Macroprolactin

Why this test?

• To diagnose a form of hyperprolactinemia, especially when there are no specific symptoms with a significant increase in prolactin concentration.
• To determine the need for treatment of patients with hyperprolactinemia, as well as to make a prognosis of the disease.
• To exclude macroprolactinemia as a cause of menstrual irregularities.
• To exclude macroprolactinemia as a cause of female and male infertility.

In what cases is it prescribed?

• In case of symptoms of hyperprolactinemia: oligo / amenorrhea, galactorrhea and infertility in women, decreased libido, erectile dysfunction and infertility in men.
• In asymptomatic hyperprolactinemia (increased serum prolactin concentration of more than 250 mg/L in the absence of symptoms of hyperprolactinemia).
• In the differential diagnosis of hyperprolactinemia caused by an increase in the concentration of prolactin monomer.

Test information

Prolactin is present in the blood in three forms: 85% - in the form of a monomer (monoprolactin), this is the most active form of prolactin, 10% - in the form of a dimer (big prolactin), and about 5% is a complex of prolactin monomer and immunoglobulin G, called macroprolactin (big-big prolactin), this form is the largest (its molecular weight is about 200 kD), but the least active.

Prolactin (from English «promotion» - «stimulation», «lactation - «lactation»«) is formed in the lactotrophs of the adenohypophysis. The main function of this hormone is to ensure lactation in the mammary glands of a breastfeeding woman. Moreover, pregnancy and lactation are the only conditions in which a persistent increase in prolactin levels is normal, in other cases it is a violation.

Regulation of prolactin synthesis is provided by interaction with hypothalamic hormones and sex hormones. In the body of a healthy non-pregnant woman and a healthy man, the synthesis and secretion of prolactin are suppressed due to the effect of dopamine secreted by the hypothalamic cells on the lactotrophs of the adenohypophysis. If the relationship between the hypothalamus and the pituitary gland is disrupted (for example, with a tumor or brain injury that destroys the anatomical connection between the hypothalamus and the pituitary gland, or with the use of drugs that block dopamine receptors), lactotrophs synthesize prolactin, its concentration in the serum increases, leading to hyperprolactinemia.

Prolactin levels can increase in many diseases (e.g. hypothyroidism, chronic renal failure, HIV). The most common cause of hyperprolactinemia in adults is a benign tumor of the adenohypophysis prolactinoma. Prolactinoma tumor cells have significantly fewer dopamine receptors and therefore function independently of the hypothalamus. On the other hand, as in the case of other benign tumors, these cells are able to synthesize normal prolactin. Since the synthesis of prolactin occurs in an autonomous mode from the hypothalamus, hyperprolactinemia occurs. As a rule, the level of hyperprolactinemia depends on the size of the prolactinoma. In microadenomas (prolactinoma size less than 10 mm in diameter), the level of prolactin reaches 200-250 mg/L, while in macroadenomas (more than 10 mm in diameter) - up to 500 mg/L and above. Although, it should be said that this dependence is not observed in all cases.

In the body of a lactating woman, high levels of prolactin suppress the secretion of gonadotropin-releasing hormone (GnRH) of the hypothalamus, disrupts the cyclic secretion of sex hormones and ensures the absence of ovulation for almost the entire period of lactation. The increased amount of prolactin in the body of a non-pregnant woman also suppresses GnRH and gonadal function, which leads to anovulation, amenorrhea and, as a result, infertility. Prolonged disruption of the cyclic secretion of sex hormones increases the risk of osteoporosis and breast cancer in women. In men, the suppression of GnRH and a decrease in testosterone levels is accompanied by a decrease in libido and erectile dysfunction.

A frequent manifestation of hyperprolactinemia (only in women) is galactorrhea, which occurs as a result of the direct effect of prolactin on breast cells. Large prolactinoma compresses the neighboring structures of the brain, which may be accompanied by visual impairment (compression of the visual crossing) and headache (increased intracranial pressure).

The second most common cause of hyperprolactinemia is medication. Hyperprolactinemia caused by them is usually not accompanied by a significant increase in prolactin concentration. However, when taking risperidone, phenothiazines and metoclopramide, the prolactin level can reach more than 200 mg/L (for comparison, the prolactin concentration in late pregnancy is 150-300 mg/L).

The severity of symptoms in hyperprolactinemia depends not only on the concentration of prolactin, but also on its form. In approximately 40% of cases, the concentration of prolactin increases due to macroprolactin (macroprolactinemia).

Macroprolactinemia has some characteristic features. In the macroprolactin molecule, prolactin is combined with autoantibodies to it - IgG immunoglobulin. Whether these autoantibodies are the direct cause of the disease (as, for example, autoantibodies to insulin in type I diabetes mellitus) or arise in response to an increase in prolactin concentration (reactive autoantibodies) is not fully understood. Unlike prolactin monomer, larger macroprolactin is excreted by the kidneys longer. Therefore, with macroprolactinemia, prolactin levels often increase significantly, up to 600 mg/L or more. At the same time, as a result of interaction with autoantibodies, the activity of prolactin in the macroprolactin molecule is very reduced. Therefore, in contrast to hyperprolactinemia caused by an increase in the concentration of prolactin in the form of a monomer (true hyperprolactinemia), macroprolactinemia is characterized by an asymptomatic course or occurs in a mild form. Its most common symptom is menstrual irregularities, while galactorrhea and infertility are less common.

Another feature of macroprolactinemia is that prolactinoma can be diagnosed only in 10-20% of patients. As a rule, prolactinomas in macroprolactinemia are microadenomas. In this regard, symptoms such as visual disturbances or headaches are not typical for macroprolactinemia. In the other, overwhelming, number of cases of macroprolactinemia, the cause of increased prolactin concentration cannot be identified and macroprolactinemia is classified as idiopathic.

Macroprolactinemia is characterized by a favorable course. Even with a steady increase in the concentration of macroprolactin, the symptoms of the disease do not progress and, unlike true hyperprolactinemia, the risk of developing complications such as osteoporosis and breast cancer does not increase.

In macroprolactinemia, the presence of autoantibodies to prolactin is noted, but there is no convincing evidence of an increased risk of autoimmune diseases in such patients.

In addition, despite the inherent features of macroprolactinemia, it is impossible to recognize true hyperprolactinemia and macroprolactinemia on the basis of clinical picture alone, so all patients with hyperprolactinemia should have their macroprolactin levels measured