What is the initial approach to managing a pituitary adenoma?

Initial Management of Pituitary Adenoma

The initial approach to managing a pituitary adenoma is determined by whether the tumor is hormonally active: dopamine agonists (specifically cabergoline) are first-line for prolactinomas, transsphenoidal surgery is first-line for growth hormone-secreting and ACTH-secreting adenomas, and observation with surveillance is appropriate for asymptomatic non-functioning microadenomas. 1

Immediate Diagnostic Workup

Imaging

• Obtain MRI with contrast using thin-sliced sequences as the imaging modality of choice for anatomical delineation of the adenoma. 2, 3
• High-resolution dynamic contrast-enhanced imaging increases sensitivity for detecting small adenomas. 1

Hormonal Assessment

Measure the following to determine if the adenoma is hormonally active: 1

• Prolactin (PRL)
• IGF-1 and morning cortisol
• ACTH
• TSH and free T4
• LH, FSH, testosterone (in men), and estradiol (in women)

Important caveat: If there is a discrepancy between tumor size and only modestly elevated prolactin levels, perform serial dilutions of serum for prolactin measurement to avoid the "high-dose hook effect." 1 Additionally, mild hyperprolactinemia can result from stalk compression by macroadenomas and does not necessarily indicate a prolactinoma. 3

Visual Assessment

• Perform visual acuity, visual fields, and fundoscopy in all patients with pituitary macroadenomas to assess for optic chiasm compression. 2, 3
• Visual assessment should be completed within 3 months of initiating first-line therapy. 2

Genetic Evaluation

• Offer genetic assessment to all patients, particularly children and young people, who have a higher likelihood of underlying genetic disease. 2, 3
• This is especially important as genetic testing informs management and family surveillance. 1

Treatment Algorithm Based on Adenoma Type

Prolactinomas (32-66% of adenomas)

Medical therapy with dopamine agonists is first-line treatment, even for macroadenomas with visual compromise. 2, 3

• Cabergoline is the preferred dopamine agonist over bromocriptine, normalizing prolactin levels in 83% of patients, inducing tumor shrinkage in 62%, and resolving galactorrhea in 86%. 1, 4
• In children and adolescents, cabergoline lowers prolactin in 60-70% and reduces tumor size by 80-88%. 1
• Effects on visual disturbances from macroadenomas are often rapid (within hours to days). 5, 6

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

Transsphenoidal surgery is first-line therapy, except for giant macroadenomas or when surgery is contraindicated. 2, 1

• Surgery should be performed by experienced pituitary surgeons in high-volume centers. 1
• Medical therapy with somatostatin analogues, cabergoline, or pegvisomant is reserved for postoperative residual disease or when surgery is contraindicated. 5

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

Transsphenoidal surgery is primary therapy, even if the microadenoma is not clearly visible on MRI. 1

• Boys with Cushing disease tend to have more aggressive disease with elevated BMI, shorter height, and higher plasma ACTH levels than girls. 3
• Medical therapies (ketoconazole, mifepristone, pasireotide) are reserved for postoperative persistent disease or while awaiting effects of radiotherapy. 5

TSH-Secreting Adenomas (1% of adenomas)

Surgery is the primary treatment. 2, 3

• Pituitary radiotherapy may be considered in patients with postoperative tumor remnant and resistance to medical therapy. 3

Non-Functioning Adenomas (15-54% of adenomas)

Macroadenomas

Transsphenoidal surgery is the treatment of choice for symptomatic cases or those threatening the visual pathway. 3

• Hypopituitarism is common in patients with macroadenomas (34-89% of cases) and requires complete endocrine evaluation and hormone replacement therapy. 3, 6

Microadenomas

Observation with surveillance is the standard approach for asymptomatic non-functioning microadenomas. 1

• MRI surveillance at 6 months, then annually for 2-3 years if stable. 1
• For symptomatic microadenomas, transsphenoidal surgery may be considered. 1

Surgical Considerations

Transsphenoidal surgery is the technique of choice, even in patients with incompletely pneumatized sphenoid sinuses. 2

• Endoscopic rather than microscopic transsphenoidal surgery may be considered for potentially superior efficacy in preserving pituitary function. 2
• Strict fluid and electrolyte balance monitoring is essential perioperatively and postoperatively to detect diabetes insipidus or SIADH. 2, 1

Post-Treatment Surveillance

For Non-Functioning Adenomas

MRI surveillance at 3 and 6 months, and 1,2,3, and 5 years after surgery. 2, 3

For Prolactinomas

Prolactin levels should be assessed at 3-6 month intervals initially. 3

For All Adenomas

• Visual assessment within 3 months of first-line therapy. 2
• Regular hormone level assessments specific to tumor type at 3 months post-surgery. 1
• If surgery is performed, histopathological assessment should include immunostaining for pituitary hormones and Ki-67. 1

Special Populations: Children and Young People

Pituitary adenomas in children tend to have more occult presentation, aggressive behavior, and are more likely to have a genetic basis than in adults. 2, 3

• All children and adolescents with pituitary adenomas should undergo genetic assessment. 1
• Treatment should be managed by a pituitary-specific multidisciplinary team with experts from both pediatric and adult practice. 2, 3
• Ki-67 staining ≥3% combined with local invasion on imaging predicts a 25% recurrence rate after surgery in pediatric patients. 1

Management of Residual or Recurrent Disease

Repeat resection is recommended for symptomatic recurrent or residual non-functioning adenomas. 2

• Radiosurgery with single-session doses of ≥12 Gy or radiation therapy with fractionated doses of 45 to 54 Gy achieves local tumor control rate of ≥90% at 5 years. 2