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Pituitary Tumors: Complete Clinical Reference

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1. Classification

Adenoma Types and Clinical Syndromes

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2. Hormonal Tests for Each Adenoma Type

A. Prolactinoma

• Serum PRL (fasting morning level; normal <20 µg/L)
  • PRL >200 µg/L = almost certainly a prolactinoma
  • PRL 100-200 µg/L = likely microadenoma or stalk compression
  • PRL <100 µg/L = microadenoma, non-lactotrope sellar mass, or non-neoplastic cause
• Macroprolactin screen - exclude biologically inactive aggregated PRL forms (falsely elevated result)
• TSH + free T4 - exclude primary hypothyroidism (TRH stimulates PRL)
• Drug review - major cause of hyperprolactinemia

• Drugs: antipsychotics (haloperidol, risperidone, chlorpromazine), metoclopramide, methyldopa, reserpine, opiates, H2 blockers (cimetidine), SSRIs (fluoxetine), verapamil, estrogens, tricyclics
• Physiologic: pregnancy, breastfeeding, stress, chest wall stimulation
• Pathologic: hypothyroidism, renal failure, liver failure, stalk compression by any sellar mass
• Note: PRL >200 µg/L after excluding the above almost invariably indicates a prolactin-secreting adenoma - Harrison's 22E, p. 3049

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B. Acromegaly / Gigantism

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C. Cushing Disease (Corticotroph Adenoma)

Step 1 - Confirm Hypercortisolism (at least two abnormal tests required)

• Midnight plasma cortisol >7.5 µg/dL (207 nmol/L): 100% specificity (requires 48h hospitalization, IV line, patient asleep at midnight)
• 2-day LDDST: 0.5 mg dexa q6h × 2 days; failure of UFC suppression confirms Cushing syndrome
• Dexamethasone-CRH combined test: LDDST followed by 100 µg oCRH 2h later; plasma cortisol >38 nmol/L at 15 min = Cushing syndrome with 100% sensitivity and specificity vs. pseudo-Cushing

Step 2 - Locate the Source (ACTH-dependent vs. independent)

• Henry's Clinical Diagnosis, pp. 477-479; Harrison's 22E

• Central:peripheral ACTH ratio >2:1 basal or >3:1 after CRH = pituitary source (100% sensitivity and specificity)
• Ratio <1.4:1 = ectopic
• Lateralization: higher-ratio side predicts tumor side in the sella
• Invasive, technically demanding - only at experienced centers

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D. TSH-Secreting Adenoma (Thyrotropinoma)

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E. Non-Functioning Adenoma / Gonadotropinoma

• Basal FSH, LH, alpha subunit - often mildly elevated or normal
• Presents via mass effects: visual field defects, headache, hypopituitarism
• Full pituitary hormone reserve testing (see below) to detect deficiencies
• MRI sella: usually macroadenoma at presentation

• 8 AM cortisol (or ITT for definitive ACTH reserve)
• TSH + free T4
• FSH, LH, testosterone (men) / estradiol + menstrual history (women)
• IGF-1 (± GHRH-arginine or glucagon test for GH reserve)
• Serum sodium + urine/plasma osmolality (screen for diabetes insipidus)

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3. Dynamic Tests - Master Reference Table

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4. Interpretation of Investigations

Biochemical Interpretation Pearls

• PRL and tumor size correlation: In true prolactinoma, PRL level correlates with tumor size. PRL >250 µg/L usually accompanies a macroadenoma. A macroadenoma with PRL <100-150 µg/L suggests stalk compression by a non-lactotrope tumor - dopamine agonists may lower PRL but will not shrink the underlying lesion.
• Post-OGTT GH: After ultrasensitive GH assays, the normal nadir is even lower (<0.05 µg/L); about 20% of acromegalic patients show a paradoxical GH rise (not suppression) after glucose.
• Cushing syndrome vs. pseudo-Cushing: Pseudo-Cushing (depression, alcoholism, obesity, poorly controlled diabetes) causes mild UFC elevation and may fail LDDST; the midnight cortisol >7.5 µg/dL discriminates with 100% specificity; the Dexa-CRH test is definitive.
• Imaging only after biochemical diagnosis: Pituitary and adrenal incidentalomas occur in up to 10% of the population - do NOT start with imaging.
• MRI in Cushing disease: Shows adenoma in only 50-60% of cases; a negative MRI does not exclude pituitary Cushing - IPSS is needed.

Radiological Interpretation

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5. Management

A. Prolactinoma

• Cabergoline (preferred): 0.5-1.0 mg twice weekly
  • Normalizes PRL in ~80% of microadenomas; ~70% of macroadenomas shrink
  • Restores gonadal function in most; galactorrhea improves in 90%
  • MRI at 16 weeks after starting in macroadenomas (striking shrinkage possible)
  • Mass effect symptoms often improve within days of starting
  • Reduce to lowest effective maintenance dose once controlled
• Bromocriptine: 0.625-1.25 mg at bedtime, titrating to 2.5 mg TID; preferred when fertility desired (short half-life; most pregnancy safety data)
• Side effects of DAs: nausea (25%), postural hypotension, constipation, dry mouth, insomnia, nightmares; impulse control disorders in ~5%; cardiac valvulopathy only at high Parkinson doses - echocardiogram recommended before starting cabergoline
• ~20% of patients are dopamine-resistant (decreased D2 receptor numbers or post-receptor defect)

• Microadenoma cure: ~70%; macroadenoma: ~40%
• Recurrence: up to 20% in year 1; >50% long-term for macroadenomas

• Stop DAs when pregnancy confirmed
• Macroadenoma: regular visual field testing; restart DA or consider surgery if tumor grows
• ~5% of microadenomas and 15-30% of macroadenomas grow during pregnancy

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B. Acromegaly

• Microadenoma cure: 80-90%; macroadenoma: <30% (but GH substantially reduced)
• GH normalization post-op = cure

• NOT effective as primary therapy (GH normalization takes 5-15 years)
• Adjunct for residual/recurrent tumor after surgery + medical therapy
• Stereotactic radiosurgery (Gamma Knife): faster than conventional
• Major risk: late hypopituitarism

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C. Cushing Disease

• Remission in ~70-80% of microadenomas (post-op morning cortisol <2 µg/dL)
• Post-operative adrenal insufficiency is expected and desired - confirms remission
• Hydrocortisone replacement until HPA recovery (6-18 months)

• Repeat TSS (if identifiable residual/recurrent tumor)
• Pituitary radiotherapy (stereotactic or conventional): adjunct; months-years for full effect; high hypopituitarism risk long-term
• Bilateral adrenalectomy: immediate cure of hypercortisolism; requires lifelong mineralocorticoid + glucocorticoid replacement; Nelson syndrome risk (rapid ACTH tumor growth + severe hyperpigmentation in up to 25%) - pituitary radiotherapy recommended before or after adrenalectomy
• Medical therapy (bridging to surgery, or adjunct):

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D. Non-Functioning Adenoma

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E. Thyrotropinoma

• TSS first-line
• SRLs (octreotide, lanreotide) highly effective pre-operatively and as adjunct; normalize TSH and thyroid hormones in >90%
• Antithyroid drugs as adjunct for pre-op euthyroid control

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6. Follow-Up Principles

Prolactinoma

• PRL every 3-6 months during DA titration; then every 6-12 months when stable
• MRI sella: macroadenoma - at 3-6 months after starting DA; then annually; microadenoma - every 1-2 years
• After DA withdrawal: PRL every 3 months × 1 year, then annually; MRI if PRL rises
• Monitor for DA side effects

Acromegaly

• IGF-1 + GH (post-OGTT nadir or random) every 3-6 months post-operatively
• Biochemical cure: IGF-1 in age-matched normal range AND GH nadir <0.4 µg/L
• MRI sella: 3 months post-op, then 6-12 months, then annually if residual tumor
• Comorbidity surveillance:
  • Colonoscopy at diagnosis and every 3-5 years (colon polyps / cancer risk)
  • Echocardiogram at diagnosis (cardiomyopathy, LVH)
  • Glucose/HbA1c annually (25% develop diabetes)
  • Sleep study (>60% have obstructive sleep apnea)
  • Liver ultrasound if on SRLs (gallstones)
  • Bone density (arthropathy, fracture risk)
  • Blood pressure monitoring

Cushing Disease

• Post-op cortisol (8 AM, within 24-48 hours): target <2 µg/dL = remission
• Glucocorticoid replacement until HPA recovery; test recovery with ITT or short Synacthen at 6-12 months
• Recurrence monitoring: 24h UFC, midnight salivary cortisol, or 1-mg DST every 6-12 months for at least 5 years (recurrence in 15-25%)
• MRI sella: 3 months post-op; then annually for 2-3 years; more often if recurrent
• After bilateral adrenalectomy: annual MRI and ACTH levels for Nelson syndrome surveillance
• Screen and manage long-term consequences: hypertension, diabetes, osteoporosis, cardiovascular disease, neuropsychiatric effects

Non-Functioning Adenoma (post-surgery)

• Full pituitary panel at 6 weeks: TSH/free T4, 8 AM cortisol, IGF-1, FSH/LH, testosterone/estradiol
• MRI sella: 3 months, 1 year, then every 1-2 years; residual tumor followed annually
• Visual fields post-op; repeat if residual suprasellar mass
• Hormone replacement as needed; reassess pituitary function periodically

General Follow-Up Principles for All Macroadenomas

• Screen for hypopituitarism before and after any treatment
• DEXA scan (bone mineral density) if hypogonadal, Cushing, or GH-deficient
• Annual metabolic review: blood pressure, glucose, lipids
• Ophthalmology if suprasellar extension was present
• Register with an endocrinologist for long-term care - follow-up is lifelong for macroadenomas

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• Robbins & Kumar Basic Pathology, p. 764 - classification and pathology
• Goldman-Cecil Medicine International Edition, pp. 2404-2406 - acromegaly, GH deficiency
• Harrison's Principles of Internal Medicine 22E (2025), pp. 3049-3052 - prolactinoma, acromegaly (full clinical management)
• Henry's Clinical Diagnosis and Management by Laboratory Methods, pp. 477-479 - Cushing syndrome diagnostic testing in detail