RESUMO
Fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitors (TKIs) are increasingly being used off label in pediatrics. Long-term safety data are limited, and serious toxicities unique to pediatrics may emerge. In a retrospective analysis of patients less than 18 years of age with recurrent/refractory FGFR altered gliomas treated with FGFR TKIs at MSKCC (n = 7), we observed slipped capital femoral epiphyses in three of seven patients along with increased linear growth velocity. Clinicians should closely monitor bone health and have a low index of suspicion for serious orthopedic complications including slipped capital femoral epiphyses and inform patients of related risks as part of consent when treating with FGFR TKIs.
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The natriuretic peptide signaling pathway has been implicated in many cellular processes, including endochondral ossification and bone growth. More precisely, different mutations in the NPR-B receptor and the CNP ligand have been identified in individuals with either short or tall stature. In this study we show that the NPR-C receptor (encoded by NPR3) is also important for the regulation of linear bone growth. We report four individuals, originating from three different families, with a phenotype characterized by tall stature, long digits, and extra epiphyses in the hands and feet. In addition, aortic dilatation was observed in two of these families. In each affected individual, we identified a bi-allelic loss-of-function mutation in NPR3. The missense mutations (c.442T>C [p.Ser148Pro] and c.1088A>T [p.Asp363Val]) resulted in intracellular retention of the NPR-C receptor and absent localization on the plasma membrane, whereas the nonsense mutation (c.1524delC [p.Tyr508∗]) resulted in nonsense-mediated mRNA decay. Biochemical analysis of plasma from two affected and unrelated individuals revealed a reduced NTproNP/NP ratio for all ligands and also high cGMP levels. These data strongly suggest a reduced clearance of natriuretic peptides by the defective NPR-C receptor and consequently increased activity of the NPR-A/B receptors. In conclusion, this study demonstrates that loss-of-function mutations in NPR3 result in increased NPR-A/B signaling activity and cause a phenotype marked by enhanced bone growth and cardiovascular abnormalities.
Assuntos
Tecido Conjuntivo/anormalidades , Perda de Heterozigosidade/genética , Mutação/genética , Peptídeo Natriurético Tipo C/genética , Adolescente , Desenvolvimento Ósseo/genética , Anormalidades Cardiovasculares/genética , Criança , GMP Cíclico/genética , Feminino , Humanos , Masculino , Transdução de Sinais/genéticaRESUMO
This case report of a 14-year-old boy with arthralgia and clinically suspected inflammatory arthropathy highlights how magnetic resonance imaging (MRI) ultimately diagnosed skeletal dysplasia. A genetic evaluation revealed a transient receptor potential vanilloid 4 (TRPV4) pathogenic variant. This is a rare description of the MRI appearance of this type of dysplasia in long bone epiphyses corresponding with the histological findings of disrupted endochondral ossification. This report offers imaging support to the description of endochondral bone growth disruption in TRPV4-related skeletal dysplasias.
Assuntos
Osteoartrite , Osteocondrodisplasias , Adolescente , Humanos , Imageamento por Ressonância Magnética , Masculino , Osteocondrodisplasias/diagnóstico por imagem , OsteogêneseRESUMO
PURPOSE: To assess the literature on indications, outcomes, and complications in pediatric patients undergoing all-epiphyseal (AE) anterior cruciate ligament reconstruction (ACLR). METHODS: PubMed, Medline, and Embase were searched for literature evaluating AE ACLR in pediatric patients. All included studies were assessed for quality using the Methodological Index for Non-Randomized Studies (MINORS). Descriptive statistics are presented where applicable. RESULTS: Overall, 17 studies comprising 545 patients, with a mean age of 12.0 ± 1.2 (range 8-19) met the inclusion criteria. The graft choices in this systematic review included hamstring tendon autografts (75.4%, n = 403), quadriceps tendon autograft (6.2%, n = 33), Achilles tendon allograft (3.6%, n = 19) and posterior tibialis tendon allograft in one patient (0.2%, n = 1). Time of return-to-sport ranged from 8 to 22 months. Postoperative subjective IKDC scores were above 90 points. The rate of return-to-sport after AE ACLR was 93.2% (n = 219/235) and 77.9% (n = 142/183) of patients returned to sport at pre-injury level. The overall complication rate was 9.8% (n = 53/545) with the most common complication being ACL re-rupture (5.0%; n = 27/545). Only 1.5% (n = 8/545) of patients demonstrated growth disturbances. CONCLUSION: Overall, the AE ACLR technique can achieve good postoperative functional outcomes while notably minimizing the incidence of primary issue of physeal disruption and potential associated leg-length discrepancies. AE ACLR should be considered in pediatric patients with at least 2 years of skeletal growth remaining based on radiographic bone age to minimize the impact of growth-related complications. LEVEL OF EVIDENCE: IV (Systematic Review of Level III and IV evidence).
Assuntos
Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior , Lâmina de Crescimento/cirurgia , Adolescente , Lesões do Ligamento Cruzado Anterior/fisiopatologia , Reconstrução do Ligamento Cruzado Anterior/efeitos adversos , Reconstrução do Ligamento Cruzado Anterior/métodos , Traumatismos em Atletas/fisiopatologia , Traumatismos em Atletas/cirurgia , Criança , Lâmina de Crescimento/fisiopatologia , Humanos , Complicações Pós-Operatórias , Volta ao Esporte , Tendões/transplante , Transplante Autólogo , Transplante Homólogo , Adulto JovemRESUMO
Osteochondrosis is an abnormality of the epiphyses or epiphyseal equivalents (round bones and apophyses) during later stages of endochondral ossification. This process of abnormal endochondral ossification can occur at various locations throughout the body. The pathogenesis of osteochondrosis is under active investigation. In humans, the process of abnormal endochondral ossification has been attributed to a combination of vascular insult and trauma. Although the proposed etiology of osteochondrosis varies based on body part affected, the overall process is defined by necrosis, revascularization and repair. As such, common radiologic findings include those of osseous destruction and associated inflammation. The purpose of this review is to discuss the current understanding of osteochondroses as a disease entity and explore imaging features of osteochondroses throughout the body.
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Imageamento por Ressonância Magnética/métodos , Osteocondrose/diagnóstico por imagem , Radiografia/métodos , Epífises/diagnóstico por imagem , HumanosRESUMO
Objective: To observe the effect of primary cilia on growth plate chondrocyte proliferation of young rats with chronic renal insufficiency (CRI). Methods: Male 2-week-old Sprague-Dawley rats were randomly divided into two groups (with 10 in each group): Sham group (only left ureter was exposed) and CRI group (left ureter was ligated). Rats were sacrificed 2 weeks after operation and the total length of tibia was measured. Histological sections of tibia were taken to observe the chondrocytes of growth plate proliferative region and the expression rate of primary cilia. Chondrocytes from growth plate in two groups were isolated and cultured in vitro to P3 generation and the chondrocyte proliferation rate at 24 h were detected. The primary cilia expression rate and cilia length of chondrocytes were measured. Western blot was used to detect the expression of intraflagellar transport 88 (IFT88) protein and the gray scale was analyzed. Results: The total length of tibia was shorter in CRI group [(35.84±4.56) mm vs (42.33±3.44) mm, P=0.002]. The results of tibial histological section showed that chondrocytes of growth plate proliferative region were unorganized and the number of chondrocyte with columnar structure was less in CRI group (2.71±1.10 vs 7.68±1.32, P<0.001). The primary cilia expression rate of chondrocytes was higher in CRI group [(35.53±7.41)% vs (18.31±5.12)%, P<0.001]. The chondrocyte proliferation rate at 24 h was lower in CRI group [(11.38±6.10)% vs (24.35±8.46)%, P=0.001]. The primary cilia expression rate of chondrocytes was higher in CRI group [(60.12±7.86)% vs (32.17±8.97)%, P<0.001], and the primary cilia length of chondrocytes was longer in CRI group [(3.54±1.61) µm vs (1.96±0.82) µm, P=0.012]. The protein IFT88 was more highly expressed in CRI group (0.47±0.23 vs 0.17±0.10, P=0.001). Conclusion: The primary cilia expression rate of growth plate chondrocytes was higher in the rats with CRI, resulting in decreased chondrocyte proliferation rate and growth retardation of tibial growth plate.
Assuntos
Lâmina de Crescimento , Insuficiência Renal Crônica , Animais , Proliferação de Células , Condrócitos , Cílios , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Chondroblastomas are very rare benign primary bone tumors occurring preferentially in the epiphyses or apophyses of long bones in children and adolescents. In most cases the typical histological and imaging findings lead to a correct diagnosis that may be substantiated by demonstrating the highly specific point mutation in the H3F3B gene (p.K36M), either by sequencing or immunohistochemistry. Recurrences occur in 5-15% of cases, postsurgical metastatic deposits to the lungs are very rare (<1%). Histologically "malignant" chondroblastomas have been reported as single case reports. The treatment of choice is a thorough curettage, also in the case of local relapses.
Assuntos
Neoplasias Ósseas , Condroblastoma , Osso e Ossos , Humanos , Imuno-Histoquímica , Recidiva Local de NeoplasiaRESUMO
Tricho-Rhino-Phalangeal syndrome is a rare autosomal dominant genetic disorder caused by mutations in the TRPS1 gene. This malformation syndrome is characterized by distinctive craniofacial features including sparse scalp hair, bulbous tip of the nose, long flat philtrum, thin upper vermilion border, and protruding ears. Skeletal abnormalities include cone-shaped epiphyses at the phalanges, hip malformations, and short stature. In this report, we describe two patients with the physical manifestations and genotype of TRPS type I but with learning/intellectual disability not typically described as part of the syndrome. The first patient has a novel heterozygous two-base-pair deletion of nucleotides at 3198-3199 (c.3198-3199delAT) in the TRPS1 gene causing a translational frameshift and subsequent alternate stop codon. The second patient has a 3.08 million base-pair interstitial deletion at 8q23.3 (113,735,487-116,818,578), which includes the TRPS1 gene and CSMD3. Our patients have characteristic craniofacial features, Legg-Perthes syndrome, various skeletal abnormalities including cone shaped epiphyses, anxiety (first patient), and intellectual disability, presenting unusual phenotypes that add to the clinical spectrum of the disease.
Assuntos
Proteínas de Ligação a DNA/genética , Disostoses/genética , Deficiência Intelectual/genética , Doença de Legg-Calve-Perthes/genética , Osteocondrodisplasias/genética , Fatores de Transcrição/genética , Adolescente , Adulto , Disostoses/diagnóstico por imagem , Disostoses/fisiopatologia , Humanos , Deficiência Intelectual/diagnóstico por imagem , Deficiência Intelectual/fisiopatologia , Doença de Legg-Calve-Perthes/diagnóstico por imagem , Doença de Legg-Calve-Perthes/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Osteocondrodisplasias/diagnóstico por imagem , Osteocondrodisplasias/fisiopatologia , Proteínas Repressoras , Deleção de Sequência , Adulto JovemRESUMO
We retrospectively reviewed 29 hips in which intertrochanteric osteotomies were performed for severe slipped capital femoral epiphyses. Mean age at surgery: 12.6 years. Mean follow-up period: 6 years. At the final follow-up evaluation, one patient had coxalgia, and six hips showed a limited range of motion. A pistol-grip deformity was observed in 13 hips, osteoarthritis in two hips, and a bump existed in 19 hips on the latest radiographs. Gradual remodeling of the bumps was observed post-operatively in 22 hips. The mean α and ß angles and offset α and ß improved over time. The remodeling proceeded rapidly for 1 year post-surgery. We compared hips classified as ß angles of ≥ 63° to < 63° at the final follow-up evaluation, the mean ß angle 1 year post-surgery, and the mean ratio of improvement of the ß angle per year from 1 year post-surgery to the final follow up, which differed significantly. Nearly all of the patients who underwent intertrochanteric osteotomies had residual morphologic abnormalities, but few had clinical symptoms. The ß angle 1 year post-surgery and the ratio of remodeling of the bump from 1 year post-surgery to the final follow-up can be regarded as a potential predictor of morphologic results after intertrochanteric osteotomy.
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Impacto Femoroacetabular/patologia , Fêmur/patologia , Fêmur/cirurgia , Osteotomia/métodos , Escorregamento das Epífises Proximais do Fêmur/cirurgia , Adolescente , Criança , Epífises/patologia , Epífises/cirurgia , Feminino , Impacto Femoroacetabular/diagnóstico por imagem , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Slipped capital femoral epiphysis (SCFE), a fracture through the physis with resultant slip of the epiphysis, is the most common hip abnormality in adolescents and is a major cause of early osteoarthritis. Plain radiograph is the initial modality used to evaluate patients with painful hip joints. Ultrasonography and magnetic resonance imaging (MRI), which do not involve radiation exposure, have also been used. This case report supports the view that ultrasound can be used as an initial, cost-effective and radiation-free modality for the evaluation of suspected SCFE. CASE REPORT: A 15-year-old male patient presented with pain in the right hip for 5 days, following a slip and fall accident while playing soccer. The patient was referred to the Department of Radio-diagnosis for ultrasound. A posterior displacement of the femoral head epiphysis with a physeal step was seen on the longitudinal section obtained over the right hip joint region. The anterior physeal step (APS) measured ~3.8 mm on the right side. The distance between the anterior rim of the acetabulum and the metaphysis measured ~20.4 mm on the affected right side and ~23.6 mm on the left side. A plain radiograph in frog leg position showed a widening of the right proximal physis below the right femoral head, with a medial and posterior slip of the right femoral head. A frontal radiograph of the pelvis taken six months before showed a widening of the proximal right femoral physis. CONCLUSIONS: Although MRI appears to be the most sensitive modality for identifying slips early, ultrasound may be used as a cost-effective and radiation-free alternative before proceeding with further evaluation of suspected SCFE, especially considering the demographics of the affected population.
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Important aspects of forensic practice are age estimation and discrimination of individuals of unknown age as adults and minors. The developing knee joint was recognized as a potential site for age examination in late adolescence. We analyzed a sample of anteroposterior x-rays of the knee joints from 446 living individuals from Umbria, Italy (234 males and 212 females), aged between 12 and 26 years. We evaluated the ossification of the distal femoral (DF), proximal tibial (PT), and proximal fibular (PF) epiphyses. We took into account possible persistence of the epiphyseal scars in the ossified epiphyses by the adopted stages of those previously introduced by Cameriere et al. (2012). We also used measurements from all three epiphyses to calculate the total score of maturation for the knee joint (SKJ). Cohen Kappa coefficients of intrarater agreement for staging the DF, PT, and PF epiphyses were 0.839, 0.894, and 0.907, while interrater agreement was 0.919, 0.791, and 0.907, respectively. The resulting receiver operating characteristic (ROC) curves of SKJ show better discriminatory power than those for DF, PT, and PF epiphyses in predicting that the participant, either male or female, was an adult or a minor. The areas under the curves for SKJ were 0.991 and 0.968 vs. 0.944, 0.962, 0.974 and 0.891, 0.910, 0.918 for males and females, respectively. The results of the 2 by 2 contingency tables showed that SKJ score of 4 in males and SKJ score of 5 in females were the most suitable cut-off value in discriminating between adults and minors. Principally, the sensitivity test for males was 0.94, with 95 % confidence interval (95 % CI) 0.90 to 0.97 and specificity was 0.96 (95 % CI 0.91 to 0.98). The proportion of correctly classified individuals was 0.95 (95 % CI 0.91 to 0.97). For females, the sensitivity test was 0.89 (95 % CI 0.84 to 0.92) and specificity was 0.92 (95 % CI 0.87 to 0.96), the proportion of correctly classified individuals was 0.90 (95 % CI 0.85 to 0.94). These results indicate that the SKJ method may give valuable supporting information in forensic procedures for discriminating individuals of legal adult age of 18 years. Further studies should address the usefulness of the SKJ method in different populations.
Assuntos
Determinação da Idade pelo Esqueleto/métodos , Epífises/crescimento & desenvolvimento , Articulação do Joelho/crescimento & desenvolvimento , Osteogênese , Adolescente , Criança , Estudos Transversais , Epífises/diagnóstico por imagem , Feminino , Antropologia Forense , Humanos , Articulação do Joelho/diagnóstico por imagem , Masculino , Estudos Retrospectivos , Adulto JovemRESUMO
The so-called transitional fractures describe articular fractures in adolescents with partial closure of the epiphyseal growth plate. This shows a specific stereotype fracture pattern, which can be differentiated into biplane, triplane I and triplane II fractures depending on the involvement of the metaphysis and the number of fragments. The diagnostics and therapy can differ from fractures where the epiphyseal growth plate is still open. The main focus for surgical treatment is the reconstruction of the articular surface whereas relevant growth disturbances no longer need to be feared when the epiphysis has already begun to close.
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Lâmina de Crescimento/cirurgia , Fraturas Intra-Articulares/cirurgia , Osteotomia/métodos , Procedimentos de Cirurgia Plástica/métodos , Fraturas Salter-Harris/cirurgia , Medicina Baseada em Evidências , Humanos , Fraturas Intra-Articulares/diagnóstico , Osteotomia/instrumentação , Procedimentos de Cirurgia Plástica/instrumentação , Fraturas Salter-Harris/diagnóstico , Resultado do TratamentoRESUMO
Age estimation is a crucial parameter involved in investigations pertaining to civil and criminal procedures. It also aids in various examinations in forensic medicine, pediatrics, endocrinology and radiology. One of the important methods for skeletal age estimation is the age of fusion of the epiphyses. But there occur variations in the skeletal ages due to environmental, hormonal, ethnic and other factors. Hence, there arises the need for separate standards of ossification for different regions. The present study was conducted to ascertain the age of fusion of the distal radial and ulnar epiphyses in Kashmiri population. A total of 160 healthy subjects, including 80 males and 80 females with ages ranging from 12 to 20years were studied. Their chronological age was obtained and the X-ray of their left hand was taken in the A.P view after taking the consent from their parents. The starting of epiphyseal fusion in lower end of radius in male was observed at 15-16years in 20% of the male population and for females, it was observed at 13-14years in 10% of the female population. The completion of epiphyseal fusion in lower end of radius in 100% males was noticed at 18-19years and for 100% females, it was noticed at 17-18years. The starting up of epiphyseal fusion in lower end of ulna in males was observed at 14-15years in 10% of the male population and for females, it was observed at 13-14years in 10% of the female population. The completion of epiphyseal fusion in lower end of ulna in 100% males was noticed at 18-19years and for 100% females, it was noticed at 17-18years. In case of males the age of fusion of the epiphyses of lower end of radius and lower end of ulna was found to be in the same age group 18 to 19years. Also in case of females the age of fusion of the epiphyses of lower end of radius and lower end of ulna was found to be in the same age group 17 to 18years. It was further observed that females showed fusion in advance of male subjects. The findings of this study were compared with those reported from other states of India and also from other countries.
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Determinação da Idade pelo Esqueleto/métodos , Epífises/diagnóstico por imagem , Osteogênese , Rádio (Anatomia)/diagnóstico por imagem , Ulna/diagnóstico por imagem , Adolescente , Criança , Epífises/crescimento & desenvolvimento , Feminino , Antropologia Forense , Humanos , Índia , Masculino , Rádio (Anatomia)/crescimento & desenvolvimento , Determinação do Sexo pelo Esqueleto/métodos , Ulna/crescimento & desenvolvimento , Adulto JovemRESUMO
People aged 18 years could be punished lightly or diminished criminal responsibility, even be spared the death sentence, which has important meaning in Chinese judicatory adjudication. The epiphysis of long bones from human limbs and the secondary sexual characteristics almost have developed completely before 18 years old. Clavicle epiphysis is one of the articular metaphysis which has a late epiphyseal closure. The recent studies in exploring the rule of clavicle epiphyseal by multi-imaging technology shows that the development of clavicle epiphysis has some value in age estimation of 18 years old. CT, especially thin-section CT, is widely used at present. However, thin-section CT scanning has great net radiation, which is not ethically acceptable if it is not for diagnosis and treatment. MRI is nonradioactive tomographic imaging and easy to evaluate, which is one of the future research directions in forensic age estimation using the medial clavicle. This paper summarizes the progress on the rule of clavicle epiphyseal closure, and analyzes and summarizes the feasibility of rule of clavicle epiphyseal closure applies on age estimation.
Assuntos
Clavícula/fisiologia , Epífises/fisiologia , Osteogênese , Adolescente , Determinação da Idade pelo Esqueleto , Povo Asiático , Morte , Antropologia Forense , Humanos , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios XRESUMO
Forensic age estimation based on staging of ossification of the medial clavicular bone is one of the methods recommended by the Study Group on Forensic Age Diagnostics of the German Association of Forensic Medicine. In the present study, we analyzed the stages of ossification of the medial clavicular epiphyses on thin-sliced (1 mm) computed tomography (CT) images using the substages defined within stages 2 and 3. The retrospective CT analysis involved 193 subjects (129 males, 64 females) ranging in age from 13 to 28 years. Spearman's correlation analysis revealed a positive correlation between age and ossification stage in both male and female subjects. Stage 3c was first observed at 19 years of age in both sexes and may thus serve as a valuable forensic marker for determining an age of 18 years. Although further research is needed on the ossification stages of the medial clavicular epiphyses, the present findings could contribute to existing reports on observers' experiences using CT analysis of ossification combined with analysis of substages.
Assuntos
Determinação da Idade pelo Esqueleto/métodos , Clavícula/diagnóstico por imagem , Osteogênese , Adolescente , Adulto , Clavícula/anatomia & histologia , Epífises/anatomia & histologia , Epífises/diagnóstico por imagem , Feminino , Antropologia Forense , Humanos , Masculino , Estudos Retrospectivos , Turquia , Adulto JovemRESUMO
We report on a consanguineous Arab family in which three sibs had an unusual skeletal dysplasia characterized by anterior defects of the spine leading to severe lumbar kyphosis and marked brachydactyly with cone epiphyses. The clinical phenotype also included dysmorphic facial features, epilepsy, and developmental delay. This constellation likely represents a previously undescribed skeletal dysplasia, most probably inherited in an autosomal recessive pattern. A homozygosity mapping approach has thus far failed to unearth the responsible gene as the region shared by these three sibs is 27.7 Mb in size and contains over 200 genes with no obvious candidate.
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Anormalidades Musculoesqueléticas/diagnóstico por imagem , Anormalidades Musculoesqueléticas/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Mãos/diagnóstico por imagem , Mãos/patologia , Haplótipos/genética , Humanos , Lactente , Recém-Nascido , Joelho/diagnóstico por imagem , Joelho/patologia , Masculino , Anormalidades Musculoesqueléticas/patologia , Linhagem , Pelve/diagnóstico por imagem , Pelve/patologia , Gravidez , Radiografia , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/patologiaRESUMO
We present 2 siblings with multiple complete pseudoepiphyses in their hands and feet with associated symptomatic enhanced growth. Physical examination of the 6-year-old boy revealed long slender fingers and hyperplastic great toes. Radiography showed complete pseudoepiphyses in the first metacarpals, proximal and middle phalanges of the hands, and proximal phalanges of the feet. The patient's younger brother had a similar phenotype with slightly milder functional complaints. Genetic analysis did not reveal an underlying syndrome in these siblings.
Assuntos
Epífises/anormalidades , Pé/crescimento & desenvolvimento , Mãos/crescimento & desenvolvimento , Ossos Metacarpais/anormalidades , Ossos do Metatarso/anormalidades , Criança , Epífises/diagnóstico por imagem , Pé/diagnóstico por imagem , Mãos/diagnóstico por imagem , Humanos , Masculino , Ossos Metacarpais/diagnóstico por imagem , Ossos Metacarpais/cirurgia , Ossos do Metatarso/diagnóstico por imagem , Ossos do Metatarso/cirurgia , Radiografia , IrmãosRESUMO
In previous reports, hypothyroidism, hypopituitrism, and hypogonadism were common endocrine causes of SCFE, but this is the first time that congenital adrenal hyperplasia has been observed. As such, patients who have undergone long-term endocrine treatment for congenital adrenal hyperplasia could potentially be subjected to a higher risk for SCFE.