Introduction: Childhood prolactinomas often occur as aggressive macro (14 cm) or giant (>4 cm) tumours, with little consensus regarding timing of optimal therapies.
Aim: To highlight the phenotype and treatment outcome of childhood macroprolactinomas.
Subjects and methods: Case-note review of 10 (five male) children (<18 years) (presenting to our centre between 2009 and 2017 with hyperprolactinaemia due to macro/giant-prolactinomas.
Results: At diagnosis children were of median (range) 13.9 (11.016.3) years and had symptoms for 24 (184) months, including headaches (10/10), visual deficit (5/10), short stature (2/10), pubertal arrest (4/10) and galactorrhoea (2/10). A family history of pituitary adenomas was identified in 4/10; one proved heterozygous for an MEN1 mutation. None harboured an AIP mutation. At diagnosis, all children had 14 anterior pituitary hormone deficits. All received first-line cabergoline treatment apart from one misdiagnosed elsewhere as craniopharyngioma. Five required surgery (two repeatedly) of whom two have also had radiotherapy, due to cabergoline side effects (1), visual compromise (2) or tumour regrowth (2). Two required urgent transsphenoidal surgery for either presenting pituitary apoplexy or CSF leak following cabergoline. Seven continue on dose-escalating cabergoline (1.07.5 mg/week). Four experienced cabergoline side effects (headaches, aggressive behaviour, impulse control disorder, CSF leak). At diagnosis the median (range) prolactin levels were 61.173 mIU/L (9,1761,238,960). After 24 (1696) months these are 4,294 mIU/l (35844,944). Prolactin levels decreased by 93% (8399.6%) in 9/10, in parallel with tumour volume shrinkage by 41.8% (24%90%), excepting the MEN1 positive patient whose prolactin increased by 62.7%., in keeping with a tumour volume increase of 70%. In two the prolactin has normalised (<450 mu/l). All had suprasellar extension and cavernous sinus infiltration, 8/10 had optic chiasm compression, 5/10 had skull base infiltration and 4/10 had haemorrhage. At diagnosis, four had normal vision which remained unchanged but six had visual deficits (hemianopia, quadrantanopia), of whom, two are now registered blind and four have persisting visual impairment.
Conclusions: Cabergoline should be the first-line treatment in childhood-onset macroprolactinomas; tumour responsiveness correlates with prolactin levels. Fast dose-escalation and prolonged administration may be necessary for disease control, but close monitoring for resistance, complications and side effects is essential. In resistant disease, surgery increases endocrine deficits, may not prevent blindness, and radiotherapy (which has proved effective) may be necessary. MEN1 and AIP analysis is strongly recommended to inform pathogenesis, allow screening for other disease manifestations and identify at-risk relatives.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology