Clinical Endocrinology最新文献

{"title":"IRS1 promotes thyroid cancer metastasis through EMT and PI3K/AKT pathways","authors":"Fang Yu,&nbsp;Dongdong Huang,&nbsp;Yeye Kuang,&nbsp;Jian Dong,&nbsp;Qingmei Han,&nbsp;Jie Zhou,&nbsp;Xiaodong Teng","doi":"10.1111/cen.15005","DOIUrl":"10.1111/cen.15005","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Insulin receptor substract 1 (IRS1) protein is an important signal transduction adapter for extracellular signal transduction from insulin-like growth factor-1 receptor and its family members to IRS1 downstream proteins. IRS1 has been reported to be involved in tumourigenesis and metastasis in some of solid tumors. Investigating the role of IRS1 in thyroid cancer can help to screen high risk patients at the initial diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design, Patients and Measurements</h3>\u0000 \u0000 <p>Immunohistochemical assay was used to detect the expression levels of IRS1 in 131 metastatic thyroid cancer tissues. Wound healing, cell invasion and colony formation assays were used to study the functions of IRS1 in vitro. RNA sequencing (RNA-seq) and Western blot analysis analyses were performed to examine the underlying regulation mechanisms of IRS1 in thyroid cancer cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>IRS1 was highly expressed in thyroid cancers and its expression was positively associated with distant metastasis and advanced clinical stages. In vitro studies demonstrated that IRS1 is an important mediator of migration, invasion and colony formation of thyroid cancer cells. RNA-seq showed that IRS1 promoted the metastasis of thyroid cancer by regulating epithelial-mesenchymal transition and phosphoinositide 3-kinase (PI3K)/AKT pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>IRS1 overexpression contributes to the aggressiveness of thyroid cancer and is expected to be a stratified marker and a potential therapeutic target for thyroid cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paediatric perspectives in the diagnosis of polyuria-polydipsia syndrome.","authors":"Tony Huynh, Dana Signal, Mirjam Christ-Crain","doi":"10.1111/cen.15011","DOIUrl":"https://doi.org/10.1111/cen.15011","url":null,"abstract":"<p><p>The elucidation of the underlying cause of polyuria-polydipsia syndrome (PPS) is a challenging-especially in the differentiation of partial defects of arginine vasopressin (AVP) secretion or action from primary polydipsia. The water deprivation test has been utilized for many decades, and its application in the paediatric population has been applied using parameters predominantly established in adult cohorts. In more recent times, the development of automated commercial assays for copeptin, a surrogate marker for AVP, has represented a significant advancement in the diagnostic approach to PPS. Measurement of copeptin concentrations has major advantages and has essentially superseded measurement of AVP in diagnostic protocols for PPS. Additionally, stimulated-copeptin protocols utilizing hypertonic saline infusion, arginine, and glucagon have been investigated, and are promising. However, further studies are required in the population-incorporating the differences in physiological regulation of water homeostasis, and safety requirements-before there is widespread adoption into clinical practice.</p>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of mild cortisol cosecretion on body composition and metabolic parameters in patients with primary hyperaldosteronism","authors":"Nabeel Mansour,&nbsp;Denise Bruedgam,&nbsp;Ulrich Dischinger,&nbsp;Lydia Kürzinger,&nbsp;Christian Adolf,&nbsp;Roman Walter,&nbsp;Osman Öcal,&nbsp;Vanessa F. Schmidt,&nbsp;Jan Rudolph,&nbsp;Jens Ricke,&nbsp;Nicole Reisch,&nbsp;Martin Reincke,&nbsp;Moritz Wildgruber,&nbsp;Daniel Heinrich","doi":"10.1111/cen.15013","DOIUrl":"10.1111/cen.15013","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate the effects of simultaneous cortisol cosecretion (CCS) on body composition in computed tomography (CT)-imaging and metabolic parameters in patients with primary aldosteronism (PA) with the objective of facilitating early detection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design</h3>\u0000 \u0000 <p>Retrospective cohort study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients</h3>\u0000 \u0000 <p>Forty-seven patients with PA and CCS confirmed by 1-mg dexamethasone suppression test (DST) with a cutoff of ≥1.8 µg/dL were compared with PA patients with excluded CCS (non-CCS, <i>n</i> = 47) matched by age and sex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Segmentation of the fat compartments and muscle area at the third lumbar region was performed on non-contrast-enhanced CT images with dedicated segmentation software. Additionally, liver, spleen, pancreas and muscle attenuation were compared between the two groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Mean cortisol after DST was 1.2 µg/dL (33.1 nmol/L) in the non-CCS group and 3.2 µg/dL (88.3 nmol/L) in the CCS group with mild autonomous cortisol excess (MACE). No difference in total, visceral and subcutaneous fat volumes was observed between the CCS and non-CCS group (<i>p</i> = .7, .6 and .8, respectively). However, a multivariable regression analysis revealed a significant correlation between total serum cholesterol and results of serum cortisol after 1-mg DST (<i>p</i> = .026). Classification of the patients based on visible lesion on CT and PA-lateralization via adrenal venous sampling also did not show any significant differences in body composition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>MACE in PA patients does not translate into body composition changes on CT-imaging. Therefore, early detection of concurrent CCS in PA is currently only attainable through biochemical tests. Further investigation of the long-term clinical adverse effects of MACE in PA is necessary.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.15013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lower creatinine to cystatin C ratio is associated with an increased risk of MASLD: A cross-sectional and prospective study of 368,634 UK Biobank participants","authors":"Jiaren Wang,&nbsp;Lin Zeng,&nbsp;Chang Hong,&nbsp;Hao Cui,&nbsp;Weizhen Wang,&nbsp;Hongbo Zhu,&nbsp;Qimei Li,&nbsp;Yan Li,&nbsp;Ruining Li,&nbsp;Jingzhe He,&nbsp;Hong Zhu,&nbsp;Li Liu,&nbsp;Lushan Xiao","doi":"10.1111/cen.14990","DOIUrl":"10.1111/cen.14990","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Metabolic dysfunction-associated steatotic liver disease (MASLD) affects many populations, and screening out the high-risk populations at an early stage is a challenge. As a sarcopenia index, the relationship between creatinine to cystatin C ratio (CCR) and MASLD remains unclear. This cross-sectional, prospective study aimed to explore the relationship between CCR and MASLD. Design Firstly, explored the correlation between CCR and MASLD in cross-sectional analyses. Then excluded the population with baseeline diagnosis of MASLD and analyzed the association with baseline CCR levels and the onset of MASLD in the population with available follow-up data. Univariate and multivariate logistic regression analyses were used to calculate odds ratios (ORs) to evaluate the association between CCR levels and MASLD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients and Measurements</h3>\u0000 \u0000 <p>This study included 368,634 participants from the UK Biobank for cross-sectional and prospective analyses. The demographic characteristics and laboratory measurements of all participants were obtained from the UK Biobank. MASLD was diagnosed according to the multi-society consensus nomenclature. Hepatic steatosis was defined as FLI  ≥60.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We grouped the study participants according to CCR tertiles. In cross-sectional analyses, participants in CCR tertile 1 had the highest MASLD risk (OR: 1.070, 95% CI: 1.053−1.088, <i>p</i> &lt; .001). And the similar association was observed in the prospective analyses (CCR tertile 1 OR: 1.340, 95% CI: 1.077−1.660, <i>p</i> = .009; CCR tertile 2 OR: 1.217, 95% CI: 1.021−1.450, <i>p</i> = .029, respectively). After stratification by gender, the significant association between CCR and the onset of MASLD was only observed in males (CCR tertile 1 OR: 1.639, 95% CI: 1.160−2.317, <i>p</i> = .005; CCR tertile 2 OR: 1.322, 95% CI: 1.073−1.628, <i>p</i> = .005, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results indicated that lower CCR was significantly associated with higher risk of MASLD, based on which predictive models can be developed to screen populations at high risk of developing MASLD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139037447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anaemia-based screening for resistance to thyroid hormone alpha in children","authors":"Gözde Akın Kağızmanlı,&nbsp;Özgür Kırbıyık,&nbsp;Ayhan Abacı,&nbsp;Ece Böber,&nbsp;Uluç Yiş,&nbsp;Korcan Demir","doi":"10.1111/cen.15007","DOIUrl":"10.1111/cen.15007","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The hypothyroid phenotype associated with resistance to thyroid hormone alpha (RTH-α) is associated with a diverse clinical picture. On the other hand, thyroid-stimulating hormone (TSH) levels are normal. Free triiodothyronine (fT3) and free thyroxine (fT4) levels can also be normal; however, normo- or macrocytic anaemia is usually present in reported cases. Diagnosis is challenging and there is limited data regarding screening methods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The study aimed to assess the efficiency of a screening strategy for RTH-α.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Subjects and Methods</h3>\u0000 \u0000 <p>Out of a total of 6540 children evaluated at the outpatient clinics of paediatric neurology over 2 years and who underwent complete blood count and thyroid function tests, 432 were found to have anaemia. Within this group, we identified 42 children without an underlying specific neurological aetiology who exhibited normo- or macrocytic anaemia, normal TSH levels, fT3 levels in the upper half of the normal range or high, and fT4 levels in the lower half of the normal range or low. We excluded one patient who had already been diagnosed with RTH-α and nine patients could not be reached. Subsequently, clinical evaluation, biochemical assessment, and <i>THRA</i> sequencing analysis were conducted on 32 children. The findings were compared with those of the known RTH-α patients in our unit.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The median age of the patients was 5.7 (5.1–7.4) years, and 22 of them were males (69%). The main reasons for assessment in paediatric neurology clinics were autism spectrum disorder (<i>n</i> = 12, 38%), epilepsy (<i>n</i> = 11, 34%), and delay in developmental stages (<i>n</i> = 8, 25%). Constipation was present in five of the cases (16%), while the closure of the anterior fontanelle and tooth eruption were delayed in two cases (6%) and one case (3%), respectively. The median length/height and weight standard deviation (SD) scores were 0.3 [(−0.8)–(1.1)] and −0.1 [(−0.8)–(0.3)], respectively. The median fT3, fT4, and TSH levels were 4.6 (4.2–5.0) pg/mL, 0.9 (0.8–1.0) ng/dL, and 2.2 (1.8–3.1) uIU/mL, respectively. Thirteen of the patients (41%) had high fT3 levels, while none of them had low fT4 levels. The normo- or macrocytic anaemia rate was 47% (normocytic/macrocytic, <i>n</i> = 8/7) at the time of reassessment. Serum creatine kinase (CK) was elevated in five patients (16%; one had anaemia). None of the subjects had a pathological variant in <i>THRA</i>. Known RTH-α patients had significantly lower median height SD score, higher rates of delayed too","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potassium levels in women with polycystic ovary syndrome using spironolactone for long-term","authors":"Thais A. deOliveira,&nbsp;Lucas B. Marchesan,&nbsp;Poli M. Spritzer","doi":"10.1111/cen.15008","DOIUrl":"10.1111/cen.15008","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Spironolactone (SPL) has been used to manage hyperandrogenic manifestations in women with polycystic ovary syndrome (PCOS), but data on the risk of hyperkalemia in this population are scarce. The aim of this study was to evaluate the incidence of hyperkalemia in women with PCOS using SPL in the long term.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design</h3>\u0000 \u0000 <p>Single-centre retrospective study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients</h3>\u0000 \u0000 <p>Inclusion and analysis of 98 treatment periods in 78 women with PCOS (20 of whom were duplicates, returning after treatment interruption for a mean of 38 months) who received SPL for a minimum of 12 months and had at least three measurements of potassium levels over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Measurements</h3>\u0000 \u0000 <p>Clinical and hormonal profiles before and during SPL treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Mean age was 29.1 (SD: 9.6) years, and body mass index was 32.2 (SD: 8.1) kg/m². Nine patients had diabetes, and 22 had prediabetes. SPL was used in combination with combined oral contraceptive pills in 55 participants and progestin-only pills/long-acting reversible contraception in 28; metformin was added in 35, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in 15. Median SPL dose was 100 (range: 50–150) mg. A total of 327 serum potassium measurements were obtained (84 pre-exposure and 243 postexposure). Four potassium measurements were above the reference range before exposure and 19 during exposure. All potassium measurements above the reference range during follow-up were classified as mild hyperkalemia (5.1–5.5 mEq/L).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The present findings suggest that women with PCOS, without kidney or heart disease, using SPL combined with hormonal contraception for managing clinical hyperandrogenism have a low incidence of hyperkalemia and well-tolerated minor adverse effects.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High prevalence of severe sleep cycle disruption in de novo acromegaly and underdiagnosis by common clinical screening tools: A prospective, observational, cross-sectional study","authors":"Andrew S. Powlson,&nbsp;Anand K. Annamalai,&nbsp;Samantha Moir,&nbsp;Alison J. Webb,&nbsp;Laksha Bala,&nbsp;Johann Graggaber,&nbsp;Narayanan Kandasamy,&nbsp;Olympia Koulouri,&nbsp;David J. Halsall,&nbsp;John M. Shneerson,&nbsp;Mark Gurnell","doi":"10.1111/cen.14994","DOIUrl":"10.1111/cen.14994","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Context</h3>\u0000 \u0000 <p>Although sleep disordered breathing (SDB) is well-recognised in acromegaly, most studies have reported heterogeneous, often heavily treated, groups and few have performed detailed sleep phenotyping at presentation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To study SDB using the gold standard of polysomnography, in the largest group of newly-diagnosed, treatment-naïve patients with acromegaly.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Setting and Patients</h3>\u0000 \u0000 <p>40 patients [22 males, 18 females; mean age 54 years (range 23–78)], were studied to:</p>\u0000 \u0000 <p><b>(i)</b> establish the prevalence and severity of SDB</p>\u0000 \u0000 <p><b>(ii)</b> assess the reliability of commonly employed screening tools [Epworth Sleepiness Scale (ESS) and overnight oxygen desaturation index (DI)] to detect SDB</p>\u0000 \u0000 <p><b>(iii)</b> determine the extent to which sleep architecture is disrupted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Obstructive sleep apnoea (OSA), defined by the apnoea-hypopnoea index (AHI), was present in 79% of subjects (mild, <i>n</i> = 12; moderate, <i>n</i> = 5; severe, <i>n</i> = 14). However, in these individuals with OSA by AHI criteria, ESS (positive in 35% [<i>n</i> = 11]) and DI (positive in 71%: mild, <i>n</i> = 11; moderate, <i>n</i> = 6; severe, <i>n</i> = 5) markedly underestimated its prevalence/extent. Seventy-eight percent of patients exhibited increased arousal, with marked disruption of the sleep cycle, despite most (82%) having normal total time asleep. Fourteen patients spent longer in stage 1 sleep. Deeper sleep stages were severely attenuated in many subjects (reduced stage 2, <i>n</i> = 18; reduced slow wave sleep, <i>n</i> = 24; reduced rapid eye movement sleep, <i>n</i> = 32).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study provides strong support for clinical guidelines that recommend screening for sleep apnoea syndrome in patients with newly-diagnosed acromegaly. Importantly, however, it highlights shortcomings in commonly recommended screening tools (questionnaires, desaturation index) and demonstrates the added value of polysomnography to allow timely detection of obstructive sleep apnoea and associated sleep cycle disruption.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.14994","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum thrombospondin-2 level changes with liver stiffness improvement in patients with type 2 diabetes","authors":"Jimmy Ho Cheung Mak,&nbsp;David Tak-Wai Lui,&nbsp;Carol Ho-Yi Fong,&nbsp;Chloe Yu-Yan Cheung,&nbsp;Ying Wong,&nbsp;Alan Chun-Hong Lee,&nbsp;Ruby Lai-Chong Hoo,&nbsp;Aimin Xu,&nbsp;Kathryn Choon-Beng Tan,&nbsp;Karen Siu-Ling Lam,&nbsp;Chi-Ho Lee","doi":"10.1111/cen.15010","DOIUrl":"10.1111/cen.15010","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Baseline circulating thrombospondin-2 (TSP2) level was identified as a potential novel hepatic fibrosis biomarker that associates with development and progression of hepatic fibrosis in patients with nonalcoholic fatty liver disease and type 2 diabetes. Here, we investigated whether circulating TSP2 levels changed with improvement in liver stiffness (LS), which reflects liver fibrosis on transient elastography.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design</h3>\u0000 \u0000 <p>Serum TSP2 levels were measured in participants from a randomized, open-label intervention study, at baseline and after 24-weeks treatment of either dapagliflozin 10 mg (<i>N</i> = 30) or sitagliptin 100 mg daily (<i>N</i> = 30). Vibration-controlled transient elastography was performed to evaluate the severity of hepatic fibrosis and steatosis using LS and controlled attenuation parameter (CAP), respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients and Measurements</h3>\u0000 \u0000 <p>Among all 60 participants with similar clinical characteristics at baseline (mean HbA1c 8.9%, CAP 289 dB/m and LS 5.8 kPa), despite similar HbA1c lowering, treatment with dapagliflozin, but not sitagliptin, led to significant improvements in body weight (BW) (<i>p</i> = .012), CAP (<i>p</i> = .015) and LS (<i>p</i> = .011) after 24 weeks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Serum TSP2 level decreased significantly from baseline in dapagliflozin-treated participants (<i>p</i> = .035), whereas no significant change was observed with sitagliptin. In correlation analysis, change in serum TSP2 levels only positively correlated with change in LS (<i>r</i> = .487, <i>p</i> = .006), but not with changes in BW, CAP or HbA1c after dapagliflozin treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Serum TSP2 level decreased with LS after dapagliflozin treatment, and was independent of improvements in BW, glycemic control and hepatic steatosis, further supporting the potential of serum TSP2 level as a novel hepatic fibrosis biomarker in type 2 diabetes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.15010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare forms of congenital adrenal hyperplasia.","authors":"Busra Gurpinar Tosun, Tulay Guran","doi":"10.1111/cen.15009","DOIUrl":"https://doi.org/10.1111/cen.15009","url":null,"abstract":"<p><p>Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders due to pathogenic variants in genes encoding enzymes and cofactors involved in adrenal steroidogenesis. Although 21-hydroxylase, 11β-hydroxylase, 3β-hydroxysteroid dehydrogenase type 2, 17α-hydroxylase/17,20-lyase, P450 oxidoreductase, steroidogenic acute regulatory protein, cholesterol side-chain cleavage enzyme deficiencies are considered within the definition of CAH, the term 'CAH' is often used to refer to '21-hydroxylase deficiency (21OHD)' since 21OHD accounts for approximately 95% of CAH in most populations. The prevalence of the rare forms of CAH varies according to ethnicity and geographical location. In most cases, the biochemical fingerprint of impaired steroidogenesis points to the specific subtypes of CAH, and genetic testing is usually required to confirm the diagnosis. Despite there are significant variations in clinical characteristics and management, most data about the rare CAH forms are extrapolated from 21OHD. This review article aims to collate the currently available data about the diagnosis and the management of rare forms of CAH.</p>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-dose diazoxide therapy in hyperinsulinaemic hypoglycaemia","authors":"Amy Yi-Lin Ng,&nbsp;Pankaj Agrawal,&nbsp;Roopa Vijayan,&nbsp;Ved B. Arya,&nbsp;Ritika R. Kapoor,&nbsp;Pratik Shah","doi":"10.1111/cen.14991","DOIUrl":"10.1111/cen.14991","url":null,"abstract":"<p>Dear Editor,</p><p>Hyperinsulinaemic hypoglycaemia (HH) is a rare condition with elevated and unregulated levels of insulin, resulting in low blood glucose concentrations. It is the most common cause of persistent hypoglycaemia in infants and children, causing a high risk of developing brain injuries such as epilepsy, cerebral palsy, or neurological impairment.<span>¹</span> Diazoxide remains the first-line medication used to treat HH.<span>¹</span> It binds to the SUR1 subunit of <i>KATP</i> channels to inhibit β-cell depolarisation and thus insulin secretion. However, it is important to note that fluid retention, hypertrichosis, and feeding problems are common side effects of diazoxide. Rare severe consequences can also occur like pulmonary hypertension and congestive heart failure. Apart from a single study reporting the use of low-dose diazoxide in small for gestational age (SGA) infants, diazoxide has been reported to be used in doses of 5−20 mg/kg/day.<span>²</span></p><p>Chandran et al. highlighted the efficacy and safety of using ≤5 mg/kg/day of diazoxide in 27 SGA babies.<span>²</span> Twenty-six (97%) of these passed a fasting study before discharge from the hospital, establishing normal glucose control on low-dose diazoxide. Furthermore, diazoxide was discontinued at a median age of 63 days, and resolution of HH was confirmed in 26/27 (96%) infants on passing a fasting study. Their study benefits from a robust trial protocol with a modest sample size considering that HH is a rare disease and that Singapore has a small population.</p><p>Similarly, we conducted a retrospective analysis evaluating the effectiveness and outcomes of using low-dose diazoxide (≤5 mg/kg/day) that have successfully managed HH. We have identified 34 patients with biochemically confirmed HH that were treated with low-dose diazoxide at two tertiary children hospitals in London from April 2020 to March 2023. Patient characteristics (birth weight and gestational age) and treatment details were collected from electronic patient records. For the comparative analysis, the patients were stratified into two groups based on their birth weight: SGA and non-SGA (appropriate for gestational age–AGA and large for gestational age–LGA). SGA was defined as birth weight &lt;10th centile. The patients were also differentiated by their gestational age: preterm (&lt;37 weeks) and term (≥37 weeks). Patient outcomes that were assessed included: (1) median age of starting and stopping treatment; (2) median dosage of diazoxide on discharge from hospital; and (3) follow-up outcomes: side effects from diazoxide, adjustment of diazoxide dose, and neurodevelopmental outcomes.</p><p>Of the 34 infants, 15 were SGA and 19 were non-SGA. The patient characteristics and details of diazoxide treatment are summarised in Table 1. All babies had their total fluid volume adjusted to approximately 130 mL/kg/day when initiating diazoxide. All infants underw","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.14991","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138497968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}