Insulinoma-Anaesthetic Implications with Review of Literature-Juniper Publishers
Juniper Publishers-Journal of Anesthesia
Abstract
Insulinomas are rare tumours that present with 
recurrent hypoglycaemic episodes. They are often misdiagnosed or 
diagnosis is often delayed due to their bizarre clinical presentation. 
Diagnosis of insulinoma is made based on history (Whipple's Triad), 
biochemical tests and imaging modalities. Treatment includes medical and
 surgical management. We intend to describe the anaesthetic management 
of three cases of insulinoma observed over a period of one year and 
review the existing literature. Though rare, when they do occur, these 
tumours pose a great challenge to anaesthesiologists. Vigilant 
monitoring of blood sugars intraoperatively is a must to counteract 
these wide swings, hence providing a better patient outcome.
 Keywords: Insulinoma; Anaesthetic management; Hypoglycaemia; Whipple's Triad; Intraoperative ultrasound (IOUS)Introduction
Insulinomas are rare tumours with an incidence of 1-4 per million per year [1].
 They are the most common functional variety of neuroendocrine tumours 
of pancreas. They are usually small (<2cm), solitary and benign 
(approximately 90%). Patients present with adrenergic or neuroglycopenic
 symptoms due to recurrent hypoglycaemia [1-4].
 Weight gain is a common finding in 20-40% and is primarily due to 
overfeeding to overcome hypoglycaemia. Diagnosis of insulinoma must be 
suspected in otherwise normal patients who present with repeated 
episodes of hypoglycaemia and they warrant further investigation [1,2].
 Because of the bizarre nature of the presenting symptoms, many patients
 will present to neurologists or psychiatrists and hence delay in early 
diagnosis or misdiagnosis. Surgical excision is the definite treatment.
Case Series

Three young patients; a 28 yr old primigravida@29 
weeks gestation, a 37 year old male with past history of seizure 
disorder on treatment and a 29 year old male, presented with complaints 
of recurrent episodes of drowsiness, excessive sweating, delayed waking 
from sleep, seizures and altered sensorium. In view of neurological 
symptoms, all three were initially evaluated by neurologists. However, 
it was incidentally observed that they had severe hypoglycaemia during 
these episodes (GRBS<50mg/ dl). Diagnosis of insulinoma was then made
 based on history (Whipple's Triad), biochemical tests and imaging 
modalities (Table 1).
Discussion
The median age of presentation is approximately 47 years, with a mild female preponderance (female: male 1.4: 1) [5-7].
 Diagnosis of insulinoma is clinical, biochemical and localization of 
the tumour. Clinical diagnosis is based on Whipple's Triad which 
includes repeated attacks of hypoglycaemia, serum blood glucose levels 
<50mg/dl during that period and relief of symptoms with glucose 
administration [1,2].
 Biochemical diagnosis includes the 72-h fasting test which is 
considered as gold standard. During the fasting period, the patient is 
allowed to drink calorie-free fluids and physical activity is 
encouraged. Blood glucose should be measured 6-hourly till it reduces to
 60mg/dL and then every 1 or 2 hours till it reduces to 40-45mg/dL. When
 symptoms of hypoglycaemia appear, blood should be sampled and diagnosis
 of insulinoma is made when-
- Plasma glucose <55mg/dl during episode of hypoglycaemia,
- Increased serum Insulin (>5-10microU/mL)
- Elevated C-peptide (>200micromol/L) and
- Increased proinsulin level (>25%).5
Localizing insulinomas are difficult with a failure rate of 10-27% [1,5,8].
 It includes CT, MRI, Somatostatin receptor scintigraphy. Recently, the 
use of Endoscopic Ultrasound is shown to have increased sensitivity. 
Intraoperative ultrasound (IOUS) with surgical palpation has a high 
success rate (85-90%) [1,5,8].
 Treatment includes medical and surgical management. Medical management 
includes dietary modification and pharmacological agents. Patient is 
advised frequent small meals throughout the day to avoid hypoglycaemia. 
Diazoxide is often started in these patients as it decreases release of 
insulin by stimulating alpha adrenergic receptors and thereby inhibits 
beta cells of islets of pancreas.
Somatostatin analogues like octreotide and lanreotide
 is used as they bind to somatostatin receptors on insulinomas and 
decrease insulin Secretion [9-11].
 Steroid therapy has been considered as it inhibits insulin mediated 
glucose uptake and promotes release of glucose. However its value is 
doubtful and even considered harmful as it can cause exaggeration of the
 normal rebound hyperglycaemia that is seen postoperatively and there is
 a high risk of infection. Surgical management includes enucleation 
which is the treatment of choice. Some cases may require distal or 
partial pancreatectomy.
Anaesthetic implications-Any neurologic damage that 
has occurred as a result of previous hypoglycaemic episodes must be 
documented. Intravenous infusion of 5% Dextrose or 10% Dextrose should 
be started during the fasting period prior to surgery. Aim is to 
maintain blood glucose of more than 50mg/ dl [1,5].
 Adequate NPO may not be achieved as patients may become symptomatic 
even after a few hours of fasting and due to poor patient compliance. 
Hence the risk of aspiration must be considered while inducing these 
patients and adequate care must be taken.
Administration of anaesthesia for removal of these 
tumours is challenging due to difficulty to maintain a normal blood 
glucose level. Wide fluctuations in blood glucose levels during tumour 
handling are often observed. Hypoglycaemia may be masked under general 
anaesthesia because signs of hypoglycaemia such as sweating, 
tachycardia, and hypertension and dilated pupils which can also occur 
due to hypovolemia, surgical stimuli, lighter surgical planes and drugs.
 Hence, detecting hypoglycaemia under anaesthesia is difficult. 
Intraoperative hypoglycaemia can cause CNS damage and such patients may 
often require postop ventillatory support.
It is recommended that blood glucose level must be 
checked before induction and every 15-30 from then on. It is imperative 
that glucose levels must be monitored in the recovery period also 
because
- Risk of rebound hyperglycaemia after resection
- Multiple adenomas may exist which can cause early postoperative hypoglycaemia which is not seen intraoperative.
Due to frequent blood sampling requirement, an 
arterial line is essential. Anaesthetics which decrease cerebral 
metabolic rate like propofol or thiopentone should be used. General 
anaesthesia with propofol combined with epidural is preferred choice of 
anaesthesia for insulinoma excision [1].
 Post resection blood sugars may be high because of anti insulin 
hormones like GH, glucagon and glucocorticoids, which persist at high 
levels for a few days after removal of tumour. This hyperglycaemia is 
self limiting. Post op hypoglycaemia however, should raise the suspicion
 of either tumour not been found or multiple other insulinomas 
persisting.
Conclusion
Though rare, when they do occur, these tumours pose a
 great challenge to anaesthesiologists due to inadequate fasting, 
preoperative neurologic damage due to repeated hypoglycaemic episodes 
and wide swings in sugars during handling of tumour. Vigilant monitoring
 of blood sugars intraoperatively is a must to counteract these wide 
swings, hence providing a better patient outcome.
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