Isolated adrenocorticotropin deficiency induced by pembrolizumab for hypopharyngeal cancer: A case report

Abstract

We report a case of isolated adrenocorticotropin deficiency caused by pembrolizumab. This condition can be fatal, but its rarity causes under‐recognition. Oncologists should pay attention to adrenal insufficiency due to pembrolizumab.

We report a case of isolated adrenocorticotropin deficiency caused by pembrolizumab. This condition can be fatal, but its rarity causes under‐recognition. Oncologists should pay attention to adrenal insufficiency due to pembrolizumab.

A 78‐year‐old man with a history of surgery for hypopharyngeal cancer presented with a 3‐day‐long fever, anorexia, and vomiting. There were no other clinical symptoms. One week ago, he received the 11th cycle of pembrolizumab for lung metastasis. Since contrast‐enhanced computed tomography (CT) showed no clear findings and empiric antibiotic therapy was ineffective, he was referred to our department for investigation of fever of unknown origin. He had hyponatremia (135 mmoL/L) and increased antidiuretic hormone level (3.0 pg/mL) without eosinophilia (242/μL) or hypoglycemia (117 mg/dL). Basal plasma adrenocorticotropin (ACTH) was undetectable, and serum cortisol level was significantly lowered (0.6 μg/dL), and free cortisol in a twenty‐four‐hour urine collection was undetectable. Pituitary magnetic resonance imaging showed no specific findings (Figure 1A) and plain adrenal CT showed no abnormality (Figure 1B). A corticotropin‐releasing hormone test showed no response of ACTH or cortisol, while results for other anterior pituitary hormones in loading tests were unremarkable (Figure 1C). We diagnosed as isolated ACTH deficiency induced by pembrolizumab, which was improved by 10 mg per day of hydrocortisone treatment.

FIGURE 1.

A, Pituitary magnetic resonance imaging showed no remarkable pituitary enlargement, no thickened pituitary stalk, and no loss of signal intensity in the posterior lobe in T1‐weighted image (sagittal plane). B, Plain computed tomography showed that the bilateral adrenals had normal shapes. C, Anterior pituitary hormonal evaluation. A corticotropin‐releasing hormone (CRH) test (upper left) showed no response of ACTH or cortisol, while a gonadotropin‐releasing hormone (GnRH) test (upper right), thyrotropin‐releasing hormone (TRH) test (lower left), and growth hormone‐releasing peptide 2 (GHRP2) test (lower right) showed no remarkable results. ACTH, adrenocorticotropin; FSH, follicle‐stimulating hormone; GH, growth hormone; LH, luteinizing hormone; PRL, prolactin; TSH, thyroid‐stimulating hormone

The programmed cell death 1 protein (PD‐1) inhibitor pembrolizumab has rarely been reported to cause isolated ACTH deficiency, in contrast to the same class agent nivolumab. ¹ As in our case, PD‐1 inhibitors induce hypophysitis with less obvious clinical signs (such as headache and vision disorder) and radiological signs than does cytotoxic T‐lymphocyte antigen‐4. ² Since this feature may lead to delayed or incorrect diagnosis, oncologists should recognize that pembrolizumab can induce ACTH deficiency.

CONFLICT OF INTEREST

None declared.

AUTHOR CONTRIBUTIONS

KY: wrote the first draft and managed all of the submission process. KT: advised on the first draft and contributed to the clinical management of the patient. KO and KH: contributed to the clinical management of the patient. FO: organized the manuscript.

ETHICAL APPROVAL

Informed consent was obtained from the patient to publish this case report.

Yamamoto K, Tokumasu K, Oka K, Hasegawa K, Otsuka F. Isolated adrenocorticotropin deficiency induced by pembrolizumab for hypopharyngeal cancer: A case report. Clin Case Rep. 2021;9:e04305. 10.1002/ccr3.4305