Immune Check Point Inhibitors Triggering Non Autoimmune Polyendocrinopathy

Abstract

The superlative therapeutic response of cancer immunotherapy is activation of the immune system against cancer cells. Currently, one of the most considered immune system enhancer are the immunomodulatory antibodies well known as checkpoint inhibitor therapy. Among this type of treatment, programed cell death-1 receptor blocker, is one of the most sought-after therapies on demand now a day. Notwithstanding the important clinical benefits of this therapeutic modality, serial autoimmune adverse effects and variety of atypical presentations of life-threatening endocrinopathies are expected to occur.We present a case of a 78-year-old man with dyslipidemia and lung CA who was referred to our clinic after developing electrolyte disturbances with associated dizziness and fatigue one month after Pembrolizumab therapy initiation. Physical exam was unremarkable. Laboratory data was consistent with mild hyponatremia, hyperkalemia and adequate fasting blood sugar levels. Aldosterone levels were extremely low, ACTH levels were extremely high with inappropriate low total cortisol response and negative 21-Hydroxylase antibodies. Diagnosis of primary adrenal insufficiency was established and Fludrocortisone 0.05 mg PO daily therapy was started with further resolution of hyponatremia and initial symptoms. In addition, concurrent primary hyperthyroidism along with thyroid RAIU-Scan results were consistent with thyroiditis, but TSI and TPO’s antibody levels were unexpectedly negative. Eventually, a suspicious thyroid nodule was identified requiring biopsy. Initial FNA results showed a follicular lesion of undetermined significance followed by a benign finding when repeated after six months. During follow up, patient’s primary hyperthyroidism converted to severe primary hypothyroidism without any intervention for her prior hyperthyroidism. Patient’s TPO’s levels remain undetectable and his current status is post-thyroiditis with residual primary hypothyroidism. Primary adrenal insufficiency also persist and its antibodies have not yet been identified either.It is known that autoimmunity can predispose to the development of primary adrenal and thyroid disorders in patients undergoing PD-1 receptor blockers therapy against cancer. Both disorders are increasingly recognized and reported as one of the most common adverse effects presenting in patients treated with these agents. However, to our knowledge, cases of non-immune related adverse effects are barely documented. This case of uncommon endocrine manifestations related to checkpoint inhibitors therapy is meritorious of being reported since it should raise awareness in the medical community for prompt identification of signs and symptoms, as well as to offer adequate management, accurate treatment and provide a better standard of care.