hyperprolactinemia
HYPERPROLACTINEMIA
Hyperprolactinemia is the presence of elevated prolactin levels that occurs in about one-thirds of patients w/ chronic kidney disease & resolves after successful transplantation.
It may cause visual field defects or headache in both men and women.
In women, signs and symptoms include menstrual irregularity, galactorrhea, infertility, vaginal dryness, dyspareunia, loss of libido and reduction in vertebral bone density (in sustained, pronounced hyperprolactinemia).
While in men, signs and symptoms include diminished libido, hypogonadism, gonadotrophin suppression, osteopenia, decreased muscle mass, and decreased facial hair that may occur in prolonged hyperprolactinemia.

Principles of Therapy

  • Goal is to decrease prolactin (PRL) levels and to alleviate symptoms
  • If possible, discontinue offending medication

Pharmacotherapy

Dopamine Agonists
  • Titrate dose to achieve maximum prolactin (PRL) suppression and to restore reproductive function
  • Therapy recommended to lower prolactin levels, decrease tumor size and restore gonadal function in patients with microadenomas or macroadenomas

Bromocriptine

  • Initial drug of choice
  • Actions: Ergot alkaloid that binds to and stimulates D2 dopamine-receptors on lactotroph cells
  • Effects: Lowers serum prolactin (PRL) levels in 70-100% of patients
    • Decreases tumor size and restores gonadal function
    • Macroadenomas shrinkage of ≥50% is observed in 40% of patients
    • Headaches and visual disturbances improve rapidly within days of commencing therapy
    • Resumption of menses and ovulation in 80-90% of hyperprolactinemic women
  • Discontinuation results in recurrent hyperprolactinemia and tumor regrowth along with the risk of visual disturbances
    • ~5% of patients do not have recurrence with discontinuation of Bromocriptine
  • May be administered intravaginally if oral dose is not tolerated
  • Pregnancy: Bromocriptine has been used to restore fertility in hyperprolactinemic women
    • Attempt to reduce neonatal exposure to the drug
    • Woman desiring to become pregnant should use barrier contraception and Bromocriptine until 3 regular menstrual cycles have occurred (to allow for conception timing)
    • Bromocriptine can be safely discontinued in women with microadenomas or intrasellar macroadenomas without significant suprasellar or parasellar extension
    • In women with larger macroadenomas, 2 options are recommended:
      • Discontinue Bromocriptine
      • Give Bromocriptine continuously throughout gestation, however with theoretical fetal risk
  • 5% of microadenomas and 15-30% of macroadenomas may grow during pregnancy
  • Prolactin (PRL) levels rise progressively in pregnancy and monitoring of prolactin (PRL) levels is not useful
  • Regular visual field exam throughout pregnancy is recommended
  • Visual field testing is recommended in patients with macroadenomas
  • Restart Bromocriptine if tumor growth occurs and explain to patient the risks and benefits of treatment
  • Surgical decompression may be used if vision is threatened

Cabergoline

  • Useful in patients who are resistant or intolerant to Bromocriptine
    • Fewer side effects than Bromocriptine and can be given 2x/week
    • Higher efficacy in normalizing prolactin levels and higher frequency of pituitary tumor shrinkage
  • Actions: Ergot derivative which is a long-acting dopamine agonist with high affinity for D2 receptors on lactotroph cells
  • Effects: Suppresses prolactin (PRL) secretion for >14 days after a single oral dose
    • Lowers serum prolactin (PRL) levels and restores gonadal function in ~80% of patients with microadenomas
    • Normalizes prolactin (PRL) and shrinks tumor in ~70% of macroadenomas

Quinagolide

  • May be useful in patients who are intolerant of ergot derivatives
  • Actions: Non-ergot Dopamine agonist
  • Effects: ~50% of patients who are resistant to Bromocriptine respond to Quinagolide
    • Efficacy is similar to other Dopamine agonists

Pergolide

  • Effects: Several studies have shown that Pergolide is as efficacious as Bromocriptine
    • Tolerance is similar to Bromocriptine

Metergoline

  • Actions: Ergot derivative which is both a dopamine agonist and a serotonin antagonist
  • Indicated for use in hyperprolactinemic amenorrhea

Non-Pharmacological Therapy

Watchful Observation

  • Appropriate in patients who present with microadenomas, are not concerned with fertility, and have minimal symptoms
  • Effects: Studies have shown that 93% of microadenomas do not grow over a 4-6 year period
  • Close observation of the adenoma is necessary to determine if it is growing
    • Serial prolactin (PRL) levels should be done regularly
    • Magnetic resonance imaging (MRI) should be performed if a significant rise in prolactin (PRL) is noticed
    • Imaging studies at yearly intervals

Formal Visual Field Testing

  • Performed prior to dopamine agonist treatment and every 6-12 months thereafter
  • More frequent monitoring initially in those with visual field deficit

Cause-specific Hyperprolactinemia

Hypothyroidism

  • Levothyroxine (T4) replacement
    • Resolution of hyperprolactinemia usually occurs after adequate thyroid replacement
  •  Please see Hypothyroidism disease management chart for further information

Drug-Induced Hyperprolactinemia

  • If possible, discontinue offending medication for 3 days or substitute an alternative drug
    • Then, repeat measurement of serum prolactin

Psychiatric patients who cannot stop medication:

  • If possible, slowly decrease dose of offending antipsychotic medications or substitute an alternative drug
  • Dopamine agonist may be added to restore normoprolactinemia and alleviate symptoms
    • Use with caution as it may worsen underlying psychiatric condition

Renal Failure

  • Treat underlying cause
    • Dialysis
    • Renal transplant

Hypothalamic-Pituitary Stalk Damage

Granulomatous Infiltrates

  • Glucocorticoids (rarely effective)

Hypothalamic or Sellar Mass Lesions

  • Surgical resection may reverse hyperprolactinemia

Irreversible Hypothalamic Damage

  • No treatment may be necessary

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