Hyperprolactinemia

What is Hyperprolactinemia?

The hormone prolactin is made and released only by a part of the brain known as the anterior pituitary gland. This gland produces between 200-536 micrograms of prolactin per day for each square meter of body surface area. The hormone is broken down (or ‘metabolized’) mostly by the liver (75%), with the kidneys handling the remaining 25%. It usually stays in your body between 25 to 50 minutes before it’s broken down.

Normally, the level of prolactin in women averages about 13 nanograms per milliliter (ng/ml), while in men, it averages about 5 ng/ml. Most laboratories consider 15 to 20 ng/ml as the upper limit of normal for this hormone. If the amount of prolactin in the blood is higher than this upper limit, it’s called ‘hyperprolactinemia’.

There are many reasons why someone might have hyperprolactinemia; it can be due to natural body processes (physiological), because of disease or conditions in the body (pathological), or due to certain medications. Some people with hyperprolactinemia may not have any symptoms, while others could experience symptoms like a decrease in sex hormone levels (‘hypogonadism’) or milky discharge from the nipple (‘galactorrhea’).

What Causes Hyperprolactinemia?

Hyperprolactinemia is a condition where there is too much prolactin, a hormone, in the body. There are three types of this condition, namely: physiological, pathological, and pharmacological. Physiologic hyperprolactinemia is temporary and natural, while pathological and pharmacological types come with unwanted long-term effects.

Let’s take a closer look at the reasons behind hyperprolactinemia:

Physioligical causes of hyperprolactinemia include:

* Pregnancy
* Stimulation of the breast and breastfeeding
* Exercise
* Stress, such as low blood sugar, heart attack, surgery
* Seizures
* Sleep
* The period just after child birth
* Sex

During pregnancy, the pituitary gland, which is responsible for secretion of prolactin doubles in size. As a result, prolactin levels increase throughout the pregnancy reaching a peak when the baby is delivered. Breasfeeding helps to normalize prolactin levels in the body after childbirth. Additionally, stimulation of the breasts like during breasfeeding can lead to increased secretion of prolactin.

Pathological causes of hyperprolactinemia are related diseases, including:

* Prolactinoma, a noncancerous tumour that accounts for 40% of all pituitary tumours
* Acromegaly
* Cushing disease
* Plurihormonal adenoma
* Inflammation of the pituitary gland
* Parasellar mass
* Macroprolactinemia

Hypothalamic diseases can also cause hyperprolactinemia through damage to the stalk of the gland, which connects the hypothalamus to the pituitary gland. This can be caused by a range of conditions including tumours, cysts, head trauma, or exposure to radiation.

Pharmacological causes relate to the medication one is taking. These can include:

* Estrogen therapy
* Thyrotropin-releasing hormone
* Antipsychotic medications: risperidone, haloperidol, fluphenazine, etc.
* Antiemetic medications: metoclopramide, domperidone, prochlorperazine
* Antidepressants: amitriptyline, clomipramine, fluoxetine
* Anticonvulsant medicine: phenytoin
* Antihypertensive medication: verapamil, methyldopa, labetalol
* Antihistamines: cimetidine, ranitidine
* Opioid painkillers: methadone, morphine, apomorphine, heroin
* Cholinergic medicine: physostigmine

Certain systemic disorders can also cause hyperprolactinemia:

* Chronic kidney failure
* Polycystic ovary disease
* Liver cirrhosis
* False pregnancy
* Chest injury, surgery, or shingles
* Underactive thyroid gland

Additionally, there can be genetic reasons for hyperprolactinemia, such as an inactive prolactin receptor mutation. Certain types of cancer, such as lung and kidney, can also cause prolactin levels to rise in the body. In some cases, the reason behind increased prolactin levels can remain unknown.

Risk Factors and Frequency for Hyperprolactinemia

Hyperprolactinemia, which is an overly high level of the hormone prolactin in the body, affects few people – less than 1% of the general population. It’s a bit more common among patients who experience secondary amenorrhea (an absence of menstrual periods), affecting 5% to 14% of these individuals. The most common cause of hyperprolactinemia is a tumor that secrets prolactin, known as a prolactinoma. This accounts for around 40% of clinically detected pituitary gland tumors, a type of gland in the brain.

• Hyperprolactinemia is a condition where the hormone prolactin is too high in the body.
• It occurs in less than 1% of all people, but 5% to 14% of those with secondary amenorrhea.
• The most common cause is a prolactin-secreting tumor called a prolactinoma, which makes up about 40% of all clinically identified pituitary gland tumors.
• Around 30 women out of 100,000 and 10 men out of 100,000 have a prolactinoma.
• It’s most prevalent in women aged 25 to 34.
• Women tend to show clear symptoms and get diagnosed earlier than men.

Signs and Symptoms of Hyperprolactinemia

Hyperprolactinemia is a condition characterized by high levels of prolactin, a hormone, in the body. It can show different symptoms based on the individual’s gender and age, and the symptoms can be the result of either the excess prolactin itself or by a physical structure causing compression. Here are some common signs and symptoms:

Signs and symptoms caused by high prolactin levels:

• For women:
• Menstrual issues: inconsistent menstrual periods, no periods, heavy menstrual bleeding, or difficulty conceiving
• Milk discharge from the breasts, though not all women with the condition will experience this
• Decreased bone density
• For men:
• Hypogonadotropic hypogonadism: Decreased sex drive, difficulty having erections, trouble fathering a child, reduced sperm count or development of breast tissue
• Erectile dysfunction
• Milk discharge from the breasts, though this is rare in men
• Decreased bone density

Signs and symptoms caused by a mass effect (a physical structure causing compression):

• Headaches
• Problems with vision
• External eye muscle weakness

Testing for Hyperprolactinemia

If your doctor suspects that you might have high levels of prolactin, a hormone that plays a role in many different bodily functions, they usually start by ordering a blood test. This is called a serum prolactin test, and it’s best done in the mid-morning after you’ve been fasting, or not eating, for a bit.

It might sound strange for the test to be scheduled at this specific time, but that’s because your body naturally makes more prolactin when you’re asleep, with the highest levels usually being around 4 to 7 in the morning. While eating typically doesn’t have a big effect on your prolactin level, being in a fasted state can help ensure a more accurate reading, especially if your prolactin was a little high when it was first measured.

If the test shows that your prolactin levels are indeed elevated, your doctor will then look for the cause. This usually involves ruling out natural causes, then medication-related causes. If those are not the issue, they may then order an imaging test to look at the pituitary gland in your brain, since it’s what produces prolactin.

All of this usually involves a thorough discussion of your health history and any symptoms you might be experiencing, as well as a thorough physical examination.

Along with the serum prolactin test, your doctor may also order other lab tests based on your age, gender, and symptoms. These tests could include things like thyroid function tests, kidney function tests, insulin-like growth factor-1, and hormone tests like adrenocorticotrophic hormone, luteinizing hormone, follicle-stimulating hormone, testosterone/estradiol, and sometimes a pregnancy test.

The imaging test of choice is usually a contrast MRI of the pituitary. Depending on the results, you might also need a visual field test. This is especially true if there’s a large pituitary tumor, called a macroadenoma, present or if a tumor is pressing on a structure in your brain responsible for your eyesight, called the optic chiasm.

Diagnosing hyperprolactinemia can be tricky at times due to certain pitfalls. One of these is the ‘Hook Effect,’ which might result in a falsely low concentration of prolactin in the tests due to an issue with how the lab test is done. This is rare, though, and can be corrected by running the test again with a diluted blood sample. Another pitfall is ‘macroprolactin,’ a large complex of prolactin and antibodies that show up in tests but don’t actually do anything in your body. This can be mistaken for hyperprolactinemia, or too much prolactin. To avoid this, your doctor might have your blood sample treated with a substance called polyethylene glycol before testing it for prolactin.

Treatment Options for Hyperprolactinemia

Firstly, we need to determine what is causing the high levels of prolactin, a hormone, in the body. This condition is known as hyperprolactinemia. After ruling out natural causes, the treatment can focus on addressing any other potential causes, often related to certain medical conditions. Different causes of hyperprolactinemia require different treatment methods.

If an underactive thyroid (hypothyroidism) is causing high prolactin levels, doctors will use therapy to replace the thyroid hormone. This treatment should restore prolactin levels to normal.

If a certain medication is causing hyperprolactinemia, the drug should be stopped temporarily if possible, to check if prolactin levels return to normal. However, this is only necessary if the patient is experiencing low levels of sex hormones, increased bone weakness, or excessive milk production from the breast. If the medication vital and cannot be stopped, it should be switched to a different type that doesn’t cause an increase in prolactin, such as quetiapine. If such a change is not feasible, then doctors may consider adding in drugs known as dopamine agonists. Speaking with a psychiatrist before making these changes is crucial. Some patients might need additional treatment, like estradiol in women and testosterone in men. If these strategies do not work or are impossible to implement, imaging of the pituitary gland, a small organ at the base of the brain, should be performed.

If the tumor or disease damaging the stalk, the connection between the pituitary gland and the brain, is removable, then this should be the first approach. If not, treatment should focus on reducing prolactin levels through the use of dopamine agonists.

In the case of idiopathic hyperprolactinemia, where there is no apparent cause, treatment with dopamine agonists is also recommended. However, sensitivity to these drugs might be decreased. The dose can be adjusted to maintain a normal prolactin level. If prolactin levels stabilize at normal levels for two years with the lowest possible dose of dopamine agonists, the medication may be stopped.

Macroprolactinemia, a condition where large molecules of prolactin circulate in the blood, does not require specific treatment.

Prolactinoma, tumors that produce a high amount of prolactin, can be treated medically, surgically, and with radiation. Asymptomatic small adenomas, benign tumors found in the pituitary gland, do not need to be treated with medication. However, both smaller and larger adenomas causing symptoms can be reduced with dopamine agonists, which also help normalize prolactin levels and restore normal hormonal function. Drugs like Cabergoline and bromocriptine are typically used. Cabergoline is a preferred treatment because of its effectiveness and lower side effects. It is administered once or twice a week. Potential side effects include nausea, vomiting, nasal stiffness, digital vasospasm, depression, and low blood pressure when standing. If Dopamine agonist therapy successfully normalizes serum prolactin levels and no adenoma is detectable via MRI for 2 years, this kind of treatment can be eased and eventually stopped.

Most prolactinomas can be managed medically. Surgery and radiation treatment are reserved for those unresponsive or resistant to dopamine agonists. Surgery involves removing the tumor via the nasal passage. Women with large prolactinomas potentially jeopardizing vision during pregnancy might undergo preemptive surgery. Radiation therapy can be considered for remaining tumor tissue. Advanced radiation techniques, like Gamma knife stereotactic radiosurgery, are often effective in treating prolactinomas resistant to dopamine agonists.

What else can Hyperprolactinemia be?

Hyperprolactinemia is a condition caused by high levels of prolactin in the body. In a medical context, it’s crucial to rule out two main causes: hypothyroidism (underactive thyroid) and the use of certain drugs that block dopamine. However, a variety of other reasons can also lead to this condition. Namely:

• Liver disease (cirrhosis)
• Medications that work against dopamine (dopamine antagonist medications)
• Disorders of the hypothalamus part of the brain (hypothalamic disease)
• Hyperprolactinemia without a known cause (idiopathic hyperprolactinemia)
• Tumors in the pituitary gland (pituitary tumors)
• Being pregnant (pregnancy)
• Underactive thyroid gland (primary hypothyroidism)
• Noncancerous tumor of the pituitary gland that produces a high amount of prolactin (prolactinoma)
• Failure of the kidneys to work properly (renal failure)

What to expect with Hyperprolactinemia

Patients with a small type of brain tumor called micro prolactinoma generally have a good outlook and can normalize their prolactin hormone levels through treatment. These patients can be managed with medical treatments for an extended period of time.

The success of surgery on the pituitary gland, where these tumors are located, often depends on the size of the tumor, the amount of prolactin hormone in the blood, and the skill and experience of the surgeon. Interestingly, the success rate of this type of surgery is better when the tumor size and prolactin levels are lower.

Although surgery for micro prolactinoma has a high likelihood of success, the recurrence of high prolactin levels is relatively high, affecting about 17% of patients initially considered cured.

When it comes to surgery for larger brain tumors called macroprolactinomas, around 50% of patients enter remission after the surgery, meaning their disease is controlled and symptoms are improved. However, for invasive tumors that are more aggressive and spread into surrounding tissue, complete removal may not be possible. Only about 32% of these patients experience normalized prolactin levels after surgery, and their disease recurs about 19% of the time.

Possible Complications When Diagnosed with Hyperprolactinemia

There are several possible effects and complications related to this condition. These might include problems that cause vision loss, issues with the cranial nerves and severe pituitary gland problems. Some people may also have trouble conceiving a child, or experience a decrease in bone density, known as osteoporosis. In severe cases, it can even result in complete loss of sight. Other potential issues are linked to cerebrospinal fluid leak and deficiency of all the pituitary hormones, a condition known as hypopituitarism. Lastly, some individuals may experience hypogonadism, where sex glands produce little or no sex hormones.

Common Side Effects:

• Visual deficits
• Cranial nerve issues
• Severe pituitary gland problems
• Infertility
• Osteoporosis
• Blindness
• Complications from cerebrospinal fluid leak
• Hypopituitarism
• Hypogonadism

Preventing Hyperprolactinemia

Prolactin is a hormone that our pituitary gland produces. There are several conditions that can cause our bodies to make too much prolactin. One of the main reasons this happens is due to a noncancerous tumor in the pituitary gland known as a prolactinoma. This tumor can often lead to irregular menstrual cycles, milk production from the breasts, weakened bones, headaches, and issues with our field of vision. To analyze this condition, a MRI, or a detailed picture of the brain, may be needed.

Frequently, medication is used to treat this condition by regulating the concentration of prolactin and shrinking the tumor in size. However, in rare cases, medication might not be efficient in managing the prolactin levels. In such circumstances, doctors might recommend surgery or, very rarely, radiation therapy.