The Focus Should Be on “Vitally Important” 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

Thus far, about 30 cases have been reported/published of immune checkpoint inhibitor (CPI) induced autoimmune polyglandular syndrome, especially for treatment with programmed death cell protein 1 (PD-1) inhibitors and in patients with the HLA-DR4-allele. Patients with severe cancer disease often have gonadotropic insufficiency / secondary hypogonadism and do not wish to have sex hormone replacement therapy during the cancer therapy. The administration of testosterone is contraindicated in patients with active prostate cancer, as is administration of estrogens in (hormone positive) breast cancer. Growth hormone treatment should be avoided in patients having active cancer treatment. For this reason, testing for growth hormone and gonadotropins can be avoided in many patients with suspected CPI induced hypophysitis, at least during active cancer treatment and immunotherapy. The focus should be on the “vitally important” hormone axes, such as that of the thyroid and adrenals. A correlation with the dosage of the CPI seems to exist for the development of hypophysitis, but less so for CPI induced hypothyroidism, hyperthyroidism, and primary adrenal failure (1). Cancer patients may also develop metastases in the adrenals, unilaterally or bilaterally; the risk of primary adrenal insufficiency is higher for bilateral adrenal metastases than for patients with unilateral adrenal metastases, as long as the second adrenal gland has not been surgically removed or affected by radiotherapeutic injury (2).

Non-alcoholic fatty liver disease is common nowadays and predisposes patients to developing cancer. CPIs can make patients with pre-existing diabetes mellitus (often detectable by means of an abnormally high HbA1c measurement) insulin dependent to a higher extent or completely, but they can also induce generalized lipodystrophy (3, 4). Immunosuppressive glucocorticoid therapy in CPI induced diabetes mellitus is usually not beneficial.

DOI: 10.3238/arztebl.m2021.0311

Prof. Dr. med. habil. Christian A. Koch, FACP, MACE
Department of Medicine
Fox Chase Cancer Center
Philadelphia, USA

Conflict of interest statement

The author declares that no conflict of interest exists.

References

1. Yang Y, Liu J, Yang K, et al.: Endocrine adverse events caused by different types and different doses of immune checkpoint inhibitors in the treatment of solid tumors: a meta-analysis and systematic review. J Clin Pharmacol 2021; 61: 282–97

2. Lutz A, Stojkovic M, Schmidt M, Arlt W, Allolio B, Reincke M: Adrenocortical function in patients with macrometastases of the adrenal gland. Eur J Endocrinol 2000; 143: 91–7

3. Haddad N, Vidal-Trecan T, Baroudjian B, et al.: Acquired generalized lipodystrophy under immune checkpoint inhibition. Br J Dermatol 2020; 182: 477–80

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