Resistant and aggressive prolactinoma treated with temozolomide

C. Cidade-Rodrigues*^a (Dr), A. Maia^b (Dr), I. Ribeiro^b (Dr), C. Amaral^b (Dr)

^a Centro Hospitalar do Tamega e Sousa, Penafiel, PORTUGAL ; ^b Centro Hospitalar Universitario do Porto, Porto, PORTUGAL

* catarinacidaderodrigues@gmail.com

Introduction: Prolactinomas are prolactin-secreting pituitary tumours, with a prevalence of 50/100000. They occur more frequently in women and most respond to treatment with dopamine agonists. When in men, they are usually larger, more resistant to medical treatment and often show aggressive features. We present the case of a male patient with a resistant and aggressive macroprolactinoma, treated with temozolomide.

Observations: Male, 30 years-old, Caucasian. Symptoms: Headaches for 6 months. No visual impairment. Reduced libido. No past medical history or medication. No family history of endocrinological disorders or malignancy. Physical examination: BMI 27.4kg/m². Bilateral nonpainful gynecomastia. Initial blood work: prolactin 3152ng/ml, total testosterone 0.382ng/ml, no other abnormalities. Pituitary MRI: intrasellar round mass, 19x26x22mm, consistent with macroadenoma, not invading the cavernous sinus, but touching the optic chiasm. Treated with cabergoline 2mg/week. Prolactin and testosterone levels returned to normal within 3 months; MRI showed tumour shrinkage. Three years later, prolactin levels started rising and there was tumour regrowth in MRI scans. First transsphenoidal surgery in 2016, initially with good response but signs of tumour progression later on. During follow-up, due to tumour relapse despite maximal tolerated doses of cabergoline, 4 more surgeries were performed, as well as 2 radiotherapy cycles (cumulative dose of 72 Grays). Histology: abundant mitosis, immunoreaction for PRL and PIT1.Ki-67 >3%.p53+. AIP gene mutation: negative. He developed hypopituitarism. Whole body CT: no signs of metastasis. In 2022: new relapse - he started treatment with temozolomide, with good analytical response (prolactin: 1331>1011>697ng/ml). Post-treatment MRI: tumor size reduction.

Discussion: Resistant prolactinomas are a therapeutic challenge, especially when other features of aggressiveness are present. Although temozolomide is recommended as fourth-line treatment in these cases, success rates are around 50-60%. In our patient, there seems to be a good initial response to this treatment. However, other therapies need to be considered in case of future relapse or progression, such as somatostatin analogues, checkpoint or mTOR inhibitors and peptide receptor radionuclide therapy.

The author has declared no conflict of interest.