Dr.Ghaniya KC , DrPraveen VP(Paed Endo)Dr.Greeshma Issac, Dr.Sajith Kesava(Paed Intensivists)Dr.C.Jayakumar
Three months old female child, presented with focal and multifocal seizures
Ba was 36 week preterm and Infant of diabetic mother on Insulin / Metformin
LGA , BW- 3.55 kg was born vaginally with no asphyxia
But due to respiratory distress,ba was put on High flow nasal cannula in NICU.
Ba developed seizures at a GRBS of 57mg% on day three of life, was intubated, treated with Phenobarbitome, Calcium and dextrose.
Neurosonogram was normal
On day five, MRI was taken and that showed hypoglycemic changes ( parieto occipital region
and splenium of corpus callosum)
Child was extubated to HFNC and then room air.
Despite of increasing GIR (15.7 mg/kg/minute – 18% dextrose and feed) ba had recurrent episodes of hypoglycemia
Hence metabolic cause was suspected.
Critical samples take ln during hypoglycemia showed raised insulin levels 65 micro IU, normal cortisol -21 , blood ketones were negative.
Metabolic work up – urine GCMS and TMS were sent.
As GIR requirement was increasing and serum insulin was noted to be high , a provisional diagnosis of hyperinsulinism was made.
On day 8 of life , ba was started on diazoxide and the dose was gradually increased from 5mg/kg/day to maximum dose of 20mg/kg/day according to the blood sugar values.
Hydrochlorothiazide(to prevent fluid over load associated with Diazoxide ) was added along with diazoxide , given for 3 days and stopped.
TSH – 1.92 uiu/ml Free T4- 1.62 ng/dl: normal limits
As the ba had refractory hypoglycemia, reducing dextrose fluids support was carried out meticulously over a period of 20 days after starting diazoxide and.
Octreotide and OG feeds were continued and thickened EBM (half scoop formula in 30ml EBM) was given to maintain blood sugar values while tapering off IV fluids
On day twenty , ba had 2 episodes of low blood sugars – 43,48 while on breast feeds and second hourly feed 60 ml with one scoop of forumula and inj hydrocortisone 2mg/kg single dose was given,
Ba responded well so continued at 5mg 8th hourly for a day.Serum electrolytes were within normal limits.
Ba had further hypoglycemia episodes , Whole exome sequencing(WES)sent showed familial hyperinsulinemic hypoglycemia – 1
Patient is currently admitted in the PICU.She is on Octredtide
40 mcg/kg/day – 0.6 ml SC TID
On EBM 43ml + 30 ml formula feed
Plan : To consider Sirolimus-Mammalian target of Rapsmycin (mTOR)till ba gains enough weight for depot Octreotide preparation.(8Kg)
Long acting Octreotide 6-8 mg every 4 weeks.
Consider Alpelisib (PI3K inhibitor) – ref NEJM 2023
Familial hyperinsulinemic hypoglycemia-1 is caused homozygous or compound
heterozygous mutations in the ABCC8 gene. Inactivating mutations in KATP-related genes, including ABCC8 and KCNJ11, are the most common cause of Congential Hyperinsulinisim, accounting for approximately 45–50% of cases.
This disorder is characterized diffuse islet cell
hyperplasia, focal adenomatous hyperplasia of beta cells, loss of consciousness due to hypoglycemia, hypoglycemic seizures, mental retardation due to repeated episodes of hypoglycemia, hyperinsulinemic hypoglycemia, insulin deficiency, and diabetes.
Congenital Hyperinsulinism is diagnosed if insulin and C-peptide levels are measurable, and hypofatty acidemia (plasma level of free fatty acids <1.5 mmol/L) and hypoketonemia (plasma β-hydroxybutyrate level <2 mmol/L) are present.
For Congenital Hyperinsulinism patients, diazoxide therapy is the first-line treatment. Octreotide can be administered as second-line therapy for patients who do not respond to diazoxide.
Prognosis is guarded in these patients
Take Home message :
Hyperinsulinemic hypoglycemia (HH) typically presents in the neonatal period, it can also occur in infancy, childhood, and adulthood with varying severity and etiology .However, owing to the higher glucose consumption rate of neonates and infants, they have a considerably higher risk of permanent brain damage. Therefore, promptly diagnosing and managing HH are important to prevent neurological complications, such as cerebral palsy, epilepsy, neurodevelopmental deficits, and death.