Workup for Pituitary Insufficiency
All patients with suspected pituitary insufficiency require comprehensive evaluation of all anterior pituitary hormone axes through morning baseline hormone measurements, combined with MRI sella using dedicated pituitary protocol imaging. 1, 2
Initial Laboratory Evaluation
Obtain morning (around 8 AM) baseline hormone panel including: 1, 2
Thyroid Axis
- TSH and free T4 (to detect central hypothyroidism, which presents as low free T4 with low or inappropriately normal TSH) 1, 2
Adrenal Axis
- ACTH and cortisol (to detect central adrenal insufficiency, which presents as low cortisol with low or inappropriately normal ACTH) 1, 2
- If morning cortisol is indeterminate (3-15 mcg/dL), perform 1 mcg cosyntropin stimulation test before administering any steroids 1, 2
Gonadal Axis
- In males: testosterone, LH, FSH 1, 2
- In females: estradiol, LH, FSH 1, 2
- Hypogonadotropic hypogonadism presents as low testosterone/estradiol with low or inappropriately normal FSH and LH 2
Growth Hormone Axis
- IGF-1 (to rule out GH hypersecretion that might not be clinically suspected, and to assess for GH deficiency) 1, 2
- GH deficiency is the most commonly affected axis, occurring in 61-100% of patients with pituitary disorders 1
Prolactin
- Baseline prolactin level (to rule out hyperprolactinemia or prolactinoma that might not be clinically suspected) 1
Metabolic Parameters
- Glucose and HbA1c (for glycemic control assessment) 1, 2
- Electrolytes (to evaluate for diabetes insipidus if hypernatremia and volume depletion present) 1
Imaging Studies
MRI of the sella with dedicated pituitary protocol is the gold standard initial imaging study and should be obtained in all patients with suspected hypopituitarism. 2 This imaging can detect:
- Microadenomas and macroadenomas 2
- Empty sella (approximately 30% of patients with empty sella demonstrate hypopituitarism) 2
- Pituitary enlargement, stalk thickening, suprasellar convexity, heterogeneous enhancement 1
- Craniopharyngiomas, Rathke cleft cysts, inflammatory lesions, and metastases 2
MRI is particularly essential when: 1
- Multiple endocrine abnormalities are present
- New severe headaches occur
- Vision changes are reported
- Diabetes insipidus is diagnosed (most commonly from metastatic disease)
Diagnostic Interpretation Patterns
Central Hypothyroidism
Low free T4 with low or inappropriately normal TSH (affects 8-81% of patients with pituitary disorders) 1, 2
Central Adrenal Insufficiency
Low cortisol with low or inappropriately normal ACTH (affects 17-62% of patients) 1, 2
Hypogonadotropic Hypogonadism
Low testosterone/estradiol with low or inappropriately normal FSH and LH (affects 36-96% of patients) 1, 2
Growth Hormone Deficiency
Low IGF-1 (affects 61-100% of patients, making it the most commonly affected axis) 1, 2
Critical Pitfalls to Avoid
Always perform dynamic stimulation tests (such as cosyntropin stimulation) BEFORE administering steroids to avoid interference with results. 1, 2
If both adrenal insufficiency and hypothyroidism are present, glucocorticoid replacement MUST be started before thyroid hormone replacement to prevent precipitating an adrenal crisis. 1, 2
Do not use TSH alone to guide diagnosis in central hypothyroidism - TSH is not accurate in this setting and free T4 must be evaluated. 1
Routine endocrine evaluation of ALL anterior pituitary axes is recommended because deficits occur at rates beyond clinical suspicion, and cutoff values for initiating replacement may differ in panhypopituitarism versus isolated deficiencies. 1
Prevalence Context
Understanding the hierarchy of axis involvement helps guide clinical suspicion: 1, 2
- GH axis: 61-100% affected (most common)
- Gonadal axis: 36-96% affected
- Adrenal axis: 17-62% affected
- Thyroid axis: 8-81% affected
- Overall hypopituitarism: 37-85% of patients
- Panhypopituitarism: 6-29% of patients
- Diabetes insipidus: only 7% (uncommon finding)