The epidemiology, diagnosis and treatment of Prolactinomas: The old and the new

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Prevalence and incidence of prolactinomas are approximately 50 per 100,000 and 3–5 new cases/100,000/year. The pathophysiological mechanism of hyperprolactinemia-induced gonadotropic failure involves kisspeptin neurons. Prolactinomas in males are larger, more invasive and less sensitive to dopamine agonists (DAs). Macroprolactin, responsible for pseudohyperprolactinemia is a frequent pitfall of prolactin assay.

DAs still represent the primary therapy for most prolactinomas, but neurosurgery has regained interest, due to progress in surgical techniques and a high success rate in microprolactinoma, as well as to some underestimated side effects of long-term DA treatment, such as impulse control disorders or impaired quality of life. Recent data show that the suspected effects of DAs on cardiac valves in patients with prolactinomas are reassuring. Finally, temozolomide has emerged as a valuable treatment for rare cases of aggressive and malignant prolactinomas that do not respond to all other conventional treatments.

Introduction

Prolactinomas are the most common types of pituitary adenomas. They are well known to endocrinologists and neurosurgeons, as well as to gynecologists and general practitioners, due to their effects on fertility, particularly in women. Their management has been transformed by the use of dopamine agonists (DAs) that were introduced in the seventies. Even if medical practice in the field of prolactinomas is now well established, our objective in this article was to highlight some data that, although they are older, are still relevant, and to provide insights into the epidemiology, diagnosis and treatment of prolactinomas in 2019. We will not describe the pathophysiology, histology or specific aspects of prolactinomas during pregnancy, because these topics have recently been reviewed in detail [1], ∗[2], [3], [4], [5].

Section snippets

Epidemiology

Prolactinomas represent the most common type of pituitary adenomas, accounting for approximately 50% of all pituitary tumors requiring medical attention [6], [7]. Previous radiological and autopsy studies have revealed a high prevalence of pituitary adenomas (10–20%), and the vast majority (>99%) are small microadenomas with a predominance (25–60%) of lactotroph tumors, based on immunohistochemistry [7], [8], [9]. In clinical settings, microadenomas are approximately four-to five-fold more

Women

Most women with a prolactinoma have a microadenoma, and therefore endocrine symptoms are much more prevalent than mass effects, at least before menopause. Classic symptoms of prolactinomas in women include oligo- or amenorrhea (which is present in almost all patients, 85–90%), galactorrhea, (present in 84% of patients, according to a recent meta-analysis [21]) and infertility [21], [22], [23], [24]. Conversely, in nearly 15% of women who experience secondary amenorrhea or oligomenorrhea

Imaging

All patients with hyperprolactinemia in whom obvious non-hypothalamic–pituitary disorders have been excluded should undergo a pituitary MRI including at least T2-weighted coronal sections and T1-weighted coronal sections before and after gadolinium enhancement [81], [82], [83]. A challenge in evaluating patients with mild hyperprolactinemia is the finding of a false-positive CT or MRI mass (pituitary incidentaloma). Because these techniques detect incidental non-secreting tumors, cysts,

Surveillance

Studies of the natural history of untreated microprolactinomas have shown that significant or persistent growth of these tumors is uncommon [87], [88]. Therefore, as recommended by the most recent guidelines for the treatment of prolactinomas [55], symptomatic eugonadal patients with microprolactinomas do not require active therapy and can be monitored with regular measurements of PRL levels. A prolactinoma is unlikely to show significant growth without a concomitant increase in hormone levels.

Conclusions

Several advances in the epidemiology, diagnosis and treatment of prolactinomas have been reported in recent years. The prevalence (approximately 50 per 100 000) and the incidence (3–5 new cases/100,000/year) have been specified by recent epidemiological studies. The mechanisms by which hyperprolactinemia induces hypogonadotropic hypogonadism have been elucidated and the substantial gender differences in the natural evolution, consequences and complications of prolactinomas are now well

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