What are the symptoms and treatment options for a pituitary adenoma?

Symptoms of Pituitary Adenoma

Pituitary adenomas present with three distinct clinical patterns: hormone hypersecretion syndromes, mass effect symptoms from tumor compression, or hypopituitarism from destruction of normal pituitary tissue. 1

Hormone Hypersecretion Symptoms (Functioning Adenomas)

Prolactinomas (Most Common - 32-66% of adenomas)

• Women: Amenorrhea, infertility, galactorrhea (breast milk production), and loss of libido 2, 3
• Men: Erectile dysfunction, decreased libido, infertility, and occasionally gynecomastia 3, 4
• These symptoms often lead to earlier diagnosis in women due to menstrual irregularities 5

Growth Hormone-Secreting Adenomas (8-16% of adenomas)

• Adults (Acromegaly): Progressive enlargement of hands, feet, lips, tongue, and nose; coarsening of facial features; joint pain; excessive sweating; sleep apnea 2, 3
• Children/Adolescents (Gigantism): Rapid linear growth velocity and tall stature 2

ACTH-Secreting Adenomas (2-6% of adenomas - Cushing Disease)

• Central obesity with fat redistribution (buffalo hump, moon face, supraclavicular fat pads) 3
• Purple striae, easy bruising, proximal muscle weakness 4
• Hypertension, diabetes, osteoporosis, psychiatric disturbances 3

TSH-Secreting Adenomas (Rare - 1% of adenomas)

• Hyperthyroid symptoms: weight loss, tremor, palpitations, heat intolerance, anxiety 3, 4

Mass Effect Symptoms (Especially Macroadenomas ≥10mm)

Visual Disturbances

• Bitemporal hemianopsia (loss of peripheral vision) from optic chiasm compression - most characteristic finding 1
• Visual field defects occur in 18-78% of patients with macroadenomas 2
• Progressive visual acuity loss if untreated 1
• In children and adolescents, visual deterioration is an urgent indication for surgical decompression 1

Headaches

• Present in 17-75% of patients with macroadenomas 2
• Typically frontal or retro-orbital in location 4, 6
• May be due to dural stretch or invasion of cavernous sinus 6

Cranial Nerve Palsies

• Diplopia (double vision) from compression of cranial nerves III, IV, or VI in the cavernous sinus 6
• Facial pain or numbness from trigeminal nerve involvement 4

Hypopituitarism Symptoms (34-89% of macroadenomas)

Gonadotropin Deficiency

• Women: Secondary amenorrhea, infertility, decreased libido, vaginal dryness 4, 5
• Men: Erectile dysfunction, decreased libido, loss of body hair, testicular atrophy 4
• Children/Adolescents: Delayed or arrested puberty, growth failure 1

Thyroid Hormone Deficiency

• Fatigue, cold intolerance, weight gain, constipation, dry skin 4

Adrenal Insufficiency (Most Dangerous)

• Fatigue, weakness, weight loss, nausea, hypotension 4
• Critical pitfall: Can be life-threatening if unrecognized perioperatively 1

Growth Hormone Deficiency

• Children: Growth failure, short stature 1
• Adults: Decreased energy, reduced muscle mass, increased body fat, reduced quality of life 4

Special Presentations

Pituitary Apoplexy (Medical Emergency)

• Sudden severe headache ("thunderclap"), visual loss, altered consciousness 1
• More common in children and adolescents than adults with nonfunctioning adenomas 1
• Requires urgent neurosurgical evaluation 1

Nonfunctioning Adenomas (15-54% of adenomas)

• Often asymptomatic until large enough to cause mass effect 1, 3
• In children, represent only 4-6% of pituitary adenomas but present later with larger tumors 1
• May present with mild hyperprolactinemia (<2,000 mU/L) from stalk compression rather than true prolactin secretion 1

Incidentalomas

• Discovered incidentally on brain imaging performed for unrelated reasons 5
• Microadenomas (<10mm) are often asymptomatic and may not require immediate intervention 7, 5

Treatment Options

Medical Therapy

Prolactinomas: First-line treatment is dopamine agonists 7, 8, 2

• Cabergoline is preferred over bromocriptine due to better efficacy and tolerability 7
• Normalizes prolactin in 83% of patients, induces tumor shrinkage in 62%, resolves galactorrhea in 86% 7
• In children/adolescents: lowers prolactin in 60-70% and reduces tumor size in 80-88% 7
• Even large macroadenomas with visual symptoms respond rapidly (within hours to days) to dopamine agonists 4

Growth Hormone-Secreting Adenomas:

• Somatostatin analogs (octreotide, lanreotide) used after surgery if not cured, or preoperatively to reduce tumor size 3, 4
• Pegvisomant (GH receptor antagonist) reserved for resistance to somatostatin analogs 4

ACTH-Secreting Adenomas:

• Medical therapy (ketoconazole, mifepristone, pasireotide) used as bridge to surgery or after failed surgery while awaiting radiation effects 3, 4

Nonfunctioning Adenomas:

• Medical therapy (dopamine agonists, somatostatin analogs) shows inconsistent results with response rates of 0-61% 1
• Not recommended as primary treatment 1

Surgical Therapy

Transsphenoidal surgery is first-line for all pituitary adenomas EXCEPT prolactinomas 7, 2, 3

Indications for surgery:

• Growth hormone-secreting adenomas: primary therapy 7, 3
• ACTH-secreting adenomas: primary therapy even if microadenoma not visible on MRI 7, 3
• Nonfunctioning macroadenomas with visual compromise or tumor growth 1
• TSH-secreting adenomas: primary therapy 3, 4

Surgical outcomes for nonfunctioning adenomas:

• Immediate tumor volume reduction in nearly all patients 1
• Visual function improvement in 75-91% of patients 1
• Hypopituitarism improvement in 35-50% of patients 1
• Residual tumor rate of 10-36% 1

In children/adolescents:

• Surgery should be performed in specialist high-volume centers 1
• Transsphenoidal approach is treatment of choice when intervention needed 1

Observation

Appropriate for:

• Asymptomatic nonfunctioning microadenomas 7, 3, 5
• Surveillance with MRI at 6 months, then annually for 2-3 years if stable 7

Risks of observation alone for symptomatic macroadenomas:

• Tumor progression in 50% of patients 1
• Requirement for surgery in 21% of patients 1

Radiation Therapy

Reserved for:

• Residual or recurrent tumor after surgery 3, 4
• Patients not surgical candidates 1
• Techniques include fractionated radiotherapy or stereotactic radiosurgery (gamma knife) 3, 4

Outcomes for nonfunctioning adenomas:

• Decreased tumor size in 38-60% of patients with primary radiosurgery 1
• Effects may take years to manifest 4

Critical Clinical Pitfalls

Always measure serum βHCG and AFP in adolescents with suspected pituitary masses, as intracranial germ-cell tumors can mimic nonfunctioning adenomas on MRI 1

Distinguish true hyperprolactinemia from stalk compression: Prolactin levels >2,000 mU/L (94 μg/L) suggest true prolactinoma; lower levels may indicate stalk compression from any macroadenoma 1

Test for macroprolactin in asymptomatic patients with elevated prolactin, as macroprolactinemia (present in 10-40% of cases) may not require treatment 7

Perform serial dilutions if discrepancy exists between large tumor size and only modestly elevated prolactin to avoid "high-dose hook effect" 7

Assess for hypopituitarism before surgery and provide hormone replacement (especially cortisol) to optimize surgical outcomes and prevent perioperative adrenal crisis 1

Genetic testing is mandatory in all children and adolescents with pituitary adenomas due to high prevalence of familial syndromes (MEN1, AIP mutations) 1, 7

Visual recovery is unlikely after the first post-operative month, emphasizing the urgency of surgical decompression when vision is threatened 1