Induction of painless thyroiditis in patients receiving programmed death 1 receptor immunotherapy for metastatic malignancies.
BACKGROUND
Immunotherapies against immune checkpoints that inhibit T cell activation [cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1)] are emerging and promising treatments for several metastatic malignancies. However, the precise adverse effects of these therapies on thyroid gland function have not been well described.


METHODS
We report on 10 cases of painless thyroiditis syndrome (PTS) from a novel etiology, following immunotherapy with anti-PD-1 monoclonal antibodies (mAb) during treatment for metastatic malignancies. Six patients presented with transient thyrotoxicosis in which thyrotropin binding inhibitory immunoglobulins (TBII) were absent for all, whereas four patients had evidence of positive antithyroid antibodies. All thyrotoxic patients required temporary beta-blocker therapy and had spontaneous resolution of thyrotoxicosis with subsequent hypothyroidism. Four patients presented with hypothyroidism without a detected preceding thyrotoxic phase, occurring 6-8 weeks after initial drug exposure. All of these patients had positive antithyroid antibodies and required thyroid hormone replacement therapy for a minimum of 6 months.


CONCLUSIONS
Patients receiving anti-PD-1 mAb therapy should be monitored for signs and symptoms of PTS which may require supportive treatment with beta-blockers or thyroid hormone replacement. The anti-PD-1 mAb is a novel exogenous cause of PTS and provides new insight into the possible perturbations of the immune network that may modulate the development of endogenous PTS, including cases of sporadic and postpartum thyroiditis.
Department of Medicine (S.O., F.S., L.K., P.G.W.), Endocrine Division, and Otolaryngology-Head and Neck Surgery Program (P.G.W.), Mt. Sinai Hospital, Toronto, ON M5G 1X5, Canada and University of Toronto School of Medicine, Toronto, ON M5S 1A8, Canada.
Steven
S
Orlov
Farnaz
F
Salari
Lawrence
L
Kashat
Paul G
PG
Walfish
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects* / Q000379:methods; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology*; D012878:Skin Neoplasms / Q000188:drug therapy; D013966:Thyroiditis / Q000139:chemically induced* / Q000276:immunology; D013971:Thyrotoxicosis / Q000139:chemically induced* / Q000276:immunology
D000911:Antibodies, Monoclonal; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor