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

Abstract

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.

Hyperprolactinaemia

“…Any lesion leading to interruption of the dopaminergic pathways due to compression of the pituitary stalk and portal vessels can lead to hyperprolactinaemia through the "stalk effect" [including pituitary adenomas with the most common cause in this setting being the non-functioning pituitary adenomas (NFA); parasellar tumours (such as Rathke's cleft cyst, craniopharyngioma, meningioma or germinoma); metastatic pituitary disease, infiltrative/inflammatory diseases (such as lymphocytic hypophysitis, Langerhans cell histiocytosis, and sarcoidosis)] [6,25,41]. Stalk compression from NFA or other parasellar tumours is typically associated with PRL levels <100 µg/L [42,43]. Hyperprolactinaemia has also been reported in 7 to 10% of patients with primary empty sella syndrome attributed to compression of the pituitary gland against the sellar walls causing stretching of the pituitary stalk [44].…”

“…The clinical manifestations of hyperprolactinaemia mainly relate with the reproductive system [25,43]. The patients may also have other signs and symptoms depending on the aetiology of the PRL excess (e.g., mass effects, in case of a pituitary tumour (headaches, visual disturbances, hypopituitarism)).…”

“…Hyperprolactinaemia suppresses GnRH (via reduction of kisspeptin in the hypothalamic arcuate and periventricular neurons) leading to a decrease in LH pulse amplitude and frequency [43]. It also decreases ovarian oestrogen and progesterone production [43].…”

“…Hyperprolactinaemia suppresses GnRH (via reduction of kisspeptin in the hypothalamic arcuate and periventricular neurons) leading to a decrease in LH pulse amplitude and frequency [43]. It also decreases ovarian oestrogen and progesterone production [43]. These result in menstrual irregularities (amenorrhoea or oligomenorrhoea), infertility, decreased libido and galactorrhoea [25].…”

“…The differentiation between a PRL-secreting tumour and a NFA or other sellar/parasellar mass causing hyperprolactinaemia through "stalk effect" is very important, as these conditions are managed differently [42]. In prolactinomas, apart from the cystic ones [43], adenoma size generally corresponds with PRL levels. Nonetheless, there is no PRL cut-off with perfect diagnostic value differentiating prolactinoma from other tumours [42].…”