Hypophysitis in a Patient on Pembrolizumab
- Onconephrology: Clinical and Research Advances - I
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
- 1600 Onconephrology
- Luo, Jack, Alameda Health System, Oakland, California, United States
- Suryadevara, Kiran, St George's University School of Medicine, St George's, St George's, Grenada
- Zaman, Warda, East Bay Nephrology Medical Group, Oakland, California, United States
Pembrolizumab is a PD-1 immune checkpoint inhibitor (ICI) used to treat advanced malignancies that may be unresectable, metastatic, or refractory to other chemotherapy regimens. We report a case of hypophysitis in a 63 year-old Asian female after receiving pembrolizumab for treatment of metastatic urothelial carcinoma.
A 63 year-old post-menopausal Asian woman presented to the hospital with dizziness, loss of appetite, and generalized fatigue for three weeks. She was found to have a blood glucose level of 55md/dL. She was on pembrolizumab for 8 months for metastatic urothelial carcinoma. She developed hypothyroidism 3 months after starting pembrolizumab. At presentation, she was hypotensive to 80/55 mmHg, euvolemic on exam, sodium level was 116mmol/L, measured serum osmolality was 246 mOsm/kg; urine osmolality was 312 mOsm/kg and urine sodium was 44 mmol/l. Liver and renal function tests were normal. Serum sodium improved to 118 mmol/L after 1 liter of lactated ringers solution. Blood glucose was 77 mg/dL on initial presentation and varied between 49-100 mg/dL throughout most of the admission. TSH was 4.06 µIU/ml and cortisol level was <1.0 mcg/dL, ACTH level was undetectable. The patient was started on hydrocortisone 10mg in the morning and 5mg in the evening and fludrocortisone 0.05mg daily. Glucose levels remained within normal limits. All her presenting symptoms resolved. Her history of hypothyroidism and now secondary adrenal insufficiency was suspicious for hypophysitis related to Pembrolizumab. Two weeks after discharge, serum sodium was 143mmol/L and was stable on follow-up labs. In addition, FSH, LH and IGF-1 were checked and were relatively low in her, which are very elevated in post-menopausal women further confirming the hypophysitis. Currently, she is on the same doses of hydrocortisone and fludrocortisone is discontinued. There is plan to restart the Pembrolizumab.
Hypophysitis is an uncommon side-effect of ICIs, especially PD-1 inhibitors. In a meta-analysis of 31 clinical trials with 7551 patients, the incidence of hypophysitis was only 0.4% with PD-1 inhibitors compared to 3.2% with CTLA-4 inhibitors and 6.4% with combination therapy. Patients may present with nonspecific symptoms such as fatigue, dizziness, and appetite loss, so it is important to have high clinical suspicion for hypophysitis and hormonal deficiencies in patients treated with pembrolizumab.