hyperprolactinemia



OVERVIEW

Definition

Hyperprolactinemia is a pathophysiological condition in which peripheral blood prolactin (PRL) levels are persistently elevated for various reasons.

The basal level of serum PRL in normal subjects is usually <20ng/ml.

Morbidity

The annual incidence of hyperprolactinemia is reported to be 23.9/100,000 in women aged 25-34 years, which is higher than that in men.

The prevalence of hyperprolactinemia is 0.4% in the general population, and can be 9% to 17% in patients with reproductive dysfunction.

Causes

Causes

Hyperprolactinemia is mainly caused by physiological factors, pharmacological factors and diseases.

Physiologic factors

Physiologic prolactin (PRL) elevation is mainly related to estrogen elevation, and PRL elevation caused by physiologic factors is usually less than 50ng/ml.

Physiologic hyperprolactinemia occurs most often during pregnancy and during postpartum lactation.

PRL also fluctuates with estrogen during the menstrual cycle, remaining high during the luteal phase.

There is a circadian rhythm to PRL secretion, with PRL beginning to rise at night about 1 hour after sleep, peaking at 3 to 6 o’clock midnight, and then slowly declining, with PRL above basal levels in the morning around awakening, and then declining to its lowest value of the day around 9 to 11 am.

PRL rises within 30 minutes of eating a meal (especially eating high-protein, high-fat foods).

Blood PRL levels can be transiently elevated during stressful situations, such as emotional stress, cold, anesthesia, surgery, low blood sugar, sex, exercise, and chest trauma.

Stimulation of the breasts and chest wall (e.g., tight underwear) can elevate blood PRL levels.

Pharmacologic Factors

A variety of drugs can cause hyperprolactinemia, the main types of drugs are as follows.

Dopamine receptor antagonists: e.g. phenothiazines, butyrophenazines (haloperidol), metoclopramide, domperidone, sulpiride, etc.

Dopamine depleting agents: e.g., methyldopa, reserpine, etc.

Anesthetics: e.g. morphine, cocaine, etc.

Dibenzazide derivatives: e.g. diazepam.

Histamine and histamine H2 receptor antagonists: e.g. cimetidine.

Monoamine oxidase inhibitors: e.g. phenelzine.

Hormones: e.g. estrogen, oral contraceptives.

Disease Factors

Diseases of the hypothalamus or neighboring areas

e.g. craniopharyngioma, glioma, head trauma causing pituitary stalk amputation, etc.

Diseases of the pituitary gland

Such as pituitary adenoma and vacuolar pterygoidism.

20% to 30% of hyperprolactinemia have pituitary tumor, the most common is prolactinoma.

Other

Primary hypothyroidism, chronic renal insufficiency, cirrhosis, hepatic encephalopathy, ectopic prolactin secretion (most commonly seen in bronchial carcinoma, renal carcinoma, etc.), herpes zoster, polycystic ovary syndrome, etc.

Unknown etiology

Some patients have abnormally elevated blood PRL levels, but the cause of the elevated blood PRL levels cannot be identified, and this type of condition is called idiopathic hyperprolactinemia.

Symptoms

Main Symptoms

Female

Menstrual disorders: mainly characterized by amenorrhea, scanty and scanty menstrual periods.

Infertility/miscarriage: Due to abnormal menstruation or the absence of ovulation during the menstrual cycle, most patients manifest infertility, and some patients are prone to miscarriage even if they succeed in conception.

Abnormal lactation: Milk secretion continues after 6 months of non-pregnancy or postpartum cessation of breastfeeding, usually manifested by discharge or extrusion of a non-bloody milky or clear fluid from both breasts. In some patients, prolactin (PRL) is excessive and lactation does not occur, or lactation may subside on its own with amenorrhea in those with prolonged disease.

Loss of libido: This is manifested by a decrease in vaginal secretions, pain and difficulty in sexual intercourse, which indirectly causes loss of libido in women.

Male

The most common manifestation is sexual dysfunction, which is mainly characterized by loss of libido and erectile dysfunction.

Other symptoms

Symptoms of nerve compression: in the case of pituitary adenoma, the enlargement of the pituitary adenoma may lead to the obstruction of cerebrospinal fluid reflux, and the compression of the peripheral brain tissues and optic nerves. The main manifestations are headache, ophthalmoplegia, visual field defect, vomiting, drowsiness and so on.

Some male patients may present with breast development, lactation, less hair, muscle atrophy, and flaccid testicular texture.

Some female patients may present with increased body hair.

Complications

Osteoporosis

Reduced estrogen levels can lead to accelerated bone loss, causing osteoporosis.

It is mainly characterized by peripheral bone and joint pain, shorter stature, hunchback, and susceptibility to fracture.

Acute pituitary stroke

If spontaneous bleeding occurs in pituitary adenoma, acute pituitary stroke may occur in a few patients.

The main manifestations are sudden severe headache, vomiting, and vision loss.

Consultation

Recommendations

Hyperprolactinemia is mainly diagnosed and treated in endocrinology.

Women with menstrual disorders, abnormal lactation, infertility, and loss of libido; men with erectile dysfunction and breast development, etc. are advised to consult the doctor promptly.

For follow-up patients, follow the doctor’s instructions.

Preparation

Registration

Before the outpatient consultation, you need to register at the hospital site or through official channels (e.g. the hospital’s official website, official app, 114 platform, etc.).

Preparation of information

Prepare your medical documents such as medical card, social security card (health insurance card), etc.

Bring information from previous visits, such as medical records, as well as results of laboratory tests (e.g. hormone measurements), MRIs, CTs, and so on.

If you are taking medication, prepare a list of medications.

What questions the doctor may ask

Is there a history of infertility? Are there any current fertility requirements?

Are menstrual cycles regular? What is the amount and duration of menstruation?

Is there any abnormal lactation? What is the color and nature of the secretions?

Is your sex life normal? Is there any loss of libido, difficulty in sexual intercourse, or erectile dysfunction (in men)?

Any loss of vision?

Any other medical conditions?

What medications have you taken recently?

What tests have you had? Any abnormal test results?

Have you been treated? What is the effect?

Questions you can ask your doctor

What tests are needed?

How to treat?

Will it come back after treatment?

Can I get pregnant in the future?

What should I pay attention to in my daily life?

Diagnosis

Diagnosis

Medical history

Taking medications that can cause elevated blood prolactin (PRL) levels, such as domperidone, cimetidine, and estrogenic birth control pills.

History of craniopharyngioma, glioma, pituitary adenoma, vacuolar pterygoidism, etc.

History of hypothyroidism, polycystic ovary syndrome, chronic renal insufficiency, cirrhosis, etc.

History of chest trauma, surgery, etc.

Clinical manifestations

The main manifestations are menstrual disorders, amenorrhea, abnormal lactation, infertility, and decreased libido in women; and erectile dysfunction in men.

It may be accompanied by headache and visual field defects.

Laboratory Tests

Hormone Measurement

Serum prolactin, luteinizing hormone, follicle stimulating hormone, estradiol, testosterone, and progesterone are measured to clarify the cause of the disease.

If the blood PRL is <100ng/ml (i.e. 4.55nmol/L), it will help to exclude hyperprolactinemia caused by many physiological or pharmacological factors, thyroid, hepatic and renal pathologies.

If the blood PRL level is persistently higher than 100ng/ml and there are clinical symptoms, imaging tests should be performed to confirm the diagnosis.

Precautions

When determining the blood PRL level, the morning of the test should be fasting or eating pure carbohydrate breakfast, and the blood test should be completed at 9~11 a.m. in order to avoid being affected by physiological hyperprolactinemia.

Before the blood draw, the patient should be awake and sit still for half an hour to minimize stress factors such as emotional tension, cold and hypoglycemia.

Other Laboratory Tests

Blood human chorionic gonadotropin (hCG), thyroid function, other pituitary hormones, liver and renal function may be performed if necessary to help clarify the cause of the disease and develop a treatment plan.

Imaging

MRI

MRI can help to exclude or determine the qualitative and localized diagnosis of saddle region lesions such as compression of the pituitary stalk, prolactin microadenoma of the pituitary gland, and vacuolar pterygoid pachydermosis, etc. It is the first choice of imaging examination for saddle region lesions.

Prolactin microadenomas often show a rounded low signal in the pituitary gland in the T1-weighted phase. The presence of microadenomas is also suggested by the presence of displaced pituitary stalks or asymmetry of the gland.

Macroadenomas are usually equivocal in T1-weighted and equivocal or hyperintense in T2-weighted images, and are often associated with bone destruction and/or cavernous sinus invasion.

Note: Remove all metal objects such as rings, earrings, keys, watches, etc. before examination.

CT

CT enhancement is helpful in confirming pituitary microadenomas or identifying their relationship to surrounding structures, and may be used if MRI is not available.

Differential Diagnosis

Endometriosis

Similarities: menstrual disorders, infertility.

Differences: endometriosis can be characterized by dysmenorrhea, chronic pelvic pain, and pain during sexual intercourse, etc. Ultrasound, hormone measurements, and laparoscopy can help to differentiate.

Treatment

The aim of treatment is to reduce the blood prolactin (PRL) level to the normal range, relieve clinical symptoms, especially sexual dysfunction, and prevent recurrence and long-term complications.

For patients with PRL tumors, especially macroadenomas, it is important to shrink or remove the tumor, relieve local compression symptoms, headache, visual field defects, blurred vision, or ocular motility disorders, and maximize the preservation of the pituitary function, avoiding further damage to the pituitary function as much as possible during the course of treatment.

General treatment

Change of medication: The medication may be changed to a comparable medication that does not raise PRL levels under the supervision of a physician.

Hyperprolactinemia due to disease can be treated accordingly after the cause is identified.

Medication

Bromocriptine

Bromocriptine is a dopamine agonist, which has been used safely for many years, and is the most commonly used medication for the treatment of this disease.

It can inhibit pituitary PRL secretion and proliferation of PRL tumor cells, thus shrinking the tumor.

Common adverse effects include nausea, vomiting, dizziness, postural hypotension, etc., which mostly disappear within a short period of time.

Blood PRL levels need to be rechecked after 1 month of continuous medication in order to make dosage adjustments according to the condition.

α-Dihydroergocryptine

It is a highly selective dopamine D2 receptor agonist and α-receptor antagonist.

The efficacy is similar to bromocriptine, with fewer cardiovascular adverse effects than bromocriptine, no postural hypotension occurs, and high long-term tolerability.

Carmeglumine

It is a highly selective dopamine D2 agonist and can be used as an alternative to bromocriptine.

It is indicated for bromocriptine-resistant individuals or for some patients who cannot tolerate bromocriptine therapy.

Adverse effects are rare, with nausea and vomiting rarely occurring.

Surgery

Surgical approach

Mostly use transsphenoidal sinus approach surgery.

Short-term administration of bromocriptine before surgery can shrink the pituitary tumor and reduce intraoperative bleeding, which can help improve the efficacy.

There is a possibility of complications after surgery, such as damage to the pituitary gland, pituitary stalk or visual crossover, resulting in urolithiasis, cerebrospinal fluid leakage, intracranial infections, etc. Therefore, it is often used as a second-line therapy.

Indications

Patients who are ineffective or ineffective on medication, intolerant of medication, or refuse to take medication for a long period of time.

Patients with giant pituitary adenoma with optic cross compression in urgent need of decompression.

Patients with normal blood PRL level after 2~3 months of drug treatment but no change of tumor body, suspected to be non-functional tumor.

Invasive pituitary adenoma with cerebrospinal fluid leakage.

Recurrent pituitary adenoma.

Relative contraindications

Poor systemic organ function that cannot tolerate surgery.

Radiation therapy

Radiation therapy is mainly indicated for patients with aggressive macroadenomas, residual or recurrent tumors after surgery, ineffective or intolerant drug therapy, contraindications to or refusal of surgery, and unwillingness to take long-term medication.

Radiation therapy may cause complications such as hypopituitarism, optic nerve damage, tumor induction, etc., and the therapeutic efficacy is slow, so simple radiation therapy is generally not advocated.

Prognosis

Cure

Most patients have a favorable prognosis after prompt and active treatment.

It has been reported that 20% of patients with idiopathic hyperprolactinemia recover spontaneously after 6 years of follow-up, 10%-15% develop microadenomas, and the development of macroadenomas is rare.

Drug therapy (bromocriptine) can only inhibit the proliferation of pituitary tumor cells, and the adenomas may regrow after short-term drug withdrawal, leading to recurrence.

The prognosis of surgical treatment depends mainly on the size of the tumor, and the recurrence rate is about 20%. The ultimate cure rate is 58% for pituitary microadenomas and 26% for macroadenomas.

Hazards

Symptoms such as menstrual disorders, abnormal lactation and gynecomastia may occur, affecting normal life and work.

It may cause infertility, decreased libido, erectile dysfunction, and difficulty in sexual intercourse, which may cause psychological burden to patients.

If not treated in time, it may cause complications such as osteoporosis and acute pituitary stroke, which may be life-threatening.

Daily

Daily management

Dietary management

Eat a balanced diet with plenty of fresh vegetables and fruits.

Avoid excessive consumption of high protein and high fat foods, such as fish, shrimp, eggs, fried chicken, barbecued meat and cakes.

Avoid spicy and stimulating foods and use less seasoning when cooking food.

Avoid estrogen-rich foods, such as royal jelly and hormone-containing tonics.

Life Management

Regular work and rest, avoid staying up late.

Take appropriate physical exercise, such as brisk walking, yoga and Tai Chi.

Quit smoking and try to avoid passive smoking.

Keep warm when going out in cold weather.

Choose cotton and comfortable underwear to avoid long-term stimulation of the breasts.

Psychological support

Relieve psychological pressure, maintain a good state of mind and avoid emotional tension.

Consult with medical personnel about disease-related knowledge, correct cognitive bias and enhance confidence in treatment.

Disease monitoring

Observe menstruation, abnormal lactation and hairiness and keep records.

If the symptoms are not relieved after treatment, it is necessary to consult the doctor in time and adjust the treatment plan according to the doctor’s instruction.

Follow-up review

Patients with hyperprolactinemia should follow the doctor’s instructions for long-term review and regular monitoring of blood prolactin levels.

Post-surgical patients should undergo imaging examination 3 months after surgery to understand the extent of tumor resection. Follow-up examinations should be performed every 6 months or 1 year as prescribed by the doctor.

Prevention

Actively treat the primary disease such as craniopharyngioma, glioma, pituitary adenoma.

For those who are taking medicines that can increase the level of prolactin in the blood (such as domperidone, lisdexamfetamine, nomefensine, diazepam, cimetidine, oral contraceptives, etc.), change the medicines or reduce the dosage under the guidance of the doctor, and follow the doctor’s instruction to monitor the level of prolactin on a regular basis.

Pay attention to keep warm and choose cotton comfortable underwear.

Keep your mood happy and avoid excessive mental stress.