Poster Presentation ESA-SRB 2023 in conjunction with ENSA

Case:

A 29-year-old female presented with a 2-year history of amenorrhoea and headache. MRI-pituitary identified a macroadenoma (24x23x19mm) with optic chiasm compression. Pituitary investigation confirmed hypogonadotropic hypogonadism (Table 1), and low prolactin (PRL). Dilution test was undertaken to exclude underlying ‘hook effect’. She subsequently underwent transsphenoidal resection. Surprisingly, tumour immunohistochemistry (IHC) stained positive for PRL, leading to the diagnosis of silent prolactinoma. Patient conceived spontaneously shortly after surgery and delivered a healthy child. Over the next 2 years, there was gradual tumour regrowth on MRI. Cabergoline (CAB) was offered instead of repeated surgery. She responded well to therapy and conceived again spontaneously. Post-partum, CAB was recommenced due to tumour recurrence (9x13x13mm), contacting optic chiasm. Her latest MRI 6 months after treatment showed marked tumour size reduction. 

Discussion:

Silent prolactinoma is a rare subtype of PitNETs, where the tumour displays positive IHC staining to PRL without evidence of hyperprolactinaemia. The current 2022 WHO classification of PitNETs endorses the testing of transcription factors (TFs) to differentiate various PitNET subtypes.¹ It is believed that antibodies against TFs are more specific and reproducible than anterior pituitary hormones on IHC. Prolactinomas (secretory or non-secretory) have PIT-1 cell-lineage and typically express dopamine-2 receptors (D2R) on cell surface.  Treatment with dopamine agonist such as CAB is effective both at normalising PRL level and reducing tumour size in 85-90% cases.²  

Hook effect is a phenomenon when high PRL concentration saturates the anti-PRL-antibodies on immunoassay, leaving some PRL molecules uncaptured and unmeasured, therefore under-estimates the true PRL level.³ It is typically seen in up to 20% of macroprolactinoma.⁴ By diluting the sample by 1:100 or using an immunoassay not affected by hook effect, a true PRL level can be obtained. It is important to exclude this at diagnosis as macroprolactinoma can be successfully treated medically instead of surgery.