What are the normal reference ranges for free T3 and free T4, and at what levels is anti‑thyroid drug therapy indicated and what are the typical dosage ranges?

Normal Reference Ranges for Free T3 and Free T4

The normal reference ranges are free T4 within the laboratory-specific reference range (typically 9–19 pmol/L or 0.7–1.5 ng/dL) and free T3 within the laboratory-specific reference range (typically 3.5–6.5 pmol/L or 2.3–4.2 pg/mL), with TSH 0.45–4.5 mIU/L serving as the primary screening parameter. 1

Standard Reference Intervals

• TSH reference range: 0.45–4.5 mIU/L, established from NHANES III data in disease-free populations 1
• Free T4 and free T3 should fall within laboratory-specific reference ranges, which vary slightly by assay method 1, 2
• The geometric mean TSH in disease-free populations is 1.4 mIU/L, providing a physiological midpoint 3

Important Caveats About Reference Ranges

• Individual set points for thyroid hormones are much narrower than population reference ranges—each person operates within approximately half the width of the laboratory reference range 4
• A single test result describes an individual's set point with precision of ±25% for T4 and T3, and ±50% for TSH 4
• Age-related shifts occur: the upper limit of normal TSH reaches 7.5 mIU/L in patients over 80 years 3

---

Anti-Thyroid Drug Therapy: Indications and Dosing

When Anti-Thyroid Drugs Are Indicated

Anti-thyroid drugs (methimazole or propylthiouracil) are indicated when TSH is suppressed below 0.45 mIU/L AND free T4 and/or free T3 are elevated above the reference range, confirming overt hyperthyroidism. 1

Diagnostic Thresholds for Treatment

• Overt hyperthyroidism: TSH suppressed (<0.45 mIU/L, often <0.01 mIU/L) with elevated free T4 and/or free T3 1, 5
• Subclinical hyperthyroidism (TSH <0.45 mIU/L with normal free T4/T3): treatment decisions depend on TSH level, age, and comorbidities 1
  • TSH **<0.1 mIU/L persistently** warrants treatment, especially if age >60, cardiac disease, or osteoporosis risk 3
  • TSH 0.1–0.45 mIU/L: monitor every 3–12 months; treat if symptomatic or high-risk features present 3

Special Consideration: Free T3 Toxicosis

• Free T3 toxicosis presents with suppressed TSH (≤0.1 mIU/L), normal free T4, normal total T3, but elevated free T3 by equilibrium dialysis 5
• This condition requires thyroid scan and radioiodine uptake to confirm autonomous thyroid function before initiating anti-thyroid drugs 5
• Treatment with radioactive iodine or surgery reverses TSH suppression in most cases 5

---

Typical Dosage Ranges for Anti-Thyroid Drugs

Methimazole (Preferred Agent)

The evidence provided does not contain specific dosing guidelines for anti-thyroid drugs. However, based on the diagnostic thresholds:

• Initiate treatment when free T4 and/or free T3 are elevated above the reference range with suppressed TSH 1
• Dose titration should aim to normalize free T4 and free T3 levels, with TSH recovery lagging behind (TSH may remain suppressed for weeks to months even after free hormones normalize) 1

Monitoring During Treatment

• Recheck TSH, free T4, and free T3 every 4–6 weeks during dose titration 3
• Free T4 can help interpret ongoing abnormal TSH levels during therapy, as TSH may take longer to normalize 3
• Once adequately treated, repeat testing every 6–12 months or if symptoms change 3

---

Critical Pitfalls to Avoid

• Do not rely on TSH alone to diagnose hyperthyroidism—always measure free T4 and free T3 when TSH is suppressed 1, 5
• Non-thyroidal illness can cause low TSH with low T3 and normal/low T4 without actual thyroid dysfunction 1
• Medications (dopamine, glucocorticoids, dobutamine) can suppress TSH without causing hyperthyroidism 1
• Pregnancy causes physiologically low TSH with normal free hormone levels 1
• Recent iodine exposure (e.g., CT contrast) can transiently affect thyroid function tests 1
• Heterophilic antibodies can cause falsely elevated TSH in some assays 1

---

Algorithmic Approach to Elevated Free T3/T4

1. Confirm hyperthyroidism: TSH <0.45 mIU/L + elevated free T4 and/or free T3 1
2. If free T4 is normal but TSH suppressed, measure free T3 by equilibrium dialysis to detect free T3 toxicosis 5
3. Obtain thyroid scan and radioiodine uptake to identify autonomous function (nodules, Graves' disease) 5
4. Initiate anti-thyroid drug therapy when autonomous function is confirmed 5
5. Monitor free T4, free T3, and TSH every 4–6 weeks during titration 3
6. Consider definitive therapy (radioactive iodine or surgery) if medical management fails 5

---

Special Populations Requiring Modified Approach

• Elderly patients or those with cardiac disease: more aggressive treatment of subclinical hyperthyroidism (TSH <0.1 mIU/L) to prevent atrial fibrillation and fractures 3
• Postmenopausal women: TSH suppression increases fracture risk, warranting earlier intervention 3
• Patients with thyroid nodules: thyroid scan is essential to distinguish toxic adenoma from Graves' disease 5