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 with pituitary adenomas 1, 5.
Additional Baseline Tests
Electrolytes and renal function: Essential for perioperative management and to assess for diabetes insipidus, though this occurs in only approximately 7% of cases at presentation 2, 1.
Glucose and HbA1c: Recommended for metabolic assessment, particularly in patients with suspected Cushing disease 6.
Hierarchy of Hormone Deficiencies
The prevalence of hypopituitarism in nonfunctioning pituitary adenomas ranges from 37-85%, with specific axis involvement occurring in predictable patterns 1:
- 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 most common (17-62% of patients) 1, 5
- Thyroid axis: Least commonly affected (8-81% of patients) 1, 5
- Panhypopituitarism: Occurs in 6-29% of patients 1, 5
Special Considerations for Functioning Adenomas
Cushing Disease (ACTH-secreting)
If Cushing syndrome is suspected based on clinical features (obesity, hypertension, diabetes), perform 1:
- 24-hour urinary free cortisol (3 collections): Diagnostic cut-off >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) after 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
TSH-secreting Adenomas
These rare tumors (0.5-2% of adenomas) require 7, 8:
- TSH with free T4 and free T3: Diagnostic criterion is normal or elevated TSH with elevated free T4 and free T3 7
- Recognition that 86% of TSH-staining tumors are plurihormonal and may co-secrete GH and/or prolactin 7, 8
Critical Clinical Pitfalls
Never start thyroid hormone replacement before ensuring adequate cortisol replacement in patients with both deficiencies, as this can precipitate adrenal crisis 2, 6.
Do not rely on TSH alone to guide thyroid replacement in central hypothyroidism; free T4 is the primary monitoring parameter 5, 6.
Routine biomarker testing (alpha-subunit, chromogranin A) or genetic testing is not recommended for sporadic adenomas unless familial syndrome is suspected 1, 2.
Genetic assessment should be offered to all children and adolescents with pituitary adenomas, particularly those with GH or prolactin excess, due to high prevalence of genetic abnormalities 1, 5.
Coordination of Care
Endocrinology consultation is necessary for interpretation of pituitary hormone testing, particularly when dynamic testing may be needed in selected cases 2. Patients with macroadenomas compressing the optic chiasm require formal ophthalmologic evaluation with visual field testing 4.