Vitamin B1 (Thiamine) Deficiency

Etiology

Deficiency of thiamine can be related to [3]:

Poor intake

• Diets primarily high in polished rice/processed grains
• Chronic alcoholism
• Parenteral nutrition without adequate thiamine supplementation
• Gastric bypass surgery

Poor absorption

• Malnutrition
• Gastric bypass surgery
• Malabsorption syndrome

Increased loss 

• Diarrhea
• Hyperemesis gravidarum
• Diuretic use
• Renal replacement therapy

Increased thiamine utilization

• Pregnancy
• Lactation
• Hyperthyroidism
• Refeeding syndrome

Drugs that can lead to thiamine deficiency

Diuretics

Epidemiology

Worldwide, thiamine deficiency is primarily due to inadequate dietary intake, specifically in diets comprised mainly of polished rice and grains. In Western countries, it most commonly presents in patients suffering from alcoholism or chronic illness. Special populations of individuals also at risk for thiamine deficiency include pregnant women, those requiring parental feeding, individuals who have undergone bariatric surgery, those with overall poor nutritional status, and patients on chronic diuretic therapy as it increases urinary losses. The deficiency of this vitamin in women can cause infantile beriberi, which this article will not specifically address.[4]

Pathophysiology

When thiamine stores are depleted (which takes about 4 weeks after stopping intake), symptoms start to appear.

Dry beriberi occurs when the CNS is involved. This condition is usually due to poor intake. The neurological features include impaired reflexes and symmetrical motor and sensory deficits in the extremities. Loss of myelin is seen without any acute inflammation.

Another variation of dry beriberi is Wernicke encephalopathy. This condition presents in well-defined steps starting with nausea and vomiting, followed by horizontal nystagmus, ocular nerve palsy, fever, ataxia, and progressive mental impairment, eventually leading to the Korsakoff syndrome. Improvement is only possible if the patient has not developed the Korsakoff syndrome. Less than 50% of patients show significant recovery after treatment.

Wet beriberi is present when the cardiovascular system is involved. The heart fails to function, leading to edema and fluid retention. The key reason for heart dysfunction is an overuse injury. Wet beriberi is a medical emergency and, without treatment, can lead to death within days. Thiamine can slowly help with recovery, but most patients require intense supportive measures in an ICU setting.

History and Physical

History

When evaluating for thiamine deficiency, the typical history may include poor nutritional intake, excessive alcohol intake, or the patient belonging to the special populations of individuals previously mentioned (pregnant women, recipients of bariatric surgery, patients with prolonged diuretic use, anyone with poor overall nutritional status, etc.).  

Initial symptoms of B1 deficiency include anorexia, irritability, and difficulties with short-term memory. With prolonged thiamine deficiency, patients may endorse loss of sensation in the extremities, symptoms of heart failure including swelling of the hands or feet, chest pain related to demand ischemia, or feelings of vertigo, double vision, and memory loss. Additionally, close friends and family of the patient may describe confusion or symptoms of confabulation. 

Physical Exam

Dry beriberi:

• Evidence of symmetric peripheral neuropathy with motor and sensory changes
• Diminished reflexes

Wet beriberi - cardiovascular compromise related to impaired myocardial energy metabolism and dysautonomia:

• Dilated cardiomyopathy
• Tachycardia
• High-output congestive heart failure
• Peripheral edema

Wet and dry beriberi often have overlapping features, and in either condition, paresthesias may be a presenting feature.

Wernicke’s encephalopathy (WE) is a classic triad of ocular abnormalities (nystagmus, ophthalmoplegia), confusion, and gait changes such as ataxia.

Wernicke’s encephalopathy with additional symptoms of memory loss and psychosis with confabulation is consistent with WKS.[1][5]

Evaluation

Detection of thiamine deficiency relies on relevant history and physical exam findings and follow-up with laboratory testing for confirmation.[6]Laboratory Studies

• Functional enzymatic assay of transketolase activity - transketolase activity is measured before and after the addition of thiamine pyrophosphate; greater than 25% stimulation response is abnormal.
• Measurement of thiamine or the phosphorylated esters of thiamine in serum or blood using high-performance liquid chromatography
• Urine studies exist but are not a reliable test for the evaluation of total body thiamine.
• Metabolic acidosis can occur with thiamine deficiency due to the accumulation of lactate.

Consider other diagnostic studies based on presentation and comorbid conditions (transthoracic echo or TSH measurements in new heart failure, for example).

Radiographic Studies

MR: most common abnormalities seen with WE are symmetric changes in the thalamus, mamillary bodies, periaqueductal area, and tectal plate.[7]

Treatment / Management

Treatment of Acute Thiamine Deficiency with Cardiovascular or Neurologic Signs/Symptoms [4]

200mg intravenous (IV) or orally (PO) thiamine three times daily until symptoms resolve or improvement plateaus, at which time the patient should transition to 10 mg/day oral thiamine until expected recovery is complete.

Another option in acute crisis is 50mg administered intramuscularly for 2-4 days, followed by oral maintenance therapy

Treatment of Thiamine Deficiency with Suspected WKS [8] 

• 500mg IV thiamine infused over 30mins three times on days 1 and 2 of therapy
• 250mg thiamine IV or intramuscularly on days 3 through 5 of therapy

**Always give thiamine during the re-feeding period in a patient with alcoholism to prevent acute thiamine deficiency with lactic acidosis.**

Symptoms consistent with Wernicke-Korsakoff syndrome may persist for several months or may be permanent.  

Other symptoms of thiamine deficiency such as anorexia and irritability are expected to improve gradually.

Differential Diagnosis

The differential diagnosis for thiamine deficiency is broad, given the number of nonspecific symptoms which may occur during the initial stages of this condition and the extensive range of cardiac and nervous dysfunction related to thiamine deficiency.

Conditions to Consider

• Delirium
• Depression
• Folic acid deficiency
• Hyperthyroidism
• Cardiomyopathy secondary to other causes such as alcoholic or diabetic heart disease
• Delusional disorder
• Nerve entrapment syndromes
• Other psychiatric disorders
• Diabetic ketoacidosis

Prognosis

The overall prognosis for patients with thiamine deficiency is good as it is easily treatable, and most signs and symptoms of the deficiency fully resolve with thiamine supplementation.  Cardiac dysfunction seen in wet beriberi can be expected to improve within 24 hours of initiation of treatment. Symptoms of dry beriberi may improve or resolve.  Unfortunately, once the deficiency has progressed to Korsakoff syndrome, the patient may show minimal improvement during initial treatment, and the remaining symptoms may be permanent.[9]

Complications

There are no known toxicities associated with thiamine repletion. Some reports of anaphylaxis and bronchospasm with high-dose intravenous thiamine exist.