Progression of Hypopituitarism and Hypothyroidism after Treatment with Pembrolizumab in a Patient with Adrenal Metastasis from Non-small-cell Lung Cancer

Abstract

Pembrolizumab, or anti-programmed death receptor 1 antibody, is an immune checkpoint inhibitor that can cause immune-related adverse events. We herein report for the first time the progression of hypopituitarism and hypothyroidism after treatment with pembrolizumab in a patient with adrenal metastasis of non-small-cell lung cancer. Severe primary hypothyroidism occurred three weeks after the first administration of pembrolizumab. Four months after the discontinuation of pembrolizumab, isolated adrenocorticotropic hormone (ACTH) deficiency was noted. Corticotropin-releasing hormone and rapid ACTH tests performed repeatedly showed that the patient's pituitary and adrenal function had been gradually deteriorating. It is important to diagnose adrenal insufficiency without delay in order to prevent adrenal crisis.

Keywords: hypopituitarism; hypothyroidism; immune-related adverse events; pembrolizumab.

Figure 1.

Abdominal computed tomography (CT). One year after chemotherapy, CT shows a right adrenal gland tumor (19 mm; arrow).

Figure 2.

Changes in thyroid hormone levels during the clinical course. Levothyroxine sodium supplementation was started three weeks after the second administration of pembrolizumab. TSH: thyrotropin-stimulating hormone, ACTH: adrenocorticotropic hormone, CRH: corticotropin-releasing hormone

Figure 3.

Thyroid ultrasonography (USG). USG shows heterogeneous echotexture mixed with diffuse hypoechoic areas in the thyroid gland.

Figure 4.

Corticotropin-releasing hormone test. Solid and dotted lines indicate tests at three and seven months, respectively, after the first administration of pembrolizumab. Each basal and peak hormonal level is shown in parentheses.

Figure 5.

Rapid adrenocorticotropic hormone (ACTH) test. Solid and dotted lines indicate tests at three and seven months, respectively, after the first administration of pembrolizumab. Each basal and peak hormonal level is shown in parentheses.

Figure 6.

Coronal T1-weighted magnetic resonance imaging (MRI) of the pituitary gland. MRI shows no enlargement of the pituitary gland or thickening of the pituitary stalk.