Macroprolactin (+prolactin) | Laboratory research

General Information

Prolactin (PRL) is a hormone produced by the lactotropic cells of the human pituitary gland, the anterior part of the adenohypophysis. Its release is regulated by the hypothalamus. Dopamine is considered to be the main prolactin inhibitory factor and thus regulates prolactin secretion.

Prolactin is synthesized in the form of a prehormone, the molecule of which is further broken down and a monomeric form of 23 kDa molecular weight is obtained, which is the main circulating form. It is also called small prolactin. It is biologically and immunologically active.

The human prolactin molecule has a heterogeneous size, and in addition to the monomeric form, a dimeric form (with a molecular weight of 50 kDa) and a tetrameric, so-called macroprolactin molecule (with a molecular weight of 150 kDa) have been found. These two forms are practically biologically inactive. The reason for macroprolactin's inactivity is its high molecular mass, which is why it cannot reach the final target tissue.

Macroprolactin  - is a non-bioactive isoform of prolactin, which consists of a prolactin monomer and an IgG molecule and is characterized by prolonged clearance characteristic of immunoglobulins. This isoform is clinically inactive, however, its detection is often the basis for receiving incorrect data in immunological research.

Macroprolactin is a frequent cause of overdiagnostics of false hyperprolactinemia, resulting in unnecessary additional investigations and treatment. Determination of macroprolactin is not possible in all laboratories, which causes incorrect management of the condition.

Causes of hyperprolactinemia

There is an increase in the level of prolactin  Physiological და pathological reasons. However, there are cases of hyperprolactinemia that are not consistent with clinical, hormonal, or instrumental research data.

Such cases can be qualified as an idiopathic form of increased prolactin level, although in most cases macroprolactinemia is observed. It is wrong to ignore macroprolactinemia during differential diagnostics.

Physiological hyperprolactinemia is caused by:

Pregnancy

stress

pain

Excessive physical exertion

Causes of pathological hyperprolactinemia

Repetitive mechanical stimulation of the breast (e.g. when expressing milk)

Chest trauma

Liver-kidney diseases

Primary hypothyroidism

pituitary adenoma

Intracranial tumors with pituitary and/or hypothalamic compression

Empty Turkish hump syndrome

Medicines that stimulate prolactin synthesis

Dopaminergic blockers

Non-catecholamine-dependent agents

H2 receptor blockers

Tricyclic antidepressant

Idiopathic causes (including macroprolactinemia)

Pathophysiology of macroprolactinemia

The condition is characterized by an excess of circulating high-molecular-weight prolactin that binds to anti-prolactin immunoglobulin.

Macroprolactinemia is considered a condition when 30-60% of circulating prolactin in serum is present as macroprolactin.

As already mentioned, the monomeric form of prolactin is bioactive, while macroprolactin is biologically inactive, however, it retains immunoreactive properties. The macroprolactin molecule (linked to immunoglobulin) fails to interact with the prolactin receptor, which inhibits hypothalamic negative feedback and ultimately leads to hyperprolactinemia. In addition, the excretion of macroprolactin by the kidneys (compared to normal prolactin) is more difficult, which is another contributing factor to the development of chronic macroprolactinemia.

Laboratory study of macroprolactin

Macroprolactinemia is often neglected in the diagnostics of hyperprolactinemia. This results in unnecessary additional tests, misinterpretation of results and unnecessary treatment.

In order not to "mix" data of inactive prolactin with active serum prolactin and not to get data of false increase of prolactin level, separate immunoanalysis of these fractions is required.

Imaging studies of macroprolactinemia

MRI and CT studies are usually negative in macroprolactinemia. In some cases, a radiological deviation from the norm may be observed, although such cases are much less frequent than in true hyperprolactinemia.

Macroprolactinemia is not related to age and sex. It can occur in anyone, but is more common in women.

Symptoms

Patients with macroprolactinemia, as a rule, rarely have cycle disturbances, minimally expressed galactorrhea.

The clinical picture of hyperprolactinemia is usually manifested in those patients who have a simultaneous increase of small and macroprolactin in the serum.

The asymptomatic course of macroprolactinemia is probably related to the binding of antibodies to prolactin receptor epitopes and their biological inactivation.

When should we take a test for macroprolactin?

• Hyperprolactinemia in asymptomatic patients;
• Hyperprolactinemia in the absence of evidence of pituitary damage.

How to prepare for the test?

Because prolactin concentrations vary at different times of the day, it is recommended that the test be performed in the morning, within 2 hours of waking up.

Blood should not be taken after a gynecological examination, physical exertion, stressful situations or breast stimulation. It is recommended to abstain from sexual intercourse and alcohol one day before the test.

Birth control pills, blood pressure medications, antidepressants can affect the results and should be discontinued as prescribed by your doctor.

Research material

Venous blood

Possible interpretation of the results

The results form shows the level of basal prolactin (quantification) and the qualitative indicator of macroprolactin: positive, borderline, negative.

Positive result:

Hyperprolactinemia is caused by the presence of a biologically inactive fraction of prolactin (Big-Big). Pituitary adenoma is not excluded.

Negative result:

Hyperprolactinemia is not caused by the presence of a biologically inactive fraction of prolactin (big-big). Looking for other causes of hyperprolactinemia.