What are the diagnostic criteria for severe hypothyroidism?

Diagnosing Severe Hypothyroidism

Severe hypothyroidism is diagnosed by a combination of significantly elevated TSH (>10 mIU/L), low free T4 levels, and the presence of significant clinical manifestations that affect multiple organ systems.

Laboratory Criteria

• TSH levels:

  • Markedly elevated (typically >10 mIU/L)
  • Values >20-30 mIU/L often indicate severe disease
  • Morning measurements preferred for accuracy 1

• Free T4 levels:

  • Significantly decreased (below reference range)
  • The combination of high TSH and low free T4 confirms overt hypothyroidism 1

• Additional testing:

  • Thyroid antibodies (TPO, thyroglobulin antibodies) to identify autoimmune etiology 1
  • Morning cortisol levels if central hypothyroidism is suspected (low TSH with low T4) 1

Clinical Manifestations of Severe Hypothyroidism

Cardiovascular

• Bradycardia
• Mild hypertension (often diastolic)
• Narrowed pulse pressure
• Pericardial effusion (in severe cases)
• Heart failure (rare but can occur in severe, long-standing cases) 1

Neurological/Psychiatric

• Mental slowing/cognitive dysfunction
• Delayed relaxation phase of deep tendon reflexes (especially ankle)
• Fatigue and lethargy
• Depression

Metabolic/Physical

• Significant weight gain
• Severe cold intolerance
• Myxedema (non-pitting edema)
• Coarse, dry skin
• Hair loss
• Hoarse voice
• Periorbital puffiness

Gastrointestinal

• Severe constipation
• Decreased appetite despite weight gain

Diagnostic Algorithm

1. Initial screening: TSH measurement is the most sensitive test 1

   • If TSH is elevated (>4.5 mIU/L), proceed to free T4 measurement
   • If TSH is normal or low with clinical suspicion, check free T4 to rule out central hypothyroidism

2. Confirmation:

   • Overt hypothyroidism: Elevated TSH with low free T4
   • Severe hypothyroidism: Markedly elevated TSH (>10 mIU/L), significantly low free T4, and prominent clinical manifestations 1

3. Assess severity:

   • Evaluate for myxedema (severe non-pitting edema)
   • Check for bradycardia, hypothermia, altered mental status
   • Assess for pericardial effusion or heart failure
   • Look for delayed relaxation of deep tendon reflexes

4. Rule out myxedema coma (medical emergency):

   • Altered mental status/coma
   • Hypothermia
   • Hypoventilation
   • Hypotension
   • Hyponatremia
   • Hypoglycemia

Important Diagnostic Considerations

1. Physical examination alone is insufficient:

   • No single physical sign can reliably diagnose hypothyroidism
   • Even combinations of signs (coarse skin, bradycardia, delayed ankle reflex) have limited diagnostic accuracy (LR+ 3.75) 2
   • Laboratory confirmation is essential

2. Elderly patients:

   • May present atypically with fewer classic symptoms
   • Cognitive changes may be the predominant feature
   • More likely to develop cardiac complications 3

3. Potential pitfalls:

   • Non-thyroidal illness can affect thyroid function tests
   • Medications can interfere with thyroid function or testing
   • Central hypothyroidism may present with low/normal TSH and low free T4 1

4. Differential diagnosis:

   • Depression
   • Chronic fatigue syndrome
   • Fibromyalgia
   • Anemia
   • Heart failure from other causes

Special Populations

Children

• Growth failure and delayed development are prominent features
• Delayed bone age
• Assess for thyroid antibodies soon after diagnosis 1
• Consider rechecking thyroid function every 1-2 years in children with type 1 diabetes

Pregnant Women

• Requires trimester-specific reference ranges for interpretation
• More aggressive treatment thresholds
• Increased monitoring frequency 3

Remember that while subclinical hypothyroidism (elevated TSH with normal free T4) is common, severe hypothyroidism represents the extreme end of the disease spectrum with significant laboratory abnormalities and clinical manifestations that can lead to substantial morbidity and mortality if left untreated.