Diabetes Insipidus Should Be Included

Letters to the Editor The Diagnosis and Management of Endocrine Side Effects of Immune Checkpoint Inhibitors by Prof. Dr. med. Knut Mai, Prof. Dr. med. Martin Fassnacht, Prof. Dr. med. Dr. rer. nat. Dagmar Führer-Sakel, Prof. Dr. med. Jürgen B. Honegger, Prof. Dr. med. Matthias M. Weber, Prof. and Dr. med. Dr. rer. nat. Matthias Kroiss in issue 23/2021

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.

DOI: 10.3238/arztebl.m2021.0312

Prof. (em.) Dr. med. Werner A. Scherbaum
Heinrich-Heine-Universität Düsseldorf, Universitätsklinikum

Conflict of interest statement

The author declares that no conflict of interest exists.

References

1. Scherbaum WA: Autoimmune diabetes insipidus. In: Aminoff MJ, Boller F, Swaab DF, eds.: Handbook of clinical neurology, 3 rd series. The human hypothalamus. Vol III, 25, Elsevier 2021

2. Zhao C, Tella SH, Del Rivero J, et al.: Anti-PD-L1 treatment induced central diabetes insipidus. J Clin Endocrinol Metab 2018; 103: 365–9

3. Deligiori MV, Siasos G, Vergadis C, et al.: Central diabetes insipidus related to anti-programmed cell-death 1 protein active immunotherapy. Int Immunopharmacol 2020; 83: 106427

4. Mai K, Fassnacht M, Führer-Sakel D, Honegger JB, Weber MM, Kroiss M: The diagnosis and management of endocrine side effects of immune checkpoint inhibitors. Dtsch Arztebl Int 2021; 118: 389–96