Endocrine Abstracts

Pembrolizumab is a monoclonal antibody (ab) that exerts antineoplastic effects by inhibiting the immunoevasive effects PD-1 grants cancer cells. It’s used to treat several forms of cancer, including melanoma and non-small cell lung cancer. Despite the promise pembrolizumab has demonstrated, it has been associated with immune-related adverse events. In this report, we describe the first case of both thyroiditis and hypophysitis occurring during active pembrolizumab therapy.

A 51-year-old male who was referred to endocrinology for subclinical hyperthyroidism. He has past medical history of hypertension, psoriatic arthritis, and poorly differentiated stage IV lung adenocarcinoma with brain metastasis. For the last 18 months, his cancer had been managed pharmacologically with pembrolizumab (200 mg every three weeks). The patient lacked a family history of thyroid disease and disclosed mild fatigue as his only symptom. Vital signs included the following: blood pressure of 92/42 mmHg, pulse of 68 beats/minute, respiratory rate of 16 breaths/minute, and body mass index of 29.94 kg/m². Physical examination was unremarkable. Pertinent laboratory test results included an elevated fT4 (1.6 ng/dl) and a suppressed TSH (< 0.005 µIU/ml). Thyroid stimulating immunoglobin, thyroid peroxidase ab, and TSH receptor ab tests were negative. Based on this work-up, the patient was diagnosed with pembrolizumab-induced thyroiditis and, given the mild presentation, was not prescribed anything.

At a follow-up visit two months later, the patient was found to have post-thyroiditis hypothyroidism, prompting levothyroxine initiation. After an additional four months, he complained of worsening fatigue and dry skin. TSH, fT4, FSH, LH, and total testosterone were within normal limits. 8 am cortisol, ACTH, free testosterone, and IGF-1 were reduced (0.7 µg/dl, 5.9 pg/ml, 6.1 pg/ml, and 37 ng/ml, respectively).ACTH stimulation test showed 0.5 mg/dl, 2.3 mg/dl, 3.1 mg/dl at morning, 30 and 60 minutes. A pituitary MRI was unremarkable. As a result, the patient was diagnosed with central adrenal insufficiency and started on hydrocortisone therapy. His condition improved with levothyroxine and hydrocortisone, and pembrolizumab was eventually discontinued after the patient switched to a new oncologist.

Hypophysitis occurs in approximately 1.1% of patients taking pembrolizumab. Pembrolizumab-induced thyroiditis is considered more common, though incidence estimates vary. Diagnosing these conditions involves clinical symptoms, laboratory test results, and imaging studies. With regard to imaging, pituitary MRI is the preferred study despite hypophysitis abnormalities appearing only 28% of the time. Finally, physician should keep hypophysitis diagnose in mind especially before starting patients on thyroid supplementation due to the chance of a frank adrenal crisis.