Objective:To explore the occurrence and clinical characteristics of thyroid dysfunction caused by sintilimab.Methods:The subjects were selected from malignant tumor patients who were treated with sintilimab during hospitalization in the Oncology Department in Heping Hospital Affiliated to Changzhi Medical College from July 1, 2021 to June 30, 2023. Electronic medical records of patients meeting the inclusion criteria were collected; the general conditions, sintilimab application, combined medication, and the thyroid function test results before and after sintilimab application were recorded. For patients with thyroid dysfunction, the causal analysis between sintilimab application and the dysfunction was conducted using Naranjo′s causality assessment scale. The clinical characteristics of sintilimab-related thyroid dysfunction were analyzed based on the medical records that had evaluation results of "certainly" or "probably".Results:A total of 145 patients were included in the analysis, and 24 (16.6%) had sintilimab-related thyroid dysfunction, with the causality assessment results "probably". Among the 24 patients, 14 were male and 10 were female, aged 37-87 years; 5 were treated with sintilimab monotherapy, 16 were with combination of chemotherapy drugs, and 3 were with combination of targeted drugs. All 24 patients had baseline thyroid function test results, of which 23 had normal thyroid function and 1 had subclinical hyperthyroidism. Twenty-four patients with thyroid dysfunction included 13 hypothyroidisms, 5 subclinical hypothyroidisms, 2 hyperthyroidisms, and 4 subclinical hyperthyroidisms; 11 occurred within 3 treatment cycles; the severity was grade 1 or 2, without obvious clinical symptoms, except that 4 hypothyroidism patients had mild fatigue. The 13 hypothyroidism patients were treated with levothyroxine sodium tablets (levothyroxine), 9 patients recovered or were improved, and 4 patients were with persistent but not worsening condition. Three of the 5 subclinical hypothyroidism patients were treated with levothyroxine, 2 patients recovered and 1 developed subclinical hyperthyroidism later; the remaining 2 patients were given intensive monitoring without medication intervention, and they developed hypothyroidism later, which recovered after treatment with levothyroxine. None of the 6 patients with hyperthyroidism or subclinical hyperthyroidism received any intervention. Of them, 1 patient with subclinical hyperthyroidism was self-healed and 5 patients developed hypothyroidism or subclinical hypothyroidism later. After giving levothyroxine, 3 patients recovered or were improved and 2 had persistent but not worsening condition.Conclusions:Thyroid dysfunction is the most common immune-related adverse events of sintilimab, mainly hypothyroidism. The clinical symptoms are not obvious, and the severity is mostly grade 1 or 2. When using sintilimab, the thyroid function of patients should be routinely monitored. When hypothyroidism occurs, timely supplementation of levothyroxine is recommended, and the prognosis is generally good.

Objective:To explore the occurrence and clinical characteristics of thyroid dysfunction caused by sintilimab.Methods:The subjects were selected from malignant tumor patients who were treated with sintilimab during hospitalization in the Oncology Department in Heping Hospital Affiliated to Changzhi Medical College from July 1, 2021 to June 30, 2023. Electronic medical records of patients meeting the inclusion criteria were collected; the general conditions, sintilimab application, combined medication, and the thyroid function test results before and after sintilimab application were recorded. For patients with thyroid dysfunction, the causal analysis between sintilimab application and the dysfunction was conducted using Naranjo′s causality assessment scale. The clinical characteristics of sintilimab-related thyroid dysfunction were analyzed based on the medical records that had evaluation results of "certainly" or "probably".Results:A total of 145 patients were included in the analysis, and 24 (16.6%) had sintilimab-related thyroid dysfunction, with the causality assessment results "probably". Among the 24 patients, 14 were male and 10 were female, aged 37-87 years; 5 were treated with sintilimab monotherapy, 16 were with combination of chemotherapy drugs, and 3 were with combination of targeted drugs. All 24 patients had baseline thyroid function test results, of which 23 had normal thyroid function and 1 had subclinical hyperthyroidism. Twenty-four patients with thyroid dysfunction included 13 hypothyroidisms, 5 subclinical hypothyroidisms, 2 hyperthyroidisms, and 4 subclinical hyperthyroidisms; 11 occurred within 3 treatment cycles; the severity was grade 1 or 2, without obvious clinical symptoms, except that 4 hypothyroidism patients had mild fatigue. The 13 hypothyroidism patients were treated with levothyroxine sodium tablets (levothyroxine), 9 patients recovered or were improved, and 4 patients were with persistent but not worsening condition. Three of the 5 subclinical hypothyroidism patients were treated with levothyroxine, 2 patients recovered and 1 developed subclinical hyperthyroidism later; the remaining 2 patients were given intensive monitoring without medication intervention, and they developed hypothyroidism later, which recovered after treatment with levothyroxine. None of the 6 patients with hyperthyroidism or subclinical hyperthyroidism received any intervention. Of them, 1 patient with subclinical hyperthyroidism was self-healed and 5 patients developed hypothyroidism or subclinical hypothyroidism later. After giving levothyroxine, 3 patients recovered or were improved and 2 had persistent but not worsening condition.Conclusions:Thyroid dysfunction is the most common immune-related adverse events of sintilimab, mainly hypothyroidism. The clinical symptoms are not obvious, and the severity is mostly grade 1 or 2. When using sintilimab, the thyroid function of patients should be routinely monitored. When hypothyroidism occurs, timely supplementation of levothyroxine is recommended, and the prognosis is generally good.

A 75-year-old male patient with lung cancer received intravenous infusion of sintilimab 200 mg on day 1, 21 days as one cycle. Three days after the 5th cycles of treatment, the patient developed edema of lower limbs and yellowish skin on whole body. Laboratory tests showed alanine aminotransferase (ALT) 914 U/L, aspartate aminotransferase (AST) 622 U/L, alkaline phosphatase (ALP) 385 U/L, total bilirubin (TBil) 152.6 μmo1/L, direct bilirubin (DBil) 87.9 μmol/L, indirect bilirubin (IBil) 64.7 μmol/L and total bile acid (TBA) 25.8 μmol/L. The liver injury caused by other reasons was excluded by laboratory and auxiliary examination, and it was diagnosed as drug-induced liver injury, which was considered to be related to sintilimab. Drugs such as reduced glutathione, compound glycyrrhizin, ademetionine, polyene phosphatidylcholine, magnesium isoglycyrrhizinate, and ursodeoxycholic acid successively were given. The patient′s edema of lower limbs and yellowish skin gradually subsided. After 25 days of treatments, laboratory tests showed ALT 33 U/L, AST 33 U/L, ALP 92 U/L, TBil 18.2 μmol/L, DBil 5.2 μmol/L, IBil 13.0 μmol/L, and TBA 7.4 μmol/L.

A 75-year-old male patient with lung cancer received intravenous infusion of sintilimab 200 mg on day 1, 21 days as one cycle. Three days after the 5th cycles of treatment, the patient developed edema of lower limbs and yellowish skin on whole body. Laboratory tests showed alanine aminotransferase (ALT) 914 U/L, aspartate aminotransferase (AST) 622 U/L, alkaline phosphatase (ALP) 385 U/L, total bilirubin (TBil) 152.6 μmo1/L, direct bilirubin (DBil) 87.9 μmol/L, indirect bilirubin (IBil) 64.7 μmol/L and total bile acid (TBA) 25.8 μmol/L. The liver injury caused by other reasons was excluded by laboratory and auxiliary examination, and it was diagnosed as drug-induced liver injury, which was considered to be related to sintilimab. Drugs such as reduced glutathione, compound glycyrrhizin, ademetionine, polyene phosphatidylcholine, magnesium isoglycyrrhizinate, and ursodeoxycholic acid successively were given. The patient′s edema of lower limbs and yellowish skin gradually subsided. After 25 days of treatments, laboratory tests showed ALT 33 U/L, AST 33 U/L, ALP 92 U/L, TBil 18.2 μmol/L, DBil 5.2 μmol/L, IBil 13.0 μmol/L, and TBA 7.4 μmol/L.