Differentiating Hypoglycemia from other diseases

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]


Hypoglycemia should be differentiated from other causes of autonomic hyperactivity symptoms. Neonatal hypoglycemia should be differentiated from other causes of neurological symptoms in neonates such as sepsis, metabolic diseases: urea cycle disorders, and branched-chain organic acidemias, hyponatremia and neonatal asphyxia. In adults, hypoglycemia should be differentiated from other diseases that may cause autonomic hyperactivity symptoms, such as hyperthyroidism, anxiety, arrhythmia, and pheochromocytoma.

Differentiating Hypoglycemia from other Diseases

Differentiating Different Causes of Hypoglycemia from each other:

Fasting symptoms Postprandial symptoms Plasma insulin C-peptide proinsulin Sulfonylurea in plasma insulin or insulin receptor antibodies
Insulinoma + - high high high - -
Oral hypoglycemia agent-induced - - high high high + -
Autoimmune hypoglycemia - - high high high - +
NIPHS* - + high high high - -
Exogenous insulin - - high low low - -
Non-islet cell tumors - - low low low - -

*(NIPHS) non-insulinoma pancreatogenous hypoglycemia syndrome

Diagnoses Laboratory Findings differentiating among causes of Hypoglycemia
C Peptide (pmol/L) S.Insulin (μU/mL) S.Proinsulin
S. Beta hydroxybutyrate Glucose increase after glucagon(mg/dL) Oral Hypoglycemic agent Antibodies to Insulin
Normal/Fasting <55 <200 <3 <5 >2.7 <25 - -
Exogenous Insulin <55 <200 >>3 <5 ≤2.7 >25 - -
Insulinoma <55 ≥200 ≥3 ≥5 ≤2.7 >25 - -
Post gastric bypass hypoglycemia (PGPH)
Insulin autoimmune hypoglycemia <55 >>200 >>3 >>5 ≤2.7 >25 - +
Oral hypoglycemic agent <55 ≥200 S. ≥5 ≤2.7 >25 + -
IGF¤ <55 <200 <3 <5 ≤2.7 >25 - -

‡ Free C-peptide and proinsulin concentrations are low
¤ IGF= Insulin Growth Factor, Increased pro-IGF-2, free IGF-2, IGF-2/IGF-1 ratio

Differentiating Hypoglycemia from other diseases that cause autonomic hyperactivity symptoms:

Disease Clinical Manifestation Investigations
Symptoms Signs
Palpitations Fever Sweating Headache
Hypoglycemia + - + +
Anxiety disorders + - + +
  • Rapid pulse and may be irregular
  • Psychiatry evaluation
Pheochromocytoma[2][3] + + + +
Arrhythmia + - - -
  • Irregular pulse
  • ECG changes according to the cause
Hyperthyroidism + + + +

Differentiating Hypoglycemia from other Diseases that Cause Neurological Symptoms in Neonates:

Disease History and symptoms Investigations
Family History Lethargy and irritability Improvement of symptoms with glucose intake Fever Hepatomegaly
Hypoglycemia + + + - -
  • Blood glucose level
Sepsis - + - + -
  • Blood cultures
Inborn errors of metabolism + + - - +
  • Positive blood tests
Hyponatremia - + - - -
  • Plasma sodium falls below 125 mEq/L
Perinatal asphyxia + + - - -
  • MRI of acute brain injury confirms the diagnosis of encephalopathy

Differentiating Hypoglycemia from other Diseases that Cause Coma and Consciousness Alterations:

Diseases Diagnostic tests Physical Examination Symptoms Past medical history Other Findings
CT /MRI CSF Findings Gold standard test Neck stiffness Motor or Sensory deficit Papilledema Bulging fontanelle Cranial nerves Headache Fever Altered mental status
Hypoglycemia Serum blood glucose


History of diabetes Palpitations, sweating, dizziness, low serum, glucose
Brain tumor[4][5] Cancer cells[6] MRI Cachexia, gradual progression of symptoms
Delirium tremens Clinical diagnosis Alcohol intake, sudden withdrawal or reduction in consumption Tachycardia, diaphoresis, hypertension, tremors, mydriasis, positional nystagmus,
Subarachnoid hemorrhage[7] Xanthochromia[8] CT scan without contrast[9][10] Trauma/fall Confusion, dizziness, nausea, vomiting
Stroke Normal CT scan without contrast TIAs, hypertension, diabetes mellitus Speech difficulty, gait abnormality
Neurosyphilis[11][12] Leukocytes and protein CSF VDRL-specific

CSF FTA-Ab -sensitive[13]

Unprotected sexual intercourse, STIs Blindness, confusion, depression,

Abnormal gait

Viral encephalitis Increased RBCS or xanthochromia, mononuclear lymphocytosis, high protein content, normal glucose Clinical assesment Tick bite/mosquito bite/ viral prodrome for several days Extreme lethargy, rash hepatosplenomegaly, lymphadenopathy, behavioral changes
Herpes simplex encephalitis Clinical assesment History of hypertension Delirium, cortical blindness, cerebral edema, seizure
Wernicke’s encephalopathy Normal History of alcohol abuse Ophthalmoplegia, confusion
CNS abscess leukocytes >100,000/ul, glucose, protein, red blood cells, and lactic acid >500mg Contrast enhanced MRI is more sensitive and specific,

Histopathological examination of brain tissue

History of drug abuse, endocarditis, immune status High-grade fever, fatigue, nausea, vomiting
Drug toxicity Lithium, Sedatives, phenytoin, carbamazepine
Conversion disorder Diagnosis of exclusion Tremors, blindness, difficulty swallowing
Electrolyte disturbance Depends on the cause Confusion, seizures
Febrile convulsion Not performed in first simple febrile seizures Clinical diagnosis and EEG Family history of febrile seizures, viral illness or gastroenteritis Age > 1 month,
Subdural empyema Clinical assessment and MRI History of relapses and remissions Blurry vision, urinary incontinence, fatigue


  1. Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, Seaquist ER; et al. (2009). "Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline". J Clin Endocrinol Metab. 94 (3): 709–28. doi:10.1210/jc.2008-1410. PMID 19088155.
  2. Lenders JW, Pacak K, Walther MM, Linehan WM, Mannelli M, Friberg P; et al. (2002). "Biochemical diagnosis of pheochromocytoma: which test is best?". JAMA. 287 (11): 1427–34. PMID 11903030.
  3. Bravo EL (1991). "Pheochromocytoma: new concepts and future trends". Kidney Int. 40 (3): 544–56. PMID 1787652.
  4. Soffer D (1976) Brain tumors simulating purulent meningitis. Eur Neurol 14 (3):192-7. PMID: 1278192
  5. Weston CL, Glantz MJ, Connor JR (2011). "Detection of cancer cells in the cerebrospinal fluid: current methods and future directions". Fluids Barriers CNS. 8 (1): 14. doi:10.1186/2045-8118-8-14. PMC 3059292. PMID 21371327.
  6. Yeh ST, Lee WJ, Lin HJ, Chen CY, Te AL, Lin HJ (2003) Nonaneurysmal subarachnoid hemorrhage secondary to tuberculous meningitis: report of two cases. J Emerg Med 25 (3):265-70. PMID: 14585453
  7. Lee MC, Heaney LM, Jacobson RL, Klassen AC (1975). "Cerebrospinal fluid in cerebral hemorrhage and infarction". Stroke. 6 (6): 638–41. PMID 1198628.
  8. Birenbaum D, Bancroft LW, Felsberg GJ (2011). "Imaging in acute stroke". West J Emerg Med. 12 (1): 67–76. PMC 3088377. PMID 21694755.
  9. DeLaPaz RL, Wippold FJ, Cornelius RS, Amin-Hanjani S, Angtuaco EJ, Broderick DF; et al. (2011). "ACR Appropriateness Criteria® on cerebrovascular disease". J Am Coll Radiol. 8 (8): 532–8. doi:10.1016/j.jacr.2011.05.010. PMID 21807345.
  10. Liu LL, Zheng WH, Tong ML, Liu GL, Zhang HL, Fu ZG; et al. (2012). "Ischemic stroke as a primary symptom of neurosyphilis among HIV-negative emergency patients". J Neurol Sci. 317 (1–2): 35–9. doi:10.1016/j.jns.2012.03.003. PMID 22482824.
  11. Berger JR, Dean D (2014). "Neurosyphilis". Handb Clin Neurol. 121: 1461–72. doi:10.1016/B978-0-7020-4088-7.00098-5. PMID 24365430.
  12. Ho EL, Marra CM (2012). "Treponemal tests for neurosyphilis--less accurate than what we thought?". Sex Transm Dis. 39 (4): 298–9. doi:10.1097/OLQ.0b013e31824ee574. PMC 3746559. PMID 22421697.