What is the approach to testing for hypopituitarism?

Diagnostic Approach to Hypopituitarism

The diagnostic approach to hypopituitarism requires comprehensive hormonal testing of all anterior pituitary axes, preferably with morning blood samples, along with MRI imaging of the sella turcica with pituitary cuts to identify structural abnormalities. 1

Initial Evaluation

Clinical Assessment

• Evaluate for symptoms of specific hormonal deficiencies:
  • Adrenal insufficiency: fatigue, weakness, weight loss, hypotension
  • Hypothyroidism: fatigue, cold intolerance, weight gain, constipation
  • Hypogonadism: decreased libido, erectile dysfunction in men; amenorrhea in women
  • Growth hormone deficiency: decreased energy, increased fat mass
  • Diabetes insipidus (rare in hypopituitarism): polyuria, polydipsia

First-Line Laboratory Testing

1. Morning hormone levels (preferably around 8 AM) 1:

   • Thyroid function: TSH and free T4 (central hypothyroidism presents with low/normal TSH and low free T4)
   • Adrenal function: ACTH and cortisol
   • Gonadal function:
     • Men: LH, FSH, testosterone
     • Women: LH, FSH, estradiol (interpret based on menstrual cycle)
   • Prolactin level
   • IGF-1 (as a screening test for GH deficiency)

2. Basic metabolic panel to assess for electrolyte abnormalities and glycemic control

Confirmatory Dynamic Testing

For equivocal basal hormone results or to diagnose partial deficiencies, dynamic stimulation tests are often required 1, 2:

1. Adrenal axis:

   • 1 mcg cosyntropin (ACTH) stimulation test
   • Insulin tolerance test (gold standard but more invasive)

2. Growth hormone axis:

   • Insulin tolerance test
   • Glucagon stimulation test
   • GHRH-arginine test

3. Gonadal axis:

   • GnRH stimulation test (less commonly used)

4. Thyroid axis:

   • TRH stimulation test (rarely used clinically)

Imaging Studies

• MRI of the sella turcica with pituitary cuts is essential to identify structural abnormalities such as pituitary adenomas, empty sella, infiltrative diseases, or evidence of pituitary apoplexy 1
• Look for specific MRI abnormalities such as stalk thickening, suprasellar convexity, heterogeneous enhancement, and increased height of the gland 1

Diagnostic Criteria for Hypophysitis

Proposed confirmation criteria for hypophysitis (a common cause of hypopituitarism) include 1:

• ≥1 pituitary hormone deficiency (TSH or ACTH deficiency required) combined with an MRI abnormality, OR
• ≥2 pituitary hormone deficiencies (TSH or ACTH deficiency required) in the presence of headache and other symptoms

Special Considerations

1. Testing sequence: Complete all hormone testing prior to initiating steroid therapy, as steroids can affect results of other tests 1, 2

2. Prevalence of deficiencies: The most commonly affected pituitary axis is the GH axis (61-100%), followed by hypogonadism (36-96%), adrenal insufficiency (17-62%), and central hypothyroidism (8-81%) 1

3. Timing of testing: In patients with suspected hypopituitarism, consider routine monitoring with early morning ACTH and cortisol levels (every month for 6 months, then every 3 months for 6 months, then every 6 months for 1 year) 1

4. Diabetes insipidus: Very uncommon in hypopituitarism unless associated with pituitary apoplexy; its presence suggests alternative diagnoses such as craniopharyngioma or histiocytosis 1

Pitfalls to Avoid

1. Missing adrenal insufficiency: Always assess adrenal function before initiating thyroid hormone replacement to prevent precipitating an adrenal crisis 1, 2

2. Misinterpreting thyroid function tests: Central hypothyroidism presents with low/normal TSH and low free T4, unlike primary hypothyroidism 1

3. Overlooking hyperprolactinemia: Stalk compression from macroadenomas can cause mild hyperprolactinemia (usually <2,000 mU/l), which should not be confused with a prolactinoma 1

4. Incomplete testing: Failure to assess all pituitary axes can lead to missed diagnoses, as hypopituitarism often affects multiple hormones 1, 2

By following this systematic approach to testing for hypopituitarism, clinicians can accurately diagnose the condition and appropriately manage hormone deficiencies to improve patient outcomes.