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Mediquest - July '07 Edition |
An interesting case of Neonatal hypoglycemia
• By.Dr. S.Ramesh, MD, Paediatrician - B.R.S.Hospital
• Dr.Binuninan (Neonatologist - SRMC)
• Prof.Rajkishore Bagdi (SRMC)
• Dr.Madhu, MS,MCh., Paediatric Surgeon - Visiting consultant – B.R.S.Hospital - Asst. Surgeon SRMC
• Dr.Krishna Shankar, MD, DNB, ICU, Registrar – BRS Hospital
Case History :
Baby E of – 2 nd child delivered by LSCS in B.R.S.Hospital was found to have low blood sugar (37mg%)on routine capillary blood glucose testing 1 hour after delivery
Course in BRS Hospital :
The neonate was commenced initially on 10% Dextrose and supplemented with oral feeds on the 2 nd hospital day, Serum Insulin done when the sugar was 37 mg% was 10 m Iu/ml. Meanwhile there was history of the 1 st sibling dying with documented hypoglycemia. This was conveyed to us on the 4 th hospital day with this information diagnosis of hyper Insulinism familial hyper insulinemic hypoglycemia (Nesido blastosis) was considered.
The Neonate needed 9mg/kg/min of glucose to maintain sugars. In addition oral diazoxide and 4 th hourly subcutaneous Octreotide was commenced. Repeat serum insulin was done 6 days after admission. When blood sugar was 32 mg% insulin level Was 26 m IU/ml.
The parents were counseled about the condition in detail and the need to Introduce a long line and stay in the hospital for a prolonged period of time. They were also informed that the child may require pancreatectomy if medical treatment fails.
Child was shifted to SRMC for further management.
Course in SRMC :
In SRMC continuous Dextrose infusion was continued through a long line along with Octreotide and Diazoxide. Sr.Cortisol was normal. While tapering IV fluids, there was few episodes of hypoglycemia. Child also had episodes of hypoglycemic seizures – which was treated with IV Dextrose and Pheno Barbitone. T.Hydro chloro thiazide was added for sugar control. Since there was persistent hypoglycemia with medical management. Near total Pancreatectomy was planned.
CT abdomen prior to surgery was normal. Explorative Laprotomy with near total pancreatectomy was done. On the table pancreas was grossly normal. There was no palpable adenoma or swelling. Post op child had Electrolyte abnormalities and sepsis which was treated with IV fluids and antibiotics. Child also had mild hypoglycemia after surgery in the post op period. Child was started on Tab.Diazoxide on 4 th post op day, Tab.Hydro chloro thiazide, with Inj.Octerotide along with high caloric diet. Child was weaned off IV fluids. With high caloric feeds and oral medications child was maintaining Euglycemic state and gained weight-hence was discharged.
Footnote :
Recently when the child was 6 months old it developed Dengue fever – and was admitted in B.R.S.Hospital during that time child developed stress induced hyperglycemia and had to be treated with Insulin infusion!!
At that time Diazoxide and Hydrochlorothiazide was stopped. 1 week after discharge, sugars dropped and child was restarted on medications.
Clinical discussion :
Hypert insulinism in infancy
Hyper insulinemic hypoglycemia has previously masqueraded under a variety of difficult descriptive names, including idiopathic hypoglycemia of child hood, leucine sensitive hypoglycemia, “Neonatal Insulinemia” , pancreatic microadenomatosis , `Nesidoblastosis`, persistent hyper insulinaemic hypoglycemia of infancy and congenital hyperinsulinism.
Familial hyper insulinemic hypoglycemia (Nesido blastosis)
It may be an autosomal recessive disease, charecterised by excessive fetal growth and severe Neonatal hypoglycemia often unresponsive to medical management. This severe from is due to defects in either of the two components of Islet ßce ll K+ATP channel (either the solphonyl urea receptor or the inward K+ channel) A milder autosomal dominant form with delayed onset has an un known cause.
Clinical presentation :
• Most infants with hyperinsulinism present during the 1 st post natal days, while other during the 1 st year.
• The first clinical manifestations of hyper insulinism include non specific features such as “Floppiness”, “ Jitteriness”, poor feeding and lethargy More dramatically the infants may have seizures, coma and evenested neonatal death
• Other manifestations include – apathy, intermittent apneic spells or tachypnoea, weak or high pitched cry & eye rolling.
• Episodes of sweating, sudden pallor, hypothermia and Cardiac arrest may occur.
• The importance of accurately measuring blood glucose in the presence of any of these symptoms cannot be over emphasised.
Diagnosis of hyper insulinism :
• Considerable controversy surrounds the definition of neonatal and infantile hypoglycemia.
• Pragmatically any infant with a persistent measure of blood glucose less than 45mg/dl (2.5 mmo/L) particularly when accompanied by symptoms, shoude be the focus of attention and the diagnosis of hyper insulinism considered. Any persistent hypoglycemia, whether symptomatic or not needs investigation and treatment.
• Diagnostic criteria for hyper insulinism.
A – Glucose requirements 6-8 mg/kg/min to maintain glucose above 45-55 mg/dl.
B- Laboratory blood glucose < 45 mg/dl
C – If insulin level at the time of confirmed hypoglycemia is greater than 10 micro IU/ml, with raised C-peptide
D - Inappropriately low blood free fatty acid and ketone body concentrations at the time of hypoglycemia
E- Glycaemic response after the administration of glucagon – when hypoglycemic.
F – absence of Ketonuria.
Management of hyper insulinism
Medical Treatment
Initial stabilization
• The main stay of initial Medical Treatment is the provision of adequate Carbohydrate to maintain blood glucose concentration above 45-55 mg/dl.
• When symptoms other than seizures are present an intra venous bolus of 2ml/kg of 10% glucose is effective in elevating the blood glucose concentration. In the presence of seizures 4ml/kg of 10% glucose as a bolus injection is indicated.
• After initial therapy a glucose infusion should be given at 8mG/kg/min. if hypoglycemia recurs, the infusion rate should be increased until 15-20% glucose is used.
In neonates and children with persisting hypoglycemia very high infusion of glucose (>20mg/kg/min) in addition to frequent enteral feeds may be required. Inspite of this if hypoglycemia permits and in order to decrease insulin secretion, addition of pharma cological agents are required.
Pharmacological agents :
The pharmacological agents used are
• Diazoxide
• Hydrochlorothazide
• Octreotide
• Glucagon
• Nifidipine
A- Diazoxide and hydrochlorothazide :
Diazoxide (10-25 mg/kg/dl in 2 to 3 divided doses)
Hydrochlorothiazide (7-10 mg/kg in 2 divided doses) are recommended and showed be always given together. Both these agents activate potassium channels by different Mechanisms – thereby reducing insulin secretion. The diuretic can also over come the fluid retaining effects of diazoxide . The frequency with which infants respond is 15-60%. The common side effects of diazoxide are hirsutism, edema and electrolyte inbalances.
B- Octerotide and glycogon :
1. The somato statin analogue octerotide in useful in controlling hyper insulinaemic hypoglycemia.
2. It can be given at the dose of 20-50 m g subcutaneously 6-12 th hourly.
3. It can be also given as an infusion in combination with glucogon, which has a powerful effect in mobilising glucose from hepatic glycogen.
4. The doses proposed for initiating treatment are 1.0 m g/kg/hour of glucagons together with 10 m g/kg/day of octerotide.
C- Nifedipine:
• Slow release form of Nifedipine at a dose of 0.25 – 2.5mg/kg/dl can be used.
• In addition to activating potassium channels by diazoxide and chlorothiazide, nifedipine is used to block the voltage dependent Ca+ channels – reducing insulin secretion.
3 - Surgical Management
1. This is indicated when there is failure of aggressive medical management to maintain sugars.
• Some exports recommended the aggressive medical management should be continued for 4-6weeks in early onset hyper insulinism.
• All children should undergo imaging of the pancreas in the event of persisting hypoglycemia.
4 – The absolute indication for surgery are :
• Demonstration of focal hyperplasia in children un responsive to medical treatment.
• Glucose infusion dependency despite maximum doses of diazoxide, nifedipine, glucagons and somatostatin.
5. Infants with diffuse disease – near total pancreatectomy (95%) infants with focal forms of disease – partial pancreatectomy (preserving) the normal tissue.
6. Post operative complications :
• Early postoperative glucose intolerance –> requires insulin
• Post operative diabetes – > requires insulin
• Post operative exocrine pancreas insufficiency requires pancreatic enzyme replacement.
• Further hypoglycemia may occur in small number of infants, despite 95% pancreatectomy possible reasons include focal lesion in the head of pancreas, or diffuse disease that is medically unresponsive. These infants requires medical treatment and consideration of total pancreatic resection at a later date if hypoglycemia persists.
Key leaning points :
• Do routine CBG for all Neonates, even in the absence of symptoms. We picked up this case only on Routine Examination, Hypoglycemia is suspected if sugars are persistently below 45mg/dl.
• Serum Insulin levels should be done at the time of occurrence of hypoglycemia. If the levels are more than 10 m IU/ml hyperinsulinism should be suspected.
