What is the initial laboratory workup for suspected central hypothyroidism?

Laboratory Workup for Suspected Central Hypothyroidism

The initial laboratory workup for suspected central hypothyroidism should include both thyroid-stimulating hormone (TSH) and free thyroxine (FT4) measurements, as central hypothyroidism is characterized by low FT4 with inappropriately low or normal TSH levels. 1

Diagnostic Approach

Initial Testing

• Measure both TSH and FT4 simultaneously, as measuring TSH alone will miss central hypothyroidism 1
• Low TSH with a low FT4 is consistent with central hypothyroidism and requires further evaluation 1
• Normal or even mildly elevated TSH with low FT4 can also indicate central hypothyroidism (due to biologically inactive TSH molecules) 1, 2

Additional Testing for Confirmed Low FT4 with Low/Normal TSH

• Morning cortisol and ACTH levels to assess adrenal function (should be done before starting any steroid therapy) 1
• Gonadal hormones: testosterone in men, estradiol in women, plus FSH and LH 1
• MRI of the sella with pituitary cuts to evaluate for structural abnormalities 1
• These tests should be performed before administration of any steroids or thyroid hormone replacement 1

Clinical Considerations

Diagnostic Challenges

• The diagnosis can be difficult due to methodological interference in FT4 or TSH measurements 3
• Concurrent systemic illness can cause low FT4 with normal TSH (euthyroid sick syndrome), mimicking central hypothyroidism 3
• TSH may appear normal or even mildly elevated in some cases of central hypothyroidism due to biologically inactive TSH molecules 1, 2
• The positive predictive value of finding low FT4 with normal/low TSH is only 2-4% for true central hypothyroidism 4

Important Diagnostic Criteria

• Proposed confirmation criteria for hypophysitis-induced central hypothyroidism include: ≥1 pituitary hormone deficiency (TSH or ACTH deficiency required) combined with an MRI abnormality, or ≥2 pituitary hormone deficiencies with headache and other symptoms 1
• Clinical suspicion should increase when routine thyroid function testing shows low TSH with low free T4 in patients with symptoms like headache and fatigue 1

Treatment Considerations

Critical Precaution

• If both adrenal insufficiency and hypothyroidism are present, steroids should always be started prior to thyroid hormone replacement to avoid precipitating an adrenal crisis 1
• If there is uncertainty about whether primary or central hypothyroidism is present, hydrocortisone should be given before thyroid hormone is initiated 1

Monitoring

• In patients with confirmed central hypothyroidism, treatment is tailored according to free T4 levels, which should be maintained in the upper half of the normal range for age 5, 6
• Unlike primary hypothyroidism where TSH is the monitoring target, in central hypothyroidism, FT4 becomes the primary monitoring parameter 5, 6

Central hypothyroidism is a rare condition with an estimated incidence of only 2 cases per 100,000 population per year, making it important to have a systematic approach to diagnosis to avoid missing these cases 4.