What labs should be ordered to evaluate hypopituitarism in a patient with hypothyroidism on long-term prednisone (corticosteroid) presenting with fatigue?

Laboratory Evaluation for Hypopituitarism in a Patient with Fatigue

A comprehensive hormonal evaluation should be ordered, focusing on all anterior pituitary axes, including thyroid, adrenal, gonadal, and growth hormone function, as these are commonly affected in hypopituitarism and can contribute to fatigue. 1

Core Laboratory Tests for Pituitary Function Assessment

Thyroid Function

• TSH and Free T4 (central hypothyroidism presents with low/normal TSH and low Free T4) 1, 2
• Free T3 (less essential if TSH and Free T4 are normal) 2

Adrenal Function

• Morning ACTH and cortisol (8 AM preferred) 1, 2
• 1 mcg cosyntropin stimulation test if morning cortisol results are indeterminate 1, 2
  • This is particularly important in a patient on long-term prednisone (20 years) who may have adrenal suppression

Gonadal Function

• FSH, LH, estradiol (for female patients) 1, 2

Growth Hormone Axis

• IGF-1 (most commonly affected axis in hypopituitarism, present in 61-100% of patients) 1, 2

Prolactin

• Serum prolactin (to rule out hyperprolactinemia which can be present in 25-65% of patients with pituitary disorders) 1

Additional Important Laboratory Tests

• Complete blood count (to evaluate for anemia) 2
• Basic metabolic panel (electrolytes, renal function) 2
• Fasting blood glucose and HbA1c (especially important in patients on glucocorticoids) 2, 3
• Serum ferritin, iron, TIBC (iron deficiency can contribute to fatigue) 2
• Vitamin B12 and folate levels (deficiencies can cause fatigue) 2
• Vitamin D level 2

Timing Considerations

• Hormone testing should be performed in the morning (around 8 AM) when possible, particularly for cortisol assessment 1
• Testing should be done prior to administration of steroids to avoid interference with results 1

Interpretation Considerations

• In patients on long-term prednisone, the hypothalamic-pituitary-adrenal axis may be suppressed, complicating interpretation 3
• TSH may not be reliable in central hypothyroidism; Free T4 levels should be used to evaluate thyroid function, with a goal in the upper half of the reference range 2, 4
• Normal laboratory values do not necessarily rule out clinically significant hormone deficiencies 2
• The TSH index (TSHI = log TSH + 0.1345 × fT4) can help identify subtle TSH deficiency within normal reference ranges 4

Pitfalls to Avoid

1. Relying solely on TSH for thyroid assessment in hypopituitarism (central hypothyroidism presents with low/normal TSH and low Free T4) 1, 4

2. Failing to test all pituitary axes - partial hypopituitarism is common (37-85% of patients) 1

3. Not considering the impact of long-term prednisone use on the HPA axis and glucose metabolism 3

4. Misinterpreting normal laboratory values in the context of hypopituitarism (reference ranges may not apply) 2, 4

5. Overlooking non-endocrine causes of fatigue that may coexist with hypopituitarism 2

By performing this comprehensive evaluation, you will be able to identify which pituitary axes are affected and guide appropriate hormone replacement therapy, which should improve the patient's fatigue symptoms.