madman
Super Moderator
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 biotin use have to be considered. A 52-year-old woman was referred to the Endocrinology clinic for oligomenorrhoea and headache. She worked as a butcher. The 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 antianimal 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.
Introduction
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) [1–3] can have different causes, physiological, pharmacological, and pathological (Table 1). The predominant physiological consequence of hyperprolactinemia is hypogonadotropic hypogonadism due to the suppression of GnRH pulsatility. Clinical manifestations vary according to the age and sex of the patient and to the magnitude of PRL secretion increase. Clinical presentation in women with oligomenorrhea, amenorrhea, galactorrhea, decreased libido, infertility, and decreased bone mass is generally more clear and occurs earlier than in men [1–9]. The most common symptoms in men are erectile dysfunction, decreased libido, infertility, gynecomastia, decreased bone mass, while galactorrhea is rare [1–9].
Prolactinomas, that account for 25–30% of functioning pituitary tumors, are the most frequent cause of high PRL [1–9]. Prolactinomas can be microadenomas, more common in premenopausal women, and macroadenomas, more common in men and postmenopausal women [1–9]. Increased PRL concentration can also be induced by pituitary adenomas co-secreting GH and PRL and by sellar/ parasellar masses causing stalk effect, as non-secreting adenomas [1–9]. When investigating the etiology of hyperprolactinemia, clinicians need to be aware of several conditions that can influence PRL measurement leading to misdiagnosis and, consequently, to inappropriate patient management. The pitfalls most frequently cited in papers and reviews are represented by acute physical and psychological stress, macroprolactin, hook effect.
Conclusion
In case of discrepancies between imaging, clinical picture, and the laboratory data, clinicians must consider the possibility of the presence of pre-, intra-, and post-analytical interferences. Recent reviews discussed many pitfalls in hyperprolactinemia diagnosis, such as venipuncture, macroprolactinemia, and hook effect. The present case report adds further pitfalls to be considered: EA interference and biotin. The development of more automated analyzers and communication between the requesting clinician and the laboratorian is essential to reduce the possibility that erroneous laboratory results cause harmful consequences to the patients.
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 biotin use have to be considered. A 52-year-old woman was referred to the Endocrinology clinic for oligomenorrhoea and headache. She worked as a butcher. The 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 antianimal 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.
Introduction
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) [1–3] can have different causes, physiological, pharmacological, and pathological (Table 1). The predominant physiological consequence of hyperprolactinemia is hypogonadotropic hypogonadism due to the suppression of GnRH pulsatility. Clinical manifestations vary according to the age and sex of the patient and to the magnitude of PRL secretion increase. Clinical presentation in women with oligomenorrhea, amenorrhea, galactorrhea, decreased libido, infertility, and decreased bone mass is generally more clear and occurs earlier than in men [1–9]. The most common symptoms in men are erectile dysfunction, decreased libido, infertility, gynecomastia, decreased bone mass, while galactorrhea is rare [1–9].
Prolactinomas, that account for 25–30% of functioning pituitary tumors, are the most frequent cause of high PRL [1–9]. Prolactinomas can be microadenomas, more common in premenopausal women, and macroadenomas, more common in men and postmenopausal women [1–9]. Increased PRL concentration can also be induced by pituitary adenomas co-secreting GH and PRL and by sellar/ parasellar masses causing stalk effect, as non-secreting adenomas [1–9]. When investigating the etiology of hyperprolactinemia, clinicians need to be aware of several conditions that can influence PRL measurement leading to misdiagnosis and, consequently, to inappropriate patient management. The pitfalls most frequently cited in papers and reviews are represented by acute physical and psychological stress, macroprolactin, hook effect.
Conclusion
In case of discrepancies between imaging, clinical picture, and the laboratory data, clinicians must consider the possibility of the presence of pre-, intra-, and post-analytical interferences. Recent reviews discussed many pitfalls in hyperprolactinemia diagnosis, such as venipuncture, macroprolactinemia, and hook effect. The present case report adds further pitfalls to be considered: EA interference and biotin. The development of more automated analyzers and communication between the requesting clinician and the laboratorian is essential to reduce the possibility that erroneous laboratory results cause harmful consequences to the patients.
