Associations of Endocrine Functions and Hormone Axes

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

In my opinion, an article about the endocrine side effects of immune checkpoint inhibitors should necessarily mention important associations of endocrine functions and hormone/hormonal axes.

For example, primary adrenal cortex insufficiency can bring about higher concentrations of thyroid stimulating hormone, reversible after cortisol substitution. On the other hand, cortisol substitution can unmask central diabetes insipidus. An already existing failure of the thyrotropic axis would have in painless thyroiditis a dampening effect on the TSH rise upon conversion into hypothyroidism. I also miss for the diagnosis of a new hypopituitarism a corticotropin releasing hormone test to check the corticotropic axis. The adrenocorticotropic hormone test with the remark “Beware of false positives in acute pituitary insufficiency” shown in Figure 3 of the article is obsolete, in my opinion.

Imaging diagnostics should have an important role in suspected hypophysitis. A recently published study pointed out that (2) only laboratory diagnostics plus headache or fatigue without magnetic resonance imaging would miss a third of cases. Obviously, imaging is also important for the differential diagnostic evaluation of other processes in the pituitary region. Metastases, however, are rare in this setting.

Thyroid dysfunction, especially hypothyroidism, is not accompanied by the typical clinical signs in severe courses of the primary disorder, such as weight gain. For this reason, some authors refer to abnormalities of the thyroid function tests (3). They also point out that thyroid dysfunction in patients being treated with immune checkpoint inhibitors is associated with a better response to the treatment and survival.

Regarding immune checkpoint inhibitor-induced diabetes mellitus, some authors deem regular blood glucose monitoring irrelevant because of the fulminant disease course (4). In this sense, there can be no talk of uncharacteristic symptoms.

DOI: 10.3238/arztebl.m2021.0313

Dr. med. Athanasios Alexopoulos

Inne Medizin, Kurparkklinik Bad Nauheim

Conflict of interest statement

The author declares that no conflict of interest exists.

References

1. 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

2. Nguyen, Shah K, Waguespack SG, et al: Immune checkpoint inhibitor related hypophysitis: diagnostic criteria and recovery patterns. Endocrine-Related Cancer 2021; 28: 419–31

3. Ferreira JL, Costa C, Marques B, et al: Improved survival in patients with thyroid function test abnormalities secdondary to immune-checkpoint inhibitors. Cancer Immunol Immunother 2021; 70: 299–309

4. Magis Q, Gaudy-Marqueste C, Basire A, et al: Diabetes and blood glucose disorders under anti-PD1. J Immunother 2018; 41: 232–40