What is the recommended diagnostic work‑up and first‑line treatment for a pituitary macroadenoma?

Pituitary Macroadenoma: Diagnostic Work-Up and First-Line Treatment

For pituitary macroadenomas, comprehensive endocrine evaluation of all pituitary axes followed by transsphenoidal surgery at a high-volume center is the recommended approach for most patients, with the critical exception of prolactinomas, which should be treated first-line with dopamine agonists (cabergoline preferred). 1, 2

Diagnostic Work-Up

Hormonal Assessment

All patients require complete endocrine evaluation of every anterior pituitary axis, regardless of clinical suspicion, because hormone deficiencies occur at rates exceeding clinical detection. 1

• Assess for hypopituitarism: Growth hormone deficiency (61-100% of patients), hypogonadism (36-96%), adrenal insufficiency (17-62%), and hypothyroidism (8-81%) are common with macroadenomas 1
• Measure prolactin in all cases: This is mandatory to distinguish prolactinomas from other adenoma types, as treatment differs fundamentally 1, 3
• Measure IGF-1 levels: Required to exclude clinically silent growth hormone-secreting tumors, which occur in up to 45% of presumed non-functioning adenomas 1
• Evaluate for Cushing disease: Late-night salivary cortisol is the best screening test for ACTH-secreting tumors 4
• Check TSH and free thyroid hormones: To identify rare TSH-secreting adenomas (TSHomas) 5

Critical pitfall: Adrenal insufficiency must be identified and treated preoperatively, as it can be life-threatening perioperatively 3, 1

Imaging

• MRI with gadolinium contrast and thin-sliced sequences is the imaging modality of choice 6
• Macroadenomas are defined as ≥10 mm in diameter 1, 2

Visual Assessment

• Formal ophthalmologic evaluation with visual field testing is mandatory for all macroadenomas due to high rates of optic chiasm compression 1, 3, 2
• Visual field defects occur in 18-78% of patients with macroadenomas 2
• Bitemporal hemianopsia is the characteristic finding from optic chiasm compression 3
• Consider optical coherence tomography for baseline documentation 6

Genetic Evaluation

Genetic testing should be considered in all children and young adults (under age 19) with pituitary adenomas, particularly for growth hormone and prolactin-secreting tumors, due to high prevalence of familial syndromes (MEN1, FIPA, AIP mutations). 1, 3, 6

• Screen for family history of pituitary adenomas, MEN1, and other endocrine tumors 6
• In pediatric patients, germline mutations are more common than in adults 1

First-Line Treatment by Adenoma Type

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

Dopamine agonists are first-line treatment, with cabergoline strongly preferred over bromocriptine due to superior efficacy and tolerability. 3, 2, 4, 7

• Cabergoline achieves prolactin normalization and tumor shrinkage in >50% of macroprolactinomas 7
• Medical therapy is preferred even for large macroadenomas with visual symptoms, as tumor shrinkage and visual improvement often occur within hours to days 8
• Surgery is reserved only for dopamine agonist resistance or intolerance 7

All Other Macroadenomas (Non-Prolactinomas)

Transsphenoidal surgery by an experienced pituitary surgeon at a high-volume center (≥50 pituitary operations per year) is first-line treatment. 1, 3, 2, 4

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

• Transsphenoidal surgery is primary therapy 4
• Somatostatin analogs (octreotide, lanreotide) are used postoperatively if IGF-1 remains elevated 8, 4
• Pegvisomant (GH receptor antagonist) is reserved for somatostatin analog resistance 8

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

• Selective adenomectomy is first-line treatment 1, 4
• Bilateral inferior petrosal sinus sampling (BIPSS) may be needed to confirm pituitary source and lateralize the tumor when MRI is negative 1
• Repeat surgery achieves remission in 93% of recurrent cases in pediatric series 1
• Medical therapy (ketoconazole, mifepristone, pasireotide) or radiotherapy is reserved for surgical failures 1, 4

TSH-Secreting Adenomas (TSHomas, 1% of adenomas)

• Transsphenoidal surgery is the treatment of choice 5
• Preoperative somatostatin analogs normalize thyroid function in 84% and cause tumor shrinkage in 61% 5
• Methimazole can control hyperthyroid symptoms preoperatively but should not delay surgical evaluation 5

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

• Transsphenoidal surgery is indicated for symptomatic tumors causing mass effect 3, 2
• Small, asymptomatic incidentally discovered tumors may be observed with serial imaging 8, 4

Surgical Considerations

• Endoscopic transsphenoidal approach is preferred over microscopic technique for potentially superior preservation of pituitary function 1
• Surgery is feasible even in children with incompletely pneumatized sphenoid sinuses 1
• Strict perioperative and postoperative fluid and electrolyte monitoring is mandatory due to high risk of diabetes insipidus and SIADH 1

Radiotherapy

• Reserved for residual or recurrent tumors after surgery, or when surgery is contraindicated 1, 3, 4
• Fractionated radiotherapy or stereotactic radiosurgery (gamma knife) are options 8

Critical Clinical Pitfalls

• Never assume a macroadenoma is non-functioning without measuring prolactin and IGF-1 1
• Always replace adrenal insufficiency and significant hypothyroidism before surgery 1
• Do not use antithyroid drugs as primary treatment for TSHomas—surgery is definitive 5
• In adolescents with pituitary masses, always measure βHCG and AFP to exclude germ cell tumors 3
• Visual deterioration is an urgent indication for surgical decompression 3