A UNIQUE PRESENTATION OF THYROID STORM AND MYOPERICARDITIS IN A YOUNG MUSCULAR MAN

Transcription

1 Case Report A UNIQUE PRESENTATION OF THYROID STORM AND MYOPERICARDITIS IN A YOUNG MUSCULAR MAN Gina M. Mathew, MD 1 ; Aleida Rodriguez, MD 2* ; Lima Lawrence, MD 2* ; Kavita P. Krishnasamy, MD 2 ; Rajinder S. Marok, MD 3 ; Sunil Pauwaa, MD 2 ; Muhyaldeen Dia, MD 2 ; Gregory P. Macaluso, MD 2 ; Erin Dana Drever, MD 2 ; Tahira Yasmeen, MD, FACE 2 ABSTRACT Objective: Thyroid storm represents the extreme manifestation of thyrotoxicosis and is a medical emergency with a high mortality rate. The clinical manifestations of a severely thyrotoxic state can be devastating, and its most significant effects occur in the cardiovascular system. Cardiac involvement is the leading cause of death in patients with thyroid storm. We report a unique case of thyroid storm precipitated by viral myopericarditis in the setting of exogenous thyroid hormone supplementation. Methods: Case report and review of the literature. Results: We report a case of a previously healthy 26-year-old male with a history of bodybuilding who developed thyroid storm with multi-organ failure, including acute-onset congestive heart failure, leading to cardiogenic shock. Investigations revealed ingestion of exogenous thyroid hormone as the source of his thyrotoxicosis. Initial labs revealed serum thyroid-stimulating hormone mu/l, free thyroxine 2.3 ng/dl, free triiodothyronine 8.8 pg/ml, total triiodothyronine of 2.22 ng/ ml, and thyroglobulin 4.4 ng/ml. There was also evidence of viral myopericarditis, as demonstrated on cardiac imaging and multiple elevated Coxsackie virus B titer levels. Submitted for publication July 6, 2015 Accepted for publication April 21, 2016 From the 1 University of Illinois at Chicago, Department of Endocrinology, Chicago, Illinois, 2 UIC Advocate Christ Medical Center, Department of Internal Medicine, Oak Lawn, Illinois, and 3 Advocate Illinois Masonic Medical Center, Chicago, Illinois. *Both of these authors are considered second-authors Address correspondence to Dr. Lima Lawrence, UIC Advocate Christ Medical Center, Department of Internal Medicine, 4440 West 95th Street, Oak Lawn, Illinois limalawrence@gmail.com DOI: /EP15911.CR To purchase reprints of this article, please visit: Conclusion: Given the patient s underlying thyrotoxic state from exogenous thyroid hormone ingestion, we believe that his acute myopericarditis was the catalyst that precipitated his thyroid storm. The combination of acute myopericarditis and thyroid storm ultimately led to cardiogenic shock. He showed rapid improvement with cardiopulmonary supportive efforts and treatment for thyroid storm. In considering the etiology of thyroid storm, it is important to exclude the possibility of exogenous thyroid hormone ingestion, especially in the setting of nonregulated, over-the-counter, bodybuilding, or weight-loss supplement use. (AACE Clinical Case Rep. 2017;3:e74-e78) Abbreviations: MRI = magnetic resonance imaging; SSKI = supersaturated potassium iodide; T3 = triiodothyronine; T4 = thyroxine INTRODUCTION Thyroid storm is a life-threatening syndrome caused by excessive amounts of thyroid hormone. The clinical presentation includes fever, agitation, tachycardia, nausea, vomiting, diarrhea, and heart failure. Thyroid storm causes a profound alteration of the cardiovascular system by causing a decrease in systemic vascular resistance and an increase in the heart rate, left ventricular contractility, and blood volume (1). These effects correlate with an increase in the basal metabolic rate, thus resulting in a hyperdynamic circulatory state (1). The underlying etiology of the thyrotoxicosis is most commonly due to an endogenous source of thyroid hormone, as seen in Graves disease, multinodular goiter, or thyroiditis. Rarely, thyrotoxicosis can result from an exogenous source of thyroid hormone (2), and fatalities related to dietary supplements adulterated with thyroid hormone have been reported (3). The e74 AACE CLINICAL CASE REPORTS Vol 3 No. 1 Winter 2017

2 Thyroid Storm and Myopericarditis, AACE Clinical Case Rep. 2017;3(No. 1) e75 transition from thyrotoxicosis to life-threatening thyroid storm requires a superimposed insult; precipitating factors include infection, parturition, surgery, major trauma, iodine exposure from radiocontrast dyes, or amiodarone (4). Here, we present a rare case of thyroid storm likely precipitated by myopericarditis in the setting of exogenous thyroid hormone supplementation. CASE REPORT A 26-year-old previously healthy male with no significant past medical history presented with sudden onset of chest pain and vomiting. He took no prescription medications but worked in a health foods store and reportedly took supplements for muscle enhancement. On initial presentation to an outside hospital, he was hemodynamically stable with an unremarkable physical examination. Initial laboratory studies revealed normal serum chemistry and renal function, an elevated white blood cell count of /µl (normal, 4.2 to /µl) with left shift, elevated aspartate aminotransferase 363 units/l (normal, <38 units/l), alanine aminotransferase 90 units/l (normal, <79 units/l), and an elevated troponin 1 level of 78 ng/ml (normal, <0.05 ng/ml). An electrocardiogram revealed diffuse ST segment elevation with diffuse PR depression. Transthoracic echocardiogram revealed global hypokinesis with left ventricular ejection fraction of 45 to 50%. Additional testing included a normal coronary angiography. The patient decompensated hemodynamically within hours. He developed acute heart failure progressing to cardiogenic shock and respiratory decompensation requiring intubation. This necessitated transfer to our cardiac unit and placement of an intra-aortic balloon pump (IABP). The patient s physical examination revealed a temperature of 38.8 C, heart rate of 145 beats per minute, blood pressure of 75/41 mm Hg, respiratory rate of 16 breaths per minute, and oxygen saturation of 99% on mechanical ventilation. Cardiovascular examination revealed tachycardia and regular rhythm without gallops or murmurs. Skin was flushed without evidence of pretibial myxedema, and no exophthalmos or thyromegaly was noted. Additional laboratory studies included thyroid function evaluation, which revealed an undetectable thyroid-stimulating hormone of mu/l (normal, 0.35 to 5.0 mu/l), free triiodothyronine (T3) of 8.8 pg/ml (normal, 2.2 to 4.0 pg/ml), free thyroxine (T4) of 2.8 ng/dl (normal, 0.8 to 1.5 ng/dl), and total T3 of 2.22 ng/ml (normal, 0.6 to 1.81 ng/ml) (Table 1). Patient s Burch-Wartofsky score was calculated to be 75, which was highly suggestive of thyroid storm (5). Treatment for thyroid storm immediately followed with methimazole 20 mg every 6 hours, supersaturated potassium iodide (SSKI) 300 mg three times daily, and hydrocortisone 100 mg every 6 hours. Due to severe hypotension requiring vasopressors, beta blockers were not administered. On day 2 of admission, patient became afebrile and less tachycardic. The patient s supplement regimen was reviewed and found to include liothyronine (T3) 25 µg up to three times per day, an over-the-counter supplement which was advertised as a muscle builder, and testosterone 200 mg intramuscularly twice per week. On day 3, a low thyroglobulin level was reported at 4.4 ng/ml (normal, 1.2 to 35.0 ng/ml), consistent with exogenous administration of thyroid hormone as the etiology for his thyrotoxicosis. In addition, patient had normal levels of anti-thyroglobulin antibody of <0.9 units/ml (normal, 0.0 to 4.0 units/ml), thyrotropin-binding inhibitory immunoglobulin (<1.0 units/ml), thyroid-stimulating immunoglobulin of 100 units/ml (normal, <150 units/ml), normal testosterone level of mg/dl (normal, 280 to 1,100 ng/dl), and a normal human chorionic gonadotropin level of <2 miu/ml. Overall trend of thyroid function tests in hospital and outpatient follow-up are noted in Table 1 and Figure 1. Follow-up transthoracic echocardiogram demonstrated a reduced left ventricular systolic function with an improvement in ejection fraction from 37 to 45%. Magnetic resonance imaging (MRI) of the heart showed evidence of diffuse myocardial inflammation with multifocal areas of dense epicardial and myocardial fibrosis involving all heart segments, along with diffuse late gadolinium enhancement of the pericardium, diagnostic of myopericarditis and TSH ( mu/l) Table 1 Trend of Thyroid Function Free T4 ( ng/dl) Free T3 ( pg/ml) Total T3 ( ng/ml) Day Day Day Day Day month follow-up Abbreviations: T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone.

3 e76 Thyroid Storm and Myopericarditis, AACE Clinical Case Rep. 2017;3(No. 1) Fig. 1. Thyroid hormone levels. T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone. suggestive of viral myopericarditis, noted in Figure 2. Viral titers were sent to investigate an etiology for the patient s cardiac involvement. The patient markedly improved by day 4 and was extubated with discontinuation of vasopressors and IABP. Titers for viruses remained negative, except for an elevated Coxsackie virus B titer level of 1:640 (normal, 1:10) that was confirmed by repeat testing. Patient s methimazole dose was lowered to 10 mg every 12 hours and discontinued 1 day later along with SSKI. The hydrocortisone dose was tapered and discontinued. DISCUSSION Thyroid storm is a life-threatening manifestation of hyperthyroidism. We report a case of a healthy 26-year-old bodybuilder who presented with thyroid storm and acute decompensated heart failure. The diagnosis of thyroid storm is made clinically based on a constellation of signs and symptoms. Oftentimes, the Burch-Wartofsky score (5) is used as an aid in the diagnosis of thyroid storm. However, this score gives a likelihood that the patient indeed has thyroid storm and is not a concrete set of diagnostic criteria. Newer criteria have been suggested, as those proposed by Akamizu et al (6) in 2012 reviewing the most common clinical presentations of thyroid storm in Japanese patients, which suggested that different combinations of symptoms (central nervous system, gastrointestinal, cardiac, and vital sign abnormalities) could categorize a patient as having definite versus suspected thyroid storm. By either of these suggested criteria, our patient s clinical picture was consistent with thyroid storm. Differential diagnoses of the patient s clinical presentation included thyroid storm from underlying Graves disease, iodine-induced thyrotoxicosis from cardiac catheterization, thyroiditis, and thyrotoxicosis from exogenous use of T3 and T4. The patient s work-up reflected exogenous thyroid hormone use causing thyrotoxicosis given the elevated T3 and T4 levels with low thyroglobulin. The patient admitted consuming liothyronine and testosterone, which he purchased via the Internet. The liothyronine and testosterone bottles read, product is not for human use for research/laboratory use only. Additionally, he was taking over-the-counter bodybuilding supplements containing beta-hydroxy-beta-methylbutyrate, advertised as a metabolism booster and believed to attenuate protein breakdown after exercise (7). These substances are very poorly regulated, and the true composition and concentration of the dose ingested are unknown. Over-the-counter supplements without U.S. Food and Drug Administration regulation have a notorious history of undisclosed ingredients, with several studies showing levels of animal thyroid hormone in supplements advertised for weight loss or as metabolism boosters (3,7). We believe that his supplements contained T4, thus explaining why both T3 and T4 levels were elevated. His testosterone use may have also contributed to his thyrotoxicosis given its role in reduction of thyroid-binding globulin, potentially increasing his unbound thyroid hormone levels (8). The main determinant in elucidating the etiology of this patient s thyrotoxicosis was his thyroglobulin level, as measured by chemiluminescence immunoassay. In addition, thyroid hormone was quickly cleared from his system even as thyroid storm treatment was discontinued, suggest-

4 Thyroid Storm and Myopericarditis, AACE Clinical Case Rep. 2017;3(No. 1) e77 A B C Fig. 2. Cardiac magnetic resonance imaging. A, T2-weighted imaging shows abnormal signal intensity throughout the myocardium. B & C, Late gadolinium imaging showing diffused patchy epicardium, myocardium enhancement, and diffused enhancement and thickening of the pericardium. ing that he did not have an underlying endogenous source of thyroid hormone. Patient was started on the standard of care treatment for thyroid storm. To decrease thyroid hormone production, he was given thionamide methimazole. To decrease thyroid hormone release, SSKI was administered. Hydrocortisone was included given its properties for modest reduction of peripheral T4 to T3 conversion. The beta blocker propranolol has the theoretical benefit of decreased peripheral T4 to T3 conversion; however, it was not used due to severe hypotension (9). Other treatment options include plasmapheresis and therapeutic plasma exchange, which can quickly reduce the levels of thyroid hormone within several hours (9). This can be considered in cases of exogenous thyroid hormone ingestion, when euthyroidism needs to be restored very quickly, or when the patient has contraindications to all other therapeutic options (10,11). Another choice is oral cholestyramine resin, which binds to T4 and T3, preventing enterohepatic recirculation, leading to excretion (9). Both options were considered in our patient; however, given his rapid clinical improvement, they were not required. The unique features of this case are the associated cardiac findings. The toxic effects of elevated thyroid hormone, specifically T3, on the heart have been well documented. The additive effects of decreased systemic vascular resistance, increased heart rate, increased left ventricular contractility, and increased blood volume lead to a state of increased cardiac output as high as 300% in the hyperthyroid patient (2). In addition, the development of pulmonary arterial hypertension leading to right heart failure has also been described in thyrotoxicosis (2). This may explain the congestive hepatopathy noted in our patient. Our patient s cardiac MRI was diagnostic of myopericarditis, which is not a common cardiac finding in the setting of thyroid storm. Direct inflammation of the pericardium and myocardium can be cytolytic and cytotoxic, with varying degrees of myocyte injury depending on the immune response. Clinical presentations reflect this gradation of variability (12). There have been case reports of myocarditis or pericarditis and thyroid storm in the setting of an underlying autoimmune thyroid disease. Chen et al (13) described a case of thyroid storm and lymphocytic myocarditis which resulted in the patient s death. However, this patient s anti thyroid peroxidase antibodies were elevated, suggesting an underlying autoimmunity which led to lymphocytic infiltration of the myocardium. This differs from our patient in that he had negative anti thyroid peroxidase antibodies and an exogenous source of thyrotoxicosis. Another case report described thyroid storm and acute pericarditis in a patient with antibodypositive Graves disease (14). Viral serologies in our patient revealed very high titers of Coxsackie virus, drawn on two occasions. Coxsackie virus is one of the common causes of viral myopericarditis in developed countries (12). We believe that this patient developed an acute myopericarditis from Coxsackie virus infection. Given his underlying thyrotoxic state from exogenous thyroid hormone ingestion, we believe that his acute myopericarditis was the catalyst that precipitated his thyroid storm. The combination of acute myopericarditis and thyroid storm ultimately led to acute heart failure and cardiogenic shock. He showed rapid improvement with cardiopulmonary supportive efforts and treatment for thyroid storm. CONCLUSION In considering the etiology of thyroid storm, it is important to exclude the possibility of exogenous thyroid

5 e78 Thyroid Storm and Myopericarditis, AACE Clinical Case Rep. 2017;3(No. 1) hormone ingestion. One should be particularly suspicious in the setting of nonregulated, over-the-counter, bodybuilding, or weight-loss supplement use. ACKNOWLEDGMENT We thank Dr. Jason Craft for his assistance in obtaining the cardiac MRI images. DISCLOSURE The authors have no multiplicity of interest to disclose. REFERENCES 1. Woeber K. Thyrotoxicosis and the heart. N Engl J Med. 1992;327: Dahl P, Danzi S, Klein I. Thyrotoxic cardiac disease. Curr Heart Fail Rep. 2008;5: Poon WT, Ng SW, Lai CK, Chan YW, Mak WL. Factitious thyrotoxicosis and herbal dietary supplement for weight reduction. Clinical Toxicol (Phila). 2008:46: Chiha M, Samarasinghe S, Kabaker AS. Thyroid storm: an updated review. J Intensive Care Med. 2015;30: Burch HB, Wartofsky L. Life-threatening thyrotoxicosis. Thyroid storm. Endocrinol Metab Clin North Am. 1993; 22: Akamizu T, Satoh T, Isozaki O, et al. Diagnostic criteria, clinical features, and incidence of thyroid storm based on nationwide surveys. Thyroid. 2012;22: Garg M, Hooda M. A recent update on undeclared chemicals in herbal formulations. J Pharm Biomed Sci. 2011;9:5. 8. Bisschop PH, Toorians AW, Edert E, Wiersinga WM, Gooren LJ, Fliers E. The effects of sex-steroid administration on the pituitary-thyroid axis in transsexuals. Eur J Endocrinol. 2006;155: Klubo-Gwiezdzinska J, Wartofsky L. Thyroid emergencies. Med Clin North Am. 2012;96: Ozbey N, Kalayoglu-Besisik S, Gul N, Bozbora A, Sencer E, Molvalilar S. Therapeutic plasmapheresis in patients with severe hyperthyroidism in whom antithyroid drugs are contraindicated. Int J Clin Pract. 2004;58: Jha S, Waghdhare S, Reddi R, Bhattacharya P. Thyroid storm due to inappropriate administration of a compounded thyroid hormone preparation successfully treated with plasmapheresis. Thyroid. 2012:22; Imazio M, Trinchero R. Myopericarditis: Etiology, management, and prognosis. Int J Cardiol. 2008;127: Chen YT, Yang GG, Hsu YH. Thyroid storm and lymphocytic myocarditis. Intern Med. 2010;49: Tsai M-S, Yang C-W. Acute pericarditis: a rare complication of Grave s thyrotoxicosis? Am J Emerg Med. 2006;24: