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  • 1
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    Bone-active drugs in premenopausal women with breast cancer under hormone-deprivation therapies
    Oxford University Press (OUP) ; 2024
    In:  European Journal of Endocrinology Vol. 191, No. 2 ( 2024-08-05), p. 117-125
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 191, No. 2 ( 2024-08-05), p. 117-125
    Abstract: Bone health management in premenopausal women with breast cancer (BC) under hormone-deprivation therapies (HDTs) is often challenging, and the effectiveness of bone-active drugs is still unknown. Methods This retrospective multicenter study included 306 premenopausal women with early BC undergoing HDTs. Bone mineral density (BMD) and morphometric vertebral fractures (VFs) were assessed 12 months after HDT initiation and then after at least 24 months. Results After initial assessment, bone-active drugs were prescribed in 77.5% of women (151 denosumab 60 mg/6 months, 86 bisphosphonates). After 47.0 ± 20.1 months, new VFs were found in 16 women (5.2%). Vertebral fracture risk was significantly associated with obesity (odds ratio [OR] 3.87, P = .028), family history of hip fractures or VFs (OR 3.21, P = .040] , chemotherapy-induced menopause (OR 6.48, P & lt; .001), preexisting VFs (OR 25.36, P & lt; .001), baseline T-score less than or equal to −2.5 standard deviation (SD) at any skeletal site (OR 4.14, P = .036), and changes at lumbar and total hip BMD (OR 0.94, P = .038 and OR 0.88, P & lt; .001, respectively). New VFs occurred more frequently in women untreated compared to those treated with bone-active drugs (14/69, 20.8% vs 2/237, 0.8%; P & lt; .001) and the anti-fracture effectiveness remained significant after correction for BMI (OR 0.03; P & lt; .001), family history of fractures (OR 0.03; P & lt; .001), chemotherapy-induced menopause (OR 0.04; P & lt; .001), and preexisting VFs (OR 0.01; P & lt; .001). Conclusions Premenopausal women under HDTs are at high risk of VFs in relationship with high BMI, densitometric diagnosis of osteoporosis, preexisting VFs, and family history of osteoporotic fractures. Vertebral fractures in this setting might be effectively prevented by bisphosphonates or denosumab.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1093/ejendo/lvae086
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 1485160-X
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  • 2
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    Aryl hydrocarbon receptor-interacting protein and pituitary adenomas: a population-based study on subjects exposed to dioxin after the Seveso, Italy, accident
    Oxford University Press (OUP) ; 2008
    In:  European Journal of Endocrinology Vol. 159, No. 6 ( 2008-12), p. 699-703
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 159, No. 6 ( 2008-12), p. 699-703
    Abstract: The pathogenesis of sporadic pituitary tumors is unknown. Loss-of-function mutations of aryl hydrocarbon receptor-interacting protein (AIP) have been identified in patients with familial pituitary tumors. AIP is a chaperone protein with multifunction properties, including modulation of the transcriptional activity of the aryl hydrocarbon receptor, which mediates toxicological and carcinogenic dioxin effects. Design We investigated the incidence of pituitary tumors in the Seveso population exposed to 2,3,7,8-tetrachlorodibenzo- para -dioxin following an industrial accident in 1976. Methods Through the hospital discharge registration system of Lombardy Region, we identified incident cases of pituitary adenomas between 1976 and 1996 in the Seveso population, subdivided in zone A ( n =804), B ( n =5.941), and R ( n =38.624) according to high, intermediate, and low exposure to dioxin respectively, and in the surrounding non-contaminated area, as reference ( n =232 745). Results We identified 42 pituitary adenomas in the reference area, 1 prolactinoma in zone A (rate ratio (RR) 6.2; 95% CI 0.9–45.5, P =0.07), 2 nonfuctioning pituitary tumors (NFPAs) in zone B (RR 1.9; 95% CI 0.5–7.7, P =0.39), and 3 prolactinomas and 2 NFPAs in zone R (RR 0.7; 95% CI 0.3–1.8, P =0.48). Conclusions The study is unique with regard to the availability of epidemiological and clinical data in an area of relatively pure dioxin exposure. The study indicates no statistically significant increase of incident pituitary tumors in this area, although the tendency toward a higher risk (three cases in zones A and B) of pituitary tumors in subjects exposed to high–intermediate dioxin concentrations in comparison with nonexposed population suggests the need for extended follow-up.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-08-0593
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2008
    detail.hit.zdb_id: 1485160-X
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  • 3
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    8-oxodG accumulation within super-enhancers marks fragile CTCF-mediated chromatin loops
    Oxford University Press (OUP) ; 2022
    In:  Nucleic Acids Research Vol. 50, No. 6 ( 2022-04-08), p. 3292-3306
    Details
    In: Nucleic Acids Research, Oxford University Press (OUP), Vol. 50, No. 6 ( 2022-04-08), p. 3292-3306
    Abstract: 8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), a major product of the DNA oxidization process, has been proposed to have an epigenetic function in gene regulation and has been associated with genome instability. NGS-based methodologies are contributing to the characterization of the 8-oxodG function in the genome. However, the 8-oxodG epigenetic role at a genomic level and the mechanisms controlling the genomic 8-oxodG accumulation/maintenance have not yet been fully characterized. In this study, we report the identification and characterization of a set of enhancer regions accumulating 8-oxodG in human epithelial cells. We found that these oxidized enhancers are mainly super-enhancers and are associated with bidirectional-transcribed enhancer RNAs and DNA Damage Response activation. Moreover, using ChIA-PET and HiC data, we identified specific CTCF-mediated chromatin loops in which the oxidized enhancer and promoter regions physically associate. Oxidized enhancers and their associated chromatin loops accumulate endogenous double-strand breaks which are in turn repaired by NHEJ pathway through a transcription-dependent mechanism. Our work suggests that 8-oxodG accumulation in enhancers–promoters pairs occurs in a transcription-dependent manner and provides novel mechanistic insights on the intrinsic fragility of chromatin loops containing oxidized enhancers-promoters interactions.
    Type of Medium: Online Resource
    ISSN: 0305-1048 , 1362-4962
    URL: Article
    DOI: 10.1093/nar/gkac143
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1472175-2
    SSG: 12
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  • 4
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    Thyrotoxicosis in patients with COVID-19: the THYRCOV study
    Oxford University Press (OUP) ; 2020
    In:  European Journal of Endocrinology Vol. 183, No. 4 ( 2020-10), p. 381-387
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 183, No. 4 ( 2020-10), p. 381-387
    Abstract: This study assessed thyroid function in patients affected by the coronavirus disease-19 (COVID-19), based on the hypothesis that the cytokine storm associated with COVID-19 may influence thyroid function and/or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may directly act on thyroid cells, such as previously demonstrated for SARS-CoV-1 infection. Design and methods: This single-center study was retrospective and consisted in evaluating thyroid function tests and serum interleukin-6 (IL-6) values in 287 consecutive patients (193 males, median age: 66 years, range: 27–92) hospitalized for COVID-19 in non-intensive care units. Results: Fifty-eight patients (20.2%) were found with thyrotoxicosis (overt in 31 cases), 15 (5.2%) with hypothyroidism (overt in only 2 cases), and 214 (74.6%) with normal thyroid function. Serum thyrotropin (TSH) values were inversely correlated with age of patients (rho −0.27; P   〈  0.001) and IL-6 (rho −0.41; P   〈  0.001). In the multivariate analysis, thyrotoxicosis resulted to be significantly associated with higher IL-6 (odds ratio: 3.25, 95% confidence interval: 1.97–5.36; P   〈  0.001), whereas the association with age of patients was lost ( P  = 0.09). Conclusions: This study provides first evidence that COVID-19 may be associated with high risk of thyrotoxicosis in relationship with systemic immune activation induced by the SARS-CoV-2 infection.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-20-0335
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1485160-X
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  • 5
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    Prognostic factors in ectopic Cushing’s syndrome due to neuroendocrine tumors: a multicenter study
    Oxford University Press (OUP) ; 2017
    In:  European Journal of Endocrinology Vol. 176, No. 4 ( 2017-04), p. 453-461
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 176, No. 4 ( 2017-04), p. 453-461
    Abstract: Evidence is limited regarding outcome of patients with ectopic Cushing’s syndrome (ECS) due to neuroendocrine tumors (NETs). Design We assessed the prognostic factors affecting the survival of patients with NETs and ECS. Methods Retrospective analysis of clinicopathological features, severity of hormonal syndrome, treatments from a large cohort of patients with NETs and ECS collected from 17 Italian centers. Results Our series included 110 patients, 58.2% female, with mean (± s.d. ) age at diagnosis of 49.5 ± 15.9 years. The main sources of ectopic ACTH were bronchial carcinoids (BC) (40.9%), occult tumors (22.7%) and pancreatic (p)NETs (15.5%). Curative surgery was performed in 56.7% (70.2% of BC, 11% of pNETs). Overall survival was significantly higher in BC compared with pNETs and occult tumors ( P  = 0.033) and in G1-NETs compared with G2 and G3 ( P  = 0.007). Negative predictive factors for survival were severity of hypercortisolism ( P   〈  0.02), hypokalemia ( P  = 0.001), diabetes mellitus ( P  = 0.0146) and distant metastases ( P   〈  0.001). Improved survival was observed in patients who underwent NET removal ( P   〈  0.001). Adrenalectomy improved short-term survival. Conclusions Multiple factors affect prognosis of ECS patients: type of NET, grading, distant metastases, severity of hypercortisolism, hypokalemia and diabetes mellitus. BCs have the highest curative surgical rate and better survival compared with occult tumors and pNETs. Hypercortisolism plays a primary role in affecting outcome and quality of life; therefore, prompt and vigorous treatment of hormonal excess by NET surgery and medical therapy should be a key therapeutic goal. In refractory cases, adrenalectomy should be considered as it affects outcome positively at least in the first 2 years.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-16-0809
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2017
    detail.hit.zdb_id: 1485160-X
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  • 6
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    Non-functioning pituitary adenoma database: a useful resource to improve the clinical management of pituitary tumors
    Oxford University Press (OUP) ; 2006
    In:  European Journal of Endocrinology Vol. 155, No. 6 ( 2006-12), p. 823-829
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 155, No. 6 ( 2006-12), p. 823-829
    Abstract: Objective : The long-term outcome of non-functioning pituitary adenoma (NFPA) patients is not clearly established, probably due to the low annual incidence and prolonged natural history of these rare tumors. The aim of this study was to evaluate clinical data at presentation and long-term post-surgery and radiotherapy outcome in a cohort of patients with NFPA. Design and methods : A computerized database was developed using Access 2000 software (Microsoft Corporation, 1999). Retrospective registration of 295 NFPA patients was performed in seven Endocrinological Centers of North West Italy. Data were analyzed by STATA software. Results : The main presenting symptoms were visual defects (67.8%) and headache (41.4%) and the most frequent pituitary deficit was hypogonadism (43.3%), since almost all tumors were macroadenomas (96.5%). Surgery was the first choice treatment (98% of patients) and total debulking was achieved in 35.5%. Radiotherapy was performed as adjuvant therapy after surgery in 41% of patients. At the follow-up, recurrence occurred in 19.2% of patients without post-surgical residual tumor after 7.5 ± 2.6 years, regrowth in 58.4% of patients with post-surgical remnant after 5.3 ± 4.0 years and residue enlargement in 18.4% of patients post-surgically treated with radiotherapy after 8.1 ± 7.3 years. Conclusions : Our database indicates that the goal of a definitive surgical cure has been achieved during the last decade in a low percentage of patients with NFPA. This tumor database may help to reduce the delay between symptom onset and diagnosis, to assess prognostic parameters for the follow-up of patients with different risk of recurrence and to define the efficacy and safety of different treatments and their association with mortality/morbidity.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/eje.1.02298
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2006
    detail.hit.zdb_id: 1485160-X
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  • 7
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    Long-term effects of radiotherapy on cardiovascular risk factors in acromegaly
    Oxford University Press (OUP) ; 2011
    In:  European Journal of Endocrinology Vol. 164, No. 5 ( 2011-05), p. 675-684
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 164, No. 5 ( 2011-05), p. 675-684
    Abstract: Radiation therapy (RT) is a useful adjuvant tool for acromegalic patients not cured by surgery and/or not responding to pharmacotherapy. However, its specific effects on cardio- and cerebrovascular morbidity are still on debate. Design Retrospective analysis of 42 acromegalic patients cured after conventional radiotherapy (CRT, n =31) or radiosurgery by gamma-knife (GKRS, n =11) followed for a median period of 16.5 years (range: 2–40). Totally, 56 patients cured by surgery alone, with similar GH/IGF1 levels and duration of disease remission, served as control group. Methods Changes in cardiovascular risk factors, such as body mass index, glucose metabolism, insulin resistance, blood pressure, and lipid profile (pre-defined primary end point) and occurrence of new major cardio- and cerebrovascular events (secondary end point) during follow-up. Results The number of obese, hypertensive, and dyslipidemic subjects increased over time only in patients cured with RT. In contrast, the glucose response to the oral glucose tolerance test and the percentage of subjects with glucose alterations improved only in controls. As expected, the percentage of patients with pituitary failure was deeply higher among RT patients than among controls (86 vs 30%, P 〈 0.0005). Despite these findings, a similar number of RT patients and controls developed major cardio- or cerebrovascular events (4/42 vs 3/56, P: NS ). No differences were found between CRT and GKRS subgroups. Conclusions Previous RT seems to be associated with a worse metabolic profile in acromegalic patients studied after a long-term follow-up. Nevertheless, a direct link between RT and cardiovascular events remains to be proven.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-10-1105
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2011
    detail.hit.zdb_id: 1485160-X
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  • 8
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    Landscape of somatic mutations in sporadic GH-secreting pituitary adenomas
    Oxford University Press (OUP) ; 2016
    In:  European Journal of Endocrinology Vol. 174, No. 3 ( 2016-03), p. 363-372
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 174, No. 3 ( 2016-03), p. 363-372
    Abstract: Alterations in the cAMP signaling pathway are common in hormonally active endocrine tumors. Somatic mutations at GNAS are causative in 30–40% of GH-secreting adenomas. Recently, mutations affecting the USP8 and PRKACA gene have been reported in ACTH-secreting pituitary adenomas and cortisol-secreting adrenocortical adenomas respectively. However, the pathogenesis of many GH-secreting adenomas remains unclear. Aim Comprehensive genetic characterization of sporadic GH-secreting adenomas and identification of new driver mutations. Design Screening for somatic mutations was performed in 67 GH-secreting adenomas by targeted sequencing for GNAS , PRKACA , and USP8 mutations ( n =31) and next-generation exome sequencing ( n =36). Results By targeted sequencing, known activating mutations in GNAS were detected in five cases (16.1%), while no somatic mutations were observed in both PRKACA and USP8 . Whole-exome sequencing identified 132 protein-altering somatic mutations in 31/36 tumors with a median of three mutations per sample (range: 1–13). The only recurrent mutations have been observed in GNAS (31.4% of cases). However, seven genes involved in cAMP signaling pathway were affected in 14 of 36 samples and eight samples harbored variants in genes involved in the calcium signaling or metabolism. At the enrichment analysis, several altered genes resulted to be associated with developmental processes. No significant correlation between genetic alterations and the clinical data was observed. Conclusion This study provides a comprehensive analysis of somatic mutations in a large series of GH-secreting adenomas. No novel recurrent genetic alterations have been observed, but the data suggest that beside cAMP pathway, calcium signaling might be involved in the pathogenesis of these tumors.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-15-1064
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
    detail.hit.zdb_id: 1485160-X
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  • 9
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    Influence of the d3GH receptor polymorphism on the metabolic and biochemical phenotype of GH-deficient adults at baseline and during short- and long-term recombinant human GH replacement therapy
    Oxford University Press (OUP) ; 2010
    In:  European Journal of Endocrinology Vol. 163, No. 3 ( 2010-09), p. 361-368
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 163, No. 3 ( 2010-09), p. 361-368
    Abstract: A common polymorphic variant of GH receptor (exon 3 deletion, d3GHR) has been linked with increased response to recombinant human GH (rhGH) in some patients with or without GH deficiency (GHD). The aim of the study was to investigate the impact of the GHR genotype on the phenotype of GHD adults and on the metabolic effect of rhGH therapy. Design Prospective study of GHD patients evaluated before and during short- (1 year, n =100) and long-term (5 years, n =50) rhGH therapy. Methods Effects of rhGH on IGF1 levels, body composition (body fat percentage, BF%), body mass index, lipid profile, and glucose homeostasis (fasting insulin and glucose, insulin sensitivity indexes) were evaluated according to the presence or the absence of the d3GHR variant. Results The different genotype did not influence basal phenotype of GHD. Short-term rhGH determined normalization of IGF1 levels, decrease in BF%, and worsening of insulin sensitivity, independently from the presence of the d3GHR allele. A significant increase in high-density lipoprotein cholesterol occurred in the d3GHR group. Normalization of IGF1 levels and decrease in BF% were maintained after 5 years. Insulin sensitivity restored to basal values, though in d3GHR patients fasting glucose remained significantly higher than at baseline. After both 1 and 5 years, percentage of subjects with impaired glucose tolerance, similar in the two groups at baseline, decreased in fl/fl while doubled in d3GHR patients. In this last group, a long-term significant reduction in total and low-density lipoprotein cholesterol was also observed. Conclusion The functional difference of d3GHR may influence some metabolic effects of rhGH on GHD adults.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-10-0317
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2010
    detail.hit.zdb_id: 1485160-X
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  • 10
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    Preliminary data on biochemical remission of acromegaly after somatostatin analogs withdrawal
    Oxford University Press (OUP) ; 2008
    In:  European Journal of Endocrinology Vol. 158, No. 1 ( 2008-01), p. 19-25
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 158, No. 1 ( 2008-01), p. 19-25
    Abstract: It is still unknown whether prolonged treatment with somatostatin analogs (SSTa) may cause a long-lasting disease remission in GH-secreting adenomas after drug discontinuation. The aim of the present study was to investigate the evolution of GH/IGF-I secretion and tumor mass after SSTa withdrawal in patients affected by acromegaly. Patients and Design A total of 27 patients with acromegaly (12 de novo and 15 previously operated) were treated with SSTa for a median period of 48 months and considered optimally controlled in hormonal and neuroradiological terms. None of them were previously irradiated. Methods Basal GH, post-glucose GH nadir, IGF-I, clinical signs/symptoms, and metabolic parameters were evaluated after 12–16 weeks from drug withdrawal. Only patients who met the current criteria for disease remission remained in drug suspension being periodically re-evaluated for biochemical/clinical data and neuroradiological imaging. Results After 12–16 weeks withdrawal, 15 of the 27 patients had disease relapse and restarted SSTa, while 12 were considered ‘in disease remission’ (44% of total). Glucose metabolism improved in both euglycemic and diabetic patients after short-term SSTa discontinuation. Only one of the ten patients who reached 24 weeks withdrawal showed biochemical disease recurrence. On the whole, five of the patients still in remission after 6 months have already prolonged the follow-up over 12 months (median: 24 months), without clinical and biochemical/neuroradiological evidence of disease recurrence. Conclusions These preliminary data indicate a successful withdrawal of SSTa at least in a subset of well-responsive patients with acromegaly and challenge the previously held concept that medical therapy is always a lifelong requirement.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-07-0488
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2008
    detail.hit.zdb_id: 1485160-X
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