How do I diagnose and rule out pituitary adenoma?

Diagnosing and Ruling Out Pituitary Adenoma

To diagnose or rule out pituitary adenoma, obtain a pre-contrast and post-contrast-enhanced thin-sliced pituitary MRI combined with targeted hormone measurements based on clinical presentation, followed by complete endocrine evaluation to assess both hormone hypersecretion and hypopituitarism. 1

Initial Clinical Assessment

Key Presenting Features to Identify

Suspect pituitary adenoma when patients present with:

• Hormone excess syndromes: Amenorrhea, galactorrhea, infertility, or loss of libido (prolactinoma); enlargement of hands, feet, lips, tongue, or nose (growth hormone excess); weight gain, hypertension, diabetes, central obesity (Cushing disease); hyperthyroidism (TSH-secreting adenoma) 2, 3, 4

• Mass effect symptoms: Headaches (17-75% of macroadenomas), visual field defects (18-78% of macroadenomas), or visual acuity changes 4, 1

• Hypopituitarism symptoms: Fatigue, cold intolerance, decreased libido, or growth/pubertal arrest in children 4, 5

• Incidental findings: Pituitary lesions discovered on imaging performed for unrelated reasons 6

Diagnostic Algorithm

Step 1: Imaging

Obtain pituitary MRI with gadolinium contrast using thin slices (≤3mm) through the sella turcica. 1 This provides detailed anatomical delineation and determines:

• Tumor size: microadenoma (<10mm) vs macroadenoma (≥10mm) 3, 4
• Extent of invasion or compression of surrounding structures 1
• Relationship to optic chiasm 1

Step 2: Hormone Evaluation

Measure specific hormones based on clinical presentation:

• For suspected prolactinoma: Serum prolactin level 5, 3

  • Prolactin >200 ng/mL strongly suggests prolactinoma
  • Mild elevation (25-100 ng/mL) may indicate stalk compression from non-functioning adenoma rather than true prolactinoma 1

• For suspected growth hormone excess: Serum IGF-1 and random GH levels 5, 3

  • IGF-1 elevated for age and sex
  • Failure of GH suppression during oral glucose tolerance test confirms diagnosis 3

• For suspected Cushing disease: Late-night salivary cortisol as best screening test 3

  • If positive, proceed to 24-hour urinary free cortisol and low-dose dexamethasone suppression test
  • Petrosal sinus sampling for ACTH may be necessary to distinguish pituitary from ectopic source 3

• For suspected TSH-secreting adenoma: TSH with free T4 and T3 2

  • Elevated or inappropriately normal TSH with elevated thyroid hormones

Step 3: Complete Pituitary Function Assessment

Evaluate all pituitary axes regardless of presenting symptoms, as hypopituitarism occurs in 34-89% of patients with macroadenomas: 4, 1

• Thyroid function (TSH, free T4)
• Adrenal function (morning cortisol, ACTH)
• Gonadal function (LH, FSH, testosterone in men, estradiol in women)
• Prolactin (even if not suspected clinically)
• IGF-1 and GH 2, 4

Step 4: Visual Assessment

Perform formal visual field testing and visual acuity assessment in all patients with macroadenomas or tumors approaching the optic chiasm. 1, 5 This should be done by an ophthalmologist, as visual compromise occurs in 18-78% of macroadenomas 4.

Step 5: Genetic Evaluation (When Indicated)

Offer genetic assessment to: 5

• All children and young people with pituitary adenomas (high prevalence of genetic disease) 5, 1
• Any patient with growth hormone or prolactin-secreting tumors in childhood/adolescence 5
• Patients with young-onset disease (<30 years) or family history 5
• Patients with syndromic features (café-au-lait spots, cardiac myxomas, multiple endocrine tumors) 5

Test for: AIP, MEN1, CDKN1B, PRKAR1A, GPR101, SDHx, MAX mutations 5

Step 6: Histopathological Confirmation (If Surgery Performed)

When surgical resection is performed, obtain histopathological assessment including: 5

• Immunostaining for all pituitary hormones
• Ki-67 proliferation index (≥3% combined with invasion predicts 25% recurrence) 5, 7
• Cytokeratin staining
• Additional transcription factors if hormone staining is negative or unusual 5, 7

Critical Pitfalls to Avoid

Stalk effect misinterpretation: Mild hyperprolactinemia (25-100 ng/mL) with a macroadenoma usually indicates stalk compression from a non-functioning adenoma, not a prolactinoma. True prolactinomas typically have prolactin >200 ng/mL. 1

Incomplete hormone evaluation: Always assess all pituitary axes even when one hormone excess is obvious, as multiple hormone abnormalities are common and hypopituitarism frequently coexists. 4, 1

Delayed visual assessment: Visual field defects can be irreversible if not identified early. Formal ophthalmologic evaluation should not be delayed in patients with macroadenomas. 1, 4

Missing genetic syndromes: Particularly in young patients, failure to recognize genetic syndromes means missing opportunities for family screening and surveillance for other manifestations (pancreatic tumors in MEN1, cardiac myxomas in Carney complex). 5