Endocrine Abstracts

Introduction: The aim of our study was to investigate clinical and morphological features of dopamine agonist-resistant prolactinomas.

Methods/design: The study included 51 patients (38 women, 13 men) with prolactin-secreting pituitary adenoma that is resistant to treatment with dopamine agonists, age 15–82 years.

Results: Median of the serum PRL level distribution at the onset of the disease was 4500 mIU/l (3480, 140 300). The MRI showed nine patients (17.6%) had microadenoma, 42 patients (82.4%) – macroadenoma, in 14.3% of the cases a giant adenoma was found. 31 patients underwent surgery (60.8%), and six patients were operated repeatedly. Radical surgical treatment, estimated as reaching normoprolactinemia and no residual adenomatous tissue, was seen in 35.5% of the cases (11 patients). In addition, five patients (16.1%) the surgery resulted in medical control of hyperprolactinemia with lower doses of cabergoline than those before the surgery. 20 adenoma samples were investigated by immunohistochemistry. In the study of the expression of PRL the diagnosis of prolactinoma was confirmed in 19 patients (95%), one patient did not reveal any expression of tropic hormones. Co-expression of the GH was found in seven patients (36.8% of the 19 patients with PRL immunopositivity), although clinical acromegaly was not observed in these patients, with normal values of IGF1. The expression of TSH, ACTH, LH, FSH was not found in any case. The expression of dopamine receptor type 2 was confirmed in 13 cases (65%). The presence of somatostatin receptor expression type 2 (SSR2) was detected in five patients (25%), SSR5 – in eight patients (40%), SSR2 and SSR5 – in three patients. Estrogen receptor expression was detected only in one case (5%). None of the patients showed expression of progesterone receptors.

Conclusion: Resistance to treatment with dopamine agonists is a serious problem; more often patients with resistant prolactinomas have macroadenoma. Surgical treatment is effective in 35.5% of cases. We can assume that resistance to treatment with dopamine agonists is associated with low expression of dopamine receptors in the cells of removed adenomas. Low expression of SSR2 and SSR5 in these patients may indicate the failure of therapy with somatostatin analogues. Thus, further study and search for effective treatments for these patients are required.