Abstract
Hyperprolactinemia can have different causes: physiological, pharmacological, and pathological. When investigating the etiology of hyperprolactinemia, clinicians need to be aware of several conditions leading to misdiagnosis. The most popular pitfalls are: acute physical and psychological stress, macroprolactin, hook effect, even though antibodies interferences and biotine use have to be considered. A 52-year-old woman was referred to Endocrinology clinic for oligomenorrhoea and headache. She worked as a butcher. Hormonal evaluation showed very high PRL (305 ng/ml, reference interval: <24 ng/ml) measured with the ECLIA immunoassay analyzer Elecsys 170. The patient’s pituitary MRI was normal and macroprolactin was normal. Hormonal workup showed LH: 71.5 mU/ml (2–10.9 mU/ml), FSH: 111.4 mU/ml (3.9–8.8 mU/ml), Estradiol: 110.7 pg/mL (27–122 pg/ml). Since an interference was suspected, the sample was sent to another laboratory using a different assay. After antibody blocking tubes treatment (Heterophilic Blocking Tube, Scantibodies) PRL was 28.8 ng/ml (reference interval < 29.2 ng/ml). Analytical interference should be suspected when assay results are not consistent with the clinical picture. Endogenous antibodies (EA) include heterophile, human anti-animal, autoimmune and other nonspecific antibodies, and rheumatoid factors, that have structural similarities and can cross-react with the antibodies employed by the immunoassay, causing hyperprolactinemia misdiagnosis. The patient’s job (butcher), led us to suspect the presence of anti-animal antibodies. Clinicians should also carefully investigate the use of supplements. Biotin can falsely increase hormone concentration in competitive assays. Many clinicians are still not informed about these pitfalls that are not mentioned in some recent reviews on PRL measurement.
Highlights
Hyperprolactinemia, the detection of serum prolactin (PRL) levels above the upper reference limit [1,2,3] can have different causes, physiological, pharmacological, and pathological (Table 1)
The “hook effect,” i.e., falsely normal or mildly elevated PRL while the true PRL concentration is many fold higher than the upper limit, can be found in presence of large pituitary macroadenomas (≥3 cm) and clinical manifestations typical of prolactinoma
Since the presence of an interference was suspected, the sample was sent to another laboratory using a different immunoassay (DxI, Beckman, Milan): PRL concentration was 30.2 ng/ml and Polyethylene glycol (PEG) precipitation research for macroprolactin was negative
Summary
Hyperprolactinemia, the detection of serum prolactin (PRL) levels above the upper reference limit (commonly >20 ng/ ml in men and 25 ng/ml in women) [1,2,3] can have different causes, physiological, pharmacological, and pathological (Table 1). The “hook effect,” i.e., falsely normal or mildly elevated PRL while the true PRL concentration is many fold higher than the upper limit, can be found in presence of large pituitary macroadenomas (≥3 cm) and clinical manifestations typical of prolactinoma When this situation is suspected, clinicians should carry out a serial dilution of serum sample to eliminate the artifact. Hormonal evaluation showed very high PRL (305 ng/ml, reference interval:
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