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Macroprolactin

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Prolactin exists in the blood in three forms:

  • 85% as a monomer (monoprolactin) – the most active form of prolactin.
  • 10% as a dimer (macroprolactin).
  • About 5% as a monomer bound to an immunoglobulin G (IgG) complex, known as macroprolactin (large-sized prolactin). This is the largest form (molecular weight ~200 kDa) but the least active.

Prolactin Synthesis and Function

Prolactin is produced by lactotrophs in the anterior pituitary (adenohypophysis).

  • Its primary function is to support lactation in the mammary glands of nursing women.
  • Pregnancy and lactation are the only conditions where persistent elevation of prolactin is considered normal.
  • In all other cases, elevated prolactin levels indicate pathology.

Regulation of Prolactin Secretion

  • Prolactin synthesis is regulated by hypothalamic hormones and sex hormones.
  • Dopamine, produced by hypothalamic neurons, inhibits prolactin synthesis in non-pregnant women and healthy men.
  • If the connection between the hypothalamus and the pituitary gland is disrupted (due to tumor, trauma, or dopamine receptor-blocking drugs), prolactin secretion increases, leading to hyperprolactinemia.

Macroprolactinemia

  • Macroprolactin molecules consist of prolactin bound to autoantibodies (IgG).
  • It is unclear whether these autoantibodies cause the condition (similar to anti-insulin antibodies in type 1 diabetes) or develop as a response to increased prolactin levels.
  • Unlike monomeric prolactin, macroprolactin is larger, remains in circulation longer, and is excreted by the kidneys more slowly.
  • Macroprolactinemia often results in prolactin levels exceeding 600 mg/L but has low biological activity due to antibody binding.
  • Unlike true hyperprolactinemia (caused by excess monomeric prolactin), macroprolactinemia is often asymptomatic or presents with mild symptoms (e.g., menstrual irregularities, galactorrhea, or infertility).
  • Avoid fatty foods for 24 hours before the test.
  • Do not eat for 12 hours before the test.
  • Do not take medications for 24 hours before the test (unless instructed otherwise by your doctor).
  • Avoid physical and emotional stress for 24 hours before the test.
  • Do not smoke for 3 hours before the test.
  • Diagnosing hyperprolactinemia, especially in cases where prolactin levels are significantly elevated but symptoms are absent.
  • Determining the need for treatment in patients with hyperprolactinemia and predicting disease progression.
  • Ruling out macroprolactinemia as a cause of menstrual irregularities.
  • Ruling out macroprolactinemia as a cause of male and female infertility.
  • Investigating hyperprolactinemia symptoms, including:
    • Oligo/amenorrhea, galactorrhea, infertility in women.
    • Decreased libido, erectile dysfunction, infertility in men.
  • Differentiating true hyperprolactinemia from macroprolactinemia, based on the type of prolactin present.
  • Evaluating women with oligomenorrhea or secondary amenorrhea.
  • Evaluating men and women with infertility.

    Pathological Hyperprolactinemia

    Causes of True Hyperprolactinemia (Excess Monomeric Prolactin)

    • Pituitary tumors (prolactinoma).
    • Other pituitary tumors (e.g., somatotropinoma, non-functioning pituitary adenomas).
    • Hypothalamic-pituitary trauma or surgery.
    • Hypothalamic and pituitary disorders (e.g., lymphocytic hypophysitis, sarcoidosis, cysts, metastases).
    • Radiation therapy for brain tumors.
    • Chronic kidney failure.
    • Liver cirrhosis.
    • Hypothyroidism.

    Drug-Induced Hyperprolactinemia (Caused by Medications)

    • Antipsychotics (e.g., risperidone).
    • Oral contraceptives (or sudden discontinuation).
    • Antidepressants (e.g., amitriptyline, fluoxetine).
    • Antihistamines (e.g., cimetidine, ranitidine).
    • Antihypertensive drugs (e.g., verapamil).
    • Prokinetic drugs (e.g., metoclopramide).
       

      Causes of Reduced Macroprolactin Levels

    • Pituitary infarction (Sheehan’s syndrome).
    • Radiation therapy.
    • Dopamine agonist medications, such as:
      • Bromocriptine
      • Cabergoline
      • Levodopa
      • Dopamine