Endocrine Abstracts

Introduction: Immunotherapy is the oncological treatment whose objective seeks, through the use of immunomodulatory monoclonal antibodies, to block the regulation of the activation and response of T cells, increasing their antitumor response. Pembrolizumab is a new monoclonal antibody directed against the surface protein PD 1, (Programmed Cell Death-1), responsible for the inhibition of the immune response, mediated by T cells, against cancer cells; indicated in the treatment of different malignant neoplasms (non-small cell lung carcinoma). Despite being well tolerated, they have a different adverse effect profile than conventional chemotherapy, with an immune-mediated profile. Among them, endocrinological ones stand out, which can be the cause, among others, of severe hormonal deficits. Our objective is to describe the case of a patient diagnosed with lung adenocarcinoma (stage IV), under treatment with Pembrolizumab, who suffered, as a rare adverse effect, lymphocytic hypophysitis, causing hypopituitarism in the form of central adrenal insufficiency (alteration of the hypothalamic-pituitary-adrenal-axis) and GH deficiency.

Clinical Case: A 39-year-old male, with the oncological history already described, being treated with Pembrolizumab and Pemetrexed (antifolate), referred to the Emergency-Department due to clinical symptoms of diarrhea, abdominal pain, nausea, involuntary vomiting and intense asthenia. He is admitted with a suspected diagnosis of immune-mediated colitis. Complementary-studies: The analysis highlights the involvement of the corticotropic axis and IGF-1 deficiency: TSH 0.175 uU/ml, fT4 1.420 ng/dl, fT3 1.630 pg/ml, FSH 11.6U/l, LH 10.30 U/l, Testosterone 6.51 ng/ml, Prolactin 4.77 ng/ml, ACTH<1.50 pg/ml, Cortisol 0.8 mg/dl, HGH 0.32 ng/ml, IGF-1 46.2 ng/ml. b. Pituitary-MRI with contrast: Loss of the normal hyperintensity of the neurohypophysis in T1 and moderate thickening of the pituitary stalk, findings that may be compatible with lymphocyti hypophysitis. Given suspicion of adrenal insufficiency, 50mg-IV hydrocortisone was prescribed along with fluid therapy with clear clinical improvement. At discharge, hydroaltesone 20 mg/8h, with progressive decrease to replacement dose. The outpatient study showed ACTH 12.0pg/ml and Cortisol 15.2 mg/dl. After clinical stability, Pembrolizumab cycles are reintroduced.

Discussion and conclusions: The side effects of immunotherapy can occur at different levels in the same patient. Hypophysitis, jointly associating corticotropic and somatotropic deficiency, is an adverse reaction not described to date after studying the available literature, with serious consequences and the need for urgent treatment. Given its potential severity, it is essential, in patients undergoing treatment based on immunotherapy, to maintain a high level of suspicion, so that, in the event of nonspecific symptoms such as nausea, vomiting and/or fatigue (very common), an urgent evaluation should be prompted, including exhaustive hormonal study.