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| 2. |
- Casar-Borota, Olivera, et al.
(författare)
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A high-throughput analysis of the IDH1(R132H) protein expression in pituitary adenomas
- 2016
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403. ; 19:4, s. 407-414
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Tidskriftsartikel (refereegranskat)abstract
- Inactivating mutations of isocitrate dehydrogenase (IDH) 1 and 2, mitochondrial enzymes participating in the Krebs tricarboxylic acid cycle play a role in the tumorigenesis of gliomas and also less frequently in acute myeloid leukemia and other malignancies. Inhibitors of mutant IDH1 and IDH2 may potentially be effective in the treatment of the IDH mutation driven tumors. Mutations in the succinate dehydrogenase, the other enzyme complex participating in the Krebs cycle and electron transfer of oxidative phosphorylation occur in the paragangliomas, gastrointestinal stromal tumors, and occasionally in the pituitary adenomas. We aimed to determine whether the IDH1(R132H) mutation, the most frequent IDH mutation in human malignancies, occurs in pituitary adenomas. We performed immunohistochemical analysis by using a monoclonal anti-IDH1(R132H) antibody on the tissue microarrays containing specimens from the pituitary adenomas of different hormonal types from 246 patients. In positive samples, the status of the IDH1 gene was further examined by molecular genetic analyses. In all but one patient, there was no expression of mutated IDH1(R132H) protein in the tumor cells by immunohistochemistry. Only one patient with a recurring clinically non-functioning gonadotroph adenoma demonstrated IDH1(R132H)-immunostaining in both the primary tumor and the recurrence. However, no mutation in the IDH1 gene was detected using different molecular genetic analyses. IDH1(R132H) mutation occurs only exceptionally in pituitary adenomas and does not play a role in their pathogenesis. Patients with pituitary adenomas do not seem to be candidates for treatment with the inhibitors of mutant IDH1.
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| 4. |
- Janson, Eva Tiensuu
(författare)
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Treatment of neuroendocrine tumors with somatostatin analogs
- 2006
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403. ; 9:3, s. 249-256
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Forskningsöversikt (populärvet., debatt m.m.)abstract
- Neuroendocrine tumors constitute a group of hormone producing tumors originating from neuroendocrine cells in different organs. Most tumors have a low proliferation index measured by Ki67 and the progression of the tumor is slow. However, many patients suffer from endocrine symptoms induced by the hormones produced and released by the tumor cells. For some patients these symptoms can be life- threatening as in midgut carcinoid patients suffering from carcinoid crises with extensive flushes and hypotension or in patients with severe diarrhea induced by tumors producing vasointestinal polypeptide. In many other patients the hormone-induced symptoms interfere with the ability to carry out ordinary daily activities. The introduction of somatostatin analogs in the treatment of these hormone related symptoms has made it possible to control most of them and has added significantly to the quality of life for this group of patients. Unfortunately, the clinical inhibitory effect on tumor growth has not been very good with only 5-10% of the patients showing an objective response. However, stabilization of tumor growth may be achieved in a significant number of patients. In the future, the hope is that development of new somatostatin analogs with broader receptor-binding profiles will give us new analogs which are more efficient with regard to their antiproliferative effect. This possibility will be studied in future trials.
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| 5. |
- Kolnes, Anders Jensen, et al.
(författare)
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TGFBR3L is associated with gonadotropin production in non-functioning gonadotroph pituitary neuroendocrine tumours
- 2023
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Ingår i: Pituitary. - : Springer. - 1386-341X .- 1573-7403. ; 26:2, s. 227-236
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Transforming growth factor-beta receptor 3-like (TGFBR3L) is a pituitary enriched membrane protein selectively detected in gonadotroph cells. TGFBR3L is named after transforming growth factor-beta receptor 3 (TGFBR3), an inhibin A co-receptor in mice, due to sequence identity to the C-terminal region. We aimed to characterize TGFBR3L detection in a well-characterized, prospectively collected cohort of non-functioning pituitary neuroendocrine tumours (NF-PitNETs) and correlate it to clinical data.Methods 144 patients operated for clinically NF-PitNETs were included. Clinical, radiological and biochemical data were recorded. Immunohistochemical (IHC) staining for FSH beta and LH beta was scored using the immunoreactive score (IRS), TGFBR3L and TGFBR3 were scored by the percentage of positive stained cells.Results TGFBR3L staining was selectively present in 52% of gonadotroph tumours. TGFBR3L was associated to IRS of LH beta (median 2 [IQR 0-3] in TGFBR3L negative and median 6 [IQR 3-9] in TGFBR3L positive tumours, p < 0.001), but not to the IRS of FSH beta (p = 0.32). The presence of TGFBR3L was negatively associated with plasma gonadotropin concentrations in males (P-FSH median 5.5 IU/L [IQR 2.9-9.6] and median 3.0 [IQR 1.8-5.6] in TGFBR3L negative and positive tumours respectively, p = 0.008) and P-LH (median 2.8 IU/L [IQR 1.9-3.7] and median 1.8 [IQR 1.1-3.0] in TGFBR3L negative and positive tumours respectively, p = 0.03). TGFBR3 stained positive in 22% (n = 25) of gonadotroph tumours with no correlation to TGFBR3L.Conclusion TGFBR3L was selectively detected in half (52%) of gonadotroph NF-PitNETs. The association to LH beta staining and plasma gonadotropins suggests that TGFBR3L may be involved in hormone production in gonadotroph NF-PitNETs.
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| 6. |
- Kreitschmann-Andermahr, Ilonka, et al.
(författare)
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Diagnosis and management of acromegaly : the patient's perspective
- 2016
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403. ; 19:3, s. 268-276
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE:Early diagnosis is a success factor for the prevention of long-term comorbidity and premature death in patients with acromegaly, but large-scale data on the diagnostic process and disease management are scarce. Therefore, we aimed to evaluate the diagnostic process, implementation of treatment and changes in life situation in patients with acromegaly, focusing on sex-specific differences.METHODS:Non-interventional patient-reported outcome study. 165 patients with clinically and biochemically proven acromegaly were questioned about the diagnostic process and utilization of health care by means of a self-developed standardized postal survey including questions on acromegaly symptoms experienced before diagnosis, number and specialty of consulted doctors, time to diagnosis and aftercare.RESULTS:The diagnostic process took 2.9 (SD 4.53) years, during which 3.4 (SD 2.99) physicians were consulted. Women waited longer [4.1 (SD 5.53) years] than men [1.6 (SD 2.69) years; p = 0.001] for the correct diagnosis, and consulted more doctors in the process [4.0 (SD 2.99) vs. 2.7 (SD 2.84) doctors, p < 0.001, respectively]. In 48.5 % of patients, acromegaly was diagnosed by an endocrinologist (men: 45.1 %; women: 52.4 %). Overall disease duration from symptom onset until last surgery was 5.5 (SD 6.85) years, with no sex differences. A change in employment status was the most commonly reported event after diagnosis and a quarter of the patients stated that the illness had changed their lives.CONCLUSIONS:Our findings confirm the urgent need to increase awareness of the clinical manifestation of acromegaly to facilitate an earlier diagnosis of the disease and to provide diagnostic equality across the sexes.
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| 7. |
- Manojlovic-Gacic, Emilija, et al.
(författare)
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Histopathological classification of non-functioning pituitary neuroendocrine tumors
- 2018
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403. ; 21:2, s. 119-129
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Forskningsöversikt (refereegranskat)abstract
- Non-functioning pituitary neuroendocrine tumors do not cause endocrine symptoms related to hypersecretion of adenohypophyseal hormones and are clinically characterized by symptoms due to growing sellar tumor mass. Histopathological classification of this tumor group has always been challenging due to their heterogeneity, limited knowledge on their biology, and diverse methodological problems. We have searched PubMed database for data related to the histopathological classification of non-functioning pituitary tumors and methods for its application. Principles of the classification and grading presented in the recently released 4th edition of the World Health Organization classification of endocrine tumors have been summarized. Based on the expression of anterior pituitary hormones and pituitary specific transcription factors, gonadotroph tumors dominate within the group of clinically non-functioning tumors, followed by corticotroph type; however, other less common types of the non-functioning tumors can be identified. Assessment of tumor cell proliferation is important to identify "high-risk adenomas." A few subtypes of non-functioning tumors belong to the category of potentially aggressive tumors, independent of the cell proliferation rate. Here, we present up to date criteria for the classification of clinically non-functioning pituitary tumors, offer a diagnostic approach for the routine clinical use, and emphasize a need for inclusion of prognostic and predictive markers in the classification.
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| 8. |
- Nyström, Helena Filipsson, 1966, et al.
(författare)
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The metabolic consequences of thyroxine replacement in adult hypopituitary patients.
- 2012
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1573-7403 .- 1386-341X. ; 15:4, s. 495-504
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Tidskriftsartikel (refereegranskat)abstract
- The metabolic consequences of thyroxine replacement in patients with central hypothyroidism (CH) need to be evaluated. The aim was to examine the outcome of thyroxine replacement in CH. Adult hypopituitary patients (n = 1595) with and without CH from KIMS (Pfizer International Metabolic Database) were studied before and after 2 years of GH replacement. CH patients (CH, n = 1080) were compared with TSH sufficient patients (TSHsuff n = 515) as one group and divided by thyroxine dose/kg/day into tertiles (CHlow-mid-high). Anthropometry, fasting glucose, glycosylated haemoglobin (HbA1c), blood pressure, lipids, IGF-I SDS, quality of life and morbidity were studied. Analyses were standardized for gender, age, number and types of pituitary insufficiencies, stimulated GH peak, age at GH deficiency onset, aetiologies and, when appropriate, for weight and GH dose. At baseline, TSHsuff patients did not differ from CH or CHmid in any outcome. CHlow (≤1.18 μg thyroxine/kg/day) had increased weight, BMI and larger waist circumference (WC), CHhigh (≥1.58 μg thyroxine/kg/day) had lower weight, BMI, WC and IGF-I than TSHsuff and compared to their predicted weights, BMIs and WCs. For every 0.1 μg/kg/day increase of thyroxine dose, body weight decreased 1.0 kg, BMI 0.3 kg/m(2), and WC 0.65 cm. The GH sensitivity of the CH group was higher (0.76 ± 0.56 SDS/mg GH) than that of TSHsuff patients (0.58 ± 0.64 SDS/mg GH), P < 0.001. The middle thyroxine dose (1.19-1.57 μg/kg/day) seems to be the most physiological. This is equivalent to 70, 100, 125 μg thyroxine/day for hypopituitary patients of 50, 70 or 90 kg weight, respectively.
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| 9. |
- Papakokkinou, Eleni, et al.
(författare)
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Prevalence of Nelson's syndrome after bilateral adrenalectomy in patients with cushing's disease: a systematic review and meta-analysis
- 2021
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403.
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Bilateral adrenalectomy (BA) still plays an important role in the management of Cushing's disease (CD). Nelson's syndrome (NS) is a severe complication of BA, but conflicting data on its prevalence and predicting factors have been reported. The aim of this study was to determine the prevalence of NS, and identify factors associated with its development. Data sources Systematic literature search in four databases. Study Selection Observational studies reporting the prevalence of NS after BA in adult patients with CD. Data extraction Data extraction and risk of bias assessment were performed by three independent investigators. Data synthesis Thirty-six studies, with a total of 1316 CD patients treated with BA, were included for the primary outcome. Pooled prevalence of NS was 26% (95% CI 22-31%), with moderate to high heterogeneity (I-2 67%, P < 0.01). The time from BA to NS varied from 2 months to 39 years. The prevalence of NS in the most recently published studies, where magnet resonance imaging was used, was 38% (95% CI 27-50%). The prevalence of treatment for NS was 21% (95% CI 18-26%). Relative risk for NS was not significantly affected by prior pituitary radiotherapy [0.9 (95% CI 0.5-1.6)] or pituitary surgery [0.6 (95% CI 0.4-1.0)]. Conclusions Every fourth patient with CD treated with BA develops NS, and every fifth patient requires pituitary-specific treatment. The risk of NS may persist for up to four decades after BA. Life-long follow-up is essential for early detection and adequate treatment of NS.
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| 10. |
- Ragnarsson, Oskar, 1971, et al.
(författare)
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The incidence of Cushing’s disease : a nationwide Swedish study
- 2019
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Ingår i: Pituitary. - : Springer. - 1386-341X .- 1573-7403. ; 22:2, s. 179-186
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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.
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