Version July 2025
ALGORITHM —
INITIAL EVALUATION —
Prolactin is usually measured to assess hypogonadism, infertility, and/or galactorrhea.
Because meals may stimulate prolactin secretion slightly, if the prolactin concentration is only slightly high (up to 40 ng/mL [40 mcg/L] in males and postmenopausal females and up to 50 ng/mL [50 mcg/L] in premenopausal females), it should be repeated on a fasting sample before the patient is considered to have hyperprolactinemia. Other physiologic causes of high prolactin include pregnancy and the first six weeks of lactation. (See "Causes of hyperprolactinemia", section on 'Physiologic causes'.)
If the repeat value is still elevated in the absence of physiologic causes, the next step is to determine the cause. Common causes include lactotroph adenomas, other hypothalamic and pituitary disorders, and medications, most commonly, antipsychotics. Other causes include idiopathic hyperprolactinemia, hypothyroidism, chest wall injury, chronic renal failure, and macroprolactinemia due to "big prolactin" (see "Clinical manifestations and evaluation of hyperprolactinemia", section on 'Evaluation of hyperprolactinemia' and "Causes of hyperprolactinemia", section on 'Physiologic causes'):
●Inquire about headache, visual symptoms, symptoms of hypothyroidism, and a history of renal disease. (See 'Chronic kidney disease' below.)
●Review medications to evaluate for a pharmacologic cause of hyperprolactinemia (eg, neuroleptic drugs such as risperidone, metoclopramide, antidepressant drugs, cimetidine, methyldopa, and verapamil) (table 1).
Medication-related hyperprolactinemia
●If the patient is taking risperidone, obtain magnetic resonance imaging (MRI) of the pituitary with and without gadolinium if the prolactin is >300 ng/mL.
●If the patient is taking a medication other than risperidone that is known to elevate prolactin (table 1), obtain an MRI of the pituitary with gadolinium if the prolactin is >100 ng/mL.
●For any degree of prolactin elevation, assess possibility of temporarily discontinuing medication or substituting an alternative medication that does not cause hyperprolactinemia (in consultation with prescribing physician). Remeasure serum prolactin approximately one week after discontinuation or substitution. Normalization of the serum prolactin confirms drug-induced hyperprolactinemia. If hyperprolactinemia persists after drug discontinuation, obtain MRI of the pituitary with and without gadolinium, if not already obtained.
Non-medication-related hyperprolactinemia — If the patient is not taking a medication known to raise serum prolactin, obtain or review:
●Creatinine, to assess for kidney impairment
●Thyroid-stimulating hormone (TSH) to assess for hypothyroidism
If hyperprolactinemia is solely the result of hypothyroidism, it will remit as the hypothyroidism is corrected.
In patients without chronic kidney disease (CKD) or hypothyroidism, obtain MRI of the pituitary with and without gadolinium to look for a mass lesion in the hypothalamic-pituitary region. If there is doubt about the diagnosis of hyperprolactinemia (due to the absence of typical symptoms), measure macroprolactin before proceeding with MRI. Macroprolactin is an aggregate of prolactin and antibodies that are detected by the prolactin assay but that are not biologically active. Therefore, macroprolactinemia does not cause symptoms. Patients with macroprolactinemia can be misdiagnosed and treated as ordinary hyperprolactinemia. (See "Clinical manifestations and evaluation of hyperprolactinemia", section on 'Macroprolactin'.)
In patients with CKD, the need for pituitary imaging depends on the degree of renal impairment. (See 'Chronic kidney disease' below.)
Chronic kidney disease — Hyperprolactinemia in chronic kidney disease (CKD) is due to decreased clearance of prolactin. Serum prolactin concentrations are typically elevated to as much as 10-fold normal in patients with end-stage kidney disease requiring dialysis. Prolactin levels of this magnitude in the setting of end-stage kidney disease (eg, CKD 4 or 5) and in the absence of other pituitary hormone abnormalities or symptoms suggestive of pituitary adenoma (eg, visual symptoms) typically need no further pituitary evaluation.
It is unclear at which threshold of kidney dysfunction prolactin begins to rise. Therefore, in the setting of lesser degrees of renal impairment, the need for pituitary imaging is uncertain. Very mild degrees of renal impairment probably do not elevate prolactin. The decision to obtain an MRI of the pituitary is based on the magnitude of the prolactin elevation, the degree of renal impairment, and on other findings, such as visual impairment and other pituitary hormone abnormalities. MRI for a patient with any degree of renal impairment should be ordered without gadolinium.
REFERENCE RANGE —
The usual normal range for serum prolactin is up to 20 ng/mL (20 mcg/L [SI units]) in males and postmenopausal females and up to 30 ng/mL (30 mcg/L) in premenopausal females. Interpretation of a specific abnormal test result should be based upon the reference range reported with that result.
CITATIONS —
The supporting references for this content are accessible in the linked topics.
