Hyperprolactinemia is a condition characterized by the abnormal concentration of prolactin in the serum.
Hyperprolactinemia is a condition in which serum prolactin levels are increased (PRL>20 ng/mL) in the absence of pregnancy or lactation. Production of prolactin may grow due to a number of different reasons – both physiologic and pathologic. Some medications when administered for a long period of time influence on the production of prolactin and may cause hyperprolactinemia. Nevertheless, prolactin-secreting tumors are the most common reason for this condition. Additionally, some drugs and substances may elevate serum prolactin. Increased prolactin levels impair a person’s fertility, influence on the functioning of the reproductive system and promote the production of milk in the absence of nursing.
What is prolactin?
Prolactin is the protein produced by the lactotroph cells of the adenohypophysis. Prolactin is necessary for breast development during pregnancy and to promote lactation (milk production). The secretion of prolactin is controlled by the hypothalamus and has a pulsatile manner. Normal values of prolactin are 25-30 ng/mL, although it may vary depending on the laboratory. Women tend to have higher prolactin concentrations in the serum.
This hormone is essential for the body as it:
- Induces growth of the breast ducts;
- Promotes the development of the breast alveoli;
- Is responsible for the synthesis of milk proteins – casein and lactalbumin;
- Controls the metabolism of subcutaneous fat;
- Influences carbohydrate, calcium and vitamin D metabolism;
- Promotes the development of the lungs of the fetus;
- Is responsible for steroidogenesis and affects the levels of estrogen and testosterone in males and females;
To comply with its functions prolactin binds to the receptors on the cells of the breast, adrenal glands, ovaries, testes, prostate, kidney, and liver.
Physiologic causes of hyperprolactinemia
- During the REM phase of sleep;
- Sexual intercourse;
- Breastfeeding, babies crying and nipple stimulation;
- Stress such as traumatic injury or surgical intervention;
- Familial due to mutant prolactin receptor;
Drugs associated with increased prolactin levels
- Cimetidine and ranitidine;
- Opiates (heroin, methadone, morphine);
- Protease inhibitors (omeprazole, pantoprazole);
- Selective serotonin reuptake inhibitors (fluoxetine);
- Tricyclic antidepressants (amitriptyline, clomipramine);
Diseases which cause hyperprolactinemia
- Disorders of the pituitary: micro- and macroadenoma secreting prolactin; acromegaly; pituitary stalk damage due to trauma or surgery;
- Hypothalamic diseases: craniopharyngioma; other tumors of the hypothalamus;
- Chest wall stimulation (after the chest surgery, mastectomy, due to herpes zoster, chest acupuncture);
- Other disorders and conditions: pseudocyesis (false pregnancy); cirrhosis; polycystic ovarian syndrome; hypothyroidism; chronic renal failure; multiple sclerosis; spinal cord lesions; systemic lupus erythematosus; epileptic seizures;
Most of the serum prolactin circulates in the blood as a free hormone, but sometimes it may be bound to an IgG antibody forming the complex called macroprolactin. As bound prolactin has a bigger molecular weight it cannot cross the vessel wall and reach the prolactin receptors. Therefore, despite the increased prolactin concentration in the blood the disorder is typically asymptomatic.
Mildly increased concentrations of prolactin do not cause any symptoms. Hyperprolactinemia leads to the development of hypogonadotropic hypogonadism and, respectively, dysfunctions of the reproductive system such as menstrual disturbances, infertility, amenorrhea, erectile dysfunction, decreased libido, etc.
- In females typical symptoms of hyperprolactinemia are amenorrhea (absence of the periods) or oligomenorrhea (light or infrequent periods), and infertility. Prolactinemia causes estrogen deficiency and, therefore, results in the vaginal dryness and dyspareunia (pain during sexual intercourse), irritability, depression, and anxiety or even osteoporosis. Unlike men, women typically develop galactorrhea (lactation in the absence of pregnancy or breastfeeding) which is accompanied by breast pain.
- Males with hyperprolactinemia have decreased libido, erectile dysfunction, decreased muscle mass, reduced body hair and sometimes gynecomastia (enlarged breasts). However, in men galactorrhea occurs rarely.
The pituitary tumor may compress the optic nerve and, therefore, the person’s vision will be affected with possible visual field deficits. The growing brain tumor also causes headaches. These symptoms are more likely to be observed in males in this case the diagnosis is typically made later when the pituitary adenoma has already reached a significant size.
Fasting prolactin should be evaluated for several times to make a diagnosis and estimate the levels of prolactin in the blood. The upper limit of normal serum prolactin is approximately 500 mIU/L (24 ng/mL). In non-pregnant and non-lactating patients, monomeric prolactin concentrations of 500–1000 mIU/L (24–47 ng/mL) may be induced by any kind of stress or drugs, so it is recommended to repeat the test. Levels between 1000 and 5000 mIU/L (47–236 ng/mL) are likely to occur due to certain drugs, microprolactinoma (small adenoma of the hypophysis) or hypothalamic disorders. Levels above 5000 mIU/L (236 ng/mL) are suggestive of a macroprolactinoma (adenoma bigger than 1 cm in diameter).
Other sexual hormones should also be measured. CT or MRI scans of the brain will be helpful to discover the pituitary adenoma. Other possible causes of hyperprolactinemia should be ruled out.
Treatment of hyperprolactinemia depends on the cause of increased prolactin concentration in the serum and requires its treatment. Dopamine agonists (cabergoline, bromocriptine) effectively decrease prolactin levels and relieve the symptoms regardless of the underlying cause. These medications can also shrink the tumor.
In case of drug-induced hyperprolactinemia, the administration of the causative drug should be ceased.
Macroadenomas should be treated surgically via transsphenoidal resection of the pituitary, whereas microadenomas typically do not require surgical interventions. In severe, poorly responsive to treatment cases radiation therapy may be administered.
Sometimes the disorder resolves spontaneously.