Macroprolactinemia in Patients with Prolactinomas: Prevalence and Clinical Significance

Abstract

In few cases, the presence of typical hyperprolactinemia-related clinical symptoms and their disappearance after treatment with DA suggests biological activity of macroprolactin comparable with that of monomeric prolactin isoform. Decrease of macroprolactin levels after DA treatment could suggest tumoral origin of the high-molecular isoform in these rare cases. Although macroprolactinemia is considered a benign condition, pituitary imaging, DA treatment, and prolonged follow-up may be necessary in certain cases. An individualized approach to the management of patients with macroprolactinemia should be applied.

Importance of macroprolactinemia in hyperprolactinemia

“…The prevalence of macroprolactinemia among newly diagnosed prolactinoma patients is similar compared with the control group of healthy subjects (3.5 vs. 3.7%), and may be explained by the coexistence of a pituitary adenoma and macroprolactinemia or macroprolactin production by the pituitary tumour itself [12].…”

“…However, macroprolactinemia may be more common, with a recently reported prevalence of 3.7% and no difference in prevalence between genders [14]. Because the reported proportion of macroprolactinemia in hyperprolactinemic populations is much higher in most studies and varies between 15 and 35% (mean prevalence 25%), macroprolactinemia is therefore considered a common finding in endocrinological practice [3,8,12,13]. One study reported a prevalence of 46%, but it is likely that this particular incidence reflected selection bias because of the specialized nature of the study center, which received samples sent from other laboratories when the possible diagnosis of macroprolactinemia was raised [15].…”

“…Therefore, pituitary magnetic resonance imaging should perhaps be mandatory in such cases [40]. However, hyperprolactinemia with high levels almost exclusively due to the presence of macroprolactin may occur in rare cases of invasive macroprolactinoma with preserved biological activity resulting in suppressed gonadotrophin levels and typical clinical presentation represents similarly to monomeric [12].…”

“…In a recent study a few cases of macroprolactinemia of pituitary origin associated with prolactinoma experienced similar clinical manifestations comparable with that of monomeric hyperprolactinemia, and their disappearance after treatment with dopamine agonists suggesting bioactivity of macroprolactin. Therefore, in spite of the fact that macroprolactinemia had been considered a benign condition, pituitary imaging and conservative treatment with dopamine agonists and prolonged follow-up should be applied in these rare cases as well as in macroprolactinemic patients with elevated monomeric hyperprolactinemia [12]. In this review we report various clinical features of macroprolactinemia explained through pathophysiologic mechanisms suggesting different approaches which would contribute to the improvement of proper identification and adequate management of such patients.…”

Challenges and pitfalls in the diagnosis of hyperprolactinemia

“…In this context, macroprolactinemia association with pituitary adenomas requires special attention (67,68), especially if PRL levels remain elevated after PEG precipitation (Figure 3) (1,4,65). However, the prevalence of macroprolactinemia did not differ in patients with prolactinomas and in the control group (3.5% vs. 3.7%; p = 1.00) in a recent study (69). Macroprolactinemia was recently reported in 5.8% of women with PCOS (70).…”