Pituitary hypoadrenocorticism and hypothyroidism after immunochemotherapy followed by salvage surgery for lung cancer: a case report

Abstract

Background: Immune checkpoint inhibitors (ICIs) have been shown to prolong the survival of patients with non-small cell lung cancer (NSCLC) and have allowed complete resection for advanced lung cancer. However, immune-related adverse events (irAEs) have been recognized as concerning side effects of ICIs.

Case presentation: A 62-year-old man visited our hospital because of fever, dyspnea, and anorexia. A tumor was found in the right hilum of the lung. It compressed the left atrium and was also thought to be invading the esophagus and a vertebral body. A bronchoscopic biopsy revealed squamous cell carcinoma of the lung (cT4N2M0-IIIB). We thought that a complete resection was impossible because of the N2 status of the tumor and because it had invaded several organs. Radiotherapy was thought to be contraindicated because of the patient's marked emphysema. Therefore, we administered 4 courses of pembrolizumab plus carboplatin plus nab-paclitaxel immunochemotherapy. After immunochemotherapy, the tumor was downstaged to ycT2bN0M0-IIA and was determined to be acceptable for salvage surgery. A right lower lobectomy and systematic dissection of the mediastinal lymph nodes were performed. The histopathological examination of the resected specimen found that the proportion of the remaining tumor cells was 5%, indicating achievement of a major pathologic response. On postoperative day 79, the patient visited the emergency room because of anorexia. Blood tests showed hyponatremia, hypoglycemia, and eosinophilia. The serum thyroid hormone and thyroid-stimulating hormone levels were low and high, respectively. A corticotropin-releasing hormone stimulation test revealed levels of adrenocorticotropic hormone and cortisol far below the normal ranges. We speculated that the patient had developed pituitary hypoadrenocorticism and hypothyroidism as irAEs associated with ICI treatment. We administered hydrocortisone and levothyroxine, with improvement in the patient's appetite and normalization of the patient's serum sodium level. The patient has been receiving ongoing supplementation with oral hydrocortisone and levothyroxine and is doing well 11 months after surgery.

Conclusions: The increasing numbers of patients treated with perioperative ICIs might lead to increasing numbers of patients who develop perioperative irAEs. Careful attention should be paid to the possible development of irAEs during the perioperative management of patients undergoing surgery for lung cancer.

Keywords: Immune checkpoint inhibitor; Immune-related adverse events; Immunochemotherapy; Lung cancer; Surgery.

Fig. 1

Preoperative computed tomography images. The tumor was 73 mm in diameter and located in the right hilum of the lung (a). It compressed the left atrium of the heart. It appeared to invade the esophagus and a vertebral body (b)

Fig. 2

Clinical course of the patient: four courses of pembrolizumab and carboplatin (CBDCA) plus nabPTX) chemotherapy were administered. After one course, because the patient developed pneumonia, the amounts of the CBDCA and nabPTX were reduced. After the treatment, CT showed that the tumor shrank (images of tumor are identified by red circles), which was considered to be a partial response. Radical surgery was performed on day 34 from the day of the last (fourth) administration of pembrolizumab. On postoperative day 39, the patient complained of anorexia, and on postoperative day 79, he went to the emergency room because of dizziness and worsening anorexia