Abstract

Aim. To determine the frequency of macroprolactinemia, its etiology, and the clinical manifestations in patients with hyperprolactinemia presenting with menstrual irregularities, galactorrhea, and/or infertility who were attended by the gynecology-endocrinology service. Methods. In a cross-sectional study, 326 hyperprolactinemic women were tested for serum prolactin (PRL) concentrations before and after chromatographic separation (gel filtration and affinity with protein G) and extraction of free PRL with polyethylene glycol (PEG). Results. Sera from 57 patients (17.5%) were found to have macroprolactinemia. The presence of macroprolactinemia was attributable to anti-PRL autoantibodies in 54 (94.7%) patients. The median serum PRL levels were similar in patients with or without macroprolactinemia (42.0 versus 38.1 ng/mL). In contrast, patients with macroprolactinemia had lower serum-free PRL levels (median 9.2 versus 31.7 ng/mL, P < 0.001). Patients without macroprolactinemia had a higher frequency of galactorrhea and abnormal pituitary imagine findings (P < 0.002). Conclusions. We can conclude that macroprolactinemia should be considered as a benign variant, and it must be ruled out in women presenting with menstrual irregularities, galactorrhea, and/or infertility in order to investigate other causes different than hyperprolactinemia. Serum PRL precipitated with PEG is a convenient and simple procedure to screen for the presence of macroprolactinemia.

Highlights

  • Prolactin (PRL) is a polypeptide hormone primarily secreted by the anterior pituitary gland.The presence of several PRL isoforms in serum and other biological fluids has been clearly established

  • Since there is scarce information on the frequency of MPRL in hyperprolactinemic women with signs and symptoms related to hyperprolactinemia, the aim of the present work was to study MPRL frequency and its etiology in hyperprolactinemic women presenting with menstrual irregularities, galactorrhea, infertility, or/and alterations in libido who were attended by the gynecology and endocrinology service of a third level care hospital, as well as to determine the utility of the percentage of serum PRL precipitated with polyethylene glycol (PEG) assay in the detection of MPRL and to establish the ideal cut-off point for this test

  • The frequency of MPRL in hyperprolactinemic women with signs and symptoms related to elevated serum PRL levels is unknown

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Summary

Introduction

Prolactin (PRL) is a polypeptide hormone primarily secreted by the anterior pituitary gland.The presence of several PRL isoforms in serum and other biological fluids has been clearly established. There are two other PRL isoforms that display higher molecular weights, referred to as big PRL (45–50 kDa) and big big PRL (>100 kDa) and known as macroprolactin [1] The presence of these isoforms has been attributed to formation of aggregates of monomeric PRL with different glycosylation degrees and binding of PRL to serum protein in circulation, mainly to anti-PRL autoantibody of IgG isotype [2,3,4,5]. These structural modifications may distinctly affect the biological and immunological properties of the hormone [5]. Predominant presence of big big PRL, a phenomenon termed macroprolactinemia (MPRL), has been reported in 15 to 46% of subjects

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