Endocrine Abstracts

Introduction: Prolactin adenomas are the most common pituitary tumors. The aim of treatment is to achieve normal prolactin levels in order to reduce tumor mass and restore the gonadotropic axis. Dopaminergic agonists, including cabergoline, are the standard treatment. But some adenomas can be resistant to this treatment and behave like aggressive tumors. We report the case of a macroprolactinoma resistant to cabergoline.

Observation: 50-year-old female patient referred from neurosurgery after a surgical management of a 63 mm giant invading macroadenoma complicated by apoplexy, with histological examination of an adenoma expressing prolactin. Postoperative biological workup revealed persistent hyperprolactinemia at 10379/ml, and a pituitary macroadenoma measuring 42×35 mm on hypothalamic-pituitary MRI. The visual field revealed a bitemporal hemianopia. The patient was put on cabergoline at a dose of 1 mg per week, gradually increasing to 3 mg per week, with persistent hyperprolactinemia at 6028 ng/ml and a macroadenoma at 38 mm. Transphenoidal revision surgery was indicated, with persistent hyperprolactinemia at 2598 ng/ml at 6 months postoperatively on 4 mg cabergoline.

Discussion : Four histological observations have been made in DARP studies increased angiogenesis, cellular atypia, increased proliferation and invasiveness. Resistance to cabergoline is due to decreased expression of dopamine receptor subtype 2. This resistance could result from the reduced dopaminergic signalling caused by these changes, or may be the result of uncharacterized mutations. As described, invasion of the cavernous sinus is a more frequent finding in DARP management is delicate and requires a multimodal approach, including transphenoidal surgery, alternative medical therapies such as somatostatin analogues and estrogen receptor antagonists.

Conclusion : The notion of resistance to dopaminergic agonists (DAs) remains controversial. Although rare, they constitute pathological entities that require the emergence of new therapies.