Hyperprolactinemia

Overview
Hyperprolactinaemia (BrE) or hyperprolactinemia (AmE) is the presence of abnormally high levels of prolactin in the blood. Normal levels are less than 580 mIU/L for women, and less than 450 mIU/L for men.

The hormone prolactin is downregulated by dopamine and is upregulated by estrogen. A falsely high measurement may occur due to the presence of the biologically inactive macroprolactin in the serum. This can show up as high prolactin in some types of tests, but is asymptomatic.

Causes
Hyperprolactinaemia may be caused by either disinhibition (e.g. compression of the pituitary stalk or reduced dopamine levels) or excess production from a prolactinoma (a pituitary gland adenoma tumour). A prolactin level of 1000–5000mIU/L could be from either mechanism, but >5000mIU/L is likely due to an adenoma with macroadenomas (large tumours over 10 mm diameter) having levels of up to 100,000mIU/L. Hyperprolactinemia inhibits gonadotropin-releasing hormone (GnRH) by increasing the release of dopamine from the arcuate nucleus of the hypothalamus (dopamine inhibits GnRH secretion), thus inhibiting gonadal steroidogenesis, which is the cause of many of the symptoms described below:

Physiological causes
Physiological causes (i.e. as result of normal body functioning): pregnancy, breastfeeding, stress, sleep.

Prescription drugs
Use of prescription drugs are the most common cause of hyperprolactinaemia. Prolactin secretion in the pituitary is normally suppressed by the brain chemical, dopamine. Drugs that block the effects of dopamine at the pituitary or deplete dopamine stores in the brain may cause the pituitary to secrete prolactin. These drugs include the major tranquilizers (phenothiazines), trifluoperazine (Stelazine), ,and haloperidol (Haldol); some antipsychotic medications; metoclopramide (Reglan), used to treat gastroesophageal reflux and the nausea caused by certain cancer drugs; and less often, alpha-methyldopa and reserpine, used to control hypertension. Finally oestrogens and TRH.

Diseases
Prolactinoma or other tumors arising in or near the pituitary—such as those that cause acromegaly or Cushing's syndrome—may block the flow of dopamine from the brain to the prolactin-secreting cells, likewise division of the pituitary stalk or hypothalamic disease. Other causes include chronic renal failure, hypothyroidism and sarcoidosis. Some women with polycystic ovary syndrome may have mildly elevated prolactin levels.

Apart from diagnosing hyperprolactinaemia and hypopituitarism, prolactin levels are often determined by physicians in patients who have suffered a seizure, when there is doubt whether this was an epileptic seizure or a non-epileptic seizure. Shortly after epileptic seizures, prolactin levels often rise, while they are normal in non-epileptic seizures.

Idiopathic
In many patients elevated levels remain unexplained and may represent a form of hypothalamic-pituitary dysregulation.

Symptoms
In women, a high blood level of prolactin often causes hypoestrogenism with anovulatory infertility and a decrease in menstruation. In some women, menstruation may disappear altogether (amenorrhea). In others, mensturation may become irregular or menstrual flow may change. Women who are not pregnant or nursing may begin producing breast milk. Some women may experience a loss of libido (interest in sex). Intercourse may become painful because of vaginal dryness.

In men, the most common symptoms of prolactinoma are impotence, decreased libido, erectile dysfunction, and infertility. Because men have no reliable indicator such as menstruation to signal a problem, many men with hyperprolactinemia being caused by an adenoma may delay going to the doctor until they have headaches or eye problems caused by the enlarged pituitary pressing against nearby eye nerves. They may not recognize a gradual loss of sexual function or libido. Only after treatment do some men realize they had a problem with sexual function.

Because of hypoestrogenism, hyperprolactinaemia can lead to osteoporosis.

Diagnosis
A doctor will test for prolactin blood levels in women with unexplained milk secretion (galactorrhea) or irregular menses or infertility, and in men with impaired sexual function and, in rare cases, milk secretion. If prolactin is high, a doctor will test thyroid function and ask first about other conditions and medications known to raise prolactin secretion. Whilst a plain X-ray of the bones surrounding the pituitary may reveal the presence of a large macro-adenoma, the small micro-adenoma will not be apparent. Magnetic resonance imaging (MRI) is the most sensitive test for detecting pituitary tumors and determining their size. MRI scans may be repeated periodically to assess tumor progression and the effects of therapy. Computed Tomography (CT scan) also gives an image of the pituitary, but it is less sensitive than the MRI.

In addition to assessing the size of the pituitary tumor, doctors also look for damage to surrounding tissues, and perform tests to assess whether production of other pituitary hormones is normal. Depending on the size of the tumor, the doctor may request an eye exam with measurement of visual fields.

Historical eponyms
On occasion the following eponyms may be encountered: These eponyms were established before prolactin measurements could be done reliably in the clinical setting.
 * 1) Ahumada-DelCastillo Syndrome, refers to the association of galactorrhea and amenorrhea.
 * 2) Chiari-Frommel Syndrome, refers to extended postpartum galactorrhea and amenorrhea.
 * 3) Forbes-Albright Syndrome, refers to galactorrhea-amenorrhea associated with a pituitary tumor.

Acknowledgements
The content on this page was first contributed by: C. Michael Gibson, M.S., M.D.