Endocrine Abstracts (2006) 11 P713

Hyperprolactinaemia due to big prolactin

JA Ahlquist1, AR Ellis2 & MN Fahie-Wilson1


1Southend Hospital, West Cliff on Sea, United Kingdom; 2UK NEQAS, Royal Infirmary, Edinburgh, United Kingdom.


Prolactin is present in serum in a variety of forms defined by different molecular masses. Macroprolactin is the best-known variant, a high molecular mass (150–170 kD) form of prolactin usually representing a prolactin–IgG complex which reacts in immunoassays causing apparent hyperprolactinaemia. Big-prolactin is a smaller high molecular mass (50–60 kDa) form of prolactin found more commonly than macroprolactin; however, the origin and significance of big-prolactin are poorly understood. Screening for larger molecular mass forms of prolactin is performed by measurement of serum prolactin after polyethylene glycol (PEG)-precipitation; low recovery (<40%) indicates the presence of macroprolactin, and intermediate recovery (40–60%) may require gel filtration chromatography (GFC) for clarification. We report the results of Sephacryl S-100 high resolution GFC to study the contribution of big-prolactin to total serum prolactin in 17 consecutive hyperprolactinaemic serum samples (total prolactin 724–7743 mU/l) with intermediate recovery after PEG-precipitation. Big-prolactin was the predominant high molecular mass prolactin form in 15 (79%) cases, representing 17–49% of total serum prolactin (56–91% of the high molecular mass forms). Chromatography of the precipitate after re-dissolution confirmed that PEG precipitates both macroprolactin and big-prolactin. Chromatography after adsorption of serum with protein G-Sepharose showed that only part of the big-prolactin peak was adsorbed, indicating an IgG component. Re-assay of big-prolactin chromatography fractions in seven commercial immunoassays confirmed that big-prolactin reacts in all prolactin assays widely used in the United Kingdom.

We conclude that, in cases of intermediate prolactin recovery after PEG-precipitation, big-prolactin is a substantial component of total serum prolactin and contributes to the hyperprolactinaemia seen in these cases. The molecular nature of big-prolactin remains unclear, but our data suggest that an IgG component is involved. Further work is required to define the biological activity of big-prolactin and thus to guide clinical interpretation of the results in these cases.

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