Prolactinoma

PROLACTIN-SECRETING PITUITARY TUMOR

Definition and Pathophysiology

• Prolactinomas: Prolactin-secreting pituitary tumors (prolactinomas) are the most common hormone-secreting pituitary tumor.
• Cell Origin: Monoclonal lactotroph cell adenomas, typically resulting from sporadic mutations.
• Association With MEN1: Although most prolactinomas are sporadic, they are the most frequent pituitary tumor in persons with multiple endocrine neoplasia type 1 (MEN1).
• Benign Nature: More than 99% of prolactinomas are benign.
• Co-secretion: Approximately 10% of prolactin-secreting pituitary tumors also secrete growth hormone (GH) due to a somatotroph or mammosomatotroph component.

CLINICAL PRESENTATION

Presentation in Women

• Prolactin-secreting Microadenomas (≤10 mm)
  • Typical presentation: Secondary amenorrhea, with or without galactorrhea.

Presentation in Men and Postmenopausal Women

• Late Diagnosis
  • Small prolactinomas often go undetected due to lack of symptoms.
  • Diagnosis is typically delayed until the adenoma enlarges and causes mass-effect symptoms.
• Mass-Effect Symptoms of Macroadenomas
  • Visual field defects (due to suprasellar extension)
  • Cranial nerve palsies with lateral (cavernous sinus) extension (e.g., diplopia, ptosis)
  • Headaches
  • Hypopituitarism due to compression of normal pituitary tissue

Effects of Hyperprolactinemia

• Decreased Gonadotropin Secretion (both men and women)
• In Men:
  • Hypogonadotropic hypogonadism → testicular atrophy, low serum testosterone, decreased libido, sexual dysfunction, decreased facial hair growth, decreased muscle mass
  • Galactorrhea is rare (lack of estrogen needed to prepare breast tissue)
• In Premenopausal Women:
  • Bilateral spontaneous or expressible galactorrhea
  • Secondary amenorrhea and estrogen deficiency symptoms (e.g., hot flashes, vaginal dryness)
• Long-Standing Hypogonadism (Men and Women):
  • Osteopenia and osteoporosis

SERUM PROLACTIN CONCENTRATION AND TUMOR SIZE

• Prolactin Levels Generally Proportional to Adenoma Size
  • Microadenoma (~5 mm): Serum prolactin usually 50–250 ng/mL (reference range, 4–30 ng/mL).
  • Macroadenoma (>2 cm): Serum prolactin often >1000 ng/mL.
• Exceptions
  • Small adenomas with very high secretory capacity (>1000 ng/mL).
  • Large adenomas (macroadenomas) with inefficient secretion (<200 ng/mL).

TREATMENT CONSIDERATIONS

Indications for Treatment

• Guided by:
  1. Symptoms related to hyperprolactinemia
  2. Mass-effect symptoms from the sellar mass
• Examples:
  • A small microadenoma (4 mm) in an asymptomatic postmenopausal woman may be observed without treatment.
  • Macroadenomas generally warrant treatment due to their tendency to grow over time and cause mass effects.

Mainstay of Therapy: Dopamine Agonists

• When Treatment Is Indicated
  • E.g., presence of secondary hypogonadism (in men or premenopausal women) or a macroadenoma.
• Orally Administered Dopamine Agonists
  • Cabergoline or bromocriptine
  • First-line choice for prolactinomas
• Effects of Dopamine Agonists
  • Rapid normalization of serum prolactin levels
  • Reduction in the size of the lactotroph adenoma

Monitoring and Dosage Adjustment

1. Serum Prolactin Concentration
   • Check every 2 weeks after starting therapy.
   • Adjust dose of bromocriptine or cabergoline until prolactin normalizes.
2. Imaging
   • Repeat pituitary MRI ~3 to 6 months after achieving normal prolactin levels to confirm tumor shrinkage.
3. Maintenance
   • Continue the minimal effective dose indefinitely.

Potential “Cure”

• Long-Term Dopamine Agonist Therapy
  • Rarely, prolactin-secreting adenomas may be cured.
  • Periodic (e.g., every 2 years) 2-month “drug holiday” is recommended to see if hyperprolactinemia recurs.

Special Considerations

• Sphenoid Sinus Extension
  • Risk of cerebrospinal fluid (CSF) rhinorrhea with tumor shrinkage.
  • CSF rhinorrhea requires urgent neurosurgical intervention to prevent pneumocephalus and bacterial meningitis.
• Intolerance or Resistance to Dopamine Agonists
  • Symptoms: Nausea, lightheadedness, mental fogginess, vivid dreams.
  • Alternative Options: Transsphenoidal surgery or Gamma Knife radiation therapy.