Investigations for suspected hypothyroidism

1. Initial test

• Serum TSH is the best screening test for primary hypothyroidism.
• If TSH is abnormal, measure free T4 (FT4) to classify severity.

2. Tests to identify the cause

• Anti-thyroid peroxidase antibody (anti-TPO): supports autoimmune thyroiditis, usually Hashimoto thyroiditis.
• Anti-thyroglobulin antibody: may also support autoimmune thyroid disease but is less routinely needed.
• Lipid profile: hypercholesterolemia can accompany hypothyroidism.
• CBC: may show normocytic or macrocytic anemia.
• Serum sodium, creatine kinase, liver enzymes, renal function: may be abnormal in significant disease.
• Blood glucose and vitamin B12: consider where autoimmune polyglandular disease or pernicious anemia is suspected.

3. If central hypothyroidism is possible

• FT4
• Other pituitary hormones: 8 to 9 AM cortisol, ACTH, prolactin, LH/FSH and sex hormones, IGF-1
• Pituitary MRI, if biochemical findings or symptoms suggest pituitary disease
• Assess visual fields if there may be a pituitary mass

4. Imaging

• Thyroid ultrasound is not routine for biochemical hypothyroidism.
• Request it only for a palpable goitre, thyroid nodule, asymmetry, cervical lymphadenopathy, or suspected structural thyroid disease.
• Do not use thyroid scintigraphy routinely to diagnose hypothyroidism.

5. Tests generally not useful routinely

• Total T3, free T3: not useful for diagnosing primary hypothyroidism. T3 can remain normal even in severe disease.
• Serial anti-TPO titres: do not monitor treatment response.
• Reverse T3: not routinely indicated.

6. Important practical points

• Interpret results using the laboratory reference interval and clinical setting.
• Check for drugs or factors affecting results, such as amiodarone, lithium, interferon, immune-checkpoint inhibitors, glucocorticoids, dopamine, biotin supplements, and recent severe illness.
• In non-pregnant adults with a mildly raised TSH and normal FT4, repeat thyroid function tests after 3 to 6 months to confirm persistent subclinical hypothyroidism, as suggested in NICE assessment guidance.
• Pregnancy uses trimester-specific interpretation and lower treatment thresholds, so test TSH and FT4 promptly if suspected.

Investigations in hypothyroidism

1. Thyroid function tests

• Serum TSH: most sensitive initial test for primary hypothyroidism.
• Free T4 (FT4): confirms and classifies hypothyroidism.

• T3 is usually not helpful, as it may remain normal until late disease.

2. Identify the aetiology

• Anti-thyroid peroxidase antibodies (anti-TPO): usually positive in autoimmune, particularly Hashimoto, thyroiditis.
• Anti-thyroglobulin antibodies: can provide additional evidence of autoimmune thyroid disease.
• If central hypothyroidism is suspected:
  • Assess other pituitary hormones, especially morning cortisol
  • Pituitary MRI when indicated

3. Assess associated abnormalities and complications

• Full blood count: normocytic or macrocytic anaemia.
• Serum electrolytes, especially sodium: hyponatraemia may occur.
• Lipid profile: hypercholesterolaemia, often raised LDL cholesterol.
• Creatine kinase (CK): may be elevated due to hypothyroid myopathy.
• Liver and renal function tests: may be abnormal.
• Blood glucose and vitamin B12 where another autoimmune condition or pernicious anaemia is suspected.
• ECG: sinus bradycardia, low-voltage complexes, and sometimes other nonspecific changes.
• Chest X-ray/echocardiography, only if clinically indicated: may demonstrate cardiomegaly or pericardial effusion in severe longstanding disease.

4. Imaging

• Thyroid ultrasound is not routinely needed to diagnose hypothyroidism. Use it if there is a goitre, nodule, asymmetry, or suspicious neck finding.
• Thyroid radionuclide scanning is not routinely useful in established hypothyroidism.