Immunotherapy has now become one of the important methods of cancer treatment. It has remarkable efficacy, covers a large number of cancer types, and is increasingly widely used in clinical applications. Various immunosuppressants have been launched one after another, and immunot

Figure 1 Burch-Wartofsky rating scale

Question 2: Based on the patient’s performance, what treatment measures should be given at this time?

The attending doctor highly suspects thyroid crisis and should not wait for complete information. Rescue treatment is urgent and he will be given sedation and cooling, iodine, adrenergic blockers, hydrocortisone, etc. according to the situation.

Question 3: So what causes hyperthyroidism crisis?

The patient had no symptoms or medical history of hyperthyroidism; The physical examination did not show thyroid enlargement, exophthalmos or thyroid tenderness. TRAb (-), TPOAb (-), TGAb (+), no adenoma or goiter was found on chest CT scan before chemotherapy.

Based on TRAb(-), TPOAb(-), Graves' disease and Hashimoto's thyroiditis are considered less likely by the treating physician.This patient developed hyperthyroidism after dual immunotherapy, which may be an adverse reaction caused by immunotherapy. The clinical course of thyroid function tests before and after combined immunotherapy supported this diagnosis (Fig. 2).

Figure 2 Changes in TSH and FT4 before and after the initial combined immunotherapy

Laboratory test results

C-reactive protein levels and amino-terminal pro-brain natriuretic peptide (NT-proBNP) increased, and echocardiography showed sinus tachycardia. The patient's thyroid function test on the day of treatment: thyroid stimulating hormone (TSH) 0.01 μIU/mL (↓); free thyroxine (FT4) 7.2 ng/dL (↑); free triiodothyronine (FT3) 16.0 pg/mL (↑).

Thyroid function tests before treatment: TSH, 1.51 μIU/mL (-); FT4, 1.3 ng/dL (-); FT3, 3.3 pg/mL. Anti-thyroid peroxidase antibody (TPOAb) (-), anti-thyroglobulin antibody (TgAb) 106 IU/mL (↑) (Table 1).

Table 1 Comparison of laboratory test results before and after chemotherapy

Follow-up treatment

1. propranolol (20 mg/day) and landiolol (750 mg/day) to achieve appropriate control of heart rate .

2. Hydrocortisone (100 mg every 8 hours) and potassium iodide (200 mg/day) neutralize excess thyroid hormone.

3. Because anti-TSH receptor antibodies were negative and the cause of thyroid storm was thought to be drug-induced destructive thyroiditis, no antithyroid drugs were used.

On the second day, the patient's temperature reached 40°C and symptoms of heart failure occurred, and non-invasive positive pressure ventilation was performed. The condition continued to worsen on the third day, with further decline in cardiac function, circulatory failure, and acute renal failure. Administer norepinephrine therapy; respiratory management shifts to invasive positive pressure ventilation; hemodialysis .

With subsequent treatment, thyroid function gradually recovered, and cardiac function also improved accordingly. The respiratory condition was stable and the patient was extubated 9 days after intubation. After transferring out of ICU, he began to continue rehabilitation treatment. Because the ECOG score only improved to 3, chemotherapy for NSCLC was terminated. She was discharged from the hospital on day 40 and continued palliative care at home.

TgAb or TPOAb positivity may be a risk factor for

immunotherapy-induced thyroid dysfunction.

This case report is an example of thyroid storm induced by combination immunotherapy, which occurred within 3 weeks of initiation of treatment. Although immunotherapy has brought new treatment options for advanced NSCLC, the occurrence of irAEs should also attract attention. In addition to abnormal thyroid function, the occurrence of myocarditis, pneumonia, etc. may affect the anti-cancer treatment and quality of life of tumor patients.

The patient in this case was TGAb positive. The incidence of thyroid dysfunction is higher in patients with positive thyroid antibodies. Okada et al reported that the incidence of thyroid dysfunction, including destructive thyroiditis and hypothyroidism, was higher in the thyroid autoantibody (ATA)-positive group than in the autoantibody-negative group [2]. Searching several databases,

found only one case report in which the "O+Y" combination induced thyroid storm in a patient receiving immunotherapy for advanced melanoma. The patient was negative for antithyroid antibodies but developed thyroid storm 21 days after starting combination therapy.

Iyer et al. reported that the median time to develop thyrotoxicosis after "O+Y" combination treatment was 2 weeks, while the median time after nivolumab monotherapy was 6 weeks [3]. When anti-thyroid antibody-positive patients are treated with a combination of anti-PD-1 and anti-CTLA-4 antibodies, it is best to perform thyroid function tests every 2 weeks, if possible, to provide early warning of thyroid-related adverse events.

The current COVID-19 epidemic situation is severe. Patients have symptoms such as high fever and difficulty breathing. In addition to considering hyperthyroidism, clinical diagnosis and treatment should also pay attention to distinguishing from the typical symptoms of COVID-19.

Reference:

[1]. Kataoka S, Matsuno K, Sugano K, Takahashi K. Thyroid storm induced by combined nivolumab and ipilimumab immunotherapy in advanced non-small cell lung cancer. BMJ Case Rep. 2022 Oct 12;15(10):e250696. doi: 10.1136/bcr-2022-250696. PMID: 36223974; PMCID: PMC9562321.

[2]. Okada N, Iwama S, Okuji T, Kobayashi T, Yasuda Y, Wada E, Onoue T, Goto M, Sugiyama M, Tsunekawa T, Takagi H, Hagiwara D, Ito Y, Suga H, Banno R, Hase T, Morise M, Kanda M, Yokota K, Hashimoto N, Ando M, Fujimoto Y, Nagino M, Kodera Y, Fujishiro M, Hibi H, Sone M, Kiyoi H, Gotoh M, Ando Y, Akiyama M, Hasegawa Y, Arima H. Anti-thyroid antibodies and thyroid echo pattern at baseline as risk factors for thyroid dysfunction induced by anti-programmed cell death-1 antibodies: a prospective study. Br J Cancer. 2020 Mar;122(6):771-777. doi: 10.1038/s41416-020-0736-7. Epub 2020 Feb 3. PMID: 32009131; PMCID: PMC7078193.

[3]. Iyer PC, Cabanillas ME, Waguespack SG, et al. Immune-Related thyroiditis with immune checkpoint inhibitors.Thyroid 2018;28:1243-51.

In order to better provide you with more interesting, useful and attitude-oriented content, the Medical Tumor Channel welcomes everyone to complete the following survey with just a few clicks. The questions are small, the content is simple, and it only takes ten seconds~

The web version of the doctor’s website is now online!

Browse more tumor information without downloading

Review of this article: Xu Weiran

Editor-in-charge: Sweet

* The medical community strives to publish professional and reliable content, but does not make any commitment to the accuracy of the content; relevant parties are requested to check separately when adopting or using it as a basis for decision-making.