Endocrine journal最新文献

{"title":"Growth hormone-releasing hormone-secreting giant pheochromocytoma causing acromegaly: a case report with a review of the literature.","authors":"Takuya Kitamura, Kazutaka Nanba, Mutsuki Mishina, Toru Kanno, Seiko Kasahara, Naoki Higashibeppu, Koki Moriyoshi, Naoko Inoshita, Noriko Kimura, Naotetsu Kanamoto","doi":"10.1507/endocrj.EJ26-0363","DOIUrl":"https://doi.org/10.1507/endocrj.EJ26-0363","url":null,"abstract":"<p><p>The ectopic secretion of growth hormone (GH) or growth hormone-releasing hormone (GHRH) is responsible for fewer than 1% of acromegaly cases. Furthermore, within this small population, GHRH-secreting pheochromocytomas/paragangliomas (PPGLs) are even rarer. A 57-year-old Japanese woman presented to our hospital for treatment of a large left-sided pheochromocytoma (PCC). A physical examination revealed enlargement of the nose and lips as well as macroglossia, thereby raising the suspicion of acromegaly, which was biochemically confirmed by a 75-g oral glucose tolerance test. Magnetic resonance imaging demonstrated a slightly enlarged pituitary gland but no definitive tumor. A left adrenalectomy was performed after careful dose titration of doxazosin and metyrosine. Postoperative biochemical improvement of GH excess and immunohistochemical analysis of the resected tumor confirmed the diagnosis of GHRH-secreting PCC. Given the possibility that PPGLs produce various ectopic hormones and peptides, thorough physical examinations remain fundamental for the accurate diagnosis and optimal management of patients with these tumors.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220061","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":"Metreleptin improves glucose metabolism and hepatic steatosis in a patient with Werner syndrome and partial lipodystrophy: a case report with review of literature.","authors":"Shogo Iwamura, Nagisa Nirei, Mari Matsuyama, Shinichiro Minami, Kana Sasaki, Sayaka Ando, Shunsuke Kato, Tatsunori Shimizu, Takehiro Sato, Tsukasa Morii, Hiroki Fujita, Katsunori Iijima, Hironori Waki","doi":"10.1507/endocrj.EJ26-0235","DOIUrl":"https://doi.org/10.1507/endocrj.EJ26-0235","url":null,"abstract":"<p><p>Werner syndrome (WS) is a rare autosomal recessive progeroid disorder caused by mutations in the WRN gene and is characterized by distinctive physical features and metabolic complications, including insulin resistance, diabetes, hypertriglyceridemia, and hepatic steatosis. Although lipodystrophy is a recognized component of WS, clinical reports of metreleptin use in this setting remain very limited. We report the case of a 38-year-old woman with WS complicated by partial lipodystrophy, diabetes with suboptimal glycemic levels, hypertriglyceridemia and severe hepatic steatosis. She presented with distal limb lipoatrophy, a bird-like facial appearance, premature hair graying, and cataracts. Genetic testing identified two pathogenic WRN variants (c.1105C>T and c.3446del) resulting in premature protein termination, confirming the diagnosis. At baseline, hemoglobin A1c (HbA1c) was 8.6% despite insulin and oral hypoglycemic agents, and imaging demonstrated hepatomegaly with marked steatosis. Metreleptin therapy was initiated and titrated. Over 26 weeks, HbA1c improved to 7.4% and the visceral-to-subcutaneous fat ratio decreased, accompanied by reduction in liver transaminases, cholestatic enzymes, and imaging-based indices of hepatic steatosis, liver stiffness, and liver volume. To date, only three cases of WS treated with metreleptin, including ours, have been reported. While glycemic improvement is consistent with prior reports, our case additionally demonstrated improvements in hepatic steatosis across biochemical, and imaging parameters. These findings suggest that metreleptin may improve both glucose metabolism and hepatic steatosis in WS-associated lipodystrophy. Further accumulation of cases is essential to clarify its role in the management of WS.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180027","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":"Excellent prognosis of oncocytic thyroid carcinoma in Japanese patients: a single-institution study.","authors":"Yasuhiro Ito, Mitsuyoshi Hirokawa, Hiroo Masuoka, Minoru Kihara, Akihiro Miya, Akira Miyauchi, Tadashi Akamizu","doi":"10.1507/endocrj.EJ26-0328","DOIUrl":"https://doi.org/10.1507/endocrj.EJ26-0328","url":null,"abstract":"<p><p>Oncocytic thyroid carcinoma (OCA) is a rare thyroid malignancy that has only recently been recognized as a distinct entity from follicular thyroid carcinoma. Till date, studies regarding the prognosis of OCA remain inadequate. In this retrospective study, we investigated the prognosis of OCA among 137 Japanese patients who underwent surgery at our institution. Two patients had distant metastasis before surgery (M1), and two showed distant metastasis after surgery. The 10-year and 15-year distant recurrence-free survival rates were 100%, and 92.7%, respectively. No deaths occurred owing to thyroid carcinoma. Four patients with distant metastasis/recurrence were aged ≥60 years, and their tumors were >4 cm. Further, two patients with M1 had both vascular invasion (VI) and wide capsular invasion (CI). One patient had a poorly differentiated component (approximately 30%), and one showed high cell proliferating activity (Ki-67 labeling index [LI] ≥5%). Of the two patients who developed distant metastasis after surgery, one had VI and wide CI, and although another had minimal CI and was negative for VI, the Ki-67 LI of his tumor was >5%. These findings suggest that Japanese patients with OCA generally had excellent prognosis after surgery; however, older age, large tumor size, wide CI, VI positivity, high Ki-67 LI, and the presence of a poorly differentiated component may be indicators of aggressive behavior. Further multicenter studies with larger samples and longer follow-up durations are necessary to identify clinicopathological factors accurately predicting poor prognosis in patients with OCA.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105804","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":"Cold exposure-induced alterations in n-3 fatty acid profiles and their associations with brown adipose tissue activity.","authors":"Naoki Sakane, Shinsuke Nirengi, Masayuki Domichi, Akiko Suganuma, Mami Matsushita, Hitoshi Wakabayashi, Masayuki Saito","doi":"10.1507/endocrj.EJ26-0271","DOIUrl":"https://doi.org/10.1507/endocrj.EJ26-0271","url":null,"abstract":"<p><p>Brown adipose tissue (BAT) contributes to energy expenditure through cold-induced thermogenesis and is closely linked to systemic lipid metabolism. However, the dynamic changes in circulating n-3 polyunsaturated fatty acids (PUFAs) during cold exposure and their association with BAT activity remain unclear. Healthy young men underwent controlled cold exposure, and BAT activity was quantified using fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). Circulating levels of n-3 PUFAs, including α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), were measured before and after cold exposure using whole-blood lipidomics. K-means clustering based on log-transformed maximum standardized uptake value (lnSUVmax) was performed. Changes in lipid parameters were evaluated using paired t-tests and multiple regression analyses. Cold exposure significantly decreased ALA levels and the ALA/EPA ratio while increasing EPA and DPA levels and the EPA/DPA and DPA/DHA ratios. Multiple regression analyses revealed that BAT activity (lnSUVmax) was independently associated with changes in several lipid parameters. Higher SUVmax was positively associated with changes in ALA levels and the ALA/EPA ratio, whereas inverse associations were observed with changes in EPA, DPA, EPA/DPA, and DPA/DHA. Baseline lipid levels were not significant predictors of lipidomic changes. Cold-induced BAT activation is associated with dynamic remodeling of circulating n-3 fatty acids. These findings suggest that thermogenic capacity may influence systemic lipid metabolism and highlight the metabolic interplay between BAT activity and circulating n-3 PUFAs. Trial registration: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), UMIN000029206.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105714","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":"Aldosterone-producing adrenocortical carcinoma presenting with severe, rapidly progressive hypokalemia: a case report and literature review.","authors":"Yukino Okimoto, Akinori Takedomi, Tsuguka Matsuda, Keisuke Monji, Akira Hirata, Ryuichi Kodama, Aoi Ono, Aya Hamaoka, Nozomu Oda, Megumu Fujihara, Takashi Yajima, Hironobu Sasano, Nozomu Kamei","doi":"10.1507/endocrj.EJ26-0173","DOIUrl":"https://doi.org/10.1507/endocrj.EJ26-0173","url":null,"abstract":"<p><p>Although previous studies have described steroidogenic enzyme expression in aldosterone-producing adrenocortical carcinoma (APAC), detailed immunohistochemical evaluations of CYP11B2 at the protein level and its clinicopathological relevance remain limited. Here, we report a rare case of APAC with a comprehensive immunohistochemical analysis focusing on CYP11B2 expression. An 82-year-old woman presented with limb weakness and severe hypokalemia (serum potassium: 1.9 mmol/L). Endocrinological evaluation revealed markedly elevated plasma aldosterone levels and suppressed renin activity, indicating autonomous aldosterone secretion. Imaging identified a rapidly enlarging left adrenal mass with intratumoral hemorrhage, and adrenal venous sampling confirmed unilateral aldosterone excess. The patient underwent laparoscopic left adrenalectomy. Histopathological examination revealed a high-grade adrenocortical carcinoma with positive surgical margins. Immunohistochemical analysis demonstrated positive expression of CYP11B2, CYP11B1, and CYP17A1, whereas dehydroepiandrosterone sulfotransferase expression was absent in the tumor cells but present in the adjacent zona reticularis, suggesting disorganized steroidogenesis. Although biochemical parameters transiently improved postoperatively, the patient developed early recurrence with peritoneal dissemination and died 10 months after surgery. This case of APAC was diagnosed following severe and rapidly progressive hypokalemia, suggesting that a detailed examination of steroidogenic enzyme expression in the tumor may be valuable in elucidating the endocrine characteristics of this rare malignancy.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105801","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":"Real-world patterns of growth hormone treatment in Japanese children with short stature associated with small for gestational age, Turner syndrome, Noonan syndrome, achondroplasia, and hypochondroplasia: a retrospective database study.","authors":"Jun Mori, Akie Nakamura, Masanobu Kawai, Satoshi Tsuboi, Yukihito Sato, Takaaki Endo, Sumito Dateki","doi":"10.1507/endocrj.EJ26-0185","DOIUrl":"https://doi.org/10.1507/endocrj.EJ26-0185","url":null,"abstract":"<p><p>In Japan, GH treatment (GHT) is used for short stature associated with small for gestational age (SGA), Noonan syndrome (NS), Turner syndrome (TS), achondroplasia (ACH), and hypochondroplasia (HCH). However, real-world data on these diagnoses and GHT use for these conditions in Japan remain limited. In this retrospective cohort study, we used the JMDC claims database (2005-2021) to extract data of children with SGA-related short stature or diagnosed with short stature diseases, namely NS, TS, ACH, or HCH, particularly in boys aged <17 years and girls aged <15 years. We reported the prevalence, comorbidities, age at diagnosis, time from diagnosis to treatment initiation, persistence to GHT, and proportion of days covered (PDC). We analyzed data from children with SGA-related short stature (n = 786), NS (n = 79), TS (n = 172), ACH (n = 107), and HCH (n = 30); the mean (standard deviation) age at initial diagnosis was 5.2 (3.5), 4.0 (4.0), 6.5 (4.2), 3.0 (4.1), and 4.5 (3.9) years, respectively. The prevalence (per 100,000) was 59.59, 5.45, 9.52, 8.31, and 2.12 for SGA-related short stature, NS, TS, ACH, and HCH, respectively. Mean PDC for SGA-related short stature, NS, TS, ACH, and HCH was 0.918, 0.984, 0.953, 0.941, and 1.000, respectively, demonstrating high persistence to GHT. This study provides insights into the current diagnosis and GHT use among children with short stature in Japan. The findings suggest that most Japanese children continue and adhere well to GHT. However, continued efforts toward early referral and diagnosis remain crucial.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105776","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":"Inter- and intratumoral heterogeneity of aldosterone-producing adenomas: recent advances and clinical implications.","authors":"Masanori Murakami","doi":"10.1507/endocrj.EJ26-0125","DOIUrl":"10.1507/endocrj.EJ26-0125","url":null,"abstract":"<p><p>Primary aldosteronism is the most common form of secondary hypertension, and aldosterone-producing adenoma (APA) is the most prevalent surgically curable subtype of primary aldosteronism. Over the past decade, the identification of recurrent somatic mutations, most notably in KCNJ5, has transformed the molecular understanding of APA and has revealed substantial heterogeneity across tumors. In parallel, advances in transcriptomic, epigenomic, and metabolomic profiling have further expanded insights into genotype-dependent differences in steroidogenic activity, cellular morphology, and clinical presentation. More recently, the application of single-cell, single-nucleus, and spatial transcriptomics technologies has revealed an additional layer of complexity, demonstrating marked heterogeneity within individual APA tissues. These studies show that APAs are composed of transcriptionally and functionally diverse cell populations with variable steroidogenic capacities, extending beyond what can be explained by the somatic mutation status alone. This review summarizes the current evidence for both intertumoral and intratumoral heterogeneity in APA, integrating findings from genomic, epigenomic, metabolomic, and single-cell-based studies. By highlighting how mutation-driven differences intersect with cell-state diversity and differentiation processes, this review aimed to provide a comprehensive framework for understanding the pathophysiology of APA and discuss the potential implications for disease classification, biomarker development, and future therapeutic strategies.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":"1095-1106"},"PeriodicalIF":2.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148316320","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":"Establishment of a prognostic score for distant recurrence in follicular thyroid carcinoma.","authors":"Yasuhiro Ito, Masashi Yamamoto, Mitsuyoshi Hirokawa, Hiroo Masuoka, Minoru Kihara, Akihiro Miya, Akira Miyauchi, Takashi Akamizu","doi":"10.1507/endocrj.EJ26-0184","DOIUrl":"10.1507/endocrj.EJ26-0184","url":null,"abstract":"<p><p>Follicular thyroid carcinoma (FTC) is known to occasionally show distant recurrence (DR); however, no prognostic scoring system has been established. Furthermore, although prognostic factors have been identified, their weights as predictors of poor prognosis remain unclear. In this study, we aimed to establish a weighted scoring system for predicting DR in FTC using conventional prognostic factors and Ki-67 labeling index (LI). We analyzed data of 597 patients with FTC without distant metastasis at initial surgery. Tumor size >4 cm, male sex, age ≥60 years, Ki-67 LI >5%, and vascular invasion (VI) ≥4 (V2) significantly and VI 0-4 (V1) marginally affected DR. Wide capsular invasion was not significantly associated with DR. Stepwise model selection using the Akaike Information Criterion identified age ≥60 years, Ki-67 LI >5%, V1, V2, and tumor size >4 cm as suitable components of the score. According to the beta coefficient value, we assigned a score of 2 to age ≥60 years, Ki-67 LI >5%, and V2, and a score of 1 to tumor size >4 cm and V1, with the sum representing the final score. We categorized patients into three categories according to the DR rates: low-risk (score 0-2; n = 388, 65.0%), intermediate-risk (score 3-4; n = 156, 26.1%), and high-risk (score 5-7; n = 53, 8.9%). The 10-year DR-free survival rates declined from the low- to the high-risk categories (96.0% vs. 90.3% vs. 54.9%). These findings indicate that high-risk patients identified using this prognostic scoring model should be carefully monitored for DR following completion thyroidectomy.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":"1141-1146"},"PeriodicalIF":2.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249941","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":"Real-world optimization of cutoff values for enzyme immunoassay-based plasma-free fractionated metanephrines for the diagnosis of pheochromocytoma and paraganglioma: a multicenter retrospective study.","authors":"Masato Yonamine, Ryota Ishii, Katsutoshi Takahashi, Yuichi Aita, Yuki Murayama, Motohiro Sekiya, Koichi Ozaki, Jun Saito, Moe Horinaka, Akiyo Tanabe, Yuka Ohmachi, Masaaki Yamamoto, Hidenori Fukuoka, Rei Hirose, Kazuhiro Takekoshi","doi":"10.1507/endocrj.EJ26-0101","DOIUrl":"10.1507/endocrj.EJ26-0101","url":null,"abstract":"<p><p>Pheochromocytoma and paraganglioma (PPGL) require sensitive biochemical screening to prevent delayed or missed diagnoses. In Japan, plasma-free metanephrines (pMN/pNMN) measured using enzyme immunoassay have been covered by national insurance since 2019; however, the real-world diagnostic performance of the currently applied cutoff values has not been evaluated. We retrospectively identified consecutive adults who underwent pMN/pNMN testing in routine practice at five endocrinology departments between 2019 and 2025, of whom 817 were included in the final analysis. Patients were classified post hoc as having PPGL (n = 107) or serving as controls (n = 710) based on pathological findings, functional imaging, and clinical follow-up. Diagnostic performance at the current cutoff values (pMN >130 pg/mL or pNMN >506 pg/mL) was evaluated by sensitivity and specificity, compared with spot and 24-hour urinary metanephrine measurements using receiver operating characteristic (ROC) analyses, and optimized cutoff combinations were determined using the Youden index. The current cutoff values showed high specificity (99.9%) but limited sensitivity (82.2%), particularly in patients with abdominal paraganglioma (76.0%). Plasma and urinary metanephrine measurements demonstrated comparable performance in the ROC analyses. False-negative cases based on the current cutoff values had significantly smaller tumors than true-positive cases (p = 0.016). Urinary biochemistry and functional imaging offered crucial complementary diagnostic value. Our optimized thresholds (pMN >120 pg/mL or pNMN >290 pg/mL) significantly enhanced sensitivity (92.5%) while maintaining high specificity (99.2%), consistent with postoperative biochemical remission. These findings suggest that current pMN/pNMN cutoff values may limit diagnostic sensitivity, necessitating optimized thresholds and a multimodal approach in accordance with the PPGL guidelines. Registration Number: UMIN000060658.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":"1127-1139"},"PeriodicalIF":2.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410879","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":"Fructose-1,6-bisphosphatase deficiency: the clinical characteristics, molecular consequences of FBP1 variants, and emerging non-canonical functions of FBP1.","authors":"Ikki Sakuma, Gerald I Shulman, Tomoaki Tanaka","doi":"10.1507/endocrj.EJ26-0243","DOIUrl":"https://doi.org/10.1507/endocrj.EJ26-0243","url":null,"abstract":"<p><p>Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare autosomal recessive disorder of gluconeogenesis caused by the biallelic pathogenic variants of FBP1. Recurrent episodes of hypoglycemia and lactic acidosis usually occur during childhood. Because the ketone levels during hypoglycemic attacks may vary in patients with FBPase deficiency, differentiation from fatty acid oxidation disorders can be challenging. A urinary organic acid analysis during hypoglycemic attacks, particularly the detection of glycerol and glycerol-3-phosphate, in conjunction with plasma acylcarnitine profiling, is useful for distinguishing between these disorders. Furthermore, targeted next-generation sequencing-based multigene panels for hypoglycemia and related inherited metabolic disorders have become increasingly valuable diagnostic tools in this field. At the molecular level, a useful working model is to interpret FBP1 variants along three functional dimensions: protein abundance/stability, catalytic activity, and non-canonical restraint of AKT signaling. Within this framework, many missense variants fall into two major classes: variants that preserve protein abundance, but impair the catalytic activity and variants that reduce both protein abundance and the catalytic activity through defective folding. Selected C-terminal variants additionally disrupt the AKT-regulatory scaffolding function. Emerging experimental evidence suggests that FBP1 influences hepatic lipid accumulation, fibrosis, and tumorigenesis through mechanisms beyond its canonical role in gluconeogenesis. This review summarizes the clinical features, diagnosis, genetics, and management of FBPase deficiency, with particular emphasis on the functional interpretation of FBP1 variants and the broader biological roles of FBP1.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105769","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}