Refractory Headache in Macroprolactinoma Resolved After Neurosurgery: A Challenging Clinical Case and Literature Review

Abstract Pituitary tumors are present in approximately 15% of the population and are often discovered incidentally during imaging for headache evaluation. Headaches are prevalent in patients with pituitary adenomas, occurring in 37-70% of cases. However, determining whether the tumor itself causes the pain is frequently challenging. A 27-year-old woman presented with progressive daily holocranial headaches, photophobia, phonophobia, nausea, and secondary amenorrhea. Laboratory tests and pituitary imaging confirmed a macroprolactinoma. Initial treatment with cabergoline and bromocriptine was unsuccessful due to intolerable side effects. Transsphenoidal surgery produced marked clinical improvement and a partial reduction in serum prolactin. However, tumor regrowth occurred with recurrence of daily headaches, and a second surgery was delayed due to the COVID-19 pandemic. Multiple medical treatments, which included topiramate, divalproex sodium, amitriptyline, propranolol, and riboflavin with magnesium resulted in no improvement. After the second neurosurgery, she presented normoprolactinemia with no residual tumor and once again a complete resolution of the headache episodes. Risk factors for headache related to adenoma include high prolactin or IGF-1 levels, cavernous sinus invasion (but not adenoma size), and a history of primary headache disorder. International diagnosis criteria emphasize headache resolution following endocrine normalization or tumor removal. This case highlights the intricate relationship between prolactinomas and headaches, underscoring the need for individualized treatment strategies.