Endocrine journal最新文献

{"title":"Real-world clinical outcomes of tirzepatide administration in older patients with type 2 diabetes, with a focus on the risk of hypoglycemia and weight loss-related parameters.","authors":"Hiroya Kitsunai, Fumika Maruyama, Yukie Miyano, Tomoe Abe, Hiroyoshi Kurihara, Ken Tsuji, Atsuko Abiko, Yoshihiro Miyamoto, Reiko Homma, Akinobu Nakamura, Hiroshi Nomoto","doi":"10.1507/endocrj.EJ26-0246","DOIUrl":"https://doi.org/10.1507/endocrj.EJ26-0246","url":null,"abstract":"<p><p>In an aging society, the establishment of safe and effective treatment strategies for older patients with type 2 diabetes is crucial. We performed a secondary analysis of the Hokkaido-TZP study (UMIN000056962), evaluating the real-world outcomes of tirzepatide in patients aged ≥65 years. Of 213 patients in the safety analysis set, 11 (5.2%) discontinued treatment because of adverse events, primarily gastrointestinal symptoms. In the effectiveness analysis set (n = 199; mean age 71.3 years, glycated hemoglobin [HbA1c] 7.79%), tirzepatide significantly reduced both HbA1c and body mass index over 6 months in the Young-old (65-74 years) and Old-old (≥75 years) groups. Notably, even among the 148 patients (74.4%) using agents associated with a risk of hypoglycemia (insulin, sulfonylureas, or glinides) at baseline, a substantial proportion (66.9%) achieved an HbA1c <7.0%. The physicians proactively adjusted these concomitant medications in 39.2% of users, but despite these preemptive reductions, this subgroup still achieved a reduction in HbA1c comparable to that of the entire cohort, and no severe hypoglycemia was reported. A significant reduction in body weight occurred, and this was more pronounced in glucagon-like peptide-1 receptor agonist-naïve patients and those taking fewer hypoglycemia-inducing agents. Furthermore, the tirzepatide dose tended to be lower in the patients who achieved greater weight loss. These findings suggest that although tirzepatide is highly effective, even in older adults, its safety must be optimized through preemptive reductions in the doses of concomitantly administered secretagogues and careful monitoring, to prevent excessive reductions in HbA1c and weight loss in this vulnerable population.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic criteria for adrenal overt Cushing syndrome: prepared jointly by the Japan Endocrine Society and the Health and Labour Sciences Research Grant (Research on Intractable Diseases) Research Group on Disorders of Adrenal Hormones.","authors":"Takuyuki Katabami, Hirotaka Shibata, Akiyo Tanabe, Masakatsu Sone, Michio Otsuki, Yoshihiro Ogawa, Tomoatsu Mune, Takamasa Ichijo, Yuichi Yoshida, Takashi Yoneda, Kazuhiko Horiguchi, Katsutoshi Takahashi, Mitsuru Nishiyama, Fumitoshi Sato, Isao Kurihara, Makito Tanabe, Toshihiro Tajima, Tomonobu Hasegawa, Tomohiro Ishii","doi":"10.1507/endocrj.EJ26-0077","DOIUrl":"https://doi.org/10.1507/endocrj.EJ26-0077","url":null,"abstract":"<p><p>Adrenal overt Cushing syndrome (CS) is a rare disease but presents with a high risk of serious, life-threatening complications. Although florid CS is less frequently reported now, the interval between symptom onset and diagnosis still remains as long as four years. In this study, we investigated the current status of patients presenting with adrenal overt CS in the 2000s using data from the \"Study of Advancing Care and Pathogenesis of Intractable Adrenal Diseases in Japan (ACPA-J study).\" Based on the findings, we have established the diagnostic criteria for adrenal overt CS through the deliberation with members of the Health and Labour Sciences Research Grant \"Research group on Disorders of adrenal hormones\" and the public comment process conducted by the Japan Endocrine Society. We expect these diagnostic criteria to facilitate the designation of adrenal overt CS as an intractable disease and enhance standards of care.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characterization of Japanese children with Cushing's disease.","authors":"Mari Yamamoto, Yuri Mukoyama, Kentaro Kishi, Shun Moriguchi, Fumihiko Takizawa, Tetsushi Ogawa, Junko Ito, Susumu Yokoya, Hirokazu Fukuhara, Noriaki Fukuhara, Masahiko Tosaka, Hiroshi Nishioka, Shozo Yamada, Masakazu Mimaki, Tsuyoshi Isojima","doi":"10.1507/endocrj.EJ26-0212","DOIUrl":"https://doi.org/10.1507/endocrj.EJ26-0212","url":null,"abstract":"<p><p>Cushing's disease (CD) is very rare in children. Nineteen children (≤18 years) with CD (median age at diagnosis: 13 [6-17] years; 12 females) were retrospectively analyzed using medical records (1994-2025) from Toranomon Hospital, Tokyo, Japan. Facial changes (88.9%), weight gain with decreased growth rate (88.9%), central obesity (88.9%) and hirsutism (94.4%) were frequently observed at diagnosis. Median time to diagnosis was 2.7 (0.25-5.8) years. Screening for endogenous hypercortisolism was assessed by 24-hour urinary free cortisol levels, serum cortisol levels at 23:00, and serum cortisol levels at 8:00 after a low-dose dexamethasone suppression test (DST), each with 100% sensitivity. Etiological diagnosis was evaluated by serum cortisol levels at 8:00 after a high-dose DST, plasma adrenocorticotropic hormone (ACTH) levels after a corticotropin-releasing hormone test, and plasma ACTH levels at 8:00, with sensitivities of 85.7%, 93.8%, and 83.3%, respectively. The actual tumor detection rate on magnetic resonance imaging (MRI) was 72.2%. Micro-pituitary neuroendocrine tumors were identified in 77.8% of patients. The total remission rate was 94.4% (median follow-up: 3.8 [0-10.4] years). The mean standard deviation scores (SDS) (SD) of height and body mass index (BMI) at onset and diagnosis were -0.45 (0.63) and -2.0 (1.1), and 0.61 (0.95) and 1.6 (0.75), respectively. Height and BMI SDS (SD) improved to -1.0 (0.80) and 0.091 (1.2) at the last visit (age: 11.4-17.5 years; follow-up: 1-8.6 years), respectively. This study revealed clinical characteristics of Japanese children with CD, including distinctive BMI SDS and a high tumor detection rate by MRI.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148367443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nationwide survey on iodine nutritional status and thyroid function in Japanese adults.","authors":"Yozen Fuse, Yo Kunii, Nobu Tsukada, Yoshiya Ito, Yoshimasa Shishiba","doi":"10.1507/endocrj.EJ25-0603","DOIUrl":"10.1507/endocrj.EJ25-0603","url":null,"abstract":"<p><p>Japan is an iodine-replete country without iodine fortification. To characterize the current iodine status and thyroid function in healthy adults, a nationwide cross-sectional observational survey was conducted between 2016 and 2023. Iodine concentration in urine (UIC), serum and scalp hair as well as serum TSH, FT4 and FT3 concentrations, thyroid antibody (ThAb), thyroid volume by sonography, dietary iodine intake by diet study and anthropometry were evaluated. A total of 2,845 adults with the mean age of 45.6 years were recruited from 20 regions across Japan. The median UIC (mUIC) was 295.0 μg/L and within the WHO's adequacy range of iodine intake. There was a regional difference in indices of iodine status, thyroid function and prevalence of ThAb positivity throughout all of the regions. The mUIC was lowest in Tanegashima Island (169 μg/L) and highest in Fukui (943 μg/L). The highest median TSH (2.11 μIU/mL) with the lowest FT4 (1.22 ng/dL) was observed in Ishikawa, Hokuriku while the lowest TSH (1.06 μIU/mL) was in Rebun Island, Hokkaido although the median values of TSH, FT4 and FT3 were within their reference range. The prevalence of ThAb positivity was 12.6%. A significant positive correlation was observed only between mUIC and median TSH. Japanese adults consume more iodine than the average intake of other ethnic groups and there were some areas with high iodine intake. Current average iodine intake was estimated to be 400 μg per day in this study population. A large-scaled epidemiological survey is required in future.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":"847-865"},"PeriodicalIF":2.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Double faces of pheochromocytoma and paraganglioma-a review of integrated pathologic diagnosis.","authors":"Noriko Kimura","doi":"10.1507/endocrj.EJ25-0559","DOIUrl":"10.1507/endocrj.EJ25-0559","url":null,"abstract":"<p><p>Pheochromocytoma (PCC) and paraganglioma (PGL) are tumors of the adrenal medulla and sympathetic and parasympathetic paraganglia. Both PCC and PGL (PPGLs) are included in neuroendocrine tumors (NETs) of dispersed neuroendocrine system. The most important issue on PPGLs for pathology has been how to differentiate malignant from benign PPGLs, and the previous articles concentrated on solving this difficult issue. However, the concept of PPGLs was dramatically changed by WHO Blue Book, 4th edition (2017), in which all PPGLs have some metastatic potential, therefore, the previous categories of benign and malignant PPGLs have been eliminated in favor of an approach based on risk stratification. This review article includes following issues; 1. historical review of PPGLs, 2. significance of Ki67 labeling index, 3. comparison of scoring system of PASS, GAPP, COPPS these were cited in WHO Tumour Classification 5^th edition (2022) with explanation of each parameter, 4. immunohistochemical approach for histopathologic diagnosis using antibodies for neuroendocrine tumors, the specific markers for catecholamine synthesis such as tyrosine hydroxylase (TH) and dopamine β-hydroxylase (DBH) for sympathetic PPGL and choline acetyltransferase for parasympathetic PGL, and additional markers such as GATA3 and Phox2B for both sympathetic and parasympathetic PGL. Then markers for familial PPGLs such as SDHB for SDH-deficient PPGLs, CA9 for VHL, and MAX for MAX-related PPGL, and added Algorithm for diagnosis. The other familial type of MEN type2 and NF1 are discussed by some characteristic features in histology. Finally, rare types such as ACTH-producing PPGL, and dopamine-producing PPGL are discussed.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":"799-810"},"PeriodicalIF":2.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Teprotumumab-associated persistent unilateral hearing loss in dysthyroid optic neuropathy: a case report with review of the literature.","authors":"Yuji Hiromatsu, Kumiko Suzuki, Shiho Watanabe, Takahiro Fukuyama, Narihito Tatsumoto, Satoe Nakamura, Yoko Sagara, Yuko Akehi, Eiji Kawasaki, Hiroki Kojima, Kimihiko Sakai","doi":"10.1507/endocrj.EJ26-0064","DOIUrl":"https://doi.org/10.1507/endocrj.EJ26-0064","url":null,"abstract":"<p><p>We report a case of severe thyroid eye disease (TED) complicated by dysthyroid optic neuropathy (DON) in a 55-year-old woman with Graves' disease. Despite insufficient response to high-dose intravenous steroid therapy, teprotumumab led to marked improvement in proptosis, orbital inflammation, and visual function. However, treatment was associated with progressive and persistent sensorineural hearing loss after completing eight infusions. Auditory symptoms began after the fifth infusion with intermittent aural fullness and sound reverberation, progressing to mild down-sloping sensorineural hearing loss. Nine days after the final infusion, the four-frequency pure-tone average (PTA4) was 21.25 dB hearing level (HL) in the right ear and 27.50 dB HL in the left ear. Despite initiation of oral prednisolone therapy (40 mg/day with tapering), progressive hearing loss was observed in the right ear, particularly in the low- to mid-frequency range (250-2,000 Hz), with thresholds worsening to 90 dB HL. At twenty days after the final infusion, PTA4 had increased to 75.00 dB HL in the right ear and 31.25 dB HL in the left ear. Serial audiometric assessments at 107, 128, and 198 days after the final infusion demonstrated no recovery. The patient's history of sudden sensorineural hearing loss suggests increased susceptibility to teprotumumab-associated ototoxicity. This case underscores the importance of individualized risk assessment, careful audiologic monitoring, and shared decision-making when balancing visual recovery against the risk of potentially irreversible auditory toxicity.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148367400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-affinity IgG-mediated macro-TSH: diagnostic limitations of peak-based gel filtration chromatography-a case report with review of literature.","authors":"Toshihiko Kasahara","doi":"10.1507/endocrj.EJ26-0019","DOIUrl":"10.1507/endocrj.EJ26-0019","url":null,"abstract":"<p><p>Macro-thyroid-stimulating hormone (macro-TSH) is a well-recognized cause of spuriously elevated TSH results. However, its characterization still relies largely on gel filtration chromatography (GFC), which may fail to detect macro-TSH associated with unstable or low-affinity immune complexes. In particular, when second-line screening tests, such as polyethylene glycol (PEG) precipitation, strongly suggest macro-TSH but GFC shows no distinct high-molecular-weight TSH fraction, macro-TSH may be incorrectly ruled out as the source of interference. A 43-year-old woman treated with levothyroxine for subclinical hypothyroidism showed persistently elevated TSH despite high-normal free thyroxine levels and no clinical signs of hypothyroidism. PEG precipitation and Protein G treatment resulted in TSH recovery rates of 8% and 23%, respectively, indicating macro-TSH mediated by immunoglobulin G, while heterophile and assay-specific interferences were considered unlikely. GFC under neutral conditions revealed a subtly broadened TSH distribution without a distinct high-molecular-weight peak. Quantitative peak analysis showed increased full width at half maximum and area under the curve, with values approximately 1.5- to 2-fold higher than those in controls in both the initial and repeat runs, confirming significant peak broadening. Under acidic conditions, the patient's TSH elution profile completely overlapped with those of the controls, supporting the presence of macro-TSH due to low-affinity TSH-IgG complexes. This case highlights the diagnostic challenge posed by macro-TSH, particularly in cases involving low-affinity antibody interactions. It underscores the importance of assessing the overall elution profile rather than relying solely on peak position. Recognizing such atypical presentations can prevent unnecessary thyroid hormone treatment and improve diagnostic accuracy.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":"899-906"},"PeriodicalIF":2.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early predictors of 6-month thyroid-stimulating antibody levels after radioactive iodine therapy for Graves' disease: implications for pregnancy planning.","authors":"Seigo Tachibana, Yuji Nagayama, Takashi Fukuda, Yusuke Taguchi, Daisuke Tatsushima, Yusuke Mori, Hisakazu Shindo, Hiroshi Takahashi, Shinya Sato, Hiroyuki Yamashita","doi":"10.1507/endocrj.EJ25-0651","DOIUrl":"10.1507/endocrj.EJ25-0651","url":null,"abstract":"<p><p>Current guidelines recommend a 6-month contraception period following radioactive iodine therapy (RAIT) for Graves' disease (GD), based primarily on radiation safety considerations; however, they do not account for the post-treatment surge in thyroid-stimulating antibodies (TSAb), which poses risks for fetal and neonatal GD. This retrospective study aimed to identify factors influencing TSAb trajectories and construct a predictive model for TSAb levels at 6 months after RAIT. We analyzed 82 patients who underwent RAIT, with TSAb values standardized to the upper limit of normal (ULN) to account for different assay methods. Multivariable linear regression identified the duration of antithyroid drug and potassium iodide administration, pre-RAIT TSAb levels, changes in TSAb at 3 months (3M), fractional reduction in TW at 3M, and assay method as significant predictors of TSAb levels at 6 months (adjusted R² = 0.87). A prediction score derived from this model demonstrated excellent diagnostic performance. Receiver operating characteristic analysis yielded an area under the curve of 0.99 for predicting TSAb >3.3 ULN, corresponding to the threshold for fetal GD monitoring at approximately 20 weeks of gestation, and 0.94 for TSAb >1.0 ULN. The prediction score significantly outperformed single predictors, including baseline TSAb levels and early post-TSAb changes. In conclusion, we developed a highly accurate predictive model for TSAb levels at 6 months after RAIT by integrating early post-treatment data with pre-RAIT clinical parameters. This model enables identification of patients at risk of persistent TSAb elevation, supporting individualized counseling regarding pregnancy planning beyond the conventional 6-month contraception period.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":"837-846"},"PeriodicalIF":2.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple thyroid cysts: a benign and stable clinical entity based on longitudinal data.","authors":"Yuji Nagayama, Seigo Tachibana, Takashi Fukuda, Daisuke Tatsushima, Yusuke Mori, Hisakazu Shindo, Hiroshi Takahashi, Shinya Sato, Hiroyuki Yamashita","doi":"10.1507/endocrj.EJ25-0573","DOIUrl":"10.1507/endocrj.EJ25-0573","url":null,"abstract":"<p><p>Multiple thyroid cysts are commonly detected by ultrasonography, and are considered clinically insignificant. On the other hand, polycystic thyroid disease (PCTD) has been proposed as a cause of antibody-negative hypothyroidism in iodine-replete regions; however, the clinical characteristics and natural history of multiple thyroid cysts as a broader entity remain unclear. To elucidate these issues, we retrospectively reviewed 7,727 consecutive new outpatients at a high-volume thyroid center between 2013 and 2016. Multiple thyroid cysts were defined as ≥4 cysts (≥3 mm in diameter) in the absence of thyroid autoantibodies. Among all patients, 164 (2.1%) met the criteria. The mean age was 58.3 years, and 91.0% were female. At presentation, 86.6% were euthyroid, 6.1% and 6.7% had subclinical hypothyroidism and subclinical hyperthyroidism, respectively, and one patient had Graves' disease. Thus, approximately 6% of multiple thyroid cysts may be PCTD. Forty-six patients were followed up for ≥5 years (mean 9.8 years) without iodine restriction. Thyroid function remained stable in most cases, with no significant progression to overt dysfunction and no requirement for surgical or interventional treatment. Ultrasonographic findings ranged from numerous diffuse cysts throughout the gland to several scattered or localized cysts. Some cysts remained stable, some increased, and others decreased in size in the follow-up periods. The cyst distribution patterns (diffuse versus localized) were not associated with thyroid function. Therefore, multiple thyroid cysts may generally represent benign and stable clinical entities, supporting conservative management with periodic monitoring in most patients.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":"883-887"},"PeriodicalIF":2.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of hypothyroidism with adverse pregnancy outcomes: a single-center cohort study in an iodine-sufficient country.","authors":"Akiko Sankoda, Nagayoshi Umehara, Yusuke Okubo, Shiori Sato, Seiji Wada, Naoko Arata","doi":"10.1507/endocrj.EJ25-0423","DOIUrl":"10.1507/endocrj.EJ25-0423","url":null,"abstract":"<p><p>Hypothyroidism is reported to associate with adverse pregnancy outcomes. However, there are few reports in iodine-sufficient or -excess areas. We investigated the association of hypothyroidism in early pregnancy with pregnancy outcomes in an iodine-rich area, Japan. We conducted a retrospective cohort study at a tertiary center between 2004 to 2013. The eligible participants were classified into three groups: euthyroidism, subclinical hypothyroidism (SCH), or overt hypothyroidism (OH) groups, based on their thyroid hormone levels in the first trimester of pregnancy (median 11.6 weeks, IQR 10.6-12.6). SCH and OH were defined as elevated TSH levels with normal and low FT4 levels, respectively, using cohort-specific reference ranges in early pregnancy. The primary outcomes were miscarriage, preterm birth, small for gestational age (SGA), and their composite. Multivariate logistic regression analyses and restricted cubic spline analyses fitted to the regression models were performed to analyze the association and dose-dependency. 5,366 pregnant women were classified as euthyroidism, 143 as SCH, and 21 as OH. The composite outcome was not associated with SCH (odds ratio [OR], 0.73; 95%CI, 0.41-1.31), but significantly associated with OH (OR, 3.43; 95%CI, 1.36-8.68). Preterm birth was not associated with SCH (OR, 0.69; 95%CI, 0.28-1.69), but significantly associated with OH (OR, 5.56; 95%CI, 1.98-15.63). In this Japanese single-center cohort, SCH diagnosed in the first trimester was not associated with selected adverse pregnancy outcomes; however, miscarriage risk in early pregnancy could not be adequately assessed. The restricted cubic spline models for the primary outcomes showed J-shaped association with TSH, while the dose-response analysis did not show a clear increase in risk within the reference range of FT4. SCH in early pregnancy was indicated to have no association with the adverse pregnancy outcomes in an iodine-rich area. The risk of adverse pregnancy outcomes was increased exclusively in the low FT4 range.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":"827-836"},"PeriodicalIF":2.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}