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Indian Pediatr 2011;48: 139-141 |
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Positron Emission Tomography in Congenital
Hyperinsulinism |
NB Mathur, Mahesh Sharma, Anil Agarwal* and Ajay Kumar
From Department of Pediatrics, Maulana Azad Medical
College and *Department of Gastrointestinal Surgery,
GB Pant Hospital, New Delhi 110002, India.
Correspondence to: Dr NB Mathur, Director Professor of
Pediatrics, Maulana Azad Medical College,
New Delhi 110002, India.
Email: [email protected]
Received: May 12, 2009;
Initial review: June 8, 2009;
Accepted: August 21, 2009.
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We report a case of congenital hyperinsulinism with diffuse pancreatic
abnormality diagnosed preoperatively by using [18-F]-L-DOPA positron
emission tomography (PET). The infant was referred to us for recurrent
hypoglycemia. Critical blood sample revealed increased insulin: glucose
ratio. DOPA PET scan revealed diffuse involvement of pancreas. Subtotal
(95%) pancreatectomy was done. Infant remained euglycemic on breast
feeds at discharge.
Key words: Congenital hyperinsulinism,
[18-F]-L-DOPA positron emission tomography, Subtotal pancreatectomy.
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Congenital hyperinsulinism, previously
called Primary islet cell hypertrophy (nesidioblastosis) is also known as
Persistent hyperinsulinemic hypoglycemia of infancy (PHHI). It is
characterized by nonketotic hypoglycemia in association with elevated
insulin levels (>10 µU/mL). It is the most common cause of persistent and
recurrent hypoglycemia in neonates [1,2]. Surgical treatment is indicated
if medical therapy fails [2,3]. The distinction between focal and diffuse
lesions is critical in planning surgical intervention but is not possible
clinically. We are presenting a case of congenital hyperinsulinism with
diffuse pancreatic abnormality diagnosed preoperatively by using
[18-F]-L-DOPA Positron emission tomography (PET).
Case Report
A female baby, product of a non-consanguineous marriage
was born to 28 year old mother at term by vaginal route at a private
hospital. Antenatal period was uneventful and mother’s random blood sugar
in third trimester was 86 mg/dL. At birth, baby cried after tactile
stimulus and breastfeeding was started at 1 hour of life. On day 2, baby
became lethargic, did not accept feeds and had multiple episodes of
seizures. Blood sugar was 20mg/dL, sepsis screen were negative and lumbar
puncture was normal. The infant was started on glucose infusion which was
hiked to 12 mg/kg/minute on which she was maintaining euglycemia. Every
attempt to decrease the glucose infusion rate resulted in hypoglycemia.
Baby had multiple episodes of hypoglycemic seizures during first three
weeks of life for which she was transferred to us. At admission, baby’s
random blood sugar was 18 mg/dL. Glucose infusion was maintained at 12
mg/kg/min to maintain euglycemia. It was not possible to decrease glucose
infusion rate. Critical blood sample sent during an episode of
hypoglycemia revealed blood sugar level 28 mg/dL, serum insulin 23µU/mL
and serum insulin to blood glucose ratio 0.8. Serum pH and ammonia were
normal and urinary ketones and reducing substance was negative. A
diagnosis of congenital hyperinsulinism was confirmed. On day 30 of life,
subcutaneous octreotide was started at 30 µg/kg/day in four divided doses.
Dextrose infusion was subsequently tapered and baby was maintaining
euglycemia on exclusive breast feeding. On day 36 of life, oral diazoxide
was started and injection octreotide was stopped (so that baby could be
discharged on oral drugs) but baby could not maintain euglycemia and
injection octreotide was restarted. To ascertain the type of pancreatic
abnormality (focal or diffuse) [18-F]-L-DOPA PET scan was done on
day 120 of life. It was suggestive of diffuse variety of congenital
hyperinsulinism.
During the entire period, baby stayed in the hospital
and remained euglycemic. Baby had developmental delay in all domains at 16
weeks of life. However, parents were not affording medical management and
surgery was planned. Spleen preserving near total pancreatectomy was done
at 5 month of life. Post operative period was uneventful. Histopathology
revealed diffuse hyperplasia of islet cells. After two weeks of
pancreactectomy, octreotide was gradually tapered and baby maintained
euglycemia on exclusive breast feeding. Baby was discharged on post
operative day 20 on exclusive breast feeding.
Discussion
In 2003, researchers in Finland reported a new imaging
technique using [18-F]-L-DOPA PET scanning to distinguish between focal
and diffuse pancreatic lesion and to localize in the case of focal lesion
[4]. The [18-F]-L-DOPA scan is currently available at only a few centers
worldwide. This technique is 96% accurate for differentiating between
focal or diffuse disease and 100% accurate in localizing the focal lesion
[5]. However, there are no reports on the use of (18-F)-L-DOPA positron
emission tomography in congenital hyperinsulinism till date from India.
Every effort should be made, both before and during
surgery, to identify or rule out a focal lesion. Finding a focal lesion
can potentially prevent unnecessary pancreatic resection. Most focal
lesions are too small to identify by CT scanning, MRI, or even
intraoperative palpation. Invasive procedures like pancreatic venous
sampling or intra-arterial calcium stimulation may help identify a focal
lesion but they are technically difficult with low sensitivity [6].
Diagnosis of congenital hyperinsulinism is based on
"critical" samples (samples drawn at a time of fasting hypoglycemia:
plasma glucose <50 mg/dL). The finding of nonketotic hypoglycemia in
association with elevated insulin levels (>10 µU/mL) and normal levels of
free fatty acids (FFA) confirms the diagnosis of hyperinsulinism. The
insulin-to-glucose ratio may range from 0.4-2.7 (normal <0.3) [7].
Surgical treatment is indicated if medical therapy
fails, if a discrete lesion is identified, or if patient’s family is
unable or unwilling to comply with medical therapy. Subtotal (95%)
pancreatectomy is the most widely accepted procedure for infants and
children [8]. Hypoglycemia often persists even after a 95-98%
pancreatectomy. Hypoglycemia may be easier to control after surgery and
may resolve or persist throughout life. Patients who undergo
pancreatectomy are at high risk for developing diabetes mellitus later in
life. In some series, a high frequency of mental retardation,
developmental delay, and non hypoglycemic seizures has been observed.
These findings are generally attributed to minimal brain damage from early
hypoglycemic events, although the existence of these disorders as inherent
co- morbid conditions along with congenital hyper-insulinism has not been
fully excluded [9]. Some data suggest that patients with early severe
disease treated with early, aggressive surgery have a better
neurodevelopment outcome [10].
To conclude, critical blood sample and [18-F]-L-DOPA
PET scan are crucial in the diagnosis of congenital hyperinsulinism. In
India,(18-F)-L-DOPA PET scanning is limited to some regional centers.
Hence, it is all the more important to be aware of its utility for optimal
utilization. Aggressive management is advocated to prevent neurological
sequel.
Contributors: NBM was involved in analysis of
findings, planning work up of the patient, finalization of draft and will
act as guarantor for the paper. MS and AK were involved in drafting the
paper and primary care of the patient. AA was involved in surgical
management of the patient and drafting the paper.
Funding: None.
Competing interests: None stated.
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