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A 36-year-old woman was admitted to the Peking Union Medical College Hospital with a history of fractures for 2 years, limb weakness for 1 year, and ostealgia for 2 months. The patient's examination identified iron deficiency anemia, significantly decreased serum calcium and 25-hydroxyvitamin D3 levels, and increased alkaline phosphatase and parathyroid hormone levels. Imaging showed several typical signs of osteomalacia. Considering the history of Roux-en-Y gastric bypass surgery, the diagnosis was considered to be osteomalacia caused by a postoperative nutritional absorption disorder. The patient was supplemented with calcitriol, calcium, and vitamin D and gradually returned to normal physical activity. The bone metabolism indicators and bone density were significantly improved.
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Objective:To analyze the clinical characteristics and molecular mechanisms of 5 cases of hypoparathyroidism caused by GATA3 gene mutation.Methods:A total of 5 childhood-onset hypoparathyroidism patients with GATA3 mutation were identified from 198 hypoparathyroidism (aged ≤18 years) from 1975 to 2021 in Peking Union Medical College Hospital. Clinical data and biochemical indices of the 5 patients were collected and analyzed retrospectively. Genetic screening was conducted by targeted next-generation sequencing (T-NGS), and bioinformatics analysis was performed to analyze the underline mechanisms.Results:The medium onset age of hypoparathyroidism of the 5 patients was 0.5 (0.1, 1.3) years old, and the time duration from onset to confirmed diagnosis of hypoparathyroidism and hypoparathyroidism- deafness-renal dysplasia syndrome was (7.0±5.2) years and (15.0±5.4) years, respectively. The clinical manifestations included carpopedal spasm accompanied by seizures (5 cases), basal ganglia calcification (5 cases), cataract (1 case), deafness (4 cases), and renal malformations or absence (2 cases). The blood calcium and blood parathormone(PTH) before treatment was (1.65±0.31) mmol/L and (4.64±2.63) ng/L, respectively. The 5 patients carried different heterozygous mutations in GATA3 gene, which caused nonsense mutations, frameshift mutations and splice site mutations, respectively. All the GATA3 gene mutations of the 5 patients are classified as pathogenic or likely pathogenic by the Clin Var database and American College of Medical Genetics and Genomics(ACMG).Conclusions:Attention should be paid to genetic diseases in patients with childhood-onset hypoparathyroidism. The possibility of hypoparathyroidism-deafness-renal dysplasia syndrome should be considered in hypoparathyroidism patients with hearing loss or renal dysplasia. GATA3 gene screening is highly recommended for the confirmation of the diagnosis.
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The majority of primary hyperparathyroidism (PHPT) are sporadic, and less than 10% of cases are hereditary or part of familial syndromes. Glial cell missing 2 (GCM2) was confirmed to be a new pathogenic gene of PHPT in 2016. At present, four GCM2 mutations have been confirmed to have certain correlations with familial or sporadic PHPT. The purpose of this review is to summarize the pathogenesis and clinical features of GCM2 mutation related primary hyperparathyroidism.
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OBJECTIVE@#To detect the genetic variant of a child with cleidocranial dysplasia (CCD) and to find out the causation of the illness.@*METHODS@#Gene variant was identified by the second generation targeted sequencing and Sanger sequencing.@*RESULTS@#The gene sequencing revealed that the RUNX2 gene had c.196C>T(p.Glu66*) nonsense variant, which was predicted to be a pathogenic variant according to the ACMG guidelines(PVS1+PS2).@*CONCLUSION@#The variant of c.196C > T in the RUNX2 gene may be the cause of the child with CCD, and the novel variant enriches the RUNX2 gene variant spectrum.
Subject(s)
Child , Humans , Asian People/genetics , China , Cleidocranial Dysplasia/genetics , Core Binding Factor Alpha 1 Subunit/genetics , MutationABSTRACT
Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.
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Objectives@#To compare the effect of eldecalcitol and alfacalcidol on skeletal microstructure by highresolution peripheral QCT (HR-pQCT). @*Methods@#This was a substudy of a randomized, double-blind, active comparator trial. Five female osteoporotic patients with 1-year 0.75 mg/day eldecalcitol and 5 with 1-year 1.0 mg/day alfacalcidol completed HR-pQCT scans before and after treatment were enrolled. @*Results@#Total vBMD [1.67 ± 1.06% (mean ± SD), P ¼ 0.043 versus baseline] and trabecular vBMD (2.91 ± 1.72%, P ¼ 0.043) at the radius increased in eldecalcitol group, while total, trabecular, and cortical vBMD tended to decrease in alfacalcidol group, with a significant reduction in cortical vBMD at the tibia (0.88 ± 0.62%, P ¼ 0.043). Cortical area (1.82 ± 1.92%, P ¼ 0.043) at the radius and thickness (0.87 ± 1.12%, P ¼ 0.043) at the tibia increased in eldecalcitol group, while these parameters decreased with alfacalcidol at the tibia (1.77 ± 1.72%, P ¼ 0.043 for cortical area; 1.40 ± 2.14%, P ¼ 0.042 for cortical thickness). Trabecular thickness at the radius (1.97 ± 1.93%, P ¼ 0.042) and number at the tibia (3.09 ± 3.04%, P ¼ 0.043) increased by eldecalcitol but did not increase by alfacalcidol. Trabecular separation decreased by eldecalcitol (2.22 ± 2.43%, P ¼ 0.043) but tended to increase by alfacalcidol at the tibia. @*Conclusions@#Eldecalcitol has the greater potential to improve cortical and trabecular microstructure at the peripheral bone than alfacalcidol which needs further more studies.
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Objectives@#To compare the effect of eldecalcitol and alfacalcidol on skeletal microstructure by highresolution peripheral QCT (HR-pQCT). @*Methods@#This was a substudy of a randomized, double-blind, active comparator trial. Five female osteoporotic patients with 1-year 0.75 mg/day eldecalcitol and 5 with 1-year 1.0 mg/day alfacalcidol completed HR-pQCT scans before and after treatment were enrolled. @*Results@#Total vBMD [1.67 ± 1.06% (mean ± SD), P ¼ 0.043 versus baseline] and trabecular vBMD (2.91 ± 1.72%, P ¼ 0.043) at the radius increased in eldecalcitol group, while total, trabecular, and cortical vBMD tended to decrease in alfacalcidol group, with a significant reduction in cortical vBMD at the tibia (0.88 ± 0.62%, P ¼ 0.043). Cortical area (1.82 ± 1.92%, P ¼ 0.043) at the radius and thickness (0.87 ± 1.12%, P ¼ 0.043) at the tibia increased in eldecalcitol group, while these parameters decreased with alfacalcidol at the tibia (1.77 ± 1.72%, P ¼ 0.043 for cortical area; 1.40 ± 2.14%, P ¼ 0.042 for cortical thickness). Trabecular thickness at the radius (1.97 ± 1.93%, P ¼ 0.042) and number at the tibia (3.09 ± 3.04%, P ¼ 0.043) increased by eldecalcitol but did not increase by alfacalcidol. Trabecular separation decreased by eldecalcitol (2.22 ± 2.43%, P ¼ 0.043) but tended to increase by alfacalcidol at the tibia. @*Conclusions@#Eldecalcitol has the greater potential to improve cortical and trabecular microstructure at the peripheral bone than alfacalcidol which needs further more studies.
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Objective@#To investigate the association of GNA11 gene polymorphisms with the risk of adult-onset non-surgical hypoparathyroidism (Ns-HypoPT).@*Methods@#Genotyping of GNA11 single nucleotide polymorphisms (SNPs) (rs28685098, rs4806907, rs11084997 and rs78003011) was carried out in 203 patients and 209 healthy participants by sequenom MassArray iPLEX System. These SNPs are located in promoter and 3′untranslated region (3′UTR) of GNA11 gene, respectively.@*Results@#Allele and genotype frequencies of rs11084997 in patients were significantly different from those of controls (genotype GG:60.5% vs. 49.8%, GC: 35.5% vs. 41.6%, CC: 4.0% vs. 8.6%, P=0.038; G allele 78.3% vs. 70.6%, C allele 21.7% vs. 29.4%, P=0.012), and the C allele of rs11084997 carriers had a lower risk to develops Ns-HypoPT in additive and dominant genetic models [OR=0.382 (0.160-0.915), 0.647 (0.437-0.957)]. CC-Haplotype formed by the minor alleles of rs4806907 and rs11084997 was associated with a decreased risk of Ns-HypoPT in additive, dominant and recessive genetic model [OR=0.317 (0.126-0.801), 0.640 (0.430-0.952), 0.367 (0.148-0.912)].@*Conclusion@#The minor allele C of rs11084997 in GNA11 gene promoter was associated with decreased risk of Ns-HypoPT in Chinese population.
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Objective:To provide more options for preoperative localization diagnosis in patients with primary hyperparathyroidism (PHPT), the diagnostic efficacy of parathyroid 4-dimensional computed tomography (4D-CT) in patients with PHPT was evaluated.Methods:This was a single-center retrospective study including 57 patients with surgical proved PHPT. All of the patients underwent 4D-CT, 99Tc m -sestamibi parathyroid imaging (MIBI), and ultrasonography (US) preoperatively. The reference standard for correct localization was based on operation reports and pathology confirmation. The patients were grouped according to the preoperative serum calcium levels, tumor diameter, or ectopic lesions (yes/no), respectively. The sensitivity, specificity, positive predictive value, negative predictive value and area under the curve (AUC) of 4D-CT, MIBI and US, alone or in combination, were analyzed in total and each subgroup patients. Results:Fifty-seven patients (39 women, 18 men; mean age of 56.5 years) were evaluated, including four cases with multi-gland disease and thirteen cases with ectopic parathyroid lesions. In all the patients, similar diagnostic efficacy was found in 4D-CT (AUC: 0.943) and MIBI (AUC: 0.927), both of which were higher than that of US (AUC: 0.847) ( P = 0.01 for 4D-CT vs. US; P = 0.04 for MIBI vs. US). In a subset analysis for ectopic quadrants, the diagnostic efficacy of 4D-CT was significantly higher than that of MIBI ( P = 0.04) or US ( P = 0.01), with the sensitivity of 100%, 69.2%, and 61.5%, and AUC of 0.989, 0.846, and 0.808 for 4D-CT, MIBI and US, respectively. Conclusions:4D-CT has similar diagnostic efficacy for preoperative localization to MIBI in patients with PHPT, and it is superior to MIBI and US in identifying the ectopic parathyroid gland. 4D-CT can be recommended as an alternative preoperative localization method, especially when parathyroid lesions could not be precisely located by US and MIBI.
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Objective:To investigate the association of GNA11 gene polymorphisms with the risk of adult-onset non-surgical hypoparathyroidism (Ns-HypoPT).Methods:Genotyping of GNA11 single nucleotide polymorphisms (SNPs) (rs28685098, rs4806907, rs11084997 and rs78003011) was carried out in 203 patients and 209 healthy participants by sequenom MassArray iPLEX System. These SNPs are located in promoter and 3′untranslated region (3′UTR) of GNA11 gene, respectively.Results:Allele and genotype frequencies of rs11084997 in patients were significantly different from those of controls (genotype GG:60.5% vs. 49.8%, GC: 35.5% vs. 41.6%, CC: 4.0% vs. 8.6%, P=0.038; G allele 78.3% vs. 70.6%, C allele 21.7% vs. 29.4%, P=0.012), and the C allele of rs11084997 carriers had a lower risk to develops Ns-HypoPT in additive and dominant genetic models [ OR=0.382 (0.160-0.915), 0.647 (0.437-0.957)]. CC-Haplotype formed by the minor alleles of rs4806907 and rs11084997 was associated with a decreased risk of Ns-HypoPT in additive, dominant and recessive genetic model [ OR=0.317 (0.126-0.801), 0.640 (0.430-0.952), 0.367 (0.148-0.912)]. Conclusion:The minor allele C of rs11084997 in GNA11 gene promoter was associated with decreased risk of Ns-HypoPT in Chinese population.
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Objective@#To investigate the effectiveness and safety of high-dose native vitamin D versus active vitamin D by retrospective analysis of clinical data in patients with non-surgical hypoparathyroidism (ns-HP) in our hospital.@*Methods@#ns-HP patients with stable therapeutic schedule in recent three years were included. According to the vitamin D agents used, patients were divided into three groups: active vitamin D group, native vitamin D group, and mixed vitamin D group. The effectiveness was evaluated by analysis of markers including post-treatment serum calcium, incidence of hypocalcemia, hypocalcemic symptoms and signs. The safety was evaluated in various groups by analyzing incidences of hypercalcemia and hypercalciuria, glomerular filtration rate, percentage of thiazide diuretic use, nephrocalcinosis or renal stone.@*Results@#Patients in active vitamin D group were more likely to experience episodes of hypocalcemia compared with those in native group (32.94%±21.46% vs 24.86%±10.1%, P<0.05). No significant differences in other indexes for assessing effectiveness and safety were found among three groups (P>0.05).@*Conclusions@#Under the circumstance of regular follow-up, both high-dose native vitamin D and active vitamin D could treat ns-HP effectively and safely. Native vitamin D may be better in maintaining eucalcemia and reducing incidence of hypocalcemia compared with active vitamin D.
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Objective To investigate the effectiveness and safety of high-dose native vitamin D versus active vitamin D by retrospective analysis of clinical data in patients with non-surgical hypoparathyroidism ( ns-HP) in our hospital. Methods ns-HP patients with stable therapeutic schedule in recent three years were included. According to the vitamin D agents used, patients were divided into three groups: active vitamin D group, native vitamin D group, and mixed vitamin D group. The effectiveness was evaluated by analysis of markers including post-treatment serum calcium, incidence of hypocalcemia, hypocalcemic symptoms and signs. The safety was evaluated in various groups by analyzing incidences of hypercalcemia and hypercalciuria, glomerular filtration rate, percentage of thiazide diuretic use, nephrocalcinosis or renal stone. Results Patients in active vitamin D group were more likely to experience episodes of hypocalcemia compared with those in native group (32.94% ± 21.46% vs 24.86% ± 10.1%, P＜0.05). No significant differences in other indexes for assessing effectiveness and safety were found among three groups ( P＞0.05). Conclusions Under the circumstance of regular follow-up, both high-dose native vitamin D and active vitamin D could treat ns-HP effectively and safely. Native vitamin D may be better in maintaining eucalcemia and reducing incidence of hypocalcemia compared with active vitamin D.
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Objective To explore the quality of life ( QoL ) and muscle strength in patients with pseudohypoparathyroidism ( PHP ) under regular treatment. Methods Twenty-three patients with PHP regularly followed at Peking Union Medical College Hospital from June 2017 to June 2018 were included. Age- and gender-matched 23 patients with nonsurgical hypoparathyroidism ( nHPT) and 23 healthy controls were also included. Short Form 36 Health Survey questionnaire version 2 ( SF36v2) were used to evaluate the QoL. Grip strength and repeated chair stand ( RCS) were used to assess muscle strength for upper and lower limbs respectively. Results Except for physical functioning, patients of PHP group had reduced scores in all other subdomains of SF36v2 compared to healthy controls ( P<0.05) . Comparing to nHPT patients, PHP patients had a higher score in social functioning, while no difference was found in other subdomains of SF36v2. Grip strength and RCS tests were similar in PHP patients and healthy controls. Conclusions Comparing to healthy controls, patients with PHP still had impaired QoL despite regular management, no significant difference of upper and lower limb muscle strength was found between PHP group and healthy controls.
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Objective@#To explore the accuracy in localizing occult insulinomas with Glucagon-like peptide-1 receptor(GLP-1R) PET-CT with 68Ga-exendin-4.@*Methods@#In this prospective cohort study, patients with biochemically proven endogenous hyperinsulinemic hypoglycemia and negative contrast-enhanced CT with pancreatic perfusion scans were enrolled consecutively at Department of Nuclear Medicine, Peking Union Medical College Hospital from February 2014 to June 2018.There were 37 males and 32 females, with age of (43.2±17.9)years. 68Ga-exendin-4 PET-CT, MRI and endoscopic ultrasound(EUS) were done before elective surgery. Sensitivity, specificity, accuracy, positive predictive value(PPV) and negative predictive value(NPV) of the above imaging modalities were calculated.@*Results@#A total of 69 patients were recruited. Thirty-two patients were diagnosed with insulinomas at histology. Four patients with positive 68Ga-exendin-4 PET-CT findings did not undergo surgery so far. Twenty-eight patients were proven to be noninsulinoma induced hyperinsulinemic hypoglycemia. Five patients were unknown of etiology of hypoglycemia. The sensitivity, specificity, accuracy, PPV and NPV of 68Ga-exendin-4 in localizing occult insulinomas were 96.9%(31/32), 100%(30/30), 98.3%(59/60), 100%(29/29), 96.8%(30/31), respectively.The sensitivity, specificity, accuracy, PPV and NPV of MRI were 74.1%(20/27), 9/11, 76.3%(29/38), 90.9%(20/22), 9/16, respectively. The sensitivity, specificity, accuracy, PPV and NPV of EUS were 75.0% (15/20), 2/2, 77.3%(17/22), 15/15, and 2/7.@*Conclusion@#68Ga-exendin-4 PET-CT has a high sensitivity, specificity and accuracy for detection of occult insulinoma, which shows superiority to MRI and EUS.
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A middle aged male presented with darkened skin and edema of lower extremities was reported. He was diagnosed as primary adrenocortical insufficiency ( Addison' s disease ) accompanied with hypergonadotropic hypogonadism, hypoparathyroidism, and subclinical hypothyroidism after endocrinological workup. In addition, the patient also had thickened skin, hirsutism, and polyserositis. The diagnosis of POEMS syndrome was confirmed by elevated M protein and VEGF level. The image of CT showed normal adrenals. Besides the autoimmune polyglandular syndrome ( APS), the possibility of POEMS syndrome in an adult patient with multiple endocrine dysfunction should be considered.
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Objective To improve the clinical understanding of glucagonoma. Methods A total of 14 cases of glucagonoma were admitted to our hospital, and the clinical features of these cases were retrospectively analyzed. Results (1) The female/ male case ratio was 1 : 1. (2) The median age of onset was 47 years (range 33-61), while the median age at diagnosis was 50 years (range 33-64). (3) The most common initial presentation was necrolytic migratory erythema (7/ 14, 50％). (4) Hyperglycemia was the most common presentation at the time of diagnosis (14/ 14, 100％), followed by necrolytic migratory erythema (13/ 14, 92.9％). (5) The misdiagnosis rate before admission to our hospital was as high as 85.7％ (12/ 14), and the most common misdiagnosis was eczema (7/ 12, 58.3％). (6) The median time from onset of probable symptoms to diagnosis was 4 years. (7) The median plasma glucagon level at diagnosis was 798 pg/ ml (range 200-2853). (8) The median length of the longest tumor diameter of the pancreatic tumors at diagnosis was 4. 0cm ( range 2. 2-8. 0). ( 9) 57. 1％ of primary pancreatic glucagonomas localized in the tail of the pancreas. (10) 57.1％ of patients (8/ 14) had metastases at the time of diagnosis. Conclusions (1)Necrolytic migratory erythema is a relatively sensitive and specific symptom for diagnosis of glucagonoma. (2) The diagnosis for glucagonoma was often delayed, and misdiagnosis was common. ( 3) Most glucagonoma patients had metastases at the time of diagnosis.
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Objective To explore the clinical manifestations, imaging and pathology features, treatment, and prognosis of endocrine glands involved patients with IgG4-related disease ( IgG4-RD) . Methods Ten patients admitted in Peking Union Medical College Hospital from 1 January 2014 to 30 June 2018 diagnosed as IgG4-RD with endocrine glands involved were enrolled in this study. All the clinical data were collected and analyzed. Results Ten patients, 4 males and 6 females, median 55 years old at the onset were enrolled, five patients with single organ involvement ( 1 case involved in pituitary, and 4 cases involved in thyroid) , while another 5 patients with 2 and more organs involved. C-reactive protein or erythrocyte sedimentation rate was elevated in 8 patients, antinuclear antibodies were positive in 7, and serum total IgE was elevated in 6 patients. Nine patients were treated with oral glucocorticoids, among whom 3 patients were treated in combination with immunosuppressive agents or rituximab. After treatment, the clinical symptoms were alleviated and imaging was improved in all patients. Serum IgG levels were significantly decreased in all patients and normalized in 5 patients. Conclusion For the patients with multiple endocrine gland diseases and elevated IgG4 level, the possibility of IgG4-RD should be carefully considered and should be confirmed by tissue biopsy and histopathology.
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Bartter syndrome (BS) is a hereditary condition transmitted as an autosomal recessive (Bartter type 1 to 4) or dominant trait (Bartter type 5).The disease associates hypokalemic alkalosis with varying degrees of hypercalciuria.Here we presented a case (BS type Ⅱ) of a 17 years old female presented with polyhydramnios,polyuria,nephrocalcinosis and hypokalemia,which was alleviated after treatment with celecoxib and vitamin D3.DNA sequencing identified compound heterozygous KCNJ1 gene mutations,c.931 C ＞ T (p.R311 W) and c.445-446insCCTGAACAC (p.V149Afs,150X),with the latter a novel mutation.Her father and mother were heterozygous carriers of c.931C ＞ T (p.R311W) and c.445-446insCCTGAACAC (p.V149Afs,150X),respectively.In conclusion,this case of BS type 1 is caused by a novel compound heterozygous KCNJ1 mutation.Further studies are needed to verify the effect of celecoxib in BS patients.
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Cushing's syndrome in pediatrics is very rare. In most child patients, the onset of Cushing's syndrome is insidious. The most common presenting symptom is growth retardationin inconsistant with the weight gain. The most common cause of Cushing's syndrome in children is exogenous administration of glucocorticoids and Cushing' s disease. Here we present a case of pediatric Cushing' s syndrome; the diagnosis and treatment are discussed.
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Bartter syndrome (BS) is a hereditary condition transmitted as an autosomal recessive (Bartter type 1 to 4) or dominant trait (Bartter type 5).The disease associates hypokalemic alkalosis with varying degrees of hypercalciuria.Here we presented a case (BS type Ⅱ) of a 17 years old female presented with polyhydramnios,polyuria,nephrocalcinosis and hypokalemia,which was alleviated after treatment with celecoxib and vitamin D3.DNA sequencing identified compound heterozygous KCNJ1 gene mutations,c.931 C ＞ T (p.R311 W) and c.445-446insCCTGAACAC (p.V149Afs,150X),with the latter a novel mutation.Her father and mother were heterozygous carriers of c.931C ＞ T (p.R311W) and c.445-446insCCTGAACAC (p.V149Afs,150X),respectively.In conclusion,this case of BS type 1 is caused by a novel compound heterozygous KCNJ1 mutation.Further studies are needed to verify the effect of celecoxib in BS patients.