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Year : 2018  |  Volume : 14  |  Issue : 10  |  Page : 818-819

Sunitinib-induced acute severe hypothyroidism in a case of metastatic gastrointestinal stromal tumor: A case report

Department of Radiotherapy, R. G. Kar Medical College and Hospitals, Kolkata, West Bengal, India

Date of Web Publication24-Sep-2018

Correspondence Address:
Kazi Sazzad Manir
Department of Radiotherapy, R. G. Kar Medical College and Hospitals, 1, Kshudiram Bose Sarani, Kolkata - 700 004, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.199443

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 > Abstract 

Thyroid abnormalities are found nearly 70% cases receiving sunitinib therapy. Mostly, patients suffer transient hypothyroidism rarely presents with overt acute symptoms requiring levothyroxine replacement. Onset is variable in published literature. We report a case of metastatic gastrointestinal stromal tumor receiving sunitinib with normal baseline thyroid function. The patient developed symptoms of acute severe hypothyroidism with high thyroid stimulating hormone level on the 4th week of therapy. The patient responded with oral levothyroxine. clinical and biochemical parameter resolved rapidly. Patient receiving sunitinib warns baseline and subsequent surveillance of thyroid function (both clinical and biochemical). This rare dreadful condition reverts promptly with thyroxine replacement.

Keywords: Hypothyroidism, sunitinib, thyroxine

How to cite this article:
Manir KS, Banerjee D, Bhowmick R, Roy C. Sunitinib-induced acute severe hypothyroidism in a case of metastatic gastrointestinal stromal tumor: A case report. J Can Res Ther 2018;14, Suppl S3:818-9

How to cite this URL:
Manir KS, Banerjee D, Bhowmick R, Roy C. Sunitinib-induced acute severe hypothyroidism in a case of metastatic gastrointestinal stromal tumor: A case report. J Can Res Ther [serial online] 2018 [cited 2022 May 28];14, Suppl S3:818-9. Available from: https://www.cancerjournal.net/text.asp?2018/14/10/818/199443

 > Introduction Top

Sunitinib is an oral multikinase inhibitor for vascular endothelial growth factor receptors 1 and 2, platelet-derived growth factor receptors alpha and beta, glial cell-line derived neurotrophic factor receptor (RET), stem cell factor receptor (KIT), and FMS-like tyrosine kinase 3 used as the second-line therapy in imatinib-refractory metastatic Gastrointestinal stromal tumor (GIST). Fatigue (34%), hypertension (30%), yellowish discoloration of skin and skin rash (30%), diarrhea (25%), and bone marrow suppression are common adverse events associated with sunitinib.[1],[2] Hypothyroidism is very rare in sunitinib-treated patients due to transient thyroid uptake blockade, rarely needing L-thyroxine supplementation. In addition, few patients develop severe symptoms that can be attributed directly to hypothyroidism.[3] We report a case of metastatic GIST on sunitinib therapy, developed acute severe hypothyroidism with high level of thyroid-stimulating hormone (TSH) needing L-thyroxine supplementation.

 > Case Report Top

A 68-year-old male patient was referred to a tertiary cancer center for metastatic GIST which was progressive on imatinib. The patient was started with tablet sunitinib 50 mg daily. Baseline performance status was good. He only had a long-standing history of hypertension which was controlled with tablet losartan 25 mg daily. His baseline liver function and renal function was normal. Baseline serum thyrotropin (TSH), free triiodothyronine (T3), and free thyroxine (T4) concentrations were 2.58 mU/L (normal range, 0.38–4.3 mU/L), 99.1 ng/dL (82.0–180.0 ng/dL), and 1.1 ng/dl (0.7–1.8 ng/dL), respectively. He had no family history of cancer or thyroid disease. After 4 months of sunitinib therapy, he was admitted to our Emergency Department with acute onset confusion and fatigue. On examination, the skin was moist and cold, his body temperature was 35.7°C, her blood pressure was 170/90 mmHg, pulse was 67 beats/min, and respiratory rate was 13 breaths/min. He was severely confused. Other physical examination was within normal limits except generalized yellowish discoloration of skin. A complete blood count revealed a white blood count of 7500/mm3, hemoglobin of 10.9 mg/dL, and platelet count of 110,000/mm3. Liver function tests, urea, creatinine, and serum electrolytes were normal. Magnetic resonance imaging brain was normal.

However, on thyroid function test analysis, TSH, free T3, and free T4 concentrations were 125.2 mU/L (normal range, 0.38–4.3 mU/L), 50 ng/dL (82.0–180.0 ng/dL), and 0.1 ng/dl (0.7–1.8 ng/dL), respectively. Thyroglobulin levels were normal (40.7 ng/mL) and anti-peroxidase antibodies <10 IU/mL. Treatment with oral L-thyroxine 150 mcg along with intravenous steroid and other supportive medications started promptly. The patient improved quickly. After 7 days, thyroid parameters also improved. TSH, free T3, and free T4 concentrations were 21 mU/L (normal range, 0.38–4.3 mU/L), 74 ng/dL (82.0–180.0 ng/dL) and 0.5 ng/dL (0.7–1.8 ng/dL), respectively. The patient was discharged after 10 days with lowered L-thyroxine dose and sunitinib was restarted. During discharge, the patient had no symptoms except fatigue.

 > Discussion Top

Thyroid function test abnormalities are found in up to 40%–85% of patients treated with sunitinib for metastatic renal cell carcinoma and imatinib-refractory GIST.[2],[4],[5] Mostly, patient presents with biochemical alteration and fatigue. As per published reports, 9%–30% of sunitinib-induced hypothyroidism patients require supplementation.[3] Acute severe hypothyroidism needing hospitalization is rare.[2],[3] Although tyrosine kinase inhibitor-related hypothyroidism is thought to be a long-term adverse effect, studies have reported a variable onset of sunitinib-induced hypothyroidism, ranges from 4 to 50 weeks of sunitinib therapy.[3],[4],[6],[7] The potential mechanisms by which sunitinib might induce thyroid dysfunction include blockade of iodine uptake, destructive thyroiditis, and inhibition of peroxidase activity.[2],[3],[4],[5]

Our patient rapidly developed severe hypothyroidism with gross biochemical alteration and high symptom burden within 4th week of sunitinib therapy. Before this acute episode, he was asymptomatic except fatigue. Since sunitinib may cause fatigue even in the absence of thyroid abnormalities; there is some uncertainty about the frequency of clinically relevant hypothyroidism associated with sunitinib.[3] The patient improved clinically and biochemically after discontinuation of sunitinib and L-thyroxine therapy, which suggests these symptoms were due to sunitinib-induced hypothyroidism. In our case, we found the resolution of clinical and biochemical alteration quickly similar to other literatures.[2],[4]


Dr. Sugata Dasgupta, Department of Anesthesiology and Critical Care, R. G. Kar Medical College, Kolkata, West Bengal, India.

Financial support and sponsorship

Department of Radiotherapy, R. G. Kar Medical College and Hospital, Kolkata, West Bengal, India.

Conflicts of interest

There are no conflicts of interest.

 > References Top

Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: A randomised controlled trial. Lancet 2006;368:1329-38.  Back to cited text no. 1
Prat A, Serrano C, Valverde C, Calvo E. Acute severe hypothyroidism induced by sunitinib. Radiother Oncol 2008;89:124-5.  Back to cited text no. 2
Del Fabbro E, Dev R, Cabanillas ME, Busaidy NL, Rodriguez EC, Bruera E. Extreme hypothyroidism associated with sunitinib treatment for metastatic renal cancer. J Chemother 2012;24:221-5.  Back to cited text no. 3
Desai J, Yassa L, Marqusee E, George S, Frates MC, Chen MH, et al. Hypothyroidism after sunitinib treatment for patients with gastrointestinal stromal tumors. Ann Intern Med 2006;145:660-4.  Back to cited text no. 4
Mannavola D, Coco P, Vannucchi G, Bertuelli R, Carletto M, Casali PG, et al. A novel tyrosine-kinase selective inhibitor, sunitinib, induces transient hypothyroidism by blocking iodine uptake. J Clin Endocrinol Metab 2007;92:3531-4.  Back to cited text no. 5
Di Lorenzo G, Porta C, Bellmunt J, Sternberg C, Kirkali Z, Staehler M, et al. Toxicities of targeted therapy and their management in kidney cancer. Eur Urol 2011;59:526-40.  Back to cited text no. 6
Wolter P, Stefan C, Decallonne B, Dumez H, Bex M, Carmeliet P, et al. The clinical implications of sunitinib-induced hypothyroidism: A prospective evaluation. Br J Cancer 2008;99:448-54.  Back to cited text no. 7

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