What is macroprolactin?

What is Macroprolactin?

Macroprolactin is a large, biologically inactive complex of prolactin hormone bound to antibodies (usually IgG) that causes falsely elevated prolactin readings on blood tests but typically produces no symptoms of high prolactin. 1

The Basic Science

Macroprolactin is essentially prolactin that has become attached to antibodies in your blood, creating a much larger molecule (>100 kDa) compared to normal prolactin (23 kDa). 2 This complex has three key characteristics:

• It's too big to work properly - The large size prevents it from reaching target tissues and binding to prolactin receptors effectively, which is why it has minimal biological activity 3
• It stays in the blood longer - Because of its large size, the kidneys can't clear it efficiently, leading to accumulation and falsely high prolactin readings 3
• It tricks lab tests - Modern prolactin assays detect this complex as if it were active prolactin, even though it isn't 4

Why It Matters Clinically

Macroprolactinemia accounts for 10-40% of all cases of elevated prolactin levels, making it extremely common and frequently misdiagnosed. 1

The critical clinical issue is that patients with macroprolactinemia usually have:

• No symptoms of high prolactin (no irregular periods, no breast milk production, no sexual dysfunction) 5
• Elevated prolactin on blood tests that prompt unnecessary worry and testing 4
• Normal amounts of actual bioactive prolactin in their system 4

The Real-World Problem

When macroprolactinemia isn't recognized, patients undergo unnecessary:

• Repeated blood tests 4
• Brain MRI scans looking for pituitary tumors 4
• Treatment with dopamine agonist medications 4
• Even pituitary surgery in extreme cases 4

How to Detect It

The polyethylene glycol (PEG) precipitation test is the simple screening method that should be performed whenever prolactin is mildly or incidentally elevated, especially in asymptomatic patients. 1, 5

This test works by:

• Removing the large macroprolactin complexes from the blood sample 6
• Re-measuring the prolactin level to see what remains 6
• If >60% of the prolactin disappears after PEG treatment, macroprolactinemia is diagnosed 3

Important Caveats

Not all patients with macroprolactinemia are symptom-free - approximately 20% may have actual pituitary adenomas, and 45% may have menstrual irregularities. 1, 7

Key pitfalls to avoid:

• Don't assume all macroprolactinemia is benign - Some patients have both macroprolactin AND elevated monomeric (active) prolactin that requires treatment 8, 3
• Check for coexisting conditions - About 20% of macroprolactinemia patients have actual pituitary tumors that need evaluation 5
• Consider imaging if symptomatic - Patients with headaches, menstrual problems, or other symptoms should still undergo pituitary MRI even with confirmed macroprolactinemia 5

Bottom Line for Clinical Practice

Think of macroprolactinemia as a "false alarm" - the lab test is elevated, but the patient's body isn't experiencing the effects of high prolactin. 2 The key is recognizing this pattern (high prolactin + no symptoms) and confirming with PEG testing before pursuing expensive imaging or unnecessary treatment. 1, 5