How to test for hypopituitarism (underactive pituitary gland)?

Testing for Hypopituitarism

Routine endocrine evaluation of all anterior pituitary axes is essential for diagnosing hypopituitarism, as this comprehensive approach reveals deficits that may not be clinically apparent and helps determine appropriate replacement therapy. 1

Diagnostic Approach

Initial Laboratory Assessment

1. Thyroid Function:

   • TSH and free T4 (central hypothyroidism shows low/normal TSH with low free T4)
   • TSH has high sensitivity (98%) and specificity (92%) for thyroid dysfunction 2

2. Adrenal Function:

   • Morning cortisol level
   • ACTH stimulation test (required for definitive diagnosis of central adrenal insufficiency)
   • Critical to diagnose as this deficiency is associated with excess mortality 3

3. Gonadal Function:

   • Males: Testosterone, LH, FSH
   • Females: Estradiol, LH, FSH (interpret based on menstrual status)

4. Growth Hormone Axis:

   • IGF-1 level (screening)
   • GH stimulation test (required for definitive diagnosis)
   • Most commonly affected axis (61-100% of patients with NFPAs) 1

5. Prolactin Level:

   • Essential to differentiate from prolactinoma
   • Hyperprolactinemia occurs in 25-65% of NFPA patients 1

Dynamic Testing

Dynamic stimulation tests are necessary for:

• Equivocal basal hormone results
• Diagnosing partial hormone deficiencies
• Confirming ACTH and GH deficiencies 4

Common Dynamic Tests:

• ACTH deficiency: Insulin tolerance test, glucagon stimulation test, or low-dose/standard ACTH stimulation test
• GH deficiency: Insulin tolerance test, GHRH-arginine test, or glucagon stimulation test
• Diabetes insipidus: Water deprivation test (for posterior pituitary function)

Prevalence and Clinical Significance

The prevalence of hypopituitarism in patients with nonfunctioning pituitary adenomas (NFPAs) is high:

• Partial hypopituitarism: 37-85% of patients
• Panhypopituitarism: 6-29% of patients 1

Deficiency prevalence by axis:

• Growth hormone deficiency: 61-100%
• Hypogonadism: 36-96%
• Adrenal insufficiency: 17-62%
• Hypothyroidism: 8-81%
• Diabetes insipidus: Uncommon (7% in NFPAs) 1

Important Clinical Considerations

• Timing of Testing: Morning samples are essential for accurate assessment of cortisol and testosterone
• Medication Effects: Assess and account for medications that may affect test results
• Pre-existing Conditions: Consider autoimmune conditions that may co-exist with hypopituitarism
• Replacement Priority: If acute hypopituitarism is diagnosed, cortisol deficiency should be replaced first before thyroid hormone to avoid precipitating adrenal crisis 3

Pitfalls to Avoid

1. Missing Central Hypothyroidism: Normal TSH with low free T4 is the hallmark of central hypothyroidism, unlike primary hypothyroidism where TSH is elevated

2. Inadequate Dynamic Testing: Single basal hormone measurements may miss partial deficiencies, particularly for GH and ACTH

3. Overlooking Hyperprolactinemia: Essential to differentiate between true prolactinoma and "stalk effect" hyperprolactinemia from NFPAs (typically <200 ng/mL) 1

4. Incomplete Axis Evaluation: Testing all axes is crucial as partial hypopituitarism is more common than panhypopituitarism

5. Failure to Reassess: Hypopituitarism can evolve over time, requiring periodic reassessment, especially after pituitary surgery or radiation 4

By systematically evaluating all pituitary hormone axes and using appropriate dynamic testing when indicated, clinicians can accurately diagnose hypopituitarism and initiate appropriate hormone replacement therapy to reduce morbidity and mortality.