Endocrine Abstracts

Introduction: Temozolomide (TMZ) can be administered as the last therapeutic option for aggressive pituitary tumors. Dopamine-agonist resistant prolactinomas are relatively frequent and remain a serious therapeutic problem. GH expressing atypical adenomas are rare and their positive response to TMZ is low. In a general opinion a lack of response to TMZ after three cycles predicts the treatment resistance.

The aim of the study was presentation of two patients with a long-standing history of atypical aggressive pituitary macroadenomas, refractory to numerous medical and ablative therapies and also to TMZ treatment.

Case 1: A 59-year-old woman with MEN1 syndrome (prolactinoma and primary hyperparathyroidism). Because of amenorrhea–galactorrhea syndrome she received dopamine agonists for 16 years. The tumor size was stable for 10 years, but PRL level was never normal. Five years ago, propter tumor expansion and resistance to dopamine-agonists she underwent non-total transsphenoidal adenomectomy but further enlargement of prolactinoma and its multidirectional expansion succeeded. She was disqualified for the next neurosurgery and gamma-knife and TMZ was implemented. Unfortunately TMZ was ineffective and it was withdrawn after three cycles.

Case 2: A 44-year-old woman with hormonal inactive macroadenoma causing secondary hypogonadism and compression of the optic chiasm. She underwent a left temporal craniotomy with subtotal adenomectomy followed by cobaltotherapy. A postoperative exploration revealed adenoma chromophobum. 18 years later, due to a re-growth of the tumor, she underwent right craniotomy. The second postoperative study revealed atypical GH (+), PRL (+) – type 3 silent adenoma. Then ⁹⁰Y/¹⁷⁷Lu DOTA-TATE, somatostatin analogue and bromocriptine were applied. Symptoms of acromegaly occurred only after 19 years from the diagnosis. Propter large tumor size and its localization the patient was disqualified for neurosurgery and gamma–knife. Three cycles of TMZ were administered without any response.

Conclusion: Long-standing, large atypical invasive pituitary dopamine-agonist refractory prolactinomas and silent somatotropinomas may be refractory to temozolomide treatment.