Endocrine Abstracts

Clinical case: We report the case of a 40-year-old woman, diagnosed with sporadic medullary thyroid carcinoma (MTC) treated with total thyroidectomy, cervical lymph node dissection and chemotherapy. During follow-up, cervical lymph node, lung, breast, bone and subcentimeter cerebellous affectation was observed. She started on Sunitinib, but withdrawal at 6 months due to severe inguinal inverse psoriasis. Then, treatment with vandetanib was started with good response. Tumor markers levels decreased with treatment with tyrosine kinase inhibitors (TKIs) from calcitonin 19 504 pg/ml and carcinoembryonic antigen (CEA) 202.1 ng/ml, to 273 pg/ml and 23.4 ng/ml respectively. While lung, cerebellous and bone lesions remained stables, breast metastasis dissappeared. Secondary adrenal insufficiency (AI) and hypogonadotropic hypogonadism developed, with other hypophyseal function preserved. Pituitary MRI and anti-hypophysis antibodies were normal.

Discussion: AI has been reported as consequence of hypophysitis secondary to anti-tumor agents as Ipilimumab. In our case, there were not data of hypophysitis. We suggest that this effect of vandetanib may be due to its anti-angiogenic effect probably by inhibiting epidermal growth factor receptor (EGFR). EGF is expressed in a lower form in nontumoral cells, as hypophysis cells, where EGFR has been detected in 5–10% of them, mainly in gonadotrope and thyrotrpe cells. Likewise, EGFR sobreexpression has been described in metastatic MTC, associated with RET mutation M819T with a specific well response to vandetanib. In the same way, ACTH-producing pituitary macroadenomas has been identified as good responders to TKIs, as gefitinib, due to the sobreexpression of EGF in tumoral corticotrope cells that could be present in nontumoral corticotrope cells.

Conclusions: In patients on treatment with TKIs, especially those with effect of EGFR, may be interesting to rule out the presence of pituitary abnormalities if it is clinically suspected.