What is the workup for a patient with low Thyroid-Stimulating Hormone (TSH) and low prolactin?

Workup for Low TSH and Low Prolactin

The workup for a patient with low TSH and low prolactin should include measurement of free T4 (FT4) to differentiate between hyperthyroidism and central hypothyroidism, followed by pituitary function testing to evaluate for hypophysitis or other pituitary disorders. 1

Initial Evaluation

• Low TSH with low FT4 is consistent with central hypothyroidism, which requires evaluation for hypophysitis or other pituitary disorders 1
• Low TSH with normal or elevated FT4 suggests primary hyperthyroidism 1
• Low prolactin is uncommon and may indicate pituitary dysfunction, particularly when combined with low TSH 1

Recommended Laboratory Testing

• Free T4 (FT4) - essential to differentiate between hyperthyroidism and central hypothyroidism 1
• Complete pituitary hormone panel:
  • Morning cortisol and ACTH (8-9 am) to assess adrenal axis 1
  • LH, FSH, estradiol (in women) or testosterone (in men) to assess gonadal axis 1
  • IGF-1 to assess growth hormone axis 1
  • Repeat prolactin measurement to confirm low level 1

Imaging

• MRI of the sella with pituitary cuts if central hypothyroidism is confirmed (low TSH with low FT4) 1
• Thyroid ultrasound if hyperthyroidism is suspected (low TSH with normal/high FT4) 1

Additional Testing Based on Clinical Context

• If central hypothyroidism is confirmed:
  • 1 mcg cosyntropin stimulation test if adrenal insufficiency is suspected 1
  • TSH receptor antibody testing if there are clinical features of Graves' disease 1
  • T3 levels if clinically indicated, especially in symptomatic patients 1

Interpretation and Management Algorithm

1. If low TSH with low FT4:

   • Diagnosis: Central hypothyroidism
   • Further workup: Complete pituitary hormone panel and MRI of pituitary
   • Management: If hypopituitarism is confirmed, replace cortisol FIRST (hydrocortisone 20/10 mg) before initiating thyroid hormone replacement 1

2. If low TSH with normal/high FT4:

   • Diagnosis: Primary hyperthyroidism
   • Further workup: Thyroid antibodies, thyroid ultrasound
   • Management: Beta-blockers for symptomatic relief while completing diagnostic workup 1

Clinical Pearls and Pitfalls

• Low TSH with low prolactin may indicate hypophysitis, particularly in patients on immune checkpoint inhibitors 1
• Hyperprolactinemia (not hypoprolactinemia) is more commonly associated with hypothyroidism 2, 3
• Always check for medication effects that could influence both TSH and prolactin levels 3
• In patients with suspected pituitary dysfunction, always replace cortisol before thyroid hormone to avoid precipitating an adrenal crisis 1
• Central hypothyroidism can be easily missed if only TSH is measured without FT4 1
• Thyroid hormone levels can influence prolactin secretion - thyroid hormone inhibits prolactin response to TRH 4

Special Considerations

• In patients on immune checkpoint inhibitors, low TSH with low FT4 is highly suggestive of immune-related hypophysitis 1
• Patients with low TSH and low prolactin should be evaluated for other pituitary hormone deficiencies 1
• Patients with total testosterone levels <150 ng/dL combined with low/low-normal LH should undergo pituitary MRI regardless of prolactin levels 1