Macroprolactinemia: a mini-review and update on clinical practice

Abstract

Hyperprolactinemia is common among infertile patients, with up to 15%-20% of women with oligomenorrhea having hyperprolactinemia. Suppression of the hypothalamic-pituitary-gonadal axis via inhibition of pulsatile gonadotropin releasing hormone because of hyperprolactinemia is a common endocrine etiology of infertility. There are 3 forms of human prolactin (PRL): monomeric PRL, dimeric PRL, and macro-PRL. Also known as big-big PRL, macro-PRL has a molecular weight >150 kDa and normally comprises 5%-10% of circulating PRL. When the predominant form of circulating PRL is macro-PRL, macroprolactinemia is diagnosed. Among patients with hyperprolactinemia, 10%-46% have macroprolactinemia. Patients with macroprolactinemia are at risk of unnecessary pituitary imaging and treatment with dopamine agonists if not correctly diagnosed. Given the high prevalence of macroprolactinemia among patients with elevated PRL levels and the different management of patients with macroprolactinemia vs true monomeric hyperprolactinemia, all patients with persistently elevated PRL levels should be screened for macro-PRL.

Keywords: Prolactin; hyperprolactinemia; macroprolactin; macroprolactinemia.

Figure 1

Macro-PRL consists of monomeric PRL complexed with IgG and nonIgG antibodies. The majority of macro-PRL (87%) consists of monomeric PRL-IgG complexes. Among the monomeric PRL-IgG complexes, 67% consist of anti-PRL autoantibodies.

Figure 2

All patients with hyperprolactinemia on serum testing should be assessed for macroprolactinemia. PEG = polyethylene glycol, PRL = prolactin. ∗Unless a patient has clinical presentation suggestive of simultaneous prolactinoma such as amenorrhea/oligomenorrhea and/or galactorrhea