OBJECTIVESEstrogen insensitivity syndrome (EIS) is a rare genetic disorder characterized by an autosomal dominant inheritance pattern. The disease results from a pathogenic variant in the ESR1 (estrogen receptor 1) gene, leading to estrogen resistance in individuals possessing the 46, XX karyotype. The alpha receptor, which is predominant in peripheral tissues, is responsible for estrogen action. As a result, pathogenic variants in the ESR1 gene can cause various disorders, such as changes in secondary sexual characteristics, increased concentrations of estrogen and gonadotropins, and delayed bone maturation.CASE PRESENTATIONHere, the case of a 13-year-old girl, with high estrogen and gonadotropin concentrations, lack of breast development, uterine growth and delayed bone age is described. The patient's parents were related. She was found to have a homozygous pathogenic variant in the ESR1 gene located on chromosome 6q25, which interferes with estrogen signaling.CONCLUSIONThis case supports that disruption of ESR1 causes profound estrogen resistance in females.
目的雌激素不敏感综合征（EIS）是一种罕见的遗传性疾病，具有常染色体显性遗传的特点。该病是由 ESR1（雌激素受体 1）基因中的一个致病变体引起的，导致 46 XX 核型的个体对雌激素产生抗性。α受体主要存在于外周组织中，负责雌激素的作用。因此，ESR1 基因的致病变异可导致各种疾病，如第二性征改变、雌激素和促性腺激素浓度升高、骨龄延迟等。病例介绍：本病例描述了一名 13 岁女孩的病例，她患有雌激素和促性腺激素浓度升高、乳房发育不良、子宫发育不良和骨龄延迟等疾病。患者的父母是亲戚。该病例证实，ESR1 基因紊乱会导致女性出现严重的雌激素抵抗。
{"title":"Estrogen-insensitivity syndrome (EIS) in a female adolescent patient - a case report.","authors":"Akbar Soltani,Mahdieh Fatollahzadeh,Pantea Izadi,Zahra Abbaspour Rad,Zahra Hoseini Tavassol,Hamid Pajavand,Masoomeh Amini,Shirin Hasani-Ranjbar","doi":"10.1515/jpem-2024-0176","DOIUrl":"https://doi.org/10.1515/jpem-2024-0176","url":null,"abstract":"OBJECTIVESEstrogen insensitivity syndrome (EIS) is a rare genetic disorder characterized by an autosomal dominant inheritance pattern. The disease results from a pathogenic variant in the ESR1 (estrogen receptor 1) gene, leading to estrogen resistance in individuals possessing the 46, XX karyotype. The alpha receptor, which is predominant in peripheral tissues, is responsible for estrogen action. As a result, pathogenic variants in the ESR1 gene can cause various disorders, such as changes in secondary sexual characteristics, increased concentrations of estrogen and gonadotropins, and delayed bone maturation.CASE PRESENTATIONHere, the case of a 13-year-old girl, with high estrogen and gonadotropin concentrations, lack of breast development, uterine growth and delayed bone age is described. The patient's parents were related. She was found to have a homozygous pathogenic variant in the ESR1 gene located on chromosome 6q25, which interferes with estrogen signaling.CONCLUSIONThis case supports that disruption of ESR1 causes profound estrogen resistance in females.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OBJECTIVESTo highlight the occurrence of premature ovarian insufficiency in pediatric cancer patients and determine which patient characteristics or treatment modalities are associated with ovarian failure and recovery.METHODSBetween August 2011-August 2021, 36 of 2,661 patients with cancer were identified to have subsequent ovarian failure. Data collected included cancer type, diagnosis age, types of chemotherapy, bone marrow transplant or radiation treatment, peak FSH, peak AMH, GnRHa treatment, type of hormone replacement therapy, and if ovarian function recovery occurred.RESULTSThe most common cancer type identified was ALL. The mean age of diagnosis was 8.5±4.3 years and mean age of peak FSH value was 12.6±2.8 years. Most patients (97.2 %) were treated with alkylating agents and 72.2 % received radiation. Most patients (72.2 %) received hormone therapy, and 15.8 % of patients received GnRHa Lupron. Ten patients (27.8 %) had ovarian function recovery. Diagnosis age and treatment type were recovery predictors in multivariate regression modeling. Each year older in age was associated with a 30 % decrease in odds of recovery (OR: 0.7, CI: 0.5-0.95, p=0.035), and alkylating agent treatment without transplant was associated with a 3-fold increase in odds of recovery (OR: 3, CI: 2.7-564, p=0.007).CONCLUSIONSThis retrospective review demonstrates that POI can occur in pediatric cancer survivors, emphasizing the importance of educating patients on potential long-term effects of cancer treatment and importance of routine surveillance. This study confirmed that recovery of ovarian function is possible, especially when diagnosed at a younger age, making continued monitoring essential.
{"title":"Premature ovarian insufficiency in pediatric cancer patients: a 10 year Rady Children's hospital experience.","authors":"Miranda Robinson,Leo Meller,Mary Patterson","doi":"10.1515/jpem-2024-0207","DOIUrl":"https://doi.org/10.1515/jpem-2024-0207","url":null,"abstract":"OBJECTIVESTo highlight the occurrence of premature ovarian insufficiency in pediatric cancer patients and determine which patient characteristics or treatment modalities are associated with ovarian failure and recovery.METHODSBetween August 2011-August 2021, 36 of 2,661 patients with cancer were identified to have subsequent ovarian failure. Data collected included cancer type, diagnosis age, types of chemotherapy, bone marrow transplant or radiation treatment, peak FSH, peak AMH, GnRHa treatment, type of hormone replacement therapy, and if ovarian function recovery occurred.RESULTSThe most common cancer type identified was ALL. The mean age of diagnosis was 8.5±4.3 years and mean age of peak FSH value was 12.6±2.8 years. Most patients (97.2 %) were treated with alkylating agents and 72.2 % received radiation. Most patients (72.2 %) received hormone therapy, and 15.8 % of patients received GnRHa Lupron. Ten patients (27.8 %) had ovarian function recovery. Diagnosis age and treatment type were recovery predictors in multivariate regression modeling. Each year older in age was associated with a 30 % decrease in odds of recovery (OR: 0.7, CI: 0.5-0.95, p=0.035), and alkylating agent treatment without transplant was associated with a 3-fold increase in odds of recovery (OR: 3, CI: 2.7-564, p=0.007).CONCLUSIONSThis retrospective review demonstrates that POI can occur in pediatric cancer survivors, emphasizing the importance of educating patients on potential long-term effects of cancer treatment and importance of routine surveillance. This study confirmed that recovery of ovarian function is possible, especially when diagnosed at a younger age, making continued monitoring essential.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OBJECTIVESThe aim of the study was to investigate whether retinal neurovascular structural impairment in children with partial biotinidase deficiency (BD) could be detected early via optical coherence tomography (OCT) and OCT angiography (OCTA).METHODSEighty patients with partial BD and 80 control cases without any known systemic or ocular diseases were enrolled in this prospective study. Retinal neurovascular structures in the macular and optic disc regions were examined in using OCT and OCTA. Data from subjects with partial BD were compared with data from healthy controls.RESULTSA statistically significant decrease in the vessel density (VD) was observed in both superior and inferior parts of the superficial capillary plexus (SCP) and the deep capillary plexus (DCP) in the partial BD patient group compared with the control group (p<0.05). A significant decrease in the VD was also observed in the superior and inferior peripapillary SCP-DCP regions of the optic disc area in the patients with partial BD (p<0.05). Both the superficial and deep foveal avascular zone (FAZ) areas were significantly enlarged in the partial BD group with respect to the control group (p=0.026, p=0.021 respectively).CONCLUSIONSIn the partial BD patients, the vascular density in the macula and optic disc region is decreased in childhood, when compared to the control group. In patients with partial BD, it would be very useful to detect the early neurovascular changes that may occur during the course of the disease by means of a noninvasive technique such as OCTA.
{"title":"Alterations in optical coherence tomography and optical coherence tomography angiography findings in children with partial biotinidase deficiency.","authors":"Gamze Karataş,Akın Çakır,Nafiye Emel Çakar,Derya Çepni Çakır,Mehmet Egemen Karataş,Ozan Akpunar,Aslı Kırmacı Kabakcı,Dilan Yıldız","doi":"10.1515/jpem-2024-0261","DOIUrl":"https://doi.org/10.1515/jpem-2024-0261","url":null,"abstract":"OBJECTIVESThe aim of the study was to investigate whether retinal neurovascular structural impairment in children with partial biotinidase deficiency (BD) could be detected early via optical coherence tomography (OCT) and OCT angiography (OCTA).METHODSEighty patients with partial BD and 80 control cases without any known systemic or ocular diseases were enrolled in this prospective study. Retinal neurovascular structures in the macular and optic disc regions were examined in using OCT and OCTA. Data from subjects with partial BD were compared with data from healthy controls.RESULTSA statistically significant decrease in the vessel density (VD) was observed in both superior and inferior parts of the superficial capillary plexus (SCP) and the deep capillary plexus (DCP) in the partial BD patient group compared with the control group (p<0.05). A significant decrease in the VD was also observed in the superior and inferior peripapillary SCP-DCP regions of the optic disc area in the patients with partial BD (p<0.05). Both the superficial and deep foveal avascular zone (FAZ) areas were significantly enlarged in the partial BD group with respect to the control group (p=0.026, p=0.021 respectively).CONCLUSIONSIn the partial BD patients, the vascular density in the macula and optic disc region is decreased in childhood, when compared to the control group. In patients with partial BD, it would be very useful to detect the early neurovascular changes that may occur during the course of the disease by means of a noninvasive technique such as OCTA.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elaine C Kennedy,Maria Stack,Eirin Carolan,Maeve Durkan,Caroline M Joyce,Colin P Hawkes
OBJECTIVESCongenital adrenal hyperplasia (CAH) is an uncommon genetic disorder which affects cortisol production in the adrenal glands. It is usually treated with glucocorticoids. We present a case of non-classical CAH caused by the partial deficiency of 11 beta-hydroxylase (11βOH) which was treated with aldosterone antagonist (eplerenone) monotherapy.CASE PRESENTATIONAn adolescent male was diagnosed with 11 beta-hydroxylase deficiency (11βOHD) at 13 years of age when he presented with hypertension, fatigue and headaches. He was initially treated with glucocorticoids, but requested an alternative therapy. Eplerenone was commenced at 25 mg with subsequent dose increases to 100 mg daily. His hypertension was controlled on this regimen, achieving a 24 h average blood pressure of 124/81 mmHg.CONCLUSIONSCAH caused by 11βOHD is a known cause of hypertension. It is usually managed with glucocorticoids, and antihypertensives are added if blood pressure remains uncontrolled. In this case, glucocorticoid therapy was not tolerated and treatment with aldosterone antagonist monotherapy was effective in controlling his hypertension.
{"title":"Mineralocorticoid receptor antagonist monotherapy in pediatric non-classical 11β-hydroxylase deficiency.","authors":"Elaine C Kennedy,Maria Stack,Eirin Carolan,Maeve Durkan,Caroline M Joyce,Colin P Hawkes","doi":"10.1515/jpem-2024-0194","DOIUrl":"https://doi.org/10.1515/jpem-2024-0194","url":null,"abstract":"OBJECTIVESCongenital adrenal hyperplasia (CAH) is an uncommon genetic disorder which affects cortisol production in the adrenal glands. It is usually treated with glucocorticoids. We present a case of non-classical CAH caused by the partial deficiency of 11 beta-hydroxylase (11βOH) which was treated with aldosterone antagonist (eplerenone) monotherapy.CASE PRESENTATIONAn adolescent male was diagnosed with 11 beta-hydroxylase deficiency (11βOHD) at 13 years of age when he presented with hypertension, fatigue and headaches. He was initially treated with glucocorticoids, but requested an alternative therapy. Eplerenone was commenced at 25 mg with subsequent dose increases to 100 mg daily. His hypertension was controlled on this regimen, achieving a 24 h average blood pressure of 124/81 mmHg.CONCLUSIONSCAH caused by 11βOHD is a known cause of hypertension. It is usually managed with glucocorticoids, and antihypertensives are added if blood pressure remains uncontrolled. In this case, glucocorticoid therapy was not tolerated and treatment with aldosterone antagonist monotherapy was effective in controlling his hypertension.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OBJECTIVESSpondylo-epimetaphyseal dysplasia-aggregan (SEMD-ACAN) is a rare form of osteo-chondrodysplasia that includes vertebral, epiphyseal and metaphyseal dysplasia. It occurs as a result of loss-of-function mutations in the ACAN gene, which encodes aggregan protein, which is the basic component of the extracellular matrix in cartilage. It results in disproportionately short stature and skeletal abnormalities. Here, we aimed to present the fourth SEMD-ACAN report in the literature.CASE PRESENTATIONA 9-year-old girl was admitted to our clinic with growth retardation. She was born from a first-degree cousin marriage with severe short stature (41 cm; -3.54 SDS). Her mother also had severe short stature. Her height was 110 cm (-4.6 SDS); she had midface hypoplasia, low-set ears, short neck, short limbs, and central obesity. Biochemical and hormonal tests were normal. Skeletal survey showed moderate platyspondylia, thoracolumbar scoliosis, lumbar lordosis, bilateral femoro-acetabular narrowing, and advanced bone age (10 years). The patient's brother was 100 cm (-3.97 SDS). He had similar but milder clinical findings. Biallelic ACAN variation (c.512C>T; p. Ala171Val) was detected in two siblings by next-generation sequencing. The parents were heterozygous carriers. Before, the heterozygous form of this variant has been reported in a 15-year-old boy with short stature, advanced bone age, and dysmorphic features.CONCLUSIONSSEMD-ACAN is a rare genetic condition that affects bone growth and development and can cause physical and developmental abnormalities. This article highlights the importance of considering genetic testing in characteristic symptoms associated with SEMD-ACAN, such as severe growth retardation and skeletal abnormalities.
{"title":"A rare case of skeletal dysplasia: biallelic variant in ACAN gene.","authors":"Gülçin Arslan,Filiz Hazan,Gülin Tabanlı,Tarık Kırkgöz,Behzat Özkan","doi":"10.1515/jpem-2024-0255","DOIUrl":"https://doi.org/10.1515/jpem-2024-0255","url":null,"abstract":"OBJECTIVESSpondylo-epimetaphyseal dysplasia-aggregan (SEMD-ACAN) is a rare form of osteo-chondrodysplasia that includes vertebral, epiphyseal and metaphyseal dysplasia. It occurs as a result of loss-of-function mutations in the ACAN gene, which encodes aggregan protein, which is the basic component of the extracellular matrix in cartilage. It results in disproportionately short stature and skeletal abnormalities. Here, we aimed to present the fourth SEMD-ACAN report in the literature.CASE PRESENTATIONA 9-year-old girl was admitted to our clinic with growth retardation. She was born from a first-degree cousin marriage with severe short stature (41 cm; -3.54 SDS). Her mother also had severe short stature. Her height was 110 cm (-4.6 SDS); she had midface hypoplasia, low-set ears, short neck, short limbs, and central obesity. Biochemical and hormonal tests were normal. Skeletal survey showed moderate platyspondylia, thoracolumbar scoliosis, lumbar lordosis, bilateral femoro-acetabular narrowing, and advanced bone age (10 years). The patient's brother was 100 cm (-3.97 SDS). He had similar but milder clinical findings. Biallelic ACAN variation (c.512C>T; p. Ala171Val) was detected in two siblings by next-generation sequencing. The parents were heterozygous carriers. Before, the heterozygous form of this variant has been reported in a 15-year-old boy with short stature, advanced bone age, and dysmorphic features.CONCLUSIONSSEMD-ACAN is a rare genetic condition that affects bone growth and development and can cause physical and developmental abnormalities. This article highlights the importance of considering genetic testing in characteristic symptoms associated with SEMD-ACAN, such as severe growth retardation and skeletal abnormalities.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vallimayil Velayutham, Suparna Chakrabarty, Ristan Greer, Andrew M. Cotterill, Gary M. Leong
Objectives We hypothesised that growth hormone (GH) deficiency (GHD) in children with attention deficit hyperactivity disorder (ADHD) is rare. This study aimed to determine any distinct clinical or biochemical parameters, including GH provocation testing, in children with ADHD on psychostimulants or idiopathic short stature (ISS). Methods Retrospective cross-sectional study of children who had GH provocative testing between 1998 and 2013 at one tertiary paediatric endocrine centre. Clinical data included age, sex, anthropometry, pubertal staging, bone age, diagnostic code as per the European Society Paediatric Endocrinology (ESPE), GH provocation test results, thyroid function tests, serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) levels. Results Four hundred ninety-three subjects underwent GH provocation testing for investigation of short stature to exclude GHD during the study period. Fifty-one children had a diagnosis of ADHD. In the remaining children, the diagnosis was Idiopathic short stature (n=240), GHD +/− hypopituitarism (n=60), and 142 subjects had other causes of short stature. Children with ADHD were older, had higher height and weight SDS and were GH-sufficient. All 51 children with ADHD had a normal serum IGFBP-3, while 20 out of these 51 subjects had a low serum IGF-1. Conclusions GHD in children with ADHD on psychostimulant medication is rare. GH testing in children with ADHD may not be necessary, particularly if serum IGFBP-3 is in the normal range. We suggest IGFBP-3 could be used as a surrogate marker of GH sufficiency in children with ADHD. However, this needs to be confirmed with a larger study group.
{"title":"Slow growth and short stature in children with attention deficit hyperactivity disorder (ADHD): a retrospective study of 493 children who underwent growth hormone provocation testing at one tertiary paediatric endocrine centre","authors":"Vallimayil Velayutham, Suparna Chakrabarty, Ristan Greer, Andrew M. Cotterill, Gary M. Leong","doi":"10.1515/jpem-2024-0268","DOIUrl":"https://doi.org/10.1515/jpem-2024-0268","url":null,"abstract":"Objectives We hypothesised that growth hormone (GH) deficiency (GHD) in children with attention deficit hyperactivity disorder (ADHD) is rare. This study aimed to determine any distinct clinical or biochemical parameters, including GH provocation testing, in children with ADHD on psychostimulants or idiopathic short stature (ISS). Methods Retrospective cross-sectional study of children who had GH provocative testing between 1998 and 2013 at one tertiary paediatric endocrine centre. Clinical data included age, sex, anthropometry, pubertal staging, bone age, diagnostic code as per the European Society Paediatric Endocrinology (ESPE), GH provocation test results, thyroid function tests, serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) levels. Results Four hundred ninety-three subjects underwent GH provocation testing for investigation of short stature to exclude GHD during the study period. Fifty-one children had a diagnosis of ADHD. In the remaining children, the diagnosis was Idiopathic short stature (n=240), GHD +/− hypopituitarism (n=60), and 142 subjects had other causes of short stature. Children with ADHD were older, had higher height and weight SDS and were GH-sufficient. All 51 children with ADHD had a normal serum IGFBP-3, while 20 out of these 51 subjects had a low serum IGF-1. Conclusions GHD in children with ADHD on psychostimulant medication is rare. GH testing in children with ADHD may not be necessary, particularly if serum IGFBP-3 is in the normal range. We suggest IGFBP-3 could be used as a surrogate marker of GH sufficiency in children with ADHD. However, this needs to be confirmed with a larger study group.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoqian Chen, Man Hu, Tingting Du, Luhong Yang, Yakun Li, Lifang Feng, Juan Luo, Hui Yao, Xiaohong Chen
Objectives Congenital hypogonadotropic hypogonadism (CHH) is a rare condition caused by a defect in the production, secretion or action of gonadotropin-releasing hormone. The absence of puberty and varying degrees of gonadotropic deficiency are common symptoms of this disorder. Heterogeneity exists in the clinical presentation of the different clinical subtypes and multiple genes have been implicated in CHH. A number of genetic defects have been identified as causes normosmic CHH, including mutations of GnRHR, GNRH1, KISS1R, KISS1, TACR3 and TAC3. Loss-of-function mutations in KISS1R gene are a rare cause of normosmic CHH. Case presentation We described an 11.5 years old Chinese patient who presented at birth with micropenis, microorchidia and bilateral cryptorchidism. Whole-exome sequencing was also performed and identified a homozygous mutation of KISS1R gene, c.1010_1028del (p.V337Afs*82). The variant was predicted as “deleterious” and classified as “likely pathogenic”. This variant has never been reported in patients with CHH. Furthermore, we summarized the clinical presentations and analyzed the phenotype-genotype correlation between CHH and KISS1R mutations in previous reports. Conclusions This study details the clinical phenotypes and hormone levels of the patient and expands the spectrum of mutations in the KISS1R gene associated with CHH.
{"title":"Homozygous mutation of KISS1 receptor (KISS1R) gene identified in a Chinese patient with congenital hypogonadotropic hypogonadism (CHH): case report and literature review","authors":"Xiaoqian Chen, Man Hu, Tingting Du, Luhong Yang, Yakun Li, Lifang Feng, Juan Luo, Hui Yao, Xiaohong Chen","doi":"10.1515/jpem-2024-0119","DOIUrl":"https://doi.org/10.1515/jpem-2024-0119","url":null,"abstract":"Objectives Congenital hypogonadotropic hypogonadism (CHH) is a rare condition caused by a defect in the production, secretion or action of gonadotropin-releasing hormone. The absence of puberty and varying degrees of gonadotropic deficiency are common symptoms of this disorder. Heterogeneity exists in the clinical presentation of the different clinical subtypes and multiple genes have been implicated in CHH. A number of genetic defects have been identified as causes normosmic CHH, including mutations of <jats:italic>GnRHR</jats:italic>, <jats:italic>GNRH1</jats:italic>, <jats:italic>KISS1R</jats:italic>, <jats:italic>KISS1</jats:italic>, <jats:italic>TACR3</jats:italic> and <jats:italic>TAC3</jats:italic>. Loss-of-function mutations in <jats:italic>KISS1R</jats:italic> gene are a rare cause of normosmic CHH. Case presentation We described an 11.5 years old Chinese patient who presented at birth with micropenis, microorchidia and bilateral cryptorchidism. Whole-exome sequencing was also performed and identified a homozygous mutation of <jats:italic>KISS1R</jats:italic> gene, c.1010_1028del (p.V337Afs*82). The variant was predicted as “deleterious” and classified as “likely pathogenic”. This variant has never been reported in patients with CHH. Furthermore, we summarized the clinical presentations and analyzed the phenotype-genotype correlation between CHH and <jats:italic>KISS1R</jats:italic> mutations in previous reports. Conclusions This study details the clinical phenotypes and hormone levels of the patient and expands the spectrum of mutations in the <jats:italic>KISS1R</jats:italic> gene associated with CHH.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142224933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amani Osman, Amr Morsi, Sherif El-Refee, Sara Suliman
Objectives To present the clinical journey and management of a 15-year-old female with SHORT syndrome, highlighting the diagnostic challenges and the novel genetic mutation identified. Case presentation A 15-year-old Filipino female was initially seen in a dermatology clinic at 9 years old for axillary skin darkening, indicative of acanthosis nigricans. Early evaluations revealed elevated blood glucose levels, resulting in a pediatric diabetes diagnosis without the usual hyperglycemic symptoms. Her medical history was notable for premature birth, intrauterine growth restriction, a cardiac murmur from patent ductus arteriosus and a bicuspid aortic valve, delayed teething, and distinct dysmorphic features. Genetic testing identified a novel PIK3R1 gene mutation. Treatment with Metformin significantly improved her glycemic control and lipid profiles. The patient also displayed delayed puberty and polycystic ovary syndrome-like symptoms, but growth hormone deficiency was excluded. Endocrine evaluation for her short stature and lipodystrophy confirmed the presence of the PIK3R1 mutation. Conclusions This case highlights the importance of thorough endocrine and genetic evaluations in patients with complex clinical presentations like SHORT syndrome. The identification of a novel PIK3R1 gene mutation expands the understanding of the genetic basis of this syndrome and underscores the need for individualized treatment approaches.
{"title":"Novel PIK3R1 gene mutation associated with SHORT syndrome: a case report of a 15-year-old female","authors":"Amani Osman, Amr Morsi, Sherif El-Refee, Sara Suliman","doi":"10.1515/jpem-2024-0244","DOIUrl":"https://doi.org/10.1515/jpem-2024-0244","url":null,"abstract":"Objectives To present the clinical journey and management of a 15-year-old female with SHORT syndrome, highlighting the diagnostic challenges and the novel genetic mutation identified. Case presentation A 15-year-old Filipino female was initially seen in a dermatology clinic at 9 years old for axillary skin darkening, indicative of acanthosis nigricans. Early evaluations revealed elevated blood glucose levels, resulting in a pediatric diabetes diagnosis without the usual hyperglycemic symptoms. Her medical history was notable for premature birth, intrauterine growth restriction, a cardiac murmur from patent ductus arteriosus and a bicuspid aortic valve, delayed teething, and distinct dysmorphic features. Genetic testing identified a novel PIK3R1 gene mutation. Treatment with Metformin significantly improved her glycemic control and lipid profiles. The patient also displayed delayed puberty and polycystic ovary syndrome-like symptoms, but growth hormone deficiency was excluded. Endocrine evaluation for her short stature and lipodystrophy confirmed the presence of the PIK3R1 mutation. Conclusions This case highlights the importance of thorough endocrine and genetic evaluations in patients with complex clinical presentations like SHORT syndrome. The identification of a novel PIK3R1 gene mutation expands the understanding of the genetic basis of this syndrome and underscores the need for individualized treatment approaches.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives The study aimed to evaluate the correlation between self-reported pubertal developmental scale (PDS) and physically assessed Tanner staging by an experienced pediatrician among girls. Methods In a school population-based study in Zhongshan, China, we recruited 1,722 girls in grades 1–3 by a multistage stratified cluster random sampling method. Participants completed self-reported PDS questionnaire prior to physical examination. Breast development was evaluated by a female pediatrician combined with ultrasound examination for overweight/obese girls; pubic hair development was evaluated. Otherwise, we tested follicle-stimulating hormone (FSH) and luteinizing hormone (LH) for some participants. Results We observed a weak association between Tanner-derived composite stage (TDCS) and puberty category scores (PCS) (τ=0.288, p<0.001) among all girls. There was correlation (τ=0.314, p=0.001) between ultrasound-derived composite stage (UDCS) and PCS among overweight/obese girls. Moreover, among overweight/obese girls, PCS was positively correlated with LH (r=0.265, p=0.008), but not FSH (r=0.155, p=0.123), and when the basal LH value was greater than 0.3 mIU/mL, the proportion of PCS stage ≥2 (9/18) was higher than the proportion of TDCS ≥2 (5/18). As for the determination of pubertal onset, when UDCS was used as the gold standard, the specificity of PCS was 0.86 and positive predictive value was 90.00 %. Conclusions There was a weak correlation between PCS and TDCS among girls early adolescence. Moreover, among overweight/obese girls, combining hormone values, ultrasonographic stage of breast, and the positive predictive value of PCS, we posit that self-reported PDS might be a more reliable method than TDCS to evaluate pubertal development among overweight/obese girls.
{"title":"Reliability of self-reported pubertal development scale for girls in early adolescent: a school population-based study","authors":"Cuilan Lin, Dongxue Pan, Tingting Yu, Sizhe Huang, Xin Lai, Jianming Peng, Bihong Zhang, Shijian Liu, Simao Fu","doi":"10.1515/jpem-2024-0272","DOIUrl":"https://doi.org/10.1515/jpem-2024-0272","url":null,"abstract":"Objectives The study aimed to evaluate the correlation between self-reported pubertal developmental scale (PDS) and physically assessed Tanner staging by an experienced pediatrician among girls. Methods In a school population-based study in Zhongshan, China, we recruited 1,722 girls in grades 1–3 by a multistage stratified cluster random sampling method. Participants completed self-reported PDS questionnaire prior to physical examination. Breast development was evaluated by a female pediatrician combined with ultrasound examination for overweight/obese girls; pubic hair development was evaluated. Otherwise, we tested follicle-stimulating hormone (FSH) and luteinizing hormone (LH) for some participants. Results We observed a weak association between Tanner-derived composite stage (TDCS) and puberty category scores (PCS) (τ=0.288, p<0.001) among all girls. There was correlation (τ=0.314, p=0.001) between ultrasound-derived composite stage (UDCS) and PCS among overweight/obese girls. Moreover, among overweight/obese girls, PCS was positively correlated with LH (r=0.265, p=0.008), but not FSH (r=0.155, p=0.123), and when the basal LH value was greater than 0.3 mIU/mL, the proportion of PCS stage ≥2 (9/18) was higher than the proportion of TDCS ≥2 (5/18). As for the determination of pubertal onset, when UDCS was used as the gold standard, the specificity of PCS was 0.86 and positive predictive value was 90.00 %. Conclusions There was a weak correlation between PCS and TDCS among girls early adolescence. Moreover, among overweight/obese girls, combining hormone values, ultrasonographic stage of breast, and the positive predictive value of PCS, we posit that self-reported PDS might be a more reliable method than TDCS to evaluate pubertal development among overweight/obese girls.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
María Lola Evia-Viscarra, Emmanuel Jacobo-Tovar, Luis Fernando Meneses-Rojas, Rodolfo Guardado-Mendoza
Mexican children with obesity are at a higher risk of developing type 2 diabetes mellitus (T2DM). Objectives To compare oral glucose tolerance test (OGTT) characteristics: time of peak glucose, glucose level ≥155 mg/dL at 1 h, presence of metabolic syndrome (MetS), sensitivity, secretion, and oral disposition index (oDI) in children with and without obesity, according to oral glucose tolerance curve shape: monophasic or biphasic. Methods Cross-sectional study including 143 children. Groups were divided into (a) obese: biphasic (B-Ob) (n=55) and monophasic (M-Ob) (n=50), (b) without obesity: biphasic (B-NonOb) (n=20) and monophasic (M-NonOb) (n=18). Results Late glucose peak was more frequent in the M-Ob group (p<0.001). Glucose levels ≥155 mg/dL and MetS were more frequent in the M-Ob group but did not show significance. The groups with obesity (biphasic and monophasic) had higher indices of insulin resistance and insulin secretion compared to the nonobese groups (biphasic and monophasic) (p<0.001). AUC glucose was higher in the M-Ob group (p<0.05), and AUC insulin was higher in the M-NonOb group. oDI (Matsuda) was significantly lower in the M-Ob group compared to the other groups (p<0.001), and oDI-HOMA IR was higher in M-NonOb group (p=0.03). Conclusions All OGTT parameters could help to identify Mexican children at increased risk of developing T2DM, not only fasting plasma glucose and 2 h glucose. M-Ob in non-T2DM Mexican children reflects an early defect in glucose metabolism. Higher level of IR indexes in M-NonOb vs. B-NonOb could indicate an increased risk for T2DM of genetic origin.
{"title":"Oral glucose tolerance test curve shape in Mexican children and adolescents with and without obesity","authors":"María Lola Evia-Viscarra, Emmanuel Jacobo-Tovar, Luis Fernando Meneses-Rojas, Rodolfo Guardado-Mendoza","doi":"10.1515/jpem-2024-0250","DOIUrl":"https://doi.org/10.1515/jpem-2024-0250","url":null,"abstract":"Mexican children with obesity are at a higher risk of developing type 2 diabetes mellitus (T2DM). Objectives To compare oral glucose tolerance test (OGTT) characteristics: time of peak glucose, glucose level ≥155 mg/dL at 1 h, presence of metabolic syndrome (MetS), sensitivity, secretion, and oral disposition index (oDI) in children with and without obesity, according to oral glucose tolerance curve shape: monophasic or biphasic. Methods Cross-sectional study including 143 children. Groups were divided into (a) obese: biphasic (B-Ob) (n=55) and monophasic (M-Ob) (n=50), (b) without obesity: biphasic (B-NonOb) (n=20) and monophasic (M-NonOb) (n=18). Results Late glucose peak was more frequent in the M-Ob group (p<0.001). Glucose levels ≥155 mg/dL and MetS were more frequent in the M-Ob group but did not show significance. The groups with obesity (biphasic and monophasic) had higher indices of insulin resistance and insulin secretion compared to the nonobese groups (biphasic and monophasic) (p<0.001). AUC glucose was higher in the M-Ob group (p<0.05), and AUC insulin was higher in the M-NonOb group. oDI (Matsuda) was significantly lower in the M-Ob group compared to the other groups (p<0.001), and oDI-HOMA IR was higher in M-NonOb group (p=0.03). Conclusions All OGTT parameters could help to identify Mexican children at increased risk of developing T2DM, not only fasting plasma glucose and 2 h glucose. M-Ob in non-T2DM Mexican children reflects an early defect in glucose metabolism. Higher level of IR indexes in M-NonOb vs. B-NonOb could indicate an increased risk for T2DM of genetic origin.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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