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Deirdre Green Academic Department of Endocrinology, Beaumont Hospital and the Royal College of Surgeons in Ireland, Dublin

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Rosemary Dineen Academic Department of Endocrinology, Beaumont Hospital and the Royal College of Surgeons in Ireland, Dublin

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Michael W O’Reilly Academic Department of Endocrinology, Beaumont Hospital and the Royal College of Surgeons in Ireland, Dublin

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Mark Sherlock Academic Department of Endocrinology, Beaumont Hospital and the Royal College of Surgeons in Ireland, Dublin

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Despite the availability of adrenal hormone replacement therapy, patients with adrenal insufficiency can be affected by reduced fertility and parity. Patients with well-managed adrenal insufficiency are expected to have uneventful pregnancies and favourable outcomes, but an increased risk of maternal and neonatal complications has been reported in some cases. Many physiological changes occur to the hypothalamic–pituitary–adrenal (HPA) axis during pregnancy, often making a new diagnosis and management of adrenal insufficiency challenging. The management of adrenal insufficiency also needs to reflect the physiologic changes of pregnancy, often requiring increased doses of glucocorticoid as pregnancy progresses and in some circumstances mineralocorticoid replacement (in primary adrenal insufficiency patients only), especially in the third trimester. To date, there are no prospective data guiding management of adrenal insufficiency in pregnancy. In this review, we focus on the impact of adrenal insufficiency on fertility and parity based on the aetiology of adrenal insufficiency and provide a practical approach to the management of patients with adrenal insufficiency before and during pregnancy.

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Caiyan Mo C Mo, Department of Endocrinology, Beijing Tiantan Hospital, Beijing, China

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Tao Tong T Tong, Department of Endocrinology, Beijing Tiantan Hospital, Beijing, China

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Ying Guo Y Guo, Department of Endocrinology, Beijing Tiantan Hospital, Beijing, China

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Zheng Li Z Li, Department of Endocrinology, Beijing Tiantan Hospital, Beijing, China

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Liyong Zhong L Zhong, Department of Endocrinology, Beijing Tiantan Hospital, Beijing, China

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Purpose: The coexistence of growth hormone-secreting pituitary adenoma (GHPA) and Graves' disease (GD) is rare. This study aimed to investigate the relationship between growth hormone (GH)/insulin-like growth factor-1 (IGF-1) levels and thyroid function in patients with GHPA combined with GD and to explore the underlying mechanisms.

Methods: Eleven patients with GHPA combined with GD during 2015-2022 were collected by searching the medical record system of Beijing Tiantan Hospital, Capital Medical University. Changes in GH/IGF-1 levels and thyroid function were compared before and after the application of antithyroid drugs (ATD) and before and after transsphenoidal surgery (TSS) or somatostatin analogue (SSA) treatment, respectively.

Results: After the application of ATD, with the decrease of thyroid hormone levels, GH/IGF-1 levels also decreased gradually. In patients without ATD application, after surgery or SSA treatment, thyroid hormone levels decreased as GH/IGF-1 decreased.

Conclusion: Hyperthyroidism due to GD promotes the secretion of GH/IGF-1, and when thyroid hormone levels were decreased by the use of ATD, GH and IGF-1 levels were also decreased, suggesting that thyroid hormones may influence the synthesis and secretion of GH/IGF-1. The use of ATD to control thyrotoxicosis before TSS is not only beneficial in reducing the risk of anesthesia, but may help to promote biochemical control of GHPA. On the other hand, high levels of GH/IGF-1 in patients with GHPA also exacerbate GD hyperthyroidism, which is ameliorated by a decrease in GH/IGF-1 levels by TSS or SSA treatment, suggesting that the GH/IGF-1 axis promotes growth, thyroid function, and thyroid hormone metabolism.

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Timothy J Morris Directorate of Biochemistry, Manchester University NHS Foundation Trust, Manchester, UK
Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK

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Andrew Whatmore Division of Developmental Biology and Medicine, University of Manchester, Royal Manchester Children’s Hospital, Manchester, UK

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Laura Hamilton Pathology Department, Clinical Biochemistry, Huddersfield Royal Infirmary, Lindley, Huddersfield, UK

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Beverly Hird Directorate of Biochemistry, Manchester University NHS Foundation Trust, Manchester, UK

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Eric S Kilpatrick Directorate of Biochemistry, Manchester University NHS Foundation Trust, Manchester, UK

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Lesley Tetlow Directorate of Biochemistry, Manchester University NHS Foundation Trust, Manchester, UK

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Peter Clayton Division of Developmental Biology and Medicine, University of Manchester, Royal Manchester Children’s Hospital, Manchester, UK

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Children with salt-wasting adrenal insufficiency are managed with glucocorticoid and mineralocorticoid replacement. Measurement of renin activity or concentration alongside blood electrolyte levels is used to monitor the adequacy of mineralocorticoid replacement. Our unit changed from using renin activity to renin concentration and carried out a service review to assess whether this influenced decision-making for fludrocortisone dosing. In total, 50 measurements of plasma renin activity and 50 of renin concentration were analysed on separate cohorts before and after the assay change, with values standardised to multiples of the upper limit of normal (MoU) to allow comparison between assays. We were more likely to increase the fludrocortisone dose for a raised renin concentration than a raised renin activity. The renin concentration MoU was more strongly related to plasma sodium (negatively) and 17α-hydroxyprogesterone (17α-OHP) (positively) than the renin activity MoU. Using a MoU cut-off of 1.5, a decision to increase the dose of fludrocortisone was more likely to be made when using the renin concentration assay compared with the activity assay. Using a cut-off of 40 nmol/L for 17α-OHP, a decision not to change the fludrocortisone dose when 17α-OHP was <40 was more likely when using the renin concentration assay. For both assays, a plasma sodium <140 mmol/L was more likely to lead to a fludrocortisone dose increase, and most likely for the renin concentration assay. Overall, the decision to adjust fludrocortisone dose in this cohort of children with adrenal insufficiency was better supported by the biochemical parameters when based on renin concentration results and clinical status.

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Lára Ósk Eggertsdóttir Claessen Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland
Department of Emergency Medicine, Landspitali – The National University Hospital of Iceland, Reykjavik, Iceland

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Hafrún Kristjánsdóttir Physical Activity, Physical Education, Sport, and Health (PAPESH) Research Centre, Sports Science Department, School of Social Sciences, Reykjavik University, Reykjavik, Iceland

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María Kristín Jónsdóttir Mental Health Services, Landspitali – The National University Hospital of Iceland, Reykjavik, Iceland
Department of Psychology, School of Social Sciences, Reykjavik University, Reykjavik, Iceland

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Sigrún Helga Lund deCODE Genetics, Inc/Amgen Inc., Reykjavik, Iceland
School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland

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Ingunn Unnsteinsdóttir Kristensen Department of Psychology, School of Social Sciences, Reykjavik University, Reykjavik, Iceland

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Helga Ágústa Sigurjónsdóttir Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland
Department of Medicine, Landspitali – The National University Hospital of Iceland, Reykjavik, Iceland

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Objective

Pituitary dysfunction following mild traumatic brain injury can have serious physical and psychological consequences, making correct diagnosis and treatment essential. To the best of our knowledge, this study is the first to study the prevalence of pituitary dysfunction following mild traumatic brain injury in an all-female population following detailed endocrinological work-up after screening for pituitary dysfunction in female athletes.

Design

This is a retrospective cohort study.

Methods

Hormone screening blood tests, including serum blood values for thyroid-stimulating hormone, free thyroxin, insulin-like growth factor 1, prolactin, cortisol, follicle-stimulating hormone, luteinizing hormone, estrogen and progesterone, were taken in 133 female athletes. Results were repeatedly outside the reference value in 88 women necessitating further endocrinological evaluation. Two of those were lost to follow-up, and further endocrinological evaluation was performed in 86 participants.

Results

Six women (4.6%, n = 131) were diagnosed with hypopituitarism, four (3.1%) with central hypothyroidism and two with growth hormone deficiency (1.5%). Ten women (7.6%) had hyperprolactinemia, and four (3.1%) of them had prolactinoma. Medical treatment was initiated in 13 (9.9%) women. Significant prognostic factors were not found.

Conclusions

As 12.2% of female athletes with a history of mild traumatic brain injury had pituitary dysfunction (hypopituitarism 4.6%, hyperprolactinemia 7.6%), we conclude that pituitary dysfunction is an important consideration in post-concussion care. Hyperprolactinemia in the absence of prolactinoma may represent pituitary or hypothalamic injury following mild traumatic brain injury.

Significance statement

Mild traumatic brain injury (mTBI) has become a growing public health concern as 50 million people worldwide sustain a traumatic brain injury annually, with mTBI being the most common (70–90%). As studies on mTBI have focused on mostly male populations this study aims to explore pituitary dysfunction (PD) in female athletes following mTBI. To the best of our knowledge, it is the first all-female study on PD following mTBI.

The study found that 12.2% of the participating women had PD after mTBI. Six (4.6%) had hypopituitarism and ten (7.6%) had hyperprolactinemia. These findings suggest that PD following mTBI is an important consideration that endocrinologists and other medical staff working with athletes need to be aware of.

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Sara Ahmadi Division of Endocrinology, Thyroid Section, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

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Iñigo Landa Division of Endocrinology, Thyroid Section, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

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The introduction and generalization of next-generation sequencing techniques have significantly increased the identification of mutations in thyroid tumors from multiple patient cohorts. The understanding of the association between specific mutations and clinical outcomes is gradually leading to individualizing the care of patients with thyroid cancer. BRAFV600 is the most common mutation seen in thyroid cancer patients and unequivocally predicts malignancy, but when considered in isolation, it is not recommended to be used as an independent prognostic factor. Mutations in RAS are the second most common alterations in thyroid cancer but can be found in benign and malignant lesions. Rearrangements involving receptor tyrosine kinases, primarily RET, are found in a subset of thyroid tumors without mutations in either BRAF or RAS. The assessment of additional mutations is increasingly employed in thyroid cancer prognostication. The coexistence of BRAF with alterations in genes such as PIK3CA, TERT promoter, or TP53 is associated with less favorable outcomes. Similar studies have also shown that additional oncogenic mutations in RAS-mutant thyroid carcinoma, such as those affecting the EIF1AX gene, likely predict a more aggressive clinicopathologic behavior. Overall, emerging evidence suggests that the co-occurrence of specific alterations in defined genes with BRAF or RAS mutations can become prognostic tools and useful predictors of thyroid tumor aggressiveness.

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Yumei Zhai Y Zhai, Baotou Medical College Second Clinical Medical School, Baotou, 014030, China

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Haiming Fu H Fu, Clinical Laboratory, Baotou Maternal and Child Health Center, baotou, China

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Yu Li Y Li, Baotou Medical College Second Clinical Medical School, Baotou, China

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Siyuan Li S Li, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, baotou, China

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Wenchen Zhang W Zhang, Baotou Medical College Second Clinical Medical School, Baotou, China

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Jianwei Yue J Yue, Baotou Medical College Second Clinical Medical School, Baotou, China

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Zichao Wang Z Wang, Baotou Medical College Second Clinical Medical School, Baotou, China

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Background: Hypertension-induced left ventricular hypertrophy (LVH) is intricately linked to insulin resistance (IR). This research aimed to elucidate the relationship of advanced indices, namely the triglyceride-glucose (TyG) index, the TyG adjusted for body mass index (TyG-BMI), the triglycerides to high-density lipoprotein cholesterol ratio (TG/HDL-c), and the metabolic score for IR (METS-IR), with LVH in hypertensive cohorts.

Methods: This analytical case-control investigation encompassed 800 individuals aged 18 or above from the Cardiology Department of the Second Affiliated Hospital of Baotou Medical College over a span from January 2021 to April 2022. Data extraction was conducted from inpatient records. The nexus between the four metrics and LVH susceptibility was ascertained via logistic regression models. Furthermore, the Receiver Operating Characteristic (ROC) curve’s area (AUC) shed light on the discriminative capacities of the distinct IR indicators for LVH, considering other concomitant risk variables.

Results: Post multifaceted covariate adjustments, the fourth quartile figures for TyG-BMI emerged as the most starkly significant (OR: 5.211, 95% CI:2.861–9.492), succeeded by METS-IR (OR:4.877, 95% CI:2.693–8.835). In juxtaposition with other IR-derived indices (TyG and TG/HDL-c), TyG-BMI manifested the paramount AUC (AUC:0.657;95% CI:0.606–0.708). Concurrently, METS-IR exhibited commendable predictive efficacy for LVH (AUC:0.646;95% CI:0.595–0.697).

Conclusion: TyG-BMI and METS-IR displayed superior discriminative capabilities for LVH, underscoring their potential as supplementary indicators in gauging LVH peril in clinical settings and prospective epidemiological research.

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David Q Pham Western University of Health Sciences, College of Pharmacy, Pomona, California, USA
Mary & Dick Allen Diabetes Center at Hoag Hospital, Newport Beach, California, USA

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Ashley Thorsell Sansum Diabetes Research Institute, Santa Barbara, California, USA

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Kristin Castorino Sansum Diabetes Research Institute, Santa Barbara, California, USA

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Brandon Cobb Sansum Diabetes Research Institute, Santa Barbara, California, USA

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The main objective of this article is to provide a comprehensive review of continuous glucose monitor (CGM) use in pregnant women with type 1 diabetes (T1D) from the CONCEPTT study including subanalyses. Literature search was accessed through MEDLINE (1966–September 2023) using the key terms: CONCEPTT, pregnancy, women, T1D, and CGM with limitations set to distinguish human subjects written in English. A total of 17 publications including one main clinical trial and 15 subanalyses have been published to date regarding the use of CGM in pregnant women with T1D which were conducted by a research group identified as the CONCEPTT Collaborative Group. While advances in maternal care have resulted in safer pregnancy for both the mother and child, women with preexisting T1D and pregnancy still experience higher rates of complications both in the short and long term. The use of CGM in pregnancy has not been studied extensively until more recently. The CONCEPTT clinical trial was a landmark study that involved several subanalyses. The main trial proved that CGM use in T1D pregnancy resulted in less hyperglycemia in the third trimester, reduced large for gestational age (LGA, >90th percentile), reduced neonatal intensive care unit admissions lasting longer than 24 h, and reduced neonatal hypoglycemia. Although subanalyses showed a variety of results including ‘inconclusive’ due to lack of prespecification, it is believed that CGM in T1D during pregnancy is to be recommended and used for overall improved outcomes.

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Sigrid Bjerge Gribsholt S Gribsholt, Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark

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Morten Schmidt M Schmidt, Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark

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Eskild Bendix Kristiansen E Kristiansen, Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark

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Bjørn Richelsen B Richelsen, Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

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Henrik T. Sorensen H Sorensen, Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark

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Objective: To examine the association between hospital-diagnosed overweight/obesity and incident cardiovascular disease (CVD) according to the time period of the overweight/obesity diagnosis.

Design: Cohort study.

Methods: From Danish national health registries, we identified all residents with a first-time hospital-based overweight/obesity diagnosis code, 1977-2018 (N=195,221), and an age and sex-matched general population comparison cohort (N=1,952,210). We computed adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) using Cox regression. We adjusted for comorbidities and educational level and applied 10 years of follow-up.

Results: The overall incidence rate was 10.1 (95% CI; 10.0-10.1) per 1000 person-years for the comparison cohort and 25.1 (95% CI; 24.8-25.4) per 1000 person-years for the overweight/obesity cohort, corresponding to an aHR of 2.5 (95% CI: 2.4-2.5). The aHR was elevated for all subtypes of CVD: heart failure: 3.9 (95% CI: 3.7-4.1), bradyarrhythmia: 2.9 (95% CI: 2.7-3.1), angina pectoris: 2.7 (95% CI: 2.7-2.8), atrial fibrillation or flutter: 2.6 (95% CI; 2.5-2.6), acute myocardial infarction: 2.4 (95% CI; 2.3-2.4), revascularization procedure: 2.4 (95% CI: 2.2-2.5), valvular heart disease: 1.7 (95% CI: 1.6-1.8), ischemic stroke: 1.6 (95% CI: 1.4-1.7), transient ischemic attack: 1.6 (95% CI: 1.5-1.7), and cardiovascular death: 1.6 (95% CI: 1.5-1.6). The 1-10-year aHR of any CVD associated with an overweight/obesity diagnosis decreased from 2.8 (95% CI; 2.7-2.9) in 1977-1987 to 1.8 (95% CI; 1.8-1.9) in 2008-2018.

Conclusion: Patients with hospital-diagnosed overweight/obesity had high rates of ischemic heart disease, heart failure, structural heart disease, arrhythmia, stroke, and death, although the strength of the association decreased in recent years.

Open access
Robert Maidstone Oxford Centre for Diabetes, Endocrinology and Metabolism, and Oxford Kavli Centre for Nanoscience Discovery, University of Oxford, Oxford, UK
Centre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK

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Martin K Rutter Centre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
Diabetes, Endocrinology and Metabolism Centre, Manchester University NHS Foundation Trust, NIHR Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, Manchester, UK

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Thomas Marjot Oxford Centre for Diabetes, Endocrinology and Metabolism, and Oxford Kavli Centre for Nanoscience Discovery, University of Oxford, Oxford, UK
Oxford Liver Unit, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, UK

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David W Ray Oxford Centre for Diabetes, Endocrinology and Metabolism, and Oxford Kavli Centre for Nanoscience Discovery, University of Oxford, Oxford, UK
NIHR Oxford Health Biomedical Research Centre, and NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK

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Matthew Baxter Oxford Centre for Diabetes, Endocrinology and Metabolism, and Oxford Kavli Centre for Nanoscience Discovery, University of Oxford, Oxford, UK
NIHR Oxford Health Biomedical Research Centre, and NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK

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Background and aims

Non-alcoholic fatty liver disease (NAFLD) has rapidly become the most common liver disease worldwide. Modern lifestyles have been linked to this rise in prevalence with changes in rhythmic human behaviour emerging as a possible mechanism. We investigated how shift working patterns and chronotype were associated with hepatic fat fraction and NAFLD in 282,303 UK Biobank participants.

Methods

We stratified participants into day, irregular-shift, and permanent night-shift workers. We then utilised multiple methods of disease identification including (i) Dallas steatosis index (DSI), (ii) ICD10 codes, and (iii) hepatic proton density fat fraction (PDFF) and examined how shift work exposure impacted these variables. We further assessed the relationship of baseline chronotype with liver phenotypes using these same outcome measures.

Results

Compared to day workers, irregular-shift workers were more likely to have a high DSI (OR 1.29 (1.2–1.4)) after adjusting for major covariates with some attenuation after additional adjustment for BMI (OR 1.12 (1.03–1.22)). Likelihood of high DSI was also increased in permanent night-shift workers (OR 1.08 (0.9–1.29)) in the fully adjusted model. Mediator analysis revealed that BMI was a significant mediator of the shift work effect. Compared to participants with intermediate chronotype, those with extreme late chronotype had a higher likelihood of high DSI defined NAFLD (OR 1.45 (1.34–1.56)) and a higher likelihood of NAFLD/NASH by ICD10 code (OR 1.23 (1.09–1.39)). Hepatic PDFF was elevated in irregular shift workers, but not permanent night-shift workers.

Conclusions

Irregular-shift work and extreme late chronotype are associated with pathological liver fat accumulation, suggesting circadian misalignment may have an underlying pathogenic role. These findings have implications for health interventions to mitigate the detrimental effect of shift work.

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Yuegui Wang Department of Ultrasound, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, China

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Liwei Hong Department of Nuclear Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, China

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Caiyun Yang Department of Ultrasound, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, China
School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, China

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Guorong Lv School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, China
Quanzhou Medical College, Quanzhou, Fujian, China

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Kangjian Wang Department of Ultrasound, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, China

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Xuepeng Huang Department of Nuclear Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, China

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Haolin Shen Department of Ultrasound, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, China

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The aim of this study was to develop a prognostic model for radioactive iodine (RAI) therapy outcome in patients with Graves‘ disease. We enrolled 127 patients. Information on RAI therapy, ultrasound indexes of thyroid, and other lifestyle factors was collected. The competing risk model was used to estimate the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for nonhealing or recurrence of hyperthyroidism (NHRH). The performance of the model was assessed by receiver operator characteristic analysis and the Brier score and internally validated by bootstrap resampling. Then, a nomogram was developed. Forty-one cases (32.2%) of NHRH were documented. Positive Ki-67 expression, a higher dose of per-unit thyroid volume, and females showed lower risks of NHRH (all P < 0.05). The HR values (95% CI) were 0.42 (0.23, 0.79), 0.01 (0.00, 0.02), and 0.47 (0.25, 0.89), respectively. The bootstrap validation showed that the model had the highest accuracy and good calibration for predicting cumulative risk of NHRH at 180 days after RAI therapy (AUC = 0.772; 95% CI: 0.640–0.889, Brier score = 0.153). By decision curve analysis, the nomogram was shown to have a satisfactory net benefit between thresholds of 0.20 and 0.40. Ki-67, ultrasound volumetry, and scintigraphy techniques can play important roles in evaluating RAI therapy outcome in Graves‘ disease patients. The prediction nomogram shows reasonable accuracy in predicting NHRH.

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