eMedicine Specialties > Endocrinology > Pituitary Gland

Hyperprolactinemia

Author: Donald Shenenberger, MD, FAAFP, Staff Dermatologist, Department of Dermatology, Naval Medical Center Portsmouth
Contributor Information and Disclosures

Updated: Aug 12, 2009

Introduction

Background

Hyperprolactinemia is a condition of elevated serum prolactin. Prolactin is a 198 – amino acid protein (23-kD) produced in the lactotroph cells of the anterior pituitary gland. Its primary function is to enhance breast development during pregnancy and to induce lactation. However, prolactin also binds to specific receptors in the gonads, lymphoid cells, and liver.¹ Secretion is pulsatile; it increases with sleep, stress, pregnancy, and chest wall stimulation or trauma, and therefore must be drawn after fasting. Normal fasting values are generally less than 30 ng/mL, depending on the individual laboratory.

Pathophysiology

The primary action of prolactin is to stimulate breast epithelial cell proliferation and induce milk production. Estrogen stimulates the proliferation of pituitary lactotroph cells, resulting in an increased quantity of these cells in premenopausal women, especially during pregnancy. However, lactation is inhibited by the high levels of estrogen and progesterone during pregnancy. The rapid decline of estrogen and progesterone in the postpartum period allows lactation to occur. During lactation and breastfeeding, ovulation may be suppressed due to the suppression of gonadotropins by prolactin.

Dopamine has the dominant influence over prolactin secretion. Secretion of prolactin is under tonic inhibitory control by dopamine, which acts via D2-type receptors located on lactotrophs. Prolactin production can be stimulated by the hypothalamic peptides, thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP). Thus, primary hypothyroidism (a high TRH state) can cause hyperprolactinemia. VIP increases prolactin in response to suckling, probably because of its action on receptors that increase adenosine 3',5'-cyclic phosphate (cAMP).

Frequency

United States

This condition occurs in less than 1% of the general population and in 10-40% of patients presenting with secondary amenorrhea. Approximately 75% of patients presenting with galactorrhea and amenorrhea have hyperprolactinemia. Of these patients, approximately 30% have prolactin-secreting tumors.

Mortality/Morbidity

• Mortality is unlikely; however, in cases where the condition is due to a large prolactin-secreting tumor, local mass effect can lead to significant morbidity.
• The condition causes systemic complaints that often resolve when the prolactin level returns to normal or once the tumor shrinks.

Sex

• Clinical presentation in women is more obvious and occurs earlier than in men. They typically present with oligomenorrhea, amenorrhea, galactorrhea, or infertility. Galactorrhea is less common in postmenopausal women due to lack of estrogen. If a pituitary tumor is present, it is a microadenoma (<10 mm) approximately 90% of the time.
• Prolactinoma is less common in men than in women, typically presenting as an incidental finding on a brain CT scan or MRI, or with symptoms of tumor mass effect. This is most evident as a complaint of visual disturbances or headache. By the time of diagnosis in men, approximately 60% have macroprolactinomas.

Clinical

History

• 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, 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 neurological 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

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

Causes

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. 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 include the following:
  • 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.²
  • 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. Macroprolactinemia is the apparent increase in serum prolactin without 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. If this condition is suspected, specific serum immunoassays must be performed to detect this form of prolactin. Consult laboratory personnel for any special collecting requirements. Women with macroprolactinemia are able to conceive. This condition generally requires no treatment.

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