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Sökning: WFRF:(Burman Pia)

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1.
  • Bengtsson, Daniel, et al. (författare)
  • Corticotroph Pituitary Carcinoma in a Patient With Lynch Syndrome (LS) and Pituitary Tumors in a Nationwide LS Cohort
  • 2017
  • Ingår i: The Journal of clinical endocrinology and metabolism. - Oxford University Press. - 1945-7197. ; 102:11, s. 3928-3932
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Lynch syndrome (LS) is a cancer-predisposing syndrome caused by germline mutations in genes involved in DNA mismatch repair (MMR). Patients are at high risk for several types of cancer, but pituitary tumors have not previously been reported.Case: A 51-year-old man with LS (MSH2 mutation) and a history of colon carcinoma presented with severe Cushing disease and a locally aggressive pituitary tumor. The tumor harbored a mutation consistent with the patient's germline mutation and displayed defect MMR function. Sixteen months later, the tumor had developed into a carcinoma with widespread liver metastases. The patient prompted us to perform a nationwide study in LS.Nationwide Study: A diagnosis consistent with a pituitary tumor was sought for in the Swedish National Patient Registry. In 910 patients with LS, representing all known cases in Sweden, another two clinically relevant pituitary tumors were found: an invasive nonsecreting macroadenoma and a microprolactinoma (i.e., in total three tumors vs. one expected).Conclusion: Germline mutations in MMR genes may contribute to the development and/or the clinical course of pituitary tumors. Because tumors with MMR mutations are susceptible to treatment with immune checkpoint inhibitors, we suggest to actively ask for a family history of LS in the workup of patients with aggressive pituitary tumors.
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2.
  • Burman, Pia, et al. (författare)
  • Dual bronchial carcinoids and Cushing's syndrome with a paradoxical response to dexamethasone and a false positive outcome of inferior petrosal sinus sampling.
  • 2008
  • Ingår i: European Journal of Endocrinology. - Society of the European Journal of Endocrinology. - 1479-683X. ; 159, s. 483-488
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Establishing the cause of Cushing's syndrome can be a considerable challenge, in particular in ectopic ACTH syndrome, and often requires a combination of biochemical tests and imaging procedures. Subject A 27-year-old man presented with signs of Cushing's syndrome. P-ACTH levels were 3 times above the ULN and free urinary cortisol in the order of 1900 nmol/24 h. The work-up showed remarkable results. Results A 2-day low-dose dexamethasone suppression test demonstrated paradoxical increases in cortisol. Sampling from the inferior petrosal sinuses (BIPSS) showed a central to peripheral ACTH ratio of 4.7 after CRH stimulation, i.e. indicated pituitary disease, but MRI of the pituitary was normal and baseline P-CRH <1.0 (ref. <5) pmol/L. CT scan of the lungs showed 2 oval-shaped masses, 1.3 x 1.8 and 1.3 x 2 cm, in the middle lobe. Both were positive at somatostatin receptor scintigraphy, compatible with tumors or inflammatory lesions. Subsequently, 11C-5-hydroxytryptophan-PET showed distinct uptake in the tumors but not elsewhere. Two carcinoids situated 3 cm apart, both staining for ACTH, were removed at surgery. Conclusion This unusual case with dual bronchial carcinoids inducing hypercortisolism illustrates the problems with identifying the source of ACTH in Cushing s syndrome. Possibly, the false positive result at BIPSS reflects an unusual sensitivity of the pituitary corticotrophs to CRH in this patient since ectopic CRH secretion and/or eucortisolism at the time of the procedure could be ruled out. The work-up illustrates the great value of 11C-5-hydroxytryptophan-PET as a diagnostic procedure when other investigations have produced ambiguous results.
3.
  • Bäcklund, Nils, et al. (författare)
  • Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in Cushing's syndrome
  • 2020
  • Ingår i: European journal of endocrinology. - Society of the European Journal of Endocrinology. - 1479-683X. ; 182:6, s. 569-582
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The challenge of diagnosing Cushing's syndrome (CS) calls for high precision biochemical screening. This study aimed to establish robust reference intervals for, and compare the diagnostic accuracy of, salivary cortisol and cortisone in late-night samples and after a low-dose (1 mg) dexamethasone suppression test (DST). Design and methods: Saliva samples were collected at 08:00 and 23:00 h, and at 08:00 h, after a DST, from 22 patients with CS and from 155 adult reference subjects. We also collected samples at 20:00 and 22:00 h from 78 of the reference subjects. Salivary cortisol and cortisone were analysed with liquid chromatography-tandem mass spectrometry. The reference intervals were calculated as the 2.5th and 97.5th percentiles of the reference population measurements. Diagnostic accuracies of different tests were compared, based on areas under the receiver-operating characteristic curves. Results: The upper reference limits of salivary cortisol and cortisone at 23:00 h were 3.6 nmol/L and 13.5 nmol/L, respectively. Using these reference limits, CS was detected with a sensitivity (95% CI) of 90% (70-99%) and specificity of 96% (91-98%) for cortisol, and a 100% (84-100%) sensitivity and 95% (90-98%) specificity for cortisone. After DST, cortisol and cortisone upper reference limits were 0.79 nmol/L and 3.5 nmol/L, respectively. CS was detected with 95% (75-100%) sensitivity and 96% (92-99%) specificity with cortisol, and 100% (83-100%) sensitivity and 94% (89-97%) specificity with cortisone. No differences in salivary cortisol or cortisone levels were found between samples collected at 22:00 and 23:00 h. Conclusion: Salivary cortisol and cortisone in late-night samples and after DST showed high accuracy for diagnosing CS, salivary cortisone being slightly, but significantly better.
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4.
  • Höybye, Charlotte, et al. (författare)
  • Change in baseline characteristics over 20 years of adults with growth hormone (GH) deficiency on GH replacement therapy
  • 2019
  • Ingår i: European journal of endocrinology. - Society of the European Journal of Endocrinology. - 0804-4643. ; 181:6, s. 629-638
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Clinical observations over time of adults with growth hormone (GH) deficiency (GHD) have indicated a shift in patient characteristics at diagnosis. The objective of this study was to compare baseline characteristics of patients diagnosed with adult-onset GHD naive to GH replacement during t hree study periods (1994-1999 (P1), 2000-2004 (P2), and 2005-2012 (P3)) using the KIMS (Pfizer's International Metab olic) database. Methods: Data were retrieved for a total of 6069 patients with adult-on set GHD from six countries (Belgium, Germany, Netherlands, Spain, Sweden, and UK): P1 (n = 1705), P2 (n = 2397), and P3 (n = 1967). Results: The proportions of patients with pituitary/hypothalamic tumors and patients with multiple pituitary hormone deficiencies decreased per entry year period, while the proporti ons with hypertension and diabetes increased. The lag time from diagnosis of pituitary disease to start of GH treatme nt decreased by 2.9 years over the entry year periods. IGF-1 increased by 0.1 standard deviation score per entry year period. Maximum GH following various stimulation tests, BMI, and waist circumference increased. The use of radio therapy, glucocorticoid replacement doses, and the proportion of women >50 years on estrogen replacement therapy decreased. The effects of 1 year of GH replacement were similar over the entry year periods despite changes in the patients' baseline characteristics. An expected increase in fasting blood glucose was seen after 1 year of GH treatment. Conclusions: The degree of confirmed GHD became less pronounced and more pat ients with co-morbidities and diabetes were considered for GH replacement therapy, possibly r eflecting increased knowledge and confidence in GH therapy gained with time.
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5.
  • Onnestam, Lisa, et al. (författare)
  • National Incidence and Prevalence of TSH-Secreting Pituitary Adenomas in Sweden.
  • 2013
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - Oxford University Press. - 1945-7197. ; 98:2, s. 626-635
  • Tidskriftsartikel (refereegranskat)abstract
    • Context:TSH-secreting pituitary adenomas (TSHomas) are rare. Epidemiological data are scant and there are no reports on national incidence.Objective:The objective of the study was to estimate the national Swedish incidence and prevalence of TSHomas.Design:This was an observational study.Setting:The study was conducted at tertiary referral centers.Patients:The Swedish Pituitary Registry and World Health Organization International Statistical Classification of Diseases and Related Health Problems coding at all university hospitals were used to identify patients diagnosed with TSHomas 1990-2010. The identified patients' medical records were studied until the latest follow-up [median 5.0 years (range < 1-20 years)].Main Outcome Measurements:Incidence, prevalence, demographics, tumor characteristics, treatment outcome, and thyroid hormone level at diagnosis were measured.Results:The age-standardized national incidence of 28 TSHoma patients was 0.15 per 1 million inhabitants per year, with an increasing incidence over time (0.05 per 1 million per year in 1990-1994 to 0.26 per 1 million per year in 2005-2009). The national prevalence in 2010 was 2.8 per 1 million inhabitants, in which 0.85 per 1 million had active disease. Most patients (n = 22) underwent pituitary surgery, 5 had radiotherapy, and 6 had somatostatin analogues. Eighteen patients were considered cured at the latest follow-up; 25% remained uncontrolled. Subjects treated for putative primary hyperthyroidism prior to diagnosis had TSH levels more than double those with intact thyroid at diagnosis (P = .013). The median time to diagnosis was longer for women than men (4 vs < 1 year, P = .026). More women than men were treated surgically (94.1% vs 54.5%, P = .022).Conclusion:This is the first estimate of a national incidence of TSHoma. Additional epidemiological studies are needed to compare these results with other geographical areas. This study suggests an increased incidence of TSHomas, in agreement with reports on other pituitary adenomas.
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6.
  • Ragnarsson, Oskar, 1971-, et al. (författare)
  • Overall and disease-specific mortality in patients with Cushing's disease: a Swedish nationwide study.
  • 2019
  • Ingår i: The Journal of clinical endocrinology and metabolism. - 1945-7197. ; 104:6
  • Tidskriftsartikel (refereegranskat)abstract
    • It is still a matter of debate whether patients with Cushing's disease (CD) in remission have increased mortality.To study overall and disease-specific mortality, and predictive factors, in an unselected nationwide cohort of patients with CD.A retrospective study on patients diagnosed with CD, identified in the Swedish National Patient Registry between 1987 and 2013. Medical records were systematically reviewed to verify the diagnosis. Standardised mortality ratios (SMRs) with 95% confidence intervals (CI) were calculated and Cox regression models were used to identify predictors of mortality.Five-hundred-and-two patients [387 women (77%)] with CD were identified, of whom 419 (83%) were confirmed to be in remission. Mean age at diagnosis was 43 years (SD 16) and median follow-up time was 13 years (IQR 6-23). The observed number of deaths was 133 versus 54 expected, resulting in an overall SMR of 2.5 (95% CI 2.1-2.9). The commonest cause of death was cardiovascular diseases [SMR 3.3 (95% CI 2.6 -4.3)]. Excess mortality was also found due to infections and suicides. SMR in patients in remission was 1.9 (95% CI 1.5-2.3), where bilateral adrenalectomy and glucocorticoid replacement therapy were independently associated with increased mortality whereas growth hormone replacement was associated with improved outcome.This large nationwide study shows that patients with CD have an excess mortality. The findings illustrate the importance of obtaining remission and continued active surveillance, along with adequate hormone replacement, and evaluation of cardiovascular risk and mental health.
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7.
  • Ragnarsson, Oskar, 1971-, et al. (författare)
  • The incidence of Cushing’s disease : : a nationwide Swedish study
  • 2019
  • Ingår i: Pituitary. - Springer. - 1386-341X. ; 22:2, s. 179-186
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Studies on the incidence of Cushing’s disease (CD) are few and usually limited by a small number of patients. The aim of this study was to assess the annual incidence in a nationwide cohort of patients with presumed CD in Sweden. Methods: Patients registered with a diagnostic code for Cushing’s syndrome (CS) or CD, between 1987 and 2013 were identified in the Swedish National Patient Registry. The CD diagnosis was validated by reviewing clinical, biochemical, imaging, and histopathological data. Results: Of 1317 patients identified, 534 (41%) had confirmed CD. One-hundred-and-fifty-six (12%) patients had other forms of CS, 41 (3%) had probable but unconfirmed CD, and 334 (25%) had diagnoses unrelated to CS. The mean (95% confidence interval) annual incidence between 1987 and 2013 of confirmed CD was 1.6 (1.4–1.8) cases per million. 1987–1995, 1996–2004, and 2005–2013, the mean annual incidence was 1.5 (1.1–1.8), 1.4 (1.0–1.7) and 2.0 (1.7–2.3) cases per million, respectively. During the last time period the incidence was higher than during the first and second time periods (P < 0.05). Conclusion: The incidence of CD in Sweden (1.6 cases per million) is in agreement with most previous reports. A higher incidence between 2005 and 2013 compared to 1987–2004 was noticed. Whether this reflects a truly increased incidence of the disease, or simply an increased awareness, earlier recognition, and earlier diagnosis can, however, not be answered. This study also illustrates the importance of validation of the diagnosis of CD in epidemiological research.
8.
  • Schill, Fredrika, et al. (författare)
  • Pituitary Metastases : A Nationwide Study on Current Characteristics with Special Reference to Breast Cancer
  • 2019
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - Oxford University Press. - 0021-972X. ; 104:8, s. 3379-3388
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To investigate the contemporary presentation of pituitary metastases. Patients Thirty-eight patients diagnosed with pituitary metastases from 1996 to 2018 in Sweden. Methods Pituitary metastases were confirmed by histopathology (n = 27) or considered highly likely according to radiological findings, including rapid tumor progression (n = 11). Medical records were reviewed and sellar images reexamined centrally. Results Breast and lung cancers were the most common primary tumors, in 45% and 21% of patients, respectively. Sixty-seven percent of breast cancers overexpressed human epidermal growth factor receptor 2 (HER2); 53% of pituitary metastases from breast cancers appeared ≥10 years after diagnosis of the primary tumor. At presentation, 71% appeared to have ACTH deficiency, 65% had TSH deficiency, and 26% had diabetes insipidus. Fatigue, nausea/vomiting, loss of appetite, weight loss, myalgia, and/or arthralgia were reported in 47% of patients with morning cortisol <100 nmol/L vs 23% with cortisol ≥200 nmol/L. Sixteen patients had visual field defects, and eight had diplopia. Intrasellar and suprasellar tumor growth was the most frequent finding. Initially, a pituitary adenoma was considered the etiology in 18% of patients. Radiotherapy, pituitary surgery, and chemotherapy were used in 68%, 68%, and 11% of patients, respectively. One and 2 years after diagnosis of pituitary metastases, 50% and 26% of patients were alive. Conclusion Pituitary metastases may be mistaken for pituitary adenomas and can appear late, especially in breast cancer. Breast cancers overexpressing HER2 seem prone to metastasize to the pituitary. Hypocortisolism may be misdiagnosed as cancer-related malaise. An increased awareness of pituitary metastases and undiagnosed pituitary failure can improve management in these patients.
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9.
  • Allen, David B, et al. (författare)
  • Growth Hormone Safety Workshop Position Paper: a critical appraisal of recombinant human growth hormone therapy in children and adults.
  • 2015
  • Ingår i: European Journal of Endocrinology. - Society of the European Journal of Endocrinology. - 1479-683X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Recombinant human growth hormone (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety including; cancer risk, impact on glucose homeostasis and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk and the need for longterm surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.
10.
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