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Important Points:

  1. Definition Plasma glucose <50 - 60mg%. Individual threshold for symptoms varies.
  2. Symptoms. Autonomic-Sweating, anxiety, hunger, tremor, palpitations.
  3. Neurological: Confusion, drowsiness, seizures, coma. Rarely focal symptoms, eg transient hemiplegia. Mutism, personality change, rest

 (Ref. Hari.18th ed. , Table 345.1, Pg - 3003) Causes of Hypoglycemia

Fasting (Postabsorptive) Hypoglycemia

  1. Drugs:  Insulin, sulfonylureas, ethanol, Quinine, pentamidine, Salicylates, sulfonamides
  2. Critical illnesses
    1. Hepatic, renal, or cardiac failure                
    2. Sepsis                    
    3. CRF
  3. Hormone deficiency:   
    1. Cortisol (Addison’s)                    
    2. Growth hormone (Hypopituitarism)   
    3. Glucagon deficiency                  
    4. Epinephrine deficiency (in insulin-deficient diabetes)
  4. Non-beta-cell tumors: Hepatomas, adrenocortical carcinomas, carcinoids
  5. Endogenous hyperinsulinism:   Insulinoma
  6. Autoimmune (autoantibodies to insulin or the insulin receptor)

Reactive (Postprandial) Hypoglycemia

  1. Alimentary (postgastrectomy)                                      
  2. Following Roux-en-Y-gastric bypass
  3. Hereditary fructose intolerance, galactosemia      
  4. Idiopathic
  1. If patient is conscious Treat with oral sugar, (Food of high glycemic index)
  2. If patient cannot swallow than give 25-50ml 50% glucose IV
  3. If patient not conscious & is not able to swallow give Glucagon 1mg I/M

Fasting Hyperglycemia Syndromes

  1. Somogyi phenomena
    1. It is the morning (8 am) hyperglycemia which follows hypoglycemia at late night (2am).
    2. Hypoglycemia occurs due to overdose of insulin at night leading to release of counter regulatory hormones (glucagon, 1st to be released, followed by adrenaline, steroids, growth hormones and thyroxine).
    3. Treatment is to reduce the night dose of insulin.
  2. Dawn phenomena
    1. It is morning (8 am) hyperglycemia which follows hyperglycemia at late night (2am).
    2. This is due to nocturnal increase release of growth hormone.
    3. Treatment: is to increase the night dose of insulin.

Pseudo Hypoglycemia

Extra edge:
  1. Hypoglycemia can be artifactual;
  2. Hyperleukocytosis from leukemia, myeloproliferative diseases, leukemoid reactions, or colony-stimulating factor treatment can increase glucose consumption in the test tube after blood is drawn, leading to pseudohypoglycemia. (Ref. Hari.18th ed. , Pg- 2274)


Insulinoma (Ref. Hari.18th ed., Pg-3003)

This pancreatic islet cell tumour is associated with MEN-l, and is usually benign. It presents as fasting hypoglycemia, with Whipple's triad:

  1. Symptoms associated with fasting or exercise
  2. Recorded hypoglycemia with symptoms
  3. Symptoms relieved with glucose.
Extra Edge:

Weight gain occurs in insulinoma



Note: There is slight change in diagnostic criteria of hypoglycemia in Harrisons-17th & 18th edition.

Diagnosis of Insulinoma  

Diagnosis of Insulinoma as given in 17th Edition of Harrison, Page. 2308; 1878)

  1. 72 hours Fasting blood glucose levels:
    1. 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.
    2. It is thought to be “gold standard” test for insulinoma.Q
  2. C peptide levels:
    1. Insulin is synthesized as proinsulin, a 21-amino-acid alpha-chain and a 30-amino-acid beta-chain connected by a 33-amino-acid connecting peptide (C peptide).
    2. In insulinomas, in addition to elevated plasma insulin levels, elevated plasma proinsulin levels are found and C-Peptide levels can be elevated.
  3. Insulin / glucose ratio:
    1. In 72 hr fasting, about 70–80% of patients will develop hypoglycemia during the first 24 h and 98% by 48 hr. In normal subjects, serum insulin levels should decrease to <43 pmol/L (<6 HU/mL) when blood glucose decreases to 2.2 mmol/L (40 mg/dL) and the ratio of insulin to glucose is <0.3 (in mg/dL).
    2. In insulinoma insulin level >6 U/mL when blood glucose is <40 mg/dL, elevated C-peptide and, an insulin/glucose ratio >0.3.

Diagnostic Criteria of Insulinoma

Diagnostic criteria of insulinoma as given in 18th edition of Harrison of Harrison Pg 3007 

  1. Critical diagnostic findings are a plasma insulin concentration ≥ 3 µU/mL (≥ 18 pmol/L), a plasma C-peptide concentration ≥ 0.6 ng/mL (≥ 0.2 nmol/L) and a plasma proinsulin concentration ≥ 5.0 pmol/L when the plasma glucose concentration is <55 mg/dL (<3 mmol/L) with symptoms of hypoglycemia.
  2. A low plasma ß-hydroxybutyrate concentration ( 2.7 mmol/L) and an increment in plasma glucose >25 mg/dL (1.4 mmol/L) following intravenous glucagon (1 mg) indicate increased insulin (or insulin-like growth factor) actions.
  3. The diagnostic strategy is to obtain measurements of plasma glucose, insulin, C-peptide, proinsulin and ß-hydroxybutyrate concentrations—and to screen for circulating oral hypoglycemic agents—during an episode of hypoglycemia and to assess symptoms during the episode and seek their resolution following correction of hypoglycemia by intravenous injection of glucagon

TABLE - Diagnostic Interpretation of the Results of a 72-hour Fast



Serum ß--hydroxy-butyrate mmol/L

Glucose mg/dL

Insulin µU/mL

C-peptide pmol/L

Proinsulin pmol/L


≥ 40






≤ 45

≥ 3

≥ 200

≥ 5

≤ 2.7

Factitious hypoglycemia

from insulin

≤ 45

≥ 3*



≤ 2.7



≤ 45

≥ 3

≥ 200


≤ 2.7

Hypoglycemia-mediated by

insulin-like growth factor

≤ 45

≤ 3



≤ 2.7

Imaging: Ct/Mri, To Locate The Tumour

  1. Enucleation of a solitary insulinoma is generally curative.
  2. Diazoxide, inhibits insulin secretion
  3. Octreotide is a somatostatin analogue. Octreotide is used to treat hypoglycemia in patients with unresectable tumors
  4. Recent Advances: In patients with unresectable tumors; Everolimus, an mTOR (Mammalian target of rapamycin) inhibitor, is used. (Hari-18th Pg- 3008) 
Recent Advances:

Other Causes of Hypoglycemia (Ref. Hari.18th ed., Pg- 3008)

  1. Nesidioblastosis some patients (usually infants and young adults) have fasting endogenous hyperinsulinemic hypoglycemia. The have diffuse islet involvement with beta-cell hypertrophy and sometimes hyperplasia, Beta-cells budding from ducts may be present.
  2. Noninsulinoma pancreatogenous hypoglycemia these patients have a similar islet pattern as in nesidioblastosis but have postprandial hypoglycemia.
  3. Post–gastric bypass postprandial hypoglycemia also involves diffuse islet involvement and endogenous hyperinsulinism. It most often follows Roux en Y gastric bypass. 


Important Points:

Glucagonoma is characterized by Necrolytic migratory erythema

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