Definitions for the quality of the evidence (+OOO, ++OO, +++O, and ++++); the strength of the recommendation (1 or 2); and the difference between a "recommendation" and a "suggestion" are provided at the end of the "Major Recommendations" field.
Diagnosis of Hyperprolactinemia
To establish the diagnosis of hyperprolactinemia, the Task Force recommends a single measurement of serum prolactin; a level above the upper limit of normal confirms the diagnosis as long as the serum sample was obtained without excessive venipuncture stress. The Task Force recommends against dynamic testing of prolactin secretion for the diagnosis of hyperprolactinemia (1|++++).
In patients with asymptomatic hyperprolactinemia, the Task Force suggests assessing for macroprolactin (2|++OO).
When there is a discrepancy between a very large pituitary tumor and a mildly elevated prolactin level, the Task Force recommends serial dilution of serum samples to eliminate an artifact that can occur with some immunoradiometric assays leading to a falsely low prolactin value ("hook effect") (1|++++).
Causes of Hyperprolactinemia
The Task Force recommends excluding medication use, renal failure, hypothyroidism, and parasellar tumors in patients with symptomatic nonphysiological hyperprolactinemia (1|++++).
Management of Drug-Induced Hyperprolactinemia
In a symptomatic patient with suspected drug-induced hyperprolactinemia, the Task Force suggests discontinuation of the medication for 3 days (d) or substitution of an alternative drug, followed by remeasurement of serum prolactin (2|++OO). Discontinuation or substitution of an antipsychotic agent should not be undertaken without consulting the patient's physician. If the drug cannot be discontinued and the onset of the hyperprolactinemia does not coincide with therapy initiation, the Task Force recommends obtaining a pituitary magnetic resonance image (MRI) to differentiate between medication-induced hyperprolactinemia and symptomatic hyperprolactinemia due to a pituitary or hypothalamic mass (1|+OOO).
The Task Force suggests that clinicians not treat patients with asymptomatic medication-induced hyperprolactinemia (2|++OO). The Task Force suggests use of estrogen or testosterone in patients with long-term hypogonadism (hypogonadal symptoms or low bone mass) related to medication-induced hyperprolactinemia (2|+OOO).
The Task Force suggests that the first step in treatment of medication-induced hyperprolactinemia is to stop the drug if this is clinically feasible. If this is not possible, a drug with a similar action that does not cause hyperprolactinemia should be substituted, and if this is not feasible the Task Force suggests considering the cautious administration of a dopamine agonist in consultation with the patient's physician (2|+OOO).
Management of Prolactinoma
The Task Force recommends dopamine agonist therapy to lower prolactin levels, decrease tumor size, and restore gonadal function for patients harboring symptomatic prolactin-secreting microadenomas or macroadenomas (1|++++). The Task Force recommends using cabergoline in preference to other dopamine agonists because it has higher efficacy in normalizing prolactin levels, as well as a higher frequency of pituitary tumor shrinkage (1|++++).
The Task Force suggests that clinicians not treat asymptomatic patients harboring microprolactinomas with dopamine agonists (2|+OOO). The Task Force suggests treatment with a dopamine agonist or oral contraceptives in patients with a microadenoma who have amenhorrhea (2|+OOO).
The Task Force suggests that with careful clinical and biochemical follow-up, therapy may be tapered and perhaps discontinued in patients who have been treated with dopamine agonists for at least 2 years, who no longer have elevated serum prolactin, and who have no visible tumor remnant on MRI (2|+OOO).
Resistant and Malignant Prolactinoma
For symptomatic patients who do not achieve normal prolactin levels or show significant reduction in tumor size on standard doses of a dopamine agonist (resistant prolactinomas), the Task Force recommends that the dose be increased to maximal tolerable doses before referring the patient for surgery (1|++++).
The Task Force recommends that patients resistant to bromocriptine be switched to cabergoline (1|++++).
The Task Force suggests that clinicians offer transsphenoidal surgery to symptomatic patients with prolactinomas who cannot tolerate high doses of cabergoline or who are not responsive to dopamine agonist therapy. For patients who are intolerant of oral bromocriptine, intravaginal administration may be attempted. For patients who fail surgical treatment or who harbor aggressive or malignant prolactinomas, the Task Force suggests radiation therapy (2|+OOO).
In patients with malignant prolactinomas, the Task Force suggests temozolomide therapy (2|+OOO).
Management of Prolactinoma During Pregnancy
The Task Force recommends that women with prolactinomas be instructed to discontinue dopamine agonist therapy as soon as they discover that they are pregnant (1|++OO).
In selected patients with macroadenomas who become pregnant on dopaminergic therapy and who have not had prior surgical or radiation therapy, it may be prudent to continue dopaminergic therapy throughout the pregnancy, especially if the tumor is invasive or is abutting the optic chiasm (1|+OOO).
In pregnant patients with prolactinomas, the Task Force recommends against performing serum prolactin measurements during pregnancy (1|++++).
The Task Force recommends against the use of routine pituitary MRI during pregnancy in patients with microadenomas or intrasellar macroadenomas unless there is clinical evidence for tumor growth such as visual field compromise (1|++OO).
The Task Force recommends that women with macroprolactinomas who do not experience pituitary tumor shrinkage during dopamine agonist therapy or who cannot tolerate bromocriptine or cabergoline be counseled regarding the potential benefits of surgical resection before attempting pregnancy (1|++OO).
The Task Force recommends formal visual field assessment followed by MRI without gadolinium in pregnant women with prolactinomas who experience severe headaches and/or visual field changes (1|++OO).
The Task Force recommends bromocriptine therapy in patients who experience symptomatic growth of a prolactinoma during pregnancy (1|++OO).
Quality of Evidence
+OOO Denotes very low quality evidence
++OO Denotes low quality evidence
+++O Denotes moderate quality evidence
++++ Denotes high quality evidence
Strength of Recommendation
1 - Indicates a strong recommendation and is associated with the phrase "The Task Force recommends."
2 - Denotes a weak recommendation and is associated with the phrase "The Task Force suggests."