The epidemiology, diagnosis and treatment of Prolactinomas: The old and the new
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
References (183)
- et al.
Prolactinoma
- et al.
The epidemiology and genetics of pituitary adenomas
Best Pract Res Clin Endocrinol Metab
(2009) Pituitary tumours: pituitary incidentalomas
Best Pract Res Clin Endocrinol Metab
(2009)- et al.
Fertility after transsphenoidal surgery in patients with prolactinomas: a meta-analysis
Clin Neurol Neurosurg
(2019) - et al.
Update on prolactinomas. Part 1: clinical manifestations and diagnostic challenges
J Clin Neurosci
(2015) - et al.
Prevalence of hyperprolactinemia and abnormal magnetic resonance imaging findings in a population with infertility
Acta Obstet Gynecol Scand
(2010) - et al.
Hyperprolactinemia in postmenopausal women
Fertil Steril
(1997) - et al.
Growth potential of prolactinomas in men: is it really different from women?
Surg Neurol
(2003) - et al.
Determination of prolactin: the macroprolactin problem
Best Pract Res Clin Endocrinol Metab
(2013) - et al.
Misleading hyperprolactinaemia in pregnancy
Lancet
(1999)
Pituitary imaging is indicated for the evaluation of hyperprolactinemia
Fertil Steril
From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an International Pituitary Pathology Club proposal
Endocr Relat Cancer
Overview of the 2017 WHO classification of pituitary tumors
Endocr Pathol
Prolactin and pregnancy
Endocrinology in pregnancy: management of the pregnant patient with a prolactinoma
Eur J Endocrinol
The prevalence of pituitary adenomas: a systematic review
Cancer
Subclinical adenomas in postmortem pituitaries: classification and correlations to clinical data
Eur J Endocrinol
Estimated age- and sex-specific incidence and prevalence of dopamine agonist-treated hyperprolactinemia
J Clin Endocrinol Metab
Clinical practice
Prolactinoma N Engl J Med
The epidemiology of hyperprolactinaemia over 20 years in the tayside region of scotland: the prolactin epidemiology, audit and research study (PROLEARS)
Clinical Endocrinology
High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium
J Clin Endocrinol Metab
Incidence of pituitary adenomas in Northern Finland in 1992-2007
J Clin Endocrinol Metab
Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK)
Clin Endocrinol (Oxf)
Epidemiology of pituitary adenoma: results of the first Swiss study
Rev Med Suisse
Prevalence and incidence of pituitary adenomas: a population based study in Malta
Pituitary
The incidence rate of pituitary adenomas in western Sweden for the period 2001-2011
Eur J Endocrinol
The epidemiology of pituitary adenomas in Iceland, 1955-2012: a nationwide population-based study
Eur J Endocrinol
Incidence and prevalence of clinically relevant pituitary adenomas: retrospective cohort study in a Health Management Organization in Buenos Aires, Argentina
Arch Endocrinol Metab
Long-term follow-up of 246 hyperprolactinemic patients
Acta Obstet Gynecol Scand
Hyperprolactinaemia in 271 women: up to three decades of clinical follow-up
Clin Endocrinol (Oxf)
Prevalence of hyperprolactinemia in adolescents and young women with menstruation-related problems
Am J Obstet Gynecol
Hyperprolactinemia-induced ovarian acyclicity is reversed by kisspeptin administration
J Clin Invest
Hypothalamic-pituitary-Ovarian Axis reactivation by kisspeptin-10 in hyperprolactinemic women with chronic amenorrhea
J Endocr Soc
Women with prolactinomas presented at the postmenopausal period
Endocrine
Prolactinomas diagnosed in the postmenopausal period: clinical phenotype and outcomes
Clin Endocrinol (Oxf)
Hyperprolactinemia/Prolactinomas in the post-menopausal period: challenges in diagnosis and management
Neuroendocrinology
A study of the clinical differences between women and men with hyperprolactinemia
Gynecol Endocrinol
Sex-related difference in the growth of prolactinomas: a clinical and proliferation marker study
J Clin Endocrinol Metab
Prolactinomas in men
Influence of parasellar extension of macroprolactinomas defined by magnetic resonance imaging on their responsiveness to dopamine agonist therapy
Clin Endocrinol (Oxf)
Clinical, pathological and molecular factors of aggressiveness in lactotroph tumours
Neuroendocrinology
Sex-related differences in lactotroph tumor aggressiveness are associated with a specific gene-expression signature and genome instability
Front Endocrinol (Lausanne)
Bone marker and bone density responses to dopamine agonist therapy in hyperprolactinemic males
J Clin Endocrinol Metab
Prolactin release during nursing and breast stimulation in postpartum and nonpostpartum subjects
J Clin Endocrinol Metab
Male prolactinomas presenting with normal testosterone levels
Pituitary
Outcome of cabergoline treatment in men with prolactinoma: effects of a 24-month treatment on prolactin levels, tumor mass, recovery of pituitary function, and semen analysis
J Clin Endocrinol Metab
Primary medical therapy of micro- and macroprolactinomas in men
J Clin Endocrinol Metab
Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients
J Clin Endocrinol Metab
Six months of treatment with cabergoline restores sexual potency in hyperprolactinemic males: an open longitudinal study monitoring nocturnal penile tumescence
J Clin Endocrinol Metab
Pituitary apoplexy
Endocr Rev
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2023, World NeurosurgeryCitation Excerpt :Infertility, gonadal, and sexual dysfunction are the most common symptoms in both sexes.5,6 Menstrual disorders and galactorrhea in women and loss of libido, erectile dysfunction, and gynecomastia in men are hyperprolactinemia-related symptoms.7 The aim of the treatment is to normalize hyperprolactinemia and related symptoms, control tumor volume, and improve quality of life.3