Immune-related hypophysitis in three patients with metastatic melanoma undergoing Ipilimumab treatment

Ipilimumab is a humanized antibody that stimulates antitumor immune response by blocking Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) on T-cells and was recently approved for treatment of advanced malignant melanoma. Adverse events due to potentiated immunoreactivity frequently affect non-endocrine and endocrine organ systems during Ipilimumab therapy. We describe three patients with anti-CTLA4-associated autoimmunity to the pituitary gland. The first two patients presented with unspecific complaints like headache and fatigue but soon developed sharply distinct clinical courses. Patient 1 presented with an Addisonian crisis as an acute onset of hypophysitis. In patient 2, the rare condition of panhypopituitarism together with diabetes insipidus as a combined affliction of both anterior and posterior pituitary lobe was diagnosed. Subsequently, patient 2 developed hepatitis as additional immune-related side effect. In patient 3, asymptomatic hypophysitis was diagnosed during routine staging and manifested as anterior lobe dysfunction. On the basis of these patients, we suggest adaption of diagnostic and therapeutic workflows to detect the diverse clinical presentations of Ipilimumab-associated hypophysitis.

In summary, careful clinical observation and functional endocrine testing together with imaging procedures help to manage both simple and complex forms of hypophysitis, for which a specific awareness is needed in cancer patients on Ipilimumab treatment.