Insulinoma.PJ Halder, P Hafeezunnisa, R Pai, AB Samsi
Dept of Surgery, Jagjivan Ram Hospital, Bombay.
A case of insulinoma who had episoic bizarre behaviour is presented here. Pre-operative fasting and two hour post-prandial blood sugar values indicated hypoglycemia with inappropriately high insulin levels. USG and CT scan of the abdomen revealed a tumor of head of the pancreas. The tumour was enucleated surgically. Histopathological examination confirmed the origin as islet cells. The post-operative blood sugar and insulin levels were found to be in normal range. Since insulinoma is a rare pancreatic tumor, differential diagnoses along with a brief review of the literature is also presented.
Keywords: Adult, Blood Glucose, analysis,Case Report, Fasting, Female, Glucose Tolerance Test, Human, Insulin, blood,Insulinoma, blood,diagnosis,surgery,Pancreatic Neoplasms, blood,diagnosis,surgery,Tomography, X-Ray Computed,
Insulinoma is a rare pancreatic tumour. A high index of suspicion is very essential in arriving at a diagnosis. Recurrent episodes of hypoglycaemia with predominantly neuroglycopenic symptoms, is the usual mode of presentation. The non-specific and often bizarre symptoms, occurring at irregular intervals, leads to a delay in diagnosis and often to mis-diagnosis as a neurologic or psychiatric disorder.
The diagnosis is usually suspected by documentation of fasting hypoglycemia with symptoms, which are relieved by administration of glucose. The diagnosis can be confirmed by demonstration of an elevated fasting insulin/glucose ratio.
A 26-year-old female patient was admitted with a 2 year history of episodic confusion, sudden drowsiness with occasional loss of consciousness followed by abnormal limb movements. There was a history of 2 episodes of convulsions limited to the upper extremities only and a single episode of right sided hemiplegia which recovered completely within 5 days.
The symptoms occurred mainly after fasting and were relieved after ingesting sugar. There was no history of taking oral hypoglycemic drugs or exogenous insulin. Her menstrual cycles and lactation were normal (last delivery was 1 ˝ years ago).
On examination, general examination and systemic examination were normal. Her abdominal examination did not reveal any palpable lump.
Pre-operative fasting blood sugar values ranged between 21 mg% to 37 mg% and the two hour post-prandial blood sugar values ranged between 27 mg% to 43 mg%. Insulin levels were assayed preoperatively by radio- immunoassay and the values were as shown in [Table - 1]
Abdominal ultrasound examination revealed a well-defined isoechoic rounded mass lesion about 2 to 3 cm in size in the region of the head of pancreas. Rest of the examination was normal.
CT scan of the abdomen showed a well-defined tumour in the antero-inferior aspect of the head of pancreas. There was no peri-pancreatic lymphadenopathy. (See [Figure:1]). CT scan of the head done in view of her episodes of unconsciousness, was normal. EEG showed bilateral cerebral dysrhythmia in the occipito-temporal region. Hemogram, urinanalysis, X-ray chest, liver function tests were all within normal limits.
At exploration, a solitary pancreatic tumour was found, well encapsulated measuring 3cm x 2cm x 1.5cm, reddish brown in colour on the antero-inferior aspect of the neck of the pancreas. There was no extra- pancreatic spread and the liver was normal. There was no peri-pancreatic lymphadenopathy. The tumour was enucleated easily.
The post-operative course was uneventful except for a transient hyperglycemia in the immediate post-operative period. The patient's post-operative fasting blood sugar was 94 mg% and the two hours post-prandial blood sugar value was 113 mg%.
The excised tumour was histopathologically confirmed to be an islet cell tumour (See [Figure:2]).
The post-operative insulin radio- immunoassay studies revealed insulin levels within the normal range as shown in [Table - 2].
Insulinoma is a rare pancreatic beta cell tumour. In about 80% cases there is a solitary benign adenoma, in about 10% cases there are multiple adenomata and in a further 10% the lesion is a metastasising carcinoma,. The majority of single benign adenomas are quite small varying between 0.5 to 3.0 cm in diameter.
The clinical presentation of insulinomas being bizarre, misdiagnoses such as seizure disorder, transient ischaemic attach, brain tumours, hysteria, depression, schizophrenia, etc,,, may be made.
The diagnosis of insulinoma is based on demonstration of hypoglycemia (provoked by prolonged fasting or by intravenous tolbutamide) accompanied by an inappropriately high plasma insulin level,,,.
The fasting insulin/glucose ratio is the most important diagnostic criterion for diagnosis of insulinoma. The insulin/glucose ratio (plasma insulin ? U/ml) / plasma glucose (mg/dl) in normal persons is always less than 0.4. In patients with insulinoma this ratio is greater than 1.0. In our patient, the pre-operative fasting insulin/glucose ratio was 1.8 which post-operatively came down to 0.1 suggesting successful removal of the tumour.
Estimation of C-peptide concentrations is advocated by some authors to rule out the possibility of exogenous insulin administration causing hypoglycemia,,. In patients with insulinoma, the C-peptide concentrations will he high along with high insulin levels but in patients with exogenous insulin administration though the insulin levels will be high, the C-peptide concentrations will not be high. In our patient, fasting hypoglycemia accompanied by high levels of insulin with no positive history of exogenous insulin administration was present. Cpeptide estimations were not done due to nonavailability of facilities.
Ultrasonography and CT Scan, localise the insulinoma preoperatively in a majority of cases as in our case too. Selective angiography is indicated in cases where the tumour is not located by ultrasonography or CT scan. However angiography is as helpful as it is misleading; 57% being true positive, 35% being false negative and 8% being false positive,, our case, angiography was not resorted to.
With a localised tumour, laparotomy and enuucleation of the tumour is possible in about 80% of the cases,. In our patient, a solitary benign adenoma found in the region of the neck of the pancreas could be easily nucleated. Multiple adenomata may be present neccesaitating palpation of,, the whole gland. Multiple adenomata may require large resections of the pancreas,.
Following excision of a solitary adenoma, the rognosis is excellent. Surgical excision of the tumour is urative and prolonged survival is possible even in malignant insulinomas,. Diazoxide and streptozotocin are useful agents for treatment of intractable hypoglycemia due to metastatic islet cell carcinoma. Kiang et al reported a case where mithramycin, an inhibitor of RNA synthesis was used successfully for the treatment of intractable hypoglycemia.
The surgeon may be in a dilemma if the tumour cannot be localised by any imaging modalities or at exploration. If the patient's hypoglycemia could be controlled pre-operatively adequately and safely with drugs like diazoxide, then the abdomen should be closed without performing a blind distal pancreatectomy and the patient can be treated with diazoxide for about 1 to 1 ˝ years by which time the tumour may have grown in size to be detected and the patient is re-explored. However, if the patient's hypoglycemia was not adequately controlled with diazoxide then a blind distal pancreatectomy is performed and about 50% of such patients are cured with this procedure.
We thank the Chief Medical Officer, Jagjivan Ram Hospital, Mumbai - 400 008, Western Railway and Dr PM Pai, the Dean of the Seth GS Medical College and King Edward Memorial Hospital, Mumbai for allowing us to publish the hospital data.
[Table - 1], [Table - 2]