SN3 SHORT NOTE 5M ★ High-yield

Describe the thyroid function tests and their interpretation.

Biochemistry · 1st Professional — Pre-Clinical

Definition

Thyroid function tests = the biochemical assessment of thyroid status, based chiefly on serum TSH with free thyroid hormone levels.

The Hormones

Hormone	Normal range	Notes
TSH	0.4–4.0 mIU/L	The single most sensitive test — changes logarithmically with small shifts in thyroid hormone
Free T4	0.8–1.8 ng/dL	The chief secretory product; a prohormone
Free T3	2.3–4.2 pg/mL	The active hormone; 80% made peripherally by deiodination
Total T4, T3	—	Affected by binding proteins — less reliable

99.97% of T4 is protein-bound, chiefly to thyroxine-binding globulin; only the free fraction is active
TBG rises in pregnancy and with oestrogen, and falls in nephrotic syndrome and liver disease — which is why free hormone is measured

Interpretation

TSH	Free T4	Diagnosis
↑	↓	Primary hypothyroidism
↑	Normal	Subclinical hypothyroidism
↓	↑	Primary hyperthyroidism
↓	Normal	Subclinical hyperthyroidism; or T3 toxicosis (check free T3)
↓ or normal	↓	Secondary (pituitary) hypothyroidism
↑	↑	TSH-secreting adenoma; thyroid hormone resistance; assay interference

CLINICAL PEARL

TSH alone is the best screening test in a stable outpatient, because the pituitary responds to tiny changes in free hormone. But it is misleading in pituitary disease, in acute illness, and in the first weeks of treatment, when it lags behind by 6–8 weeks.

Other Tests

Anti-TPO and anti-thyroglobulin antibodies — Hashimoto thyroiditis
TSH receptor antibodies (TRAb) — Graves disease
Thyroglobulin — a tumour marker in follow-up of differentiated thyroid carcinoma
Radioiodine uptake scan — distinguishes Graves disease (high, diffuse) from thyroiditis (low uptake)
Calcitonin — medullary carcinoma

Pitfalls

Situation	Effect
Sick euthyroid syndrome	Low T3, normal or low TSH in any severe illness; do not test thyroid function in an acutely ill patient
Pregnancy	HCG stimulates the TSH receptor → low TSH in the first trimester; trimester-specific ranges are needed
Amiodarone	Can cause either hypo- or hyperthyroidism; contains large amounts of iodine
Biotin supplements	Interfere with immunoassays → falsely low TSH with high T4, mimicking thyrotoxicosis
Recent treatment change	TSH takes 6–8 weeks to equilibrate

Applied Aspects

Congenital hypothyroidism screening by neonatal TSH is among the most valuable of all screening programmes — treatment within the first two weeks prevents retardation entirely, while delay causes irreversible damage
Hypothyroidism raises LDL cholesterol and creatine kinase, and should be excluded in unexplained dyslipidaemia or myopathy
Subclinical hypothyroidism in pregnancy should be treated, since the fetus depends entirely on maternal thyroxine in the first trimester
Iodine deficiency remains the commonest cause of hypothyroidism worldwide, though autoimmune thyroiditis predominates where salt is iodised

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