with caution with 11 C-MTO-PET in case of discordant lateralization studies.
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Adrenalectomía , Hiperaldosteronismo , Humanos , Hiperaldosteronismo/diagnóstico por imagen , Hiperaldosteronismo/etiología , Glándulas Suprarrenales/diagnóstico por imagen , Glándulas Suprarrenales/patología , Glándulas Suprarrenales/cirugía , Estudios Retrospectivos , Tomografía de Emisión de PositronesRESUMEN
BackgroundApolipoprotein C-III (apoC-III) is a regulator of triglyceride (TG) metabolism, and due to its association with risk of cardiovascular disease, is an emergent target for pharmacological intervention. The impact of substantially lowering apoC-III on lipoprotein metabolism is not clear.MethodsWe investigated the kinetics of apolipoproteins B48 and B100 (apoB48 and apoB100) in chylomicrons, VLDL1, VLDL2, IDL, and LDL in patients heterozygous for a loss-of-function (LOF) mutation in the APOC3 gene. Studies were conducted in the postprandial state to provide a more comprehensive view of the influence of this protein on TG transport.ResultsCompared with non-LOF variant participants, a genetically determined decrease in apoC-III resulted in marked acceleration of lipolysis of TG-rich lipoproteins (TRLs), increased removal of VLDL remnants from the bloodstream, and substantial decrease in circulating levels of VLDL1, VLDL2, and IDL particles. Production rates for apoB48-containing chylomicrons and apoB100-containing VLDL1 and VLDL2 were not different between LOF carriers and noncarriers. Likewise, the rate of production of LDL was not affected by the lower apoC-III level, nor were the concentration and clearance rate of LDL-apoB100.ConclusionThese findings indicate that apoC-III lowering will have a marked effect on TRL and remnant metabolism, with possibly significant consequences for cardiovascular disease prevention.Trial registrationClinicalTrials.gov NCT04209816 and NCT01445730.FundingSwedish Heart-Lung Foundation, Swedish Research Council, ALF grant from the Sahlgrenska University Hospital, Novo Nordisk Foundation, Sigrid Juselius Foundation, Helsinki University Hospital Government Research funds, Finnish Heart Foundation, and Finnish Diabetes Research Foundation.
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Enfermedades Cardiovasculares , Lipoproteínas VLDL , Apolipoproteína B-48/genética , Apolipoproteína B-48/metabolismo , Apolipoproteína C-III/genética , Apolipoproteína C-III/metabolismo , Enfermedades Cardiovasculares/genética , Proteínas Portadoras/genética , Quilomicrones/genética , Quilomicrones/metabolismo , Humanos , Lipoproteínas/metabolismo , Lipoproteínas VLDL/metabolismo , Mutación , Triglicéridos/metabolismoRESUMEN
PURPOSE: Carcinoid heart disease (CHD) is a life-threatening complication of carcinoid syndrome (CS) characterised by tricuspid regurgitation (TR). However, there is an unmet need for earlier diagnosis of CHD. We cross-sectionally assessed the prevalence and potential predictive or diagnostic markers for CS and CHD in a contemporary cohort of patients with small intestinal neuroendocrine tumours (SI-NETs). METHODS: Biochemical characteristics, hepatic tumour load, measures of arterial and endothelial function, atherosclerosis, and transthoracic echocardiography were analysed in a prospective cross-sectional setting. RESULTS: Among the 65 patients studied, 29 (45%) had CS (CS+ ), and 3 (5%) CHD. CS+ was characterised by significantly higher hepatic tumour load, S-5-HIAA and fP-CgA, higher frequency of diarrhoea and flushing, and more frequent PRRT compared to CS- (for all, P < 0.05). Central systolic, central mean, and central end-systolic blood pressures were significantly higher in CS+ than in CS- (for all, P < 0.05). Subjects with grades 2-4 TR had higher hepatic tumour burden, fP-CgA, and S-5-HIAA compared to those with grades 0-1 TR, but measures of vascular function did not differ. fP-CgA (P = 0.017) and S-5-HIAA (P = 0.019) but not proBNP increased significantly according to the severity of TR. CONCLUSION: Although CS is common, the prevalence of CHD was found to be lower in a contemporary cohort of SI-NET patients than previously anticipated. Measures of arterial or endothelial function or carotid atherosclerosis do not identify subjects with mild TR. Echocardiography remains the most sensitive means to diagnose CHD in CS patients with high tumour burden and elevated CgA and 5-HIAA.
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Cardiopatía Carcinoide , Tumor Carcinoide , Neoplasias Intestinales , Neoplasias Hepáticas , Síndrome Carcinoide Maligno , Tumores Neuroendocrinos , Biomarcadores , Cardiopatía Carcinoide/diagnóstico , Cardiopatía Carcinoide/diagnóstico por imagen , Estudios Transversales , Humanos , Ácido Hidroxiindolacético , Neoplasias Intestinales/complicaciones , Neoplasias Intestinales/diagnóstico , Síndrome Carcinoide Maligno/complicaciones , Síndrome Carcinoide Maligno/diagnóstico , Síndrome Carcinoide Maligno/epidemiología , Tumores Neuroendocrinos/complicaciones , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/patología , Estudios ProspectivosRESUMEN
Objective: Incretins are known to influence lipid metabolism in the intestine when administered as pharmacologic agents. The aggregate influence of endogenous incretins on chylomicron production and clearance is less clear, particularly in light of opposing effects of co-secreted hormones. Here, we tested the hypothesis that physiological levels of incretins may impact on production or clearances rates of chylomicrons and VLDL. Design and methods: A group of 22 overweight/obese men was studied to determine associations between plasma levels of glucagon-like peptides 1 and 2 (GLP-1 and GLP-2) and glucose-dependent insulinotropic polypeptide (GIP) after a fat-rich meal and the production and clearance rates of apoB48- and apoB100-containing triglyceride-rich lipoproteins. Subjects were stratified by above- and below-median incretin response (area under the curve). Results: Stratification yielded subgroups that differed about two-fold in incretin response. There were neither differences in apoB48 production rates in chylomicrons or VLDL fractions nor in apoB100 or triglyceride kinetics in VLDL between men with above- vs below-median incretin responses. The men with above-median GLP-1 and GLP-2 responses exhibited higher postprandial plasma and chylomicron triglyceride levels, but this could not be related to altered kinetic parameters. No differences were found between incretin response subgroups and particle clearance rates. Conclusion: We found no evidence for a regulatory effect of endogenous incretins on contemporaneous chylomicron or VLDL metabolism following a standardised fat-rich meal. The actions of incretins at pharmacological doses may not be reflected at physiological levels of these hormones.
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Incretinas , Periodo Posprandial , Apolipoproteína B-48/metabolismo , Quilomicrones/metabolismo , Polipéptido Inhibidor Gástrico , Péptido 1 Similar al Glucagón , Humanos , Lipoproteínas/metabolismo , Masculino , TriglicéridosAsunto(s)
Diabetes Gestacional , Ejercicio Físico , Terapia por Ejercicio , Femenino , Humanos , EmbarazoRESUMEN
OBJECTIVE: We examined if measurement of adrenal androgens adds to subtype diagnostics of primary aldosteronism (PA) under cosyntropin-stimulated adrenal venous sampling (AVS). DESIGN: A prospective pre-specified secondary endpoint analysis of 49 patients with confirmed PA, of whom 29 underwent unilateral adrenalectomy with long-term follow-up. METHODS: Concentrations of androstenedione, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) were measured during AVS in addition to aldosterone and cortisol. Subjects with lateralisation index (LI) of ≥4 were treated with unilateral adrenalectomy, and the immunohistochemical subtype was determined with CYP11B2 and CYP11B1 stains. The performance of adrenal androgens was evaluated by receiver operating characteristics (ROC) curve analyses in adrenalectomy and medical therapy groups. RESULTS: During AVS, the correlations between cortisol and androstenedione, DHEA and DHEAS for LI and selectivity index (SI) were highly significant. The right and left side SIs for androstenedione and DHEA were higher (p < .001) than for cortisol. In ROC analysis, the optimal LI cut-off values for androstenedione, DHEA and DHEAS were 4.2, 4.5 and 4.6, respectively. The performance of these LIs for adrenal androgens did not differ from that of cortisol. CONCLUSIONS: Under cosyntropin-stimulated AVS, the measurement of androstenedione and DHEA did not improve the cannulation selectivity. The performance of cortisol and adrenal androgens are confirmatory but not superior to cortisol-based results in lateralisation diagnostics of PA.
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Hiperaldosteronismo , Glándulas Suprarrenales , Aldosterona , Andrógenos , Androstenodiona , Cosintropina , Deshidroepiandrosterona , Humanos , Hidrocortisona , Hiperaldosteronismo/diagnóstico , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
BACKGROUND: The phospholipase domain-containing 3 gene (PNPLA3)-148M variant is associated with liver steatosis but its influence on the metabolism of triglyceride-rich lipoproteins remains unclear. Here, we investigated the kinetics of large, triglyceride-rich very-low-density lipoprotein (VLDL), (VLDL1 ), and smaller VLDL2 in homozygotes for the PNPLA3-148M variant. METHODS AND RESULTS: The kinetics of apolipoprotein (apo) B100 (apoB100) and triglyceride in VLDL subfractions were analysed in nine subjects homozygous for PNPLA3-148M and nine subjects homozygous for PNPLA3-148I (controls). Liver fat was >3-fold higher in the 148M subjects. Production rates for apoB100 and triglyceride in VLDL1 did not differ significantly between the two groups. Likewise, production rates for VLDL2 -apoB100 and -triglyceride, and fractional clearance rates for both apoB100 and triglyceride in VLDL1 and VLDL2 , were not significantly different. CONCLUSIONS: Despite the higher liver fat content in PNPLA3 148M homozygotes, there was no increase in VLDL production. Equally, VLDL production was maintained at normal levels despite the putative impairment in cytosolic lipid hydrolysis in these subjects.
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Aciltransferasas/genética , Metabolismo de los Lípidos , Lipoproteínas VLDL , Hígado , Fosfolipasas A2 Calcio-Independiente/genética , Humanos , Lípidos , Lipoproteínas VLDL/metabolismo , Hígado/metabolismo , Triglicéridos/metabolismoRESUMEN
Calcium plays a key role in skeletal mineralization and several intracellular and extracellular homeostatic networks. It is an essential element that is only available to the body through dietary sources. Daily acquisition of calcium depends, in addition to the actual intake, on the hormonally regulated state of calcium homeostasis through three main mechanisms: bone turnover, intestinal absorption, and renal reabsorption. These procedures are regulated by a group of interacting circulating hormones and their key receptors. This includes parathyroid hormone (PTH), PTH-related peptide, 1,25-dihydroxyvitamin D, calcitonin, fibroblast growth factor 23, the prevailing calcium concentration itself, the calcium-sensing receptor, as well as local processes in the bones, gut, and kidneys.
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Calcio , Hormona Paratiroidea , Huesos/metabolismo , Calcio/metabolismo , Calcio de la Dieta , Homeostasis , Humanos , Hormona Paratiroidea/fisiología , Vitamina D/metabolismoRESUMEN
Introduction: Rare FGF23-producing mesenchymal tumors lead to paraneoplastic tumor-induced osteomalacia (TIO) presenting with phosphate wasting, hypophosphatemia, chronic hypomineralization of the bone, fragility fractures and muscle weakness. Diagnosis of TIO requires exclusion of other etiologies and careful search for a mesenchymal tumor that often is very small and can appear anywhere in the body. Surgical removal of the tumor is the only definitive treatment of TIO. Surgical complications due to chronic hypophosphatemia are not well recognized. Case Description: The current case describes severe fragility fractures in a 58-year-old woman, who lost her ability to walk and was bedridden for two years. First, the initial diagnostic laboratory work-up did not include serum phosphorus measurements, second, the suspicion of adverse effects of pioglitazone as an underlying cause delayed correct diagnosis for at least two years. After biochemical discovery of hyperphosphaturic hypophosphatemia at a tertiary referral centre, a FGF23-producing tumor of the mandible was discovered on physical examination, and then surgically removed. Postoperatively, severe hypophosphatemia and muscle weakness prolonged the need for ventilation support, intensive care and phosphate supplementation. After two years of rehabilitation, the patient was able to walk short distances. The tumor has not recurred, and serum phosphate concentration has remained within normal limits during 3.5 years of follow-up. Conclusions: The case report illustrates knowledge gaps in the diagnostic work-up of rare causes of low bone mass and fragility fractures. Compared to other low phosphate conditions, surgical recovery from TIO-induced hypophosphatemia warrants special attention. Increased alkaline phosphatase concentration may indicate impaired postsurgical recovery due to prolonged hypophosphatemia, underlining the need for proactive perioperative correction of hypophosphatemia.
Asunto(s)
Hipofosfatemia/etiología , Neoplasias Mandibulares/cirugía , Osteomalacia/cirugía , Síndromes Paraneoplásicos/cirugía , Fosfatos/sangre , Femenino , Factores de Crecimiento de Fibroblastos/sangre , Humanos , Hipofosfatemia/sangre , Hipofosfatemia/patología , Neoplasias Mandibulares/sangre , Neoplasias Mandibulares/complicaciones , Neoplasias Mandibulares/patología , Persona de Mediana Edad , Osteomalacia/sangre , Osteomalacia/patología , Síndromes Paraneoplásicos/sangreRESUMEN
PURPOSE: Ectopic ACTH syndrome (EAS) is rare. We established a national cohort to increase awareness and address unmet needs. METHODS: The Finnish national EAS cohort includes 60 patients diagnosed in 1997-2016. We assessed clinical features, diagnostic work-ups, treatments, incidence, and outcomes of subgroups occult tumor (OT), well-differentiated neuroendocrine tumor G1/G2 (NETG1/G2) and NET G3/neuroendocrine carcinoma (NETG3/NEC). RESULTS: The distribution of OT, NETG1/G2, and NETG3/NEC was 10 (17%), 20 (33%), and 30 (50%), respectively; and median follow-up 22 months (0-249). Annual incidence (0.20-0.93 per million inhabitants) and tumor subgroups (OT vs. NEC) varied across the country. The longest diagnostic delay from EAS onset to radiological tumor identification was 48 months. In NET/NEC, 6/50 (12%) were diagnosed 1-24 years before EAS onset. Osteoporotic fractures (32%) and severe infections (55%) were common. The CRH stimulation test accurately diagnosed EAS in 25/31 (81%). Metyrapone (≤6 g daily, prescribed in 88%) was well tolerated. In NETG1/G2, 13/20 (65%) underwent curative resection of the primary tumor; four experienced recurrence within 2-12 years. In OT, 70% underwent bilateral adrenalectomy. Five-year overall survival in OT, NETG1/G2, and NETG3/NEC was 90%, 55%, and 0%, respectively (P < 0.001). Morning cortisol, hypokalemia, infections, metastatic disease, and acute onset were negative, whereas resection of the primary tumor and bilateral adrenalectomy were positive predictors of survival. CONCLUSIONS: NET/NEC may precede EAS onset by several years. In NETG1/G2, recurrences may occur > 10 years after successful primary surgery. Tumor subgroup (OT, NETG1/G2, NEC) was an independent predictor of survival.