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]

Overview

Hypoglycemia should be differentiated from other causes of autonomic hyperactivity symptoms. Physicians should have history, signs and laboratory results sufficient to help them to identify the cause of hypoglycemia. 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.

Differentiating Hypoglycemia from other Diseases

Hypoglycemia should be differentiated from other causes of autonomic hyperactivity symptoms(tachycardia, hypertension) which include:

Disease Clinical Manifestation Investigations
Symptoms Signs
Tachycardia Fever Sweating Headache
Anxiety disorders + - + + Normal investigations
Pheochromocytoma + + + + Plasma fractionated metanephrines, 24-hour urinary fractionated metanephrines, catecholamines.[1]

2]Computed tomography: Radiological evaluation should follow lab tests to locate site of thetumour..[2]

Arrhythmia + - - - ECG changes according to the cause.
Hyperthyroidism + + + + Measuring the level of thyroid-stimulating hormone (TSH) in the blood

Levels of T4 and/or T3 in the blood. Measuring specific antibodies, such as anti-TSH-receptor antibodies in Graves' disease, may contribute to the diagnosis.

After the diagnosis of any patient with hypoglycemia, Defining the cause of hypoglycemia is the most important step using history, clinical picture and investigations to diagnose as follow:

Fating 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

Neonatal hypoglycemia should be differentiated from other causes of 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 Comma related to Hypoglycemia from other Diseases

Diseases Diagnostic tests Physical Examination Symptoms Past medical history Other Findings
Na+, K+, Ca2+ CT /MRI CSF Findings Gold standard test Neck stiffness Motor or Sensory deficit Papilledema Bulging fontanelle Cranial nerves Headache Fever Altered mental status
Brain tumor[3][4] Cancer cells[5] 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[6] Xanthochromia[7] CT scan without contrast[8][9] Trauma/fall Confusion, dizziness, nausea, vomiting
Stroke Normal CT scan without contrast TIAs, hypertension, diabetes mellitus Speech difficulty, gait abnormality
Neurosyphilis[10][11] Leukocytes and protein CSF VDRL-specific

CSF FTA-Ab -sensitive[12]

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 or 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
Hypoglycemia ↓ or Serum blood glucose

HbA1c

History of diabetes Palpitations, sweating, dizziness, low serum, glucose

References

  1. 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.
  2. Bravo EL (1991). "Pheochromocytoma: new concepts and future trends". Kidney Int. 40 (3): 544–56. PMID 1787652.
  3. Soffer D (1976) Brain tumors simulating purulent meningitis. Eur Neurol 14 (3):192-7. PMID: 1278192
  4. 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.
  5. 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
  6. Lee MC, Heaney LM, Jacobson RL, Klassen AC (1975). "Cerebrospinal fluid in cerebral hemorrhage and infarction". Stroke. 6 (6): 638–41. PMID 1198628.
  7. Birenbaum D, Bancroft LW, Felsberg GJ (2011). "Imaging in acute stroke". West J Emerg Med. 12 (1): 67–76. PMC 3088377. PMID 21694755.
  8. 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.
  9. 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.
  10. Berger JR, Dean D (2014). "Neurosyphilis". Handb Clin Neurol. 121: 1461–72. doi:10.1016/B978-0-7020-4088-7.00098-5. PMID 24365430.
  11. 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.