Hormone Assays for Suspected Pituitary Adenoma
All patients with suspected pituitary adenoma require comprehensive anterior pituitary axis testing to assess for both hormone hypersecretion and hypopituitarism, including prolactin, IGF-1, thyroid function (TSH and free T4), adrenal function (morning cortisol and ACTH), and gonadal hormones (testosterone/estradiol, LH, FSH). 1, 2
Essential Baseline Hormone Panel
Mandatory Tests for All Patients
Prolactin (PRL): Must be measured in every patient to rule out prolactinoma, which accounts for 32-66% of all pituitary adenomas 3, 4. Even in nonfunctioning adenomas, hyperprolactinemia occurs in 25-65% of patients, with mean levels around 39 ng/mL 1.
Insulin-like Growth Factor 1 (IGF-1): Required to detect growth hormone excess, as up to 46% of apparently nonfunctioning adenomas show GH immunostaining despite lacking clinical acromegaly features 2. Growth hormone-secreting tumors account for 8-16% of adenomas 3.
Thyroid axis: Measure TSH and free T4 to detect central hypothyroidism, which occurs in 8-81% of patients with pituitary adenomas 1, 2. Central hypothyroidism presents with low free T4 and low or inappropriately normal TSH, unlike primary hypothyroidism where TSH is elevated 5.
Adrenal axis: Obtain morning (08:00-09:00h) cortisol and ACTH to assess for adrenal insufficiency, present in 17-62% of patients 1, 2. This is critical as preoperative cortisol replacement is mandatory before any surgical intervention 2.
Gonadal axis: Check testosterone (in men), estradiol (in premenopausal women), LH, and FSH to detect hypogonadism, which affects 36-96% of patients—making it one of the most commonly affected axes 1, 5.
Additional Baseline Tests
Electrolytes and renal function: Essential for perioperative management and to assess for diabetes insipidus, though this occurs in only ~7% of cases at presentation 2, 1.
Glucose and HbA1c: Particularly important when evaluating for Cushing disease or acromegaly 6.
Hierarchy of Hormone Deficiencies
The prevalence of hypopituitarism in pituitary adenomas is substantial, affecting 37-85% of patients overall 1, 5. Understanding the frequency helps prioritize clinical suspicion:
- Growth hormone axis: Most commonly affected (61-100% of patients) 1, 5
- Gonadal axis: Second most common (36-96% of patients) 1, 5
- Adrenal axis: Third (17-62% of patients) 1, 5
- Thyroid axis: Fourth (8-81% of patients) 1, 5
- Panhypopituitarism: Occurs in 6-29% of patients 1, 5
Special Considerations for Functioning Adenomas
If Cushing Disease is Suspected
When clinical features suggest ACTH excess, perform:
- 24-hour urinary free cortisol (3 collections): Diagnostic if >193 nmol/24h (>70 μg/m²), with 89% sensitivity and 100% specificity 1
- Late-night salivary cortisol: Best screening test with 95% sensitivity and 100% specificity 1, 3
- Low-dose dexamethasone suppression test: Serum cortisol ≥50 nmol/L (≥1.8 μg/dL) at 48 hours has 95% sensitivity 1
- Morning plasma ACTH: Levels >1.1 pmol/L (>5 ng/L) support pituitary origin with 68% sensitivity and 100% specificity 1
- CRH stimulation test: ≥20% increase in cortisol from baseline supports Cushing disease with 74-100% sensitivity 1
If TSH-Secreting Adenoma is Suspected
These rare tumors (0.5-2% of adenomas) present with elevated or inappropriately normal TSH combined with elevated free T4 and free T3 7. This distinguishes them from primary hyperthyroidism where TSH is suppressed. Most TSH-staining adenomas (84%) are actually silent and plurihormonal, commonly co-secreting growth hormone 8.
If Acromegaly is Suspected
- IGF-1: Elevated levels confirm growth hormone excess 3, 4
- Growth hormone: Measured after glucose load; failure to suppress confirms autonomous secretion 9
Critical Preoperative Requirements
Before any surgical intervention, patients with documented adrenal insufficiency and significant hypothyroidism must receive hormone replacement. 2, 5 This is a mandatory safety measure, not optional. When both deficiencies exist, always initiate glucocorticoid replacement before thyroid hormone to avoid precipitating adrenal crisis 5, 6.
Tests NOT Routinely Recommended
- Routine biomarker testing (alpha-subunit, chromogranin A): No evidence supports routine use in sporadic adenomas 1
- Genetic testing: Not recommended unless familial syndrome is suspected, particularly in children and adolescents with growth hormone or prolactin excess 1, 2, 5
Coordination with Endocrinology
Interpretation of pituitary hormone testing requires endocrine expertise, particularly for dynamic testing that may be needed in selected cases 2. The pattern of central hormone deficiencies differs from primary endocrine disorders: central hypothyroidism shows low free T4 with low/normal TSH, central adrenal insufficiency shows low cortisol with low/normal ACTH, and hypogonadotropic hypogonadism shows low sex steroids with low/normal gonadotropins 5, 6.