Sarantis Livadas, Bulent O Yildiz, George Mastorakos, Alessandra Gambineri, Duarte Pignatelli, Francesco Giorgino, Marianne Skovsager Andersen, Barbara Obermayer-Pietsch, Djuro Macut
Background: Although polycystic ovary syndrome (PCOS) is a very common endocrinopathy, there are several issues related to this disorder which perplex clinicians in their everyday practice.
Objective: To determine the current state of knowledge among European endocrinologists concerning the full spectrum of PCOS.
Methods: An online survey comprising 41 items covering various aspects of PCOS diagnosis and management was distributed to members of the European Society of Endocrinology.
Results: A total of 505 European endocrinologists (64% females), with a mean age of 47 ± 11.6 years, participated in the survey. The Rotterdam criteria were the primary diagnostic tool for 85% of respondents. Most referrals (87.1%) occurred between ages 20 and 40 years. Twenty-five percent of physicians have access to mass spectrometry for the evaluation of androgen levels. While an extended metabolic profile was commonly employed as part of the workup, there was uncertainty regarding chronic anovulation diagnosis. Diabetes, including gestational or type 2, was recognized as a significant risk factor with universal screening irrespective of BMI status. Lifestyle modification and metformin were considered as standard interventions by all participants alongside oral contraceptives, though there was significant discrepancy in treatment duration.
Conclusions: The Rotterdam diagnostic criteria are widely adopted for PCOS diagnosis among European endocrinologists. The current updated survey shows an emphasis on steroid profiling as an important part of diagnostic workup and a strong position held for recognition of PCOS as a metabolic condition with potentially serious implications. Current therapy thus shifted to the demand for prioritizing lifestyle interventions and metabolic therapies, either as monotherapy or in combination with standard hormone compounds.
{"title":"European survey of diagnosis and management of the polycystic ovary syndrome: full report on the ESE PCOS Special Interest Group's 2023 Questionnaire.","authors":"Sarantis Livadas, Bulent O Yildiz, George Mastorakos, Alessandra Gambineri, Duarte Pignatelli, Francesco Giorgino, Marianne Skovsager Andersen, Barbara Obermayer-Pietsch, Djuro Macut","doi":"10.1093/ejendo/lvae085","DOIUrl":"10.1093/ejendo/lvae085","url":null,"abstract":"<p><strong>Background: </strong>Although polycystic ovary syndrome (PCOS) is a very common endocrinopathy, there are several issues related to this disorder which perplex clinicians in their everyday practice.</p><p><strong>Objective: </strong>To determine the current state of knowledge among European endocrinologists concerning the full spectrum of PCOS.</p><p><strong>Methods: </strong>An online survey comprising 41 items covering various aspects of PCOS diagnosis and management was distributed to members of the European Society of Endocrinology.</p><p><strong>Results: </strong>A total of 505 European endocrinologists (64% females), with a mean age of 47 ± 11.6 years, participated in the survey. The Rotterdam criteria were the primary diagnostic tool for 85% of respondents. Most referrals (87.1%) occurred between ages 20 and 40 years. Twenty-five percent of physicians have access to mass spectrometry for the evaluation of androgen levels. While an extended metabolic profile was commonly employed as part of the workup, there was uncertainty regarding chronic anovulation diagnosis. Diabetes, including gestational or type 2, was recognized as a significant risk factor with universal screening irrespective of BMI status. Lifestyle modification and metformin were considered as standard interventions by all participants alongside oral contraceptives, though there was significant discrepancy in treatment duration.</p><p><strong>Conclusions: </strong>The Rotterdam diagnostic criteria are widely adopted for PCOS diagnosis among European endocrinologists. The current updated survey shows an emphasis on steroid profiling as an important part of diagnostic workup and a strong position held for recognition of PCOS as a metabolic condition with potentially serious implications. Current therapy thus shifted to the demand for prioritizing lifestyle interventions and metabolic therapies, either as monotherapy or in combination with standard hormone compounds.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: Previous studies focusing on primary aldosteronism (PA) and thyroid diseases were controversial. Hence, this study aimed to examine associations between thyroid function, thyroid diseases, and PA and its subtypes.
Design and methods: This was a cross-sectional study, which enrolled 1023 patients with PA and 6138 patients with essential hypertension (EH) admitted to Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region from August 2011 to June 2022. All patients with PA were accurately classified into aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) by adrenal vein sampling (AVS). Multivariate logistic regression analysis was used to assess the relationship of thyroid function, thyroid nodules, and PA and its subtypes.
Results: A total of 7161 patients (327 APA and 696 IHA, and 6138 EH) were included with a mean age of 48.20 ± 8.83 years. PA patients and PA subtypes showed lower FT4, FT3, TT4, TT3, and prevalence of positive TPOAb, meanwhile higher prevalence of thyroid nodules than EH patients (PA: 56.10%, IHA: 56.90%, APA: 54.80%, and EH: 48.90%, respectively). PA (adjusted OR: 1.290, 95% CI: 1.035-1.607, P = .02) and its subtype (IHA) (adjusted OR: 1.316, 95% CI: 1.005-1.724, P = .04) were significantly associated with thyroid nodules. Compared to patients with lower plasma aldosterone concentration (PAC) levels (<12 ng/dL), patients with PAC levels ≥ 12 ng/dL presented a higher prevalence of thyroid nodules.
Conclusions: PA patients had lower thyroid function and higher prevalence of thyroid nodules compared to EH patients. Therefore, the screening of thyroid function and thyroid nodules may be indispensable for PA patients.
{"title":"Associations between thyroid function, thyroid diseases, and primary aldosteronism.","authors":"Mayire Maiturouzi, Qing Zhu, Delian Zhang, Qin Luo, Menghui Wang, Xintian Cai, Mulalibieke Heizhati, Li Cai, Ting Wu, Shasha Liu, Yujie Dang, Adilakezi Aimudula, Jing Hong, Nanfang Li","doi":"10.1093/ejendo/lvae087","DOIUrl":"https://doi.org/10.1093/ejendo/lvae087","url":null,"abstract":"<p><strong>Objective: </strong>Previous studies focusing on primary aldosteronism (PA) and thyroid diseases were controversial. Hence, this study aimed to examine associations between thyroid function, thyroid diseases, and PA and its subtypes.</p><p><strong>Design and methods: </strong>This was a cross-sectional study, which enrolled 1023 patients with PA and 6138 patients with essential hypertension (EH) admitted to Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region from August 2011 to June 2022. All patients with PA were accurately classified into aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) by adrenal vein sampling (AVS). Multivariate logistic regression analysis was used to assess the relationship of thyroid function, thyroid nodules, and PA and its subtypes.</p><p><strong>Results: </strong>A total of 7161 patients (327 APA and 696 IHA, and 6138 EH) were included with a mean age of 48.20 ± 8.83 years. PA patients and PA subtypes showed lower FT4, FT3, TT4, TT3, and prevalence of positive TPOAb, meanwhile higher prevalence of thyroid nodules than EH patients (PA: 56.10%, IHA: 56.90%, APA: 54.80%, and EH: 48.90%, respectively). PA (adjusted OR: 1.290, 95% CI: 1.035-1.607, P = .02) and its subtype (IHA) (adjusted OR: 1.316, 95% CI: 1.005-1.724, P = .04) were significantly associated with thyroid nodules. Compared to patients with lower plasma aldosterone concentration (PAC) levels (<12 ng/dL), patients with PAC levels ≥ 12 ng/dL presented a higher prevalence of thyroid nodules.</p><p><strong>Conclusions: </strong>PA patients had lower thyroid function and higher prevalence of thyroid nodules compared to EH patients. Therefore, the screening of thyroid function and thyroid nodules may be indispensable for PA patients.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yaron Rudman, Maria Fleseriu, Laura Dery, Hiba Masri-Iraqi, Liat Sasson, Tzipora Shochat, Shiri Kushnir, Ilan Shimon, Amit Akirov
Objective: Cancer incidence in patients with endogenous Cushing's syndrome (CS) has never been established. Here, we aimed to assess the cancer risk in patients with CS as compared with individually matched controls.
Design: A nationwide retrospective matched cohort study of patients with endogenous CS diagnosed between 2000 and 2023 using the database of Clalit Health Services in Israel.
Methods: Patients with adrenal carcinoma or ectopic CS were excluded. Patients with CS were matched in a 1:5 ratio, with controls individually matched for age, sex, socioeconomic status, and body mass index. The primary outcome was defined as the first diagnosis of any malignancy following a CS diagnosis. Risk of malignancy was calculated using the Cox proportional hazard model, with death as a competing event.
Results: A total of 609 patients with CS and 3018 controls were included [mean age at diagnosis, 48.0 ± 17.2 years; 2371 (65.4%) women]. The median follow-up was 14.7 years (IQR, 9.9-20.2 years). Patients with CS had an increased cancer risk, with a hazard ratio (HR) of 1.78 (95% CI 1.44-2.20) compared with their matched controls. The risk of malignancy was elevated in patients with Cushing's disease (251 cases and 1246 controls; HR 1.65, 95% CI 1.15-2.36) and in patients with adrenal CS (200 cases and 991 controls; HR 2.36, 95% CI 1.70-3.29). The increased cancer risk in patients with CS persists after exclusion of thyroid malignancies.
Conclusion: Endogenous CS is associated with increased malignancy risk. These findings underscore the need for further research to establish recommendations for cancer screening in this population.
{"title":"Endogenous Cushing's syndrome and cancer risk.","authors":"Yaron Rudman, Maria Fleseriu, Laura Dery, Hiba Masri-Iraqi, Liat Sasson, Tzipora Shochat, Shiri Kushnir, Ilan Shimon, Amit Akirov","doi":"10.1093/ejendo/lvae098","DOIUrl":"10.1093/ejendo/lvae098","url":null,"abstract":"<p><strong>Objective: </strong>Cancer incidence in patients with endogenous Cushing's syndrome (CS) has never been established. Here, we aimed to assess the cancer risk in patients with CS as compared with individually matched controls.</p><p><strong>Design: </strong>A nationwide retrospective matched cohort study of patients with endogenous CS diagnosed between 2000 and 2023 using the database of Clalit Health Services in Israel.</p><p><strong>Methods: </strong>Patients with adrenal carcinoma or ectopic CS were excluded. Patients with CS were matched in a 1:5 ratio, with controls individually matched for age, sex, socioeconomic status, and body mass index. The primary outcome was defined as the first diagnosis of any malignancy following a CS diagnosis. Risk of malignancy was calculated using the Cox proportional hazard model, with death as a competing event.</p><p><strong>Results: </strong>A total of 609 patients with CS and 3018 controls were included [mean age at diagnosis, 48.0 ± 17.2 years; 2371 (65.4%) women]. The median follow-up was 14.7 years (IQR, 9.9-20.2 years). Patients with CS had an increased cancer risk, with a hazard ratio (HR) of 1.78 (95% CI 1.44-2.20) compared with their matched controls. The risk of malignancy was elevated in patients with Cushing's disease (251 cases and 1246 controls; HR 1.65, 95% CI 1.15-2.36) and in patients with adrenal CS (200 cases and 991 controls; HR 2.36, 95% CI 1.70-3.29). The increased cancer risk in patients with CS persists after exclusion of thyroid malignancies.</p><p><strong>Conclusion: </strong>Endogenous CS is associated with increased malignancy risk. These findings underscore the need for further research to establish recommendations for cancer screening in this population.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emese Boros, Catheline Vilain, Natacha Driessens, Claudine Heinrichs, Guy Van Vliet, Cécile Brachet
Biallelic loss-of-function variants in the IYD gene cause hypothyroidism resulting from iodine wasting. We describe 8 patients (from 4 families in which the parents are first cousins) who are homozygous for a variant in IYD (including a novel missense deleterious variant, c.791C>T [P264L], in 1 family). Seven patients presented between 5 and 16 years of age with a large goiter, overt hypothyroidism, and a high serum thyroglobulin. The goiter subsided with levothyroxine therapy in most. Upon stopping levothyroxine in 5 patients, goiter and hypothyroidism reappeared in 3. In these 3 patients, a rising serum thyroglobulin concentration preceded hypothyroidism and goiter and urinary iodine excretion was low. In patients who remained euthyroid, urinary iodine was normal. In conclusion, these patients bearing biallelic pathogenic variants in IYD developed a large goiter, a high serum thyroglobulin, and overt hypothyroidism when their iodine intake was low.
{"title":"Hypothyroidism due to biallelic variants in IYD: description of 4 families and a novel variant.","authors":"Emese Boros, Catheline Vilain, Natacha Driessens, Claudine Heinrichs, Guy Van Vliet, Cécile Brachet","doi":"10.1093/ejendo/lvae100","DOIUrl":"10.1093/ejendo/lvae100","url":null,"abstract":"<p><p>Biallelic loss-of-function variants in the IYD gene cause hypothyroidism resulting from iodine wasting. We describe 8 patients (from 4 families in which the parents are first cousins) who are homozygous for a variant in IYD (including a novel missense deleterious variant, c.791C>T [P264L], in 1 family). Seven patients presented between 5 and 16 years of age with a large goiter, overt hypothyroidism, and a high serum thyroglobulin. The goiter subsided with levothyroxine therapy in most. Upon stopping levothyroxine in 5 patients, goiter and hypothyroidism reappeared in 3. In these 3 patients, a rising serum thyroglobulin concentration preceded hypothyroidism and goiter and urinary iodine excretion was low. In patients who remained euthyroid, urinary iodine was normal. In conclusion, these patients bearing biallelic pathogenic variants in IYD developed a large goiter, a high serum thyroglobulin, and overt hypothyroidism when their iodine intake was low.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dario De Alcubierre, Grigorios Gkasdaris, Margaux Mordrel, Anthony Joncour, Claire Briet, Fabien Almairac, Julien Boetto, Celine Mouly, Delphine Larrieu-Ciron, Alexandre Vasiljevic, Chiara Villa, Camille Sergeant, François Ducray, Loic Feuvret, Philippe Chanson, Bertrand Baussart, Gerald Raverot, Emmanuel Jouanneau
Objective: Targeted therapy (TT) with BRAF/MEK inhibitors has emerged as a potential treatment in papillary craniopharyngiomas (PCPs). However, standardized data on large cohorts are lacking. Our study aimed to assess real-life efficacy and safety of BRAF/MEK inhibition in patients with PCPs.
Design: Retrospective French multicenter study involving BRAF V600E-mutated PCP patients, treated with BRAF/MEK inhibitor combination dabrafenib and trametinib, from April 2019 to July 2023.
Methods: Objective response and clinical and safety outcomes were assessed after 3 months and at the last available follow-up during TT.
Results: Sixteen patients (8 females, mean age 50.5 ± 15.75 years), receiving either neoadjuvant therapy (NEO) for non-resectable tumors (n = 6), post-surgical adjuvant therapy (ADJ; n = 8), or palliative therapy (PAL) following failure of multimodal treatment (n = 2), were included.At the last follow-up (mean 7.6 ± 5.3 months), 12 patients showed subtotal response, 3 exhibited partial response, and 1 maintained stable disease. Mean volume reduction was 88.9 ± 4.4%, 73.3 ± 23.4%, and 91.8 ± 4.3% in the NEO, ADJ, and PAL groups, respectively.Targeted therapy resolved headaches in 5/5 patients and visual impairment in 6/9; 2/3 patients had improved neurological symptoms, 1/4 presented weight loss, and 2/14 recovered endocrine function.Targeted therapy was well-tolerated in 62.5% of cases; adverse events led to treatment discontinuation in 5 patients and definitive discontinuation in 3 cases.
Conclusions: In this study, 94% of patients showed partial response or better to TT. Adverse events were acceptable. Further research is needed to establish standardized protocols; however, these results advocate for a NEO approach in invasive PCPs.
{"title":"BRAF and MEK inhibitor targeted therapy in papillary craniopharyngiomas: a cohort study.","authors":"Dario De Alcubierre, Grigorios Gkasdaris, Margaux Mordrel, Anthony Joncour, Claire Briet, Fabien Almairac, Julien Boetto, Celine Mouly, Delphine Larrieu-Ciron, Alexandre Vasiljevic, Chiara Villa, Camille Sergeant, François Ducray, Loic Feuvret, Philippe Chanson, Bertrand Baussart, Gerald Raverot, Emmanuel Jouanneau","doi":"10.1093/ejendo/lvae091","DOIUrl":"https://doi.org/10.1093/ejendo/lvae091","url":null,"abstract":"<p><strong>Objective: </strong>Targeted therapy (TT) with BRAF/MEK inhibitors has emerged as a potential treatment in papillary craniopharyngiomas (PCPs). However, standardized data on large cohorts are lacking. Our study aimed to assess real-life efficacy and safety of BRAF/MEK inhibition in patients with PCPs.</p><p><strong>Design: </strong>Retrospective French multicenter study involving BRAF V600E-mutated PCP patients, treated with BRAF/MEK inhibitor combination dabrafenib and trametinib, from April 2019 to July 2023.</p><p><strong>Methods: </strong>Objective response and clinical and safety outcomes were assessed after 3 months and at the last available follow-up during TT.</p><p><strong>Results: </strong>Sixteen patients (8 females, mean age 50.5 ± 15.75 years), receiving either neoadjuvant therapy (NEO) for non-resectable tumors (n = 6), post-surgical adjuvant therapy (ADJ; n = 8), or palliative therapy (PAL) following failure of multimodal treatment (n = 2), were included.At the last follow-up (mean 7.6 ± 5.3 months), 12 patients showed subtotal response, 3 exhibited partial response, and 1 maintained stable disease. Mean volume reduction was 88.9 ± 4.4%, 73.3 ± 23.4%, and 91.8 ± 4.3% in the NEO, ADJ, and PAL groups, respectively.Targeted therapy resolved headaches in 5/5 patients and visual impairment in 6/9; 2/3 patients had improved neurological symptoms, 1/4 presented weight loss, and 2/14 recovered endocrine function.Targeted therapy was well-tolerated in 62.5% of cases; adverse events led to treatment discontinuation in 5 patients and definitive discontinuation in 3 cases.</p><p><strong>Conclusions: </strong>In this study, 94% of patients showed partial response or better to TT. Adverse events were acceptable. Further research is needed to establish standardized protocols; however, these results advocate for a NEO approach in invasive PCPs.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Miriam Sommer-Ballarini, Thu-Huong Nguyen, Laura Pletsch-Borba, Charlotte Wernicke, Frank Tacke, Tanja Schwerdtle, Denny Pellowski, Jürgen Machann, Joachim Spranger, Eva Katrin Wirth, Knut Mai
Objective: Hypothyroidism has been proposed as a potential contributor to steatotic liver disease (SLD), but existing data shows conflicting results in euthyroid subjects. Therefore, we investigated the association between thyroid function and intrahepatic lipids (IHLs) during a 36-month randomized controlled trial evaluating a diet known to reduce liver fat.
Design: 502 eligible subjects (aged 50-80 years, ≥1 risk factor for unhealthy aging) were randomly assigned to either follow a diet rich in unsaturated fatty acids, plant protein, and fiber (intervention group, IG), or dietary recommendations of the German Nutrition Society (control group, CG).
Methods: Serum levels of thyroid hormones (THs) as well as IHLs, defined via magnetic resonance spectroscopy, were measured within an euthyroid subgroup without significant alcohol consumption at baseline (n = 332) and after 12 months (n = 243). A ratio of T3/T4 was used to assess whole-body deiodinase activity. Estimates of glucose and lipid metabolism were analyzed.
Results: Only fT3 and T3/T4 ratios showed a significant positive correlation with IHL at baseline. We observed a significant decline in fT3, T3, fT3/fT4 ratio, and T3/T4 ratio in CG and IG after 12 months without significant differences between groups. TSH, fT4, and T4 remained stable. A larger improvement of IHL during dietary intervention was seen in those subjects with a lower decline in T3 concentrations.
Conclusions: Altered TH balance indicates a possible compensatory upregulation of whole-body TH activity in subjects with increased liver fat. This might be also relevant during the improvement of hepatic steatosis.
{"title":"Impact of peripheral thyroid hormone balance on liver fat: insights from the NutriAct trial.","authors":"Miriam Sommer-Ballarini, Thu-Huong Nguyen, Laura Pletsch-Borba, Charlotte Wernicke, Frank Tacke, Tanja Schwerdtle, Denny Pellowski, Jürgen Machann, Joachim Spranger, Eva Katrin Wirth, Knut Mai","doi":"10.1093/ejendo/lvae093","DOIUrl":"10.1093/ejendo/lvae093","url":null,"abstract":"<p><strong>Objective: </strong>Hypothyroidism has been proposed as a potential contributor to steatotic liver disease (SLD), but existing data shows conflicting results in euthyroid subjects. Therefore, we investigated the association between thyroid function and intrahepatic lipids (IHLs) during a 36-month randomized controlled trial evaluating a diet known to reduce liver fat.</p><p><strong>Design: </strong>502 eligible subjects (aged 50-80 years, ≥1 risk factor for unhealthy aging) were randomly assigned to either follow a diet rich in unsaturated fatty acids, plant protein, and fiber (intervention group, IG), or dietary recommendations of the German Nutrition Society (control group, CG).</p><p><strong>Methods: </strong>Serum levels of thyroid hormones (THs) as well as IHLs, defined via magnetic resonance spectroscopy, were measured within an euthyroid subgroup without significant alcohol consumption at baseline (n = 332) and after 12 months (n = 243). A ratio of T3/T4 was used to assess whole-body deiodinase activity. Estimates of glucose and lipid metabolism were analyzed.</p><p><strong>Results: </strong>Only fT3 and T3/T4 ratios showed a significant positive correlation with IHL at baseline. We observed a significant decline in fT3, T3, fT3/fT4 ratio, and T3/T4 ratio in CG and IG after 12 months without significant differences between groups. TSH, fT4, and T4 remained stable. A larger improvement of IHL during dietary intervention was seen in those subjects with a lower decline in T3 concentrations.</p><p><strong>Conclusions: </strong>Altered TH balance indicates a possible compensatory upregulation of whole-body TH activity in subjects with increased liver fat. This might be also relevant during the improvement of hepatic steatosis.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria Francesca Birtolo, Rebecca Pedersini, Andrea Palermo, Walter Vena, Emanuela Morenghi, Giacomo Cristofolini, Barbara Presciuttini, Gaia Tabacco, Anda Mihaela Naciu, Stella Pigni, Marta Laganà, Federica Mazzoleni, Deborah Cosentini, Antea Ciafardini, Mauro Pagani, Davide Farina, Luca Balzarini, Alberto Zambelli, Rosalba Torrisi, Luisella Cianferotti, Nicola Napoli, Antonio Carlo Bossi, Andrea Gerardo Lania, Alfredo Berruti, Gherardo Mazziotti
Background: 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 < .001), preexisting VFs (OR 25.36, P < .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 < .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 < .001) and the anti-fracture effectiveness remained significant after correction for BMI (OR 0.03; P < .001), family history of fractures (OR 0.03; P < .001), chemotherapy-induced menopause (OR 0.04; P < .001), and preexisting VFs (OR 0.01; P < .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.
{"title":"Bone-active drugs in premenopausal women with breast cancer under hormone-deprivation therapies.","authors":"Maria Francesca Birtolo, Rebecca Pedersini, Andrea Palermo, Walter Vena, Emanuela Morenghi, Giacomo Cristofolini, Barbara Presciuttini, Gaia Tabacco, Anda Mihaela Naciu, Stella Pigni, Marta Laganà, Federica Mazzoleni, Deborah Cosentini, Antea Ciafardini, Mauro Pagani, Davide Farina, Luca Balzarini, Alberto Zambelli, Rosalba Torrisi, Luisella Cianferotti, Nicola Napoli, Antonio Carlo Bossi, Andrea Gerardo Lania, Alfredo Berruti, Gherardo Mazziotti","doi":"10.1093/ejendo/lvae086","DOIUrl":"10.1093/ejendo/lvae086","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 < .001), preexisting VFs (OR 25.36, P < .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 < .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 < .001) and the anti-fracture effectiveness remained significant after correction for BMI (OR 0.03; P < .001), family history of fractures (OR 0.03; P < .001), chemotherapy-induced menopause (OR 0.04; P < .001), and preexisting VFs (OR 0.01; P < .001).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tor-Arne Hegvik, YanYan Zhou, Katrin Brauckhoff, Kari Furu, Vidar Hjellvik, Tone Bjørge, Anders Engeland
Objective: Little is known about thyroid cancer survivors' risk of chronic conditions. We, therefore, investigated the prevalence of drugs used for chronic conditions among thyroid cancer patients using population-wide register data.
Methods: We linked data from the Cancer Registry of Norway to the Norwegian Prescription Database and other databases for a study population of 3.52 million individuals, including 3486 individuals with thyroid cancer diagnosed during 2005-2019. Prevalence ratios (PRs) with 95% CIs of reimbursed prescribed drugs in thyroid cancer patients up to 15 years after thyroid cancer diagnosis were estimated by log-binomial regression, with the cancer-free population as reference.
Results: Individuals (both males and females) with thyroid cancer had higher use of drugs for several chronic conditions in the years after diagnosis; eg, 5 years after thyroid cancer diagnosis, there was elevated use of drugs for hypoparathyroidism (PRmales = 35.4, 95% CI, 25.2-49.7; PRfemales = 42.8, 95% CI, 34.2-53.6), hypertension (PRfemales = 1.20, 95% CI, 1.12-1.28), anxiety and tension (PRmales = 4.01, 95% CI, 1.80-8.92; PRfemales = 2.01, 95% CI, 1.15-3.52), gastric acid disorders (PRmales = 1.52, 95% CI, 1.22-1.91; PRfemales = 1.45, 95% CI, 1.27-1.66), and pain (PRmales = 1.48, 95% CI, 1.11-1.97; PRfemales = 1.24, 95% CI, 1.08-1.42) as compared with the cancer-free population. In addition, males with thyroid cancer had long-term elevated use of drugs for depression (eg, year 10+, PRmales = 1.66, 95% CI, 1.06-2.59). Individuals with thyroid cancer also had higher use of drugs for several conditions prior to the thyroid cancer diagnosis, eg, hypertension, gastric acid disorders, and pain.
Conclusions: Individuals diagnosed with thyroid cancer had elevated long-term use of drugs for several chronic conditions, as compared with the cancer-free population.
{"title":"Prevalence of drugs used for chronic conditions after diagnosis of thyroid cancer: a register-based cohort study.","authors":"Tor-Arne Hegvik, YanYan Zhou, Katrin Brauckhoff, Kari Furu, Vidar Hjellvik, Tone Bjørge, Anders Engeland","doi":"10.1093/ejendo/lvae092","DOIUrl":"10.1093/ejendo/lvae092","url":null,"abstract":"<p><strong>Objective: </strong>Little is known about thyroid cancer survivors' risk of chronic conditions. We, therefore, investigated the prevalence of drugs used for chronic conditions among thyroid cancer patients using population-wide register data.</p><p><strong>Methods: </strong>We linked data from the Cancer Registry of Norway to the Norwegian Prescription Database and other databases for a study population of 3.52 million individuals, including 3486 individuals with thyroid cancer diagnosed during 2005-2019. Prevalence ratios (PRs) with 95% CIs of reimbursed prescribed drugs in thyroid cancer patients up to 15 years after thyroid cancer diagnosis were estimated by log-binomial regression, with the cancer-free population as reference.</p><p><strong>Results: </strong>Individuals (both males and females) with thyroid cancer had higher use of drugs for several chronic conditions in the years after diagnosis; eg, 5 years after thyroid cancer diagnosis, there was elevated use of drugs for hypoparathyroidism (PRmales = 35.4, 95% CI, 25.2-49.7; PRfemales = 42.8, 95% CI, 34.2-53.6), hypertension (PRfemales = 1.20, 95% CI, 1.12-1.28), anxiety and tension (PRmales = 4.01, 95% CI, 1.80-8.92; PRfemales = 2.01, 95% CI, 1.15-3.52), gastric acid disorders (PRmales = 1.52, 95% CI, 1.22-1.91; PRfemales = 1.45, 95% CI, 1.27-1.66), and pain (PRmales = 1.48, 95% CI, 1.11-1.97; PRfemales = 1.24, 95% CI, 1.08-1.42) as compared with the cancer-free population. In addition, males with thyroid cancer had long-term elevated use of drugs for depression (eg, year 10+, PRmales = 1.66, 95% CI, 1.06-2.59). Individuals with thyroid cancer also had higher use of drugs for several conditions prior to the thyroid cancer diagnosis, eg, hypertension, gastric acid disorders, and pain.</p><p><strong>Conclusions: </strong>Individuals diagnosed with thyroid cancer had elevated long-term use of drugs for several chronic conditions, as compared with the cancer-free population.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elisabeth Nowak, Frederick Vogel, Leah Braun, Stephanie Zopp, German Rubinstein, Katharina Schilbach, Martin Bidlingmaier, Petra Zimmermann, Jun Thorsteinsdottir, Júnia R O L Schweizer, Katrin Ritzel, Felix Beuschlein, Martin Reincke
Background: Secondary hypogonadism (SH) is common in men with Cushing's syndrome (CS), but its impact on comorbidities is largely unknown and longitudinal data are scarce. If SH also affects men with mild autonomous cortisol secretion (MACS) is unknown.
Methods: We included 30 treatment-naïve adult men with CS and 17 men with MACS diagnosed since 2012. Hypogonadism was diagnosed based on total testosterone (TT) concentrations < 10.4 nmol/L and age-specific cut-offs. Outcomes were compared to age- and BMI-matched controls. In 20 men in remission of CS, a longitudinal analysis was conducted at 6, 12, and 24 months.
Results: Men with CS had significantly lower concentrations of TT, bioavailable T, and free T compared to controls (P < .0001) with lowest concentrations in ectopic CS. Likewise, TT was lower in men with MACS compared to controls. At baseline, 93% of men with CS and 59% of men with MACS had SH. Testosterone correlated negatively with late night salivary cortisol and serum cortisol pre- and post-1 mg dexamethasone suppression test. Following successful surgery, TT increased significantly (P = .001), normalising within 6 months. Despite normalisation, several RBC parameters remained lower in men with CS even 2 years after successful surgery.
Conclusions: Secondary hypogonadism is common in men with CS and MACS but usually reversible after successful surgery. The persisting changes observed in RBC parameters need to be further investigated in larger cohorts and longer follow-up durations.
{"title":"Prevalence and outcome of secondary hypogonadism in male patients with Cushing's syndrome and mild autonomous cortisol secretion.","authors":"Elisabeth Nowak, Frederick Vogel, Leah Braun, Stephanie Zopp, German Rubinstein, Katharina Schilbach, Martin Bidlingmaier, Petra Zimmermann, Jun Thorsteinsdottir, Júnia R O L Schweizer, Katrin Ritzel, Felix Beuschlein, Martin Reincke","doi":"10.1093/ejendo/lvae097","DOIUrl":"10.1093/ejendo/lvae097","url":null,"abstract":"<p><strong>Background: </strong>Secondary hypogonadism (SH) is common in men with Cushing's syndrome (CS), but its impact on comorbidities is largely unknown and longitudinal data are scarce. If SH also affects men with mild autonomous cortisol secretion (MACS) is unknown.</p><p><strong>Methods: </strong>We included 30 treatment-naïve adult men with CS and 17 men with MACS diagnosed since 2012. Hypogonadism was diagnosed based on total testosterone (TT) concentrations < 10.4 nmol/L and age-specific cut-offs. Outcomes were compared to age- and BMI-matched controls. In 20 men in remission of CS, a longitudinal analysis was conducted at 6, 12, and 24 months.</p><p><strong>Results: </strong>Men with CS had significantly lower concentrations of TT, bioavailable T, and free T compared to controls (P < .0001) with lowest concentrations in ectopic CS. Likewise, TT was lower in men with MACS compared to controls. At baseline, 93% of men with CS and 59% of men with MACS had SH. Testosterone correlated negatively with late night salivary cortisol and serum cortisol pre- and post-1 mg dexamethasone suppression test. Following successful surgery, TT increased significantly (P = .001), normalising within 6 months. Despite normalisation, several RBC parameters remained lower in men with CS even 2 years after successful surgery.</p><p><strong>Conclusions: </strong>Secondary hypogonadism is common in men with CS and MACS but usually reversible after successful surgery. The persisting changes observed in RBC parameters need to be further investigated in larger cohorts and longer follow-up durations.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wasita W Parksook, Jenifer M Brown, Julia Milks, Laura C Tsai, Justin Chan, Anna Moore, Yvonne Niebuhr, Brooke Honzel, Andrew J Newman, Anand Vaidya
Background: Extracellular calcium critically regulates physiologic aldosterone production. Moreover, abnormal calcium flux and signaling are involved in the pathogenesis of the majority of primary aldosteronism cases.
Methods: We investigated the influence of the saline suppression test (SST) on calcium homeostasis in prospectively recruited participants (n = 86).
Results: During SST, 100% of participants had decreases in serum calcium, with 48% developing frank hypocalcemia. Serum calcium declined from 2.30 ± 0.08 mmol/L to 2.13 ± 0.08 mmol/L (P < .001) with parallel increases in parathyroid hormone from 6.06 ± 2.39 pmol/L to 8.13 ± 2.42 pmol/L (P < .001). In contrast, serum potassium and bicarbonate did not change, whereas eGFR increased and serum glucose decreased (P < .001). Lower body surface area (translating to greater effective circulating volume expansion during SST) was associated with greater reductions in (β = .33, P = .001), and absolutely lower, serum calcium levels (β = .25, P = .001). When evaluating clinically-relevant diagnostic thresholds, participants with post-SST aldosterone levels <138 pmol/L had lower post-SST calcium and 25-hydroxyvitamin D levels (P < .05), and higher post-SST parathyroid hormone levels (P < .05) compared with those with post-SST aldosterone levels >277 pmol/L.
Conclusion: SST uniformly decreases serum calcium, which is likely to be due to the combination of variable dilution, increased renal clearance, and vitamin D status. These acute reductions in bioavailable calcium are associated with lower post-SST aldosterone. Given the critical role of extracellular calcium in regulating aldosterone production, these findings warrant renewed inquiry into the validity of SST interpretations for excluding primary aldosteronism.
{"title":"Saline suppression testing-induced hypocalcemia and implications for clinical interpretations.","authors":"Wasita W Parksook, Jenifer M Brown, Julia Milks, Laura C Tsai, Justin Chan, Anna Moore, Yvonne Niebuhr, Brooke Honzel, Andrew J Newman, Anand Vaidya","doi":"10.1093/ejendo/lvae099","DOIUrl":"10.1093/ejendo/lvae099","url":null,"abstract":"<p><strong>Background: </strong>Extracellular calcium critically regulates physiologic aldosterone production. Moreover, abnormal calcium flux and signaling are involved in the pathogenesis of the majority of primary aldosteronism cases.</p><p><strong>Methods: </strong>We investigated the influence of the saline suppression test (SST) on calcium homeostasis in prospectively recruited participants (n = 86).</p><p><strong>Results: </strong>During SST, 100% of participants had decreases in serum calcium, with 48% developing frank hypocalcemia. Serum calcium declined from 2.30 ± 0.08 mmol/L to 2.13 ± 0.08 mmol/L (P < .001) with parallel increases in parathyroid hormone from 6.06 ± 2.39 pmol/L to 8.13 ± 2.42 pmol/L (P < .001). In contrast, serum potassium and bicarbonate did not change, whereas eGFR increased and serum glucose decreased (P < .001). Lower body surface area (translating to greater effective circulating volume expansion during SST) was associated with greater reductions in (β = .33, P = .001), and absolutely lower, serum calcium levels (β = .25, P = .001). When evaluating clinically-relevant diagnostic thresholds, participants with post-SST aldosterone levels <138 pmol/L had lower post-SST calcium and 25-hydroxyvitamin D levels (P < .05), and higher post-SST parathyroid hormone levels (P < .05) compared with those with post-SST aldosterone levels >277 pmol/L.</p><p><strong>Conclusion: </strong>SST uniformly decreases serum calcium, which is likely to be due to the combination of variable dilution, increased renal clearance, and vitamin D status. These acute reductions in bioavailable calcium are associated with lower post-SST aldosterone. Given the critical role of extracellular calcium in regulating aldosterone production, these findings warrant renewed inquiry into the validity of SST interpretations for excluding primary aldosteronism.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11322817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}