Clinical Endocrinology最新文献

{"title":"Supraphysiological Glucocorticoid Doses and Pitfalls of Annual Biomarker Monitoring in Adults With CAH","authors":"Jakob Bolinder, Oskar Ragnarsson, Gudmundur Johansson","doi":"10.1111/cen.70172","DOIUrl":"10.1111/cen.70172","url":null,"abstract":"<p>Management of congenital adrenal hyperplasia (CAH) remains a balancing act between androgen excess and glucocorticoid overexposure. We performed a retrospective review of 58 adults with 21-hydroxylase deficiency (21-OHD) followed at the Department of Endocrinology at the Sahlgrenska University Hospital during the period 2020–2024. While the limited study size and retrospective design warrant cautious interpretation, the findings nonetheless point to important challenges in current practice.</p><p>The cohort included all forms of confirmed 21-OHD (<i>n</i> = 58), predominantly classic CAH (salt-wasting and simple virilizing; <i>n</i> = 50). Half of the patients (<i>n</i> = 29) used daily doses above 13 mg/m<sup>2</sup>/day, approximating the midpoint of the recommended dosing range in pediatric care (10–15 mg/m<sup>2</sup>/day). Furthermore, a total of 11 patients followed a reverse-circadian regimen, most commonly with prednisolone at bedtime (<i>n</i> = 9) (Table 1). Treatment was individualized; the number of daily doses was influenced by glucocorticoid type, phenotype, and patient preferences, with long-standing stable regimens sometimes maintained in the absence of clear adverse effects or unsatisfactory response to treatment changes. Although sick day rules and emergency care are addressed with patients, parenteral hydrocortisone rescue treatment was prescribed in only 27.6% overall and 36.4% of patients with salt-wasting CAH, representing an important area for improvement.</p><p>In addition to controlling clinical hyperandrogenism in women and supporting fertility in both men and women, a central aim in the long-term follow-up of patients with CAH has been to reduce supraphysiological doses and to avoid non-physiological regimens such as reverse-circadian dosing. This is motivated by previous reports linking glucocorticoid overexposure in adults with CAH to obesity, hypertension, insulin resistance, and reduced bone mineral density [<span>2</span>], and by studies suggesting that evening cortisol elevations exert more detrimental metabolic effects than morning elevations [<span>1</span>].</p><p>Blood samples were mostly collected in the morning before each out-patient visit without any instructions related to last glucocorticoid dose. Mean 17-hydroxyprogesterone (17-OHP) levels exceeded reference values in the majority of patients (<i>n</i> = 49). Testosterone in women, particularly in the presence of hirsutism or fertility concerns, and androstenedione in men may offer greater clinical utility [<span>3</span>]. These concentrations were frequently outside the reference intervals, as illustrated in Figure 1. Importantly, however, normalization of these biomarkers should not be the therapeutic goal in most patients, as they may instead lead to glucocorticoid excess and overtreatment [<span>3</span>]. Nevertheless, the same patient frequently presented with values both above and below the reference range at different time points, often in ","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"105 3","pages":"360-362"},"PeriodicalIF":2.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.70172","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270573","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":"Lupus‑Associated Hypophysitis: A Narrative Systematic Review of Clinical, Radiological and Endocrine Features.","authors":"Abdellatif Zhalka, Shadi Shinnawi, Rami Jabareen, Awad Karem, Muhammad Zahlaka","doi":"10.1111/cen.70197","DOIUrl":"https://doi.org/10.1111/cen.70197","url":null,"abstract":"<p><strong>Background: </strong>Lupus-associated hypophysitis is a rare but clinically important manifestation of systemic lupus erythematosus (SLE), characterised by heterogeneous pituitary dysfunction and inflammatory sellar changes that may mimic other pituitary disorders. Evidence is limited to isolated reports. We aimed to summarise clinical, radiological, endocrine features, management, and outcomes.</p><p><strong>Methods: </strong>A narrative systematic review of MEDLINE, Embase, Web of Science, and Google Scholar to 10 November 2025. Reports were included if accepted SLE criteria were met and hypophysitis or hypothalamic-pituitary inflammation was attributed to SLE after exclusion of alternative sellar pathology. Demographic, clinical, endocrine, imaging, treatment, and outcome data were synthesised descriptively.</p><p><strong>Results: </strong>Eleven cases (63% female; median age 23 years) were identified, most presenting at or near SLE diagnosis. Common symptoms included polyuria/polydipsia, fatigue, amenorrhoea, and headache. Arginine vasopressin deficiency (AVP-D) frequently coexisted with multi-axis anterior hypopituitarism. MRI typically demonstrated pituitary stalk thickening, gland enlargement, and loss of the posterior pituitary bright spot. High-dose glucocorticoids, with or without additional immunosuppression, led to improvement in most cases, although persistent adrenal and gonadal deficits were common; one patient died from severe hyponatraemia.</p><p><strong>Conclusions: </strong>Lupus-associated hypophysitis is a rare manifestation of SLE with heterogeneous endocrine and radiological presentations that may create diagnostic challenges. Early endocrine evaluation and pituitary imaging are important in patients with suspected hypothalamic-pituitary involvement.</p>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668670","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":"Ethnicity, TSH-Receptor Antibody (TRAb) and Thyrotoxicosis Severity Are Determinants of Neutrophil Count in Newly Diagnosed Hyperthyroidism","authors":"Aman Kaur More,&nbsp;Rokaiba Afrin,&nbsp;Rachel L. Griffiths,&nbsp;Clare Ford,&nbsp;Harit Buch,&nbsp;Tejas Kalaria","doi":"10.1111/cen.70151","DOIUrl":"10.1111/cen.70151","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>A retrospective cross-sectional analysis with an ethnicity-matched control cohort examining the relationship between free thyroxine (FT4), thyroid-stimulating hormone receptor antibody (TRAb) and absolute neutrophil count (ANC) in newly diagnosed hyperthyroidism, and assessing the influence of ethnicity on ANC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Adults with newly diagnosed hyperthyroidism between August 2020 to July 2025 and concurrently available FT4, TRAb and ANC were included. Graves' disease (GD) was defined by Roche Elecsys TRAb ≥ 1.75 IU/L. An ANCOVA tested main effects of TRAb and FT4 on ANC and their interaction. ANC was compared between GD and non-GD hyperthyroidism and with euthyroid controls, stratified by Asian, Black and White ethnicities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 237 individuals (152 GD, 85 non-GD), median [Q1–Q3] ANC was lower in GD (3.44 [2.67–4.64] × 10⁹/L) than non-GD (3.71 [2.92–5.12] × 10⁹/L; <i>p</i> = 0.045), and 9.9% and 3.5%, respectively, had low ANC &lt; 2.0 × 10⁹/L. There was a significant TRAb and FT4 interaction for ANC (<i>p</i> &lt; 0.001) with higher FT4 associated with lower ANC in patients with high TRAb, but not in TRAb-negative patients. In hyperthyroidism and controls, Black ethnicities had lower ANC and higher prevalence of low ANC compared to Asian or White ethnicities. In GD with a low ANC at diagnosis, ANC increased on average 1.14 × 10⁹ (95% CI 0.50–1.77 × 10⁹, <i>p</i> = 0.002) upon achieving euthyroidism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Graves' hyperthyroidism is associated with ANC decrease that is greatest when substantially high TRAb and FT4 coexist. ANC is further influenced by ethnicity. Mild neutropenia, particularly in ethnicities predisposed to benign ethnic neutropenia, should not delay antithyroid treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"105 3","pages":"339-349"},"PeriodicalIF":2.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764357","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":"Repeated Measurements of Vitamin D: Common and Very Unlikely to Indicate Deficiency","authors":"Mark J. Bolland,&nbsp;Cam Kyle,&nbsp;Andrew Grey","doi":"10.1111/cen.70145","DOIUrl":"10.1111/cen.70145","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Vitamin D testing uses considerable resources and has increased recently. We investigated repeating testing in Auckland, New Zealand.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design, Measurement and Patients</h3>\u0000 \u0000 <p>We analysed repeated 25-hydroxyvitamin D (25OHD) tests in three databases from the Auckland region from 2005 to 2024 (362,618 tests). We assessed annual numbers, time between tests, characteristics associated with repeat tests, and relationships between requestors and repeated tests.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-four percent of individuals had ≥ 2 25OHD tests. 34% of all 25OHD tests were repeats. A disproportionately high number of repeat tests were done in a small number of individuals: 57% had one repeated test (i.e., two tests total) but 5.3% had ≥ 6 and 1.4% had ≥ 11 repeated tests. Fifty eight percentage of repeat tests were done within 1 y and 77% within 2 y. 85% of people with repeated tests had a first 25OHD &gt; 25 nmol/L, but in only 9.8% a repeated 25OHD was ≤ 25 nmol/L. Most repeat tests (77%) when the first 25OHD was &gt; 75 nmol/L were &gt; 75 nmol/L A small number of high-volume requestors ordered most tests: 3/7637 ordered &gt; 5000 tests, collectively 7% (21,092) of the total, and 98 ordered &gt; 500 tests (collectively 44%). The most frequent requestors were primary care doctors and bariatric surgeons. Simple restrictions based on the result and time since previous 25OHD could reduce repeated tests by &gt; 60%–90% with only 4%–5% of 'avoided' tests ≤ 25 nmol/L.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Repeated vitamin D testing is common, and most results are not low. Restricting test availability and targeting those at risk of clinical complications of vitamin D deficiency are likely to reduce unnecessary tests.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"105 3","pages":"298-306"},"PeriodicalIF":2.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687375","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":"A Simplified Method for Assessing Bone Age in Adolescents","authors":"Yehuda Limony,&nbsp;Alon Haim,&nbsp;Michael Friger,&nbsp;Emad Alamour,&nbsp;Eyal Kristal,&nbsp;Eli Hershkovitz","doi":"10.1111/cen.70160","DOIUrl":"10.1111/cen.70160","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To develop and evaluate a simplified method for skeletal age assessment in adolescents as a rapid alternative to the Greulich–Pyle (GP) method.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design</h3>\u0000 \u0000 <p>Retrospective methodological study comparing the simplified method with the GP atlas, with duplicate readings by experienced and inexperienced raters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients</h3>\u0000 \u0000 <p>One hundred and seventeen hand and wrist radiographs (67 boys, 50 girls) from adolescents referred for short stature but otherwise healthy. Radiographs with GP-assessed bone age ≥ 9 years in girls and ≥ 11 years in boys were included.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Measurements</h3>\u0000 \u0000 <p>Bone age was scored independently using GP and simplified methods in two rounds by two paediatric endocrinologists and, for the simplified method, two residents. Outcomes included measures of agreement between methods, the proportion of readings within ±1 year of GP, and inter- and intra-rater reliability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among experienced raters, the simplified method showed minimal bias relative to GP, with about 91% of readings within ±1 year. Reliability coefficients for both methods exceeded 0.9. Repeatability of the simplified method was slightly lower than GP but remained within clinically acceptable limits and close to predefined acceptability thresholds for inexperienced raters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The simplified method offers a transparent, standardised, and reproducible approach to adolescent skeletal age assessment. Although not intended to replace the GP method, it is particularly suited to research involving large datasets or resource-limited environments and to population-level skeletal analyses. In busy clinics, it may also serve as a quick check of radiologists' GP-based interpretations, allowing review of reported bone ages without repeating a full atlas assessment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"105 3","pages":"314-321"},"PeriodicalIF":2.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.70160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147948076","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":"Early Transient Hypothyroidism Is Associated With Long-Term Outcomes of 131I Treatment in Graves' Disease: A Retrospective Cohort Study","authors":"Pei Yin,&nbsp;Jiangmeng Wu,&nbsp;Huayi Zhao,&nbsp;Lei Jiang,&nbsp;Yanchao Lu,&nbsp;Dan Liu,&nbsp;Yan Zhang,&nbsp;Yong Wang","doi":"10.1111/cen.70153","DOIUrl":"10.1111/cen.70153","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Radioactive iodine (&lt;sup&gt;131&lt;/sup&gt;I) is a cornerstone therapy for Graves' disease (GD), yet predicting long-term thyroid functional outcomes remains challenging. Early transient hypothyroidism (ETH) is a common phenomenon post-therapy, but its prognostic value for differentiating between permanent hypothyroidism and persistent hyperthyroidism is not fully elucidated.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This retrospective cohort study included 222 GD patients treated with &lt;sup&gt;131&lt;/sup&gt;I. Patients were categorized based on thyroid function within the first 6 months: the ETH group (occurrence of transient hypothyroidism, &lt;i&gt;n&lt;/i&gt; = 59) and the Non-ETH group (&lt;i&gt;n&lt;/i&gt; = 163). ETH was defined as TSH &gt; 4.2 mIU/L with or without low FT4 on at least one measurement, with temporary levothyroxine support provided if symptomatic. Detailed baseline characteristics, including calculated dose per gram of thyroid tissue (mCi/g), were analyzed. The primary endpoints were permanent hypothyroidism, euthyroidism, or persistent/recurrent hyperthyroidism. Kaplan-Meier survival analysis and multinomial logistic regression models were employed to identify independent predictors of long-term outcomes.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Baseline analysis revealed that the ETH group had significantly higher pretreatment TRAb levels (median 19.30 vs. 14.35 IU/L, &lt;i&gt;p&lt;/i&gt; = 0.021) and a higher prevalence of palpitations (84.7% vs. 64.4%, &lt;i&gt;p&lt;/i&gt; = 0.004) compared to the Non-ETH group. Importantly, the ETH group had a significantly higher rate of developing permanent hypothyroidism (52.5% vs. 20.9%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), whereas the Non-ETH group was prone to persistent hyperthyroidism (55.8% vs. 28.8%). In multinomial logistic regression adjusted for dose intensity (mCi/g), Non-ETH status was a strong independent predictor for persistent hyperthyroidism (OR = 3.888, 95% CI: 1.435–10.535, &lt;i&gt;p&lt;/i&gt; = 0.008) relative to permanent hypothyroidism. Furthermore, higher dose intensity (mCi/g) was universally associated with permanent hypothyroidism, while older age favored euthyroidism outcomes (OR = 1.055, &lt;i&gt;p&lt;/i&gt; = 0.002).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Early transient hypothyroidism following &lt;sup&gt;131&lt;/sup&gt;I therapy serves as a clinical indicator associated with effective glandular destruction and a high trajectory toward permanent hypothyroidism. Conversely, the absence of ETH signals a high risk of treatment failure. These findings suggest that patients with ETH require careful long-term monitoring for hypothyroidism rather than aggressive anti-thyroid drug re-initiation, and t","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"105 3","pages":"350-357"},"PeriodicalIF":2.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834511","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":"Growth Hormone Treatment Response and Machine Learning-Based Prediction in Idiopathic GHD and ISS: Analysis of the Korean LG Growth Study","authors":"Jisun Park,&nbsp;Eun Young Joo,&nbsp;Su Jin Kim,&nbsp;Myung Ji Yoo,&nbsp;Ji Eun Lee","doi":"10.1111/cen.70163","DOIUrl":"10.1111/cen.70163","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Individual responses to recombinant human growth hormone (rhGH) therapy vary widely among children with idiopathic growth hormone deficiency (iGHD) and idiopathic short stature (ISS), making accurate prediction of treatment outcomes clinically important. This study aimed to develop and compare machine learning (ML)-based and conventional statistical models to predict short-term growth response and mid-parental height (MPH) attainment following rhGH therapy in iGHD and ISS patients.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Design&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Retrospective observational cohort study using a nationwide, real-world registry.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Patients&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A total of 2215 children (1877 with iGHD and 338 with ISS) treated with rhGH were identified from the Korean LG Growth Study database. All included patients had at least 1 year of follow-up with available clinical data.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Measurements&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Primary outcomes were 1- and 2-year changes in height SDS (ΔHSDS) and achievement of MPH SDS. Predictive models included multiple linear regression, logistic regression, Random Forest, eXtreme Gradient Boosting, and Elastic Net. Model performance was evaluated using &lt;i&gt;R&lt;/i&gt;², error metrics and area under the receiver operating characteristic curve. Model interpretability was assessed using SHAP values.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In the iGHD group, ensemble ML models modestly outperformed linear regression for predicting 1-year ΔHSDS (&lt;i&gt;R&lt;/i&gt;² ≈ 0.19 vs. 0.16), but predictive performance declined at 2 years across all models. Prediction of MPH attainment showed high specificity but very low sensitivity at 1 year, with no clear advantage of ML over logistic regression. In ISS patients, all models demonstrated poor predictive performance for both ΔHSDS and MPH attainment, reflecting substantial clinical heterogeneity.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;ML approaches provided limited but clinically meaningful improvements in predicting short-term growth response in iGHD, while offering no clear benefit in ISS. These findings highlight both the potential and limitations of ML models based solely on routine clinical variables and underscore the need for integrating multimodal data to improve growth prediction, particularly in heterogeneous ISS populations.&lt;/p&gt;\u0000 ","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"105 3","pages":"322-330"},"PeriodicalIF":2.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.70163","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962428","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":"Regarding Non-Classical Presentations of Rare Hereditary Hypoparathyroidism: A Case Series of CASR, GNA11, and GATA3 Mutations in Parathyroidology","authors":"Ilker Sengul,&nbsp;Demet Sengul","doi":"10.1111/cen.70170","DOIUrl":"10.1111/cen.70170","url":null,"abstract":"<div>\u0000 \u0000 <p>This correspondence critically evaluates the diagnostic and therapeutic paradigms presented by Ekaterina Bibik et al. in their analysis of rare hereditary hypoparathyroidism involving <i>CASR</i>, <i>GNA11</i>, and <i>GATA3</i> mutations. While the case series provides valuable genomic data, the reported decade-long diagnostic delays—particularly the misidentification of mineral disorders as primary epilepsy—unmask a profound systemic failure in clinical vigilance regarding neuroimaging findings like Fahr syndrome. We emphasize that current “conventional” management, characterized by aggressive calcium and vitamin D supplementation, constitutes a precarious pharmacological tightrope that risks irreversible iatrogenic organ injury, as evidenced by the acute renal failure reported in Case 3. The necessity for early molecular screening is underscored not merely for academic classification but as an essential conduit to physiological homeostasis through emerging PTH analogs. Ultimately, we kindly argue for a transition from reactive symptom suppression to a precision-medicine framework that mitigates the long-term systemic sequelae of these rare endocrinopathies.</p></div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"105 3","pages":"358-359"},"PeriodicalIF":2.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148216679","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":"Diagnostic Options in Graves' or Non-Graves' Thyrotoxicosis: A Review for Clinical Practice.","authors":"Lorenzo Scappaticcio, Pierpaolo Trimboli, Paola Caruso, Chiara Porcellini, Daniela Forestiere, Maria Ida Maiorino, Katherine Esposito, Giuseppe Bellastella","doi":"10.1111/cen.70192","DOIUrl":"10.1111/cen.70192","url":null,"abstract":"<p><strong>Objective: </strong>Distinguishing Graves' disease (GD) from the other causes of thyrotoxicosis is essential for appropriate management. The clinical phenotype of GD has evolved over time and is currently more heterogenous and milder than in the past. Consequently, the differential diagnosis of thyrotoxicosis is often challenging. We aim to provide clinicians with a practical guide to achieve a more reliable etiological diagnosis of thyrotoxicosis.</p><p><strong>Methods: </strong>We reviewed international guidelines and the main papers indexed in PubMed from inception to March 1, 2026, on the diagnosis of thyrotoxicosis.</p><p><strong>Results: </strong>Three major diagnostic tools are currently available: thyroid scintigraphy, thyrotropin receptor antibodies (TRAbs), and thyroid ultrasonography (US). The diagnostic accuracy of scintigraphy is approximately 96%. However, GD may also present with non-uniform or normal uptake in 5-12% of cases. The diagnostic accuracy of TRAbs is approximately 95%. Nevertheless, TRAbs have limited utility in three specific settings: TRAb-negative GD, TRAb positivity in non-GD patients, and type 1 amiodarone-induced thyrotoxicosis (AIT). Thyroid US is the third most accurate diagnostic tool, with an accuracy of approximately 77%. Minor diagnostic tools include: T3/T4 and fT3/fT4 ratios; fT3/TSH and fT4/TSH ratios; serum diiodotyrosine; blood cell line ratios; and selected extrathyroidal manifestations of GD, such as neutropenia, abnormal liver function tests, and thymic hyperplasia.</p><p><strong>Conclusions: </strong>One or more major diagnostic tools may be used to establish the final etiological diagnosis of thyrotoxicosis, depending on test availability, turnaround time, and clinician expertise. Minor diagnostic tools may provide additional diagnostic information in selected or equivocal cases.</p>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629702","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":"Predictors of Malignancy and False-Negative Risk in Large (≥ 3 cm) Thyroid Nodules: Insights From a Single-Centre Thyroidectomy Cohort.","authors":"Ömer Komaç, Elif Bilgili, Merve Yetişken, Deniz Çetin, Nesibe Kahraman Çetin, Ogün Aydoğan, Göksel Tuzcu, İmran Kurt Ömürlü, Mustafa Ünübol, Mustafa Gökhan Ünsal, Engin Güney","doi":"10.1111/cen.70185","DOIUrl":"10.1111/cen.70185","url":null,"abstract":"<p><strong>Background: </strong>Whether nodule size compromises cytologic reliability remains controversial in managing large thyroid nodules. This study evaluated malignancy prevalence, predictors and false-negative (FN) cytology in a surgical cohort enriched for nodules ≥ 3 cm.</p><p><strong>Methods: </strong>We retrospectively analyzed 285 thyroidectomy patients (2018-2024) with a ≥ 3 cm dominant nodule. Each patient represented one analytic unit. The study assessed malignancy rates, clinical and imaging predictors, and FN risk among cytologically benign (Bethesda II) nodules. Demographic, biochemical and sonographic data-including nodule size, composition, EU-TIRADS category and suspicious lymphadenopathy (LAP)-were retrieved from records. Multivariable logistic regression with bootstrap validation identified independent predictors of malignancy and factors linked to false negativity.</p><p><strong>Results: </strong>Observed malignancy proportion was 13.3% in this thyroidectomy cohort (38/285), predominantly papillary carcinoma. Independent predictors: EU-TIRADS TR4-5 (OR 7.6) and suspicious LAP (OR 6.0); size ≥ 4 cm (OR 2.6) and solid composition (OR 3.3) exerted smaller effects. Among 111 Bethesda II cases, postoperative malignancy occurred in five (4.5%), all in ≥ 4 cm nodules (7.5% vs. 0%; p = 0.023). Post hoc review of FN cases suggested cystic/infiltrative features potentially contributing to sampling limitations. Nodule size had a moderate association with FN probability (AUC 0.75).</p><p><strong>Conclusions: </strong>In this surgically selected cohort of large thyroid nodules, sonographic risk, suspicious LAP and clinical context outperformed size alone in predicting malignancy. Even with benign cytology, nodules ≥ 4 cm with higher-risk imaging or structural features may warrant repeat or targeted FNAB, core biopsy, or surgery, whereas lower-risk phenotypes may still be considered for surveillance. These findings support a risk-stratified, node-informed approach beyond purely size-driven surgery in surgically referred large nodules, although extrapolation to all large nodules in the general population should be made cautiously.</p>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618755","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}