Diabetes Insipidus Should Be Included

For completeness’s sake, diabetes insipidus (DI) should be added as an entity to this very clear and balanced description of the endocrine side affects of immune checkpoint inhibitors.

Central diabetes insipidus (CDI) is extremely rare during treatment with immune checkpoint inhibitors (1). CDI has been described in only five cases of such treatment. Two of these cases occurred during treatment for prostate carcinoma using ipilimumab; in both cases the CDI was cured by administering high-dose glucocorticoids. In a further case, CDI developed during treatment for Merkel cell carcinoma after three months of avelumab. In this case, CDI disappeared spontaneously once avelumab was stopped (2). In another case, during treatment of metastatic melanoma with a combination of nivolumab and ipilimumab, CDI, lymphocytic adenohypophysitis, and type 1 diabetes developed. In all four cases, MRI scanning showed a thickening of the pituitary stalk and contrast medium enhancement of the stalk as well as the posterior pituitary/neurohypophysis. A case of nivolumab induced CDI was reported in a man with advanced lung cancer, who developed the disease five months after the treatment had been initiated (3). The man died before treatment for CDI was started. Symptomatic treatment of CDI was given by means of administering 1-desamino-8-D-arginin-vasopressin (DDAVP) as tablets or nasal drops at an adequate dosage.

The question of why CDI as an expression of lymphocytic infundibuloneurohypophysitis is rare compared with lymphocytic adenohypophysitis during treatment with immune checkpoint inhibitors remains unanswered. It is possible that the diagnosis of incomplete CDI with mild polyuria is made only rarely in view of the often severe underlying disorder.