What is a prolactinoma?

What is a Prolactinoma?

A prolactinoma is a benign pituitary adenoma (tumor) that secretes excessive amounts of the hormone prolactin, representing the most common type of pituitary adenoma, occurring in approximately 0.1 million children yearly and comprising 30-50% of all pituitary neuroendocrine tumors. 1, 2

Clinical Characteristics

Demographics and Presentation

• Most common in females aged 20-50 years, with a 3-4.5 times higher prevalence in females than males 1
• Typically presents during adolescence, but can rarely occur in the first decade of life 1
• Median duration of symptoms before diagnosis is approximately 12 months 1
• Macroprolactinomas (≥1 cm) and giant prolactinomas occur more frequently in children and adolescents than adults 1

Clinical Features

• In females: Delayed or arrested puberty, menstrual disturbances (oligomenorrhea/amenorrhea), galactorrhea, infertility 1, 3
• In males: Hypogonadism, impotence, infertility, and more commonly mass effects 1, 3
• Mass effects: Headache, visual field defects, cranial nerve deficits, hypopituitarism 3
• Other symptoms: Growth failure, short stature, obesity (46% of children with macroprolactinomas have overweight/obesity) 1

Pathophysiology

• High serum prolactin inhibits gonadotropin secretion via inhibition of hypothalamic kisspeptin, leading to hypogonadism 1
• Recent research has identified somatic SF3B1 mutations in some prolactinomas, though molecular mechanisms remain largely unknown in most cases 2
• A small percentage of pediatric prolactinomas are related to genetic conditions such as familial isolated pituitary adenoma or multiple endocrine neoplasia type 1 syndrome (MEN1) 1

Diagnosis

Laboratory Testing

• Serum prolactin measurement is essential in patients presenting with:
  • Delayed puberty
  • Galactorrhea
  • Visual field loss
  • Growth or pubertal arrest
  • Menstrual disturbances in females 1

Imaging

• Magnetic resonance imaging (MRI) of the pituitary is crucial for detecting the tumor and assessing its size 2
• Prolactinomas are classified as:
  • Microprolactinomas (<1 cm)
  • Macroprolactinomas (≥1 cm)
  • Giant prolactinomas (particularly large tumors) 4

Diagnostic Pitfalls

• "Hook effect": Laboratory artifact causing falsely low prolactin readings in cases of very high prolactin levels 3
• Macroprolactin: A high-molecular-weight form of prolactin that can cause laboratory confusion 3
• Other causes of hyperprolactinemia must be excluded (medications, hypothyroidism, renal failure, etc.) 2

Treatment

Medical Therapy

• Dopamine agonists (DAs) are the first-line treatment 2, 3, 5
  • Cabergoline is preferred over bromocriptine due to better tolerance and efficacy 3, 4
  • Effective in normalizing prolactin levels and shrinking tumor size in 80-90% of cases 6
  • Can restore gonadal function and fertility 3

Surgical Therapy

• Indications for surgical referral include:
  • Resistance to dopamine agonist therapy
  • Intolerance to medical therapy
  • Patient preference for definitive treatment
  • Deteriorating vision despite medical therapy 7
• Transsphenoidal surgery is curative in approximately 60% of microprolactinomas but only 25% of macroprolactinomas 6

Special Considerations

• Pregnancy: Careful monitoring is required as tumor growth may occur during pregnancy; dopamine agonists should be discontinued once pregnancy is confirmed unless there's risk of tumor expansion 7, 8
• Cardiac monitoring: Echocardiography is recommended before starting treatment and periodically during treatment due to potential cardiac valve alterations with dopamine agonists 7
• Side effects of dopamine agonists include:
  • Nausea, dizziness, headache (in about 13% of patients) 7
  • Impulse control disorders (gambling, increased sexual urges, uncontrolled spending) 8, 2
  • Symptomatic hypotension 8

Long-term Management

• Approximately one-third of patients may achieve definitive cure and discontinue medication 3
• Patients with normal prolactin levels for ≥6 months can consider dose reduction 7
• After discontinuation, prolactin levels should be monitored every 3 months for the first year and every 6 months for the second year 7
• Smaller initial tumor size correlates with better outcomes after discontinuation 7

Complicated Cases

• Dopamine agonist resistance: Defined as failure to normalize prolactin levels or achieve significant tumor shrinkage after 3-6 months of maximally tolerated doses 7
• Giant or malignant prolactinomas: May require multimodal therapy involving surgery, radiotherapy, or both 2, 5
• Visual field monitoring: Essential in macroprolactinomas to detect secondary field loss due to chiasmal herniation 8