A Case of HPA Axis Recovery in the Setting of Immune Checkpoint Inhibitor-induced Hypophysitis

Introduction:
Immune checkpoint inhibitor-related hyophysitis resulting in the loss of anterior pituitary hormones is well described in the literature. Patients with hypophysitis frequently develop secondary adrenal insufficiency, which is usually permanent. We present an unusual case of a patient who had recovery of her hypothalamic pituitary adrenal (HPA) axis.

Case Description:
A 32-year-old woman was diagnosed with locally advanced estrogen, progesterone, and human epidermal growth factor 2 receptor negative breast cancer. She received neoadjuvant chemotherapy with pembrolizumab and then underwent a bilateral mastectomy. While on pembrolizumab the patient’s thyroid and cortisol axis were monitored every month. She endorsed increasing fatigue after eight months of pembrolizumab therapy. Her workup showed morning ACTH level was 6.6 (reference range 7.2-63 pg/mL), and her cortisol level was 2.2 (6.7-22.6 mcg/dL), which was confirmed on repeat testing. A diagnosis of secondary adrenal insufficiency was made, and the patient was started on hydrocortisone 10 mg at 8 am and 5 mg at 2 pm. Her pituitary hormonal profile was otherwise normal. An MRI brain was not done as the patient denied any symptoms of headache or visual changes. The pembrolizumab was held and the patient had repeat HPA axis testing. She was asked to hold her hydrocortisone 24 hours prior to the assessment of her pituitary adrenal axis. This was conducted every month. After four months of hydrocortisone replacement, her cortisol axis recovered as her labs showed an ACTH of 47.2 and cortisol of 17.4 (6.7-22.6 mcg/dL). The patient was asked to discontinue hydrocortisone and counseled to report if she had any symptoms of adrenal insufficiency. The patient continued to feel well off hydrocortisone therapy with no symptoms of adrenal insufficiency. Her ACTH and cortisol levels remained normal. 

Discussion:
Recovery from secondary adrenal insufficiency associated with immune checkpoint inhibitor related hypophysitis is rarely seen. This case suggests that certain individuals may recover, potentially those who are younger or do not completely lose ACTH secretion. Repeated pituitary hormone testing for the first six months after the development of hypophysitis may identify more patients with HPA axis recovery and lead to less long-term use of steroids.