Novel Insights from Clinical Practice
HOR MON E RE SE ARCH I N PÆDIATRIC S
Received: September 23, 2014 Accepted: October 9, 2014 Published online: January 21, 2015
Horm Res Paediatr 2015;83:217–220 DOI: 10.1159/000369014
Postprandial Hyperinsulinaemic Hypoglycaemia Secondary to a Congenital Portosystemic Shunt Senthil Senniappan a Katherine Pitt a Pratik Shah a Ved Arya a Sanjay Jaiswal e Munther Haddad b Jonathan Hind c Anil Dhawan c Mark Davenport d Khalid Hussain a
a
Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children, b Department of Paediatric Surgery, Chelsea and Westminster Hospital, and Departments of c Paediatric Hepatology and d Paediatric Surgery, King’s College Hospital, London, and e Department of Paediatrics, Frimley Park Hospital, Frimley, UK
Established Facts • Postprandial hyperinsulinaemic hypoglycaemia is a rare cause of hypoglycaemia in children.
Novel Insights • We report for the first time the association of postprandial hyperinsulinaemic hypoglycaemia with PSS that resolved following the closure of the shunt.
Key Words Hyperinsulinaemic hypoglycaemia · Portosystemic shunt · Down’s syndrome
Abstract Background: Portosystemic shunts (PSS) are abnormal vascular connections between the portal vein or its tributaries and the systemic vein that allow mesenteric blood to reach the systemic circulation without first passing through the liver. PSS can be associated with various syndromes and can
© 2015 S. Karger AG, Basel 1663–2818/15/0833–0217$39.50/0 E-Mail [email protected] www.karger.com/hrp
lead to serious complications. We report a rare case of a child with PSS and recurrent hypoglycaemia. Case: A 20-monthold girl with Down’s syndrome presented with recurrent hypoglycaemic episodes. She had multiple anomalies including a ventricular septal defect, oesophageal atresia and tracheo-esophageal fistula, gastro-oesophageal reflux, and conjugated hyperbilirubinaemia. The initial investigations suggested hyperinsulinaemic hypoglycaemia (HH). She did not respond to diazoxide. An oral glucose tolerance test suggested postprandial HH. Further vascular imaging showed a side-to-side portocaval shunt (Abernethy malformation)
Dr. Khalid Hussain Developmental Endocrinology Research Group/Clinical Molecular Genetics Unit UCL Institute of Child Health and Great Ormond Street Hospital for Children 30 Guilford Street, London WC1N 1EH (UK) E-Mail Khalid.hussain @ ucl.ac.uk
with relative hypoperfusion of the liver. Hypoglycaemia resolved following surgical closure of the portocaval shunt. Conclusion: PSS can rarely be associated with HH, possibly due to lack of insulin degradation in the liver. Surgical closure of the shunt resolves the hypoglycaemia. © 2015 S. Karger AG, Basel
Table 1. OGTT at presentation
Time, min
Glucose, mmol/l Insulin, mU/l
–30
00
30
60
90
180
4.5 2.1
4.6 2.3
5.2 120
7.7 >300
7.4 >300
2.6 101
Introduction
Congenital portosystemic shunts (PSS) are characterised by the flow of splanchnic blood through a congenital fistula, bypassing the liver, into the systemic circulation. PSS are single (occasionally multiple) abnormal vascular connections between the portal vein or its tributaries and the systemic veins (typically the vena cava), which allow portal blood to reach the systemic circulation without first passing through the liver [1]. PSS can be intrahepatic or extrahepatic and can be associated with congenital heart disease [2]. This extremely rare abnormality of early embryonic life was first described by Abernethy in 1793 [3]. They can lead to lifethreatening complications such as encephalopathy, pulmonary hypertension, hepatopulmonary syndrome and (in children) developmental delay. Presumably because of the compensatory increase in hepatic arterial flow to the liver to compensate for reduction in hepatic portal venous flow and consequent change in sinusoidal oxygenation, there is a tendency to neoplastic change. This may be benign in the form of focal nodular hyperplasia or malignant, typically with the development of hepatoblastoma [4–6]. Portocaval shunts have also been reported to cause hyperammonaemia and encephalopathy [7]. Neonatal galactosaemia can also be caused by portohepatic venous shunts or portocaval shunts [8]. We report a rare case of a child with PSS and hypoglycaemia. The hypoglycaemia resolved after surgical closure of the shunt. Case Report A 20-month-old girl with Down’s syndrome presented with hypoglycaemic generalised tonic-clonic convulsion. She was managed with a dextrose bolus, followed by intravenous dextrose infusion. She had persistent hypoglycaemia and was unable to come off the intravenous fluids. She was previously on continuous gastrostomy feeds and was recently converted to 3 boluses of 240 ml Nutrini multifibre during the daytime. She was born at 35 weeks of gestation by normal delivery with a birth weight of 2.3 kg. She had multiple anomalies including a ventricular septal defect (repaired), oesophageal atresia and tra-
218
Horm Res Paediatr 2015;83:217–220 DOI: 10.1159/000369014
Portal vein PSS Inferiorvena cava
Fig. 1. Abdominal MRI revealing the PSS.
cheo-esophageal fistula (repaired), and gastro-oesophageal reflux (requiring Nissen’s fundoplication and gastrostomy feeds). The hypoglycaemia screen in the local hospital suggested HH (laboratory glucose 1.6 mmol/l, insulin 88 pmol/l and C-peptide 531 pmol/l). The rest of the screening bloods were normal (lactate 1.3 mmol/l, ammonia 41 μmol/l, cortisol 385 nmol/l, T4 13.5 pmol/l, TSH 4.4 mU/l). The blood spot carnitine profile, plasma amino acids and urine organic acids were all normal. She was commenced on 5 mg/kg/day of diazoxide and 7.5 mg/kg/day of chlorothiazide for the management of HH. However, she continued to have hypoglycaemic episodes despite the maximal dose of diazoxide (15 mg/kg/day). She was transferred to our tertiary centre for further management. Her glucose requirement was 10 mg/kg/min. She had a controlled fast, which revealed hypoglycaemia after 4 h. However, insulin was suppressed at the end of the fast. The serum galactose level was normal. She subsequently underwent an oral glucose tolerance test (OGTT) which revealed post-prandial HH (table 1). A liver ultrasound scan demonstrated a PSS between the inferior vena cava and portal vein through a patent ductus venosus, which was subsequently confirmed with an abdominal MRI (fig. 1). Given her marked postprandial hyperinsulinism, a working diagnosis of postprandial shunting of insulin across the liver causing effective hyperinsulinaemia, which was previously masked by continuous feeds, was considered. The diazoxide and chlorothiazide were stopped. She was started on continuous feeds, after which her hypoglycaemia settled and she was able to come off the intravenous fluids. She developed episodes of
Senniappan et al.
Table 2. OGTT after surgery
Time, min –30
00
30
60
90
120 150 180
Glucose, mmol/l 4.5 Insulin, mU/l 3.7
4.8 4.9
6.3 7.1 4.6 4.1 81 20.6 17.7 9.7
4.6 6.5
4.1 4.5
hypoglycaemia whenever a short break from her continuous feeds was tried. In view of the persistent issues with hypoglycaemia, she underwent surgical closure of the shunt. Laparotomy confirmed a small but normal liver with no other evident anomalies. The shunt arose from the back of the portal vein bifurcation to the distal intrahepatic cava. Ligation of the shunt restored the normal antegrade haemodynamic flow into her portal venous system without undue rise in mesenteric venous pressures. Her hypoglycaemic episodes resolved after surgery and she was able to fast for 10 h without any hypoglycaemia. Much more importantly, the repeat OGTT after surgery did not reveal any hypoglycaemia and the insulin concentrations were not as elevated as before the surgery (table 2). She was established on bolus feeds after surgery.
Discussion
We report a challenging case of PSS who presented with postprandial HH that resolved with the closure of the shunt. To our knowledge, this is the first case report of PSS with HH. Cirrhosis of the liver in adult patients has been noted to be associated with spontaneous portosystemic collaterals leading to hyperinsulinism and insulin resistance due to diminished insulin degradation [9]. Reduced glycogen stores of the liver also contribute to hypoglycaemia in adults with cirrhosis [10]. PSS prevents partial degradation of insulin by the liver. In a study, plasma C-peptide and insulin response to an oral glucose load was assessed in 14 cirrhotic and 7 normal subjects [11]. Cirrhotic patients were divided into hyperinsulinaemic and normoinsulinaemic groups based on fasting plasma insulin concentrations. After oral glucose, all the cirrhotic patients showed the same glucose intolerance. C-peptide concentrations were also the same, but insulin concentrations were markedly increased in the hyperinsulinaemic group [11]. Hence, the authors suggest that pancreatic insulin secretion is not increased in cirrhosis and that the peripheral hyperinsulinism is due solely to decreased hepatic insulin degradation secondary to spontaneous portosystemic shunting [11]. PSS and Hypoglycaemia
Two adolescent Japanese females were described with liver dysfunction, PSS, primary amenorrhoea and virilisation [12]. Hyperandrogenism and hyperinsulinaemia were attributed to the reduced hepatic degradation secondary to shunting which reversed on closure [12]. In our patient, the postprandial shunting of insulin across the liver potentially caused the recurrent episodes of HH. This became more obvious once the patient was switched to bolus feeds. HH resolved once the PSS was surgically closed, thereby lending support that the shunt was the primary cause of hypoglycaemia. Diazoxide did not have any effect, as the defect was not in insulin secretion. The fast tolerance also increased after surgery, possibly due to increased glycogen storage in the liver. Nissen’s fundoplication can cause postprandial HH, but the fact that the HH disappeared once the shunt was repaired supports our hypothesis that the PSS caused the HH. Congenital anomalies of the umbilical and portal venous system are rare vascular malformations which could be associated with anomalies of the heart and gastrointestinal tract [13]. It has been described in patients with Turner’s syndrome, Noonan syndrome, trisomy 18, Goldenhar syndrome, Ellis Van Crevald syndrome, velocardiofacial syndrome and Down’s syndrome [13, 14]. Two patients with trisomy 21 have been reported with PSS possibly due to altered angiogenesis of the vitelloumbilical plexus [13]. A male fetus was noted with absence of the intrahepatic portal vein and ductus venosus with a direct communication between the portal sinus and inferior vena cava exhibiting an umbilicosystemic total shunt during the fetal life and a portosystemic total shunt after birth [13]. A female infant showed absence of the intrahepatic portal vein and a total portocaval shunt. In another study, three children with Down’s syndrome were reported with various portal anomalies (PSS, simple arterioportal shunt, complex arterioportal shunt) [15]. The PSS was clinically insignificant and resolved without any intervention, whilst the arterioportal shunt was successfully treated with embolisation in this group of patients [15]. In the past, concerns have been raised about the closure of the shunt as it could result in an eventual fatal portal hypertension because of an inability of the tiny intrahepatic portal venous system to expand [2]. However, it was confirmed that the visible intrahepatic portal venous system is actually also present in patients with PSS and surgical closure of PSS can be successfully done [16]. Surgical treatment options for PSS include ligation, banding, coiling and stenting [17, 18]. Horm Res Paediatr 2015;83:217–220 DOI: 10.1159/000369014
219
Disclosure Statement
Conclusion
PSS could be an associated feature of Down’s syndrome. PSS should be considered in patients with postprandial HH, especially in those with syndromic features. Surgical closure of a PSS is likely to resolve episodes of hypoglycaemia.
The authors have nothing to disclose.
References 1 Park JH, Cha SH, Han JK, Han MC: Intrahepatic portosystemic venous shunt. AJR Am J Roentgenol 1990;155:527–528. 2 Barsky MF, Rankin RN, Wall WJ, Ghent CN, Garcia B: Patent ductus venosus: problems in assessment and management. Can J Surg 1989;32:271–275. 3 Abernethy J: Account of two instances of uncommon formation in the viscera of the human body. Philos Trans R Soc 1793;83:59–66. 4 Witters P, Maleux G, George C, Delcroix M, Hoffman I, Gewillig M, Verslype C, Monbaliu D, Aerts R, Pirenne J, Van Steenbergen W, Nevens F, Fevery J, Cassiman D: Congenital veno-venous malformations of the liver: widely variable clinical presentations. J Gastroenterol Hepatol 2008;23:e390–e394. 5 Alvarez AE, Ribeiro AF, Hessel G, Baracat J, Ribeiro JD: Abernethy malformation: one of the etiologies of hepatopulmonary syndrome. Pediatr Pulmonol 2002;34:391–394. 6 Howard ER, Davenport M: Congenital extrahepatic portocaval shunts – the Abernethy malformation. J Pediatr Surg 1997; 32: 494– 497. 7 Kitagawa S, Gleason WA, Northrup H, Middlebrook MR, Ueberschar E: Symptomatic hyperammonemia caused by a congenital portosystemic shunt. J Pediatr 1992;121:917– 919.
220
8 Ono H, Mawatari H, Mizoguchi N, Eguchi T, Sakura N: Clinical features and outcome of eight infants with intrahepatic porto-venous shunts detected in neonatal screening for galactosaemia. Acta Paediatr 1998;87:631–634. 9 Bosch J, Gomis R, Kravetz D, Casamitjana R, Terés J, Rivera F, Rodés J: Role of spontaneous portal-systemic shunting in hyperinsulinism of cirrhosis. Am J Physiol 1984; 247: G206–G212. 10 Krähenbühl L, Lang C, Lüdes S, Seiler C, Schäfer M, Zimmermann A, Krähenbühl S: Reduced hepatic glycogen stores in patients with liver cirrhosis. Liver Int 2003; 23: 101– 109. 11 Johnson DG, Alberti KG, Faber OK, Binder C: Hyperinsulinism of hepatic cirrhosis: diminished degradation or hypersecretion? Lancet 1977;1:10–13. 12 Satoh M, Yokoya S, Hachiya Y, Hachiya M, Fujisawa T, Hoshino K, Saji T: Two hyperandrogenic adolescent girls with congenital portosystemic shunt. Eur J Pediatr 2001;160:307– 311.
Horm Res Paediatr 2015;83:217–220 DOI: 10.1159/000369014
13 Pipitone S, Garofalo C, Corsello G, Mongiovì M, Piccione M, Maresi E, Sperandeo V: Abnormalities of the umbilico-portal venous system in down syndrome: a report of two new patients. Am J Med Genet A 2003;120A: 528–532. 14 Rahemtullah A, Lieberman E, Benson C, Norton ME: Outcome of pregnancy after prenatal diagnosis of umbilical vein varix. J Ultrasound Med 2001;20:135–139. 15 Golewale N, Paltiel HJ, Fishman SJ, Alomari AI: Portal vascular anomalies in Down syndrome: spectrum of clinical presentation and management approach. J Pediatr Surg 2010; 45:1676–1681. 16 Blanc T, Guerin F, Franchi-Abella S, Jacquemin E, Pariente D, Soubrane O, Branchereau S, Gauthier F: Congenital portosystemic shunts in children: a new anatomical classification correlated with surgical strategy. Ann Surg 2014;260:188–198. 17 Kamimatsuse A, Onitake Y, Kamei N, Tajima G, Sakura N, Sueda T, Hiyama E: Surgical intervention for patent ductus venosus. Pediatr Surg Int 2010;26:1025–1030. 18 Yoshimoto Y, Shimizu R, Saeki T, Harada T, Sugio Y, Nomura S, Tanaka H: Patent ductus venosus in children: a case report and review of the literature. J Pediatr Surg 2004; 39: E1– E5.
Senniappan et al.
Copyright: S. Karger AG, Basel 2015. Reproduced with the permission of S. Karger AG, Basel. Further reproduction or distribution (electronic or otherwise) is prohibited without permission from the copyright holder.
HOR MON E RE SE ARCH I N PÆDIATRIC S
Received: September 23, 2014 Accepted: October 9, 2014 Published online: January 21, 2015
Horm Res Paediatr 2015;83:217–220 DOI: 10.1159/000369014
Postprandial Hyperinsulinaemic Hypoglycaemia Secondary to a Congenital Portosystemic Shunt Senthil Senniappan a Katherine Pitt a Pratik Shah a Ved Arya a Sanjay Jaiswal e Munther Haddad b Jonathan Hind c Anil Dhawan c Mark Davenport d Khalid Hussain a
a
Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children, b Department of Paediatric Surgery, Chelsea and Westminster Hospital, and Departments of c Paediatric Hepatology and d Paediatric Surgery, King’s College Hospital, London, and e Department of Paediatrics, Frimley Park Hospital, Frimley, UK
Established Facts • Postprandial hyperinsulinaemic hypoglycaemia is a rare cause of hypoglycaemia in children.
Novel Insights • We report for the first time the association of postprandial hyperinsulinaemic hypoglycaemia with PSS that resolved following the closure of the shunt.
Key Words Hyperinsulinaemic hypoglycaemia · Portosystemic shunt · Down’s syndrome
Abstract Background: Portosystemic shunts (PSS) are abnormal vascular connections between the portal vein or its tributaries and the systemic vein that allow mesenteric blood to reach the systemic circulation without first passing through the liver. PSS can be associated with various syndromes and can
© 2015 S. Karger AG, Basel 1663–2818/15/0833–0217$39.50/0 E-Mail [email protected] www.karger.com/hrp
lead to serious complications. We report a rare case of a child with PSS and recurrent hypoglycaemia. Case: A 20-monthold girl with Down’s syndrome presented with recurrent hypoglycaemic episodes. She had multiple anomalies including a ventricular septal defect, oesophageal atresia and tracheo-esophageal fistula, gastro-oesophageal reflux, and conjugated hyperbilirubinaemia. The initial investigations suggested hyperinsulinaemic hypoglycaemia (HH). She did not respond to diazoxide. An oral glucose tolerance test suggested postprandial HH. Further vascular imaging showed a side-to-side portocaval shunt (Abernethy malformation)
Dr. Khalid Hussain Developmental Endocrinology Research Group/Clinical Molecular Genetics Unit UCL Institute of Child Health and Great Ormond Street Hospital for Children 30 Guilford Street, London WC1N 1EH (UK) E-Mail Khalid.hussain @ ucl.ac.uk
with relative hypoperfusion of the liver. Hypoglycaemia resolved following surgical closure of the portocaval shunt. Conclusion: PSS can rarely be associated with HH, possibly due to lack of insulin degradation in the liver. Surgical closure of the shunt resolves the hypoglycaemia. © 2015 S. Karger AG, Basel
Table 1. OGTT at presentation
Time, min
Glucose, mmol/l Insulin, mU/l
–30
00
30
60
90
180
4.5 2.1
4.6 2.3
5.2 120
7.7 >300
7.4 >300
2.6 101
Introduction
Congenital portosystemic shunts (PSS) are characterised by the flow of splanchnic blood through a congenital fistula, bypassing the liver, into the systemic circulation. PSS are single (occasionally multiple) abnormal vascular connections between the portal vein or its tributaries and the systemic veins (typically the vena cava), which allow portal blood to reach the systemic circulation without first passing through the liver [1]. PSS can be intrahepatic or extrahepatic and can be associated with congenital heart disease [2]. This extremely rare abnormality of early embryonic life was first described by Abernethy in 1793 [3]. They can lead to lifethreatening complications such as encephalopathy, pulmonary hypertension, hepatopulmonary syndrome and (in children) developmental delay. Presumably because of the compensatory increase in hepatic arterial flow to the liver to compensate for reduction in hepatic portal venous flow and consequent change in sinusoidal oxygenation, there is a tendency to neoplastic change. This may be benign in the form of focal nodular hyperplasia or malignant, typically with the development of hepatoblastoma [4–6]. Portocaval shunts have also been reported to cause hyperammonaemia and encephalopathy [7]. Neonatal galactosaemia can also be caused by portohepatic venous shunts or portocaval shunts [8]. We report a rare case of a child with PSS and hypoglycaemia. The hypoglycaemia resolved after surgical closure of the shunt. Case Report A 20-month-old girl with Down’s syndrome presented with hypoglycaemic generalised tonic-clonic convulsion. She was managed with a dextrose bolus, followed by intravenous dextrose infusion. She had persistent hypoglycaemia and was unable to come off the intravenous fluids. She was previously on continuous gastrostomy feeds and was recently converted to 3 boluses of 240 ml Nutrini multifibre during the daytime. She was born at 35 weeks of gestation by normal delivery with a birth weight of 2.3 kg. She had multiple anomalies including a ventricular septal defect (repaired), oesophageal atresia and tra-
218
Horm Res Paediatr 2015;83:217–220 DOI: 10.1159/000369014
Portal vein PSS Inferiorvena cava
Fig. 1. Abdominal MRI revealing the PSS.
cheo-esophageal fistula (repaired), and gastro-oesophageal reflux (requiring Nissen’s fundoplication and gastrostomy feeds). The hypoglycaemia screen in the local hospital suggested HH (laboratory glucose 1.6 mmol/l, insulin 88 pmol/l and C-peptide 531 pmol/l). The rest of the screening bloods were normal (lactate 1.3 mmol/l, ammonia 41 μmol/l, cortisol 385 nmol/l, T4 13.5 pmol/l, TSH 4.4 mU/l). The blood spot carnitine profile, plasma amino acids and urine organic acids were all normal. She was commenced on 5 mg/kg/day of diazoxide and 7.5 mg/kg/day of chlorothiazide for the management of HH. However, she continued to have hypoglycaemic episodes despite the maximal dose of diazoxide (15 mg/kg/day). She was transferred to our tertiary centre for further management. Her glucose requirement was 10 mg/kg/min. She had a controlled fast, which revealed hypoglycaemia after 4 h. However, insulin was suppressed at the end of the fast. The serum galactose level was normal. She subsequently underwent an oral glucose tolerance test (OGTT) which revealed post-prandial HH (table 1). A liver ultrasound scan demonstrated a PSS between the inferior vena cava and portal vein through a patent ductus venosus, which was subsequently confirmed with an abdominal MRI (fig. 1). Given her marked postprandial hyperinsulinism, a working diagnosis of postprandial shunting of insulin across the liver causing effective hyperinsulinaemia, which was previously masked by continuous feeds, was considered. The diazoxide and chlorothiazide were stopped. She was started on continuous feeds, after which her hypoglycaemia settled and she was able to come off the intravenous fluids. She developed episodes of
Senniappan et al.
Table 2. OGTT after surgery
Time, min –30
00
30
60
90
120 150 180
Glucose, mmol/l 4.5 Insulin, mU/l 3.7
4.8 4.9
6.3 7.1 4.6 4.1 81 20.6 17.7 9.7
4.6 6.5
4.1 4.5
hypoglycaemia whenever a short break from her continuous feeds was tried. In view of the persistent issues with hypoglycaemia, she underwent surgical closure of the shunt. Laparotomy confirmed a small but normal liver with no other evident anomalies. The shunt arose from the back of the portal vein bifurcation to the distal intrahepatic cava. Ligation of the shunt restored the normal antegrade haemodynamic flow into her portal venous system without undue rise in mesenteric venous pressures. Her hypoglycaemic episodes resolved after surgery and she was able to fast for 10 h without any hypoglycaemia. Much more importantly, the repeat OGTT after surgery did not reveal any hypoglycaemia and the insulin concentrations were not as elevated as before the surgery (table 2). She was established on bolus feeds after surgery.
Discussion
We report a challenging case of PSS who presented with postprandial HH that resolved with the closure of the shunt. To our knowledge, this is the first case report of PSS with HH. Cirrhosis of the liver in adult patients has been noted to be associated with spontaneous portosystemic collaterals leading to hyperinsulinism and insulin resistance due to diminished insulin degradation [9]. Reduced glycogen stores of the liver also contribute to hypoglycaemia in adults with cirrhosis [10]. PSS prevents partial degradation of insulin by the liver. In a study, plasma C-peptide and insulin response to an oral glucose load was assessed in 14 cirrhotic and 7 normal subjects [11]. Cirrhotic patients were divided into hyperinsulinaemic and normoinsulinaemic groups based on fasting plasma insulin concentrations. After oral glucose, all the cirrhotic patients showed the same glucose intolerance. C-peptide concentrations were also the same, but insulin concentrations were markedly increased in the hyperinsulinaemic group [11]. Hence, the authors suggest that pancreatic insulin secretion is not increased in cirrhosis and that the peripheral hyperinsulinism is due solely to decreased hepatic insulin degradation secondary to spontaneous portosystemic shunting [11]. PSS and Hypoglycaemia
Two adolescent Japanese females were described with liver dysfunction, PSS, primary amenorrhoea and virilisation [12]. Hyperandrogenism and hyperinsulinaemia were attributed to the reduced hepatic degradation secondary to shunting which reversed on closure [12]. In our patient, the postprandial shunting of insulin across the liver potentially caused the recurrent episodes of HH. This became more obvious once the patient was switched to bolus feeds. HH resolved once the PSS was surgically closed, thereby lending support that the shunt was the primary cause of hypoglycaemia. Diazoxide did not have any effect, as the defect was not in insulin secretion. The fast tolerance also increased after surgery, possibly due to increased glycogen storage in the liver. Nissen’s fundoplication can cause postprandial HH, but the fact that the HH disappeared once the shunt was repaired supports our hypothesis that the PSS caused the HH. Congenital anomalies of the umbilical and portal venous system are rare vascular malformations which could be associated with anomalies of the heart and gastrointestinal tract [13]. It has been described in patients with Turner’s syndrome, Noonan syndrome, trisomy 18, Goldenhar syndrome, Ellis Van Crevald syndrome, velocardiofacial syndrome and Down’s syndrome [13, 14]. Two patients with trisomy 21 have been reported with PSS possibly due to altered angiogenesis of the vitelloumbilical plexus [13]. A male fetus was noted with absence of the intrahepatic portal vein and ductus venosus with a direct communication between the portal sinus and inferior vena cava exhibiting an umbilicosystemic total shunt during the fetal life and a portosystemic total shunt after birth [13]. A female infant showed absence of the intrahepatic portal vein and a total portocaval shunt. In another study, three children with Down’s syndrome were reported with various portal anomalies (PSS, simple arterioportal shunt, complex arterioportal shunt) [15]. The PSS was clinically insignificant and resolved without any intervention, whilst the arterioportal shunt was successfully treated with embolisation in this group of patients [15]. In the past, concerns have been raised about the closure of the shunt as it could result in an eventual fatal portal hypertension because of an inability of the tiny intrahepatic portal venous system to expand [2]. However, it was confirmed that the visible intrahepatic portal venous system is actually also present in patients with PSS and surgical closure of PSS can be successfully done [16]. Surgical treatment options for PSS include ligation, banding, coiling and stenting [17, 18]. Horm Res Paediatr 2015;83:217–220 DOI: 10.1159/000369014
219
Disclosure Statement
Conclusion
PSS could be an associated feature of Down’s syndrome. PSS should be considered in patients with postprandial HH, especially in those with syndromic features. Surgical closure of a PSS is likely to resolve episodes of hypoglycaemia.
The authors have nothing to disclose.
References 1 Park JH, Cha SH, Han JK, Han MC: Intrahepatic portosystemic venous shunt. AJR Am J Roentgenol 1990;155:527–528. 2 Barsky MF, Rankin RN, Wall WJ, Ghent CN, Garcia B: Patent ductus venosus: problems in assessment and management. Can J Surg 1989;32:271–275. 3 Abernethy J: Account of two instances of uncommon formation in the viscera of the human body. Philos Trans R Soc 1793;83:59–66. 4 Witters P, Maleux G, George C, Delcroix M, Hoffman I, Gewillig M, Verslype C, Monbaliu D, Aerts R, Pirenne J, Van Steenbergen W, Nevens F, Fevery J, Cassiman D: Congenital veno-venous malformations of the liver: widely variable clinical presentations. J Gastroenterol Hepatol 2008;23:e390–e394. 5 Alvarez AE, Ribeiro AF, Hessel G, Baracat J, Ribeiro JD: Abernethy malformation: one of the etiologies of hepatopulmonary syndrome. Pediatr Pulmonol 2002;34:391–394. 6 Howard ER, Davenport M: Congenital extrahepatic portocaval shunts – the Abernethy malformation. J Pediatr Surg 1997; 32: 494– 497. 7 Kitagawa S, Gleason WA, Northrup H, Middlebrook MR, Ueberschar E: Symptomatic hyperammonemia caused by a congenital portosystemic shunt. J Pediatr 1992;121:917– 919.
220
8 Ono H, Mawatari H, Mizoguchi N, Eguchi T, Sakura N: Clinical features and outcome of eight infants with intrahepatic porto-venous shunts detected in neonatal screening for galactosaemia. Acta Paediatr 1998;87:631–634. 9 Bosch J, Gomis R, Kravetz D, Casamitjana R, Terés J, Rivera F, Rodés J: Role of spontaneous portal-systemic shunting in hyperinsulinism of cirrhosis. Am J Physiol 1984; 247: G206–G212. 10 Krähenbühl L, Lang C, Lüdes S, Seiler C, Schäfer M, Zimmermann A, Krähenbühl S: Reduced hepatic glycogen stores in patients with liver cirrhosis. Liver Int 2003; 23: 101– 109. 11 Johnson DG, Alberti KG, Faber OK, Binder C: Hyperinsulinism of hepatic cirrhosis: diminished degradation or hypersecretion? Lancet 1977;1:10–13. 12 Satoh M, Yokoya S, Hachiya Y, Hachiya M, Fujisawa T, Hoshino K, Saji T: Two hyperandrogenic adolescent girls with congenital portosystemic shunt. Eur J Pediatr 2001;160:307– 311.
Horm Res Paediatr 2015;83:217–220 DOI: 10.1159/000369014
13 Pipitone S, Garofalo C, Corsello G, Mongiovì M, Piccione M, Maresi E, Sperandeo V: Abnormalities of the umbilico-portal venous system in down syndrome: a report of two new patients. Am J Med Genet A 2003;120A: 528–532. 14 Rahemtullah A, Lieberman E, Benson C, Norton ME: Outcome of pregnancy after prenatal diagnosis of umbilical vein varix. J Ultrasound Med 2001;20:135–139. 15 Golewale N, Paltiel HJ, Fishman SJ, Alomari AI: Portal vascular anomalies in Down syndrome: spectrum of clinical presentation and management approach. J Pediatr Surg 2010; 45:1676–1681. 16 Blanc T, Guerin F, Franchi-Abella S, Jacquemin E, Pariente D, Soubrane O, Branchereau S, Gauthier F: Congenital portosystemic shunts in children: a new anatomical classification correlated with surgical strategy. Ann Surg 2014;260:188–198. 17 Kamimatsuse A, Onitake Y, Kamei N, Tajima G, Sakura N, Sueda T, Hiyama E: Surgical intervention for patent ductus venosus. Pediatr Surg Int 2010;26:1025–1030. 18 Yoshimoto Y, Shimizu R, Saeki T, Harada T, Sugio Y, Nomura S, Tanaka H: Patent ductus venosus in children: a case report and review of the literature. J Pediatr Surg 2004; 39: E1– E5.
Senniappan et al.
Copyright: S. Karger AG, Basel 2015. Reproduced with the permission of S. Karger AG, Basel. Further reproduction or distribution (electronic or otherwise) is prohibited without permission from the copyright holder.
