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| CASE REPORT |
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| Year : 2016 | Volume
: 4
| Issue : 1 | Page : 64-67 |
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A case of severe autoimmune hepatitis associated with Graves' disease
Samia Abdulla Bokhari1, Patan Murthuza Khan1, Ahmad F Akl1, Ali A AlTayib2
1 Department of Endocrinology, King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia
2 Department of Histopathology, King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia
| Date of Web Publication | 13-Jan-2016 |
Correspondence Address:
Dr. Patan Murthuza Khan
King Fahd Armed Forces Hospital, P. O. Box 9862, Jeddah 21159
Saudi Arabia
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DOI: 10.4103/1658-600X.173836 
Graves' disease is a common condition and is known to have a wide range of effects on a variety of organs. Hepatic dysfunction ranging from mild to severe due to direct effect of high circulating thyroid hormones as well as a deleterious effect of antithyroid medications (methimazole and propylthiouracil) has been well - documented in literature. However, severe autoimmune hepatitis (AIH) associated with Graves' disease is rare and limited to few case reports only. A 38-year-old woman presented with abdominal pain and yellowish discolouration of conjunctivae. On investigation, she was found to have Graves' disease and AIH. The liver histopathology showed typical features of AIH. She responded excellently to glucocorticoid therapy with normalisation of thyroid function and liver histology. The case is discussed with relevant literature review. Keywords: Autoimmune hepatitis, glucocorticoid therapy, Graves' disease
How to cite this article:
Bokhari SA, Khan PM, Akl AF, AlTayib AA. A case of severe autoimmune hepatitis associated with Graves' disease. J Health Spec 2016;4:64-7 |
How to cite this URL:
Bokhari SA, Khan PM, Akl AF, AlTayib AA. A case of severe autoimmune hepatitis associated with Graves' disease. J Health Spec [serial online] 2016 [cited 2021 Jan 17];4:64-7. Available from: https://www.thejhs.org/text.asp?2016/4/1/64/173836 |
| Introduction | |  |
Graves' disease is an immunological disease, targeting the thyroid-stimulating hormone receptor, while AIH is also an autoimmune disease with inflammatory changes and autoantibodies. Thus, these autoimmune mechanisms may rarely lead to development of these two autoimmune diseases concomitantly. Recognition of this association is important for specific treatment and good outcomes.
| Case Report | | |
A 38-year-old Saudi female presented to the emergency room with 2 days history of vomiting and loose motion, in addition to a 2 months history of weight loss. There was no history of alcohol abuse, heat intolerance, insomnia, abdominal pain or family history contributing to autoimmune disorder. On physical examination abdomen was soft, lax without organomegaly and no stigmata of chronic liver disease. Her vital signs were as follows: pulse 88/min, blood pressure 110/68 mmHg and temperature 38°C. Neck examination revealed diffuse symmetrical thyromegaly without bruits. Eye examination revealed icterus of conjunctiva bulbi with no exophthalmos. Chest X-ray was normal. Ultrasound abdomen was unremarkable except for inhomogeneous liver. Thyroid scan revealed diffused increase uptake of tracer in both thyroid lobes (21.8%). Liver biopsy showed interface hepatitis in keeping with autoimmune hepatitis [Figure 1]. The laboratory results are shown in [Table 1]. | Figure 1: Histopathology of liver showing interface hepatitis with numerous plasma cells typical of autoimmune hepatitis
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The diagnoses of Graves' disease were confirmed with results of thyroid function tests (TFT), strongly positive thyroid stimulating hormone (TSH) receptor antibodies and increased diffuse uptake on NM scan of thyroid. The cause of the diagnosed hepatitis was found to be due to AIH type I with increased titres of antinuclear antibodies (ANA), carefully excluding other causes of hepatitis and histopathology of liver biopsy showing interface hepatitis, typical for AIH.
Glucocorticoids were started for the treatment of AIH and as the second-line treatment of Graves' disease. The use of antithyroid medications (methimazole and propylthiouracil) was deferred due to severe hepatitis. The patient showed excellent response to glucocorticoids. The liver function normalised, and ANA titre came down to 1:40 and a repeat liver biopsy showed significant improvement in histopathology [Figure 2]. There was rapid improvement in thyroid function test, with thyroid stimulating hormone and free thyroxine normalising with glucocorticoids alone [Figure 3]. The patient subsequently underwent ablative RAI-131 treatment as she started to develop hyperthyroidism with tapering doses of glucocorticoids. Her AIH was controlled with a small dose of glucocorticoids and azathioprine subsequently. | Figure 2: Histopathology of liver after treatment showing normal architecture of liver parenchyma
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 | Figure 3: Graph showing plasma levels (IU/L) of alanine transferase and free thyroxine before and after treatment with glucocorticoids
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| Discussion | | |
The hepatic manifestations of hyperthyroidism are polymorphic and of multiple aetiologies. Hepatic dysfunction due to antithyroid medications (methimazole and propylthiouracil) are well known, and a certain history of these drugs will make the diagnosis obvious. A mild derangement in liver function is common in Graves' disease. In a study, 76.7% of untreated Graves' disease patients were found to have at least one liver function abnormality, but severe hepatitis and hepatic failure were rare.[1],[2] In a retrospective study of hepatic dysfunction conducted in hospitalised patients not on antithyroid medications, 81.8% had some degree of hepatic dysfunction and 18.2% had both increase in transaminases and isolated synthetic dysfunction manifested as an elevated prothrombin time and decreased albumin.[3] The exact mechanism of association between excess thyroid hormone and hepatic dysfunction is unclear. It could be due to indirect pathways or due to direct hormone effects on the target organ, such as an interaction with nuclear receptors at the plasma membrane, mitochondria and other cellular sites.[4] AIH is a chronic hepatitis of unknown aetiology associated with inflammatory changes and auto-antibodies. It has been reported that 28% of AIH cases are associated with extra-hepatic autoimmune diseases mainly rheumatoid arthritis, Jogren syndrome and chronic hepatitis.[5] However, the combination of AIH and Graves' disease is rare and limited to a few case reports only.[6],[7],[8] The present case is a combination of severe AIH and Graves' disease. AIH with severe hepatitis as evidenced by high transaminases, high bilirubin, prolonged prothrombin time and low albumin with Graves' disease is rarely described in literature. The diagnosis of AIH (type I) was established by carefully excluding other causes of hepatic dysfunction and presence of ANA in 1:80 titres and typical histopathological findings and excellent response to glucocorticoids.
The case also demonstrates the potential value of glucocorticoids in rapid control of thyrotoxic state prior to planned definitive treatment, either surgery or RAI-131 treatment. Glucocorticoids are the drug of second choice in the treatment of Graves' disease if conventional antithyroid medications could not be used.[9] Rapid improvement of thyroid function was achieved with glucocorticoids alone in several studies.[10] There are two reasons why Graves' disease patients respond to corticosteroids in a twofold manner. First, the more immediate effect could be inhibition of conversion of thyroxine to triiodothyronine in peripheral tissue and blocking the release of thyroxin from the thyroid gland. Second, glucocorticoids may lead to suppression of the immune response and hence decreased stimulation of the thyroid gland by the altered immune response and cell-mediated immunity. The patient was treated with glucocorticoids alone and the use of antithyroid medication was deferred due to severe dysfunction. Rapid improvement in liver function and thyroid function was achieved. A repeat liver biopsy showed marked improvement in histopathology compared to pre-treatment biopsy findings.
| Conclusion | | |
Majority of patients with Graves' disease have hepatic dysfunction, making the recognition of this association important. Specific diagnosis should be considered after ruling out common causes, and definitive treatment may be considered if specific diagnosis is established.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Kubota S, Amino N, Matsumoto Y, Ikeda N, Morita S, Kudo T, et al. Serial changes in liver function tests in patients with thyrotoxicosis induced by Graves' disease and painless thyroiditis. Thyroid 2008;18:283-7.  |
| 2. | Babb RR. Association between diseases of thyroid and the liver. Am J Gastroenterol 1984;79:421-3. [ PUBMED] |
| 3. | Goto K, Mori M, Kuribara M, Yamada S, Igarashi T, Takezawa J, et al. A case of autoimmune hepatitis associated with Graves' disease. Nihon Naika Gakkai Zasshi 1986;75:1443-8. [ PUBMED] |
| 4. | Elias RM, Dean DS, Barsness GW. Hepatic dysfunction in hospitalized patients with acute thyrotoxicosis: A decade of experience. ISRN Endocrinol 2012;2012:325092. |
| 5. | Onji M, Nonaka T, Horiike N, Moriwaki H, Muto Y, Ohta Y. Present status of autoimmune hepatitis in Japan. Gastroenterol Jpn 1993;28 Suppl 4:134-8. |
| 6. | Sarkhy A, Persad R, Tarnopolsky M. Muscle weakness in a girl with autoimmune hepatitis and Graves' disease. Eur J Pediatr 2009;168:241-3. |
| 7. | Inoue K, Okajima T, Tanaka E, Ando B, Takeshita M, Masuda A, et al. A case of Graves' disease associated with autoimmune hepatitis and mixed connective tissue disease. Endocr J 1999;46:173-7. |
| 8. | Marinò M, Latrofa F, Menconi F, Chiovato L, Vitti P. An update on the medical treatment of Graves' hyperthyroidism. J Endocrinol Invest 2014;37:1041-8. |
| 9. | Williams DE, Chopra IJ, Orgiazzi J, Solomon DH. Acute effects of corticosteroids on thyroid activity in Graves' disease. J Clin Endocrinol Metab 1975;41:354-61. [ PUBMED] |
| 10. | Chopra IJ, Williams DE, Orgiazzi J, Solomon DH. Opposite effects of dexamethasone on serum concentrations of 3,3',5'-triiodothyronine (reverse T3) and 3,3'5-triiodothyronine (T3). J Clin Endocrinol Metab 1975;41:911-20. [ PUBMED] |
[Figure 1], [Figure 2], [Figure 3]
[Table 1]
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