What diagnostic tests are used to evaluate a patient with suspected pituitary gland issues?

Diagnostic Tests for Pituitary Gland Issues

All patients with suspected pituitary pathology require comprehensive endocrine evaluation of all anterior pituitary axes (TSH, ACTH/cortisol, prolactin, IGF-1, and gonadotropins) combined with MRI of the sella with pituitary cuts, as routine testing reveals hormone deficiencies beyond clinical suspicion in 37-85% of cases. 1

Initial Laboratory Evaluation

Mandatory Hormone Testing for All Patients

• Morning (8 AM) paired measurement of serum cortisol and plasma ACTH to assess adrenal axis function 1, 2
• TSH and free T4 to evaluate thyroid function 1
• Prolactin level to rule out hypersecretion that may not be clinically suspected, as prolactinomas account for 32-66% of pituitary adenomas 1, 3
• IGF-1 level to exclude clinically silent growth hormone-secreting tumors, as 45.9% of nonfunctioning adenomas show GH immunostaining despite lack of clinical acromegaly 1
• Gonadal hormones: testosterone in men, estradiol in women, plus FSH and LH to assess for hypogonadism 1
• Baseline metabolic panel including glucose, sodium, and potassium 1

Prevalence of Hormone Deficiencies

The most commonly affected axes in patients with pituitary adenomas are:

• GH deficiency: 61-100% of patients 1
• Central hypogonadism: 36-96% of patients 1
• Adrenal insufficiency: 17-62% of patients 1
• Central hypothyroidism: 8-81% of patients 1
• Diabetes insipidus: only 7% at presentation 1

Confirmatory Testing When Initial Results Are Equivocal

ACTH Stimulation Test (Cosyntropin/Synacthen Test)

When morning cortisol is neither clearly normal (>550 nmol/L or >18-20 μg/dL) nor clearly diagnostic (<250 nmol/L or <9 μg/dL), perform the cosyntropin stimulation test to definitively rule in or rule out adrenal insufficiency. 2, 4

Test protocol:

• Administer 0.25 mg (250 mcg) cosyntropin intramuscularly or intravenously 1, 2
• Measure serum cortisol at baseline, 30 minutes, and 60 minutes post-administration 2, 4
• Peak cortisol <500 nmol/L (<18 μg/dL) is diagnostic of adrenal insufficiency 1, 2, 4
• Peak cortisol >550 nmol/L (>18-20 μg/dL) is normal and excludes adrenal insufficiency 2

Imaging Studies

MRI of the Sella (First-Line Imaging)

MRI with pituitary cuts is the gold standard for evaluating pituitary pathology, as it provides superior soft tissue characterization compared to CT and can detect microadenomas, assess for mass effect on the optic chiasm, and evaluate for pituitary enlargement, stalk thickening, and heterogeneous enhancement. 1

• Obtain MRI with gadolinium contrast to characterize lesions and assess for cavernous sinus invasion 1
• Thin-section acquisition with multiplanar reformatting is essential for surgical planning 1
• MRI abnormalities in hypophysitis include stalk thickening, suprasellar convexity, heterogeneous enhancement, and increased gland height 1

CT of the Sella (Limited Role)

• CT is insensitive compared to MRI and should not be considered first-line imaging 1
• CT is useful for detecting bone-destructive lesions and assessing sphenoid sinus anatomy prior to transsphenoidal surgery 1
• Dual-energy CT may discriminate larger pituitary masses from meningiomas 1

Additional Testing Based on Clinical Presentation

For Suspected Cushing Disease (ACTH-Secreting Adenomas)

• Late-night salivary cortisol is the best screening test for hypercortisolism 3
• Petrosal sinus sampling for ACTH may be necessary to distinguish pituitary from ectopic ACTH sources 3

For Suspected Acromegaly (GH-Secreting Tumors)

• Elevated IGF-1 levels combined with failure to suppress GH to <1 μg/L during oral glucose tolerance test confirms the diagnosis 3

For Suspected Hypophysitis (Immune Checkpoint Inhibitor-Related)

When routine thyroid testing shows low TSH with low free T4 (suggesting central etiology), immediately evaluate for hypophysitis with:

• Morning (8 AM) thyroid function (TSH, free T4) 1
• Morning adrenal function (ACTH, cortisol) 1
• Gonadal hormones (testosterone in men, estradiol in women, FSH, LH) 1
• MRI of the sella with pituitary cuts before administering steroids 1

Critical Pitfalls to Avoid

Preoperative Hormone Replacement

Replace adrenal insufficiency and significant hypothyroidism preoperatively before any surgical intervention. 1 When treating both conditions simultaneously, always start steroids before thyroid hormone to avoid precipitating adrenal crisis. 1, 2

Distinguishing Physiologic Pituitary Hypertrophy from Tumors

• In young nulliparous women (15-27 years old) with pituitary height >9 mm but normal hormone levels and homogeneous MRI signal, consider physiologic pituitary hypertrophy rather than tumor 5
• Serial MRI surveillance shows stable size over years without tumor formation 5

Testing Patients on Corticosteroids

Never attempt diagnostic cortisol testing in patients actively taking corticosteroids (including prednisone, dexamethasone, or inhaled fluticasone), as exogenous steroids suppress the HPA axis and cause false-positive results. 2 Wait until corticosteroid treatment is discontinued with sufficient washout time before performing definitive testing 2

Emergency Situations

If adrenal crisis is suspected (severe hypotension, altered mental status, severe vomiting), immediately administer IV hydrocortisone 100 mg plus 0.9% saline infusion at 1 L/hour—never delay treatment for diagnostic procedures. 1, 2, 4

Ophthalmologic Evaluation

All patients with macroadenomas (≥10 mm) or tumors compressing the optic chiasm require formal visual field testing by an ophthalmologist, as visual field defects occur in 18-78% of patients with macroadenomas 6