PSAT332 Immune Checkpoint Inhibitor Related Hypothyroidism - a Complication of Ipilimumab/ Nivolumab Therapy
Authors: Kennedy Randol , Ciltea Daniela 
Published: November 2022

Abstract

Introduction
Endocrine dysfunctions are among the most recognized immune related adverse drug events associated with immune checkpoint inhibitor (ICPi) therapy, with thyroid dysfunction being the most common. This case highlights the risk of thyroid dysfunction with mono and combined immunotherapy.

Clinical Case
We present a case of a 61 year old male with no significant endocrine history, who was diagnosed and treated for lung adenocarcinoma. His initial stage was cT4N0M0 Stage III-A based on CT chest, bronchoscope lymph node biopsies and PET/CT imaging. Initial MRI brain was also negative for metastasis. He was treated with neoadjuvant carboplatin/taxol with radiation therapy and subsequent right upper lobectomy with mediastinal lymph node dissection. Surgical pathology showed residual tumor present in chest wall structures but negative lymph nodes (ypT3N0MX). After two weeks of consolidative chemotherapy, the patient became intolerable to treatment and chemotherapy was discontinued. Surveillance CT chest scans did not reveal disease reoccurrence.
Sixteen months post-surgery, a cystic lesion in the left cerebral hemisphere was found on CT after presenting with vomiting and gait instability. He underwent parietal craniotomy, with surgical pathology showing metastatic adenocarcinoma. Immuno-histochemistry was positive for PD-L1 expression. Post-operatively, he was treated with tumor bed directed gamma knife stereotactic radiosurgery and immunotherapy with ipilimumab/ nivolumab. His pretreatment TSH was normal (3.87 microU/mL; ref 0.270-4.200 microU/mL). Six days after immunotherapy he was admitted for generalized weakness, fatigue and chills where blood cultures and other infectious work up was negative. TSH increased to 6.12 µU/L. He was assessed as immunotherapy adverse reaction and was treated with 80mg prednisone therapy with a two week taper. He was then switched to nivolumab monotherapy. TSH repeated one month later was normal (3.86 µU/L) and his fatigue improved. However, surveillance TSH showed a gradual increase (5.34 µU/L at 4 months and 8.3 µU/L at 8 months), associated with fatigue. The patient was assessed as immunotherapy induced hypothyroidism and started on levothyroxine therapy. AM cortisol, ACTH, FSH and prolactin were within normal limits. Other values were testosterone 93 ng/dL (ref 87 -780 ng/dL); LH 1.4 mU/mL (ref 1.5–9.3 mU/mL), HbA1c 5.9%. Free T4 and T3 while on levothyroxine 25µg were 1.1ng/dL and 3.3ng/dL respectively. Thyroid peroxidase antibodies (TPO Ab) were undetectable. The patient is remaining on indefinite levothyroxine therapy.

Conclusion
Thyroid dysfunction is one of the most common ICPi related endocrinopathies, with the time of onset ranging from weeks to months post therapy. However, dysfunction can occur after one cycle as with our patient and combination therapy with ipilimumab/ nivolumab significantly increases the risk. The exact mechanism of ICI induced thyroid dysfunction is unclear. Many patients who develop ICPi related hypothyroidism do not have elevated TPO Ab, suggesting a TPO Ab independent pathway.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.