What are the typical lab findings in central hypothyroidism?

Typical Laboratory Findings in Central Hypothyroidism

The hallmark laboratory finding in central hypothyroidism is low free thyroxine (FT4) with inappropriately low or normal thyroid-stimulating hormone (TSH) levels, which distinguishes it from primary hypothyroidism where TSH is elevated. 1, 2

Key Laboratory Findings

Essential Thyroid Function Tests

• Low FT4 with low, normal, or occasionally mildly elevated TSH - This paradoxical pattern is the diagnostic cornerstone of central hypothyroidism 1, 3
• Normal TSH in majority of cases - Despite hypothyroidism, TSH remains within normal range in most patients, making diagnosis challenging if only TSH is measured 4
• Low TSH in approximately 8% of cases - A minority of patients will present with suppressed TSH 4
• Elevated TSH in approximately 8% of cases - Some patients may have mildly elevated TSH due to biologically inactive TSH molecules 4, 3

Additional Thyroid Parameters

• Free T3 (FT3) levels - Often low but may remain in the low-normal range 4, 5
• Total T4 (TT4) and Total T3 (TT3) - May be within normal range in a significant subset of patients, particularly those with child-onset central hypothyroidism 4
• Lower free T3 to free T4 ratio compared to euthyroid individuals 5

Associated Pituitary Hormone Abnormalities

• Low morning cortisol with low ACTH - Indicates concomitant central adrenal insufficiency, which is present in the majority of patients with hypophysitis-induced central hypothyroidism 3
• Low gonadotropins (FSH, LH) - Often present in hypophysitis-induced central hypothyroidism 3
• Approximately 50% of patients with hypophysitis present with panhypopituitarism (adrenal insufficiency plus hypothyroidism plus hypogonadism) 3

Diagnostic Considerations

Laboratory Testing Algorithm

1. Initial screening: Always measure both TSH and FT4 simultaneously 1, 3
2. If low FT4 with normal/low TSH is found: Proceed with comprehensive pituitary hormone evaluation 3
3. Morning hormone panel: ACTH, cortisol, gonadotropins (FSH, LH), and sex hormones (testosterone in men, estradiol in women) 3
4. Imaging: MRI of the sella with pituitary cuts when central hypothyroidism is suspected 3

Common Pitfalls

• TSH-only screening strategies will miss central hypothyroidism - Always include FT4 measurement when hypothyroidism is suspected 1, 6
• Methodological interference in free T4 or TSH measurements can hinder correct diagnosis 2
• Concurrent systemic illness can cause low FT4 with normal TSH, mimicking central hypothyroidism 2
• FT4 may remain in low-normal range in 28% of central hypothyroidism cases (especially in child-onset cases), potentially leading to missed diagnoses 4

Treatment Monitoring Considerations

• Target upper normal FT4 and low-normal FT3 levels when monitoring treatment adequacy 4
• TSH is suppressed in 75% of adequately treated patients and cannot be used to guide therapy 4
• Hormone replacement therapy adjustments may be needed, as estrogen treatment in women and GH treatment in men can increase levothyroxine requirements 4
• If both adrenal insufficiency and hypothyroidism are present, steroids should always be started prior to thyroid hormone replacement to avoid precipitating an adrenal crisis 3

Central hypothyroidism remains a challenging diagnosis that requires a high index of clinical suspicion and appropriate laboratory testing strategy that includes both TSH and FT4 measurements.