What to do with low free T4 (free thyroxine) and low TSH (thyroid-stimulating hormone) during pregnancy?

Low Free T4 and Low TSH in Pregnancy: Central Hypothyroidism

This pattern of low free T4 with low (or inappropriately normal) TSH during pregnancy suggests central hypothyroidism due to pituitary dysfunction, which requires immediate evaluation for hypopituitarism and prompt hormone replacement therapy starting with corticosteroids before thyroid hormone to prevent adrenal crisis.

Immediate Diagnostic Workup

The combination of low free T4 with low/normal TSH indicates a central (secondary) etiology rather than primary thyroid disease 1. This requires urgent evaluation for hypopituitarism:

• Morning (8 AM) laboratory testing should include:

  • ACTH and cortisol levels (or 1 mcg cosyntropin stimulation test) 1
  • Repeat TSH and free T4 to confirm 1
  • Gonadal hormones (estradiol), FSH, and LH 1
  • Prolactin level 1

• MRI of the sella with pituitary cuts should be obtained to evaluate for pituitary pathology 1

• Clinical assessment for symptoms of hypopituitarism:

  • Headache (present in 85% of hypophysitis cases) 1
  • Fatigue (66% of cases) 1
  • Visual changes (uncommon but critical) 1

Critical Treatment Sequence

If both adrenal insufficiency and central hypothyroidism are confirmed, corticosteroids MUST be started before thyroid hormone replacement to avoid precipitating an adrenal crisis 1. This is the most important management principle.

Step 1: Corticosteroid Replacement (If Adrenal Insufficiency Present)

• Start physiologic doses of hydrocortisone or equivalent immediately 1
• All patients with confirmed adrenal insufficiency should obtain and carry a medical alert bracelet 1

Step 2: Thyroid Hormone Replacement

Once corticosteroid replacement is initiated (or adrenal insufficiency is ruled out):

• Start levothyroxine immediately - untreated maternal hypothyroidism causes adverse fetal neurocognitive development, spontaneous abortion, gestational hypertension, pre-eclampsia, stillbirth, and premature delivery 2, 3, 4

• Dosing for new-onset hypothyroidism in pregnancy:

  • If TSH ≥10 IU/L: start 1.6 mcg/kg/day 2
  • If TSH <10 IU/L: start 1.0 mcg/kg/day 2
  • For central hypothyroidism, use free T4 levels (not TSH) to guide therapy 1

• Target free T4 in the upper half of the normal range during pregnancy 2, 3, 5

Monitoring During Pregnancy

• Check TSH and free T4 every 4 weeks until stable, then at minimum once per trimester 2
• For central hypothyroidism, free T4 is the primary monitoring parameter since TSH will remain low 1
• Adjust levothyroxine dose by 12.5 to 25 mcg increments as needed 2
• Most pregnant women with pre-existing hypothyroidism require a 25-50% increase in levothyroxine dose during the first trimester 3, 6

Postpartum Management

• Reduce levothyroxine to pre-pregnancy dose immediately after delivery 2
• Monitor TSH and free T4 at 4-8 weeks postpartum 2
• Both adrenal insufficiency and central hypothyroidism from hypopituitarism typically require lifelong hormonal replacement 1

Key Clinical Pitfalls

• Never start thyroid hormone before ruling out or treating adrenal insufficiency - this can precipitate life-threatening adrenal crisis 1
• Do not rely on TSH alone for monitoring central hypothyroidism - use free T4 levels 1
• Inadequate treatment has severe fetal consequences including impaired neuropsychological development, low birth weight, fetal distress, preterm birth, and intrauterine growth retardation 3, 7, 4
• Pituitary enlargement on MRI may precede clinical symptoms, and most cases show stalk thickening, suprasellar convexity, or heterogeneous enhancement 1