Macroprolactinomas generally demonstrate an excellent biochemical response to dopamine agonists, with surgery reserved for selected cases. Persistent hyperprolactinaemia despite maximal medical therapy and transsphenoidal surgery in the absence of identifiable residual tumour presents a significant therapeutic challenge.

A 26-year-old man presented in 2024 with headache and clinical features of secondary hypogonadism, including reduced libido, erectile dysfunction, gynaecomastia, and attenuated secondary sexual characteristics. Serum prolactin was markedly elevated at 93,095 mIU/L. MRI demonstrated a 27 × 28 mm haemorrhagic suprasellar macroadenoma consistent with pituitary apoplexy.

He was commenced cabergoline therapy, which was gradually escalated to 4.5 mg/week.Serial MRI demonstrated small reduction in size of tumour and prolactin concentrations plateaued at approximately 7,000 mIU/L despite maximal tolerated medical therapy.  

Given persistent biochemical disease, he underwent endoscopic transsphenoidal resection. Histopathology confirmed macroprolactinoma. Postoperative MRI in December 2025 demonstrated no definite residual tumour. Despite surgery, prolactin remained elevated at approximately 6,000 mIU/L, improving only to around 3,300 mIU/L while continuing cabergoline 0.5 mg four times weekly. 

This case illustrates dopamine agonist-resistant macroprolactinoma with persistent biochemical activity despite apparent complete surgical resection. The discordance raises possibilities of  microscopic residual adenoma or invasive tumour within the cavernous sinus. 

Our plan is to  escalate cabergoline therapy to the maximum tolerated dose. Radiotherapy as next treatment option; however,  it carries significant long-term risks, including hypopituitarism and potential development of secondary neoplasms. If disease control is not achieved with these treatment modalities, systemic therapies, including temozolomide for aggressive prolactinomas, would be considered as  next line of treatment. 

Learning points

• Persistent hyperprolactinaemia following maximal dopamine agonist therapy and transsphenoidal surgery without radiological residual disease is uncommon and presents a difficult management dilemma.  
• Management should occur within a multidisciplinary pituitary service, with consideration of expert consensus and emerging therapies where conventional treatment options have been exhausted.