Insulinoma

Insulinoma


INSULINOMA

  • Most common of all functioning pancreatic endocrine tumors (PET)
  • Highest incidence in 4th to 6th decade
  • Women are slightly more affected
  • All insulinomas are located in the pancreas and tumors are equally distributed
  • 90% are solitary and 90% are small ( < 2cm)
  • 10% are multiple (always associated with MEN 1) and 10% are malignant 

Clinical features: Abdominal discomfort, sweating, hunger, dizziness, diplopia, overeating, and obesity

Whipple’s triad

  • Symptoms of hypoglycemia after fasting or exercise
  • Symptoms of hypoglycemia (blood sugar < 45mg %)
  • Immediate relief after I.V. glucose administration 

Diagnosis

  • A fasting test that lasts for upto 72 hours is the most sensitive test
  • Insulin, Proinsulin, C-peptide and blood glucose are measured at 1 to 2 hour intervals to demonstrate high secretion of insulin in relation to blood glucose
  • Continuous C-peptide levels demonstrate the endogenous insulin secretion and exclude factitious hypoglycemia caused by insulin injection

Insulin radioimmunoassay

  • Insulin level > 7 µU/ml
  • Insulin/glucose ration > 0.3
  • Increased circulating C-peptide
  • Proinsulin level >24% of total insulin signifies insulinoma
  • Proinsulin level >40% of total insulin signifies malignant insulinoma
  • For preoperative localization: Endoscopic ultrasound(EUS) has the highest sensitivity 

Treatment

  • Enucleationis the treatment of choice for benign insulinomas
  • For superficial tumors: laparoscopic enucleation
  • Tumors located deep in the body or tail and those in close proximity to pancreatic duct: distal pancreatectomy
  • Diazoxide suppresses insulin secretion and offers good control of hypoglycemia
  • Malignant insulinomas: aggressive resection
  • When surgery cannot be applied for malignant insulinomas: Chemotherapy (Doxorubicin + Streptozocin)
  •  v  Nesidioblastosis: normal pancreatic islets replaced by diffuse hyperplasia of islet cells

Exam Question

  • Xylose test is used in the diagnosis of malabsorption due to intestinal mucosal disease. This test is not used for the diagnosis of Insulinomas
  • Fasting blood glucose, C- peptide levels and Insulin Glucose Ratio are all used in the diagnosis of Insulinomas.

Diagnosis of Insulinomas

  • 6,uU/m1 when blood glucose in < 40 mg/dl ” align=”left” height=”40″ width=”237″>Serum insulin levels (fasting)
  • Serum glucose levels (fasting)
  • Serum C- peptide levels (Elevated)
  • Serum proinsulin levels (Elevated)
  • Insulin / Glucose Ratio (> 0.3)
  • Plasma fl-Hydroxybulyrate (Decreased)
  • The most reliable test is a fast upto 72 hours with serum glucose, C-peptide and insulin levels measurements every 4-8 hours
  • The Gold standard test for diagnosis of Insulinoma is a supervised ’72 hour fast’ test
  • Diagnosis of lnsulinoma requires demonstration of inappropriately high levels of plasma Insulin ( and C- peptide) in the presence of documented hypoglycemia (Achieved by 72 hour fast test).
  • Absolute values of Insulin or C- peptide are not reliable in establishing a diagnosis unless hypoglycemia is documented The ’72 hour fast test’ allows demonstration of hypoglycemia, together will elevated levels of Insulin and C-peptide and thus becomes the most reliable – gold standard test for establishing a diagnosis of Insulinoma

Diagnosis of Insulinoma: ’72 hour fast’ test

  • The diagnosis of Insulinoma requires the demonstration of an inappropriately elevated plasma insulin (and C-peptide) at the time of hypoglycemia
  • The ’72 hour fast’ test involves supervised fasting for upto 72 hours or until hypoglycemia can be documented (
  • The test is considered positive if at any time when blood glucose levels drop to < 2.2mmo1/1 (40 mg/dl), the serum insulin levels are recorded to be greater than 6µU/ml. (and C- peptide levels > 100 pmo1/1)
  • Studies indicate that 100% of patient with insulinoma will he detected after a supervised 72 hour fast and hence this test is considered the gold standard test
  1. First 24 hours → 70-80% of patients with insulinoma can be detected
  2. Upto 48 hours→ 98% of patients with insulinoma can be detected
  3. By 72 hours→ 100% of patients with insulinoma can he detec
  • nsulinomas and Sulfonylureas, both produce endogenous hyperinsulinemia leadink to the same biochemical pattern.  These can only be distinguished by directly measuring the drug concentration of sullOnylureas in the plasma
  • ‘It is necessary to screen the plasma for sulphonylureas and other insulin secretagogues (repaglinide, nateglinide) at the time of hypoglycemia since these produce an insulin, C- peptide„ proinsulin and glucose pattern, indistinguishable from that produced by an insulinoma’ – Harrison
  • Biochemical Patterns In Patients With Various Causes Of Hyperinsulinemic Hypoglycmia
  • The most common site of Insulinomas is the Pancreas.
  • sulinomas are usually single and not multiple (>90%) – Harrison’s
  • Insulinomas are endocrine tumors of pancreas derived from Beta cells.
  • They are generally small (>90% < 2 cm), usually not multiple (90%) and only 5-15% are malignant (usually benign).

Symptoms due to Hypoglycemia

Most common symptoms are due to the effect of hypoglycemia on the central nervous system (Neuroglycemic Symptoms)

  • Confusion
  • Headache
  • Disorientation
  • Visual difficulties
  • Irrational behavior (even coma)

Symptoms due to Excessive Catecholamine Release secondary to Hypoglycemia 

  • Tremor
  • Palpitation
  • The most important examination is intraoperative ultrasound, which can identify a pancreatic tumor in nearly all cases. It is more sensitive than any preoperative test.” – CSDT
  • nsulinomas invariably occur only in the pancreas, distributed equally in the pancreatic head, body and tail”.
  • → Harrison 17/e
  •  • Insulinomas are a cell endocrinal tumur of the pancreas.
  • • Insulinomas are the most common pancreatic endocrine neoplasms.
  • The symptoms are produced due to excessive secretion of insulin causing hypoglycemia
  • Most of the insulinomas are solitary and benign,
  • Only about 10-15% of insulinomas are malignant. (keep in mind that all other endocrine tumours of pancreas are usually malignant).
  • Symptoms of insulinoma ?
  • The most common symptom is due to the effect of hypoglycemia on the central nervous system. – These symptoms are – confusion, disorientation, visual difficulties, irrational behaviour, coma
  • Other symptoms are due to increased secretion of catecholamines which includes sweating, tremor and
  • palpitations.
  • Classic diagnostic criteria is – Whipple’s triad
  • Signs and symptoms of hypoglycemia during fasting.
  • Blood glucose below 2.8 mmol/L (50mg/d1) during symptomatic episodes.
  • Relief of symptoms by intravenous administration of Glucose.
  • The most useful diagnostic test and the only one indicated in almost all patients is demonstration of fasting hypoglycemia in the presence of inappropriately high level of insulin.
  • The patient is fasted for 72 hrs or till the symptoms of hypoglycemia develop.
  • When hypoglycemia develops, serum level of insulin is measured. A ratio of plasma insulin to glucose > 0.3 is diagnostic.
  • Localization of the tumour
  • Once the diagnosis has been made, localization of the tumour is must for surgery.
  • The most important examination for localization of tumour is intraoperative ultrasound, which can indentify pancreatic tumour in all cases.

It is more sensitive than any other method

  • Other important methods of localization ?
  • High resolution CT and MRI.
  • Endoscopic ultrasound examination of pancreas.

Selective arteriography

  • T/T – Surgical excision is the t/t of choice ?
  • Since most insulinomas are benign simple enucleation is done.
  • “The most reliable test to diagnose insulinoma is a fast up to 72 h with serum glucose, C-peptide, and insulin measurements every 4-8 h.”—Harrison
  • An insulinoma is an endocrine tumor of the pancreas derived from beta cells that ectopically secretes insulin, which results in hypoglycemia.
  • The clinical symptoms are because of.the effects of hypoglycaemia (sweating, tremor, palpitations, confusion, headache, disorientation, visual difficulties, irrational behavior, or even coma)
  • The diagnosis of insulinoma requires the demonstration of an elevated plasma insulin level at the time of hypoglycemia. This is because insulinomas do not reduce the secretion of insulin in the presence of hypoglycaemia. Whereas in a normal person, insulin levels would decrease with decrease in blood glucose levels.
  • The most reliable test to diagnose insulinoma is a fast up to 72 h with serum glucose, and insulin measurements every 4-8 h.
  • The test is terminated if the the patient becomes symptomatic or glucose levels are

Diagnosis of insulinoma is made if:

  • A serum insulin level of 6 microunit/mL or more in the presence of blood glucose values below 40 mg/dL
  • ratio of plasma insulin to glucose is > 0.3

In addition to the above criteria, some other measurements are also required before making the diagnosis of insulinoma

  • C-peptide level
  • serum proinsulin level,
  • serum sulfonylurea levels
  • These additional tests are used because any hidden use of insulin or oral hypoglycemics taken by the patient would resemble insulinoma causing high levels of insulin in presence of hypoglycaemia.
  • The combination of elevated proinsulin levels (normal in exogenous insulin/hypoglycemic agent users), elevated C-peptide levels (low in exogenous insulin users), antibodies to insulin (positive in exogenous insulin users), and measurement of sulfonylurea levels in serum or plasma will allow the correct diagnosis to be made.
Don’t Forget to Solve all the previous Year Question asked on Insulinoma

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