Insulinoma

INSULINOMA

Q. 1

Gold standard test for for insulinoma

 A >72 hr fasting test
 B Plasma insulin levels
 C C-paptide levels
 D

Low glucose levels < 30 mg/di

Q. 1

Gold standard test for for insulinoma

 A >72 hr fasting test
 B Plasma insulin levels
 C C-paptide levels
 D

Low glucose levels < 30 mg/di

Ans. A

Explanation:

72 hr fasting test [Ref: Harrison 17/e p23541

  • “The most reliable test to diagnose insulinonza 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 <40 mg/dL (2.2 mmol/L).
  • 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.


Q. 2

For differentiating between Insulinoma and Sulfonylurea related hypoglycemia, the test which is useful is ?

 A

Antibody to Insulin

 B

Plasma C-peptide level

 C

Plasma Insulin level

 D

Insulin: Glucose ratio

Q. 2

For differentiating between Insulinoma and Sulfonylurea related hypoglycemia, the test which is useful is ?

 A

Antibody to Insulin

 B

Plasma C-peptide level

 C

Plasma Insulin level

 D

Insulin: Glucose ratio

Ans. D

Explanation:

Insulin : Glucose ratio (Ref. Harrison 16th/e p 2184, Harrison 17th/e p 2354-2355] 932

Both insulinoma and sulfonylurea produce endogenous hypoglycemia.

Hypoglycemia due to endogenous hyperinsulinism can be caused by:-

(i) Primary 13 cell disorder (insulinoma)

(ii) cell secretagoque such as sulfonylureas

(iii) An autoantibody to insulin

(iv) Rarely, ectopic insulin secretion

The fundamental pathophysiological feature of endogenous hyperinsulinism caused by a primary 1i cell disorder or an insulin secretagogue is the failure of the increased insulin to fall to very low levels during hypoglycemia This is assessed by measuring

Plasma insulin

– C peptide (the connection peptide that is cleaved. from proinsulin to produce insulin)

– Glucose concentrations

Critical diagnostic findings in endogenous hyperinsulinism are

  • Plasma insulin concentration > 3 pu/m1
  • Plasma C peptide concentration > •6 ng/ml (with a plasma)
  • Proinsulin concentration > 5.0 p mol/L

When

  • The plasma glucose concentration is < 55 mg/dl (<3.0 mmol/L) with symptoms of hypoglycemia So, how to differentiate between the hypoglycemia produed due to insulinoina and that of sulfonyl urea. These two disorders are distinguished by measuring the plasma sulfonylurea level

Harrison clearly states

“It is necessary to screen the plasma for sulfonylureas and other insulin secretagogues (repaglidine, nateglinide) at the time of hypoglycemia since these produce insulin, C peptides, proinsulin and glucose pattern indistinguishable from that produced by an insulinoma



Q. 3

A Syndrome is characterized by Pancreaticneoplasm (insulinoma), Pituitary, and Parathyroid involvement. The syndrome is:

 A Polyglandular Type I
 B Polyglangular Type 2
 C Wermer
 D Sipple
Q. 3

A Syndrome is characterized by Pancreaticneoplasm (insulinoma), Pituitary, and Parathyroid involvement. The syndrome is:

 A Polyglandular Type I
 B Polyglangular Type 2
 C Wermer
 D Sipple
Ans. C

Explanation:

Wermer


Q. 4

What is the gold standard test for diagnosing insulinoma?

 A

72 hr fasting test

 B

Plasma insulin levels

 C

C-peptide levels

 D

Low glucose levels < 30 mg/dl

Q. 4

What is the gold standard test for diagnosing insulinoma?

 A

72 hr fasting test

 B

Plasma insulin levels

 C

C-peptide levels

 D

Low glucose levels < 30 mg/dl

Ans. A

Explanation:

The gold standard test for diagnosing an insulinoma is 72 hour fast test.

 75% of insulinoma patients develop symptoms and blood glucose levels of less than 40mg/dl within the first 24 hour fast, 90% within 48h and 100% within 72hrs.

“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

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 clinical symptoms are because of the effects of hypoglycaemia (sweating, tremor, palpitations, confusion, headache, disorientation, visual difficulties, irrational behavior, or even coma).


Q. 5

Which of the following tests is not used in the diagnosis of insulinoma?

 A

Fasting blood glucose

 B

Xylose test

 C

C- peptide levels

 D

Insulin /Glucose Ratio

Q. 5

Which of the following tests is not used in the diagnosis of insulinoma?

 A

Fasting blood glucose

 B

Xylose test

 C

C- peptide levels

 D

Insulin /Glucose Ratio

Ans. B

Explanation:

Xylose test is used in the diagnosis of malabsorption syndrome of intestines. This test is of no value in insulinoma.

 

The diagnosis of insulinoma requires a demonstration of an elevated plasma insulin level at the time of hypoglycaemia.

The most reliable test is a fast up to 72 hrs with serum glucose, C-peptide and insulin requirements every 4-8 hrs.

In addition to having an insulin level >6µU/mL when blood glucose ≤ 40mg/dL, some investigators also require an elevated C-peptide and serum proinsulin level and/or insulin:glucose ratio >0.3 for diagnosis.

Ref: Harrison’s 16th Edition, Page 2227-2228.


Q. 6

Which of the following is the Gold standard diagnostic test for Insulinoma?

 A

’72 hour’ fast test

 B

Plasma Glucose levels < 3 mmol/L

 C

Plasma Insulin levels > 6 uU/ml

 D

C- peptide levels < 50 p mol/L

Q. 6

Which of the following is the Gold standard diagnostic test for Insulinoma?

 A

’72 hour’ fast test

 B

Plasma Glucose levels < 3 mmol/L

 C

Plasma Insulin levels > 6 uU/ml

 D

C- peptide levels < 50 p mol/L

Ans. A

Explanation:

Gold standard test for the diagnosis of insulinoma is a supervised 72 hour fast test with measurement of serum glucose, C-peptide, proinsulin, and insulin every 4–8 hour. In non obese normal subjects, serum insulin levels should decrease to <6  U/mL when blood glucose decreases to <40 mg/dL and the ratio of insulin to glucose is <0.3 (in mg/dL). In a case of insulinoma, level of insulin increases >6  U/mL when blood glucose is <40 mg/dL. Other tests positive in insulinoma are an elevated C-peptide and serum proinsulin level, an insulin/glucose ratio >0.3, and a decreased plasma-hydroxybutyrate level.

Ref: Harrison’s Internal Medicine, 18th Edition, Chapter 350


Q. 7

Gold standard test for for insulinoma 

 A

72 hr fasting test

 B

Plasma insulin levels

 C

C-peptide levels

 D

Low glucose levels < 30 mg/di

Q. 7

Gold standard test for for insulinoma 

 A

72 hr fasting test

 B

Plasma insulin levels

 C

C-peptide levels

 D

Low glucose levels < 30 mg/di

Ans. A

Explanation:

Ans is ‘a’ i.e. 72 hr fasting test

  • “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 <40 mg/dL (2.2 mmol/L).
  • 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.


Q. 8

Insulinoma is most commonly located in which part of the pancreas –

 A

Head

 B

Body

 C

Tail

 D

Equally distributed

Q. 8

Insulinoma is most commonly located in which part of the pancreas –

 A

Head

 B

Body

 C

Tail

 D

Equally distributed

Ans. D

Explanation:

Ans is ‘d’ i.e. is equally distributed

Insulinomas 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.


Q. 9

Insulinoma true are

 A

Present in pancreas

 B

Mostly malignant

 C

Surgical therapy indicated if diagnosed

 D

a and c

Q. 9

Insulinoma true are

 A

Present in pancreas

 B

Mostly malignant

 C

Surgical therapy indicated if diagnosed

 D

a and c

Ans. D

Explanation:

Ans. is ‘a’ i.e. Present in pancreas & ‘c’ i.e. Surgical therapy indicated if diagnosed 

Only about 10-15% of insulinomas are malignant (whereas all other endocrine tumors of pancreas are usually malignant)


Q. 10

Gold standard test in insulinoma –

 A

CT scan

 B

Ultrasound

 C

MRI

 D

Arteriography

Q. 10

Gold standard test in insulinoma –

 A

CT scan

 B

Ultrasound

 C

MRI

 D

Arteriography

Ans. B

Explanation:

Answer ‘b’ i.e. Ultrasound

“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


Q. 11

Which is not true regarding Insulinoma ‑

 A

Hypoglycemic attacks

 B

Weight loss

 C

Usually Solitary tumour

 D

Mostly benign tumour

Q. 11

Which is not true regarding Insulinoma ‑

 A

Hypoglycemic attacks

 B

Weight loss

 C

Usually Solitary tumour

 D

Mostly benign tumour

Ans. B

Explanation:

Ans is ‘b’ ie Weight loss 

As already discussed :

  • Hypoglycemic attacks are part of Whipple’s triad
  • Insulinoma is usually solitary (-90%)
  • Only 5 to 15% are malignant

Q. 12

Gold standard test for diagnosis of Insulinoma is

 A

’72 hour’ fast test

 B

Plasma Glucose levels < 3 mmo1/1

 C

Plasma Insulin levels > 6µU/ml

 D

C- peptide levels < 50 p mol/e

Q. 12

Gold standard test for diagnosis of Insulinoma is

 A

’72 hour’ fast test

 B

Plasma Glucose levels < 3 mmo1/1

 C

Plasma Insulin levels > 6µU/ml

 D

C- peptide levels < 50 p mol/e

Ans. A

Explanation:

Answer is A (’72 hour’ fast test)

The Gold standard test for diagnosis of Insulinoma is a supervised ’72 hour fast’ test

Diagnosis of Insulinoma 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 (<2.2 mmol/L or < 40 mg/dl)
  • 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% ofpatient with insulinoma will be detected after a supervised 72 hour fast and hence this test is considered the gold standard test

First 24 hours :        70-80% of patients with insulinoma can be detected

Upto 48 hours :       98% of patients with insulinoma can be detected

By 72 hours:            100% of patients with insulinoma can be detected


Q. 13

All of the following statements about Insulinoma are true Except:

 A

Most commonly found in ‘Pancreas’

 B

Usually Benign

 C

Usually multiple

 D

Derived from Beta cells

Q. 13

All of the following statements about Insulinoma are true Except:

 A

Most commonly found in ‘Pancreas’

 B

Usually Benign

 C

Usually multiple

 D

Derived from Beta cells

Ans. C

Explanation:

Answer is C (Usually multiple)

Insulinomas 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

Q. 14

Which of the following statements about Insulinoma is true:

 A

Present in Pancreas

 B

Mostly malignant

 C

Surgery is usually not required

 D

Usually multiple

Q. 14

Which of the following statements about Insulinoma is true:

 A

Present in Pancreas

 B

Mostly malignant

 C

Surgery is usually not required

 D

Usually multiple

Ans. A

Explanation:

Answer is A (Present in Pancreas):

The most common site of Insulinomas is the Pancreas.


Q. 15

Which of the following test is useful to distinguish between Insulinoma and Sulfonylurea related hypoglycemia:

 A

Antibody to Insulin

 B

Plasma – C- peptide level

 C

Plasma Insulin level

 D

None

Q. 15

Which of the following test is useful to distinguish between Insulinoma and Sulfonylurea related hypoglycemia:

 A

Antibody to Insulin

 B

Plasma – C- peptide level

 C

Plasma Insulin level

 D

None

Ans. D

Explanation:

Answer is None (None of the above):

Insulinomas 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


Q. 16

Gold standard test for diagnosis of Insulinoma is:

 A

’72 hour’ fast test

 B

Plasma Glucose levels < 3 mmol/l

 C

Plasma Insulin levels > 6µU/ml

 D

C- peptide levels < 50 p mol/e

Q. 16

Gold standard test for diagnosis of Insulinoma is:

 A

’72 hour’ fast test

 B

Plasma Glucose levels < 3 mmol/l

 C

Plasma Insulin levels > 6µU/ml

 D

C- peptide levels < 50 p mol/e

Ans. A

Explanation:

Answer is A (’72 hour’ fast test):

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 (<2.2 mmol/L or < 40 mg/dl)
  • 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

First 24 hours :        70-80% of patients with insulinoma can be detected

Upto 48 hours :        98% of patients with insulinoma can be detected

By 72 hours:             100% of patients with insulinoma can he detected


Q. 17

Which of the following tests is not used in the diagnosis of insulinoma

 A

Fasting blood glucose

 B

Xylose test

 C

C- peptide levels

 D

Insulin /Glucose Ratio

Q. 17

Which of the following tests is not used in the diagnosis of insulinoma

 A

Fasting blood glucose

 B

Xylose test

 C

C- peptide levels

 D

Insulin /Glucose Ratio

Ans. B

Explanation:

Answer is B (Xylose test) :

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



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