How the thyroid system works — the feedback loop
The thyroid does not operate alone. It is part of the hypothalamic-pituitary-thyroid (HPT) axis:
- The hypothalamus releases TRH (thyrotropin-releasing hormone)
- TRH signals the pituitary gland to release TSH (thyroid-stimulating hormone)
- TSH tells the thyroid gland to produce T4 (thyroxine) and some T3 (triiodothyronine)
- Most T4 is converted to the active form T3 in peripheral tissues (liver, kidneys)
- When thyroid hormone levels are adequate, they feed back to suppress TSH
This is why TSH moves in the opposite direction to thyroid hormones: a low-functioning thyroid → low T4 → high TSH. An overactive thyroid → high T4/T3 → low TSH.
What each thyroid marker measures
| Marker | Unit | Typical range | Low | High | When ordered |
|---|---|---|---|---|---|
| TSH | mIU/L | 0.4–4.0 | < 0.4 | > 4.0 | The primary screening test — most sensitive indicator of thyroid status. |
| Free T4 (FT4) | pmol/L or ng/dL | 9–24 pmol/L (0.7–1.9 ng/dL) | < 9 pmol/L | > 24 pmol/L | Ordered when TSH is abnormal to confirm and classify thyroid function. |
| Free T3 (FT3) | pmol/L or pg/mL | 3.5–7.8 pmol/L (2.3–5.0 pg/mL) | < 3.5 pmol/L | > 7.8 pmol/L | Less commonly ordered first-line; useful in T3 toxicosis and monitoring. |
Note: Ranges are approximate and vary by laboratory. Pregnancy has its own trimester-specific TSH ranges (generally lower, particularly in the first trimester). Always use your lab's printed interval.
Common thyroid result patterns and what they mean
| TSH + FT4/FT3 pattern | Interpretation | Clinical context |
|---|---|---|
| High TSH + Low FT4 | Primary hypothyroidism | The thyroid is underactive. The pituitary gland raises TSH to stimulate it. |
| High TSH + Normal FT4 | Subclinical hypothyroidism | Early thyroid underactivity. May progress to overt hypothyroidism over years. |
| Low TSH + High FT4 / FT3 | Primary hyperthyroidism | The thyroid is overactive, suppressing TSH. Graves' disease is a common cause. |
| Low TSH + Normal FT4 / FT3 | Subclinical hyperthyroidism | Mild excess thyroid hormone. Risk of atrial fibrillation and bone loss if persistent. |
| Low TSH + Low FT4 | Central hypothyroidism | Rare — the pituitary or hypothalamus is failing to stimulate the thyroid adequately. |
| Normal TSH | Euthyroid (normal thyroid function) | In the absence of pituitary disease or other complicating factors, normal TSH generally indicates normal thyroid function. |
TSH: the most important first-line test
TSH is the most sensitive indicator of thyroid function and is the recommended first test for screening. A normal TSH almost always means the thyroid is working correctly — in the absence of pituitary disease or other complicating factors, Free T4 does not need to be added.
TSH has a wide physiological range between individuals and a logarithmic scale — a TSH of 0.5 and a TSH of 4.0 are both within the reference interval, but represent very different points on the thyroid function spectrum for a given individual. This is one reason symptoms and trends over time matter alongside the number.
Free T4 (FT4): measuring the available hormone
T4 circulates mostly bound to proteins (mainly TBG — thyroid-binding globulin). Free T4 measures only the unbound fraction that is biologically active. It is ordered when TSH is abnormal, to determine whether thyroid hormone levels are genuinely low (hypothyroidism) or high (hyperthyroidism).
Why "free" rather than total T4?
Total T4 is affected by changes in binding proteins — pregnancy, oral contraceptives, and liver disease all raise TBG, inflating total T4 without changing active thyroid function. Free T4 is less susceptible to these confounders and is preferred for clinical decisions.
Free T3 (FT3): when is it ordered?
T3 is the biologically active form of thyroid hormone — about 3–4 times more potent than T4. Most circulating T3 comes from peripheral conversion of T4, not direct thyroid secretion.
FT3 is ordered in specific situations:
- T3 toxicosis — a form of hyperthyroidism where FT3 is elevated but FT4 is normal
- Monitoring thyrotoxicosis treatment — FT3 normalises later than FT4 and TSH
- Assessing conversion in sick euthyroid syndrome — severe illness reduces T4-to-T3 conversion, causing low FT3 with normal TSH
FT3 is not routinely ordered for initial thyroid screening and should not be used to dose thyroid medication without specialist guidance.
Additional thyroid tests your doctor may order
- TPO antibodies (anti-thyroid peroxidase) — elevated in Hashimoto's thyroiditis (autoimmune hypothyroidism) and Graves' disease
- TSI / TRAb (TSH receptor antibodies) — specific for Graves' disease; positive in most cases of autoimmune hyperthyroidism
- Thyroglobulin (Tg) — used as a tumour marker after treatment for differentiated thyroid cancer, not for routine thyroid function assessment
- Thyroid ultrasound — not a blood test, but often ordered alongside abnormal results to look for nodules or goitre
Factors that interfere with thyroid test results
- Pregnancy — hCG stimulates the thyroid, causing lower TSH (especially in the first trimester)
- Thyroid medication (levothyroxine) — TSH timing relative to dose matters; most guidelines recommend testing before the morning dose
- Biotin supplements — high-dose biotin interferes with many immunoassay methods and can cause false results; stop biotin 2–3 days before testing
- Severe illness (sick euthyroid syndrome) — acute illness suppresses TSH transiently; avoid interpreting thyroid tests during hospitalisation for unrelated conditions
- Certain medications — amiodarone, lithium, steroids, dopamine, and others significantly affect thyroid function or test results
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