Diagnosis: Primary Hypothyroidism (Overt)
This patient has overt primary hypothyroidism requiring immediate levothyroxine therapy. The combination of elevated TSH, low Free Thyroxine Index (FTI), and normal total T4 indicates inadequate thyroid hormone production with compensatory TSH elevation 1.
Understanding the Laboratory Pattern
The low FTI with normal total T4 reflects decreased free (biologically active) thyroid hormone despite normal total hormone levels 2. This occurs when thyroid binding proteins are altered or when the thyroid gland is failing but still producing some hormone 2.
This pattern represents overt hypothyroidism, not subclinical disease, because the FTI (which estimates free T4) is below normal 1. Subclinical hypothyroidism would show elevated TSH with normal free T4 1, 3.
The normal total T4 can be misleading - it may reflect changes in binding proteins rather than adequate free hormone availability 2. The FTI corrects for this by estimating the free hormone fraction 2.
Confirm the Diagnosis
Repeat TSH and measure free T4 directly (not just FTI) after 3-6 weeks to confirm the diagnosis, as 30-60% of elevated TSH values normalize spontaneously 1. However, given the low FTI suggesting overt disease, treatment should not be delayed if the patient is symptomatic 1.
Measure anti-thyroid peroxidase (anti-TPO) antibodies to identify autoimmune thyroiditis (Hashimoto's disease), the most common cause of primary hypothyroidism 3. Positive antibodies predict higher progression risk and confirm the diagnosis 1, 3.
Check for symptoms of hypothyroidism including fatigue, bradycardia, constipation, cold intolerance, weight gain, and cognitive slowing 3. These clinical findings support the diagnosis and indicate treatment urgency 1.
Treatment Algorithm
Initial Levothyroxine Dosing
For patients <70 years without cardiac disease, start levothyroxine at full replacement dose of approximately 1.6 mcg/kg/day 1. This rapidly normalizes thyroid function and prevents complications 1.
For patients >70 years or with cardiac disease/multiple comorbidities, start with 25-50 mcg/day and titrate gradually 1. Rapid normalization can unmask cardiac ischemia or precipitate arrhythmias in these populations 1.
Take levothyroxine on an empty stomach, 30-60 minutes before breakfast, as a single daily dose 1. This ensures consistent absorption 1.
Critical Safety Consideration
Before initiating levothyroxine, rule out concurrent adrenal insufficiency, especially in patients with autoimmune hypothyroidism who have increased risk of Addison's disease 1. Starting thyroid hormone before corticosteroids can precipitate life-threatening adrenal crisis 1.
Screen for adrenal insufficiency if the patient has unexplained hypotension, hyponatremia, hyperpigmentation, or hypoglycemia 1. Consider morning cortisol or cosyntropin stimulation testing 1.
Monitoring and Dose Adjustment
Recheck TSH and free T4 in 6-8 weeks after starting therapy or any dose adjustment 1. This represents the time needed to reach steady state 1.
Target TSH within the reference range (0.5-4.5 mIU/L) with normal free T4 levels 1. Note that TSH normalization lags behind T4 normalization by several weeks 2.
Adjust levothyroxine dose in 12.5-25 mcg increments based on TSH response 1. Use smaller increments (12.5 mcg) for elderly patients or those with cardiac disease 1.
Once adequately treated, monitor TSH every 6-12 months or if symptoms change 1.
Special Considerations
Understanding TSH Lag
TSH may remain elevated for 3-6 weeks after T4 and T3 normalize with treatment 2. Do not increase the levothyroxine dose prematurely based on TSH alone if free T4 is already normal 2.
In newly treated patients, free T4 normalizes by day 8, free T3 by day 18, but TSH may take 21-42 days to normalize 2. This lag reflects pituitary adaptation to restored thyroid hormone levels 2.
Pitfalls to Avoid
Do not treat based on a single elevated TSH without confirmation, as transient elevations occur in 30-60% of cases 1. However, the low FTI makes this less likely to be transient 2.
Avoid overtreatment, which occurs in 14-21% of patients and increases risk for atrial fibrillation, osteoporosis, fractures, and cardiac complications 1. Approximately 25% of patients are unintentionally maintained on excessive doses 1.
Never assume hypothyroidism is permanent without reassessment 1. Some cases represent transient thyroiditis in recovery phase 1.
Consider recent iodine exposure (CT contrast) or medications affecting thyroid function 1, 4. These can transiently alter thyroid tests 1.
Long-Term Management
Levothyroxine is safe for lifelong use when properly dosed 1. The primary risks come from overtreatment, not the medication itself at replacement doses 1.
Ensure adequate calcium (1200 mg/day) and vitamin D (1000 units/day) intake, especially if TSH becomes suppressed, to prevent bone demineralization 1.
Monitor for development of other autoimmune conditions if anti-TPO antibodies are positive, including adrenal insufficiency, type 1 diabetes, and celiac disease 1.