What further workup and treatment are recommended for a 56-year-old female with a mildly elevated TSH and low T4?

Management of Subclinical Hypothyroidism in a 56-Year-Old Female

The patient should be started on levothyroxine replacement therapy due to the combination of a normal TSH (1.460) with a low T4 (0.68), which is consistent with central hypothyroidism requiring further evaluation and treatment.

Initial Assessment and Diagnosis

This patient presents with laboratory findings showing:

• TSH: 1.460 (within normal range)
• T4: 0.68 (low)

These values represent a pattern consistent with central (secondary) hypothyroidism, where the pituitary gland is not producing adequate TSH to stimulate sufficient thyroid hormone production.

Further Workup Required

1. Complete pituitary hormone evaluation:

   • Morning cortisol (9 am) or random cortisol if patient is unwell 1
   • ACTH, LH, FSH, estradiol (as patient is female)
   • Prolactin
   • IGF-1 1

2. Imaging:

   • MRI of the pituitary with specific protocol for pituitary visualization 1

3. Additional thyroid testing:

   • Free T3 to complete thyroid profile
   • Thyroid antibodies to rule out concurrent autoimmune thyroid disease

Treatment Approach

Immediate Management

1. Hormone replacement:

   • Start levothyroxine at 0.5-1.5 μg/kg/day based on weight and age 2
   • For a 56-year-old female, consider starting at a lower dose (25-50 mcg daily) and titrate upward 1
   • Administer once daily on an empty stomach, 30-60 minutes before breakfast 2

2. Cortisol assessment before thyroid replacement:

   • Important: Always check cortisol status before starting thyroid hormone replacement 1
   • If cortisol is low, replace cortisol for at least one week prior to starting levothyroxine to prevent precipitating adrenal crisis 1

Monitoring and Dose Adjustment

1. Initial monitoring:

   • Check thyroid function tests (TSH, free T4) every 4-6 weeks initially 1
   • Adjust levothyroxine dose based on free T4 levels rather than TSH, as TSH may be unreliable in central hypothyroidism 3
   • Target free T4 in the mid to upper half of the reference range 1

2. Long-term monitoring:

   • Once stable, monitor every 6-12 months 1
   • Continue to monitor other pituitary hormones as indicated

Special Considerations

Referral to Endocrinology

• Endocrinology consultation is strongly recommended for management of central hypothyroidism 1
• The patient requires expert evaluation of potential hypopituitarism

Common Pitfalls to Avoid

1. Misdiagnosis: Normal TSH with low T4 is often misinterpreted as laboratory error rather than central hypothyroidism 3

2. Inadequate evaluation: Failing to evaluate other pituitary hormones can miss potentially life-threatening adrenal insufficiency 1

3. Inappropriate treatment: Starting levothyroxine without checking cortisol status can precipitate adrenal crisis in patients with concurrent adrenal insufficiency 1

4. Overreliance on TSH: In central hypothyroidism, TSH cannot be used to monitor treatment adequacy; free T4 levels should guide therapy 3

Potential Causes to Investigate

• Pituitary adenoma
• Previous radiation to the head/neck
• Pituitary apoplexy
• Infiltrative diseases (sarcoidosis, hemochromatosis)
• Traumatic brain injury
• Sheehan syndrome (if history of postpartum hemorrhage)

Central hypothyroidism is much less common than primary hypothyroidism but requires prompt diagnosis and treatment to prevent complications and improve quality of life.