垂体柄阻断综合征4例

目的 通过对垂体柄阻断综合征(PSIS)患者临床特点进行分析,加强对本类疾病的认识.方法 总结本院2010年7月-2011年3月收治的4例PSIS患者的临床表现、实验室检查和影像学资料,采用回顾性分析方法,对其特点进行分析.结果 PSIS患儿4例.其中男3例,女1例.4例均以生长发育迟缓为主诉,1例还有步态不稳、反复抽搐.4例患儿身高78.0～130.0 cm,均低于同年龄、同性别健康儿童平均身高的第3百分位以下.有腺垂体功能减退的临床表现和实验室检查:生长激素激发试验峰值均低于5 000 ng·L-1;其中2例伴垂体性甲状腺功能减低和垂体性肾上腺皮质功能减退.神经垂体功能正常.垂体MRI增强扫描均表现为垂体柄未见显示,垂体小,后叶异位.1例并Chiari畸形I型.结论 PSIS的发病率低,以生长发育迟缓为主要临床表现,伴部分性或完全性腺垂体功能减退,但神经垂体功能正常.部分患儿合并其他先天发育畸形.MRI检查的特征性表现为垂体柄缺如,垂体小,神经垂体异位,应提高临床对PSIS的认识和诊治能力.     

生长激素缺乏并垂体柄中断13例临床分析

目的 分析垂体柄中断综合征(PSIS)患者的临床特点,提高对该类疾病的认识.方法 回顾分析对2008年1月至2009年6月间浙江大学医学院附属儿童医院内分泌科收治的13例PSIS患者的临床表现、实验室检查和影像学表现.结果 PSIS患儿13例,男性9例,女性4例.均以生长迟缓为主诉,身高81.5～135.0cm,均低于同年龄、同性别正常儿童平均身高的2个标准差以下,生长激素激发试验峰值均低于5μg/L;其中1例合并性发育迟缓,1例合并中枢性尿崩症;1例伴垂体性甲低,1例伴垂体性肾上腺皮质功能减退.结论 PSIS以生长迟缓为主要临床表现,部分性或完全性垂体前叶功能减退,磁共振检查特点为垂体小,垂体柄缺如,垂体后叶异位.     

进行性家族性肝内胆汁淤积症2型3例临床及遗传学分析

目的研究进行性家族性肝内胆汁淤积症2型(PFIC-2)的临床特点及基因突变位点。方法搜集2015—2017年首都儿科研究所附属儿童医院消化内科确诊的3例PFIC-2患儿,其中女2例、男1例,回顾性总结患儿临床资料、相关基因检测确定基因位点及随访预后。结果 3例均为婴儿早期起病,临床以皮肤黄染为主要表现,伴或不伴皮肤瘙痒症状,监测生化提示转氨酶升高,胆红素升高,直接胆红素为主,伴有胆汁酸升高,但γ-谷氨酰转肽酶(GGT)正常或稍低。1例肝脏病理提示肝组织内肝小叶结构紊乱,早期假小叶形成,大量多核巨肝细胞,中度肝细胞及毛细胆管性淤胆,可见胆管狭窄。3例均行二代基因测序检查,均提示ABCB11存在突变,3例均为复合杂合突变。结论 PFIC-2起病早,病情进展快,早期基因筛查,有助于明确诊断、评估预后。     

特发性生长激素缺乏症少儿垂体磁共振成像研究

摘要：目的　研究特发性生长激素缺乏症（IGHD）少儿垂体磁共振成像（MRI）表现。方法　选取北京协和医院内分泌科2005年1月至2010年1月确诊的100例IGHD患儿, 均行MRI平扫及增强检查, 与152例同年龄同性别健康少儿（正常组）匹配分析比较。结果　IGHD少儿鞍区MRI主要表现为垂体发育不良、垂体后叶异位或缺如、垂体柄变细中断甚至消失。IGHD组与正常组垂体上缘形态及信号特点差异具有统计学意义。IGHD组垂体高度和垂体柄宽度明显低于正常组（P < 0.01）。结论　IGHD少儿垂体形态有特征性改变, 根据临床与实验室检查再结合垂体MRI表现对诊断IGHD具有明显帮助。     

citrin缺陷导致的新生儿肝内胆汁淤积症12例临床和实验室研究

目的探讨citrin缺陷导致的新生儿肝内胆汁淤积症（NICCD）患儿的临床表现和实验室检查的特点。方法对12例肝内胆汁淤积和黄疸患儿进行常规实验室检查，结合血串联质谱分析、尿气相色谱质谱分析诊断为NICCD。对确诊患儿的临床表现、常规实验室检查、血氨基酸谱和酰基肉碱谱、尿有机酸等进行分析。结果NICCD患儿出生体重偏低。实验室改变包括γ-谷氨酰转移酶、碱性磷酸酶以及甲胎蛋白升高、高胆红素血症、低蛋白血症、凝血酶原时间延长。有明显低血糖6例，有轻度高氨血症3例，有半乳糖血症仅1例。3例肝活检病理提示肝内胆汁淤积和肝细胞脂肪变性。串联质谱分析发现多数患儿有特异性瓜氨酸、蛋氨酸、苏氨酸和酪氨酸明显升高，以及游离肉碱、C2、C3和长链酰基肉碱升高。尿气相色谱质谱有机酸分析有尿4-羟基苯乳酸、4-羟基苯丙酮酸和4-羟基苯乙酸升高。结论不明原因黄疸患儿鉴别诊断应考虑到NICCD，早期进行串联质谱分析对明确NICCD的诊断具有重要意义。     

新生儿期起病的垂体柄阻断综合征二例并文献复习

目的:通过对新生儿期起病的2例垂体柄阻断综合征(PSIS)患儿的临床特点进行总结分析,加强对该病的认识。方法:总结我院新生儿科2018年7月至2020年7月诊治的2例PSIS患儿的临床表现、实验室检查和影像学资料,采用回顾性分析方法,对该病特点进行分析。结果:PSIS患儿2例,男1例,女1例,2例均为小于胎龄儿,住院期...     

致新生儿胆汁淤积症的遗传性疾病研究进展

新生儿胆汁淤积症( neonatal cholestasis)是由于肝细胞不能正常合成胆汁酸,或由于胆管系统功能异常不能有效地将胆汁排泄,导致胆红素、胆酸及胆固醇在血液及肝外组织蓄积的临床过程,临床表现为高直接胆红素血症、黄疸持续时间延长、肝肿大、白陶土样大便和尿色加深等.当新生儿黄疸持续时间超过2～4周时,应考虑胆汁淤积症的可能[1].     

新生儿高未结合胆红素血症与胆汁酸的关系临床分析

目的探讨新生儿高未结合胆红素血症与胆汁酸的关系。方法对40例标准肝功能指标正常的新生儿未结合胆红素升高为主的病理性黄疸(TBA)检测。结果新生儿黄疸患儿血清TBA有不同程度的增高。结论以未结合胆红素升高为主的病理性黄疸中存在胆汁淤积，因此，在治疗黄疸的同时适当用些加快胆汁排泄、减少胆汁淤积、保护肝功能的药物有重要意义。     

TJP2基因突变致进行性家族性肝内胆汁淤积症3例报告及文献复习

目的探讨紧密连接蛋白2(TJP2)基因变异致进行性家族性肝内胆汁淤积症(PFIC)的临床及基因特征。方法总结3例因TJP2基因变异致PFIC患儿的临床资料,并复习相关文献。结果3例患儿中女性1例、男性2例,均为婴儿期起病;临床以皮肤黄染为主要表现,伴或不伴皮肤瘙痒。血清总胆红素升高,以直接胆红素升高为主,丙氨酸氨基转移酶、天冬氨酸氨基转移酶、总胆汁酸升高,γ-谷氨酰转肽酶(GGT)正常或稍低,提示低GGT胆汁淤积症。二代基因测序发现3例患儿均存在TJP2复合杂合变异,确诊为TJP2变异引起的PFIC 4。文献复习显示,TJP2基因变异可引起PFIC、高胆烷血症、渐进非综合征性耳聋以及近视等儿童疾病。结论采用基因检测技术确诊3例TJP2基因复合杂合变异引起的PFIC 4。     

糖尿病母亲婴儿并发症的临床观察

目的 探讨糖尿病母亲婴儿(infants of diabetic mothers,IDMS)并发症的发生情况.方法回顾性分析52例IDMS和50例非糖尿病母亲娩出的正常新生儿(对照组)的并发症发生情况.结果52例IDMS患儿发生低血糖23例(44.2％,23/52),高胆红素血症16例(31.4％,16/52),红细胞增多症11例(21.2％,11/52),巨大儿11例(21.2％,11/52),新生儿呼吸窘迫综合征4例(7.7％,4/52),先天畸形1例(1.9％,1/52).对照组50例患儿中有1例发生低血糖(2％,1/50),高胆红素血症7例(14.0％,7/50),红细胞增多症1例(2％,1/50).两组患儿在低血糖、高胆红素血症、红细胞增多症3种并发症方面比较,差异有统计学意义(P值分别为0.000、0.043和0.009).结论IDMS出现并发症的发生率高于正常新生儿,应对其进行严密监护.     

Neonatal cholestasis and hypoglycemia like form of congenital hypopituitarism presentation

Congenital hypopituitarism is a rare disease, of variable clinic. The neonatal hypoglycemia is one of the habitual forms of presentation; the cholestasis is a rare symptom of this disease. This is the case of a 2-months-old infant hospitalized for cholestatic jaundice. He added repeated episodes of severe hypoglycemia. We investigated metabolic and endocrine causes. The etiology was clarified by obtaining a critical sample that demonstrated the counterregulatory hormone deficiency. The diagnosis of congenital hypopituitarism was completed with confirmation of thyroid hormone and growth hormone deficiencies. It was confirmed the neuro-anatomical defect of “syndrome of pituitary stalk section” determined by pituitary stalk agenesis, pituitary hipoplasia, and ectopic neurohypophysis. Hormone replacement therapy was started with good response and outcome.     

Magnetic resonance imaging in the diagnosis of growth hormone deficiency.

Forty-six patients with idiopathic growth hormone deficiency were examined by magnetic resonance imaging at a mean (+/- SEM) age of 9 +/- 1 years (range 15 days to 20 years). They were classified into two groups according to MRI images: group 1 (n = 29) had pituitary stalk interruption syndrome and group 2 (n = 17) had normal pituitary anatomy. All patients with pituitary stalk interruption had a pituitary height at less than -2 SD for age; three had no visible anterior pituitary lobe. By contrast, the pituitary height was less than normal in only 10 patients (60%) with normal pituitary anatomy. Growth hormone deficiency was transient in one of the seven patients with normal pituitary anatomy and height. The group with pituitary stalk interruption had the first symptom of growth hormone deficiency at an earlier age (2.8 +/- 0.6 vs 5.5 +/- 1.2 years; p less than 0.001), were of smaller stature (-4 +/- 0.2 vs -3 +/- 0.2 SD; p less than 0.01) and had lower GH peak response to provocative testing (3 +/- 0.4 vs 5 +/- 0.5 ng/ml; p less than 0.001) than did the group with normal pituitary anatomy. Their pituitary gland was also shorter (2.5 +/- 0.2 vs 3.5 +/- 0.2 mm; p less than 0.01). All the patients with multiple pituitary deficiencies except one (n = 19) belonged to this group. One girl with pituitary stalk interruption and deficiencies in growth hormone and thyroid-stimulating hormone had advanced central precocious puberty. We conclude that the evaluation of the shape and height of the pituitary gland by MRI is an additional tool for the diagnosis of growth hormone deficiency. The presence of pituitary stalk interruption confirms this diagnosis and is predictive of multiple anterior pituitary deficiencies. The lack of a significant increase in perinatal abnormalities in this group and the association of pituitary stalk interruption with microphallus and with facial or sella abnormalities suggest that this appearance may have an early antenatal origin. The finding of a familial case of pituitary stalk interruption suggests a genetic origin.     

Ursodeoxycholic acid therapy in children with cholestatic liver disease

The beneficial effect of ursodeoxycholic add have been documented in adults but experience with this agent is limited in the pediatric population. The objective of this study was to evaluate ursodeoxycholic acid treatment in children with cholestatic liver disease. Twenty-four patients with intrahepatic cholestasis (neonatal hepatitis 7, Byler disease 7, idiopathic intrahepatic cholestasis 10) whose ages ranged from 1.5 months to 15 years were treated with ursodeoxycholic acid (15-20 mg/kg/day) for 12 months. Liver biopsy was performed initially on all patients and on 17 at the end of the twelve months. The outcome was evaluated by monitoring clinical and biochemical markers of cholestasis, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, cholesterol, total serum tasting bile acids and total and conjugated bilirubin at entry and every three months of treatment. Pruritus was ameliorated in all patients; there was complete disappearance of itching in 16.7 percent. There were significant decreases in mean serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin and gamma-glutamyl transpeptidase. Liver biopsy specimens showed a significant improvement in the cholestasis but not in fibrosis. No adverse effects of therapy were noted. The improvements in the clinical and biochemical parameters and tolerability of the drug suggest that ursodeoxycholic acid is a safe and effective treatment in children with intrahepatic cholestasis.     

LIVER DISEASE IN CHILDREN WITH ALPHA1-ANTITRYPSIN DEFICIENCY WITHOUT NEONATAL CHOLESTASIS

ABSTRACT. Thirteen children with α₁-antitrypsin deficiency (8 PiZ and 5 PiSZ) were investigated at ages ranging from 4 to 6. None had had neonatal cholestasis. Nine, mainly the PiZ individuals, had increased serum concentration of transaminases. Liver biopsy was performed in 7 patients with increased serum levels of transaminases. One of these patients had cirrhosis and 4 had moderate to severe fibrosis. The results indicate that α₁-antitrypsin deficient individuals, also without neonatal cholestasis syndrome run a high risk of developing serious liver disease, already in childhood. The cirrhotic patient was the only one who had increased excretion of bile acids in urine.     

Thyroid function in young children with Down syndrome

A retrospective review of thyroid function tests (TFTs) was performed on 49 young children (aged 4 months to 3 years) with Down syndrome compared with age-matched controls screened for hypothyroidism because of developmental delay or failure to thrive. Three of the 49 children with Down syndrome had congenital hypothyroidism; of the three, one had Hirschsprung's disease and two had duodenal atresia. Thyroiditis was uncommon, with only two children having thyroid antibodies present: one had acquired hypothyroidism and the other acquired hyperthyroidism. Twenty-seven percent of the Down syndrome cohort had mildly increased thyrotropin (TSH) and normal thyroxine levels. When compared with children with Down syndrome who had normal TFTs, no significant differences in sex, growth rate, maternal age, associated anomalies, developmental or specific thyroid symptoms were present. Transient elevations of TSH level were common in children with Down syndrome whether or not TSH values were initially normal or elevated. Routine neonatal and sequential thyroid screening in young children with Down syndrome is warranted.     

A retrospective review of pituitary MRI findings in children on growth hormone therapy

Background

Patients with congenital hypopituitarism might have the classic triad of pituitary stalk interruption syndrome, which consists of: (1) an interrupted or thin pituitary stalk, (2) an absent or ectopic posterior pituitary (EPP), and (3) anterior pituitary hypoplasia or aplasia.

Objective

To examine the relationship between pituitary anatomy and the degree of hormonal dysfunction.

Materials and methods

This study involved a retrospective review of MRI findings in all children diagnosed with congenital growth hormone deficiency from 1988 to 2010 at a tertiary-level pediatric hospital.

Results

Of the 52 MRIs reviewed in 52 children, 26 children had normal pituitary anatomy and 26 had one or more elements of the classic triad. Fourteen of fifteen children with multiple pituitary hormone deficiencies had structural anomalies on MRI. Twelve of 37 children with isolated growth hormone deficiency had an abnormal MRI.

Conclusion

Children with multiple pituitary hormone deficiencies were more likely to have the classic triad than children with isolated growth hormone deficiency. A normal MRI was the most common finding in children with isolated growth hormone deficiency.     

Parenteral nutrition-associated cholestasis in preterm neonates: evaluation of ursodeoxycholic acid treatment.

BACKGROUND/OBJECTIVE: Parenteral nutrition is an integral part of the care of premature infants. Cholestatic liver disease is a frequent complication of prolonged parenteral nutrition, especially in premature infants. It has been suggested that ursodeoxycholic acid may alter the course of parenteral nutrition-associated cholestasis in children and adults. We attempted to determine the efficacy of ursodeoxycholic acid in premature infants with parenteral nutrition-associated cholestasis. METHODS: Retrospective chart review of all infants receiving ursodeoxycholic acid for parenteral nutrition-associated cholestasis in a 40 bed neonatal intensive care unit. Efficacy of ursodeoxycholic acid was evaluated by response of bilirubin, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase over a treatment period of at least 1 month. RESULTS: Six infants with parenteral nutrition-associated cholestasis who had received ursodeoxycholic acid for one month were identified. Doses of ursodeoxycholic acid ranged from 15-30 mg/kg/day. Cholestasis appeared at a mean age of 47 +/- 17 (mean +/- SD) days after a mean of 42 +/- 15 days of parenteral nutrition. Transaminase levels decreased in three, and either increased or did not change in the other three infants. Bilirubin levels decreased in all infants. Alkaline phosphatase showed a non significant trend to decreased levels. Consistent improvement in all infants was noted only after 10 days of full enteral nutrition. No toxicity was found during ursodeoxycholic acid treatment. CONCLUSIONS: Ursodeoxycholic acid treatment in premature infants appears to be safe, and leads to an early sustained decrease in bilirubin levels by two weeks of therapy. The response of transaminase levels was not sustained in our small cohort.     

Association of serum interleukin-8 levels with the degree of fibrosis in infants with chronic liver disease

OBJECTIVE: Biliary atresia is a neonatal obstructive cholangiopathy characterized by a destructive, obliterative process affecting both the intrahepatic and extrahepatic ducts of the biliary tree that uniquely presents in the first months of life. The consequence of progressive inflammatory and sclerotic reaction is the development of obstructive jaundice. To determine the proinflammatory cytokine profile in children with biliary atresia, we measured circulating levels of interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha and IL-8. METHODS: Twelve children, five males and seven females, with biliary atresia were studied. In addition, four patients with progressive familial intrahepatic cholestasis and three with Alagille syndrome were also included. Five patients with neonatal hepatitis were studied as controls of a liver disease without portal fibrosis. Serum concentration of total and conjugated bilirubin, gamma-glutamyl transferase and glutamic-pyruvic transaminase were measured by routine methods in all patients at time of sampling for the study. The degree of fibrosis in liver biopsies was scored using the histologic activity index. RESULTS: In our study IL-8 was detectable in 11 of 12 patients with biliary atresia with a median level of 262 pg/ml and a highly statistically significant difference (P < 0.0001) from controls. In patients with progressive familial intrahepatic cholestasis or with Alagille syndrome serum IL-8 levels were similarly elevated. In patients with neonatal hepatitis, IL-8 levels were marginally increased. Serum IL-8 levels were significantly correlated (Rs = 0.725, P < 0.0001) with the histologic activity index. CONCLUSIONS: Although further studies are needed to determine the role of IL-8 in portal inflammation, our results suggest that increased production of IL-8 may be a mechanism leading to the progressive portal inflammation and fibrosis in patients with chronic liver disease.