Hyperprolactinemia -Diagnosis, Symptoms, and Treatment

What is Hyperprolactinemia?

Hyperprolactinemia is a medical condition characterized by elevated prolactin levels in the serum.  Prolactin is a hormone secreted by the pituitary gland, which sits underneath the brain in a region called the sella turcica.  Elevated prolactin levels may occur due to normal processes of the body, such as pregnancy, nipple stimulation, and stress.  However, conditions such as pituitary tumors (e.g., prolactinoma) or the use of certain medications can also lead to increased serum prolactin levels and their manifestations.

Women with hyperprolactinemia often develop menstrual irregularities, infertility, and mild letdown from the breast.  Men usually have decreased libido, erectile dysfunction, and breast enlargement (gynecomastia).  Patients with prolactinoma may develop a headache and visual changes due to tumor enlargement and nerve compression.

What Causes Hyperprolactinemia?

Normal physiologic processes or pathologic conditions can cause hyperprolactinemia. Typical conditions that lead to elevated prolactin levels usually include pregnancy, nipple stimulation, and stress.

Pathologic conditions associated with hyperprolactinemia typically include pituitary adenoma (prolactinoma) or the use of drugs that block dopamine receptors.  Dopamine (prolactin-inhibitory factor) typically inhibits the release of prolactin from the pituitary gland – therefore, drugs that block dopamine consequently result in increased prolactin levels.

The most common drugs implicated in hyperprolactinemia include antipsychotics such as risperidone and haloperidol.  Antiemetic medications such as metoclopramide can also increase prolactin.  Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine and paroxetine may also contribute to hyperprolactinemia.

How Common is Hyperprolactinemia?

Hyperprolactinemia is relatively uncommon in the United States.  The condition may require referral to an endocrinology or neurosurgery specialist, especially if first-line measures are unsuccessful.

Hyperprolactinemia affects <1% of the general population in the United States.  About 5%-14% of individuals evaluated for secondary amenorrhea (absence of menstrual periods) have hyperprolactinemia.  One of the most common causes of the condition is pituitary adenomas (prolactinomas), which account for about 30%-40% of pituitary tumors.  The diagnosis of prolactinoma is more commonly made in women compared to men and typically occurs around age 20-40.

Signs and Symptoms

The symptoms and signs of hyperprolactinemia depend on your gender.  If you are a woman, your symptoms also depend on whether or not you have had menopause. Some hyperprolactinemia symptoms overlap between men and women.

In men, hyperprolactinemia typically causes the following symptoms:

• Decreased libido – loss of sexual desire
• Infertility
• Erectile dysfunction
• Osteoporosis
• Gynecomastia – breast enlargement

The symptoms of hyperprolactinemia in premenopausal women typically include:

• Abnormal menstruation – oligo- or amenorrhea
• Infertility
• Decreased libido
• Osteoporosis
• Galactorrhea – mild letdown from breasts

Patients with large prolactinoma may develop a headache and impaired vision due to tumor expansion and compression over the optic chiasm.  The optic chiasm is a nerve structure near the sella turcica and pituitary gland – this structure is critical for normal vision.  Pituitary tumors can expand, injuring these nerves, and resulting in loss of peripheral vision.

Headaches and visual changes may be the only manifestations of hyperprolactinemia in postmenopausal women as these individuals do not have menstrual periods and are already infertile.  Sometimes a pituitary tumor is detected incidentally on brain MRI.

Diagnosis

The diagnosis of hyperprolactinemia is suggested based on the patient’s history, symptoms, and physical examination but typically confirmed with laboratory and imaging studies.

Your doctor will usually obtain a serum prolactin level.  If this test is elevated, this may suggest pregnancy, a medication side effect, or pituitary adenoma.  Your doctor will likely want to obtain other pituitary hormone levels such a growth hormone and thyroid-stimulating hormone (TSH).  They may order a urine pregnancy test if you are a woman of childbearing age.

Patients with confirmed hyperprolactinemia often undergo brain MRI to evaluate for pituitary tumors such as prolactinoma.  Additional blood tests commonly include a CMP (comprehensive metabolic panel), CBC (complete blood cell count), and thyroid function studies (TSH, free T4).

Hyperprolactinemia Medication and Treatment

Hyperprolactinemia is typically treated by tapering, discontinuing, or switching any implicated medications such as antipsychotics (e.g., haloperidol) or antiemetics (e.g., metoclopramide).  Patients with pituitary adenomas (prolactinomas) typically benefit from initial treatment with dopamine agonists such as Dostinex (cabergoline).  Dopamine agonists are effective because they inhibit the release of prolactin from the pituitary gland.

Patients who fail to respond to cabergoline may benefit from transsphenoidal surgery to remove the prolactinoma.  This is also true in patients with large prolactinomas that produce symptoms related to brain compressions such as headache and visual changes.  Radiation therapy may also be required after tumor resection to prevent the regrowth of residual adenoma.

References:

1. Molitch ME. Drugs and prolactin. Pituitary 2008; 11:209. - https://www.ncbi.nlm.nih.gov/pubmed/18404390
2. Bayrak A, Saadat P, Mor E, et al. Pituitary imaging is indicated for the evaluation of hyperprolactinemia. Fertil Steril 2005; 84:181. - https://www.ncbi.nlm.nih.gov/pubmed/16009175
3. Casanueva FF, Molitch ME, Schlechte JA, et al. Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol (Oxf) 2006; 65:265. -https://www.ncbi.nlm.nih.gov/pubmed/16886971