What is the workup for central hyperthyroidism?

Workup for Central Hyperthyroidism

The workup for central hyperthyroidism should focus on distinguishing between TSH-secreting pituitary adenoma (TSHoma) and resistance to thyroid hormone β (RTHβ), as these are the two main causes of this rare condition. 1

Initial Laboratory Evaluation

• TSH levels: Normal or elevated (inappropriately non-suppressed) 1
• Free T4 and Free T3: Elevated 1, 2
• Alpha-subunit to TSH molar ratio: Elevated in TSHoma, normal in RTHβ 2, 3
• TSH receptor antibodies: To rule out concurrent Graves' disease 1
• Thyroid peroxidase antibodies: To assess for autoimmune thyroid disease 4

Diagnostic Testing

• TRH stimulation test:

  • TSHoma: Blunted or absent TSH response 3
  • RTHβ: Normal or exaggerated TSH response 2

• T3 suppression test:

  • TSHoma: Failure of T3 to suppress TSH 2
  • RTHβ: Variable response 2

• Imaging studies:

  • Pituitary MRI: Essential to identify pituitary adenoma 1, 2
  • Thyroid ultrasound: To assess thyroid size and nodularity 4
  • Thyroid scintigraphy: May show diffuse uptake 4

• Genetic testing: For mutations in thyroid hormone receptor β gene in suspected RTHβ 1

Differential Diagnosis

1. TSH-secreting pituitary adenoma (TSHoma)
2. Resistance to thyroid hormone β (RTHβ)
3. Assay interference from anti-T4/T3 antibodies
4. Heterophile antibodies affecting lab results
5. Altered thyroid binding proteins
6. Drug effects on peripheral thyroid hormone metabolism
7. Concurrent Graves' disease with central hyperthyroidism 1, 2, 3

Management Considerations

• TSHoma: Transsphenoidal surgery is the primary treatment 1, 2
• RTHβ: Medical management with D-thyroxine, TRIAC, octreotide, or bromocriptine 2
• For patients with concurrent Graves' disease: Control thyrotoxicosis before addressing pituitary pathology 1
• Octreotide may be useful for preoperative reduction of tumor size or management of surgical failures 2, 3

Monitoring

• Serial TSH and free thyroid hormone measurements to assess treatment response 5
• Regular pituitary imaging to monitor tumor size in TSHoma cases 2
• Assessment for other pituitary hormone deficiencies 6

Common Pitfalls

• Misdiagnosing as primary hyperthyroidism (which has suppressed TSH)
• Failing to recognize concurrent Graves' disease with central hyperthyroidism
• Initiating antithyroid drugs without confirming diagnosis, which is contraindicated in generalized thyroid hormone resistance 6
• Not evaluating for other pituitary hormone deficiencies, particularly in TSHoma 6
• Relying on a single TSH value rather than serial measurements 5

Central hyperthyroidism requires careful diagnostic evaluation to distinguish between its causes and to guide appropriate treatment decisions that will improve morbidity, mortality, and quality of life outcomes.