Macroprolactinemia: new insights in hyperprolactinemia

Kasum, Miro; Orešković, Slavko; Zec, Ivana; Ježek, Davor; Tomić, Vlatka; Gall, Vesna; Adžić, G.

doi:10.11613/bm.2012.020

Cited by 29 publications

(30 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Their overall prevalence was somewhat lower than those observed in patients with monomeric hiperprolactinemia (Table 3). Similar data has been reported in subsequent studies (16,17,21,45,60,65) (Table 3) (Figure 4). Asymptomatic patients are more numerous in the macroprolactinemic group (44,65).…”

Section: Other Clinical Featuressupporting

confidence: 91%

“…The gold standard for the diagnosis of macroprolactinemia is gel-filtration chromatography, but because this method is laborious and expensive, polyethylene glycol (PEG) serum precipitation has been widely used as a screening method (16,17,44,45,61,63). The test, which enables the diagnosis in at least 80% of cases, is based on the observation that immunoglobulins exposure to defined concentrations of PEG lead to their insolubilization (1,4,63).…”

Section: Methods For Detection Of Macroprolactinmentioning

confidence: 99%

“…The predominant form in healthy subjects and in patients with prolactinomas is monomeric PRL (molecular mass 23 kDa), while dimeric or big PRL (45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60), and big-big PRL or macroprolactin (150-170 kDa) correspond to less than 20% of the total PRL (13)(14)(15). When the serum of a patient with hyperprolactinemia contains mostly macroprolactin, the condition is termed macroprolactinemia (16,17). In approximately 90% of cases, macroprolactin is composed of a complex formed by an IgG and a monomeric PRL (17,18).…”

Section: Prolactin Serum Isoformsmentioning

confidence: 99%

“…These antibodies reduce PRL bioactivity and delay its clearance, inducing macroprolactinemia. Antibody-bound PRL is big enough to be confined to vascular spaces and, therefore, macroprolactinemia seems to develop mostly due to the delayed PRL clearance, rather than its increased production (16,17).…”

Section: Macroprolactinemiamentioning

confidence: 99%

See 3 more Smart Citations

Challenges and pitfalls in the diagnosis of hyperprolactinemia

Vilar

Fleseriu

Bronstein

2014

Arq Bras Endocrinol Metab

View full text Add to dashboard Cite

The definition of the etiology of hyperprolactinemia often represents a great challenge and an accurate diagnosis is paramount before treatment. Although prolactin levels > 200-250 ng/mL are highly suggestive of prolactinomas, they can occasionally be found in other conditions. Moreover, as much as 25% of patients with microprolactinomas may present prolactin levels < 100 ng/mL, which are found in most patients with pseudoprolactinomas, drug-induced hyperprolactinemia, or systemic diseases. On the other hand, some conditions may lead to falsely low PRL levels, particularly the so-called hook effect, that is an assay artifact caused by an extremely high level of PRL, and can be confirmed by repeating assay after a 1:100 serum sample dilution. The hook effect must be considered in all patients with large pituitary adenomas and PRL levels within the normal range or only modestly elevated (e.g., < 200 ng/mL). An overlooked hook effect may lead to incorrect diagnosis and unnecessary surgical intervention in patients with prolactinomas. Another important challenge is macroprolactinemia, a common finding that needs to be identified, as it usually requires no treatment. Although most macroprolactinemic patients are asymptomatic, many of them may present galactorrhea or menstrual disorders, as well as neuroradiological abnormalities, due to the concomitance of other diseases. Finally, physicians should be aware that pituitary incidentalomas are found in at least 10% of adult population. Arq Bras Endocrinol Metab. 2014;58(1):9-22 Keywords Hyperprolactinemia; diagnostic pitfalls; hook effect; macroprolactinemia; pituitary incidentalomas RESUMO A definição da etiologia da hiperprolactinemia muitas vezes representa um grande desafio e um diagnóstico preciso é fundamental antes do tratamento. Embora níveis de prolactina > 200-250 ng/mL sejam altamente sugestivos de prolactinomas, ocasionalmente podem ser encontrados em outras condições. Além disso, até 25% dos pacientes com microprolactinomas podem apresentar-se com níveis de prolactina < 100 ng/mL, os quais são evidenciados na maioria dos pacientes com pseudoprolactinomas, hiperprolactinemia induzida por drogas ou doenças sistêmicas. Por outro lado, deve--se atentar às condições que podem levar a valores de prolactina falsamente baixos, particularmente o chamado efeito gancho. Este último é um artefato causado por um nível extremamente elevado de PRL e que pode ser confirmado pela repetição do exame após diluição do soro a 1:100. O efeito gancho deve ser considerado em todo paciente com grandes adenomas hipofisários e níveis de prolactina dentro da faixa normal ou apenas moderadamente elevados (p. ex., < 200 ng/mL). Um efeito gancho não detectado pode levar a diagnóstico incorreto e intervenção cirúrgica desnecessária em pacientes com prolactinomas. Outro desafio importante é a macroprolactinemia, um achado comum que precisa ser identificado visto que geralmente não requer tratamento. Ainda que a maioria dos pacientes seja assintomática devido à concomitância de outr...

show abstract

Section: Other Clinical Featuressupporting

confidence: 91%

Section: Methods For Detection Of Macroprolactinmentioning

confidence: 99%

Section: Prolactin Serum Isoformsmentioning

confidence: 99%

Section: Macroprolactinemiamentioning

confidence: 99%

See 2 more Smart Citations

Challenges and pitfalls in the diagnosis of hyperprolactinemia

Vilar

Fleseriu

Bronstein

2014

Arq Bras Endocrinol Metab

View full text Add to dashboard Cite

show abstract

“…The monomeric isoform accounts for 80%-95% of PRL and is known to be both biologically and immunologically active in vivo [9]. Macroprolactinemia is a condition in which big-big PRL is substantially increased in the serum, and is usually diagnosed when the proportion of polyethylene glycol (PEG)-induced precipitable PRL exceeds 60% of the total PRL (recovery < 40%) [8,10,11]. The prevalence of macroprolactinemia is reportedly 10%-26% in patients with hyperprolactinemia [4,11,[12][13][14][15]] and 3.68% in the general population [16].…”

mentioning

confidence: 99%

Impact of macroprolactin on galactorrhea and the rate of patients possibly affected by macroprolactin

Aisaka¹,

Tsuchiya²,

Sueta³

et al. 2018

Endocr J

View full text Add to dashboard Cite

Abstract. The clinical influence of macroprolactin (MPRL) is not clearly understood and the rate of patients potentially affected by MPRL is unknown. We investigated the influence of MPRL on the onset of galactorrhea and estimated the rate of patients with a proportion of MPRL fraction that may possibly affect galactorrhea. Data of patients with obstetric or gynecological symptoms who had undergone PRL fractionation testing were retrospectively analyzed. To evaluate factors influencing galactorrhea, a multivariate logistic regression analysis was performed and the adjusted odds ratios of MPRL for galactorrhea were calculated. Cutoff values for the total PRL level and the proportion of MPRL fractions for galactorrhea were determined by ROC analysis using a multivariate logistic model. The prevalence of patients with a proportion of MPRL fraction greater than or equal to the cutoff value for galactorrhea was estimated. The median proportion of MPRL fraction was 30.1% and increased as PRL level increased. Total PRL and MPRL had a significant influence on the onset of galactorrhea and the adjusted odds ratio was 1.09 in total PRL and 0.94 in MPRL. The rate of patients with a proportion of MPRL fraction that may possibly affect galactorrhea was estimated to be 33.5% of the study population, and thus found to be twelve times or more the number of macroprolactinemia patients. Future prospects for hyperprolactinemia may require diagnostic criteria using free prolactin levels and so MPRL fraction measurement is important for the diagnosis and treatment of patients with obstetric and gynecological symptoms. HYPERPROLACTINEMIA is one of the most common hypothalamic pituitary endocrine disorders [1][2][3]. The causes of hyperprolactinemia include pregnancy, prolactinoma, intracranial tumors, medication, and hypothyroidism [1], and 9%-39% of hyperprolactinemia cases are classified as idiopathic [4,5]. On the other hand, Sapin et al. reported that macroprolactin (MPRL) fraction accounts for 31.6% of total PRL in hyperprolactinemia patients with a MPRL fraction in the normal range [6]. In many cases, MPRL fraction may be affecting the prolactin level and the diagnosis of hyperprolactinemia. Human PRL is heterogeneous in molecular size: the major circulating form is little PRL (MW 23 kDa), Submitted Aug. 14, 2017; Accepted Oct. 24, 2017 as EJ17-0358 Released online in J-STAGE as advance publication Nov. 22, 2017 Correspondence to: Kohzo Aisaka, Department of Obstetrics and Gynecology, Hamada Hospital, 2-5 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan. E-mail: aisaka-k@umin.ac.jp the remainder consisting of big PRL (MW 50 kDa), and big-big PRL (MW greater than 150 kDa) [7,8]. The monomeric isoform accounts for 80%-95% of PRL and is known to be both biologically and immunologically active in vivo [9]. Macroprolactinemia is a condition in which big-big PRL is substantially increased in the serum, and is usually diagnosed when the proportion of polyethylene glycol (PEG)-induced precipitable PRL exceeds 60% of the total PRL ...

show abstract

Hypeprolactinemia: still an insidious diagnosis

et al. 2020

View full text Add to dashboard Cite

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.

show abstract

Macroprolactinemia: new insights in hyperprolactinemia

Cited by 29 publications

References 44 publications

Challenges and pitfalls in the diagnosis of hyperprolactinemia

Challenges and pitfalls in the diagnosis of hyperprolactinemia

Impact of macroprolactin on galactorrhea and the rate of patients possibly affected by macroprolactin

Hypeprolactinemia: still an insidious diagnosis

Contact Info

Product

Resources

About