Steroid responsive encephalopathy associated with autoimmune thyroiditis following ipilimumab therapy: a case report

Abstract

BackgroundIpilimumab is a cytotoxic T-lymphocyte-associated protein 4 receptor antibody used for immunotherapy in cancer. Several immune-related adverse events are known. Steroid responsive encephalopathy associated with autoimmune thyroiditis is an autoimmune encephalopathy associated with Hashimoto’s Disease and elevated serum levels of the related antibodies (anti-thyroid-peroxidase antibody or anti-thyroglobulin antibody). Our case implies that steroid responsive encephalopathy associated with autoimmune thyroiditis may be another previously unreported side effect of ipilimumab therapy.Case presentationWe report the case of a 64 years old caucasian patient with prostatic cancer who received ipilimumab therapy in a clinical trial. He presented with aphasia, tremor and ataxia, myocloni, hallucinations, anxiety and agitation in turns with somnolence. Cranial nerves, deep tendon reflexes, motor and sensory functions were normal. Electroencephalography showed background slowing but no epileptic discharges. Brain magnetic resonance imaging was normal and showed no signs of hypophysitis. Cerebrospinal fluid findings ruled out infection and neoplastic meningitis. Anti-thyroid antibodies (anti-thyroid-peroxidase antibody and anti-thyroglobulin antibody) were heavily increased. Assuming steroid responsive encephalopathy associated with autoimmune thyroiditis the patient was treated with 1,000 mg methylprednisolone i.v. for 3 days and continued with 1 mg/kg orally. On the 3rd day of treatment the patient’s condition started to improve. Within the next few days he gradually returned to his previous state, and electroencephalography eventually showed only slight slowing. Seven months later the patient’s condition was stable, and anti-thyroid antibodies were no more detectable.ConclusionSteroid responsive encephalopathy associated with autoimmune thyroiditis may be a hitherto unrecognized complication of ipililumab treatment and should be taken into consideration in patients developing central nervous symptoms undergoing this treatment.

Pembrolizumab-Induced Encephalopathy: A Review of Neurological Toxicities with Immune Checkpoint Inhibitors

“…The rates of irAEs of any grade in a phase III trial of pembrolizumab were as follows: fatigue, 20%; diarrhea, 14%; rash; 13%; hypothyroidism, 8%; hyperthyroidism, 3%; and hepatitis, 1.8%. 1 Neurological adverse events are rare but have been documented with ICI therapy (Table 1 [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. Although most are responsive to corticosteroid therapy, many are associated with long-term disability, making the prompt identification and treatment of these irAEs paramount when using ICIs.…”

Endocrine side effects of cancer immunotherapy

“…The spectrum of thyroid disturbances associated with immune checkpoint inhibitors include painless thyroiditis with transient thyrotoxicosis, transient or long-standing hypothyroidism, thyroid eye disease and occasionally severe forms of thyroid disease such as thyroid storm (Borodic et al 2011, Hamnvik et al 2011, Min et al 2011, McElnea et al 2014, Min & Hodi 2014, Carl et al 2015, Orlov et al 2015, Yu et al 2015, Joshi et al 2016. Rare cases of Graves' ophtalmopathy have been reported with elevation of TSH-receptor antibodies but normal thyroid function (Borodic et al 2011, Min et al 2011.…”

Immune checkpoint inhibitor‐related hypophysitis and endocrine dysfunction: clinical review

“…The pattern of primary thyroid disturbances reported with immune checkpoint inhibitors includes transient thyrotoxicosis, transient or long‐standing hypothyroidism, thyroid eye disease, painless thyroiditis and occasionally severe forms of thyroid disease such as thyroid storm, steroid responsive encephalopathy . The incidence of thyroid disorders or abnormalities in thyroid function tests are seen in 1–6% cases for ipilimumab .…”

“…The pattern of primary thyroid disturbances reported with immune checkpoint inhibitors includes transient thyrotoxicosis, transient or long-standing hypothyroidism, thyroid eye disease, [46][47][48] painless thyroiditis 49,50 and occasionally severe forms of thyroid disease such as thyroid storm, steroid responsive encephalopathy. [51][52][53] The incidence of thyroid disorders or abnormalities in thyroid function tests are seen in 1-6% cases for ipilimumab. 17 Researchers have reported relatively similar rates of incidence with use of nivolumab 54 and tremelimumab 55 ; but much higher incidence of hyper and hypothyroidism when combination therapy with ipilimumab and nivolimumab was used (9Á9-22%, respectively).…”