Diagnosis and Treatment > Signs and Symptoms
Search for other papers by Tomomi Nakao in
Google Scholar
PubMed
Search for other papers by Ken Takeshima in
Google Scholar
PubMed
Search for other papers by Hiroyuki Ariyasu in
Google Scholar
PubMed
Search for other papers by Chiaki Kurimoto in
Google Scholar
PubMed
Search for other papers by Shinsuke Uraki in
Google Scholar
PubMed
Search for other papers by Shuhei Morita in
Google Scholar
PubMed
Search for other papers by Yasushi Furukawa in
Google Scholar
PubMed
Search for other papers by Hiroshi Iwakura in
Google Scholar
PubMed
Search for other papers by Takashi Akamizu in
Google Scholar
PubMed
Summary
Thyroid storm (TS) is a life-threatening condition that may suffer thyrotoxic patients. Therapeutic plasma exchange (TPE) is a rescue approach for TS with acute hepatic failure, but it should be initiated with careful considerations. We present a 55-year-old male patient with untreated Graves’ disease who developed TS. Severe hyperthyroidism and refractory atrial fibrillation with congestive heart failure aggregated to multiple organ failure. The patient was recovered by intensive multimodal therapy, but we had difficulty in introducing TPE treatment considering the risk of exacerbation of congestive heart failure due to plasma volume overload. In addition, serum total bilirubin level was not elevated in the early phase to the level of indication for TPE. The clinical course of this patient instructed delayed elevation of bilirubin until the level of indication for TPE in some patients and also demonstrated the risk of exacerbation of congestive heart failure by TPE.
Learning points:
-
Our patient with thyroid storm could be diagnosed and treated promptly using Japan Thyroid Association guidelines for thyroid storm.
-
Delayed elevation of serum bilirubin levels could make the decision of introducing therapeutic plasma exchange difficult in cases of thyroid storm with acute hepatic failure.
-
The risk of worsening congestive heart failure should be considered carefully when performing therapeutic plasma exchange.
Centre for Endocrine and Diabetes Sciences, University Hospital of Wales, Heath Park, Cardiff, UK
Search for other papers by J K Witczak in
Google Scholar
PubMed
Search for other papers by N Ubaysekara in
Google Scholar
PubMed
Search for other papers by R Ravindran in
Google Scholar
PubMed
Search for other papers by S Rice in
Google Scholar
PubMed
Search for other papers by Z Yousef in
Google Scholar
PubMed
Search for other papers by L D Premawardhana in
Google Scholar
PubMed
Summary
Graves’ disease is associated with tachydysrythmia, cardiac ischaemia and cardiomyopathy – all uncommon in young adults without previous cardiac disease. We present three young individuals who developed cardiac complications after periods of uncontrolled Graves’ disease. Subject 1: A 34-year-old female had severe thyrotoxic symptoms for weeks. Investigations showed fT4: 98.4 (11–25 pmol/L), fT3: 46.9 (3.1–6.8 pmol/L), TSH <0.01 (0.27–4.2 mU/L) and thyrotrophin receptor antibody (TRAb): 34.8 (<0.9 U//l). She had appropriate treatment but several weeks later she became breathless despite improving thyroid function. Echocardiography showed a pericardial effusion of 2.9 cm. She responded well to steroids and NSAIDs but developed active severe Graves’ orbitopathy after early total thyroidectomy. Subject 2: A 28-year-old male developed thyrotoxic symptoms (fT4: 38 pmol/L, fT3: 13.9 pmol/L, TSH <0.01 (for over 6 months) and TRAb: 9.3 U/L). One month after starting carbimazole, he developed acute heart failure (HF) due to severe dilated cardiomyopathy – EF 10–15%. He partially recovered after treatment – EF 28% and had early radioiodine treatment. Subject 3: A 42-year-old woman who had been thyrotoxic for several months (fT4: 54.3; fT3 >46.1; TSH <0.01; TRAb: 4.5) developed atrial fibrillation (AF) and heart failure. Echocardiography showed cardiomegaly – EF 29%. She maintains sinus rhythm following early total thyroidectomy (EF 50%). Significant cardiac complications may occur in previously fit young adults, who have had uncontrolled Graves’ disease for weeks to months. Cardiac function recovers in the majority, but early definitive treatment should be discussed to avoid Graves’ disease relapse and further cardiac decompensation.
Learning points:
-
Cardiac complications of Graves’ disease are uncommon in young adults without previous cardiac disease.
-
These complications may however occur if Graves’ disease had been poorly controlled for several weeks or months prior to presentation.
-
Persistent symptoms after adequate control should alert clinicians to the possibility of cardiac disease.
-
Specific treatment of Graves’ disease and appropriate cardiac intervention results in complete recovery in the majority and carries a good prognosis.
-
Early definitive treatment should be offered to them to prevent cardiac decompensation at times of further relapse.
Search for other papers by Yuri Tanaka in
Google Scholar
PubMed
Search for other papers by Taisuke Uchida in
Google Scholar
PubMed
Search for other papers by Hideki Yamaguchi in
Google Scholar
PubMed
Search for other papers by Yohei Kudo in
Google Scholar
PubMed
Search for other papers by Tadato Yonekawa in
Google Scholar
PubMed
Search for other papers by Masamitsu Nakazato in
Google Scholar
PubMed
Summary
We report the case of a 48-year-old man with thyroid storm associated with fulminant hepatitis and elevated levels of soluble interleukin-2 receptor (sIL-2R). Fatigue, low-grade fever, shortness of breath, and weight loss developed over several months. The patient was admitted to the hospital because of tachycardia-induced heart failure and liver dysfunction. Graves’ disease with heart failure was diagnosed. He was treated with methimazole, inorganic iodide, and a β-blocker. On the day after admission, he became unconscious with a high fever and was transferred to the intensive care unit. Cardiogenic shock with atrial flutter was treated with intra-aortic balloon pumping and cardioversion. Hyperthyroidism decreased over 10 days, but hepatic failure developed. He was diagnosed with thyroid storm accompanied by fulminant hepatitis. Laboratory investigations revealed elevated levels of sIL-2R (9770 U/mL). The fulminant hepatitis was refractory to plasma exchange and plasma filtration with dialysis, and no donors for liver transplantation were available. He died of hemoperitoneum and gastrointestinal hemorrhage due to fulminant hepatitis 62 days after admission. Elevated circulating levels of sIL-2R might be a marker of poor prognosis in thyroid storm with fulminant hepatitis.
Learning points:
-
The prognosis of thyroid storm when fulminant hepatitis occurs is poor.
-
Liver transplantation is the preferred treatment for fulminant hepatitis induced by thyroid storm refractory to plasma exchange.
-
Elevated levels of soluble interleukin-2 receptor might be a marker of poor prognosis in patients with thyroid storm.
Search for other papers by Haruhiro Sato in
Google Scholar
PubMed
Department of Pediatrics, Keio Hachioji Clinic, Hchioji, Tokyo, Japan
Search for other papers by Yuichiro Tomita in
Google Scholar
PubMed
Summary
Resistance to thyroid hormone (RTH), which is primarily caused by mutations in the thyroid hormone (TH) receptor beta (THRB) gene, is dominantly inherited syndrome of variable tissue hyposensitivity to TH. We herein describe a case involving a 22-year-old Japanese man with RTH and atrial fibrillation (AF) complaining of palpitation and general fatigue. Electrocardiography results revealed AF. He exhibited elevated TH levels and an inappropriately normal level of thyroid-stimulating hormone (TSH). Despite being negative for anti-TSH receptor antibody, thyroid-stimulating antibody and anti-thyroperoxidase antibody, the patient was positive for anti-thyroglobulin (Tg) antibody. Genetic analysis of the THRB gene identified a missense mutation, F269L, leading to the diagnosis of RTH. Normal sinus rhythm was achieved after 1 week of oral bisoprolol fumarate (5 mg/day) administration. After 3 years on bisoprolol fumarate, the patient had been doing well with normal sinus rhythm, syndrome of inappropriate secretion of TSH (SITSH) and positive titer of anti-Tg antibody.
Learning points:
-
Atrial fibrillation can occur in patients with RTH.
-
Only a few cases have been reported on the coexistence of RTH and atrial fibrillation.
-
No consensus exists regarding the management of atrial fibrillation in patients with RTH.
-
Administration of bisoprolol fumarate, a beta-blocker, can ameliorate atrial fibrillation in RTH.
Search for other papers by Carolina Shalini Singarayar in
Google Scholar
PubMed
Search for other papers by Foo Siew Hui in
Google Scholar
PubMed
Search for other papers by Nicholas Cheong in
Google Scholar
PubMed
Search for other papers by Goay Swee En in
Google Scholar
PubMed
Summary
Thyrotoxicosis is associated with cardiac dysfunction; more commonly, left ventricular dysfunction. However, in recent years, there have been more cases reported on right ventricular dysfunction, often associated with pulmonary hypertension in patients with thyrotoxicosis. Three cases of thyrotoxicosis associated with right ventricular dysfunction were presented. A total of 25 other cases of thyrotoxicosis associated with right ventricular dysfunction published from 1994 to 2017 were reviewed along with the present 3 cases. The mean age was 45 years. Most (82%) of the cases were newly diagnosed thyrotoxicosis. There was a preponderance of female gender (71%) and Graves’ disease (86%) as the underlying aetiology. Common presenting features included dyspnoea, fatigue and ankle oedema. Atrial fibrillation was reported in 50% of the cases. The echocardiography for almost all cases revealed dilated right atrial and or ventricular chambers with elevated pulmonary artery pressure. The abnormal echocardiographic parameters were resolved in most cases after rendering the patients euthyroid. Right ventricular dysfunction and pulmonary hypertension are not well-recognized complications of thyrotoxicosis. They are life-threatening conditions that can be reversed with early recognition and treatment of thyrotoxicosis. Signs and symptoms of right ventricular dysfunction should be sought in all patients with newly diagnosed thyrotoxicosis, and prompt restoration of euthyroidism is warranted in affected patients before the development of overt right heart failure.
Learning points:
-
Thyrotoxicosis is associated with right ventricular dysfunction and pulmonary hypertension apart from left ventricular dysfunction described in typical thyrotoxic cardiomyopathy.
-
Symptoms and signs of right ventricular dysfunction and pulmonary hypertension should be sought in all patients with newly diagnosed thyrotoxicosis.
-
Thyrotoxicosis should be considered in all cases of right ventricular dysfunction or pulmonary hypertension not readily explained by other causes.
-
Prompt restoration of euthyroidism is warranted in patients with thyrotoxicosis complicated by right ventricular dysfunction with or without pulmonary hypertension to allow timely resolution of the abnormal cardiac parameters before development of overt right heart failure.
Search for other papers by Christine Yu in
Google Scholar
PubMed
Search for other papers by Inder J Chopra in
Google Scholar
PubMed
Search for other papers by Edward Ha in
Google Scholar
PubMed
Summary
Ipilimumab, a novel therapy for metastatic melanoma, inhibits cytotoxic T-lymphocyte apoptosis, causing both antitumor activity and significant autoimmunity, including autoimmune thyroiditis. Steroids are frequently used in treatment of immune-related adverse events; however, a concern regarding the property of steroids to reduce therapeutic antitumor response exists. This study describes the first reported case of ipilimumab-associated thyroid storm and implicates iopanoic acid as an alternative therapy for immune-mediated adverse effects. An 88-year-old woman with metastatic melanoma presented with fatigue, anorexia, decreased functional status, and intermittent diarrhea for several months, shortly after initiation of ipilimumab – a recombinant human monoclonal antibody to the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4). On arrival, she was febrile, tachycardic, and hypertensive with a wide pulse pressure, yet non-toxic appearing. She had diffuse, non-tender thyromegaly. An electrocardiogram (EKG) revealed supraventricular tachycardia. Blood, urine, and stool cultures were collected, and empiric antibiotics were started. A computed tomography (CT) angiogram of the chest was negative for pulmonary embolism or pneumonia, but confirmed a diffusely enlarged thyroid gland, which prompted thyroid function testing. TSH was decreased at 0.16 μIU/ml (normal 0.3–4.7); free tri-iodothyronine (T3) was markedly elevated at 1031 pg/dl (normal 249–405), as was free thyroxine (T4) at 5.6 ng/dl (normal 0.8–1.6). With iopanoic acid and methimazole therapy, she markedly improved within 48 h, which could be attributed to lowering of serum T3 with iopanoic acid rather than to any effect of the methimazole. Ipilimumab is a cause of overt thyrotoxicosis and its immune-mediated adverse effects can be treated with iopanoic acid, a potent inhibitor of T4-to-T3 conversion.
Learning points
-
While ipilimumab more commonly causes autoimmune thyroiditis, it can also cause thyroid storm and clinicians should include thyroid storm in their differential diagnosis for patients who present with systemic inflammatory response syndrome.
-
Immune-related adverse reactions usually occur after 1–3 months of ipilimumab and baseline thyroid function testing should be completed before initiation with ipilimumab.
-
Conflicting data exist on the use of prednisone for treatment of CTLA4 adverse effects and its attenuation of ipilimumab's antitumor effect. Iopanoic acid may be considered as an alternative therapy in this setting.
