Hyperprolactinemia: new assay more specific for the monomeric form does not eliminate screening for macroprolactin with polyethylene glycol precipitation

Vieira, José Gilberto H.; Tachibana, Teresinha T.; Ferrer, Claudia; Sá, José de; Biscolla, Rosa Paula M.; Hoff, Ana O.; Kanashiro, Ina

doi:10.1590/s0004-27302010000900013

Cited by 7 publications

(4 citation statements)

References 13 publications

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“…Moreover, macroprolactinemic patients cannot be differentiated by their monomeric hyperprolactinemia counterparts in terms of clinical and neuroradiological findings (16,44), nor by PRL levels, unless they are very high (e.g., > 700 ng/mL) (59,61,65). Although there is no consensus yet on the indications for macroprolactinemia screening, there is an increasing number of endocrinologists who consider this approach for all patients without an obvious etiology for the PRL elevation (9,16,17,21,(43)(44)(45)60,61,64,(94)(95)(96). Noteworthy, PRL measurement should be avoided in asymptomatic patients in the absence of a known pituitary adenoma to prevent challenges associated with macropro lactinemia.…”

Section: Resultsmentioning

confidence: 99%

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Challenges and pitfalls in the diagnosis of hyperprolactinemia

Vilar

Fleseriu

Bronstein

2014

Arq Bras Endocrinol Metab

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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...

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Section: Resultsmentioning

confidence: 99%

“…PEG precipitates macroprolactin, whose levels in the supernatant decrease significantly. Recoveries < 40% are indicative Diagnosis of hyperprolactinemia of predominance of macroprolactin whereas recoveries > 60% point to the diagnosis of monomeric hyperprolactinemia (44,63,64).…”

Section: Methods For Detection Of Macroprolactinmentioning

confidence: 99%

Challenges and pitfalls in the diagnosis of hyperprolactinemia

Vilar

Fleseriu

Bronstein

2014

Arq Bras Endocrinol Metab

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“…It is noteworthy that different assays recognize macroprolactin differently (64). It has been demonstrated that some of the new assays show lower cross-reactivity with macroprolactin; however, the number of samples defined as macroprolactin is still significant (65).…”

Section: Macroprolactinemia Screening: Routinely or Just In Asymptomamentioning

confidence: 99%

Controversial issues in the management of hyperprolactinemia and prolactinomas – An overview by the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism

Vilar¹,

Abucham²,

Albuquerque³

et al. 2018

Archives of Endocrinology and Metabolism

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Prolactinomas are the most common pituitary adenomas (approximately 40% of cases), and they represent an important cause of hypogonadism and infertility in both sexes. The magnitude of prolactin (PRL) elevation can be useful in determining the etiology of hyperprolactinemia. Indeed, PRL levels > 250 ng/mL are highly suggestive of the presence of a prolactinoma. In contrast, most patients with stalk dysfunction, drug-induced hyperprolactinemia or systemic diseases present with PRL levels < 100 ng/mL. However, exceptions to these rules are not rare. On the other hand, among patients with macroprolactinomas (MACs), artificially low PRL levels may result from the so-called "hook effect". Patients harboring cystic MACs may also present with a mild PRL elevation. The screening for macroprolactin is mostly indicated for asymptomatic patients and those with apparent idiopathic hyperprolactinemia. Dopamine agonists (DAs) are the treatment of choice for prolactinomas, particularly cabergoline, which is more effective and better tolerated than bromocriptine. After 2 years of successful treatment, DA withdrawal should be considered in all cases of microprolactinomas and in selected cases of MACs. In this publication, the goal of the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism (SBEM) is to provide a review of the diagnosis and treatment of hyperprolactinemia and prolactinomas, emphasizing controversial issues regarding these topics. This review is based on data published in the literature and the authors' experience.

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“…Polyethylene glycol (PEG) acts as a "sponge," which absorbs water of hydration from proteins, reducing their solubility and leading to their precipitation, and has been widely proposed and used as a screening method [5][6][7][8][9]. Many authors reported that the assays and the automated analyzers used by different laboratories differently recognize macroprolactin [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Hypeprolactinemia: still an insidious diagnosis

et al. 2020

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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.

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Hyperprolactinemia: new assay more specific for the monomeric form does not eliminate screening for macroprolactin with polyethylene glycol precipitation

Cited by 7 publications

References 13 publications

Challenges and pitfalls in the diagnosis of hyperprolactinemia

Challenges and pitfalls in the diagnosis of hyperprolactinemia

Controversial issues in the management of hyperprolactinemia and prolactinomas – An overview by the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism

Hypeprolactinemia: still an insidious diagnosis

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