Which laboratory tests should be ordered to evaluate a suspected pituitary disorder?

Laboratory Evaluation for Suspected Pituitary Dysfunction

All patients with suspected pituitary disorders require comprehensive baseline evaluation of all anterior pituitary hormone axes, as hypopituitarism affects 37-85% of patients with pituitary pathology. 1, 2

Initial Baseline Laboratory Panel

The following tests should be obtained as morning (8-9 AM) fasting samples to evaluate all pituitary axes:

Thyroid Axis

• TSH and free T4 to assess for central hypothyroidism 1, 2, 3
• Central hypothyroidism presents with low free T4 accompanied by low or inappropriately normal TSH, unlike primary hypothyroidism where TSH is elevated 2, 3

Adrenal Axis

• Morning (8 AM) cortisol and ACTH to evaluate for secondary adrenal insufficiency 1, 2, 3
• Central adrenal insufficiency shows low cortisol with low or normal ACTH 2, 3
• If morning cortisol is equivocal (between 3-15 mcg/dL), perform a 1 mcg cosyntropin stimulation test 2

Gonadal Axis

• In males: testosterone, LH, and FSH 2, 3, 4
• In premenopausal females: estradiol, LH, FSH 2, 3
• Hypogonadotropic hypogonadism presents with low sex hormones accompanied by low or inappropriately normal gonadotropins 2, 3

Growth Hormone Axis

• IGF-1 (insulin-like growth factor 1) as the screening test for both GH deficiency and excess 1, 2, 3
• GH deficiency is the most commonly affected axis in pituitary disorders, occurring in 61-100% of patients with nonfunctioning adenomas 1, 2

Prolactin

• Serum prolactin should be routinely measured in all patients to detect hypersecretion that may not be clinically apparent 1, 2
• Hyperprolactinemia occurs in 25-65% of patients with nonfunctioning pituitary adenomas, with mean levels around 39 ng/mL 1

Metabolic Parameters

• Glucose and HbA1c to assess glycemic control 2, 3
• Electrolytes to evaluate for potential SIADH or diabetes insipidus 1

Prevalence of Specific Deficiencies

Understanding the frequency of each axis involvement helps prioritize evaluation:

• Growth hormone axis: 61-100% affected (most common) 1, 2
• Gonadal axis: 36-96% affected 1, 2
• Adrenal axis: 17-62% affected 1, 2
• Thyroid axis: 8-81% affected 1, 2
• Panhypopituitarism: 6-29% of patients 1, 5
• Diabetes insipidus: Only 7% at presentation (uncommon) 1, 2

Dynamic Testing Considerations

Dynamic stimulation tests are reserved for equivocal baseline results:

• ACTH stimulation test (1 mcg cosyntropin): when baseline morning cortisol is 3-15 mcg/dL 2
• GH stimulation testing: valuable for confirming GH deficiency, though patients with 3 or more pituitary hormone deficiencies likely have GH deficiency and may not require dynamic testing 2
• All dynamic tests must be performed before initiating steroid replacement to avoid interference with results 2

Imaging Recommendation

MRI of the sella with dedicated pituitary cuts (with and without contrast) should be obtained in all patients with confirmed hormonal deficiencies or suspected structural pituitary disease. 1, 2, 5

MRI is superior to CT for detecting pituitary pathology and should include evaluation for:

• Pituitary adenomas (micro- or macroadenomas) 1, 4
• Empty sella syndrome 1, 2
• Hypophysitis or inflammatory processes 1
• Mass effect on optic chiasm 1

Critical Clinical Pitfalls to Avoid

Never initiate thyroid hormone replacement before ensuring adequate cortisol replacement or correction of adrenal insufficiency, as this can precipitate life-threatening adrenal crisis. 1, 2, 3

Additional important considerations:

• Do not rely on TSH alone to guide thyroid replacement in central hypothyroidism—use free T4 levels targeting the upper half of the reference range 1, 2
• Ensure all patients with confirmed adrenal insufficiency receive education on stress dosing, emergency injectable steroids, and obtain a medical alert bracelet 1, 2, 3
• Genetic testing should be offered to children and young adults with pituitary adenomas, particularly those with GH or prolactin excess 2

When to Refer to Endocrinology

Early endocrinology consultation is appropriate for all patients with confirmed pituitary hormone deficiencies to guide:

• Interpretation of equivocal results 1, 2
• Initiation and titration of hormone replacement therapy 1, 3
• Education on emergency management of adrenal crisis 1, 2
• Preoperative optimization if surgery is planned 1, 2