Hematopoietic stem cell transplantation (HSCT)-associated partial lipodystrophy (HSCT-PL) is a serious metabolic complication that develops in remote period among childhood cancer survivors treated with HSCT with total body irradiation (TBI). Since the first proposal in 2013, HSCT-PL seems to be increasingly recognized as a distinct disease entity. The patients with HSCT-PL show profound metabolic dysfunction including insulin resistance, diabetes, elevated triglycerides, and hepatic steatosis. Their body mass index is low–normal, although they show visceral fat accumulation and increased waist-to-hip ratio. In addition, HSCT-PL is characterized by Dunnigan phenotype: lipoatrophy in buttock and extremities combined with lipohypertrophy in face and neck. Although the precise pathogenesis is still obscure, radiation-induced damage to adipose progenitor cells, leading to accelerated senescence, seems to be a main pathway. Literature survey identified 17 patients of HSCT-PL with sufficient information from 12 reports. Among them, clear female predominance (15 females) and possible ethnic difference in disease prevalence (11 Japanese) were ascertained. Genetic factors may be involved in those epidemiological traits. There remains much to be clarified, including establishment of reliable diagnostic procedure, elucidation of long-term prognosis, and invention of effective treatment. Metreleptin is one of the promising options, and the accumulation of its therapeutic efficacy are warranted.
Hematopoietic stem cell transplantation-associated partial lipodystrophy (HSCT-PL) is a serious complication that develops about a decade after HSCT in childhood cancer survivors. Typically, patients present with a unique combination of lipoatrophy and lipohypertrophy, known as Dunnigan phenotype. Despite low-to-normal BMI, they often develop metabolic dysfunctions, such as insulin resistance, diabetes, hypertriglyceridemia, and fatty liver. This review discusses current hypotheses for pathogenesis of HSCT-PL. Among the proposed theories, radiation-induced damage of adipose progenitor cells in both subcutaneous and visceral adipose tissue appears to be primary, suggesting that HSCT-PL may reflect accelerated senescence. A literature survey revealed that nearly 90% of reported patients were female. Although the underlying cause of this disparity remains unclear, this is consistent with the greater disease severity in females observed in other adipose tissue-related disorders, including familial partial lipodystrophy and lipoedema. Since patients with HSCT-PL develop severe metabolic dysfunction early in life, they will be at a particularly high risk of premature atherosclerosis. Increased risk of mortality and potential predisposition to malignancy were also identified as important concerns. The development of effective therapeutics is urgently needed. Metreleptin may represent one such option, given its readily availability and demonstrated efficacy in some patients.
Vitamin D deficiency and rickets are important pediatric health concerns, particularly in high-latitude regions. This study investigated the incidence and clinical characteristics of pediatric vitamin D deficiency in Hokkaido, Japan, between 2015 and 2019. A cross-sectional survey was distributed to the pediatric departments of 88 major hospitals across the region, achieving a response rate of 97.7%. Clinical data were collected from 262 children with vitamin D deficiency (25(OH)D < 20 ng/mL), including 153 with rickets. In 2019, the incidence of vitamin D deficiency rickets was 25.4 per 100,000 live births, approximately threefold higher than 15 yr earlier and eightfold greater than the national average. Most cases (median age 1.4–1.5 yr) occurred in children younger than four years. Patients with rickets exhibited considerably lower Ca/P and higher ALP/iPTH levels than those without rickets, despite having similar 25(OH)D levels. Exclusive breastfeeding was significantly more common in the rickets group. Approximately 90% of patients received alfacalcidol. The incidence of pediatric vitamin D deficiency and rickets in Hokkaido has increased. These findings underscore the need for continued public health education on vitamin D intake, expanded access to native vitamin D supplementation, and attention to maternal vitamin D status.
Vitamin D deficiency (VDD) and rickets are increasing pediatric health concerns, particularly in high-latitude regions. This comprehensive survey in Hokkaido, Japan (2015–2019), reveals that VDD rickets incidence has surged to 25.4 per 100,000 live births. This rate represents a threefold increase over the past 15 years and is approximately eight times higher than the national average of 3.5 per 100,000 reported by Kubota et al. (2018). The study identified important clinical insights: Exclusive breastfeeding was significantly more common among children with rickets than among those without rickets (83.0% vs. 65.2%), although both groups had similarly low serum 25(OH)D levels. Furthermore, patients with rickets demonstrated substantially lower calcium and phosphorus concentrations. Notably, the incidence of rickets has not decreased despite the recent implementation of national insurance coverage for 25(OH)D testing and the commercial availability of infant vitamin D supplements. These findings highlight the need for strengthened public health education, improved access to native vitamin D supplementation, and proactive management of maternal vitamin D status. Overall, the study underscores the importance of re-evaluating pediatric preventive care strategies in high-risk region.
Octreotide is considered a second-line treatment for congenital hyperinsulinism unresponsive to diazoxide. Necrotizing enterocolitis (NEC) is a serious adverse effect of octreotide, typically occurring in a dose-dependent manner. Here, we report a case of necrotizing enterocolitis following a single administration of a very low dose of octreotide. A female infant was admitted on day 3 of life with severe hypoglycemia. Laboratory findings revealed hyperinsulinemia and hypoketotic hypoglycemia, confirming a diagnosis of congenital hyperinsulinism. Despite diazoxide therapy, adequate glycemic control was not achieved. As a second-line intervention, a single subcutaneous injection of octreotide (1.6 μg/kg) was administered. Two days post-administration, the patient developed abdominal distension and significant vomiting. NEC was diagnosed, necessitating bowel decompression surgery. Subsequent 18F-DOPA positron emission tomography/computed tomography revealed a focal lesion extending from the pancreatic head to the body. The lesion was successfully resected with preservation of nearly the entire normal pancreas. This case highlights that even a very low dose of octreotide may precipitate necrotizing enterocolitis, warranting close monitoring. Lesion localization using 18F-DOPA positron emission tomography/computed tomography is critical in guiding surgical management of congenital hyperinsulinism.
Integrated
imaging and histopathological findings in a neonate with congenital
hyperinsulinism (CHI) complicated by necrotizing enterocolitis (NEC) following
a single, very low subcutaneous dose of octreotide (1.6 μg/kg). On day 133, 18F-DOPA positron emission
tomography/computed tomography (18F-DOPA PET/CT) revealed a well-defined focal
region of increased tracer uptake at the junction of the pancreatic head and
body (A, white arrow). This uptake corresponded to a smoothly protruding lesion
on CT, with no abnormal accumulations elsewhere, allowing precise preoperative
localization of the hyperfunctional lesion and enabling a limited,
pancreas-sparing resection. Histopathological analysis further supported the
diagnosis: hematoxylin
and eosin staining (B)
demonstrated a nodular proliferation of islet-like endocrine cells, while immunostaining for insulin (C) showed strong, diffuse positivity
consistent with focal β-cell hyperplasia. Postoperatively, the patient achieved
stable normoglycemia without the need for glucose supplementation. Together,
panels A–C in this composite figure highlight how accurate localization with
18F-DOPA PET/CT guides curative, tissue-preserving surgery in focal CHI, even
in clinically complex contexts such as cases complicated by severe adverse
events—including NEC—during medical therapy.
Clinical practice guidelines for the management of differences of sex development in Japan
Released on J-STAGE: January 06, 2026 | Volume 35 Issue 1 Pages 1-49
Tomohiro Ishii, Kenichi Kashimada, Masanobu Kawai, Tomoyo Itonaga, Takeshi Iwasa, Akari Utsunomiya, Kayo Ozaki, Kazuhiro Kawamura, Junko Kanno, Jun Koh, Yoshiyuki Kojima, Shoko Sasaki, Hiroyuki Sato, Koji Shiraishi, Yasuhiro Naiki, Mitsuru Nishiyama, Takashi Hamajima, Yasuko Fujisawa, Noriko Makita, Katsuyuki Matsui, Toshihiro Yanai, Reiko Horikawa, Tsutomu Ogata
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Bone age: assessment methods and clinical applications
Released on J-STAGE: October 24, 2015 | Volume 24 Issue 4 Pages 143-152
Mari Satoh
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Analysis of 24-Hour Growth Hormone (GH) Profiles in Normal Children in Relation to Puberty
Released on J-STAGE: November 18, 2010 | Volume 3 Issue Supple5 Pages 237
Kerstin Albertsson-Wikland, Sten Rosberg, Johan Karlberg, Torgny Groth
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Assessment of Skeletal and Sexual Maturity: Theoretical and Practical Aspects
Released on J-STAGE: November 18, 2010 | Volume 2 Issue Supple3 Pages 15-33
Milo Zachmann
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Osteogenesis imperfecta: pathogenesis, classification, and treatment
Released on J-STAGE: July 01, 2025 | Volume 34 Issue 3 Pages 152-161
Kosei Hasegawa
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