RESUMO
BACKGROUND & AIMS: Small intestinal neuroendocrine tumor (SI-NET) is a rare disease, but its incidence has increased over the past 4 decades. Understanding the genetic risk factors underlying SI-NETs can help in disease prevention and may provide clinically beneficial markers for diagnosis. Here the results of the largest genome-wide association study of SI-NETs performed to date with 405 cases and 614,666 controls are reported. METHODS: Samples from 307 patients with SI-NETs and 287,137 controls in the FinnGen study were used for the identification of SI-NET risk-associated genetic variants. The results were also meta-analyzed with summary statistics from the UK Biobank (n = 98 patients with SI-NET and n = 327,529 controls). RESULTS: We identified 6 genome-wide significant (P < 5 × 10-8) loci associated with SI-NET risk, of which 4 (near SEMA6A, LGR5, CDKAL1, and FERMT2) are novel and 2 (near LTA4H-ELK and in KIF16B) have been reported previously. Interestingly, the top hit (rs200138614; P = 1.80 × 10-19) was a missense variant (p.Cys712Phe) in the LGR5 gene, a bona-fide marker of adult intestinal stem cells and a potentiator of canonical WNT signaling. The association was validated in an independent Finnish collection of 70 patients with SI-NETs, as well as in the UK Biobank exome sequence data (n = 92 cases and n = 392,814 controls). Overexpression of LGR5 p.Cys712Phe in intestinal organoids abolished the ability of R-Spondin1 to support organoid growth, indicating that the mutation perturbed R-Spondin-LGR5 signaling. CONCLUSIONS: Our study is the largest genome-wide association study to date on SI-NETs and reported 4 new associated genome-wide association study loci, including a novel missense mutation (rs200138614, p.Cys712Phe) in LGR5, a canonical marker of adult intestinal stem cells.
Assuntos
Neoplasias Intestinais , Tumores Neuroendócrinos , Adulto , Humanos , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/patologia , Mutação de Sentido Incorreto , Estudo de Associação Genômica Ampla , Neoplasias Intestinais/genética , Neoplasias Intestinais/patologia , Receptores Acoplados a Proteínas G/genética , Cinesinas/genéticaRESUMO
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 terapêutico , Países Escandinavos e Nórdicos/epidemiologia , Consenso , Hormônio do Crescimento Humano/uso terapêutico , Hormônio do Crescimento Humano/análogos & derivados , Inquéritos e QuestionáriosRESUMO
Many hereditary cancer syndromes are associated with an increased risk of small and large intestinal adenocarcinomas. However, conditions bearing a high risk to both adenocarcinomas and neuroendocrine tumors are yet to be described. We studied a family with 16 individuals in four generations affected by a wide spectrum of intestinal tumors, including hyperplastic polyps, adenomas, small intestinal neuroendocrine tumors, and colorectal and small intestinal adenocarcinomas. To assess the genetic susceptibility and understand the novel phenotype, we utilized multiple molecular methods, including whole genome sequencing, RNA sequencing, single cell sequencing, RNA in situ hybridization and organoid culture. We detected a heterozygous deletion at the cystic fibrosis locus (7q31.2) perfectly segregating with the intestinal tumor predisposition in the family. The deletion removes a topologically associating domain border between CFTR and WNT2, aberrantly activating WNT2 in the intestinal epithelium. These consequences suggest that the deletion predisposes to small intestinal neuroendocrine tumors and small and large intestinal adenocarcinomas, and reveals the broad tumorigenic effects of aberrant WNT activation in the human intestine.
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Adenocarcinoma , Adenoma , Neoplasias Colorretais , Tumores Neuroendócrinos , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenoma/genética , Adenoma/patologia , Neoplasias Colorretais/genética , Humanos , Mucosa Intestinal/patologia , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/patologia , Proteína Wnt2RESUMO
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 , Glândulas Suprarrenais , Aldosterona , Androgênios , Androstenodiona , Cosintropina , Desidroepiandrosterona , Humanos , Hidrocortisona , Hiperaldosteronismo/diagnóstico , Estudos Prospectivos , Estudos RetrospectivosRESUMO
OBJECTIVE: Insulinomas are rare pancreatic neoplasms, which can usually be cured by surgery. As the diagnostic delay is often long and the prolonged hyperinsulinemia may have long-term effects on health and the quality of life, we studied the long-term health-related quality of life (HRQoL) in insulinoma patients. DESIGN, PATIENTS AND MEASUREMENTS: The HRQoL of adults diagnosed with an insulinoma in Finland in 1980-2010 was studied with the 15D instrument, and the results were compared to those of an age- and gender-matched sample of the general population. The minimum clinically important difference in the total 15D score has been defined as ±0.015. The clinical characteristics, details of insulinoma diagnosis and treatment, and the current health status of the subjects were examined to specify the possible determinants of long-term HRQoL. RESULTS: Thirty-eight insulinoma patients participated in the HRQoL survey (response rate 75%). All had undergone surgery with a curative aim, a median of 13 (min 7, max 34) years before the survey. The insulinoma patients had a clinically importantly and statistically significantly better mean 15D score compared with the controls (0.930 ± 0.072 vs 0.903 ± 0.039, P = .046) and were significantly better off regarding mobility, usual activities and eating. Among the insulinoma patients, younger age at the time of survey, higher level of education and smaller number of chronic diseases were associated with better overall HRQoL. CONCLUSIONS: In the long term, the overall HRQoL of insulinoma patients is slightly better than that of the general population.
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Insulinoma , Qualidade de Vida , Adulto , Diagnóstico Tardio , Finlândia , Humanos , Insulinoma/cirurgia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Small intestinal neuroendocrine tumors (SI-NETs) are difficult to diagnose in the early stage of disease. Current blood biomarkers such as chromogranin A (CgA) and 5-hydroxyindolacetic acid have low sensitivity (SEN) and specificity (SPE). This is a first preplanned interim analysis (Nordic non-interventional, prospective, exploratory, EXPLAIN study [NCT02630654]). Its objective is to investigate if a plasma protein multi-biomarker strategy can improve diagnostic accuracy (ACC) in SI-NETs. METHODS: At the time of diagnosis, before any disease-specific treatment was initiated, blood was collected from patients with advanced SI-NETs and 92 putative cancer-related plasma proteins from 135 patients were analyzed and compared with the results of age- and sex-matched controls (n = 143), using multiplex proximity extension assay and machine learning techniques. RESULTS: Using a random forest model including 12 top ranked plasma proteins in patients with SI-NETs, the multi-biomarker strategy showed SEN and SPE of 89 and 91%, respectively, with negative predictive value (NPV) and positive predictive value (PPV) of 90 and 91%, respectively, to identify patients with regional or metastatic disease with an area under the receiver operator characteristic curve (AUROC) of 99%. In 30 patients with normal CgA concentrations, the model provided a diagnostic SPE of 98%, SEN of 56%, and NPV 90%, PPV of 90%, and AUROC 97%, regardless of proton pump inhibitor intake. CONCLUSION: This interim analysis demonstrates that a multi-biomarker/machine learning strategy improves diagnostic ACC of patients with SI-NET at the time of diagnosis, especially in patients with normal CgA levels. The results indicate that this multi-biomarker strategy can be useful for early detection of SI-NETs at presentation and conceivably detect recurrence after radical primary resection.
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Neoplasias Duodenais/sangue , Neoplasias do Íleo/sangue , Neoplasias do Jejuno/sangue , Tumores Neuroendócrinos/sangue , Biomarcadores/sangue , Neoplasias Duodenais/diagnóstico , Humanos , Neoplasias do Íleo/diagnóstico , Neoplasias do Jejuno/diagnóstico , Aprendizado de Máquina , Tumores Neuroendócrinos/diagnósticoRESUMO
BACKGROUND: The diagnostic work-up and treatment of patients with gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) has undergone major advances and new methods are introduced. Furthermore, an update of the WHO classification has resulted in a new nomenclature for GEP-NEN that is implemented in the clinic. AIM: These Nordic guidelines summarise the Nordic Neuroendocrine Tumour Group's current view on how to diagnose and treat GEP-NEN patients and aims to be useful in the daily practice for clinicians.
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Neoplasias Gastrointestinais , Neoplasias Intestinais , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Neoplasias Gástricas , Humanos , Neoplasias Intestinais/diagnóstico , Neoplasias Intestinais/tratamento farmacológico , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapiaRESUMO
BACKGROUND: Cardiovascular disease (CVD) and thyroid dysfunction are common in older people, but little is known about how they affect health-related quality of life (HRQoL). METHODS: We assessed HRQoL with the 15D instrument in 329 home-dwelling patients aged ≥ 75 years with stable CVD and compared the results to those of an age- and gender-matched general population (n = 103). We also studied the impact of age, BMI, number of medications, thyroid-stimulating hormone (TSH) concentration, levothyroxine (L-T4) substitution and Mini-Mental State Examination (MMSE) on HRQoL. RESULTS: Overall HRQoL was impaired in older people with stable CVD (mean 15D score 0.777 vs 0.801, p = 0.001), and also on single dimensions of breathing, sleeping, discomfort and symptoms, distress, vitality (all p < 0.001), and depression (p = 0.016) compared to the age- and gender-matched general population. Furthermore, in the patients, L-T4 substitution associated with impaired sleeping (p = 0.018) and sexual activity (p = 0.030). Moreover, MMSE points, number of medications used, age (all p < 0.001) and BMI (p = 0.009) predicted impaired HRQoL. CONCLUSIONS: Older people with stable CVD are characterized by impaired HRQoL compared to age- and gender-matched controls. We demonstrate that this is the consequence of impaired breathing, sleeping, discomfort and symptoms, distress, vitality, and depression. L-T4 substitution has a negative impact on HRQoL in old patients with stable CVD. MMSE score, number of medications, age and BMI predict worse HRQoL.
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Doenças Cardiovasculares , Tiroxina , Idoso , Idoso de 80 Anos ou mais , Depressão , Feminino , Humanos , Masculino , Qualidade de Vida , Sono , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The prevalence of small intestine neuroendocrine tumors (SI-NETs) is increasing. Disease progression is often slow and treatment options and long-term survival rates have improved, but little is known about health-related quality of life (HRQoL) in these patients. OBJECTIVE: To assess HRQoL and its predictors in SI-NET patients receiving contemporary treatments. METHODS: We measured HRQoL with 15D and SF-36 questionnaires in 134 SI-NET patients and compared the 15D results to those of an age- and gender-standardized sample of the general population (n = 1,153). In the patients, we studied the impact of treatments, Ki-67, liver metastases, circulating tumor markers, comorbidities, and/or socioeconomic factors on HRQoL with linear regression analysis. RESULTS: The mean disease duration of the patients was 81 (4-468) months, 91% had metastatic disease, and 79% received somatostatin analog treatment. Hepatic tumor load was 0% in 44.8%, < 10-25% in 44.0%, and > 25% in 11.2%, respectively. Mean fP-CgA and S-5HIAA concentrations were 15 (1.3-250) and 344 (24-7,470) nmol/L, respectively. Overall, HRQoL was significantly impaired in patients compared to controls (15D score 0.864 ± 0.105 vs. 0.905 ± 0.028, p < 0.001). SI-NET patients scored worse on 9 of 15 dimensions: sleep, excretion (i.e., bladder and bowel function), depression, distress, vitality, sexual activity (p < 0.001), breathing, usual activities, and discomfort and symptoms (p < 0.01-0.05). SF-36 scores were impaired and highly correlated with 15D scores (p < 0.001). HRQoL was impaired in patients with (n = 85) compared to patients without (n = 49) impaired excretion (0.828 vs. 0.933, p < 0.001). In the patient group, number of medications predicted impaired HRQoL. CONCLUSIONS: Despite contemporary treatments, SI-NET patients have severely impaired HRQoL, including diarrhea, sleep, depression, vitality, and sexual activity.
Assuntos
Neoplasias Intestinais/epidemiologia , Intestino Delgado/patologia , Tumores Neuroendócrinos/epidemiologia , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Finlândia/epidemiologia , Nível de Saúde , Humanos , Neoplasias Intestinais/patologia , Neoplasias Intestinais/terapia , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/terapia , Inquéritos e QuestionáriosRESUMO
Surgery for primary hyperparathyroidism (PHPT) improves health-related quality of life (HRQoL), but it is unclear whether the effects are sustained after medium-term (>2 years) follow-up, and whether the results on some or all dimensions of HRQoL will reach that of the general population. We performed a follow-up of HRQoL on average 3.3 years after surgery for PHPT using the 15D in our patient cohort (n=124) and compared the results to those of an age- and gender-standardized general population (n=1099). We studied self-reported blood pressure and current medications; new comorbidities were retrieved from electronic patient records. A total of 104 (83%) patients [eight with serum calcium (1.34-1.46 mmol/l)] returned the questionnaires. After a follow-up of 3.3 years (range 23 to 55 months), systolic and diastolic blood pressure had decreased significantly compared to baseline (the situation before surgery, p<0.001). Thirty-four (33%) had acquired a new diagnosis (range 1-7), the most common being cardiovascular disease and cancer. Mean 15D score was significantly better compared to baseline (p<0.001), the dimensions of sleeping, mental function, discomfort and symptoms, and depression had further improved (p<0.01), and no longer differed from that of the general population. In PHPT, after >2 years follow-up, surgery improves blood pressure and restores neurocognitive function and sleep to the level of the general population. The improvements observed in overall HRQoL at one year after surgery are sustained, but overall HRQoL does not reach that of the general population.
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Pressão Sanguínea , Cognição , Hiperparatireoidismo Primário/fisiopatologia , Hiperparatireoidismo Primário/cirurgia , Comportamento Sexual , Sono , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Hiperparatireoidismo Primário/diagnóstico , Masculino , Pessoa de Meia-Idade , Paratireoidectomia , Estudos Prospectivos , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Parathyroid carcinoma (PC) is rare and diagnostically challenging. Reported outcomes are rather poor and the incidence might be increasing. MATERIAL AND METHODS: We performed a nationwide study on all cases (n= 32) diagnosed in 2000-2011 in Finland, and compared clinical and histopathological characteristics and outcome to atypical parathyroid (APA; n= 28) and parathyroid adenomas (PA; n= 72). The incidence in years 1955-1999 was compared to that in 2000-2013. RESULTS: Preoperatively, calcium and parathyroid hormone concentrations were higher in PC compared to APA and PA (1.76, 1.56 and 1.44 mmol/l, p < .001; and 989, 355 and 160 µmol/l, p < .001, respectively). Calcium was ≤1.77 mmol/l for all PAs. Hospitalization (44% vs. 22% and 3%, respectively, p = .01), renal (50% vs. 48% vs. 22%, respectively, p = .01) and bone (47% vs. 15% vs. 38%, respectively p = .002) manifestations were more common. PC and APA tumors were larger than PA (p < .001). Histopathological characteristics of PC compared to PA are increased mitotic activity (p= .001), chief cells (p = .003), diffuse growth pattern (p < .001), higher Ki67 (p< .001) and negative parafibromin (p < .001). One PC (1/18) and one APA (1/16) patient had a CDC73 mutation. After 6.7 (2-13.9) years of follow-up, 9.4% of PC had residual, 21% recurrent disease and 12.5% died of disease. Overall mortality did not differ between subgroups (p = .094). Recurrent PC was characterized by vascular invasion, lymph node metastases, high mitotic activity, necrosis and negative parafibromin. Incidence increased from 1.42 (range 0.52-2.14) to 7.14 (range 3.42-10.38)/10.000.000/years; (p < .001). CONCLUSIONS: PC associates with severe primary hyperparathyroidism and must be suspected if calcium ≥1.77 mmol/l. The prevalence of CDC73 germline mutations in PC and APA in Finland is 6%. PC has distinct histopathological characteristics and its incidence has increased over the past decades.
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Recidiva Local de Neoplasia/epidemiologia , Neoplasias das Paratireoides/epidemiologia , Paratireoidectomia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Feminino , Seguimentos , Mutação em Linhagem Germinativa , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Incidência , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Neoplasias das Paratireoides/patologia , Neoplasias das Paratireoides/cirurgia , Prognóstico , Estudos Retrospectivos , Proteínas Supressoras de Tumor/genética , Adulto JovemRESUMO
OBJECTIVE: The published data on health-related quality of life (HRQoL) after treatment of nonfunctioning pituitary adenomas (NFPAs) are conflicting. We evaluated HRQoL in a recent series of patients who had surgery for an NFPA. DESIGN: Cross-sectional study including a large control population. PATIENTS AND MEASUREMENTS: A HRQoL questionnaire (15D) was sent to all patients (n = 161) having undergone transsphenoidal surgery for NFPA in the years 2000-2010 at the Helsinki University Hospital. The 15D score and dimension scores of the study population (n = 137) were compared with those of a large (n = 4967) gender- and age-standardized control population. Possible independent predictors of HRQoL in the patients were estimated with multivariate regression analysis. RESULTS: Postoperatively, 57% of the patients had normal visual function. After a mean follow-up of 7·4 ± 3·2 years (mean ± SD), 62% suffered from hypopituitarism. Overall, HRQoL was near-normal in patients compared to controls (15D scores 0·885 ± 0·114 vs 0·903 ± 0·093, respectively, P = 0·07). On single dimensions, patients had impaired vision and sexual activity (both P < 0·0005), more depression and distress (both P < 0·005) and less discomfort and symptoms (P < 0·05). Age, body mass index, diabetes, depression and reoperation were independent predictors of impaired HRQoL (all P < 0·05). Thyroxine substitution was associated with impaired and hydrocortisone and testosterone substitution (males only) with better HRQoL (all P < 0·05). CONCLUSIONS: This recent series of NFPA patients demonstrates that overall HRQoL is near-normal after medium term follow-up; the most impaired dimensions were in vision and sexual activity. Comorbidities are strong predictors of impaired HRQoL.
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Adenoma/cirurgia , Neoplasias Hipofisárias/cirurgia , Qualidade de Vida , Inquéritos e Questionários , Idoso , Estudos Transversais , Depressão/etiologia , Procedimentos Cirúrgicos Endócrinos/efeitos adversos , Procedimentos Cirúrgicos Endócrinos/métodos , Feminino , Seguimentos , Humanos , Hipopituitarismo/etiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/métodos , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Complicações Pós-Operatórias/etiologia , Análise de Regressão , Osso Esfenoide/cirurgia , Transtornos da Visão/etiologiaRESUMO
BACKGROUND: high TSH concentrations and cognitive decline are both very common among older people and could be linked. OBJECTIVE: to assess cognition in our cohort of 335 home-dwelling older people (75 years and older) and to cross-sectionally relate the results to thyroid-stimulating hormone (TSH) concentrations. Our special focus was on the upper normal TSH range and subclinical hypothyroidism. METHODS: cognitive performance was evaluated using the Consortium to Establish a Registry for Alzheimer's disease neuropsychological battery (CERAD-nb). The Clinical Dementia Rating (CDR) scale was used to evaluate severity of cognitive disorder. The APOEε4 genotype was also defined. Subjects were divided into quartiles based on the TSH concentrations, and results were compared between these groups. RESULTS: expected relations were observed between CERAD domains and both educational level and APOEε4 genotype. Female sex significantly associated with better performance in Boston naming (OR = 0.48; 95% CI = 0.27-0.85). In the whole cohort, higher TSH concentrations tended to associate with better scores in most parts of the CERAD-nb tests, but differences were not statistically significant. However, subjects with the highest TSH concentration (90th TSH percentile, range 4.14-14.4 mU/l) had better CDR scores compared with subjects with the lowest TSH concentration (10th percentile, range 0.001-0.63 mIU/l; OR 0.10; 95% CI 0.014-0.76). CONCLUSIONS: our results do not support the notion that higher TSH concentrations, not even in the range of subclinical hypothyroidism, would adversely affect cognition among older people.
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Envelhecimento , Transtornos Cognitivos/etiologia , Cognição , Hipotireoidismo/complicações , Tireotropina/sangue , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Envelhecimento/psicologia , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Transtornos Cognitivos/sangue , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Estudos Transversais , Feminino , Avaliação Geriátrica , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico , Modelos Logísticos , Masculino , Razão de Chances , Sistema de Registros , Medição de Risco , Fatores de Risco , Regulação para CimaRESUMO
The diagnosis of hypothyroidism is based on the findings of an increased serum TSH (above the reference range) and decreased serum free T4 (below the reference range) concentration. Treatment of subclinical hypothyroidism is indicated if serum THS is above 10 mU/l. For less severe forms of subclinical hypothyroidism, the treatment should be individually tailored. The treatment of choice is synthetic human levothyroxine. The goals for treatment are amelioration of symptoms and normalization of TSH and free T4 concentrations.
Assuntos
Hipotireoidismo/tratamento farmacológico , Tiroxina/uso terapêutico , Adulto , Biomarcadores/sangue , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico , Tireotropina/sangue , Tiroxina/sangueRESUMO
BACKGROUND: Previous studies report impaired health-related quality of life (HRQoL) in patients with functional pituitary adenomas (FPA). We assessed HRQoL in FPA patients having undergone surgery at our University Central Hospital between 2000 and 2010, with combined adjuvant treatment given to achieve strict hormonal control. DESIGN: A cross-sectional study including a large control population. PATIENTS AND METHODS: HRQoL was assessed by the 15D in 100 FPA patients (acromegaly n = 47, Cushing's disease n = 21, prolactinoma n = 26, TSH-adenoma n = 2, gonadotropinoma n = 4), operated on a mean 7·4 (range 2·1-13·0) years earlier. An age- and gender-standardized sample of the general population (n = 4924) served as controls. HRQoL determinants were assessed by independent samples t-test and multiple regression analysis. RESULTS: Hormonal remission rate was 90·9% and 43·9% of the patients received replacement therapy. The mean 15D scores were similar in patients and controls (0·917 vs 0·922, P = 0·568). On single dimensions, patients were worse off regarding speech and sexual activity (both P < 0·05) and better off regarding discomfort and symptoms (P < 0·05). Age (P = 0·001), co-morbidities (P = 0·009), Cushing's disease (P = 0·034), and thyroxine dose (P = 0·002) predicted impaired HRQoL, but not hypopituitarism, hydrocortisone replacement, radiotherapy, or time after surgery. CONCLUSIONS: It is possible to achieve near-normal HRQoL in surgically treated FPA patients given adjuvant treatment to achieve strict hormonal remission. However, in addition to age and co-morbidities, Cushing's disease and need for thyroxine replacement therapy predict impaired HRQoL.
Assuntos
Neoplasias Hipofisárias/fisiopatologia , Acromegalia/fisiopatologia , Acromegalia/cirurgia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hipersecreção Hipofisária de ACTH/fisiopatologia , Hipersecreção Hipofisária de ACTH/cirurgia , Neoplasias Hipofisárias/cirurgia , Prolactinoma/fisiopatologia , Prolactinoma/cirurgia , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Patients with Addison's disease (AD) on conventional replacement therapy have impaired health-related quality of life (HRQoL). It is possible that lower hydrocortisone (HC) doses recommended by current guidelines could restore HRQoL. We compared HRQoL in AD patients treated according to current HC recommendations to that of the age- and gender-standardized general population. SUBJECTS, DESIGN AND MEASUREMENT: We assessed HRQoL in a cross-sectional setting with the 15D instrument in a Finnish AD cohort (n = 107) and compared the results with those of a large sample of general population (n = 5671). We examined possible predictors of HRQoL in AD. Within the patient group, HRQoL was also assessed by SF-36. RESULTS: Mean HC dose was 22 mg/d, corresponding to 12 ± 4 mg/m2. HRQoL was impaired in AD compared with the general population (15D score; 0·853 vs 0·918, P < 0·001). Within single 15D dimensions, discomfort and symptoms, vitality and sexual activity were most affected. Stepwise regression analysis demonstrated that Patient's Association membership (P = 0·02), female gender (P < 0·01), presence of other autoimmune or inflammatory comorbidity (P < 0·02), lower education (P < 0·02) and longer disease duration (P < 0·05) independently predicted impaired HRQoL, whereas replacement regimens, autoimmune-related comorbidities, total number of comorbidities or level of healthcare follow-up did not. In AD, HRQoL was impaired also as assessed by SF-36. CONCLUSIONS: HRQoL is significantly impaired in AD compared with the general population despite use of recommended HC doses. Patient's Association membership was the most significant predictor of impaired HRQoL. This finding should be explored in more detail in the future.
Assuntos
Doença de Addison/tratamento farmacológico , Hidrocortisona/uso terapêutico , Adulto , Idoso , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The diagnostic work-up and treatment of patients with neuroendocrine neoplasms (NENs) has undergone major recent advances and new methods are currently introduced into the clinic. An update of the WHO classification has resulted in a new nomenclature dividing NENs into neuroendocrine tumours (NETs) including G1 (Ki67 index ≤ 2%) and G2 (Ki67 index 3-20%) tumours and neuroendocrine carcinomas (NECs) with Ki67 index > 20%, G3. Aim. These Nordic guidelines summarise the Nordic Neuroendocrine Tumour Group's current view on how to diagnose and treat NEN-patients and are meant to be useful in the daily practice for clinicians handling these patients.
Assuntos
Carcinoma Neuroendócrino , Neoplasias Gastrointestinais , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/análise , Carcinoma Neuroendócrino/química , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/terapia , Diagnóstico por Imagem/métodos , Neoplasias Gastrointestinais/química , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/terapia , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Tumores Neuroendócrinos/química , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , PrognósticoRESUMO
Parathyroid tumors are mostly sporadic but can also occur in familial forms, including different kinds of genetic syndromes with varying phenotypes and penetrance. Recently, somatic mutations of the tumor suppressor gene PRUNE2 were found to be frequent in parathyroid cancer (PC). The germline mutation status of PRUNE2 was investigated in a large cohort of patients with parathyroid tumors from the genetically homogenous Finnish population, 15 of which had PC, 16 atypical parathyroid tumors (APT), and 6 benign parathyroid adenomas (PA). Mutations in previously established hyperparathyroidism-related genes were screened with a targeted gene panel analysis. Nine PRUNE2 germline mutations with a minor allele frequency (MAF) of <0.05 were found in our cohort. Five of these were predicted to be potentially damaging and were identified in two patients with PC, two with APT, and three with PA. The mutational status was not associated with the tumor group nor related to the clinical picture or severity of the disease. Still, the frequent finding of rare germline mutations of PRUNE2 may point to the gene playing a role in the pathogenesis of parathyroid neoplasms.
RESUMO
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.
Assuntos
Neoplasia Endócrina Múltipla Tipo 1 , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Receptores de Somatostatina , Neoplasias Pancreáticas/diagnóstico , Pâncreas/patologia , Tumores Neuroendócrinos/patologiaRESUMO
The current study aims to assess the development of the knowledge generation program of the European Reference Network on Rare Endocrine Conditions (Endo-ERN) from its start in 2019 until December 2021, with special reference to webinars. We analyzed the number of webinars and live/postevent participants and whether participation and engagement of the attendees changed over time. A total of 30 (86%) self-prepared webinars comprising 300 h of knowledge and competence sharing were broadcasted (2019 - 3; 2020 - 13; 2021 - 14). A total of six webinars were broadcasted live prior to the coronavirus disease 2019 pandemic (https://endo-ern.eu/events/webinars/). The most active main thematic group (MTG) was MTG3 Genetic Disorders of Glucose and Insulin Homeostasis with eight (27%) webinars. Two (25%) MTGs fulfilled the goal to prepare at least two to three webinars per year. Patients were actively involved in 20% of the accounted webinars as both creators and presenters. The total number of live and postevent participants was 3023. The availability of the webinars after the live broadcast increased their outreach with a larger number of postevent viewers (n = 1629, 54%). Within the formal structured evaluation of the webinars, 40-85% of the participants replied on separate occasions and helped improve content. The free webinar access is among the perceived reasons for the rapidly increasing number of total hits to the Endo-ERN website. In conclusion, for its short existence, the Endo-ERN rapidly developed educational outreach, and further efforts to attract creators and learners are warranted.