What is the recommended treatment for a patient with hypothyroidism (low free T4 level of 0.90) and normal Thyroid-Stimulating Hormone (TSH) levels?

Low Free T4 with Normal TSH: Central Hypothyroidism Until Proven Otherwise

This patient requires immediate evaluation for central hypothyroidism, and you must check an 8 AM cortisol level BEFORE initiating any thyroid hormone replacement to avoid precipitating a life-threatening adrenal crisis. 1

Critical First Steps

The combination of low free T4 (0.90) with normal TSH strongly suggests central (secondary or tertiary) hypothyroidism, where the pituitary or hypothalamus fails to produce adequate TSH despite low thyroid hormone levels 1, 2. This is not primary hypothyroidism, where TSH would be elevated.

Before doing anything else:

• Obtain 8 AM cortisol and ACTH levels immediately - central hypothyroidism coexists with adrenal insufficiency in more than 75% of cases 1
• Do not start levothyroxine until adrenal status is secured - thyroid hormone increases cortisol metabolism and can trigger adrenal crisis if cortisol deficiency exists 1, 2
• If cortisol is low, start physiologic dose steroids at least 1 week before any thyroid hormone replacement 1, 3

Diagnostic Workup

Repeat thyroid function tests (TSH, free T4) to confirm the pattern, as 30-60% of abnormal results normalize on repeat testing 1, 4

Complete pituitary hormone panel:

• ACTH and 8 AM cortisol (or 1 mcg cosyntropin stimulation test if cortisol is borderline) 1
• FSH, LH, and gonadal hormones (testosterone in men, estradiol in women) 1
• Consider thyroid antibodies (TPO) to evaluate for concurrent autoimmune disease 1

MRI of the sella with pituitary cuts is essential to evaluate for pituitary pathology, including adenomas, hypophysitis, or structural lesions 1

Treatment Algorithm

If cortisol deficiency is confirmed:

1. Start physiologic dose steroids FIRST (hydrocortisone 15-20 mg/day in divided doses) 1
2. Wait at least 1 week before initiating thyroid hormone 1
3. Patient should obtain and carry a medical alert bracelet 1

Once adrenal status is secured:

• Start levothyroxine at 1.5 mcg/kg/day for younger patients without cardiac disease 1, 3
• Use lower starting dose (0.5-1.0 mcg/kg/day) in elderly patients or those with cardiac history 1, 3
• Administer as single daily dose on empty stomach, 30-60 minutes before breakfast 3, 5

Monitoring Strategy

For central hypothyroidism, TSH is unreliable and should NOT be used to monitor therapy 3, 2. Instead:

• Use serum free T4 to titrate dosing until the patient is clinically euthyroid 3, 2
• Target free T4 in the upper half of the normal range 3, 2
• Recheck free T4 every 6-8 weeks during dose titration 1
• Once stable, repeat testing every 6-12 months or sooner if symptoms change 1

Critical Pitfalls to Avoid

Never start thyroid hormone before ruling out adrenal insufficiency - this is the most dangerous error in managing central hypothyroidism and can be fatal 1, 2

Do not rely on TSH for diagnosis or monitoring - in central hypothyroidism, TSH may be normal, low, or even slightly elevated despite inadequate thyroid hormone 3, 2

Do not assume this is transient - lifelong hormone replacement is typically required for central hypothyroidism 1

Refer to endocrinology if the pattern persists after initial workup or if management becomes complex, particularly given the high likelihood of multiple pituitary hormone deficiencies 1