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. 2]Computed tomography: Radiological evaluation should follow lab tests to locate site of thetumour..
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		✔	Cancer cells	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		✔	Xanthochromia	CT scan without contrast	✔	✔	✔	✔	✔	✔	✔	✔	Trauma/fall	Confusion, dizziness, nausea, vomiting
Stroke		✔	Normal	CT scan without contrast		✔	✔		✔	✔		✔	TIAs, hypertension, diabetes mellitus	Speech difficulty, gait abnormality
Neurosyphilis		✔	↑ Leukocytes and protein	CSF VDRL-specific CSF FTA-Ab -sensitive	✔	✔	✔	✔		✔		✔	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