Prolactinoma

PROLACTIN-SECRETING PITUITARY TUMOR

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.

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

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

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

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).

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.

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

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

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.

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.