Challenges and pitfalls in the diagnosis of hyperprolactinemia

Abstract

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...

Prolactinomas: evolution after menopause

“…In patients with macroprolactinomas the PRL levels after treatment suspension were in the normal range; and in the latest control some patients, including the three patients with tumor persistence, showed slightly increased levels above the upper normal limit, this situation might be due to the effects of menopause. Most of the prolactinomas are microadenomas (15,16) and this was also observed in this study. In prolactinomas there is a close relation between PRL levels and the tumor size; the bigger the tumor is, the higher the PRL levels are.…”

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“…Six weeks after delivery, PRL levels normalize due to a decrease in oestrogen level [19]. Other conditions can also cause physiological hyperprolactinemia, such as: stress, sleep, meals, exercise, sexual intercourse and chest wall stimulation [20]. It is important to note that physiological causes of hyperprolactinemia can coexist with pathological forms.…”

“…Other diseases of the hypothalamic and pituitary region can cause hyperprolactinemia by either disrupting synthesis or transmission of PIF. This includes primary or secondary hypothalamic and pituitary tumours (craniopharyngiomas, meningiomas), granulomatous or infiltrative diseases (sarcoidosis, histiocytosis), hypophysitis, aneurysms, empty sella, trauma, or radiotherapy [20]. There are several systemic diseases that can cause hyperprolactinemia.…”

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

“…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].…”