Background: The frequency of spontaneous CSF rhinorrhea in macroprolactinoma patients is poorly documented and was previously thought to be a very rare occurrence.Methods: Thirty patients with macroprolactinomas (>1.0 cm diameter) identified from the Swansea neuroendocrine database were studied retrospectively.Results: At presentation, the median serum prolactin was 28 354 (range, 1844 to >6 000 000) mU/L; radiologically, 4 adenomas were invading the cavernous sinus, one the sphenoid sinus and 5 both the cavernous and sphenoid sinus. After commencement of medical therapy, 4 subjects developed CSF rhinorrhea requiring surgical correction; all 4 had tumors invading both the cavernous and sphenoid sinus and an initial serum prolactin more than 75 000 mU/L. One subject. developed an acute psychosis, and a man who presented with delayed puberty committed a serious sexual offense.Conclusions: Serious adverse effects are not uncommon in medically treated macroprolactinoma patients. Subjects with adenomas invading the sphenoid sinus have a high risk of developing CSF rhinorrhea that requires neurosurgical intervention. (C) 2009 Elsevier Inc. All rights reserved.