Hypothyroidism Workup Based on Clinical Practice Guidelines
The initial workup for hypothyroidism should include measurement of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels, as these are the essential laboratory tests for diagnosis. 1, 2
Initial Laboratory Testing
- TSH is the preferred test for initial evaluation of suspected primary hypothyroidism, with an elevated TSH level almost always signaling primary hypothyroidism 2
- Both TSH and FT4 should be measured simultaneously in symptomatic patients to properly distinguish between primary and central hypothyroidism 1
- Low TSH with low FT4 is consistent with central hypothyroidism (pituitary or hypothalamic origin) and requires further evaluation 1
- Normal TSH with low FT4 may indicate non-thyroidal illness or assay interference 3
Diagnostic Criteria
- Primary hypothyroidism: Elevated TSH with low FT4 (overt) or normal FT4 (subclinical) 4
- Overt hypothyroidism: TSH > 4.5 mIU/L with FT4 below reference range 1, 3
- Subclinical hypothyroidism: TSH > 4.5 mIU/L with normal FT4 4, 3
- Central hypothyroidism: Low or inappropriately normal TSH with low FT4 1
Additional Testing When Indicated
- Consider thyroid peroxidase (TPO) antibodies to identify autoimmune thyroiditis (Hashimoto's), which is the most common cause of primary hypothyroidism 5
- In cases of suspected central hypothyroidism, evaluate other pituitary hormones, especially the hypothalamic-pituitary-adrenal axis 4
- Morning ACTH and cortisol levels should be checked if central hypothyroidism is suspected, as hypocortisolism needs to be corrected before initiating thyroid hormone replacement 4
- TSH receptor antibody testing if there are clinical features suggesting Graves' disease 1
Special Considerations
- For pregnant women or those planning pregnancy, thyroid function should be evaluated promptly as hypothyroidism increases risk of pregnancy complications and impaired cognitive development in offspring 4
- In patients with persistent symptoms despite apparently adequate replacement therapy, check for poor compliance, malabsorption, or drug interactions 4
- For elderly patients (>70 years), consider a more conservative approach to treatment of subclinical hypothyroidism 4
Treatment Initiation
- All patients with overt hypothyroidism should be treated with levothyroxine 3
- Subclinical hypothyroidism with TSH >10 mIU/L should be treated 4
- For subclinical hypothyroidism with TSH ≤10 mIU/L, treatment should be considered in:
Levothyroxine Dosing
- For most young patients without comorbidities, full calculated dose can be started at approximately 1.6 mcg/kg/day 1, 6
- For patients >70 years old, frail patients, or those with coronary artery disease, start with lower doses (25-50 mcg/day) and titrate gradually 1, 7
- For patients with severe, long-standing hypothyroidism, start with lower doses to avoid precipitating cardiac events 4
Monitoring and Follow-up
- Monitor TSH levels 6-8 weeks after initiating treatment or changing dose 6, 5
- Target TSH for primary hypothyroidism is 0.5-2.0 mIU/L 4
- For central hypothyroidism, monitor free T4 levels, which should be maintained in the upper half of the normal range 4
- Once stable, monitor TSH annually to avoid overtreatment or undertreatment 5
Common Pitfalls to Avoid
- Failing to check both TSH and FT4 in symptomatic patients, which can miss central hypothyroidism 1
- Starting full replacement doses in elderly patients or those with cardiac disease, which can precipitate arrhythmias or ischemia 4, 7
- Overreplacement with levothyroxine, which increases risk of atrial fibrillation and osteoporosis 4
- Not considering drug interactions or absorption issues in patients with persistently elevated TSH despite adequate replacement doses 4
- Failing to evaluate the hypothalamic-pituitary-adrenal axis in suspected central hypothyroidism before starting thyroid hormone replacement 4