What is the difference between pituitary adenoma and pituitary hyperplasia?

Pituitary Adenoma vs Pituitary Hyperplasia: Key Differences

Pituitary adenomas are benign neoplasms of pituitary adenohypophyseal cell lineage, while pituitary hyperplasia represents non-neoplastic proliferation of pituitary cells without disruption of the normal gland architecture. 1

Fundamental Differences

Definition and Pathology

• Pituitary Adenoma:

  • Neoplastic growth (tumor) of pituitary cells
  • Classified by size: microadenomas (<10mm) and macroadenomas (≥10mm) 1, 2
  • Discrete lesion with abnormal tissue architecture
  • Often has a capsule or clear demarcation from normal pituitary tissue
  • May show monoclonal expansion of cells

• Pituitary Hyperplasia:

  • Non-neoplastic proliferation of normal pituitary cells
  • Diffuse or focal enlargement of the pituitary gland
  • Preserves normal tissue architecture
  • No capsule or clear demarcation
  • Polyclonal expansion of cells

Etiology

• Pituitary Adenoma:

  • Often sporadic with somatic mutations (e.g., GNAS, USP8) 3
  • Can be associated with genetic syndromes (MEN1, Carney complex) 1
  • May have isolated genetic mutations (AIP, GPR101) 3

• Pituitary Hyperplasia:

  • Usually secondary to hormonal stimulation or feedback mechanisms
  • Associated with specific syndromes like McCune-Albright syndrome, Carney complex, X-linked acrogigantism 4
  • Can be caused by GH-releasing hormone-secreting tumors (often with MEN1 syndrome) 4
  • May be physiological (e.g., pregnancy, puberty)

Clinical Presentation

Symptoms and Signs

• Pituitary Adenoma:

  • Mass effects: headache, visual field defects, hypopituitarism 5, 2
  • Hormone hypersecretion syndromes specific to the cell type involved 2
  • Discrete lesion visible on MRI

• Pituitary Hyperplasia:

  • Usually milder symptoms
  • Hormone excess related to the stimulating factor
  • Diffuse enlargement of the pituitary on imaging
  • In children with GH excess: accelerated growth velocity (>+2 SDS), tall stature, acral enlargement 4

Specific Presentations in Children

• In children with GH excess from hyperplasia (e.g., X-linked acrogigantism):

  • Tall stature onset before 5 years (usually before 2 years)
  • Disproportionately enlarged hands and feet
  • Teeth separation, acanthosis nigricans
  • Increased BMI and appetite 4

• In McCune-Albright syndrome with hyperplasia:

  • Early-onset GH excess (from 3 years)
  • Café-au-lait pigmentation
  • Fibrous dysplasia
  • Precocious puberty 4

Diagnostic Approach

Imaging

• Pituitary Adenoma:

  • Discrete lesion on MRI with pre-contrast T1-weighted and T2-weighted sequences
  • Post-contrast enhancement with gadolinium 1
  • Clear borders and often displacement of normal pituitary tissue

• Pituitary Hyperplasia:

  • Diffuse enlargement of the pituitary gland
  • Homogeneous enhancement
  • No discrete lesion
  • Normal pituitary architecture preserved

Laboratory Testing

• Both conditions require comprehensive hormonal evaluation:
  • Serum prolactin, IGF-1, GH suppression test
  • 24-hour urinary free cortisol, nocturnal salivary cortisol
  • TSH, free T4, FSH, LH, estradiol/testosterone 1

Special Testing

• Bilateral inferior petrosal sinus sampling (BIPSS) may be needed to differentiate ACTH-secreting adenomas from other causes of Cushing's syndrome 1
• Genetic testing should be considered, especially in children and young people with pituitary disorders 1

Treatment Approaches

Pituitary Adenoma

• Transsphenoidal surgery is first-line for most adenomas except prolactinomas 1, 5
• Medical therapy based on adenoma type:
  • Prolactinomas: dopamine agonists (cabergoline, bromocriptine) 1, 2
  • GH-secreting: somatostatin analogs, pegvisomant 1
  • ACTH-secreting: ketoconazole, mifepristone, pasireotide 1
• Radiation therapy for incomplete resection or recurrence 1

Pituitary Hyperplasia

• Treatment targets the underlying cause:
  • Remove stimulus (e.g., primary hypothyroidism, ectopic GHRH-secreting tumor)
  • Manage underlying syndrome (e.g., McCune-Albright syndrome)
• Medical therapy to control hormone excess
• Rarely requires surgical intervention unless causing significant mass effect

Common Pitfalls and Caveats

• Misdiagnosis between the two conditions can lead to inappropriate treatment
• Overlooking genetic syndromes, especially in children with pituitary disorders
• Failure to perform comprehensive hormonal evaluation
• Not considering hyperplasia in the differential diagnosis of pituitary enlargement
• Neglecting visual assessment in patients with pituitary enlargement 1
• Missing the underlying cause of hyperplasia, which is crucial for effective treatment

Monitoring and Follow-up

• Regular monitoring of hormonal levels and serial imaging is essential for both conditions 1
• Periodic ophthalmological evaluation for larger lesions
• Lifelong monitoring for tumor recurrence in adenomas
• Evaluation of health-related quality of life to adapt treatment and psychological support 1