Pituitary Workup
All patients with suspected pituitary disorders require comprehensive hormonal evaluation including prolactin, IGF-1, free T4, TSH, morning cortisol, ACTH, LH, FSH, and sex steroids (testosterone in men, estradiol in premenopausal women), combined with dedicated pituitary MRI without and with contrast. 1
Hormonal Assessment
Screening for Hormone Hypersecretion
Screen all patients regardless of symptoms:
- Prolactin: Essential first test—hyperprolactinemia occurs in 6-18% of incidentalomas and responds to oral dopamine agonists 2, 1
- IGF-1: Mandatory screening for growth hormone excess, even without acromegaly symptoms—GH-secreting tumors are curable surgically when detected early 2
- Cushing's screening: Perform only if clinical suspicion exists (diabetes, hypertension, obesity, osteoporosis) due to high false-positive rates 2
For Cushing's evaluation when indicated, use one high-accuracy initial test: 24-hour urine free cortisol (at least 2 measurements), late-night salivary cortisol (2 measurements), 1-mg overnight dexamethasone suppression test, or 2-mg 48-hour dexamethasone suppression test 3. Never use random cortisol or plasma ACTH levels for screening 3.
Evaluation for Hypopituitarism
Baseline testing for all patients with sellar lesions (hypopituitarism occurs in 37-85% of nonfunctioning adenomas) 4:
- Morning cortisol and ACTH (before 10 AM, after overnight fast)
- Free T4 and TSH
- LH, FSH, testosterone (men), estradiol (women)—skip gonadal testing in premenopausal women with regular menses 1
- IGF-1 for growth hormone deficiency assessment
Dynamic testing indications 5:
- Adrenal axis: If morning cortisol 3-15 µg/dL, perform corticotropin stimulation test—peak cortisol <18.1 µg/dL at 30 or 60 minutes confirms adrenal insufficiency. Cortisol <3 µg/dL confirms deficiency; >15 µg/dL excludes it 5
- Growth hormone: Single GH measurements are useless—perform GH stimulation testing with BMI-adjusted cutoffs. Skip testing if patient has clear GH deficiency features plus 3 other documented pituitary deficits 5
- Avoid TRH and GnRH testing—they provide no useful diagnostic information 5
Central Hypothyroidism Specifics
Free T4 below reference range with low, normal, or mildly elevated TSH in pituitary disease confirms central hypothyroidism. For low-normal free T4 with symptoms, either start levothyroxine or monitor—treat if free T4 drops ≥20% 5.
Central Diabetes Insipidus
In polyuria (>50 mL/kg/24h or 3.5 L/day in 70-kg person), simultaneously measure serum and urine osmolarity. High serum osmolarity (>295 mOsmol/L) should produce urine osmolarity ~600 mOsmol/L (urine/plasma ratio ≥2) with negative glucose dipstick 5.
Hypogonadism Assessment
Males: Measure testosterone, FSH, LH, and prolactin before 10 AM after overnight fast, excluding acute illness 5.
Females: With oligomenorrhea/amenorrhea, measure estradiol, FSH, LH—exclude pregnancy, hyperprolactinemia, hyperandrogenism, and thyroid disease. In postmenopausal women, absence of elevated FSH/LH (off hormone replacement) confirms gonadotrope dysfunction 5.
Imaging
MRI sella without and with gadolinium contrast is the gold standard for all suspected pituitary disorders 6. Contrast enhancement increases conspicuity of microadenomas (typically hypoenhancing) and is essential for characterizing lesions 6. Use high-resolution pituitary protocols with 1-2 mm slices through the sellar/suprasellar region 7.
Non-contrast MRI alone is acceptable but provides less diagnostic detail for small lesions 6. CT has no role in initial evaluation except when MRI is contraindicated 7.
Critical Pitfalls
Replace adrenal insufficiency BEFORE thyroid hormone—starting levothyroxine without cortisol replacement precipitates adrenal crisis 5, 8.
Mild prolactin elevation (typically <200 ng/mL) may indicate stalk compression from non-prolactinoma rather than true prolactinoma—these tumors won't shrink with dopamine agonists and require continued imaging surveillance 2.
Test hypothalamic-pituitary-adrenal axis ≥18-24 hours after last hydrocortisone dose (longer for synthetic glucocorticoids) to avoid false results 5.
Hypopituitarism develops in 37-85% of macroadenomas, with GH axis most commonly affected (61-100%), followed by hypogonadism (36-96%), adrenal insufficiency (17-62%), and hypothyroidism (8-81%) 4. Diabetes insipidus is rare (7%) 4.
Follow-up Timing
Repeat hormonal evaluation at 1-2 years for all microadenomas and macroadenomas, or earlier with new symptoms—new hypopituitarism can develop without tumor growth 1. Always reassess hormones in enlarging adenomas 1.