Combination therapy of ipilimumab and nivolumab induced thyroid storm in a patient with Hashimoto’s disease and diabetes mellitus: a case report

Abstract

BackgroundRecently, immune checkpoint inhibitors have widely been used for the management of advanced melanoma. However, high-grade immune-related adverse events can occur, particularly with combination immunotherapy. We report a case of a patient with melanoma who developed thyroid storm following treatment with ipilimumab and nivolumab.Case presentationAn 85-year-old Japanese man with a history of malignant melanoma presented to our department with severe thyrotoxicosis and poor blood glucose control. He was already being treated for Hashimoto’s disease and type 2 diabetes mellitus before the treatment for the melanoma. During admission, laboratory investigations revealed the following thyroid functions: thyroid-stimulating hormone below sensitivity, free triiodothyronine 31.7 pg/ml, and thyroglobulin 48,000 IU/ml. Thyroid-stimulating hormone receptor antibody was negative, and a 99mTc-labeled thyroid scan revealed a markedly decreased uptake. He was treated with beta-blocker, orally administered potassium iodine, a relatively low dose of prednisolone, and insulin injection therapy to control his blood glucose, resulting in an improvement in thyroid function and his symptoms.ConclusionIt might be important to be aware of the possibility of thyroid storm induced by immune checkpoint inhibitors.

Efficacy and Toxicity of Immune -Checkpoint Inhibitors in Patients With Preexisting Autoimmune Disorders

“…In general, people with skin autoimmune disorders can be managed safely even in case of very severe flares (50). The same apply for those with thyroid dysfunction but severe hyperthyroidism can be encountered even in previously chronic hypothyroid patients (55).…”

Intractable hiccups as a rare gastrointestinal manifestation in severe endocrine and metabolic crisis: case report and review of the literature

“…It has been reported that the identification of TS tends to be delayed in patients with DKA because of suppression by fever 13,44,45 and relatively low thyroid hormone levels. 40,56 Our patient presented a high fever even after DKA was corrected, and this clinical presentation might delay the diagnosis of TS. In addition, thyroid hormones may decrease the possible compensation mechanism, leading to multi-organ dysfunction.…”

“…11 The literature related to TS was searched from 2016 to 2019, and the clinical characteristics of gastrointestinal symptoms in patients with TS were found to mainly be nausea, and the main cause of TS to be Graves' disease with unknown or poor compliance with anti-thyroid drugs (Table 3). [33][34][35][36][37][38][39][40][41][42][43][44][45][46] Considering that hiccups are not common in either DKA or TS, we speculate that the incidence of intractable hiccups is rare when DKA overlaps with TS. By carefully searching the literature, we found the following related cases.…”

Immune Checkpoint Inhibitors-Related Thyroid Dysfunction: Epidemiology, Clinical Presentation, Possible Pathogenesis, and Management

“…Patients may be asymptomatic or only show non-specific symptoms, such as fatigue, dizziness, weight changes, and emotional or behavioral changes ( 18 ). Thyroid disorders are often neglected because their presentation is often inconspicuous and only a few patients have thyroid storms ( 16 ). It can also be easily deduced from the aforementioned literature that the median time from the beginning of drug commencement to the development of thyroid dysfunction varies in different immunotherapies.…”

“…Thyroid dysfunction is a common pathological state of thyroid hormone disorder, most commonly hypothyroidism ( 15 ). It needs active surveillance and treatment; otherwise, severe thyroid dysfunction may seriously affect health in some cases ( 16 , 17 ). The specific mechanism of hypothyroidism is still unclear and warrants further laboratory and clinical exploration.…”