40 research outputs found
Thymic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1
Objective MEN1 is associated with an increased risk of developing tumors in different endocrine organs. Neuroendocrine tumors of the thymus (TNETs) are very rare but often have an aggressive nature. We evaluated patients with MEN1 and TNET in three university hospitals in Finland. Design/Methods We evaluated patient records of 183 MEN1-patients from three university hospitals between the years 1985-2019 with TNETs. Thymus tumor specimens were classified according to the new WHO 2021 classification of TNET. We collected data on treatments and outcomes of these patients. Results There were six patients (3.3%) with MEN1 and TNET. Five of them had the same common gene mutation occurring in Finland. They originated from common ancestors encompassing two pairs of brothers from sequential generations. The mean age at presentation of TNET was 44.7 +/- 11.9 years. TNET was classified as atypical carcinoid (AC) in five out of six patients. One patient had a largely necrotic main tumor with very few mitoses and another nodule with 25 mitoses per 2 mm(2), qualifying for the 2021 WHO diagnosis of large cell neuroendocrine carcinoma (LCNEC). In our patients, the 5-year survival of the TNET patients was 62.5% and 10-year survival 31.3%. Conclusion In this study, TNETs were observed in one large MEN1 founder pedigree, where an anticipation-like earlier disease onset was observed in the most recent generation. TNET in MEN1 patients is an aggressive disease. The prognosis can be better by systematic screening. We also show that LCNEC can be associated with TNET in MEN1 patients.Peer reviewe
Long-term health-related quality of life in persons diagnosed with an insulinoma in Finland 1980-2010
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.Peer reviewe
Population-level effects of the national diabetes prevention programme (FIN-D2D) on the body weight, the waist circumference, and the prevalence of obesity
BACKGROUND: The implementation project of the national diabetes prevention programme in Finland, FIN-D2D, was carried out in primary health care in the area of five hospital districts during 2003-2007. METHODS: The population strategy of FIN-D2D was primarily aimed at increasing the awareness of type 2 diabetes and preventing obesity. To investigate the effects of this strategy, we studied the changes in the prevalence of obesity, overweight, and central obesity among a random independent sample of individuals aged 45-74 years in the FIN-D2D area; and assessed whether they differed from a sample of individuals in the control area, which consisted of four geographical areas not participating in FIN-D2D (FINRISK study). Data was obtained for 5850/ 6406 (in the beginning/ in the end) individuals. The duration of the observation period varied from three to five years. RESULTS: The mean body weight decreased from 78.7 to 78.1 kg (p = 0.041) in the FIN-D2D area, and from 78.7 to 78.0 kg (p = NS) in the control area. The prevalence of obesity (BMI â„30 kg/m(2)) decreased in the FIN-D2D area (26.5% vs. 24.4%, p = 0.015), and in the control area (28.4% vs. 25.2%, p = 0.005). The prevalence of morbid obesity (BMI â„40 kg/m(2)) remained unchanged in the FIN-D2D area, but increased in the control area (1.2% vs. 2.3%, p = 0.007). The mean waist circumference remained unchanged in the FIN-D2D area, but increased in the control area (92.8 vs. 94.0 cm, p = 0.005). CONCLUSIONS: The prevalence of obesity may be decreasing among 45-74 year old Finns. We still need a longer time perspective and future studies to see whether this favourable trend can be sustained in Finland. The actions of this implementation project can at least partly explain the differences in the mean waist circumference and the prevalence of morbid obesity between the intervention and control areas.Peer reviewe
Genetic Variants in SGLT1, Glucose Tolerance, and Cardiometabolic Risk
BACKGROUND Loss-of-function mutations in the SGLT1 (sodium/glucose co-transporter-1) gene result in a rare glucose/galactose malabsorption disorder and neonatal death if untreated. In the general population, variants related to intestinal glucose absorption remain uncharacterized. OBJECTIVES The goat of this study was to identify functional SGLT1 gene variants and characterize their clinical consequences. METHODS Whole exome sequencing was performed in the ARIC (Atherosclerosis Risk in Communities) study participants enrolled from 4 U.S. communities. The association of functional, nonsynonymous substitutions in SGLT1 with 2-h oral glucose tolerance test results was determined. Variants related to impaired glucose tolerance were studied, and Mendelian randomization analysis of cardiometabotic outcomes was performed. RESULTS Among 5,687 European-American subjects (mean age 54 +/- 6 years; 47% mate), those who carried a haplotype of 3 missense mutations (frequency of 6.7%)-Asn51Ser, Ala411Thr, and His615Gln-had lower 2-h glucose and odds of impaired glucose tolerance than noncarriers (beta-coefficient: -8.0; 95% confidence interval [CI]: -12.7 to -3.3; OR: 0.71; 95% CI: 0.59 to 0.86, respectively). The association of the haplotype with oral glucose tolerance test results was consistent in a replication sample of 2,791 African-American subjects (beta = -16.3; 95% CI: -36.6 to 4.1; OR: 0.39; 95% CI: 0.17 to 0.91) and an external European-Finnish population sample of 6,784 subjects (beta = -3.2; 95% CI: -6.4 to 0.02; OR: 0.81; 95% CI: 0.68 to 0.98). Using a Mendelian randomization approach in the index cohort, the estimated 25-year effect of a reduction of 20 mg/dl in 2-h glucose via SGLT1 inhibition would be reduced prevalent obesity (OR: 0.43; 95% CI: 0.23 to 0.63), incident diabetes (hazard ratio [HR]: 0.58; 95% CI: 0.35 to 0.81), heart failure (HR: 0.53; 95% CI: 0.24 to 0.83), and death (HR: 0.66; 95% CI: 0.42 to 0.90). CONCLUSIONS Functionally damaging missense variants in SGLT1 protect from diet-induced hyperglycemia in multiple populations. Reduced intestinal glucose uptake may protect from long-term cardiometabolic outcomes, providing support for therapies that target SGLT1 function to prevent and treat metabolic conditions. (C) 2018 Published by Elsevier on behalf of the American College of Cardiology Foundation.Peer reviewe
Characteristics and Outcomes of 79 Patients with an Insulinoma : A Nationwide Retrospective Study in Finland
Objective. Insulinomas are rare pancreatic tumours. Population-based data on their incidence, clinical picture, diagnosis, and treatment are almost nonexistent. The aim of this study was to clarify these aspects in a nationwide cohort of insulinoma patients diagnosed during three decades. Design and Methods. Retrospective analysis on all adult patients diagnosed with insulinoma in Finland during 1980-2010. Results. Seventy-nine patients were diagnosed with insulinoma over the research period. The median follow-up from diagnosis to last control visit was one (min 0, max 31) year. The incidence increased from 0.5/million/year in the 1980s to 0.9/million/year in the 2000s (p = 0 002). The median diagnostic delay was 13 months and did not change over the study period. The mean age at diagnosis was 52 (SD 16) years. The overall imaging sensitivity improved from 39% in the 1980s to 98% in the 2000s (p <0 001). Seventy- one (90%) of the patients underwent surgery with a curative aim, two (3%) had palliative surgery, and 6 (8%) were inoperable. There were no significant differences in the types of surgical procedures between the 1980s, 1990s, and 2000s; tumour enucleations comprised 43% of the operations, distal pancreatic resections 45%, and pancreaticoduodenectomies 12%, over the whole study period. Of the patients who underwent surgery with a curative aim, 89% had a full recovery. Postoperative complications occurred in half of the patients, but postoperative mortality was rare. Conclusions. The incidence of insulinomas has increased during the past three decades. Despite the improved diagnostic options, diagnostic delay has remained unchanged. To shorten the delay, clinicians should be informed and alert to consider the possibility of hypoglycemia and insulinoma, when symptomatic attacks are investigated in different sectors of the healthcare system. Developing the surgical treatment is another major target, in order to lower the overall complication rate, without compromising the high cure rate of insulinomas.Peer reviewe
Long-term morbidity and mortality in patients diagnosed with an insulinoma
Objective: Insulinomas are rare functional pancreatic neuroendocrine tumours. As previous data on the long-term prognosis of insulinoma patients are scarce, we studied the morbidity and mortality in the Finnish insulinoma cohort. Design: Retrospective cohort study. Methods: Incidence of endocrine, cardiovascular, gastrointestinal and psychiatric disorders, and cancers was compared in all the patients diagnosed with an insulinoma in Finland during 1980-2010 (n = 79, including two patients with multiple endocrine neoplasia type 1 syndrome), vs 316 matched controls, using the Mantel-Haenszel method. Overall survival was analysed with Kaplan-Meier and Cox regression analyses. Results: The median length of follow-up was 10.7 years for the patients and 12.2 years for the controls. The long-term incidence of atrial fibrillation (rate ratio (RR): 2.07 (95% CI: 1.02-4.22)), intestinal obstruction (18.65 (2.09-166.86)), and possibly breast (4.46 (1.29-15.39) and kidney cancers (RR not applicable) was increased among insulinoma patients vs controls, P < 0.05 for all comparisons. Endocrine disorders and pancreatic diseases were more frequent in the patients during the first year after insulinoma diagnosis, but not later on. The survival of patients with a non-metastatic insulinoma (n = 70) was similar to that of controls, but for patients with distant metastases (n = 9), the survival was significantly impaired (median 3.4 years). Conclusions: The long-term prognosis of patients with a non-metastatic insulinoma is similar to the general population, except for an increased incidence of atrial fibrillation, intestinal obstruction, and possibly breast and kidney cancers. These results need to be confirmed in future studies. Metastatic insulinomas entail a markedly decreased survival.publishedVersionPeer reviewe
Characteristics and Outcomes of 79 Patients with an Insulinoma: A Nationwide Retrospective Study in Finland
Objective. Insulinomas are rare pancreatic tumours. Population-based data on their incidence, clinical picture, diagnosis, and treatment are almost nonexistent. The aim of this study was to clarify these aspects in a nationwide cohort of insulinoma patients diagnosed during three decades. Design and Methods. Retrospective analysis on all adult patients diagnosed with insulinoma in Finland during 1980-2010. Results. Seventy-nine patients were diagnosed with insulinoma over the research period. The median follow-up from diagnosis to last control visit was one (min 0, max 31) year. The incidence increased from 0.5/million/year in the 1980s to 0.9/million/year in the 2000s (p = 0 002). The median diagnostic delay was 13 months and did not change over the study period. The mean age at diagnosis was 52 (SD 16) years. The overall imaging sensitivity improved from 39% in the 1980s to 98% in the 2000s (p < 0 001). Seventy- one (90%) of the patients underwent surgery with a curative aim, two (3%) had palliative surgery, and 6 (8%) were inoperable. There were no significant differences in the types of surgical procedures between the 1980s, 1990s, and 2000s; tumour enucleations comprised 43% of the operations, distal pancreatic resections 45%, and pancreaticoduodenectomies 12%, over the whole study period. Of the patients who underwent surgery with a curative aim, 89% had a full recovery. Postoperative complications occurred in half of the patients, but postoperative mortality was rare. Conclusions. The incidence of insulinomas has increased during the past three decades. Despite the improved diagnostic options, diagnostic delay has remained unchanged. To shorten the delay, clinicians should be informed and alert to consider the possibility of hypoglycemia and insulinoma, when symptomatic attacks are investigated in different sectors of the healthcare system. Developing the surgical treatment is another major target, in order to lower the overall complication rate, without compromising the high cure rate of insulinomas
Rare and low-frequency coding variants alter human adult height
Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways
Prognostic factors in differentiated thyroid carcinomas and their implications for current staging classifications
Sattumalta löydetyistÀ lisÀmunuaiskasvaimista valtaosa ei vaadi seurantaa
TiivistelmÀ
LÀhtökohdat: Kuvantamisen lisÀÀntyessÀ sattumalta löydettyjen lisÀmunuaiskasvainten mÀÀrÀ on kasvanut. Jatkotutkimusten ja seurannan kÀytÀnnöt ovat olleet vaihtelevia ja hyöty kyseenalainen. Selvitimme lisÀmunuaisinsidentaloomien luonnetta ja tietokonetomografian osuvuutta kasvainten luokittelussa ja seurannan ohjauksessa Pohjois-Pohjanmaan sairaanhoitopiirin potilasaineistossa.
MenetelmĂ€t: Aineisto muodostui 451 tĂ€ysi-ikĂ€isestĂ€ potilaasta vuosilta 2003â2013. LisĂ€munuaisinsidentaloomien radiologiset ja hormonaaliset löydökset kartoitettiin.
Tulokset: Adenoomia oli 352 (78,0 %), feokromosytoomia 10 (2,2 %), kortikaalisia karsinoomia 5 (1,1 %) ja etĂ€pesĂ€kkeitĂ€ 6 (1,3 %). Adenoomat olivat lĂ€pimitaltaan keskimÀÀrin 2,1 cm (0,5â5,5 cm). Alle 20 Hounsfieldin yksikön tiheyksisistĂ€ kasvaimista ei löytynyt yhtÀÀn pahanlaatuista primaarikasvainta. TT-kuvauksessa adenoomiksi lausutut kasvaimet eivĂ€t kasvaneet tai osoittautuneet seurannassa pahanlaatuisiksi potilailla, joilla ei ollut syöpĂ€historiaa.
PÀÀtelmÀt: Tuloksemme on sopusoinnussa European Society of Endocrinologyn suosituksen kanssa, jonka mukaan pienitiheyksisten (†10 HU) ja pienikokoisten (†4 cm), hormonaalisesti toimimattomien kasvainten kuvantamisseurannasta voidaan luopua.Abstract
Most adrenal incidentalomas do not require routine follow-up
Background: Increased used of computerized tomography (CT) imaging has led to an increased number of incidentally found adrenal masses. Guidelines for management of adrenal incidentalomas have been extensive and inconsistent.
Methods: We examined the biochemical characteristics and unenhanced density of adrenal incidentalomas in the Northern Ostrobothnia Hospital District in 2003â2013.
Results: In this retrospective study, 451 adult patients with incidentally found adrenal tumours were identified. Of these tumours, 352 (78.0%) were adenomas, 10 (2.2%) phaeochromocytomas, 5 (1.1%) cortical carcinomas and 6 (1.3%) metastases. In the group of low attenuation (< 20 Hounsfield units, HU), none of the patients had a primary adrenal malignancy. The attenuation value was > 25 HU in all phaeochromocytomas. If the adrenal tumour was classified as an adenoma in the initial imaging, no growth or malignant transformation was observed if the patient did not have an earlier history of malignancy.
Conclusions: Our results are consistent with the European Society of Endocrinology Clinical Practice Guideline. When a small (†4 cm), hormonally inactive adrenal incidentaloma with an unenhanced attenuation †10 HU is found, further routine follow-up is not needed