Start low, go slowly – mental abnormalities in young prolactinoma patients under cabergoline therapy

Abstract

Background Prolactin-secreting pituitary adenomas in childhood and adolescence are rare. First-line therapy consists of dopamine agonists (DAs) like cabergoline. Experience in treating prolactinomas in paediatric and adolescent patients is limited. Methods This study was a retrospective analysis of clinical data, laboratory data, radiological findings and medical treatment of paediatric and adolescent patients with prolactinomas between 2009 and 2018. Results Our cohort of nine patients had a median age at diagnosis of 13 years (range 5–17). Main presenting symptoms were weight gain, disorders of the pituitary-gonadal axis and headache. Treatment with cabergoline resulted in a marked reduction in prolactin concentration in all nine patients. Tumour mass reduction was confirmed by magnetic resonance imaging (MRI) scan in seven patients. Noteworthy is that cabergoline therapy triggered frequent adverse effects in a total of eight patients – seven of whom suffered from mental disorders, five of whom had neurological symptoms and five of whom had gastrointestinal problems. The adverse effects occurred at a median dose of only 0.5 mg/week (range 0.25–2.0). Most symptoms were alleviated after the cabergoline dose was lowered. Therapy discontinuation was not necessary in any patient. Conclusions Cabergoline effectively lowers prolactin levels and may reduce tumour mass in paediatric and adolescent patients with prolactinomas. Potential adverse effects may include mental disorders and behavioural problems even at low cabergoline doses. Low starting doses and careful individual dose adjustments are required to enable therapy adherence.

Diagnosis and management of prolactin-secreting pituitary adenomas: a Pituitary Society international Consensus Statement

“…Dopamine agonists are first-line therapy, starting at a low dose and individualizing dose adjustments due to the potentially increased susceptibility to adverse effects in children 161,162 . Surgery should be considered in children with threatened vision 163 .…”

Consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: Part 2, specific diseases

“…Small nocturnal dose increments of cabergoline can effectively diminish the adverse effects of gastrointestinal intolerance and postural hypotension, thereby avoiding trials of less effective dopamine agonists (bromocriptine or quinagolide). Dose-independent psychological intolerance (mood changes, depression, aggression, hypersexuality and impulse control disorder) is similar between agents and described in adults as well as CYP 37,43 , but the frequency of these adverse events might be higher in CYP than in adults 11,44 . Dopamine agonist resistance is usually defined in adults and CYP as failure to achieve normoprolactinaemia (biochemical resistance) and less than 50% reduction in tumour area in the coronal plane and/or less than 30% reduction of the longest diameter of the tumour (tumour size resistance, assessed by Response Evaluation Criteria In Solid Tumours (RECIST) criteria) after 3-6 months of maximally tolerated dopamine agonist doses (at least 2 mg per week) 18,41,45,46 .…”

Shrinkage by the third month predicts long-term response of macroprolactinoma after cabergoline

“…This means the possibility of side effects related to a high cumulative dose of CBG, such as heart valves abnormalities (7). Furthermore, recent evidence suggests an increased prevalence of impulse control disorder symptoms and behaviour problems in patients treated with dopamine agonists (9,22,23,24,25,26). For all these reasons, keeping patients on lifelong CBG treatment, especially with high doses, seems currently inadvisable.…”