Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder affecting 5%–10% of reproductive-age women, accounting for 50%–70% of anovulatory infertility. Thyroid function, particularly the relationship between subclinical hypothyroidism (SCH) and PCOS, has garnered attention due to its potential impact on metabolic and reproductive health.
Methods
This study included 143 infertile women with PCOS diagnosed based on the Rotterdam criteria. Participants underwent ovulation induction using clomiphene citrate following pretreatment with Diane-35. Serum levels of triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) were measured pre- and posttherapy. Outcomes were compared between therapy-responsive (n = 97) and nonresponsive (n = 46) groups. Receiver operating characteristic (ROC) analysis evaluated the predictive value of T3, T4, and TSH levels for treatment outcomes.
Results
Significant differences in baseline T3, T4, and TSH levels were observed between responsive and nonresponsive groups (p < 0.001). Posttreatment, serum T3 and T4 increased while TSH decreased in the responsive group, whereas no significant changes were noted in the nonresponsive group. Combined ROC analysis of T3, T4, and TSH improved predictive accuracy (AUC = 0.88, sensitivity = 76.09%, specificity = 86.60%). Endometrial thickness positively correlated with T3 and T4 and negatively with TSH.
Conclusions
Thyroid hormones significantly influence the efficacy of ovulation induction in infertile women with PCOS. Combined T3, T4, and TSH measurements enhance predictive accuracy for therapeutic responses, providing a foundation for personalized treatment strategies.
{"title":"Thyroid Hormones Correlate to the Therapeutic Effect of Ovulation Induction in Infertile Women With Polycystic Ovary Syndrome","authors":"Xuefei Hao, Shasha Liu, Hanjing Zheng, Qiuchen Wang, Lizhen Jin, Jing Ma","doi":"10.1111/cen.70030","DOIUrl":"10.1111/cen.70030","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder affecting 5%–10% of reproductive-age women, accounting for 50%–70% of anovulatory infertility. Thyroid function, particularly the relationship between subclinical hypothyroidism (SCH) and PCOS, has garnered attention due to its potential impact on metabolic and reproductive health.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study included 143 infertile women with PCOS diagnosed based on the Rotterdam criteria. Participants underwent ovulation induction using clomiphene citrate following pretreatment with Diane-35. Serum levels of triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) were measured pre- and posttherapy. Outcomes were compared between therapy-responsive (<i>n</i> = 97) and nonresponsive (<i>n</i> = 46) groups. Receiver operating characteristic (ROC) analysis evaluated the predictive value of T3, T4, and TSH levels for treatment outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Significant differences in baseline T3, T4, and TSH levels were observed between responsive and nonresponsive groups (<i>p</i> < 0.001). Posttreatment, serum T3 and T4 increased while TSH decreased in the responsive group, whereas no significant changes were noted in the nonresponsive group. Combined ROC analysis of T3, T4, and TSH improved predictive accuracy (AUC = 0.88, sensitivity = 76.09%, specificity = 86.60%). Endometrial thickness positively correlated with T3 and T4 and negatively with TSH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Thyroid hormones significantly influence the efficacy of ovulation induction in infertile women with PCOS. Combined T3, T4, and TSH measurements enhance predictive accuracy for therapeutic responses, providing a foundation for personalized treatment strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"104 2","pages":"152-159"},"PeriodicalIF":2.4,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029016","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}
Mingjun Wang, Wenjie Chen, Peiheng Li, Yanping Gong
Background
Improved cancer survival rates have highlighted second primary malignancies (SPMs), with the thyroid gland being one of the most common organs developing SPMs in cancer survivors. Second primary papillary thyroid carcinoma (2-PTC) is the predominant type, yet it remains poorly understood. This study aims to delineate the clinicopathological features and survival outcomes of 2-PTC and assess the efficacy of postoperative radioactive iodine therapy (post-RAIT) in reducing mortality risks in intermediate-risk 2-PTC patients.
Methods
Using the SEER-17 database (2004–2019), we identified 6399 2-PTC patients as Cohort 1 to analyze characteristics and outcomes, and 1743 as Cohort 2 to examine post-RAIT effects. Competing risk regression models were applied to assess mortality risks from prior primary malignancies (PPMs) and other causes. Propensity score matching and stabilized inverse probability treatment weighting with 500 bootstrap samples were used for robust analysis.
Results
Predominant demographic characteristics of 2-PTC patients included older age, female sex, and white ethnicity. Breast (25.5%), prostate (9.8%), and skin cancer (6.7%) were the most common PPMs. Unfavorable PPMs were found in 6.3% of patients. Despite lower cumulative mortality from 2-PTC compared to PPMs and other causes, post-RAIT did not significantly reduce mortality risks in Cohort 2, even among patients aged ≥ 55 years, with clinical stage IV disease, or unfavorable PPMs. Sensitivity analyses confirmed these findings.
Conclusion
The survival prognosis for 2-PTC patients is generally favorable, and post-RAIT does not significantly affect mortality in intermediate-risk cases, indicating a need for reevaluation of its use.
{"title":"Second Primary Papillary Thyroid Carcinoma: Insights From Competing Risk Analysis and Post-RAIT","authors":"Mingjun Wang, Wenjie Chen, Peiheng Li, Yanping Gong","doi":"10.1111/cen.70031","DOIUrl":"10.1111/cen.70031","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Improved cancer survival rates have highlighted second primary malignancies (SPMs), with the thyroid gland being one of the most common organs developing SPMs in cancer survivors. Second primary papillary thyroid carcinoma (2-PTC) is the predominant type, yet it remains poorly understood. This study aims to delineate the clinicopathological features and survival outcomes of 2-PTC and assess the efficacy of postoperative radioactive iodine therapy (post-RAIT) in reducing mortality risks in intermediate-risk 2-PTC patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the SEER-17 database (2004–2019), we identified 6399 2-PTC patients as Cohort 1 to analyze characteristics and outcomes, and 1743 as Cohort 2 to examine post-RAIT effects. Competing risk regression models were applied to assess mortality risks from prior primary malignancies (PPMs) and other causes. Propensity score matching and stabilized inverse probability treatment weighting with 500 bootstrap samples were used for robust analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Predominant demographic characteristics of 2-PTC patients included older age, female sex, and white ethnicity. Breast (25.5%), prostate (9.8%), and skin cancer (6.7%) were the most common PPMs. Unfavorable PPMs were found in 6.3% of patients. Despite lower cumulative mortality from 2-PTC compared to PPMs and other causes, post-RAIT did not significantly reduce mortality risks in Cohort 2, even among patients aged ≥ 55 years, with clinical stage IV disease, or unfavorable PPMs. Sensitivity analyses confirmed these findings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The survival prognosis for 2-PTC patients is generally favorable, and post-RAIT does not significantly affect mortality in intermediate-risk cases, indicating a need for reevaluation of its use.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"104 1","pages":"53-66"},"PeriodicalIF":2.4,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014007","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}
Cardiovascular disease (CVD) remains the leading cause of mortality and morbidity among women worldwide. However, CVD continues to be perceived as a predominantly male issue. CVD in women therefore remains understudied, underrecognized and undertreated. Starting in adolescence and extending into older age, lifestyle factors, psychosocial stressors, hormonal changes and pregnancy, significantly influence the cardiovascular health of women. This review provides a comprehensive overview of CVD in women, focusing on sex-specific risk factors, presentation, diagnosis, and treatment across the lifespan. The article seeks to raise awareness and provide insights into sex-specific prevention, diagnosis and management strategies. We highlight gaps in knowledge to underscore the importance of sex-based research that is crucial to improving outcomes for women with CVD.
{"title":"Cardiovascular Health in Women-Across the Lifespan.","authors":"Jaya Chandrasekhar, Jessica Yao, Simone Gong, Madhuka Wijayarathne, Monique Watts, Swati Mukherjee","doi":"10.1111/cen.70027","DOIUrl":"https://doi.org/10.1111/cen.70027","url":null,"abstract":"<p><p>Cardiovascular disease (CVD) remains the leading cause of mortality and morbidity among women worldwide. However, CVD continues to be perceived as a predominantly male issue. CVD in women therefore remains understudied, underrecognized and undertreated. Starting in adolescence and extending into older age, lifestyle factors, psychosocial stressors, hormonal changes and pregnancy, significantly influence the cardiovascular health of women. This review provides a comprehensive overview of CVD in women, focusing on sex-specific risk factors, presentation, diagnosis, and treatment across the lifespan. The article seeks to raise awareness and provide insights into sex-specific prevention, diagnosis and management strategies. We highlight gaps in knowledge to underscore the importance of sex-based research that is crucial to improving outcomes for women with CVD.</p>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999876","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}
Sara Fletcher-Sandersjöö, Annelies van′t Westeinde, Tim Spelman, Tatja Hirvikosi, Svetlana Lajic, Sophie Bensing
Objective
Standard glucocorticoid (GC) replacement therapy in autoimmune Addison′s disease (AAD) fails to replicate natural cortisol rhythms. Despite adherence, patients report persistent fatigue, reduced vitality, and impaired wellbeing, ultimately lowering health-related quality of life (HRQoL). Cortisol is essential for sleep regulation, yet the impact of cortisol imbalance on sleep and HRQoL in AAD remains poorly understood. This study investigates self-reported sleep impairments and their associations with fatigue and HRQoL in young adults with AAD.
Patients and Methods
Sixty-four patients with AAD and 128 healthy controls completed validated questionnaires assessing sleep (Karolinska Sleep Questionnaire), fatigue (Multidimensional Fatigue Inventory), and HRQoL (Short Form-36).
Results
Patients reported significantly more non-restorative sleep (p = 0.015) than controls. While overall rates of clinically relevant sleep impairments were similar, patients more frequently experienced awakening difficulties (p = 0.011) and struggling to stay awake (p = 0.036). Patients also reported poorer physical health (p < 0.001) and greater general fatigue (p = 0.007), with female patients experiencing more mental fatigue (p = 0.013). Poor sleep and fatigue were associated with reduced HRQoL across the cohort, with patients showing a more pronounced decline in physical health in relation to these factors. Mental health scores remained similar between groups.
Conclusion
Non-restorative sleep emerged as a distinct feature of AAD. While the prevalence and severity of sleep impairments were similar to controls, the association with poorer physical health was stronger in patients. Mental health remained similar despite sleep disturbances. These findings highlight the importance of addressing even modest sleep disturbances, which may worsen fatigue and reduce physical wellbeing in AAD.
{"title":"The Relationship Between Sleep, Fatigue and Quality of Life in Young Adults With Autoimmune Addison′s Disease","authors":"Sara Fletcher-Sandersjöö, Annelies van′t Westeinde, Tim Spelman, Tatja Hirvikosi, Svetlana Lajic, Sophie Bensing","doi":"10.1111/cen.70028","DOIUrl":"10.1111/cen.70028","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Standard glucocorticoid (GC) replacement therapy in autoimmune Addison′s disease (AAD) fails to replicate natural cortisol rhythms. Despite adherence, patients report persistent fatigue, reduced vitality, and impaired wellbeing, ultimately lowering health-related quality of life (HRQoL). Cortisol is essential for sleep regulation, yet the impact of cortisol imbalance on sleep and HRQoL in AAD remains poorly understood. This study investigates self-reported sleep impairments and their associations with fatigue and HRQoL in young adults with AAD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients and Methods</h3>\u0000 \u0000 <p>Sixty-four patients with AAD and 128 healthy controls completed validated questionnaires assessing sleep (Karolinska Sleep Questionnaire), fatigue (Multidimensional Fatigue Inventory), and HRQoL (Short Form-36).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients reported significantly more non-restorative sleep (<i>p</i> = 0.015) than controls. While overall rates of clinically relevant sleep impairments were similar, patients more frequently experienced awakening difficulties (<i>p</i> = 0.011) and struggling to stay awake (<i>p</i> = 0.036). Patients also reported poorer physical health (<i>p</i> < 0.001) and greater general fatigue (<i>p</i> = 0.007), with female patients experiencing more mental fatigue (<i>p</i> = 0.013). Poor sleep and fatigue were associated with reduced HRQoL across the cohort, with patients showing a more pronounced decline in physical health in relation to these factors. Mental health scores remained similar between groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Non-restorative sleep emerged as a distinct feature of AAD. While the prevalence and severity of sleep impairments were similar to controls, the association with poorer physical health was stronger in patients. Mental health remained similar despite sleep disturbances. These findings highlight the importance of addressing even modest sleep disturbances, which may worsen fatigue and reduce physical wellbeing in AAD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"103 6","pages":"795-804"},"PeriodicalIF":2.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945183","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}
Berçem Ayçiçek, Mazhar Müslüm Tuna, Ismail Engin, Mustafa Şahin, Sayid Zuhur, Neşe Ersöz Gülçelik, Hüseyin Yağcı, Ersen Karakılıç, Evin Bozkur, Bekir Çakır, Elif Güneş, Süleyman Baldane, Özen Öz Gül, Gulhan Akbaba, Cevdet Duran, Faruk Kılınç, Güven Barış Cansu, Cüneyt Bilginer, Ramazan Sarı, Nurdan Gul, Ayten Oğuz, Bekir Uçan, Eren Gürkan, Murat Çalapkulu, Mehmet Güven, Arzu Or Koca, Sema Taban, Nergis Basmacı
Objective
This study aimed to evaluate the diagnostic performance of biochemical markers in normocalcemic primary hyperparathyroidism (nPHPT), analyse their temporal variations, and assess their correlation with adenoma localisation and size.
Methods
In this multicenter retrospective study—the largest patient cohort reported in the literature to date (n = 474) we comprehensively profiled normocalcemic patients diagnosed with primary hyperparathyroidism nPHPT was diagnosed based on persistently elevated PTH levels with normal serum calcium after excluding secondary causes such as vitamin D deficiency, renal impairment, and other conditions. This retrospective multicenter study included a large cohort of patients whose biochemical markers—including serum calcium, phosphorus, magnesium, vitamin D, parathyroid hormone (PTH), and glomerular filtration rate (GFR)—were measured at three time points, using standardised laboratory protocols. Although in routine clinical practice these measurements are typically performed at regular intervals of 3−6 months, resulting in approximately three assessments during an 18-month follow-up period. Urinary calcium and creatinine levels were also determined, and imaging modalities (ultrasonography, sestamibi scintigraphy, and computed tomography) were employed for adenoma detection. Statistical analyses comprised repeated measures ANOVA, logistic regression, correlation analysis, and ROC analysis, performed using Jamovi software.
Results
Serial evaluations revealed significant temporal changes in key biochemical parameters, including a significant decline in serum calcium and PTH levels alongside a significant increase in urinary calcium excretion. Logistic regression analysis identified higher PTH levels, higher corrected calcium, and larger adenoma size as independent predictors of adenoma localisation, while ROC analysis confirmed that PTH exhibited the highest diagnostic accuracy (AUC = 0.91, 95% CI: 0.84–0.95, p < 0.001).
Conclusion
The large scale of our patient cohort reinforces the robustness of our statistical analyses and provides comprehensive insight into the dynamic nature of nPHPT.
Our findings demonstrate that, even in normocalcemic patients, higher PTH levels and relatively higher calcium levels within the normal range are important indicators of parathyroid adenoma. Integrating serial biochemical measurements with targeted imaging can facilitate earlier diagnosis, potentially preventing future com
{"title":"Temporal Variation of Biochemical Markers and Adenoma Predictors in Normocalcemic Primary Hyperparathyroidism: A Multicenter Retrospective Analysis","authors":"Berçem Ayçiçek, Mazhar Müslüm Tuna, Ismail Engin, Mustafa Şahin, Sayid Zuhur, Neşe Ersöz Gülçelik, Hüseyin Yağcı, Ersen Karakılıç, Evin Bozkur, Bekir Çakır, Elif Güneş, Süleyman Baldane, Özen Öz Gül, Gulhan Akbaba, Cevdet Duran, Faruk Kılınç, Güven Barış Cansu, Cüneyt Bilginer, Ramazan Sarı, Nurdan Gul, Ayten Oğuz, Bekir Uçan, Eren Gürkan, Murat Çalapkulu, Mehmet Güven, Arzu Or Koca, Sema Taban, Nergis Basmacı","doi":"10.1111/cen.70024","DOIUrl":"10.1111/cen.70024","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to evaluate the diagnostic performance of biochemical markers in normocalcemic primary hyperparathyroidism (nPHPT), analyse their temporal variations, and assess their correlation with adenoma localisation and size.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this multicenter retrospective study—the largest patient cohort reported in the literature to date (<i>n</i> = 474) we comprehensively profiled normocalcemic patients diagnosed with primary hyperparathyroidism nPHPT was diagnosed based on persistently elevated PTH levels with normal serum calcium after excluding secondary causes such as vitamin D deficiency, renal impairment, and other conditions. This retrospective multicenter study included a large cohort of patients whose biochemical markers—including serum calcium, phosphorus, magnesium, vitamin D, parathyroid hormone (PTH), and glomerular filtration rate (GFR)—were measured at three time points, using standardised laboratory protocols. Although in routine clinical practice these measurements are typically performed at regular intervals of 3−6 months, resulting in approximately three assessments during an 18-month follow-up period. Urinary calcium and creatinine levels were also determined, and imaging modalities (ultrasonography, sestamibi scintigraphy, and computed tomography) were employed for adenoma detection. Statistical analyses comprised repeated measures ANOVA, logistic regression, correlation analysis, and ROC analysis, performed using Jamovi software.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Serial evaluations revealed significant temporal changes in key biochemical parameters, including a significant decline in serum calcium and PTH levels alongside a significant increase in urinary calcium excretion. Logistic regression analysis identified higher PTH levels, higher corrected calcium, and larger adenoma size as independent predictors of adenoma localisation, while ROC analysis confirmed that PTH exhibited the highest diagnostic accuracy (AUC = 0.91, 95% CI: 0.84–0.95, <i>p</i> < 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The large scale of our patient cohort reinforces the robustness of our statistical analyses and provides comprehensive insight into the dynamic nature of nPHPT.</p>\u0000 \u0000 <p>Our findings demonstrate that, even in normocalcemic patients, higher PTH levels and relatively higher calcium levels within the normal range are important indicators of parathyroid adenoma. Integrating serial biochemical measurements with targeted imaging can facilitate earlier diagnosis, potentially preventing future com","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"103 6","pages":"805-814"},"PeriodicalIF":2.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945237","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}
<p>We read with great interest the recent article by Seo et al. [<span>1</span>], which presents a retrospective analysis of patients with low to high-risk differentiated thyroid carcinoma (DTC) who underwent thyroidectomy, with or without adjuvant or ablative radioiodine therapy, between 2010 and 2023. These patients subsequently underwent fine-needle aspiration cytology (FNAC) for ultrasound (US)-suspicious findings. The study categorised pre-FNAC serum thyroglobulin (Tg) and anti-Tg antibody (TgAb) levels into three groups: negative (Tg < 0.2 µg/L and negative TgAb), positive (Tg ≥ 0.2 µg/L and negative TgAb), and TgAb-positive. A total of 118 patients (146 FNACs) were included: 33 (23%) had negative Tg, 84 (57%) had positive Tg, and 29 (20%) were TgAb-positive. The positive predictive value (PPV) of neck US was 3%, 50%, and 52% in patients with negative Tg, positive Tg, and positive TgAb, respectively. A sub-analysis within the Tg-positive groups using different Tg thresholds revealed PPVs of 29%, 38%, and 58% for Tg concentrations of 0.2 µg/L, < 1.0 µg/L, and ≥ 1.0 µg/L, respectively. The authors concluded that neck US should be reserved for DTC patients with positive Tg (i.e., > 0.2 µg/L) and those with positive TgAb. While the data presented are consistent with previous studies, the observed PPV in patients with Tg levels between 0.2 and 1.0 µg/L appears significantly higher than that reported by Verburg et al. [<span>2</span>]. They evaluated 3176 cervical US exams performed in 773 patients between 1996 and 2012 and found an overall PPV of 23.8% (confidence interval 18.1%–29.5%), with no significant differences between low- and high-risk patients. Notably, no significant differences between patients with undetectable and low detectable (< 1 μg/L) Tg levels were found, contrasting with Seo et al.‘s findings. Several factors may account for these differences. Seo et al. systematically performed FNAC on suspicious findings, whereas Verburg et al. employed a composite outcome. Additionally, Verburg et al. included only patients who underwent radioiodine treatment, whereas Seo et al. also included patients who did not. These methodological differences may partially explain the observed discrepancies. In addition, methodological aspects regarding Tg measurement and interpretation criteria warrant consideration [<span>3</span>].</p><p>Firstly, Tg and TgAb immunoassays exhibit significant inter-assay variability, and different quantitative results are not directly comparable. Van Kinschot et al. tested serum Tg and TgAb in 793 samples derived from 413 patients with DTC using two platforms (Kryptor and Immulite 2000XPi) and found a mean Tg concentration 37.4% lower with the latter. Among 125 samples with positive TgAb in at least one assay, 68 (54.4%) showed discrepancies in TgAb status. Applying guideline-based cut-off values for Tg, 33 (4.7%) samples had a Tg concentration ≥ 1.0 μg/L with Immulite and < 1.0 μg/L with Kryptor. Nota
{"title":"Optimizing Thyroglobulin Interpretation to Reduce Ultrasound Examinations in the Follow-Up of Differentiated Thyroid Carcinoma","authors":"Luca Giovanella, Petra Petranović Ovčariček","doi":"10.1111/cen.70029","DOIUrl":"10.1111/cen.70029","url":null,"abstract":"<p>We read with great interest the recent article by Seo et al. [<span>1</span>], which presents a retrospective analysis of patients with low to high-risk differentiated thyroid carcinoma (DTC) who underwent thyroidectomy, with or without adjuvant or ablative radioiodine therapy, between 2010 and 2023. These patients subsequently underwent fine-needle aspiration cytology (FNAC) for ultrasound (US)-suspicious findings. The study categorised pre-FNAC serum thyroglobulin (Tg) and anti-Tg antibody (TgAb) levels into three groups: negative (Tg < 0.2 µg/L and negative TgAb), positive (Tg ≥ 0.2 µg/L and negative TgAb), and TgAb-positive. A total of 118 patients (146 FNACs) were included: 33 (23%) had negative Tg, 84 (57%) had positive Tg, and 29 (20%) were TgAb-positive. The positive predictive value (PPV) of neck US was 3%, 50%, and 52% in patients with negative Tg, positive Tg, and positive TgAb, respectively. A sub-analysis within the Tg-positive groups using different Tg thresholds revealed PPVs of 29%, 38%, and 58% for Tg concentrations of 0.2 µg/L, < 1.0 µg/L, and ≥ 1.0 µg/L, respectively. The authors concluded that neck US should be reserved for DTC patients with positive Tg (i.e., > 0.2 µg/L) and those with positive TgAb. While the data presented are consistent with previous studies, the observed PPV in patients with Tg levels between 0.2 and 1.0 µg/L appears significantly higher than that reported by Verburg et al. [<span>2</span>]. They evaluated 3176 cervical US exams performed in 773 patients between 1996 and 2012 and found an overall PPV of 23.8% (confidence interval 18.1%–29.5%), with no significant differences between low- and high-risk patients. Notably, no significant differences between patients with undetectable and low detectable (< 1 μg/L) Tg levels were found, contrasting with Seo et al.‘s findings. Several factors may account for these differences. Seo et al. systematically performed FNAC on suspicious findings, whereas Verburg et al. employed a composite outcome. Additionally, Verburg et al. included only patients who underwent radioiodine treatment, whereas Seo et al. also included patients who did not. These methodological differences may partially explain the observed discrepancies. In addition, methodological aspects regarding Tg measurement and interpretation criteria warrant consideration [<span>3</span>].</p><p>Firstly, Tg and TgAb immunoassays exhibit significant inter-assay variability, and different quantitative results are not directly comparable. Van Kinschot et al. tested serum Tg and TgAb in 793 samples derived from 413 patients with DTC using two platforms (Kryptor and Immulite 2000XPi) and found a mean Tg concentration 37.4% lower with the latter. Among 125 samples with positive TgAb in at least one assay, 68 (54.4%) showed discrepancies in TgAb status. Applying guideline-based cut-off values for Tg, 33 (4.7%) samples had a Tg concentration ≥ 1.0 μg/L with Immulite and < 1.0 μg/L with Kryptor. Nota","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"103 6","pages":"909-910"},"PeriodicalIF":2.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.70029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945229","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}
Alice Nervo, Giovanni Gruosso, Marta Marino, Enrica Migliore, Matteo Rubiolo, Elisa Vaccaro, Emanuela Arvat
Objective and Background
Early identification of adrenal insufficiency (AI) during immune-checkpoint inhibitors (ICIs) is crucial to prevent life-threatening consequences; however, the diagnosis is challenging.
Design, Patients and Measurement
In this prospective observational study, ICI-treated cancer patients with morning serum cortisol (SC) within the grey zone (83–414 nmol/L) were enroled. A low-dose adrenocorticotropic hormone (ACTH) stimulation test was performed to assess peak stimulated SC, preceded by re-evaluation of morning SC. The analysis aimed to refine morning SC cut-offs to minimize the diagnostic grey zone reducing the need for ACTH stimulation. To interpret the results of ACTH test, it was employed both the threshold for peak stimulated SC provided by the Endocrine Society guidelines (500 nmol/L) and an assay-specific cut-off for the Abbott platform recently proposed in literature (414 nmol/L). Moreover, the utility of salivary cortisol and cortisone upon awakening was explored.
Results
In 30 ICI-treated patients, a good positive correlation between morning and peak stimulated SC was confirmed (r = 0.72, p < 0.001); peak stimulated SC ≤ 500 nmol/L and ≤ 414 nmol/L was detected in 36.7% and 20% of subjects, respectively; all cases were secondary AI. ROC curve analysis identified optimal morning SC thresholds for AI prediction and exclusion (> 196 nmol/L and ≤ 397 nmol/L in case of pathological peak stimulated SC ≤ 500 nmol/L; > 163 nmol/L and ≤ 251 nmol/L in case of pathological peak stimulated SC ≤ 414 nmol/L). Salivary cortisol and cortisone upon awakening positively correlated with peak stimulated SC (r = 0.49 and r = 0.56, respectively, p < 0.01).
Conclusions
Morning SC is a reliable tool for the screening of ICI-related AI; the need for dynamic stimulation would be reduced by the application of assay-specific cut-offs. Salivary hormone analysis of cortisol and cortisone upon awakening may represent a viable alternative in selected cases.
{"title":"Adrenal Insufficiency During Treatment With Immune-Checkpoint Inhibitors: How to Simplify the Diagnostic Pathway?","authors":"Alice Nervo, Giovanni Gruosso, Marta Marino, Enrica Migliore, Matteo Rubiolo, Elisa Vaccaro, Emanuela Arvat","doi":"10.1111/cen.70023","DOIUrl":"10.1111/cen.70023","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective and Background</h3>\u0000 \u0000 <p>Early identification of adrenal insufficiency (AI) during immune-checkpoint inhibitors (ICIs) is crucial to prevent life-threatening consequences; however, the diagnosis is challenging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design, Patients and Measurement</h3>\u0000 \u0000 <p>In this prospective observational study, ICI-treated cancer patients with morning serum cortisol (SC) within the grey zone (83–414 nmol/L) were enroled. A low-dose adrenocorticotropic hormone (ACTH) stimulation test was performed to assess peak stimulated SC, preceded by re-evaluation of morning SC. The analysis aimed to refine morning SC cut-offs to minimize the diagnostic grey zone reducing the need for ACTH stimulation. To interpret the results of ACTH test, it was employed both the threshold for peak stimulated SC provided by the Endocrine Society guidelines (500 nmol/L) and an assay-specific cut-off for the Abbott platform recently proposed in literature (414 nmol/L). Moreover, the utility of salivary cortisol and cortisone upon awakening was explored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In 30 ICI-treated patients, a good positive correlation between morning and peak stimulated SC was confirmed (<i>r</i> = 0.72, <i>p</i> < 0.001); peak stimulated SC ≤ 500 nmol/L and ≤ 414 nmol/L was detected in 36.7% and 20% of subjects, respectively; all cases were secondary AI. ROC curve analysis identified optimal morning SC thresholds for AI prediction and exclusion (> 196 nmol/L and ≤ 397 nmol/L in case of pathological peak stimulated SC ≤ 500 nmol/L; > 163 nmol/L and ≤ 251 nmol/L in case of pathological peak stimulated SC ≤ 414 nmol/L). Salivary cortisol and cortisone upon awakening positively correlated with peak stimulated SC (<i>r</i> = 0.49 and <i>r</i> = 0.56, respectively, <i>p</i> < 0.01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Morning SC is a reliable tool for the screening of ICI-related AI; the need for dynamic stimulation would be reduced by the application of assay-specific cut-offs. Salivary hormone analysis of cortisol and cortisone upon awakening may represent a viable alternative in selected cases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"104 1","pages":"39-46"},"PeriodicalIF":2.4,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.70023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945197","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}
Iván Muñoz, Marlín Solórzano, Ignacio Fuentes, José Miguel González, Joel Falcón Acevedo, Catalina Ruiz Rademacher, Joaquín Viñambres Giavio, Rodolfo Cabello Torres, Pablo Montero Miranda, Hernán González Díaz, Antonieta Solar, Francisco Cruz Olivos, Lorena Mosso Gómez, Nicole Lustig Franco, José Miguel Domínguez
<div> <section> <h3> Introduction</h3> <p>Noninvasive follicular thyroid neoplasia with papillary-like nuclear characteristics (NIFTP) is characterised by an indolent behaviour and was defined in 2016 to avoid overtreatment in differentiated thyroid cancer (DTC).</p> </section> <section> <h3> Objectives</h3> <p>To report the clinicopathological characteristics and outcomes of patients with NIFTP treated at a Chilean centre between 2016 and 2023.</p> </section> <section> <h3> Design</h3> <p>Observational retrospective study.</p> </section> <section> <h3> Methods</h3> <p>Of 1103 patients with thyroid neoplasia treated with surgery, 104 (9.42%) had NIFTP. Clinicopathological variables were recorded, including ultrasound characteristics, fine-needle aspiration biopsy (FNAB) results, genetic testing when available, type of surgery, tumour size, and follow-up data.</p> </section> <section> <h3> Results</h3> <p>Of 104 patients, 85 (81.7%) were female, age of 44 ± 14.2 years and a median tumour size of 1.7 cm (range 0.1–7.1). Eighty-six (82.7%) had available preoperative staging ultrasound: 1 (1.2%), 39 (45.3%), 38 (44.2%), and 8 (9.3%) were ACR-TIRADS 2, 3, 4, and 5, respectively. Sixteen (15%) NIFTP were incidental, which were smaller than non-incidental NIFTP (median 0.4 cm (0.1–2.2) vs. 1.9 cm (0.6–7.1), <i>p</i> < 0.001). Of the 86 FNAB results available, 2 (2.3%), 10 (11.6%), 20 (23.3%), 24 (27.9%), and 30 (34.9%) were Bethesda I, II, III, IV, and V, respectively. Forty-three patients (41.3%) were treated with lobectomy, 58 (55.8%) with total thyroidectomy (TT), and only 3 (2.9%) with TT and lymph node dissection. In Bethesda II patients, surgery was indicated in cases of nodule growth, showing a larger tumour size than other Bethesda categories (3.0 ± 1.4 vs. 1.8 ± 1.02 cm, <i>p</i> = 0.015). ThyroidPrint® was performed in 12 patients with Bethesda III or IV, resulting suspicious in 11 (92%): of these, 8 (67%) underwent lobectomy. There were no significant differences between lobectomy and TT regarding sex, ACR-TIRADS, tumour size, or ThyroidPrint® results. Twelve (11.5%) were multifocal and 5 (4.8%) bilateral. Fifty-two patients (54%) were followed for ≥ 1 year using follow-up criteria and response to treatment for low-risk DTC recurrence. Thirty-four (65%) had excellent response, 15 (28.8%) indeterminate (13 (25%) by biochemical criteria and 2 (3.8%) by ultrasound), 3 (5.7%) incomplete biochemical (2 (3.8%) due to elevated Tg and 1 (1.9%) due to elevated anti-Tg antibodies), and none with incomplete structural response. There were no differences b
具有乳头状核特征的无创滤泡性甲状腺瘤（NIFTP）以惰性行为为特征，于2016年被定义为避免分化型甲状腺癌（DTC）的过度治疗。目的：报告2016年至2023年在智利某中心治疗的NIFTP患者的临床病理特征和结局。设计：观察性回顾性研究。方法：1103例手术治疗的甲状腺肿瘤患者中，104例（9.42%）有NIFTP。记录临床病理变量，包括超声特征、细针穿刺活检（FNAB）结果、可用的基因检测、手术类型、肿瘤大小和随访数据。结果：104例患者中，85例（81.7%）为女性，年龄44±14.2岁，中位肿瘤大小为1.7 cm（范围0.1-7.1）。术前超声分期86例（82.7%）：ACR-TIRADS 2、3、4、5分别为1例（1.2%）、39例（45.3%）、38例（44.2%）、8例（9.3%）。16例（15%）NIFTP为偶发性，小于非偶发性NIFTP(中位0.4 cm (0.1-2.2) vs. 1.9 cm (0.6-7.1)， p结论：本组患者NIFTP表现为无痛行为，预后良好。超声检查，90%表现为ACR-TIRADS 3或4，不到10%表现为ACR-TIRADS 5。对于FNAB，近一半不确定，三分之一为Bethesda V型，没有Bethesda VI型。肺叶切除术与TT的临床结果无显著差异。
{"title":"Noninvasive Follicular Thyroid Neoplasia With Papillary-Like Nuclear Characteristics (NIFTP): Clinico-Pathological Analysis in a Chilean Centre","authors":"Iván Muñoz, Marlín Solórzano, Ignacio Fuentes, José Miguel González, Joel Falcón Acevedo, Catalina Ruiz Rademacher, Joaquín Viñambres Giavio, Rodolfo Cabello Torres, Pablo Montero Miranda, Hernán González Díaz, Antonieta Solar, Francisco Cruz Olivos, Lorena Mosso Gómez, Nicole Lustig Franco, José Miguel Domínguez","doi":"10.1111/cen.70026","DOIUrl":"10.1111/cen.70026","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Noninvasive follicular thyroid neoplasia with papillary-like nuclear characteristics (NIFTP) is characterised by an indolent behaviour and was defined in 2016 to avoid overtreatment in differentiated thyroid cancer (DTC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To report the clinicopathological characteristics and outcomes of patients with NIFTP treated at a Chilean centre between 2016 and 2023.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design</h3>\u0000 \u0000 <p>Observational retrospective study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Of 1103 patients with thyroid neoplasia treated with surgery, 104 (9.42%) had NIFTP. Clinicopathological variables were recorded, including ultrasound characteristics, fine-needle aspiration biopsy (FNAB) results, genetic testing when available, type of surgery, tumour size, and follow-up data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 104 patients, 85 (81.7%) were female, age of 44 ± 14.2 years and a median tumour size of 1.7 cm (range 0.1–7.1). Eighty-six (82.7%) had available preoperative staging ultrasound: 1 (1.2%), 39 (45.3%), 38 (44.2%), and 8 (9.3%) were ACR-TIRADS 2, 3, 4, and 5, respectively. Sixteen (15%) NIFTP were incidental, which were smaller than non-incidental NIFTP (median 0.4 cm (0.1–2.2) vs. 1.9 cm (0.6–7.1), <i>p</i> < 0.001). Of the 86 FNAB results available, 2 (2.3%), 10 (11.6%), 20 (23.3%), 24 (27.9%), and 30 (34.9%) were Bethesda I, II, III, IV, and V, respectively. Forty-three patients (41.3%) were treated with lobectomy, 58 (55.8%) with total thyroidectomy (TT), and only 3 (2.9%) with TT and lymph node dissection. In Bethesda II patients, surgery was indicated in cases of nodule growth, showing a larger tumour size than other Bethesda categories (3.0 ± 1.4 vs. 1.8 ± 1.02 cm, <i>p</i> = 0.015). ThyroidPrint® was performed in 12 patients with Bethesda III or IV, resulting suspicious in 11 (92%): of these, 8 (67%) underwent lobectomy. There were no significant differences between lobectomy and TT regarding sex, ACR-TIRADS, tumour size, or ThyroidPrint® results. Twelve (11.5%) were multifocal and 5 (4.8%) bilateral. Fifty-two patients (54%) were followed for ≥ 1 year using follow-up criteria and response to treatment for low-risk DTC recurrence. Thirty-four (65%) had excellent response, 15 (28.8%) indeterminate (13 (25%) by biochemical criteria and 2 (3.8%) by ultrasound), 3 (5.7%) incomplete biochemical (2 (3.8%) due to elevated Tg and 1 (1.9%) due to elevated anti-Tg antibodies), and none with incomplete structural response. There were no differences b","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"103 6","pages":"888-894"},"PeriodicalIF":2.4,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945270","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}
Kristin Potthoff, Tamara Prodanov, Lara M. Knigge, Angela Hübner, Stefan Bornstein, Jacques Lenders, Karel Pacak, Graeme Eisenhofer, Christina Pamporaki
Introduction
Currently, it is unclear whether plasma free or 24-h urinary fractionated metanephrines are preferable for diagnosis of phaeochromocytoma/paraganglioma (PPGL) in children.
Objectives
To investigate whether measurements of plasma free and 24-h urinary fractionated metanephrines are reliable tests for screening for PPGL in children.
Methods
This retrospective study included a cohort of 138 paediatric patients (5 to 18 years), 64 with and 74 without PPGL. Data included sex, age, plasma concentrations of free metanephrines, and genetic test results. For a subset of 89 children tested for PPGL, concentrations of 24-h urinary fractionated metanephrines were also available. For patients with PPGL, data also included tumour location, size, catecholamine tumour phenotype, and presence of recurrent and/or metastatic disease.
Results
Among children with PPGL, results of plasma metanephrines showed larger fold increases of normetanephrine above the upper cut-off compared to the urinary metabolites (9.5-fold vs 7.1-fold, p < 0.001). Plasma metanephrines showed a diagnostic sensitivity of 92% and specificity of 96%, whereas for urinary metanephrines sensitivity and specificity of 92% and 91% respectively. Sub-analysis of intra-individual temporal measurements of metabolites showed that subsequent increases of plasma normetanephrine may be associated with early-stage development of a noradrenergic PPGL.
Conclusions
Plasma free and 24-h urinary fractionated metanephrines are both reliable screening tests for PPGL in children and adolescents. The plasma panel may be useful for early detection of noradrenergic PPGL relevant for children tested within surveillance programs due to hereditary risk of noradrenergic tumours.
{"title":"Biochemical Diagnosis of Phaeochromocytoma and Paraganglioma in Children and Adolescents: A Retrospective Cohort Study","authors":"Kristin Potthoff, Tamara Prodanov, Lara M. Knigge, Angela Hübner, Stefan Bornstein, Jacques Lenders, Karel Pacak, Graeme Eisenhofer, Christina Pamporaki","doi":"10.1111/cen.70025","DOIUrl":"10.1111/cen.70025","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Currently, it is unclear whether plasma free or 24-h urinary fractionated metanephrines are preferable for diagnosis of phaeochromocytoma/paraganglioma (PPGL) in children.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To investigate whether measurements of plasma free and 24-h urinary fractionated metanephrines are reliable tests for screening for PPGL in children.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study included a cohort of 138 paediatric patients (5 to 18 years), 64 with and 74 without PPGL. Data included sex, age, plasma concentrations of free metanephrines, and genetic test results. For a subset of 89 children tested for PPGL, concentrations of 24-h urinary fractionated metanephrines were also available. For patients with PPGL, data also included tumour location, size, catecholamine tumour phenotype, and presence of recurrent and/or metastatic disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among children with PPGL, results of plasma metanephrines showed larger fold increases of normetanephrine above the upper cut-off compared to the urinary metabolites (9.5-fold vs 7.1-fold, <i>p</i> < 0.001). Plasma metanephrines showed a diagnostic sensitivity of 92% and specificity of 96%, whereas for urinary metanephrines sensitivity and specificity of 92% and 91% respectively. Sub-analysis of intra-individual temporal measurements of metabolites showed that subsequent increases of plasma normetanephrine may be associated with early-stage development of a noradrenergic PPGL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Plasma free and 24-h urinary fractionated metanephrines are both reliable screening tests for PPGL in children and adolescents. The plasma panel may be useful for early detection of noradrenergic PPGL relevant for children tested within surveillance programs due to hereditary risk of noradrenergic tumours.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"103 6","pages":"787-794"},"PeriodicalIF":2.4,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.70025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945227","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}
Michael Stedman, Peter Taylor, Ian Halsall, David Halsall, Buchi Okosieme, Suhani Bahl, Lakdasa Premawardhana, Colin Dayan, Anthony A. Fryer, Adrian Heald
<p>There continues to be much discussion around optimization of thyroid hormone status in hypothyroid individuals. The ideal therapeutic goal in hypothyroidism would be to restore clinical and biochemical euthyroidism via physiologic thyroid hormone replacement. The relation between circulating thyroid hormone levels (FreeT4 [fT4] and FreeT3) and thyroid stimulating hormone (TSH) is integral to this. This concept may seem straightforward, but there are subtleties that have only recently been recognized [<span>1</span>].</p><p>Over 10 million thyroid function tests (TFT) are undertaken in England annually. To reduce test numbers, laboratories very often measure TSH and then only reflex measure fT4 if TSH results fall outside the reference range (RR) [<span>2</span>].</p><p>We analysed the relation between fT4 and TSH results for patients both on and off thyroid medication using a city-wide population database.</p><p>Simultaneous TSH and fT4 results from 47,869 diagnosed hypothyroid individuals (including information on dose) and 393,101 untreated/euthyroid individuals who had been tested once or twice were included. Data were extracted from the Greater Manchester Care Record (GMCR) [<span>3</span>].</p><p>The data used in the analyses presented was obtained with the permission of the Greater Manchester Care Record Board (reference number R 2023 065) and was fully anonymised before being made available to the investigators.</p><p>Diagnostic data were validated and cleaned before analysis. Only patients with a coded diagnosis of primary hypothyroidism were included.</p><p>Our findings showed:</p><p><b><i>Untreated individuals</i></b> (Table 1)</p><p>Of the 452,463 results in the untreated/euthyroid population (<i>n</i> = 393,101 people), 89.9% (406,700) were within the TSH-RR and 99.1% (448,171) were within the fT4-RR.</p><p>Of those 406,700 with a TSH within the RR, 3319 (0.82%) had a fT4 < 9 and 175 (0.043%) had a fT4 > 25. These account for 83.1% of all results with a fT4 < 9 and 58.3% of all those with a fT4 > 25.</p><p><b>Both these groups might not receive a reflex fT4 result if REFLEX testing were applied.</b></p><p><b><i>Treated individuals</i></b> (Table 1)</p><p>Of 407,075 results in the treated population (<i>n</i> = 47,869 people), 176,833 (43.4%) were in TSH-RR.</p><p>Of those 176,833 with a TSH within the RR, 1368 (0.77%) had a fT4 < 9 and 3065 (1.73%) had a fT4 > 25. These account for 15.1% of all results with a fT4 < 9 and 21.7% of all those with a fT4 > 25.</p><p><b>Both these groups might not receive a reflex fT4 result if REFLEX testing was applied.</b></p><p>These effects were more prevalent in people taking a higher dose of levothyroxine.</p><p>When only those with normal TSH results were considered, we found that in the untreated cohort, 0.043% had an FT4 > 25 pmol/L. However, within the population being treated with levothyroxine, this was 1.73%, showing that the relative risk of high FT4 in treated
{"title":"Evaluation of Thyroid Hormone Status: Are Simultaneous TSH and FT4 Tests Necessary? Analysis of Thyroid Function Test Results Taken From the Greater Manchester Care Record 2010–2023","authors":"Michael Stedman, Peter Taylor, Ian Halsall, David Halsall, Buchi Okosieme, Suhani Bahl, Lakdasa Premawardhana, Colin Dayan, Anthony A. Fryer, Adrian Heald","doi":"10.1111/cen.70012","DOIUrl":"10.1111/cen.70012","url":null,"abstract":"<p>There continues to be much discussion around optimization of thyroid hormone status in hypothyroid individuals. The ideal therapeutic goal in hypothyroidism would be to restore clinical and biochemical euthyroidism via physiologic thyroid hormone replacement. The relation between circulating thyroid hormone levels (FreeT4 [fT4] and FreeT3) and thyroid stimulating hormone (TSH) is integral to this. This concept may seem straightforward, but there are subtleties that have only recently been recognized [<span>1</span>].</p><p>Over 10 million thyroid function tests (TFT) are undertaken in England annually. To reduce test numbers, laboratories very often measure TSH and then only reflex measure fT4 if TSH results fall outside the reference range (RR) [<span>2</span>].</p><p>We analysed the relation between fT4 and TSH results for patients both on and off thyroid medication using a city-wide population database.</p><p>Simultaneous TSH and fT4 results from 47,869 diagnosed hypothyroid individuals (including information on dose) and 393,101 untreated/euthyroid individuals who had been tested once or twice were included. Data were extracted from the Greater Manchester Care Record (GMCR) [<span>3</span>].</p><p>The data used in the analyses presented was obtained with the permission of the Greater Manchester Care Record Board (reference number R 2023 065) and was fully anonymised before being made available to the investigators.</p><p>Diagnostic data were validated and cleaned before analysis. Only patients with a coded diagnosis of primary hypothyroidism were included.</p><p>Our findings showed:</p><p><b><i>Untreated individuals</i></b> (Table 1)</p><p>Of the 452,463 results in the untreated/euthyroid population (<i>n</i> = 393,101 people), 89.9% (406,700) were within the TSH-RR and 99.1% (448,171) were within the fT4-RR.</p><p>Of those 406,700 with a TSH within the RR, 3319 (0.82%) had a fT4 < 9 and 175 (0.043%) had a fT4 > 25. These account for 83.1% of all results with a fT4 < 9 and 58.3% of all those with a fT4 > 25.</p><p><b>Both these groups might not receive a reflex fT4 result if REFLEX testing were applied.</b></p><p><b><i>Treated individuals</i></b> (Table 1)</p><p>Of 407,075 results in the treated population (<i>n</i> = 47,869 people), 176,833 (43.4%) were in TSH-RR.</p><p>Of those 176,833 with a TSH within the RR, 1368 (0.77%) had a fT4 < 9 and 3065 (1.73%) had a fT4 > 25. These account for 15.1% of all results with a fT4 < 9 and 21.7% of all those with a fT4 > 25.</p><p><b>Both these groups might not receive a reflex fT4 result if REFLEX testing was applied.</b></p><p>These effects were more prevalent in people taking a higher dose of levothyroxine.</p><p>When only those with normal TSH results were considered, we found that in the untreated cohort, 0.043% had an FT4 > 25 pmol/L. However, within the population being treated with levothyroxine, this was 1.73%, showing that the relative risk of high FT4 in treated ","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"103 6","pages":"906-908"},"PeriodicalIF":2.4,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871718","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}
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