|Year : 2012 | Volume
| Issue : 3 | Page : 99-101
Icterus in Graves': Grave implications of disease and therapy
Jyothi Idiculla1, Harshad Devarbhavi2, Seena Sankar1, Vageesh Ayyar3
1 Department of Internal Medicine, St John's Medical College Hospital, Sarjapur Road, Bangalore, Karnataka, India
2 Department of Gastroenterology, St John's Medical College Hospital, Sarjapur Road, Bangalore, Karnataka, India
3 Department of Endocrinology, St John's Medical College Hospital, Sarjapur Road, Bangalore, Karnataka, India
|Date of Web Publication||11-Aug-2012|
Department of Internal Medicine, St John's Medical College Hospital, Sarjapur Road, Bangalore 560 034, Karnataka
Source of Support: None, Conflict of Interest: None
Jaundice in Graves' disease maybe multifactorial in etiology. Two such cases are discussed in this paper. The patient presented with icterus on commencement of neomercazole and improved on stoppage of the drug. The second patient went into hepatic encephalopathy following radio-iodine therapy. She was managed intensively with anti-encephalopathic and anti-thyroid measures.
Keywords: Graves′, hepatic encephalopathy, icterus, jaundice
|How to cite this article:|
Idiculla J, Devarbhavi H, Sankar S, Ayyar V. Icterus in Graves': Grave implications of disease and therapy. Thyroid Res Pract 2012;9:99-101
|How to cite this URL:|
Idiculla J, Devarbhavi H, Sankar S, Ayyar V. Icterus in Graves': Grave implications of disease and therapy. Thyroid Res Pract [serial online] 2012 [cited 2020 Oct 28];9:99-101. Available from: https://www.thetrp.net/text.asp?2012/9/3/99/99657
| Introduction|| |
Graves' disease is a familiar diagnosis in endocrine outpatients and most patients undergo an uneventful course with thionamides or radio-iodine therapy. Clinically discernible icterus, first reported in 1874,  is a rather uncommon occurrence in hyperthyroidism and may be multifactorial in etiology.  In this article, we report two such cases of Graves' disease complicated by jaundice, discussing the pathogenesis of hepatic dysfunction in this disease.
| Case Reports|| |
A 59-year-old male, who was diagnosed as having Graves' disease and commenced on neo-mercazole 3 months back, presented to our emergency department with jaundice, generalized itching, increasing breathlessness, and swelling of feet. He was also on losartan, spironolactone, frusemide, and carvedilol as he had congestive cardiac failure. He had discontinued medications 2 weeks back. On examination, he was icteric and pale. The heart rate was 136 beats/minute, regular and blood pressure 96/38 mm Hg. Clinical examination revealed a small goiter and a 3 cm hepatomegaly. The provisional diagnosis was worsening cardiac failure secondary to hyperthyroidism, with hepatitis. The initial investigations revealed microcytic hypochromic anemia. The random blood glucose was 110 mg/dl and serum creatinine within the normal range. The liver functions tests showed elevated AST [Table 1] and ALT and a suppressed thyroid-stimulating hormone was observed in the thyroid function tests [Table 2].
Echo showed sinus tachycardia and echo demonstrated concentric LVH with an ejection fraction of 61%. Viral serology including hepatitis A, B, C, E, and HIV were negative. In addition to therapy for cardiac failure, he was also commenced on cholestyramine 4 g TID, propranalol 40 mg once daily. He improved symptomatically during his stay of 1 week in the hospital. The serial liver function test improved and he was administered 7 mci of radio-iodine. On follow-up, he became hypothyroid and is now on replacement with i-thyroxine. The liver function tests have normalized with an AST of 24 U/l and ALT of 18 U/l.
A 50-year-old lady who was admitted in the department of cardiology with high-output cardiac failure was clinically diagnosed as hyperthyroidism and was referred to the department of medicine for evaluation of icterus. Her heart rate was 150 beats/minute, collapsing, and blood pressure 172/40 mm Hg. She had a grade 2 smooth diffuse goiter with a bruit, fine tremors of the hand and a staring anxious look. Eye signs [Von Graefe's (lid lag) and [Stelwag's (infrequent blinking)] were positive, but exophthalmometry and B scan failed to detect any significant opthalmopathy. The jugular venous pulse was elevated 9 cm above the sternal angle and there was cardiomegaly with hyperdynamic apex, a 6 cm hepatomegaly and basal crackles. Her thyroid functions tests indicated hyperthyroidsim [Table 3]. She was on propranalol, frusemide, and digoxin. The liver function tests were predominantly cholestatic [Table 4]. The viral markers were negative and ultrasound abdomen revealed hepatomegaly with congestion. ECG showed left ventricular hypertrophy with strain and echocardiogram an ejection fraction of 76%. After controlling the cardiac failure, she underwent technetium 99 m scan which was diagnostic of Graves' disease. She was administered 14 mci of radio-iodine and was discharged on propranalol and frusemide. 18 days later she came to the emergency department with increasing drowsiness, fatigability, and vomiting. On examination, she was deeply icteric and pale with a heart rate of 60/minute and blood pressure of 90/20 mm Hg. She was drowsy but arousable and had flapping tremors of her hands. The respiratory rate was 18/minute and the JVP raised at 9 cm. Her cardiac findings were as noted earlier. In addition to a tender enlarged liver she had bilateral crackles over the lung fields. Her thyroid function tests [Table 3] were consistent with hyperthyroidism and liver tests revealed cholestatic predominantly jaundice.
She was provisionally diagnosed as having a combination of hepatic encephalopathy with thyroid storm and was shifted to the intensive treatment room. The serum ammonia was 148 μg/dl. Anti-encephalopathy measures (lactulose, rifaximne, and bowel wash) were stated. In addition, the thyroid storm was treated with oral colloid iodine, cholestyramine, and intravenous dexamethasone. Beta-blockers were discontinued temporarily in view of hypotension. Blood transfusion was given and a culture positive UTI was treated. She was monitored meticulously and her sensorium and clinical parameters improved. The conjugated bilirubin at discharge had improved to a level of 6.1 mg/dl and serum ammonia to 24 μg/dl. On follow-up, her thyroid functions normalized [free T3 and free T4 (2.42 pg/ml and 0.98 ng/dl, respectively] and icterus came down. Due to severe monetary issues, she was unwilling for further tests.
She was discharged only on frusemide and propranalol. At subsequent OPD visits, she was stable with improving LFTs with serum total bilirubin of 8.4 mg/dl and conjugated of 6.1 mg/dl and normal free T3 and free T4 (2.42 pg/ml and 0.98 ng/dl) but later lost to follow-up.
| Discussion|| |
Jaundice in hyperthyroidism may be due to hyperthyroidism per se or various associated factors.  The high metabolic rate in hyperthyroidism increases oxygen consumption in the liver with decrease in oxygen tension leading to hypoxia in the centrilobar zones. This resulting in cholestasis and a possible direct toxic effect are postulated to cause icterus.  Medical therapy with thionamides can cause hepatic dysfunction in some patients. , While PTU causes hepatocellular necrosis, methimazole (and neo-mercazole) induced hypersensitivity is more common. Mild increases of liver enzymes may occur even in most patients commenced on these drugs. Congestive cardiac failure associated with hyperthyroidism with less oxygen supply to the hepatocytes along with fluid accumulation may result in impaired excretory function.  Rarely autoimmune conditions such as autoimmune hepatitis and primary biliary cirrhosis may coexist with Graves' disease resulting in jaundice.  Also like in any other patient with jaundice usage of toxic drugs, viral hepatitis and Gilbert's syndrome should also be ruled out while evaluating icterus in Graves'.
In our first patient, the hepatitis is most likely induced by neo-mercazole therapy with contributions from hyperthyroidism per se and congestive cardiac failure. In the second patient, however, following radio-iodine the transient elevation of thyroid hormones precipitated hepatic encephalopathy. She was previously noticed to have cholestatic jaundice which may have been secondary to hyperthyroidism and CCF. The rise in serum ammonia suggests encephalopathy which came down to normal following anti-encepahalopathic measures. In addition, she received treatment for thyroid storm and managed intensively in the ITU.
Similar case reports of jaundice in patients with hyperthyroidism with thionamides and following radio-iodine have been published in the literature. , Like in our first patient anti-thyroid drug induced hepatotoxicity occurs in only about 0.5% of patients commenced on thionamides.  However, PTU-induced liver failure can be severe and life-threatening.  Lithium as a therapeutic option may be considered in patients with hepatic dysfunction. 
In our second patient, the second admission with hepatic encephalopathy was a more serious scenario. In a similar report in the laryngoscope, a patient who had fulminant hepatitis and multiorgan dysfunction improved with liver transplant followed by thyroidectomy.  In another article, plasmapheresis with subsequent decrease in thyroid hormone levels resulted in improvement in a Chinese patient who had severe viral hepatitis and thyroid storm.  Cholestyramine which was used in our patient prevents eneterohepatic circulation of thyroid hormones thereby reducing the levels. 
These cases are being reported for their rarity of presentation and also to highlight the need for vigilant therapy and meticulous monitoring. Ruling out other causes of hepatic dysfunction including exposure to drugs and toxins, associated viral infection, and obstruction of biliary system is mandatory in similar situations. Autoimmune markers to diagnose associated autoimmune liver disease may be necessary in some patients where etiology remains unclear while treating patients with hepatic dysfunction and Graves' thionamides are best avoided as they may contribute to liver disease. Our patient may be the first reported patient with such severe thyroid and hepatic disease who improved solely with medical management.
| References|| |
|1.||Habershon O. Exophthalmic goitre, heart disease, jaundice and death. Lancet 1874;103:510-2. |
|2.||Bal CS, Chawla M. Hyperthyroidism and jaundice. Indian J Nucl Med 2010;25:131-4. |
|3.||Yao JD, Gross JB Jr, Ludwig J, Purnell DC. Cholestatic jaundice in hyperthyroidism. Am J Med 1989;86:619-20. |
|4.||Cooper Ds, Rivkees SA. Putting propylthiouracil in perspectives. J Clin Endocrinol Metab 2009;94:1881-2. |
|5.||Fisher MG, Nayer HR, Miller A. Methimazole induced jaundice. JAMA 1973;223:1028-9. |
|6.||Woeber KA. Thyrotoxicosis and the heart. N Engl J Med 1992;327:94-8. |
|7.||Owen PJD, Baghomien A, Lazarus JH, Godkin AJ. An unusual cause of jaundice. BMJ 2007;335:773-4. |
|8.||Bellassoued M, Mnif M, Kaffel N, Rekik N, Rebai T, Tahri N, et al. Thyrotoxic hepatitis a case report. Ann Endocrinol (Paris) 2001;62:235-8. |
|9.||Hasan MK, Tierney WM, Baker MZ. Severe cholestatic jaundice in hyperthyroidism after treatment with radio iodine. Am J Med 2004;328:348-50. |
|10.||Cooper DS. Treatment of thyrotoxicosis. In: Braverman LE, Utiger RD, eds. Werner and Ingbar's The Thyroid: A Fundamental and Clinical Text. 7 th ed. Philadelphia, Pa: JB Lippincott Co; 1996:713-743. |
|11.||Nayak B, Burman K. Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin North Am 2006;35:663-86. |
|12.||Kandil E, Khalek MA, Thethi T, Abd Elmageed Z, Khan A, Jaffe BM. Thyroid storm in a patient with fulminant hepatic failure. Laryngoscope 2011;121:164-6. |
|13.||Enghofer M, Badenhoop K, Zeuzem S, Schmidt-Matthiesen A, Betz C, Encke A, et al. Fulminat hepatitiis A in a patient with severe hyperthyroidism rapid recovery from hepatic coma after plasmapheresis and thyroidectomy. J Clin Endocrinol Metab 2000;85:1765-69. |
[Table 1], [Table 2], [Table 3], [Table 4]