Pub Date : 2024-08-10DOI: 10.1007/s40618-024-02435-x
M Bonomi, B Cangiano, S Cianfarani, A Garolla, D Gianfrilli, F Lanfranco, G Rastrelli, E Sbardella, G Corona, A M Isidori, V Rochira
Purpose: Andrological pathologies in the adulthood are often the results of conditions that originate during childhood and adolescence and sometimes even during gestation and neonatal period. Unfortunately, the reports in the literature concerning pediatric andrological diseases are scares and mainly concerning single issues. Furthermore, no shared position statement are so far available.
Methods: The Italian Society of Andrology and Sexual Medicine (SIAMS) commissioned an expert task force involving the Italian Society of Pediatric Endocrinology and Diabetology (SIEDP) to provide an updated guideline on the diagnosis and management of andrological disorders from childhood and adolescence to transition age. Derived recommendations were based on the grading of recommendations, assessment, development, and evaluation (GRADE) system.
Results: A literature search of articles in English for the term "varicoceles", "gynecomastia", "fertility preservation", "macroorchidism", "precocious puberty" and "pubertal delay" has been performed. Three major aspects for each considered disorder were assessed including diagnosis, clinical management, and treatment. Recommendations and suggestions have been provided for each of the mentioned andrological disorders.
Conclusions: These are the first guidelines based on a multidisciplinary approach that involves important societies related to the field of andrological medicine from pediatric to transition and adult ages. This fruitful discussion allowed for a general agreement on several recommendations and suggestions to be reached, which can support all stakeholders in improving andrological and general health of the transitional age.
{"title":"\"Management of andrological disorders from childhood and adolescence to transition age: guidelines from the Italian Society of Andrology and Sexual Medicine (SIAMS) in collaboration with the Italian Society for Pediatric Endocrinology and Diabetology (SIEDP)-Part-1\".","authors":"M Bonomi, B Cangiano, S Cianfarani, A Garolla, D Gianfrilli, F Lanfranco, G Rastrelli, E Sbardella, G Corona, A M Isidori, V Rochira","doi":"10.1007/s40618-024-02435-x","DOIUrl":"https://doi.org/10.1007/s40618-024-02435-x","url":null,"abstract":"<p><strong>Purpose: </strong>Andrological pathologies in the adulthood are often the results of conditions that originate during childhood and adolescence and sometimes even during gestation and neonatal period. Unfortunately, the reports in the literature concerning pediatric andrological diseases are scares and mainly concerning single issues. Furthermore, no shared position statement are so far available.</p><p><strong>Methods: </strong>The Italian Society of Andrology and Sexual Medicine (SIAMS) commissioned an expert task force involving the Italian Society of Pediatric Endocrinology and Diabetology (SIEDP) to provide an updated guideline on the diagnosis and management of andrological disorders from childhood and adolescence to transition age. Derived recommendations were based on the grading of recommendations, assessment, development, and evaluation (GRADE) system.</p><p><strong>Results: </strong>A literature search of articles in English for the term \"varicoceles\", \"gynecomastia\", \"fertility preservation\", \"macroorchidism\", \"precocious puberty\" and \"pubertal delay\" has been performed. Three major aspects for each considered disorder were assessed including diagnosis, clinical management, and treatment. Recommendations and suggestions have been provided for each of the mentioned andrological disorders.</p><p><strong>Conclusions: </strong>These are the first guidelines based on a multidisciplinary approach that involves important societies related to the field of andrological medicine from pediatric to transition and adult ages. This fruitful discussion allowed for a general agreement on several recommendations and suggestions to be reached, which can support all stakeholders in improving andrological and general health of the transitional age.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-02-01DOI: 10.1007/s40618-023-02296-w
E D da Silva, P M Spritzer, T M Fighera
Purpose: While it is common for menstrual cycles to cease within the initial 6 months of treatment, there are instances where some transgender men may not experience this cessation. We analyzed transgender men undergoing gender-affirming hormone therapy (GAHT) with testosterone who experienced breakthrough bleeding in order to identify the factors associated with this condition.
Methods: In this case-control study, 24 transgender men in the case group and 48 in the control group were assessed for clinical, sociodemographic, hormonal, and body composition variables using dual-energy X-ray absorptiometry. All participants had been on GATH for at least 6 months.
Results: A few transgender men experienced persistent breakthrough bleeding, which was associated with decreased testosterone levels and free androgen index (FAI) compared with controls (p = 0.002 and p = 0.008, respectively). Among individuals with breakthrough bleeding, 50% had testosterone levels below the lowest tertile calculated for the sample, compared with 18.8% on controls (p = 0.007). After therapy adjustment, testosterone levels increased compared with the values obtained in the initial bleeding episode (p = 0.031). Eight transgender men required the addition of an oral progestogen to achieve amenorrhea, and these individuals had higher BMI than those in whom the adjustment of the parenteral testosterone dose was adequate (p = 0.026). A univariate prevalence ratio analysis revealed a negative association of persistent bleeding with testosterone levels (p = 0.028) and FAI levels (p = 0.019).
Conclusion: Higher BMI and lower levels of testosterone and FAI were the main factors associated with breakthrough bleeding in transgender men.
目的:虽然月经周期在治疗的最初 6 个月内停止很常见,但有些变性男性可能不会经历这种停止。我们分析了接受睾酮性别确认激素疗法(GAHT)并出现突破性出血的变性男性,以确定与这种情况相关的因素:在这项病例对照研究中,病例组和对照组分别有 24 名和 48 名变性男性接受了临床、社会人口学、荷尔蒙和身体成分等变量的双能 X 射线吸收测量法评估。所有参与者均已接受 GATH 治疗至少 6 个月:结果:与对照组相比,少数变性男性出现持续性突破性出血,这与睾酮水平和游离雄激素指数(FAI)下降有关(分别为 p = 0.002 和 p = 0.008)。在出现突破性出血的患者中,50%的人的睾酮水平低于样本计算出的最低三等分位数,而对照组的这一比例为 18.8%(p = 0.007)。经过治疗调整后,睾酮水平与最初出血时的数值相比有所上升(p = 0.031)。有 8 名变性男性需要添加口服孕激素才能实现闭经,这些人的体重指数高于那些肠外睾酮剂量调整充分的人 (p = 0.026)。单变量患病率比分析显示,持续出血与睾酮水平(p = 0.028)和FAI水平(p = 0.019)呈负相关:结论:较高的体重指数以及较低的睾酮和 FAI 水平是变性男性突破性出血的主要相关因素。
{"title":"Persistent vaginal bleeding during gender-affirming hormone therapy in transgender men.","authors":"E D da Silva, P M Spritzer, T M Fighera","doi":"10.1007/s40618-023-02296-w","DOIUrl":"10.1007/s40618-023-02296-w","url":null,"abstract":"<p><strong>Purpose: </strong>While it is common for menstrual cycles to cease within the initial 6 months of treatment, there are instances where some transgender men may not experience this cessation. We analyzed transgender men undergoing gender-affirming hormone therapy (GAHT) with testosterone who experienced breakthrough bleeding in order to identify the factors associated with this condition.</p><p><strong>Methods: </strong>In this case-control study, 24 transgender men in the case group and 48 in the control group were assessed for clinical, sociodemographic, hormonal, and body composition variables using dual-energy X-ray absorptiometry. All participants had been on GATH for at least 6 months.</p><p><strong>Results: </strong>A few transgender men experienced persistent breakthrough bleeding, which was associated with decreased testosterone levels and free androgen index (FAI) compared with controls (p = 0.002 and p = 0.008, respectively). Among individuals with breakthrough bleeding, 50% had testosterone levels below the lowest tertile calculated for the sample, compared with 18.8% on controls (p = 0.007). After therapy adjustment, testosterone levels increased compared with the values obtained in the initial bleeding episode (p = 0.031). Eight transgender men required the addition of an oral progestogen to achieve amenorrhea, and these individuals had higher BMI than those in whom the adjustment of the parenteral testosterone dose was adequate (p = 0.026). A univariate prevalence ratio analysis revealed a negative association of persistent bleeding with testosterone levels (p = 0.028) and FAI levels (p = 0.019).</p><p><strong>Conclusion: </strong>Higher BMI and lower levels of testosterone and FAI were the main factors associated with breakthrough bleeding in transgender men.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139651973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-03-24DOI: 10.1007/s40618-024-02339-w
F Coperchini, A Greco, M Rotondi
Background: The family of perfluoroalkyl and polyfluoroalkyl substances (PFAS) raised concern for their proven bioaccumulation and persistence in the environment and animals as well as for their hazardous health effects. As a result, new congeners of PFAS have rapidly replaced the so-called "old long-chain PFAS" (mainly PFOA and PFOS), currently out-of-law and banned by most countries. These compounds derive from the original structure of "old long-chain PFAS", by cutting or making little conformational changes to their structure, thus obtaining new molecules with similar industrial applications. The new congeners were designed to obtain "safer" compounds. Indeed, old-long-chain PFAS were reported to exert thyroid disruptive effects in vitro, and in vivo in animals and humans. However, shreds of evidence accumulated so far indicate that the "restyling" of the old PFAS leads to the production of compounds, not only functionally similar to the previous ones but also potentially not free of adverse health effects and bioaccumulation. Studies aimed at characterizing the effects of new-PFAS congeners on thyroid function indicate that some of these new-PFAS congeners showed similar effects.
Purpose: The present review is aimed at providing an overview of recent data regarding the effects of novel PFAS alternatives on thyroid function.
Results and conclusions: An extensive review of current legislation and of the shreds of evidence obtained from in vitro and in vivo studies evaluating the effects of the exposure to novel PFOA and PFOS alternatives, as well as of PFAS mixture on thyroid function will be provided.
{"title":"Changing the structure of PFOA and PFOS: a chemical industry strategy or a solution to avoid thyroid-disrupting effects?","authors":"F Coperchini, A Greco, M Rotondi","doi":"10.1007/s40618-024-02339-w","DOIUrl":"10.1007/s40618-024-02339-w","url":null,"abstract":"<p><strong>Background: </strong>The family of perfluoroalkyl and polyfluoroalkyl substances (PFAS) raised concern for their proven bioaccumulation and persistence in the environment and animals as well as for their hazardous health effects. As a result, new congeners of PFAS have rapidly replaced the so-called \"old long-chain PFAS\" (mainly PFOA and PFOS), currently out-of-law and banned by most countries. These compounds derive from the original structure of \"old long-chain PFAS\", by cutting or making little conformational changes to their structure, thus obtaining new molecules with similar industrial applications. The new congeners were designed to obtain \"safer\" compounds. Indeed, old-long-chain PFAS were reported to exert thyroid disruptive effects in vitro, and in vivo in animals and humans. However, shreds of evidence accumulated so far indicate that the \"restyling\" of the old PFAS leads to the production of compounds, not only functionally similar to the previous ones but also potentially not free of adverse health effects and bioaccumulation. Studies aimed at characterizing the effects of new-PFAS congeners on thyroid function indicate that some of these new-PFAS congeners showed similar effects.</p><p><strong>Purpose: </strong>The present review is aimed at providing an overview of recent data regarding the effects of novel PFAS alternatives on thyroid function.</p><p><strong>Results and conclusions: </strong>An extensive review of current legislation and of the shreds of evidence obtained from in vitro and in vivo studies evaluating the effects of the exposure to novel PFOA and PFOS alternatives, as well as of PFAS mixture on thyroid function will be provided.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-02-20DOI: 10.1007/s40618-024-02302-9
A Garolla, M Kiesswetter, S Angelini, F Cavalieri, C Foresta, M Panzeri, A Ferlin
Purpose: Klinefelter syndrome (KS) is the most prevalent sex chromosome disorder among males. The communication of the KS diagnosis holds significant implications for the diagnosis's acceptance. Recently, the increased use of prenatal diagnostic procedures has raised the question of whether, when, and by whom information, once provided to parents, should be communicated to their children/adolescents. Currently, there is limited information on this topic. This study aims to investigate the most suitable timing, content, and healthcare professionals (HCPs) according to KS patients' suggestions for conveying the diagnosis, analyzing the impact of communicating the KS diagnosis on patients and their reception of the communication in real-life situations. Furthermore, research entails a comparison of the actual communication and the patients' preferred mode of communication.
Methods: Self-reported interview data was collected from 196 adults diagnosed with KS. The interview was structured, consisting of 32 multiple-choice questions covering various areas related to diagnosis communication.
Results: Most patients with Klinefelter syndrome reported that earlier communication would have been beneficial. Communication before the age of 18 and by parents increased the likelihood of overcoming negative consequences and relying on psychological support.
Conclusion: To mitigate the adverse effects of poorly timed and inadequately delivered communication, typically by a single person, it is advisable that such communication be carried out at the onset of adolescence by an interdisciplinary team of HCPs (including psychologists, geneticists, endocrinologists) and parents. The information provided should not solely concentrate on hormonal and fertility aspects, but also consider other factors such as psychological variables.
{"title":"Communication of the diagnosis to Klinefelter subjects: an observational study on a key moment of the patient's life.","authors":"A Garolla, M Kiesswetter, S Angelini, F Cavalieri, C Foresta, M Panzeri, A Ferlin","doi":"10.1007/s40618-024-02302-9","DOIUrl":"10.1007/s40618-024-02302-9","url":null,"abstract":"<p><strong>Purpose: </strong>Klinefelter syndrome (KS) is the most prevalent sex chromosome disorder among males. The communication of the KS diagnosis holds significant implications for the diagnosis's acceptance. Recently, the increased use of prenatal diagnostic procedures has raised the question of whether, when, and by whom information, once provided to parents, should be communicated to their children/adolescents. Currently, there is limited information on this topic. This study aims to investigate the most suitable timing, content, and healthcare professionals (HCPs) according to KS patients' suggestions for conveying the diagnosis, analyzing the impact of communicating the KS diagnosis on patients and their reception of the communication in real-life situations. Furthermore, research entails a comparison of the actual communication and the patients' preferred mode of communication.</p><p><strong>Methods: </strong>Self-reported interview data was collected from 196 adults diagnosed with KS. The interview was structured, consisting of 32 multiple-choice questions covering various areas related to diagnosis communication.</p><p><strong>Results: </strong>Most patients with Klinefelter syndrome reported that earlier communication would have been beneficial. Communication before the age of 18 and by parents increased the likelihood of overcoming negative consequences and relying on psychological support.</p><p><strong>Conclusion: </strong>To mitigate the adverse effects of poorly timed and inadequately delivered communication, typically by a single person, it is advisable that such communication be carried out at the onset of adolescence by an interdisciplinary team of HCPs (including psychologists, geneticists, endocrinologists) and parents. The information provided should not solely concentrate on hormonal and fertility aspects, but also consider other factors such as psychological variables.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-02-08DOI: 10.1007/s40618-024-02305-6
D Costa, C Pellicano, V Mercuri, E D'Ascanio, G Buglione, G Cicolani, U Basile, G Leodori, P Gargiulo, E Rosato
Aim: Acromegaly is a rare chronic disease, caused by the over-secretion of growth hormone (GH), that creates a pro-inflammatory state, but the exact mechanisms by which GH or insulin-like growth factor 1 (IGF-1) act on inflammatory cells are not fully understood. Aim of the study was to evaluate Interleukin-33 (IL33) and the skin perfusion of hands in patients with acromegaly (AP) and healthy controls (HC).
Methods: IL33 have been assessed in 40 AP and 40 HC. IL 33 was determined and skin perfusion of hands was assessed by laser speckle contrast analysis (LASCA) in both populations.
Results: IL33 was significantly higher in AP compared to HC [45.72 pg/ml (IQR 28.74-60.86) vs 14 pg/ml (IQR 6.5535); p < 0.05]. At LASCA, peripheral blood perfusion (PBP) was significantly lower in AP compared to HC [53.39 pU (IQR 40.94-65.44) vs 87 pU (IQR 80-98) p < 0.001]. The median values of ROI1, ROI2 and ROI3 were significantly lower in AP compared to HC [97.32 pU (IQR 50.89-121.69) vs 131 pU (IQR 108-135); p < 0.001], [58.68 pU (IQR 37.72-84.92) vs 83 pU (IQR 70-89), p < 0.05] and HC [52.16 (34.47-73.78) vs 85 (78-98), p < 0.001], respectively. The proximal-distal gradient (PDG) was observed in 18 of 40 (45%) AP.
Conclusion: Serum IL33 is higher in AP compared to HC; conversely a reduction of PBP of hands was present in AP compared to HC, probably due to endothelial dysfunction, strictly dependent on acromegaly and are not influenced by the choice of treatment.
目的:肢端肥大症是一种罕见的慢性疾病,由生长激素(GH)分泌过多引起,会产生一种促炎状态,但GH或胰岛素样生长因子1(IGF-1)作用于炎症细胞的确切机制尚不完全清楚。本研究旨在评估白细胞介素-33(IL33)与肢端肥大症患者(AP)和健康对照组(HC)手部皮肤灌注情况:方法:对 40 名肢端肥大症患者和 40 名健康对照者的 IL33 进行评估。方法:对 40 名肢端肥大症患者和 40 名健康对照者进行 IL33 评估,并通过激光斑点对比分析(LASCA)测定 IL33 和评估手部皮肤灌注情况:结果:AP 的 IL33 明显高于 HC [45.72 pg/ml (IQR 28.74-60.86) vs 14 pg/ml (IQR 6.5535); p 结论:AP 的血清 IL33 明显高于 HC:与 HC 相比,AP 患者的血清 IL33 更高;相反,与 HC 相比,AP 患者的手 PBP 降低,这可能是由于内皮功能障碍所致,与肢端肥大症密切相关,且不受治疗选择的影响。
{"title":"Role of IL33 in chronic inflammation and microvascular damage as a reflection of organ damage on a cohort of patients with acromegaly.","authors":"D Costa, C Pellicano, V Mercuri, E D'Ascanio, G Buglione, G Cicolani, U Basile, G Leodori, P Gargiulo, E Rosato","doi":"10.1007/s40618-024-02305-6","DOIUrl":"10.1007/s40618-024-02305-6","url":null,"abstract":"<p><strong>Aim: </strong>Acromegaly is a rare chronic disease, caused by the over-secretion of growth hormone (GH), that creates a pro-inflammatory state, but the exact mechanisms by which GH or insulin-like growth factor 1 (IGF-1) act on inflammatory cells are not fully understood. Aim of the study was to evaluate Interleukin-33 (IL33) and the skin perfusion of hands in patients with acromegaly (AP) and healthy controls (HC).</p><p><strong>Methods: </strong>IL33 have been assessed in 40 AP and 40 HC. IL 33 was determined and skin perfusion of hands was assessed by laser speckle contrast analysis (LASCA) in both populations.</p><p><strong>Results: </strong>IL33 was significantly higher in AP compared to HC [45.72 pg/ml (IQR 28.74-60.86) vs 14 pg/ml (IQR 6.5535); p < 0.05]. At LASCA, peripheral blood perfusion (PBP) was significantly lower in AP compared to HC [53.39 pU (IQR 40.94-65.44) vs 87 pU (IQR 80-98) p < 0.001]. The median values of ROI1, ROI2 and ROI3 were significantly lower in AP compared to HC [97.32 pU (IQR 50.89-121.69) vs 131 pU (IQR 108-135); p < 0.001], [58.68 pU (IQR 37.72-84.92) vs 83 pU (IQR 70-89), p < 0.05] and HC [52.16 (34.47-73.78) vs 85 (78-98), p < 0.001], respectively. The proximal-distal gradient (PDG) was observed in 18 of 40 (45%) AP.</p><p><strong>Conclusion: </strong>Serum IL33 is higher in AP compared to HC; conversely a reduction of PBP of hands was present in AP compared to HC, probably due to endothelial dysfunction, strictly dependent on acromegaly and are not influenced by the choice of treatment.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139703800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-02-02DOI: 10.1007/s40618-023-02295-x
M Wang, L Qin, W Bao, Z Xu, L Han, F Yan, W Yang
Purpose: To assess coronary inflammation by measuring the volume and density of the epicardial adipose tissue (EAT), perivascular fat attenuation index (FAI) and coronary plaque burden in patients with Cushing's syndrome (CS) based on coronary computed tomography angiography (CCTA).
Methods: This study included 29 patients with CS and 58 matched patients without CS who underwent CCTA. The EAT volume, EAT density, FAI and coronary plaque burden were measured. The high-risk plaque (HRP) was also evaluated. CS duration from diagnosis, 24-h urinary free cortisol (UFC), and abdominal visceral adipose tissue volume (VAT) of CS patients were recorded.
Results: The CS group had higher EAT volume (146.9 [115.4, 184.2] vs. 119.6 [69.0, 147.1] mL, P = 0.006), lower EAT density (- 78.79 ± 5.89 vs. - 75.98 ± 6.03 HU, P = 0.042), lower FAI (- 84.0 ± 8.92 vs. - 79.40 ± 10.04 HU, P = 0.038), higher total plaque volume (88.81 [36.26, 522.5] vs. 44.45 [0, 198.16] mL, P = 0.010) and more HRP plaques (7.3% vs. 1.8%, P = 0.026) than the controls. The multivariate analysis suggested that CS itself (β [95% CI], 29.233 [10.436, 48.03], P = 0.014), CS duration (β [95% CI], 0.176 [0.185, 4.242], P = 0.033), and UFC (β [95% CI], 0.197 [1.803, 19.719], P = 0.019) were strongly associated with EAT volume but not EAT density, and EAT volume (β [95% CI] - 0.037[- 0.058, - 0.016], P = 0.001) not CS was strongly associated with EAT density. EAT volume, FAI and plaque burden increased (all P < 0.05) in 6 CS patients with follow-up CCTA. The EAT volume had a moderate correlation with abdominal VAT volume (r = 0.526, P = 0.008) in CS patients.
Conclusions: Patients with CS have higher EAT volume and coronary plaque burden but less inflammation as detected by EAT density and FAI. The EAT density is associated with EAT volume but not CS itself.
{"title":"Epicardial and pericoronary adipose tissue and coronary plaque burden in patients with Cushing's syndrome: a propensity score-matched study.","authors":"M Wang, L Qin, W Bao, Z Xu, L Han, F Yan, W Yang","doi":"10.1007/s40618-023-02295-x","DOIUrl":"10.1007/s40618-023-02295-x","url":null,"abstract":"<p><strong>Purpose: </strong>To assess coronary inflammation by measuring the volume and density of the epicardial adipose tissue (EAT), perivascular fat attenuation index (FAI) and coronary plaque burden in patients with Cushing's syndrome (CS) based on coronary computed tomography angiography (CCTA).</p><p><strong>Methods: </strong>This study included 29 patients with CS and 58 matched patients without CS who underwent CCTA. The EAT volume, EAT density, FAI and coronary plaque burden were measured. The high-risk plaque (HRP) was also evaluated. CS duration from diagnosis, 24-h urinary free cortisol (UFC), and abdominal visceral adipose tissue volume (VAT) of CS patients were recorded.</p><p><strong>Results: </strong>The CS group had higher EAT volume (146.9 [115.4, 184.2] vs. 119.6 [69.0, 147.1] mL, P = 0.006), lower EAT density (- 78.79 ± 5.89 vs. - 75.98 ± 6.03 HU, P = 0.042), lower FAI (- 84.0 ± 8.92 vs. - 79.40 ± 10.04 HU, P = 0.038), higher total plaque volume (88.81 [36.26, 522.5] vs. 44.45 [0, 198.16] mL, P = 0.010) and more HRP plaques (7.3% vs. 1.8%, P = 0.026) than the controls. The multivariate analysis suggested that CS itself (β [95% CI], 29.233 [10.436, 48.03], P = 0.014), CS duration (β [95% CI], 0.176 [0.185, 4.242], P = 0.033), and UFC (β [95% CI], 0.197 [1.803, 19.719], P = 0.019) were strongly associated with EAT volume but not EAT density, and EAT volume (β [95% CI] - 0.037[- 0.058, - 0.016], P = 0.001) not CS was strongly associated with EAT density. EAT volume, FAI and plaque burden increased (all P < 0.05) in 6 CS patients with follow-up CCTA. The EAT volume had a moderate correlation with abdominal VAT volume (r = 0.526, P = 0.008) in CS patients.</p><p><strong>Conclusions: </strong>Patients with CS have higher EAT volume and coronary plaque burden but less inflammation as detected by EAT density and FAI. The EAT density is associated with EAT volume but not CS itself.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139673380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-03-26DOI: 10.1007/s40618-023-02299-7
R Pirchio, R S Auriemma, A Vergura, R Pivonello, A Colao
Purpose: Pasireotide is a novel therapeutic option for patients with acromegaly resistant to first-generation somatostatin receptor ligands. To date, real-life data are still scant, therefore, the aim of the current study is to evaluate the impact of long-term pasireotide therapy on disease control, pituitary tumor size, gluco-insulinemic and lipid profile in a real-life setting.
Methods: Retrospective study of data prospectively collected, evaluating hormonal, tumoral, and metabolic data of 28 patients with acromegaly administered with pasireotide in a pituitary tertiary referral center.
Results: Within the first 12 months of treatment, 70.4% of patients achieved normal IGF-I levels, which was maintained at 36-month evaluation in these responders patients. Patients who started with pasireotide 60 mg monthly exhibited significantly lower IGF-I levels after 36 months (p = 0.05) as compared to patients administered first with pasireotide 20 or 40 mg monthly. The maximal tumoral diameter was significantly decreased after 12 months of pasireotide (p < 0.001) and a further reduction was registered throughout the following months, with 41.2% of patients achieving a significant reduction (> 25% of baseline measurement) after 36 months of treatment. Fasting glucose significantly increased during the first 6 months (p < 0.001) with a gradual rise in diabetes prevalence during the following months, resulting diabetes prevalence after 36 months of pasireotide significantly increased compared to baseline (p = 0.003), although with glycated hemoglobin levels within the normal range. Diabetes was managed using oral glucose-lowering drugs or glucagon-like peptide 1 agonists, with no patient requiring insulin therapy. Pasireotide improved lipid profile, mainly during the first 12 months of treatment, by increasing HDL and decreasing triglycerides levels.
Conclusion: Pasireotide is effective and safe in the long-term. Hyperglycemia is a common event and is manageable even without insulin treatment.
{"title":"Long-term pasireotide therapy in acromegaly: extensive real-life experience of a referral center.","authors":"R Pirchio, R S Auriemma, A Vergura, R Pivonello, A Colao","doi":"10.1007/s40618-023-02299-7","DOIUrl":"10.1007/s40618-023-02299-7","url":null,"abstract":"<p><strong>Purpose: </strong>Pasireotide is a novel therapeutic option for patients with acromegaly resistant to first-generation somatostatin receptor ligands. To date, real-life data are still scant, therefore, the aim of the current study is to evaluate the impact of long-term pasireotide therapy on disease control, pituitary tumor size, gluco-insulinemic and lipid profile in a real-life setting.</p><p><strong>Methods: </strong>Retrospective study of data prospectively collected, evaluating hormonal, tumoral, and metabolic data of 28 patients with acromegaly administered with pasireotide in a pituitary tertiary referral center.</p><p><strong>Results: </strong>Within the first 12 months of treatment, 70.4% of patients achieved normal IGF-I levels, which was maintained at 36-month evaluation in these responders patients. Patients who started with pasireotide 60 mg monthly exhibited significantly lower IGF-I levels after 36 months (p = 0.05) as compared to patients administered first with pasireotide 20 or 40 mg monthly. The maximal tumoral diameter was significantly decreased after 12 months of pasireotide (p < 0.001) and a further reduction was registered throughout the following months, with 41.2% of patients achieving a significant reduction (> 25% of baseline measurement) after 36 months of treatment. Fasting glucose significantly increased during the first 6 months (p < 0.001) with a gradual rise in diabetes prevalence during the following months, resulting diabetes prevalence after 36 months of pasireotide significantly increased compared to baseline (p = 0.003), although with glycated hemoglobin levels within the normal range. Diabetes was managed using oral glucose-lowering drugs or glucagon-like peptide 1 agonists, with no patient requiring insulin therapy. Pasireotide improved lipid profile, mainly during the first 12 months of treatment, by increasing HDL and decreasing triglycerides levels.</p><p><strong>Conclusion: </strong>Pasireotide is effective and safe in the long-term. Hyperglycemia is a common event and is manageable even without insulin treatment.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-01-29DOI: 10.1007/s40618-023-02293-z
C He, Y Li, L Gan, Y Lin, B Zhang, L Ma, H Xue
Purpose: Autoimmune Thyroiditis (AIT) is the most common thyroid disease; however, there were no measures to prevent the progression of the disease. The present study attempts to identify that Notch signaling regulates the differentiation of T helper 17 (Th17) cells by activating downstream Phosphatidylinositol-3 kinase/protein kinase/mechanistic target of rapamycin complex 1 (PI3K/AKT/mTORC1) pathway participating in the thyroid injury of the experimental autoimmune thyroiditis (EAT).
Methods: In vivo experiments, mice were randomly divided into 4 groups: a control group, an EAT group, and two groups with LY294002 treatment (pTg plus 25 mg/kg or 50 mg/kg LY294002, respectively). The degrees of thyroiditis were evaluated, and the percentage of Th17 cells, expression of interleukin-17A (IL-17A), and the main components of the Notch-PI3K signaling pathway were detected in different groups. In vitro experiments, two different dosages of LY294002 (25 and 50 μM) were used to intervene splenic mononuclear cells (SMCs) from EAT mice to further evaluate the regulatory effect of Notch-PI3K pathway on Th17 cells.
Results: Our data demonstrate that the infiltration of Th17 cells and the expressions of IL-17A, Notch, hairy and split 1 (Hes1), p‑AKT (Ser473), p‑AKT (Thr308), p‑mTOR (Ser2448), S6K1, and S6K2 increased remarkably in EAT mice. After PI3K pathway was blocked, the degrees of thyroiditis were significantly alleviated, and the proportion of Th17 cells, the expression of IL-17A, and the above Notch-PI3K pathway-related molecules decreased in a dose-dependent manner. Additionally, the proportion of Th17 cells was positively correlated with the concentration of serum thyroglobulin antibody (TgAb), IL-17A, and Notch-PI3K pathway-related molecules mRNA levels.
Conclusions: Notch signal promotes the secretion of IL-17A from Th17 cells by regulating the downstream PI3K/AKT/mTORC1 pathway through Hes-Phosphatase and tensin homolog (PTEN) and participates in thyroid autoimmune damage, and the PI3K pathway inhibitor may play important effects on AIT by affecting Th17 cells differentiation.
{"title":"Notch signaling regulates Th17 cells differentiation through PI3K/AKT/mTORC1 pathway and involves in the thyroid injury of autoimmune thyroiditis.","authors":"C He, Y Li, L Gan, Y Lin, B Zhang, L Ma, H Xue","doi":"10.1007/s40618-023-02293-z","DOIUrl":"10.1007/s40618-023-02293-z","url":null,"abstract":"<p><strong>Purpose: </strong>Autoimmune Thyroiditis (AIT) is the most common thyroid disease; however, there were no measures to prevent the progression of the disease. The present study attempts to identify that Notch signaling regulates the differentiation of T helper 17 (Th17) cells by activating downstream Phosphatidylinositol-3 kinase/protein kinase/mechanistic target of rapamycin complex 1 (PI3K/AKT/mTORC1) pathway participating in the thyroid injury of the experimental autoimmune thyroiditis (EAT).</p><p><strong>Methods: </strong>In vivo experiments, mice were randomly divided into 4 groups: a control group, an EAT group, and two groups with LY294002 treatment (pTg plus 25 mg/kg or 50 mg/kg LY294002, respectively). The degrees of thyroiditis were evaluated, and the percentage of Th17 cells, expression of interleukin-17A (IL-17A), and the main components of the Notch-PI3K signaling pathway were detected in different groups. In vitro experiments, two different dosages of LY294002 (25 and 50 μM) were used to intervene splenic mononuclear cells (SMCs) from EAT mice to further evaluate the regulatory effect of Notch-PI3K pathway on Th17 cells.</p><p><strong>Results: </strong>Our data demonstrate that the infiltration of Th17 cells and the expressions of IL-17A, Notch, hairy and split 1 (Hes1), p‑AKT (Ser473), p‑AKT (Thr308), p‑mTOR (Ser2448), S6K1, and S6K2 increased remarkably in EAT mice. After PI3K pathway was blocked, the degrees of thyroiditis were significantly alleviated, and the proportion of Th17 cells, the expression of IL-17A, and the above Notch-PI3K pathway-related molecules decreased in a dose-dependent manner. Additionally, the proportion of Th17 cells was positively correlated with the concentration of serum thyroglobulin antibody (TgAb), IL-17A, and Notch-PI3K pathway-related molecules mRNA levels.</p><p><strong>Conclusions: </strong>Notch signal promotes the secretion of IL-17A from Th17 cells by regulating the downstream PI3K/AKT/mTORC1 pathway through Hes-Phosphatase and tensin homolog (PTEN) and participates in thyroid autoimmune damage, and the PI3K pathway inhibitor may play important effects on AIT by affecting Th17 cells differentiation.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139571103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-01-04DOI: 10.1007/s40618-023-02271-5
C Cipriani, J Pepe, L Colangelo, M Cilli, L Nieddu, S Minisola
Purpose: We sought to assess the clinical presentation of hypoparathyroidism (HypoPT) in Italy.
Methods: We performed a nationwide study retrieving data from the hospital discharge ICD-9 codes database of the Italian Health Ministry, from 2007 through 2017. The codes corresponding to diagnosis of cardiovascular disease, cancer, infection, renal failure, psychiatric disease, upper airway tract infection and pneumonia, seizures, nephrolithiasis, cognitive impairment, cerebral calcifications, skin disorders, fracture, and cataract were retrieved when associated with the diagnosis of HypoPT (252.1). We excluded codes corresponding to diagnoses of cancer of the neck region. In-hospital mortality rate was calculated. We retrieved the same data from an age- and sex-matched non-HypoPT control population.
Results: Fourteen thousand five hundred seventy-nine hospitalizations for HypoPT and controls were analyzed. Hospitalization for cardiovascular disease, cancer, infection, renal failure, seizures, nephrolithiasis, cerebral calcifications (p < 0.0001), and cognitive impairment (p < 0.05) were more common in HypoPT compared to controls. Mean age of HypoPT with cardiovascular disease, cancer, and renal failure was younger compared to controls (p < 0.0001). The OR of hospitalization for cardiovascular disease, cancer, renal failure, seizures (OR 2, 40, 48 and 1.6, respectively), and nephrolithiasis (OR 1.6) were significant in HypoPT compared to non-HypoPT. The OR of hospitalization for infection and cognitive impairment were significant only in HypoPT women (OR 1.3 and 2.3, respectively). In-hospital mortality rate was lower in HypoPT vs controls (0.5% and 3.7%; p < 0.0001).
Conclusion: Hospitalizations for cardiovascular disease, cancer, and renal failure are more prevalent and occur at a younger age in HypoPT vs non-HypoPT. Hospitalizations for seizures and nephrolithiasis are frequent in HypoPT; those for infection and cognitive impairment are more common in HypoPT women.
{"title":"Presentation of hypoparathyroidism in Italy: a nationwide register-based study.","authors":"C Cipriani, J Pepe, L Colangelo, M Cilli, L Nieddu, S Minisola","doi":"10.1007/s40618-023-02271-5","DOIUrl":"10.1007/s40618-023-02271-5","url":null,"abstract":"<p><strong>Purpose: </strong>We sought to assess the clinical presentation of hypoparathyroidism (HypoPT) in Italy.</p><p><strong>Methods: </strong>We performed a nationwide study retrieving data from the hospital discharge ICD-9 codes database of the Italian Health Ministry, from 2007 through 2017. The codes corresponding to diagnosis of cardiovascular disease, cancer, infection, renal failure, psychiatric disease, upper airway tract infection and pneumonia, seizures, nephrolithiasis, cognitive impairment, cerebral calcifications, skin disorders, fracture, and cataract were retrieved when associated with the diagnosis of HypoPT (252.1). We excluded codes corresponding to diagnoses of cancer of the neck region. In-hospital mortality rate was calculated. We retrieved the same data from an age- and sex-matched non-HypoPT control population.</p><p><strong>Results: </strong>Fourteen thousand five hundred seventy-nine hospitalizations for HypoPT and controls were analyzed. Hospitalization for cardiovascular disease, cancer, infection, renal failure, seizures, nephrolithiasis, cerebral calcifications (p < 0.0001), and cognitive impairment (p < 0.05) were more common in HypoPT compared to controls. Mean age of HypoPT with cardiovascular disease, cancer, and renal failure was younger compared to controls (p < 0.0001). The OR of hospitalization for cardiovascular disease, cancer, renal failure, seizures (OR 2, 40, 48 and 1.6, respectively), and nephrolithiasis (OR 1.6) were significant in HypoPT compared to non-HypoPT. The OR of hospitalization for infection and cognitive impairment were significant only in HypoPT women (OR 1.3 and 2.3, respectively). In-hospital mortality rate was lower in HypoPT vs controls (0.5% and 3.7%; p < 0.0001).</p><p><strong>Conclusion: </strong>Hospitalizations for cardiovascular disease, cancer, and renal failure are more prevalent and occur at a younger age in HypoPT vs non-HypoPT. Hospitalizations for seizures and nephrolithiasis are frequent in HypoPT; those for infection and cognitive impairment are more common in HypoPT women.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-03-05DOI: 10.1007/s40618-024-02306-5
A Giandalia, A Nicolucci, M Modugno, G Lucisano, M C Rossi, V Manicardi, A Rocca, G Di Cianni, P Di Bartolo, R Candido, D Cucinotta, G T Russo
Aims: Opportunities and needs for starting insulin therapy in Type 2 diabetes (T2D) have changed overtime. We evaluated clinical characteristics of T2D subjects undergoing the first insulin prescription during a 15-year-observation period in the large cohort of the AMD Annals Initiative in Italy.
Methods: Data on clinical and laboratory variables, complications and concomitant therapies and the effects on glucose control after 12 months were evaluated in T2D patients starting basal insulin as add-on to oral/non-insulin injectable agents, and in those starting fast-acting in add-on to basal insulin therapy in three 5-year periods (2005-2019).
Results: We evaluated data from 171.688 T2D subjects who intensified therapy with basal insulin and 137.225 T2D patients who started fast-acting insulin. Overall, intensification with insulin occurred progressively earlier over time in subjects with shorter disease duration. Moreover, the percentage of subjects with HbA1c levels > 8% at the time of basal insulin initiation progressively decreased. The same trend was observed for fast-acting formulations. Clinical characteristics of subjects starting insulin did not change in the three study-periods, although all major risk factors improved overtime. After 12 months from the starting of basal or fast-acting insulin therapy, mean HbA1c levels decreased in all the three investigated time-periods, although mean HbA1c levels remained above the recommended target.
Conclusions: In this large cohort of T2D subjects, a progressively earlier start of insulin treatment was observed during a long observation period, suggesting a more proactive prescriptive approach. However, after 12 months from insulin prescription, in many patients, HbA1c levels were still out-of-target.
{"title":"Temporal trends in the starting of insulin therapy in type 2 diabetes in Italy: data from the AMD Annals initiative.","authors":"A Giandalia, A Nicolucci, M Modugno, G Lucisano, M C Rossi, V Manicardi, A Rocca, G Di Cianni, P Di Bartolo, R Candido, D Cucinotta, G T Russo","doi":"10.1007/s40618-024-02306-5","DOIUrl":"10.1007/s40618-024-02306-5","url":null,"abstract":"<p><strong>Aims: </strong>Opportunities and needs for starting insulin therapy in Type 2 diabetes (T2D) have changed overtime. We evaluated clinical characteristics of T2D subjects undergoing the first insulin prescription during a 15-year-observation period in the large cohort of the AMD Annals Initiative in Italy.</p><p><strong>Methods: </strong>Data on clinical and laboratory variables, complications and concomitant therapies and the effects on glucose control after 12 months were evaluated in T2D patients starting basal insulin as add-on to oral/non-insulin injectable agents, and in those starting fast-acting in add-on to basal insulin therapy in three 5-year periods (2005-2019).</p><p><strong>Results: </strong>We evaluated data from 171.688 T2D subjects who intensified therapy with basal insulin and 137.225 T2D patients who started fast-acting insulin. Overall, intensification with insulin occurred progressively earlier over time in subjects with shorter disease duration. Moreover, the percentage of subjects with HbA1c levels > 8% at the time of basal insulin initiation progressively decreased. The same trend was observed for fast-acting formulations. Clinical characteristics of subjects starting insulin did not change in the three study-periods, although all major risk factors improved overtime. After 12 months from the starting of basal or fast-acting insulin therapy, mean HbA1c levels decreased in all the three investigated time-periods, although mean HbA1c levels remained above the recommended target.</p><p><strong>Conclusions: </strong>In this large cohort of T2D subjects, a progressively earlier start of insulin treatment was observed during a long observation period, suggesting a more proactive prescriptive approach. However, after 12 months from insulin prescription, in many patients, HbA1c levels were still out-of-target.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140029326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}