Diagnostic Approach for an Acute Hypothyroidism Flare
The diagnosis of an acute hypothyroidism flare requires measurement of both thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels, with elevated TSH and low FT4 confirming primary hypothyroidism. 1
Clinical Presentation
When evaluating a patient with suspected acute hypothyroidism flare, look for:
- Severe symptoms: Fatigue, cold intolerance, bradycardia, hypothermia, altered mental status
- Physical findings: Myxedema (bradycardia, hypothermia, altered mental status), coarse skin, puffy face, slow movements, pretibial edema, delayed ankle reflexes 1, 2
- Life-threatening presentation: Myxedema coma, which is a medical emergency requiring immediate treatment 1
Diagnostic Algorithm
Step 1: Laboratory Testing
- First-line tests: Paired measurement of serum TSH and FT4 1, 3
- Interpretation:
- Primary hypothyroidism: Elevated TSH with low FT4
- Subclinical hypothyroidism: Elevated TSH with normal FT4
- Central hypothyroidism: Low or inappropriately normal TSH with low FT4 1
Step 2: Additional Testing Based on Clinical Context
- Electrolytes: Check for hyponatremia (present in 90% of new cases) and hyperkalaemia (present in ~50%) 1
- Additional labs: Consider complete blood count (anemia, mild eosinophilia, lymphocytosis) and liver function tests 1
- Antibody testing: Measure anti-thyroid antibodies (anti-TPO, anti-thyroglobulin) to determine autoimmune etiology 1, 4
Step 3: Severity Assessment
- Grade 1: TSH > 4.5 and < 10 mIU/L with minimal or no symptoms
- Grade 2: Moderate symptoms with TSH persistently > 10 mIU/L
- Grade 3-4: Severe symptoms including myxedema (bradycardia, hypothermia, altered mental status) 1
Special Considerations
Immune Checkpoint Inhibitor-Related Hypothyroidism
For patients on immunotherapy:
- Monitor TSH every 4-6 weeks during the first 3 months of treatment
- Check both TSH and FT4 in symptomatic patients
- A falling TSH across two measurements with normal or lowered T4 may suggest pituitary dysfunction 1
Pregnancy
- Pregnant women require more aggressive management with target TSH < 2.5 mIU/L 4
- Monitor TSH every 4 weeks until stable 4
Elderly Patients
- Clinical presentation may be more subtle
- Treatment decisions should be individualized for patients over 80-85 years 4
Pitfalls and Caveats
Physical examination alone is insufficient: No single physical sign can reliably diagnose hypothyroidism (positive likelihood ratios range from 1.0 to 3.88) 2
Thyrotoxicosis phase: Hypothyroidism may develop after a thyrotoxicosis phase of thyroiditis, so monitor TSH and FT4 in patients with recent hyperthyroidism 1
Central vs. Primary Hypothyroidism: Low TSH with low FT4 suggests central hypothyroidism rather than primary hypothyroidism 1
Adrenal Insufficiency: If there is uncertainty about whether primary or central hypothyroidism is present, evaluate for adrenal insufficiency before initiating thyroid hormone replacement 1
Myxedema coma: This life-threatening emergency requires immediate treatment with IV levothyroxine, steroids, and supportive care 1
Remember that symptoms of hypothyroidism can be nonspecific and may overlap with other conditions, making laboratory confirmation essential for diagnosis 5. Never delay treatment of suspected acute adrenal insufficiency for diagnostic procedures if the patient is critically ill 1.