Prolactinoma

What is prolactinoma?

A prolactinoma is an abnormal growth of the cells that produce the hormone prolactin in the pituitary gland, a small endocrine gland at the base of the brain. Prolactinoma leads to hyperprolactinemia or excess levels of prolactin in the bloodstream. Prolactinomas can occur in men or women but are more common in women of childbearing age.

Common symptoms in women include amenorrhea (absence of a menstrual period), infertility and nipple discharge. Symptoms in men include decreased libido, erectile dysfunction, infertility, breast tissue enlargement, and rarely, nipple discharge. Additionally, because the prolactinoma occurs at the base of the brain, it can cause headaches or vision changes.

Prolactinomas can be treated with medications to lower the prolactin levels, with surgery to remove the tumor, or with radiation.

Prolactinoma symptoms

Because many of the prolactinoma symptoms are due to sex hormone dysregulation, they differ between premenopausal women, postmenopausal women, and men.

Symptoms in premenopausal women

The following symptoms are likely in premenopausal women.

• Infertility
• Amenorrhea: This is an absence of a menstrual period.
• Irregular menstrual periods
• Nipple discharge
• Inappropriate breast milk production
• Headache
• Impaired vision
• Vision loss
• Low bone density

Symptoms in postmenopausal women

Women who have already gone through menopause may experience the following.

• Headache
• Impaired vision
• Vision Loss

Symptoms in men

Symptoms likely in men include the following.

• Decreased libido
• Erectile dysfunction
• Inability to maintain an erection
• Enlargement of breast tissue
• Nipple discharge
• Infertility

Prolactinoma causes

Most prolactinomas are due to sporadic mutations, meaning they are not inherited in families. However, there is a genetic condition multiple endocrine dysplasia or MEN1 which predisposes people to a variety of endocrine tumors including prolactinoma. Prolactinomas are almost always benign tumors and typically, once treated, the symptoms of infertility and sexual dysfunction completely resolve.

Pituitary tumor development

As mentioned in the synopsis, a prolactinoma is abnormal growth of cells in the pituitary gland, a small endocrine gland at the base of the brain. The pituitary gland is responsible for the production of multiple different hormones; one of these, prolactin, is produced by the lactotroph cells of the pituitary. The primary function of prolactin is to increase breast milk production during pregnancy and after childbirth. Normally, prolactin is only released during pregnancy and otherwise suppressed. Prolactin also affects estrogen, progesterone, and testosterone levels.

Prolactinemia development

Increased prolactin in the bloodstream is the cause of most of the symptoms of prolactinoma. However, it is important to note that although prolactinoma is the most common cause of prolactinemia, it is not the only cause. Many different conditions can cause prolactinemia, including the following.

• Normal physiology of pregnancy
• Extreme stress
• Medications like antidepressants and antipsychotics
• Hypothyroidism
• Chronic kidney disease or kidney failure

Causes details

Details regarding specific causes of this condition include the following.

• Sporadic mutations: Most prolactinomas develop from sporadic mutations. A sporadic mutation — also called a spontaneous mutation or a somatic mutation — refers to a mutation that occurs from an error in cell division during a person's lifetime. This is in contrast to a genetic mutation that was inherited from a person's parents and was present at birth.
• MEN1: Multiple endocrine neoplasia (MEN1) is a rare heritable genetic condition in which people are predisposed to multiple types of endocrine tumors. The most common tumors in MEN1 include parathyroid gland tumors, pituitary tumors like prolactinomas, and pancreatic tumors. Although the specific gene mutation in MEN1 has been identified, researchers are still unclear as to the function of the mutated gene and how it leads to tumor development.

Diagnosis

Diagnosing a prolactinoma will involve the following.

• Prolactin level: The first step in being evaluated if you have symptoms of hyperprolactinemia is having the level of prolactin in your blood tested (a serum prolactin level).
• Brain MRI: Almost all people with elevated serum prolactin levels require imaging of the brain to look for a tumor in the pituitary region. Prolactinoma is the most common cause of high prolactin levels in people who are not pregnant. It is possible to have prolactinomas that are so small they do not show up on a brain MRI. In some instances, you may need to have additional MRIs to monitor for enlargement of pituitary tumors over time.
• Other hormone testing: If a pituitary mass is visualized on MRI, you will require additional hormone level testing. The pituitary produces multiple types of hormones, and it is possible a tumor in the pituitary region is affecting the production of other hormones as well.

Treatment options and prevention for prolactinoma

Medication

The initial treatment for a prolactinoma is a dopamine agonist medication. Dopamine, a neurotransmitter, controls pituitary hormone secretion through receptors on the pituitary cells. Prolactinoma cells have a high density of dopamine receptors. Dopamine agonists bind to the dopamine receptors and block the ability of dopamine to bind, preventing the cells of the tumor from secreting prolactin. These typically improve symptoms of hyperprolactinemia and cause the tumor to shrink, improving the visual symptoms as well. The two most commonly used dopamine agonists are cabergoline and bromocriptine.

Surgery

In some people, pituitary adenomas may not respond to medical therapy. Surgery involves accessing the pituitary region through the nose and sphenoid sinus and removing as much of the tumor as possible. Unfortunately, recurrence of symptoms following surgery is relatively common as it is difficult to remove all of the abnormal cells.

Steroid replacement therapy

In women with prolactinomas who do not wish to become pregnant, treatment with estrogen and progesterone replacement is an option. However these typically will not improve fertility, so if pregnancy is desired, women need to pursue other treatment strategies. In men, testosterone replacement is an option as well.

Radiation

Radiation is typically reserved for people who have undergone surgery and have a recurrence of symptoms.

Prognosis

Prolactinomas are benign and almost always respond to medication or surgery with progressive improvement in all symptoms, including visual symptoms and headache from tumor compression of the optic nerves as well as hormonal symptoms including infertility, amenorrhea, decreased libido, and nipple discharge.

• For medication: Almost all people will have a resolution of symptoms with medication therapy.
• For surgery or radiation: Some people will require surgical removal or radiation therapy for symptom resolution.
• If medication is stopped: Approximately 25 percent of people will have a recurrence of symptoms with cessation of medication therapy.
• No treatment: About 33 percent of people will have a resolution of symptoms without any treatment at all.

Screening

People at a high risk for pituitary adenoma may be screened with period serum prolactin levels. This group includes people taking certain antipsychotics, and people with a diagnosis or family history of MEN1. It is recommended to start to screen individuals with MEN1 for pituitary adenoma at 5 years of age.

When to seek further consultation for prolactinoma

If you have any of the symptoms described above, seek medical treatment. If you have been diagnosed with MEN1, hyperprolactinemia, or pituitary adenoma, expert consultation with an endocrinologist is advised.