Hyperprolactinemia Clinical Presentation

Updated: Feb 09, 2022
  • Author: Donald Shenenberger, MD, FAAD, FAAFP; Chief Editor: George T Griffing, MD  more...
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Women typically present with a history of oligomenorrhea, amenorrhea, or infertility, which generally results from prolactin suppression of gonadotropin-releasing hormone (GnRH). Galactorrhea is due to the direct physiologic effect of prolactin on breast epithelial cells.

Men typically present with complaints of sexual dysfunction (although the aforementioned study by Rubio-Abadal et al found the prevalence of sexual dysfunction equal between men and women), [3] visual problems, or headache and are subsequently diagnosed with hyperprolactinemia in the evaluation process. Prolactin suppresses GnRH, causing a decrease in luteinizing hormone and follicle-stimulating hormone, ultimately leading to decreased serum testosterone levels and hypogonadism. Prolactinoma in men also may cause neurologic symptoms, particularly visual-field defects.

In both sexes, the presence of a pituitary tumor may cause visual-field defects or headache. Most patients with a prolactinoma (the most common type of pituitary adenoma) are women.



Physical findings most commonly encountered in patients with hyperprolactinemia are galactorrhea and, in the case of prolactinomas, visual-field defects. Typically, the diagnosis is made via the aid of laboratory studies.



The diagnosis of hyperprolactinemia should be included in the differential for female patients presenting with oligomenorrhea, amenorrhea, galactorrhea, or infertility or for male patients presenting with sexual dysfunction (although the aforementioned study by Rubio-Abadal et al found the prevalence of sexual dysfunction equal between men and women). [3] The condition is discovered in the course of evaluating the patient's problem. Once discovered, hyperprolactinemia has a broad differential that includes many normal physiologic conditions.

Pregnancy should always be excluded unless the patient is postmenopausal or has had a hysterectomy. In addition, hyperprolactinemia is a normal finding in the postpartum period.

Other common conditions to exclude include a nonfasting sample, excessive exercise, a history of chest wall surgery or trauma, renal failure, and cirrhosis. Postictal patients also develop hyperprolactinemia within 1-2 hours after a seizure. These conditions usually produce a prolactin level of less than 50 ng/mL.

Hypothyroidism, an easily treated disorder, also may produce a similar prolactin level.

Detailed drug history should be obtained because many common medications cause hyperprolactinemia, usually with prolactin levels of less than 100 ng/mL. Drugs that may cause the condition can include the following [9] :

  • Dopamine-receptor antagonists (eg, phenothiazines, butyrophenones, thioxanthenes, risperidone, metoclopramide, sulpiride, pimozide)

  • Dopamine-depleting agents (eg, methyldopa, reserpine)

  • Others (eg, isoniazid, danazol, tricyclic antidepressants, monoamine antihypertensives, verapamil, estrogens, antiandrogens, cyproheptadine, opiates, H2-blockers [cimetidine], cocaine)

If no obvious cause is identified or if a tumor is suspected, MRI should be performed.

Although no single test can help determine the etiology of hyperprolactinemia, a prolactinoma is likely if the prolactin level is greater than 250 ng/mL and less likely if the level is less than 100 ng/mL. [10] Although medications can cause significant elevation of prolactin, a level of 500 ng/mL or greater is diagnostic of a macroprolactinoma.

Prolactin-secreting adenomas are divided into 2 groups: (1) microadenomas (more common in premenopausal women), which are smaller than 10 mm and (2) macroadenomas (more common in men and postmenopausal women), which are 10 mm or larger.

If the prolactin level is greater than 100 ng/mL or less than 250 ng/mL, the evaluating physician must decide whether a radiographic study is indicated. In many cases, with the availability of MRI scanners, imaging is performed earlier and at lower prolactin levels to rule out a non–prolactin-producing tumor.

When the underlying cause (physiologic, medical, pharmacologic) cannot be determined and an MRI does not identify an adenoma, idiopathic hyperprolactinemia is diagnosed.

Another potential cause of hyperprolactinemia is macroprolactinemia. The majority of prolactin in the bloodstream is monomeric (approximately 85%). However, dimeric and polymeric forms may also coexist. Macroprolactinemia is the apparent increase in serum prolactin without typical symptoms. In this condition, serum prolactin molecules can polymerize and subsequently bind to immunoglobulin G (IgG). This form of prolactin is unable to bind to prolactin receptors and exhibits no systemic response. In the asymptomatic patient with hyperprolactinemia, this condition should be considered. The discovery of macroprolactinemia could save the patient the inconvenience and cost of an in-depth evaluation for a microadenoma. Consult laboratory personnel for any special collecting requirements. Women with macroprolactinemia are able to conceive. This condition generally requires no treatment.