Investigations for Suspected Hypopituitarism
All patients with suspected hypopituitarism require comprehensive evaluation of all anterior pituitary hormone axes through morning baseline hormone measurements and MRI of the sella with dedicated pituitary protocol, as hypopituitarism affects 37-85% of patients with pituitary disorders and panhypopituitarism occurs in 6-29% of cases. 1
Initial Laboratory Evaluation
Morning Baseline Hormone Panel (Fasting, 8-9 AM)
Obtain the following baseline measurements simultaneously 1:
- Thyroid axis: TSH and free T4 1
- Adrenal axis: ACTH and cortisol 1
- Gonadal axis:
- Growth hormone axis: IGF-1 (insulin-like growth factor 1) 1
- Prolactin: To rule out hypersecretion that might not be clinically suspected 1
- Metabolic parameters: Glucose and HbA1c 1
Dynamic Stimulation Tests (When Indicated)
Perform these tests BEFORE administering any steroids to avoid interference with results 1:
- 1 mcg cosyntropin stimulation test: Required when baseline morning cortisol levels are equivocal (typically <3 mcg/dL suggests deficiency, >15 mcg/dL excludes it, but 3-15 mcg/dL requires dynamic testing) 1
- Growth hormone stimulation testing: Not needed if patient has 3 or more pituitary hormone deficiencies, as GH deficiency is virtually certain in this scenario 1
Imaging Studies
MRI Sella (First-Line Imaging)
MRI with dedicated pituitary protocol is the gold standard initial imaging study 2, 1:
- High-resolution pituitary cuts with thin sections 2
- Can be performed without IV contrast for diagnosis 2
- Essential for detecting microadenomas, macroadenomas, empty sella, craniopharyngiomas, Rathke cleft cysts, inflammatory lesions, and metastases 2
- Approximately 30% of patients with empty sella demonstrate hypopituitarism upon testing 2, 1
CT Sella (Not Recommended as First-Line)
CT is insensitive compared to MRI and should not be the initial imaging test 2:
- Only useful for detecting bone-destructive lesions or larger macroadenomas 2
- May be used for preoperative planning to assess sphenoid sinus anatomy 2
Diagnostic Interpretation Patterns
Recognizing Central vs. Primary Hormone Deficiency
The pattern of hormone abnormalities distinguishes hypopituitarism from primary gland failure 1:
- Central hypothyroidism: Low free T4 with low or inappropriately normal TSH 1
- Central adrenal insufficiency: Low cortisol with low or inappropriately normal ACTH 1
- Hypogonadotropic hypogonadism: Low testosterone/estradiol with low or inappropriately normal FSH and LH 1
Hierarchy of Pituitary Axis Involvement
The GH axis is most commonly affected (61-100% of patients), followed by gonadal axis (36-96%), adrenal axis (17-62%), and thyroid axis (8-81%) 1. Diabetes insipidus is uncommon, occurring in only 7% of patients at presentation 1.
Additional Investigations in Specific Scenarios
When Pituitary Imaging is Normal
Screen for hemochromatosis with iron studies (serum iron, ferritin, transferrin saturation) in all patients with hypopituitarism and normal pituitary imaging 3:
- Genetic testing for C282Y mutation if iron studies are abnormal 3
- This may lead to reversal of hypopituitarism and prevent systemic complications 3
Pediatric and Young Adult Patients
Offer genetic assessment to all children and young people with pituitary adenomas or growth hormone/prolactin excess 1:
- Next-generation sequencing of genes involved in pituitary development 4
- Array-based comparative genomic hybridization 4
Critical Management Pitfall
If both adrenal insufficiency and hypothyroidism are present, always start glucocorticoid replacement BEFORE thyroid hormone replacement to avoid precipitating an adrenal crisis 1, 5. Verify adequate cortisol replacement is established before initiating any other hormone therapy 6.
Monitoring Schedule After Initial Diagnosis
For confirmed hypopituitarism, establish the following monitoring protocol 1: