How to manage elevated prolactin levels due to macroprolactinemia?

From the Guidelines

Management of macroprolactinemia typically involves monitoring rather than medication since this condition rarely causes symptoms or health complications. Macroprolactinemia occurs when prolactin molecules form larger complexes that remain in circulation but have limited biological activity. According to a recent consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence, published in Nature Reviews Endocrinology in 2024 1, it is recommended to assess baseline macroprolactin levels where serum prolactin is found to be mildly or incidentally elevated.

Some key points to consider in the management of macroprolactinemia include:

• If a patient has confirmed macroprolactinemia with normal levels of bioactive prolactin (monomeric prolactin), no treatment is generally necessary.
• Regular monitoring with prolactin measurements every 6-12 months is usually sufficient.
• For patients with persistent symptoms despite confirmed macroprolactinemia, a trial of dopamine agonists like cabergoline or bromocriptine may be considered, though response is often limited.
• It's essential to distinguish macroprolactinemia from true hyperprolactinemia caused by pituitary adenomas or other conditions, which would require different management approaches.
• Polyethylene glycol precipitation testing can help determine the percentage of biologically active prolactin, as noted in the guideline 1.

Patients should be reassured that macroprolactinemia is a benign condition that doesn't typically affect fertility or require long-term medication, though follow-up is important to ensure stability of prolactin levels and absence of developing symptoms. The guideline suggests that macroprolactinaemia was present in 10–40% of individuals with hyperprolactinaemia, with few patients developing clinical features of prolactin excess 1.

From the FDA Drug Label

Hyperprolactinemic States Visual field impairment is a known complication of macroprolactinoma. Effective treatment with bromocriptine leads to a reduction in hyperprolactinemia and often to a resolution of the visual impairment

To manage elevated prolactin levels due to macroprolactinemia, bromocriptine can be used as it has been shown to reduce plasma levels of prolactin in patients with hyperprolactinemia.

• The treatment should be started with a careful assessment of the pituitary to detect the presence of a prolactin-secreting adenoma.
• Patients should be monitored closely for signs and symptoms that may signal the enlargement of a previously undetected or existing prolactin-secreting tumor.
• Bromocriptine dosage may need to be adjusted to prevent secondary deterioration of visual fields due to chiasmal herniation.
• It is essential to monitor visual fields in patients with macroprolactinoma for early recognition of secondary field loss and adaptation of drug dosage 2.
• Bromocriptine significantly reduces plasma levels of prolactin in patients with physiologically elevated prolactin as well as in patients with hyperprolactinemia 2.

From the Research

Definition and Causes of Macroprolactinemia

• Macroprolactinemia is a condition where the concentration of macroprolactin, a complex of monomeric prolactin and immunoglobulin G, exceeds 60% of the total serum prolactin concentration 3.
• The prevalence of macroprolactinemia in hyperprolactinemic populations varies between 15% and 35% 3.
• Macroprolactinemia is considered a benign clinical condition in patients with normal concentrations of bioactive monomeric prolactin, with a lack of hyperprolactinemic symptoms and negative pituitary imaging 3, 4.

Diagnosis of Macroprolactinemia

• The gold standard technique for the diagnosis of macroprolactinemia is gel filtration chromatography 3.
• Polyethylene glycol precipitation is also used to diagnose macroprolactinemia, with a concentration of macroprolactin exceeding 60% of the total serum prolactin concentration indicating macroprolactinemia 3.
• Pituitary imaging, such as MRI, is essential to exclude a "pseudoprolactinoma" which would require surgery 5.

Management of Elevated Prolactin Levels due to Macroprolactinemia

• In cases of macroprolactinemia with normal concentrations of bioactive monomeric prolactin, no pharmacological treatment, diagnostic investigations, or prolonged follow-up are required 3, 4.
• However, in cases with excess monomeric prolactin levels, routine evaluation to identify the exact pathological state and introduce adequate treatment is necessary, regardless of the presence of macroprolactin 3.
• Dopamine agonists, such as bromocriptine and cabergoline, are the mainstay of treatment for hyperprolactinemia, but may not be effective in cases of macroprolactinemia 6, 7, 5.
• Individualized diagnostic investigations and treatment strategies, including dopamine agonists and prolonged follow-up, may be necessary in cases of macroprolactinemia with hyperprolactinemic signs and pituitary findings 4.