Cholestatic hepatic injury due to a thyroid storm: a case report from a resource limited setting

  • Davis Kibirige1, 3Email author,

    Affiliated with

    • Daniel Sekikubo Kiggundu2,

      Affiliated with

      • Richard Sanya2 and

        Affiliated with

        • Edrisa Mutebi2

          Affiliated with

          Thyroid Research20125:6

          DOI: 10.1186/1756-6614-5-6

          Received: 23 January 2012

          Accepted: 9 July 2012

          Published: 28 July 2012

          Abstract

          Introduction

          Thyroid storm is an endocrinological emergency caused by an exacerbation of the hyperthyroid state and is characterized by multi organ dysfunction. Liver dysfunction or injury predominantly of a cholestatic type is one of the atypical manifestations of thyroid storm and has been previously described in literature. However, there have been few published case reports among African patients and from resource limited settings.

          Case report

          We report a case of a 21 year old Ugandan female patient who presented with a thyroid storm due to untreated Graves’ disease complicated by cholestatic hepatic injury, congestive heart failure and acute kidney injury.

          Conclusion

          This case highlights the varied multi organ dysfunctions seen in a patient with thyroid storm with emphasis on liver injury mainly to increase awareness among clinicians in resource limited settings. Mechanisms of liver injury due to thyroid storm or hyperthyroidism are discussed in the literature review.

          Keywords

          Thyroid storm Cholestatic hepatic injury Cholestasis

          Introduction

          Thyroid storm refers to the sudden onset of life-threatening manifestations of hyperthyroidism. Usually, it complicates Graves’ disease but can also occur in association with toxic multinodular goitre [1].

          The condition is often evoked by a precipitating factor such as untreated hyperthyroidism, infectious diseases, acute trauma, thyroidal surgery, excessive iodine intake in diet and administration of iodine-containing materials like amiodarone. The clinical picture is predominated mainly by fever, tachycardia or supraventricular arrhythmias, central nervous system symptoms like severe agitation and altered mentation and gastrointestinal symptoms [2].

          Hepatic injury as part of the multi organ dysfunction due to thyroid storm has been described in several case reports and in literature ranging from severe liver dysfunction to acute liver failure and resultant death. A cholestatic picture mainly predominates [36].

          Case report

          A 21 year old female patient, newly diagnosed with Graves’ disease was referred from a peripheral hospital with a two week history of progressive yellowing of the eyes associated with generalised abdominal distension, marked right hypochondrial pain and mild generalised pruritis. Ten days prior to her admission, she developed worsening exertional dyspnea, easy fatigability, bilateral lower limb swelling , palpitations, orthopnea , profound weight loss and generalised muscular weakness and heat intolerance. She had been amenorrheic for 4 months and was not taking any medications. She had no history of smoking or alcohol consumption.

          Clinical examination on admission revealed a thin, diaphoretic and mildly agitated lady. Her axillary temperature was 39.2°C. She had jaundice with bilateral pitting lower limb oedema, a fine resting tremor, exophthalmos and eyelid lag. The thyroid gland was palpable, diffusely enlarged and non tender with a bruit. Cardiovascular examination revealed a rapid, large volume and regular pulse of 140 beats/min with an isolated systolic hypertension of 150/70 mmHg. The jugular venous pressure was raised and neck veins engorged. She had a heaving apex beat displaced to the 6th intercostal space anterior axillary line with a gallop and a soft apical systolic murmur. Abdominal and respiratory examinations revealed a tender hepatomegaly with ascites and reduced breathe sounds on the right infra axillary and scapular areas respectively.

          A chest radiograph done revealed a cardiomegaly with a right sided pleural effusion. An abdominal Ultra sound scan done showed an enlarged liver with a normal echo texture, ascites, normal biliary ducts and gall bladder. A thyroid ultra sound scan was not done. Electrocardiography showed sinus tachycardia, with a rate of 142 beats/min and left ventricular hypertrophy by voltage criteria. The Echocardiography showed globally dilated cardiac chambers with moderate mitral and tricuspid regurgitation, an elevated ejection fraction of 82% (40-70%) and moderate pulmonary hypertension.

          The laboratory investigations done are summarised in Table 1 below.
          Table 1

          Laboratory investigations of the patient

          LABORATORY PARAMETER

          PATIENT’S VALUE

          NORMAL RANGE

          1.Total white blood cell count (x109)

          8.7

          4.0-9.0

          2.Absolute Neutrophil count (x109)

          6.6

          1.7-7.7

          3. Haemoglobin level (g/dl)

          8.0

          12-17

          4.Serum albumin (g/l)

          21.4

          35-50

          5. Corrected Calcium (mg/dl)

          11.2

          9-10.6

          6. Alanine transaminase (U/L)

          17.9

          0-40

          7. Aspartate transaminase (U/L)

          48.2

          0-40

          8.Alkaline Phosphatase (U/L)

          212

          40-129

          9.Gamma-glutamyl transpeptidase (U/L)

          82.4

          0-55

          9.Total bilirubin (μmol/l)

          233.2

          0-40

          10.Direct bilirubin (μmol/l)

          215.75

          0-3.4

          11.Serum urea (mmol/l)

          12.4

          2.7-6.4

          12. Serum creatinine (μmol/l)

          120.7

          44-106

          13. Urea/Creatinine ratio

          56.4

          < 20

          14. Serum Sodium (mmol/l)

          130

          135-150

          15. Serum Creatinine kinase (U/L)

          815

          26-308

          16. Serum lactate dehydrogenase (U/L)

          409

          135-225

          17. Serum creatinine kinase-MB isoform-CK-MB (U/L)

          100.9 U/L

          0-25

          18. Random blood sugar (mg/dl)

          7.4 mmol/l

          3.5-11

          19. Urine pregnancy test

          Negative.

           

          20. HIV serology, Hepatitis Bs Ag test, Hepatitis C antibodies

          Negative.

           

          Thyroid function tests revealed a suppressed thyroid stimulating hormone level (TSH) of <0.005 uIUml (0.27–4.2), raised free thyroxine levels of 267.5 nmol/L (normal range: 66–181) and free triiodothyronine of 10 nmol/L (normal range: 1.3-3.1).

          A thyroid nuclear scan showed a diffuse homogenous increased uptake of radioactive iodine with no background uptake. Thyroid stimulating hormone receptor antibody, Antithyroglobulin and antithyroid peroxidase antibodies were not done due to financial constraints.

          An impression of thyroid storm due to untreated Graves’ disease with cholestatic liver injury, high output congestive heart failure due to thyrotoxic heart disease and acute kidney injury was made. The patient’s Burch-Wartofsky score for thyroid storm was 90 [7].

          She was started on oral carbimazole, Prednisolone, Propranolol, Lugol’s iodine, intra venous fluid replacement, oral anti histamines for the pruritis, oral frusemide and Captopril for the heart failure.

          The patient was discharged 10 days later with great improvement and on a follow-up assessment 10 weeks later; she was feeling generally well with resolution of the jaundice and clinically euthyroid. A repeat electrocardiography, echocardiography, renal and liver function tests were all normal.

          Discussion

          Thyroid storm is a sudden, life-threatening exacerbation of thyrotoxicosis that is associated with multi organ dysfunction and increased mortality if untreated.

          Possible mechanisms responsible for progression to thyroid storm include a steady increase of tissue iodothyronine levels, an augmented cellular response to the circulating thyroid hormones and their effect of enhancing cellular expression of adrenoceptors and sensitivity to circulating cathechoamines [7, 8].

          The case reported illustrates a thyroid storm due to untreated Graves’ disease with mainly cardiac, renal and gastrointestinal dysfunctions in a 21 year old girl. The diagnosis of Graves’ disease was made basing on the prominent eye signs (exophthalmos and eyelid lag) and a suggestive thyroid nuclear scan (diffuse homogenous increased uptake of radioactive iodine with no background uptake).

          Excessive dietary iodine intake is one of the recognised trigger factors of thyroid storm and Graves’ disease [1, 2]. However, excessive dietary intake of iodine has been documented to be very uncommon in Uganda. It has been reported in only one district in central Uganda [9].

          The patient discussed is from an iodine repleted area with adequate iodine intake in the diet.

          Causes of liver injury in hyperthyroidism or thyroid storm are multifactorial. A cholestatic type of hepatic injury of centrilobular intrahepatic form predominates as demonstrated in this case. Cholestatic liver injury is mainly depicted by a raised direct hyperbilirubinemia and alkaline phosphatase levels as shown in the patient’s workup. The latter however may signify an increased osteoblastic response to increased thyroid hormone induced bone resorption [10].

          Hepatic damage occurring solely due to thyrotoxicosis or hyperthyroidism has also been thought to be due to ischemic injury resulting from a relative decrease in blood flow despite presence of an increased hepatic metabolic activity [10].

          Cholestatic liver injury in patients with hyperthyroidism or thyroid storm due to Graves’ disease can also be associated with other pre existing auto immune liver conditions especially primary biliary cirrhosis (PBC) or autoimmune hepatitis. These are seen in up to 10% of patients [11, 12].

          Other proposed mechanisms of hepatic dysfunction in hyperthyroidism or thyroid storm include hepatic congestion resulting from heart failure due to thyrotoxic heart disease as showed in the case report. This often leads to hepatic abnormalities like acute hepatocellular injury with hyperbilirubinemia and resultant coagulopathy [13, 14]. Anti thyroid drugs especially propylthiouracil also cause cholestatic liver injury and the effect is usually dose dependent [15].

          However in this patient, we were unable to exclude any intrinsic co-existing auto immune liver conditions due to limitation of resources. The patient declined a liver biopsy.

          Conclusion

          It is of paramount importance to recognise liver injury due to a thyroid storm or hyperthyroidism and to promptly diagnose and treat thyroid storm especially in resource limited settings where intensive care units aren’t easily accessible. This is because severe liver impairment and thyroid storm are associated with increased mortality.

          Consent

          Written informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

          Declarations

          Acknowledgements

          The entire team of nursing staff and doctors attached to the emergency and endocrinology units, Mulago national referral and teaching hospital Kampala, Uganda who participated in the care of this patient.

          Authors’ Affiliations

          (1)
          Department of Medicine, Makerere University College of Health Sciences and Emergency Medicine unit, Mulago national referral and teaching hospital
          (2)
          Department of Medicine, Makerere University College of Health Sciences and Endocrine unit, Mulago national referral and teaching hospital
          (3)
          Department of Medicine, Makerere University College of Health Sciences

          References

          1. Cooper DS: Hyperthyroidism. Lancet 2003, 362: 459–68. 10.1016/S0140-6736(03)14073-1PubMedView Article
          2. Sarlis JN, Gourgiotis : Thyroid Emergencies. Rev End Metab Dis 2003, 4: 129–136. 10.1023/A:1022933918182View Article
          3. Habershon SO: Exophtalmic goitre, heart disease, jaundice, death. Lancet 1874, 1: 510.View Article
          4. Vassilopoulou-Sellin R, Sellin J: The gastrointestinal tract and liver in thyrotoxicosis. In Werner and Ingbar’s the thyroid: a fundamental and clinical text. 7th edition. Edited by: Braverman LE, Utiger RD. Lippincott-Raven Publishers, Philadelphia; 1996:632–6.
          5. Choudhary AM, Roberts I: Thyroid storm presenting with liver failure. J Clin Gastroenterol 1999, 29: 318–21. 10.1097/00004836-199912000-00004PubMedView Article
          6. Hull K, Horenstein R, Naglieri R, Munir K, Ghany M, Celi FS: Two cases of thyroid storm–associated cholestatic jaundice. Endocr Pract 2007, 13: 476–480.PubMedView Article
          7. Burch HB, Wartofsky L: Life-threatening thyrotoxicosis and Thyroid storm. Endocrinol Metab Clin North Am 1993, 22: 263–77.PubMed
          8. Silva JE: Catecholamines and the sympathoadrenal system in thyrotoxicosis. In Werner and Ingbar’s the thyroid: a fundamental and clinical text. Edited by: Braveman LE, Utiger R. Lippincott Williams and Wilkins, Philadelphia PA; 2000:642–651.
          9. Bimenya GS, Olico-Okui , Kaviri D, Mbona N, Byarugaba W: Monitoring the severity of iodine deficiency disorders in Uganda. Afr Health Sci 2002,2(2):63–68.PubMed CentralPubMed
          10. Malik R, Hodgson H: The relationship between the thyroid gland and the liver. Q J Med 2002, 95: 559–569. 10.1093/qjmed/95.9.559View Article
          11. Boelaert K, Newby PR, Simmonds MJ, et al.: Prevalence and relative risk of other autoimmune diseases in subjects with autoimmune thyroid disease. Am J Med 2010, 123: 183.e1–183.e9. 10.1016/j.amjmed.2009.06.030View Article
          12. Czaja AJ, Carpenter HA, Santrach PJ, Moore SB: Genetic predispositions for the immunological features of chronic active hepatitis. Hepatology 1993, 18: 816–822. 10.1002/hep.1840180411PubMedView Article
          13. Myers RP, Cerini R, Sayegh R, et al.: Cardiac hepatopathy: clinical, hemodynamic and histologic characteristics and correlations. Hepatology 2003, 37: 393–400. 10.1053/jhep.2003.50062PubMedView Article
          14. Giallourakis CC, Rosenberg PM, Friedman LS: The liver in heart failure. Clin Liver Dis 2002, 6: 947–967. 10.1016/S1089-3261(02)00056-9PubMedView Article
          15. Williams KV, Nayak S, Becker D, Reyes J, Burmeister LA: Fifty years of experience with propylthiouracil-associated hepatotoxicity: what have we learned? J Clin Endocrinol Metab 1997, 82: 1727–33. 10.1210/jc.82.6.1727PubMed

          Copyright

          © Kibirige et al.; licensee BioMed Central Ltd. 2012

          This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://​creativecommons.​org/​licenses/​by/​2.​0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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