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Simultaneous occurrence of inflammatory bowel disease and thyroid disease
THE AMERICAN JOURNAL OF GASTROENTEROLOGY © 2001 by Am. Coll. of Gastroenterology Published by Elsevier Science Inc.
Vol. 96, No. 6, 2001 ISSN 0002-9270/01/$20.00 PII S0002-9270(01)02459-5
Simultaneous Occurrence of Inflammatory Bowel Disease and Thyroid Disease Eugene S. Bonapace, M.D., and Radhika Srinivasan, M.D. Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania
ABSTRACT We report a case of simultaneous occurrence of inflammatory bowel disease (IBD) and Graves’ disease. A review of reported cases of simultaneous onset of ulcerative colitis (UC) and autoimmune hyperthyroidism is presented. A discussion of the prevalence of thyroid disease in patients with UC and possible common autoimmune etiology is entertained. The concurrent presentation has implications for the diagnosis and treatment of both diseases. At the time of suspected initial presentation or exacerbation or preexisting IBD, we emphasize the need to consider both IBD and thyroid disease in the differential diagnosis for optimal patient management. (Am J Gastroenterol 2001;96: 1925–1926. © 2001 by Am. Coll. of Gastroenterology)
INTRODUCTION The coexistence of inflammatory bowel disease (IBD) and thyroid disease is uncommon. Case reports (1–3) and controlled studies (4, 5) have alluded to an association of IBD with autoimmune thyroid disease. In most cases the diagnosis of thyroid disease has preceded that of IBD. We report a case of ulcerative colitis (UC) and Graves’ disease with simultaneous onset, and review the literature suggesting a possible autoimmune pathogenesis.
CASE REPORT A 41-yr-old white woman developed bloody diarrhea, abdominal pain, and low-grade fever and was diagnosed with UC. At the same time, blood work and iodine-131 (I131) thyroid scintigraphy were consistent with Graves’ disease. The patient was treated with prednisone, tapazole, and propranolol with initial improvement. However, she developed recurrent diarrhea and weight loss and was transferred to our institution. She was a former smoker and had no prior history of IBD or thyroid disease. On physical examination, her blood pressure was 98/67, pulse 105, and temperature 98.0. There was no tremor, goiter or exophthalmos. The abdomen had normal bowel sounds, with no distension or tenderness. Laboratory data were significant for white blood cell counts of 14.1 K/mm3, TSH ⬍0.03 mIU/ml (0.29 – 5.10), T-uptake 41% (25–35), and ESR 85 mm/h. Sulfasalazine was added to her regimen of i.v. corticosteroids, hy-
drocortisone enemas, tapazole, propranolol, and TPN. She slowly improved after several days of additional therapy. At follow-up several months later, the patient had gained weight, was off steroids, and clinically asymptomatic from both diseases.
DISCUSSION Case reports have suggested an association between inflammatory bowel disease and autoimmune thyroid disease (1– 3). Population studies have demonstrated a 2- to 4-fold increase in the prevalence of thyroid disease in patients with UC (4, 5). In most cases, thyroid disease has preceded the diagnosis of UC; only three patients with simultaneous onset of UC and thyroid disease have been reported (Table 1). Our patient was seen for persistent diarrhea and weight loss, although the absence of abdominal tenderness, hematochezia, and fever in the setting of tachycardia made us believe that hyperthyroidism rather than IBD was predominantly responsible for her symptoms. She ultimately improved with medical management of both diseases. The association between thyroid disease and UC may suggest a common autoimmune etiology. It has been suggested that the inflamed colonic mucosa may be either the source of or a target for disease-producing factors, which may be autoantibodies or circulating immune complexes (8). Investigators have demonstrated antibodies against a colonic antigen in patients with active UC, and these antibodies may be directed at a specific colonic epithelial protein that complexes with human tropomyosin isoform 5 (9). Cross-reactivity of this antibody with epidermis, biliary and ciliary epithelium, and chondrocytes may help explain the basis for some of the extraintestinal manifestations of UC (10). However, because the colon and thyroid do not have the same embryological origin, the same trigger antibodies may not be the cause of the association between UC and Graves’ disease (5). Alterations in T-cell function in Graves’ disease may help explain this association. T-cells are critical in the induction, development and maintenance of autoimmune diseases. The Th1/Th2 balance has been shown to control physiological defense reactions against bacterial, viral, or parasitic agents. In Graves’ disease there is increased Th2 activity, resulting in circulating antibodies to TSH-R (11).
1926
Bonapace and Srinivasan
AJG – Vol. 96, No. 6, 2001
Table 1. Reported Cases of Simultaneous Onset of UC and Autoimmune Hyperthyroidism Reference
Age (yr)
Powell (6)
34
Jarnerot (5)
73
Triantafillidis (7)
42
Bonapace (current report)
41
Treatment Sex
Other History
IBD
Female Does not give specific etiology of hyperthyroidism Female Distal colitis, does not give specific etiology of hyperthroidism Male Grave’s disease, d/c tob 1 mo Female Pan-colitis, Grave’s disease, dc tob 5 yr, FHx of hypothryoidism
Thyroid
ACTH, hydrocortisone enemas*
PTU, later I131 therapy
Not specified
Antithyroid drugs, I131
5-ASA, prednisolone, sulfasalazine* Methylprednisolone, 5-ASA*
Methimazole, unimazol, lobectomy Tapazole, propranolol
ACTH ⫽ adrenocoticotropic hormone; dc ⫽ discontinued; FHx ⫽ family history; tob ⫽ tobacco. * Symptoms improved after adequate treatment of thyroid disease. No patient required surgical treatment of UC.
Increased Th2 activity may explain the antibody production that may contribute to the pathogenesis of UC and its extraintestinal manifestations. Infection seems to be an essential factor in many autoimmune diseases, as micro-organisms may provide a high concentration of cross-reactive determinants by molecular mimicry (10). Indeed, in an animal model of IBD, an oligoclonal increase in antibodies to cecal bacteria was associated with autoantibodies to tropomyosin (12). Exogenous environmental factors, including normal colonic flora, may thereby induce colonic and thyroid autoimmunity (13). In summary, the simultaneous onset of UC and Graves’ disease in a patient is presented. The concurrent presentation has clinical implications in the pathophysiology, diagnosis and treatment of both diseases. At the time of suspected initial presentation or exacerbation of IBD, one should consider both IBD and thyroid disease in the differential diagnosis. Reprint requests and correspondence: Radhika Srinivasan, M.D., Gastroenterology Section, Temple University Hospital, 3401 N. Broad Street, 8 Parkinson Pavilion, Philadelphia, PA 19140. Received Dec. 16, 1998; accepted July 7, 1999.
REFERENCES 1. Clubb JS, Black PJ, Wallace DC. An association of thyroid disease, ulcerative colitis, and diabetes mellitus: Report of three cases in young women. Aust Ann Med 1970;2:159 – 64. 2. Modebe O. Autoimmune thyroid disease with ulcerative colitis. Postgrad Med J 1986;62:475– 6. 3. Govindarajan R, Galpin OP. Coexistence of Addison’s dis-
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
ease, ulcerative colitis, hypothyroidism and pernicious anemia. J Clin Gastroenterol 1992;15:82–3. Snook LA, de Silva HJ, Jewell DP. The association of autoimmune disorders with inflammatory bowel disease. Q J Med 1989;72:835– 40. Jarnerot G, Azad Khan AK, Truelove SC. The thyroid in ulcerative colitis and Crohn’s disease. II. Thyroid enlargement and hyperthyroidism in ulcerative colitis. Acta Med Scand 1975;197:83–7. Powell J, Shapiro HA, Carbone JV. Therapeutic problems of ulcerative colitis with hyperthyroidism. Am J Gastroenterol 1968;50:116 –24. Triantafillidis JK, Cherakakis P, Zervakakis A, et al. Coexistence of hyperthyroidism and ulcerative colitis: Report of 4 cases and a review of the literature. Ital J Gastroenterol 1992; 24:494 –7. Monsen U, Sorstad J, Hellers G, et al. Extracolonic diagnoses in ulcerative colitis: An epidemiological study. Am J Gastroenterol 1990;85:711– 6. Geng X, Biancone L, Dai HH, et al. Tropomyosin isoforms in intestinal mucosa: Production of autoantibodies to tropomyosin isoforms in ulcerative colitis. Gastroenterology 1998;114: 912–22. Brandtzaeg P. Autoimmunity and ulcerative colitis: Can two enigmas make sense together? Gastroenterology 1995;109: 307–22. Roura-Mir C, Catalfamo M, Sospedra M, et al. Single-cell analysis of intrathyroidal lymphocytes show differential cytokine expression in Hashimoto’s, and Graves’ disease. Eur J Immunol 1997;27:3290 –302. Mizoguchi A, Mizoguchi E, Tonegawa S, et al. Alteration of a polyclonal to an oligoclonal immune response to cecal aerobic bacterial antigens in TCR alpha mutant mice with inflammatory bowel disease. Int Immunol 1996;8:1387–94. Penhale WJ, Young PR. The influence of the normal microbial flora on the susceptibility of rats to experimental autoimmune thyroiditis. Clin Exp Immunol 1988;72:288 –92.
Vol. 96, No. 6, 2001 ISSN 0002-9270/01/$20.00 PII S0002-9270(01)02459-5
Simultaneous Occurrence of Inflammatory Bowel Disease and Thyroid Disease Eugene S. Bonapace, M.D., and Radhika Srinivasan, M.D. Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania
ABSTRACT We report a case of simultaneous occurrence of inflammatory bowel disease (IBD) and Graves’ disease. A review of reported cases of simultaneous onset of ulcerative colitis (UC) and autoimmune hyperthyroidism is presented. A discussion of the prevalence of thyroid disease in patients with UC and possible common autoimmune etiology is entertained. The concurrent presentation has implications for the diagnosis and treatment of both diseases. At the time of suspected initial presentation or exacerbation or preexisting IBD, we emphasize the need to consider both IBD and thyroid disease in the differential diagnosis for optimal patient management. (Am J Gastroenterol 2001;96: 1925–1926. © 2001 by Am. Coll. of Gastroenterology)
INTRODUCTION The coexistence of inflammatory bowel disease (IBD) and thyroid disease is uncommon. Case reports (1–3) and controlled studies (4, 5) have alluded to an association of IBD with autoimmune thyroid disease. In most cases the diagnosis of thyroid disease has preceded that of IBD. We report a case of ulcerative colitis (UC) and Graves’ disease with simultaneous onset, and review the literature suggesting a possible autoimmune pathogenesis.
CASE REPORT A 41-yr-old white woman developed bloody diarrhea, abdominal pain, and low-grade fever and was diagnosed with UC. At the same time, blood work and iodine-131 (I131) thyroid scintigraphy were consistent with Graves’ disease. The patient was treated with prednisone, tapazole, and propranolol with initial improvement. However, she developed recurrent diarrhea and weight loss and was transferred to our institution. She was a former smoker and had no prior history of IBD or thyroid disease. On physical examination, her blood pressure was 98/67, pulse 105, and temperature 98.0. There was no tremor, goiter or exophthalmos. The abdomen had normal bowel sounds, with no distension or tenderness. Laboratory data were significant for white blood cell counts of 14.1 K/mm3, TSH ⬍0.03 mIU/ml (0.29 – 5.10), T-uptake 41% (25–35), and ESR 85 mm/h. Sulfasalazine was added to her regimen of i.v. corticosteroids, hy-
drocortisone enemas, tapazole, propranolol, and TPN. She slowly improved after several days of additional therapy. At follow-up several months later, the patient had gained weight, was off steroids, and clinically asymptomatic from both diseases.
DISCUSSION Case reports have suggested an association between inflammatory bowel disease and autoimmune thyroid disease (1– 3). Population studies have demonstrated a 2- to 4-fold increase in the prevalence of thyroid disease in patients with UC (4, 5). In most cases, thyroid disease has preceded the diagnosis of UC; only three patients with simultaneous onset of UC and thyroid disease have been reported (Table 1). Our patient was seen for persistent diarrhea and weight loss, although the absence of abdominal tenderness, hematochezia, and fever in the setting of tachycardia made us believe that hyperthyroidism rather than IBD was predominantly responsible for her symptoms. She ultimately improved with medical management of both diseases. The association between thyroid disease and UC may suggest a common autoimmune etiology. It has been suggested that the inflamed colonic mucosa may be either the source of or a target for disease-producing factors, which may be autoantibodies or circulating immune complexes (8). Investigators have demonstrated antibodies against a colonic antigen in patients with active UC, and these antibodies may be directed at a specific colonic epithelial protein that complexes with human tropomyosin isoform 5 (9). Cross-reactivity of this antibody with epidermis, biliary and ciliary epithelium, and chondrocytes may help explain the basis for some of the extraintestinal manifestations of UC (10). However, because the colon and thyroid do not have the same embryological origin, the same trigger antibodies may not be the cause of the association between UC and Graves’ disease (5). Alterations in T-cell function in Graves’ disease may help explain this association. T-cells are critical in the induction, development and maintenance of autoimmune diseases. The Th1/Th2 balance has been shown to control physiological defense reactions against bacterial, viral, or parasitic agents. In Graves’ disease there is increased Th2 activity, resulting in circulating antibodies to TSH-R (11).
1926
Bonapace and Srinivasan
AJG – Vol. 96, No. 6, 2001
Table 1. Reported Cases of Simultaneous Onset of UC and Autoimmune Hyperthyroidism Reference
Age (yr)
Powell (6)
34
Jarnerot (5)
73
Triantafillidis (7)
42
Bonapace (current report)
41
Treatment Sex
Other History
IBD
Female Does not give specific etiology of hyperthyroidism Female Distal colitis, does not give specific etiology of hyperthroidism Male Grave’s disease, d/c tob 1 mo Female Pan-colitis, Grave’s disease, dc tob 5 yr, FHx of hypothryoidism
Thyroid
ACTH, hydrocortisone enemas*
PTU, later I131 therapy
Not specified
Antithyroid drugs, I131
5-ASA, prednisolone, sulfasalazine* Methylprednisolone, 5-ASA*
Methimazole, unimazol, lobectomy Tapazole, propranolol
ACTH ⫽ adrenocoticotropic hormone; dc ⫽ discontinued; FHx ⫽ family history; tob ⫽ tobacco. * Symptoms improved after adequate treatment of thyroid disease. No patient required surgical treatment of UC.
Increased Th2 activity may explain the antibody production that may contribute to the pathogenesis of UC and its extraintestinal manifestations. Infection seems to be an essential factor in many autoimmune diseases, as micro-organisms may provide a high concentration of cross-reactive determinants by molecular mimicry (10). Indeed, in an animal model of IBD, an oligoclonal increase in antibodies to cecal bacteria was associated with autoantibodies to tropomyosin (12). Exogenous environmental factors, including normal colonic flora, may thereby induce colonic and thyroid autoimmunity (13). In summary, the simultaneous onset of UC and Graves’ disease in a patient is presented. The concurrent presentation has clinical implications in the pathophysiology, diagnosis and treatment of both diseases. At the time of suspected initial presentation or exacerbation of IBD, one should consider both IBD and thyroid disease in the differential diagnosis. Reprint requests and correspondence: Radhika Srinivasan, M.D., Gastroenterology Section, Temple University Hospital, 3401 N. Broad Street, 8 Parkinson Pavilion, Philadelphia, PA 19140. Received Dec. 16, 1998; accepted July 7, 1999.
REFERENCES 1. Clubb JS, Black PJ, Wallace DC. An association of thyroid disease, ulcerative colitis, and diabetes mellitus: Report of three cases in young women. Aust Ann Med 1970;2:159 – 64. 2. Modebe O. Autoimmune thyroid disease with ulcerative colitis. Postgrad Med J 1986;62:475– 6. 3. Govindarajan R, Galpin OP. Coexistence of Addison’s dis-
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
ease, ulcerative colitis, hypothyroidism and pernicious anemia. J Clin Gastroenterol 1992;15:82–3. Snook LA, de Silva HJ, Jewell DP. The association of autoimmune disorders with inflammatory bowel disease. Q J Med 1989;72:835– 40. Jarnerot G, Azad Khan AK, Truelove SC. The thyroid in ulcerative colitis and Crohn’s disease. II. Thyroid enlargement and hyperthyroidism in ulcerative colitis. Acta Med Scand 1975;197:83–7. Powell J, Shapiro HA, Carbone JV. Therapeutic problems of ulcerative colitis with hyperthyroidism. Am J Gastroenterol 1968;50:116 –24. Triantafillidis JK, Cherakakis P, Zervakakis A, et al. Coexistence of hyperthyroidism and ulcerative colitis: Report of 4 cases and a review of the literature. Ital J Gastroenterol 1992; 24:494 –7. Monsen U, Sorstad J, Hellers G, et al. Extracolonic diagnoses in ulcerative colitis: An epidemiological study. Am J Gastroenterol 1990;85:711– 6. Geng X, Biancone L, Dai HH, et al. Tropomyosin isoforms in intestinal mucosa: Production of autoantibodies to tropomyosin isoforms in ulcerative colitis. Gastroenterology 1998;114: 912–22. Brandtzaeg P. Autoimmunity and ulcerative colitis: Can two enigmas make sense together? Gastroenterology 1995;109: 307–22. Roura-Mir C, Catalfamo M, Sospedra M, et al. Single-cell analysis of intrathyroidal lymphocytes show differential cytokine expression in Hashimoto’s, and Graves’ disease. Eur J Immunol 1997;27:3290 –302. Mizoguchi A, Mizoguchi E, Tonegawa S, et al. Alteration of a polyclonal to an oligoclonal immune response to cecal aerobic bacterial antigens in TCR alpha mutant mice with inflammatory bowel disease. Int Immunol 1996;8:1387–94. Penhale WJ, Young PR. The influence of the normal microbial flora on the susceptibility of rats to experimental autoimmune thyroiditis. Clin Exp Immunol 1988;72:288 –92.