Oral Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2017

An Endocrinologist’s View: Diagnosis and Management of Immunotherapy Related Endocrinopathies (#50)

Venessa Tsang 1
  1. University of Sydney and Royal North Shore Hospital, Royal North Shore, NSW, Australia

Immunomodulator therapy is used in the management of a number of malignancies, initially in metastatic melanoma, but also approved in an increasing number of other malignancies including locally advanced or metastatic non small cell lung cancer, head and neck squamous cell carcinoma, clear cell renal cell carcinoma, and classical Hodgkin lymphoma.  Endocrine related immune related adverse reactions (iRAE) are one of the more common manifestations developing in 5-10%1 of patients on either single of combination cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) or programmed cell death -1 receptor or ligand (PD-1) therapy.  iRAE are more common in combination therapy and with high does, and generally occur within 12 weeks of treatment2 though there are reports development of later side effects.  The majority of endocrine iRAE are grade 1 and 2.

The main endocrine iRAE involve the pituitary (hypophysitis resulting in adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH) or gonadotrophin hormone deficiencies), the thyroid (thyroiditis, resulting in hyperthyroidism or hypothyroidism), the pancreas (resulting in insulin deficiency and diabetes mellitus), and the adrenal glands (resulting in corticosteroid deficiencies.  The challenges in the assessment and management of these iRAEs are how best to predict their occurrence, how and when to screen for endocrinopathies, and how to treat them.  It is not clear currently whether development of endocrine iRAE is predictive of response to iRAE. 

A final emerging challenge in endocrine iRAE is its recognition and diagnosis. There are increasing numbers of patients presenting with adrenal crisis related to infection on a background of hypophysitis.  Awareness of this problem by patients and medical staff is integral in prevention of adverse outcomes.

  1. Michot JM, Bigenwald C, Champiat S, Collins M, Carbonnel F, Postel-Vinay S, et al. Immune-related adverse events with immune checkpoint blockade: a comprehensive review. European journal of cancer (Oxford, England : 1990) 2016 Feb;54:139-48.
  2. Champiat S, Lambotte O, Barreau E, Belkhir R, Berdelou A, Carbonnel F, et al. Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper. Annals of oncology : official journal of the European Society for Medical Oncology 2016 Apr;27(4):559-74.