Thyroid dysfunctions secondary to cancer immunotherapy.

BACKGROUND: Immunotherapy is a firmly established pillar in the treatment of cancer, alongside the traditional approaches of surgery, radiotherapy, and chemotherapy. Like every treatment, also cancer immunotherapy causes a diverse spectrum of side effects, collectively referred to as immune-related adverse events. OBJECTIVE: This review will examine the main forms of immunotherapy, the proposed mechanism(s) of action, and the incidence of thyroid dysfunctions. METHODS: A comprehensive MEDLINE search was performed for articles published up to March 30, 2017. RESULTS: Following the pioneering efforts with administration of cytokines such as IL-2 and IFN-g, which caused a broad spectrum of thyroid dysfunctions (ranging in incidence from 1 to 50%), current cancer immunotherapy strategies comprise immune checkpoint inhibitors, oncolytic viruses, adoptive T-cell transfer, and cancer vaccines. Oncolytic viruses, adoptive T-cell transfer, and cancer vaccines cause thyroid dysfunctions only rarely. In contrast, immune checkpoint blockers (such as anti-CTLA-4, anti-PD-1, anti-PD-L1) are associated with a high risk of thyroid autoimmunity. This risk is highest for anti-PD-1 and increases further when a combination of checkpoint inhibitors is used. CONCLUSIONS: Cancer patients treated with monoclonal antibodies that block immune checkpoint inhibitors are at risk of developing thyroid dysfunctions. Their thyroid status should be assessed at baseline and periodically after initiation of the immunotherapy.

Hashimoto thyroiditis: clinical and diagnostic criteria.

Hashimoto thyroiditis (HT), now considered the most common autoimmune disease, was described over a century ago as a pronounced lymphoid goiter affecting predominantly women. In addition to this classic form, several other clinico-pathologic entities are now included under the term HT: fibrous variant, IgG4-related variant, juvenile form, Hashitoxicosis, and painless thyroiditis (sporadic or post-partum). All forms are characterized pathologically by the infiltration of hematopoietic mononuclear cells, mainly lymphocytes, in the interstitium among the thyroid follicles, although specific features can be recognized in each variant. Thyroid cells undergo atrophy or transform into a bolder type of follicular cell rich in mitochondria called Hürthle cell. Most HT forms ultimately evolve into hypothyroidism, although at presentation patients can be euthyroid or even hyperthyroid. The diagnosis of HT relies on the demonstration of circulating antibodies to thyroid antigens (mainly thyroperoxidase and thyroglobulin) and reduced echogenicity on thyroid sonogram in a patient with proper clinical features. The treatment remains symptomatic and based on the administration of synthetic thyroid hormones to correct the hypothyroidism as needed. Surgery is performed when the goiter is large enough to cause significant compression of the surrounding cervical structures, or when some areas of the thyroid gland mimic the features of a nodule whose cytology cannot be ascertained as benign. HT remains a complex and ever expanding disease of unknown pathogenesis that awaits prevention or novel forms of treatment.