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An Unusual Case of Myxedema Megacolon With Features of Ischemic and Pseudomembranous Colitis

1992; Elsevier BV; Volume: 67; Issue: 4 Linguagem: Inglês

10.1016/s0025-6196(12)61554-7

1942-5546

Robin Patel, Rollin W. Hughes,

Adrenal Hormones and Disorders

Myxedema megacolon is rare; usually, it manifests with abdominal distention, flatulence, and constipation. Herein we describe a 72-year-old man who had intermittent diarrhea, bloating, and abdominal pain for more than a year. Cultures of stool specimens for Clostridium difficile enterotoxin were variably positive and negative. Colonoscopic biopsy specimens were thought to be consistent with chronic ischemia. Thyroid function tests showed severe hypothyroidism; the patient's symptoms resolved with thyroid hormone replacement. We hypothesize that gross dilatation of the colon, attributed to myxedema, was followed by intestinal ischemia and complicated by recurrent episodes of pseudomembranous colitis. A review of the relevant literature is provided. This unusual manifestation of myxedema should be considered in the differential diagnosis when a patient has diarrhea, bloating, and abdominal pain. Myxedema megacolon is rare; usually, it manifests with abdominal distention, flatulence, and constipation. Herein we describe a 72-year-old man who had intermittent diarrhea, bloating, and abdominal pain for more than a year. Cultures of stool specimens for Clostridium difficile enterotoxin were variably positive and negative. Colonoscopic biopsy specimens were thought to be consistent with chronic ischemia. Thyroid function tests showed severe hypothyroidism; the patient's symptoms resolved with thyroid hormone replacement. We hypothesize that gross dilatation of the colon, attributed to myxedema, was followed by intestinal ischemia and complicated by recurrent episodes of pseudomembranous colitis. A review of the relevant literature is provided. This unusual manifestation of myxedema should be considered in the differential diagnosis when a patient has diarrhea, bloating, and abdominal pain. A 72-year-old man who had had recurrent episodes of painful abdominal distention and bloody diarrhea for more than a year was referred to the Mayo Clinic during such an episode in October 1989. During the summer of 1989, as part of an assessment elsewhere for abdominal bloating and diarrhea, he underwent sigmoidoscopy, results of which were unremarkable; a roentgenogram revealed a dilated colon with air-fluid levels. Two weeks before he was transferred to our institution, he was rehospitalized and reassessed for abdominal bloating and bloody diarrhea. During this hospitalization, an abdominal flat plate showed an enlarged, distended colon; flexible sigmoidoscopy (to 20 cm) revealed inflamed mucosa and pseudomembranes. A stool assay for Clostridium difficile enterotoxin was positive, and the patient was treated with orally administered vancomycin and intravenously administered metronidazole. Because his condition did not improve clinically, he was transferred to the Mayo Clinic. Eight months before admission, the patient had received cephalexin and trimethoprim-sulfamethoxazole. His other medications were timolol maleate and pilocarpine hydrochloride eyedrops for glaucoma and hydrochlorothiazide (25 mg) and triamterene (50 mg) for hypertension. On admission to our institution, the patient's temperature was 36.4°C, pulse was 68 beats/min and regular, and blood pressure was 130/80 mm Hg. He was lethargic yet oriented and cooperative. On auscultation, his lungs were clear, and heart sounds were distant. His abdomen was distended and tympanitic; bowel sounds were decreased. No organomegaly was found; abdominal masses were not palpable, but bilateral inguinal hernias and edema of the scrotum were noted. In addition, he had edema of the ankles and doughy skin; deep tendon reflexes were decreased. Laboratory tests yielded the following results: hemoglobin, 11.7 g/dl; mean corpuscular volume, 97.8 fl; leukocytes, 6.9 × 103/mm3; aspartate aminotransferase, 74 U/liter; total protein, 5 g/dl; cholesterol, 87 mg/dl; and triglycerides, 173 mg/dl. An electrocardiogram revealed a normal sinus rhythm, a first-degree atrioventricular block, low-voltage QRS complexes, low anterior forces, and nonspecific T-wave abnormalities. An echocardiogram disclosed moderate pericardial effusion without evidence of tamponade. An abdominal roentgenogram showed gaseous distention of the colon, several loops of small bowel, and a horseshoe-shaped loop of colon on the left. The maximal diameter of the ascending colon was 9 cm and of the transverse colon was 8 cm (Fig. 1). An enema preparation of diatrizoate distributed to the mid-ascending colon failed to demonstrate a volvulus. An abdominal computed tomographic scan revealed dilated loops of small bowel, thickening of the wall of the descending and sigmoid colon, and pericolonic fluid (Fig. 2). Small bilateral pleural effusions were noted.Fig. 2Abdominal computed tomographic scan, revealing dilated loops of small bowel, thickening of wall of descending and sigmoid colon, and pericolonic fluid (arrow).View Large Image Figure ViewerDownload (PPT) Colonoscopy showed scattered aphthous lesions to 28 cm and circumferential ulcerations above that level; a membrane firmly adherent to the ulcerations extended to 60 cm. Examination of stool specimens revealed numerous leukocytes but few erythrocytes. Stool cultures were negative for pathogens, and C. difficile toxin was negative. Colonoscopic biopsy specimens demonstrated extensive granulation tissue that extended deeply into the wall of the colon. These biopsy specimens were thought to be consistent with chronic ischemia. Thyroid function tests showed severe hypothyroidism; the patient's total thyroxine was 0.2 μg/dl, and the sensitive thyroid-stimulating hormone was 33 mIU/liter. Thus, a regimen of levothyroxine sodium was initiated. After 6 weeks of treatment with levothyroxine, 50 mg daily, the patient's abdominal bloating and diarrhea had completely resolved (per communication with the patient's local physician). At that time, the total thyroxine was 3.7 μg/dl, and the sensitive thyroid-stimulating hormone was 16.8 mIU/liter. Unfortunately, the dose of levothyroxine could not be increased because of the onset of angina, for which the patient wished no further evaluation. Three diagnoses need to be considered in analyzing our patient's medical history. The first and principal consideration is that he had myxedema megacolon based on the finding of a megacolon, lethargy, scrotal edema, doughy skin, pericardial effusion, pleural effusions, anemia, a low level of thyroxine, an increased level of serum thyroid-stimulating hormone, and electrocardiographic findings. Our patient clearly had a megacolon, as defined by Preston and associates,1Preston DM Lennard-Jones JE Thomas BM Towards a radiologic definition of idiopathic megacolon.Gastrointest Radiol. 1985; 10: 167-169Crossref PubMed Scopus (95) Google Scholar inasmuch as the width of his transverse colon was 8 cm (in comparison with 7.8 ± 1 to 1.4 cm in their study) and the width of his ascending colon was 9 cm (in comparison with 8.2 ± 1 to 1.6 cm in their study). Myxedema was first recognized clinically by Sir William Gull2Gull WM On a cretinoid state supervening in adult life in women.Trans Clin Soc London. 1874; 7: 180-185Google Scholar in 1873, and Sir William Ord3Ord W On myxedema, a term proposed to be applied to an essential condition in the "cretinoid" affection occasionally observed in middle-aged women.Medicochir Trans. 1878; 43: 57-78Google Scholar coined the term "myxedema" after he noted mucin-yielding edema in the connective tissue. Escamilla and colleagues4Escamilla RF Lisser H Shepardson HC Internal myxedema: report of a case showing ascites, cardiac, intestinal and bladder atony, menorrhagia, secondary anemia and associated carotinemia.Ann Intern Med. 1935; 9: 297-316Crossref Google Scholar used the label "internal myxedema" to describe intestinal atony due to hypothyroidism, and Lester5Lester CW Endocrine disturbances simulating surgical conditions of the abdomen.N Y State J Med. 1937; 37: 406-409Google Scholar recognized the association of hypothyroid function and intestinal obstruction. Bastenie6Bastenie PA Paralytic ileus in severe hypothyroidism.Lancet. 1946; 1: 413-416Abstract PubMed Scopus (33) Google Scholar emphasized that myxedema can eventuate in megacolon. Typically, patients complain of distention, flatulence, and constipation. Hypotonia occurs primarily in the colon and less commonly in the esophagus, stomach, duodenum, gallbladder, small bowel, and urinary bladder.7Castleman B McNeely BU Case records of the Massachusetts General Hospital (Case 24–1965).N Engl J Med. 1965; 272: 1118-1127Crossref PubMed Google Scholar, 8Bacharach T Evans JR Enlargement of the colon secondary to hypothyroidism.Ann Intern Med. 1957; 47: 121-124Crossref PubMed Scopus (20) Google Scholar, 9Boruchow IB Miller LD Fitts Jr, WT Paralytic ileus in myxedema.Arch Surg. 1966; 92: 960-963Crossref PubMed Scopus (15) Google Scholar, 10Brown TR The effect of hypothyroidism on gastric and intestinal function.JAMA. 1931; 97: 511-513Crossref Scopus (6) Google Scholar, 11Douglass RC Jacobson SD Pathologic changes in adult myxedema: survey of 10 necropsies.J Clin Endocrinol. 1957; 17: 1354-1364Crossref PubMed Scopus (47) Google Scholar, 12Haley HB Leigh C Bronsky D Waldstein SS Ascites and intestinal obstruction in myxedema.Arch Surg. 1962; 85: 328-333Crossref Scopus (15) Google Scholar, 13Hohl RD Nixon RK Myxedema ileus.Arch Intern Med. 1965; 115: 145-150Crossref PubMed Scopus (31) Google Scholar Megacolon is characterized by massive distention of the colon; its frequency in association with myxedema varies from seldom14Watanakunakorn C Hodges RE Evans TC Myxedema: a study of 400 cases.Arch Intern Med. 1965; 116: 183-190Crossref PubMed Scopus (87) Google Scholar to 4 in 100 cases.13Hohl RD Nixon RK Myxedema ileus.Arch Intern Med. 1965; 115: 145-150Crossref PubMed Scopus (31) Google Scholar Grossly, the bowel wall becomes thickened, whitish, inelastic, and dilated. Myxedematous and cellular infiltration of the layers of the bowel wall, areas of interstitial mucoid substance, and mucosal atrophy constitute the microscopic picture.15Liechty RD Miller RF Cohen WN Myxedema causing adynamic ileus, serous effusions, and inappropriate secretion of antidiuretic hormone.Surg Clin North Am. October 1970; 50: 1087-1098PubMed Google Scholar The pathogenesis of myxedema megacolon is unsettled.16Solano Jr, FX Starling RC Levey GS Myxedema megacolon (editorial).Arch Intern Med. 1985; 145: 231Crossref PubMed Scopus (9) Google Scholar Wells and co-workers17Wells I Smith B Hinton M Acute ileus in myxoedema.Br Med J. 1977; 1: 211-212Crossref PubMed Scopus (31) Google Scholar attribute it to a neuropathy or a plexopathy. Douglass and Jacobson11Douglass RC Jacobson SD Pathologic changes in adult myxedema: survey of 10 necropsies.J Clin Endocrinol. 1957; 17: 1354-1364Crossref PubMed Scopus (47) Google Scholar believe that the interstitial mucoid substance represents mucopolysaccharides that separate the muscle fibers from the ganglia of Auerbach's plexus and result in atony. In colonic manometric studies in 20 patients affected with refractory constipation and myxedema, Duret and Bastenie18Duret RL Bastenie PA Intestinal disorders in hypothyroidism: clinical and manometric study.Am J Dig Dis. 1971; 16: 723-727Crossref PubMed Scopus (50) Google Scholar concluded that the intestinal muscle undergoes degeneration in some patients. Radiographically, patients with myxedema may have distended loops of colon and small bowel that contain numerous air-fluid levels,19Moss AA Goldberg HI Intestinal pseudo-obstruction.CRC Crit Rev Radiol Sci. 1972; 3: 363-387PubMed Google Scholar as did our patient. In radiographic contrast studies in 15 patients with myxedema, Burrell and associates20Burrell M Cronan J Megna D Toffler R Myxedema megacolon.Gastrointest Radiol. 1980; 5: 181-186Crossref PubMed Scopus (12) Google Scholar noted that 4 had simple megacolon and 3 had megacolon with "transverse ridging," which was attributed to submucosal infiltration with myxoid material.7Castleman B McNeely BU Case records of the Massachusetts General Hospital (Case 24–1965).N Engl J Med. 1965; 272: 1118-1127Crossref PubMed Google Scholar Our patient did not undergo a barium enema examination. Biopsy specimens from our patient's sigmoid colon showed extensive granulation tissue that extended deep into the wall of the colon. The manifestations suggest chronic ischemia. Kale and Woodward21Kale VR Woodward DAK Ischaemic colitis due to myxoedema (letter to the editor).Br Med J. 1974; 3: 42-43Crossref PubMed Scopus (2) Google Scholar described a case of ischemic colitis attributed to myxedema in a 53-year-old woman who had long-term constipation, abdominal distention, and clinical features of myxedema. At laparotomy, the transverse colon was dilated and necrotic, particularly at the splenic flexure. The affected area of the bowel demonstrated histologic features of acute ischemic colitis; the patient recovered after resection of the necrotic segment and treatment with thyroxine. Perhaps a similar, but less severe, situation occurred in our patient. We postulate that gross dilatation of the colon resulted in ischemia of the bowel and that bacterial invasion ensued. (Recall that the patient had pseudomembranous colitis when he was hospitalized in his hometown.) Both necrosis and bacterial invasion could occur if the blood supply is sufficient to prevent transmural necrosis but insufficient to maintain a mucosal barrier.22Marston A Pheils MT Thomas ML Morson BC Ischaemic colitis.Gut. 1966; 7: 1-15Crossref PubMed Scopus (334) Google Scholar A second explanation for our patient's symptoms is primary pseudomembranous colitis. Typically, it develops 5 to 10 days after antimicrobial therapy has been instituted, although cases have been reported as late as 8 weeks after completion of treatment.23Baker SW Vandivier JM Pseudomembranous colitis: case report and review of the literature.Indiana Med. 1987; 80: 1162-1164PubMed Google Scholar Agents most commonly implicated are ampicillin, cephalosporins, and clindamycin, although most antimicrobial agents may be involved. Our patient had not received antibiotic therapy for 8 months. Pseudomembranous colitis was first described in 1893,24Finney JMT Gastro-enterostomy for cicatrizing ulcer of the pylorus.Johns Hopkins Hosp Bull. 1893; 4: 53-55Google Scholar clearly before the era of antibiotic agents. It has been associated with several conditions such as abdominal operation, spinal fracture, intestinal obstruction, cancer, hemolytic-uremic syndrome, inflammatory bowel disease, Hirschsprung's disease, shigellosis, and intestinal ischemia. On the basis of a study by George,25George WL Antimicrobial agent-associated colitis and diarrhea: historical background and clinical aspects.Rev Infect Dis. 1984; 6: S208-S213Crossref PubMed Google Scholar in many of these cases the development of pseudomembranous colitis most likely represents a response of the bowel to profound ischemia. Our patient's symptoms of intermittent abdominal bloating and pain for more than a year were atypical for pseudomembranous colitis.26Tedesco FJ Barton RW Alpers DH Clindamycin-associated colitis: a prospective study.Ann Intern Med. 1974; 81: 429-433Crossref PubMed Scopus (495) Google Scholar Fever and a megacolon can be associated with pseudomembranous colitis, but the findings on biopsy were more supportive of chronic ischemia. Our patient's symptoms did not resolve with vancomycin therapy, which usually provides a 97% response rate for pseudomembranous colitis.27Bartlett JG Clostridium difficile: clinical considerations.Rev Infect Dis. 1990; 12: S243-S251Crossref PubMed Scopus (185) Google Scholar Intravenous administration of metronidazole is also thought to be effective treatment.23Baker SW Vandivier JM Pseudomembranous colitis: case report and review of the literature.Indiana Med. 1987; 80: 1162-1164PubMed Google Scholar Because our patient's stool specimen was positive for C. difficile enterotoxin, we thought he had pseudomembranous colitis; however, because this condition was likely attributable to myxedema, it did not completely resolve with the usual treatment. Subacute ischemic colitis is the third diagnostic consideration in our patient. Certainly, this condition could explain the abdominal pain and bloody diarrhea as well as the findings on colonoscopy and results of biopsy. The fact that he had symptoms of bloating for a year is difficult to explain with ischemic colitis alone. Ischemic colitis is confirmed by the finding of mucosal ischemia by endoscopy or contrast examination. Most episodes (85%) are mild, transient, and reversible. Angiography is unnecessary for diagnosis or management. Proper therapy is symptomatic support. Most patients heal within a few days, although rarely the problem may become chronic.28Williams Jr, LF Mesenteric ischemia.Surg Clin North Am. April 1988; 68: 331-353PubMed Google Scholar Dilatation of the colon is not explained by ischemic colitis alone.29Reeders JWAJ Rosenbusch G Tytgat GNJ Radiological aspects of ischaemic colitis: a review.Diagn Imaging. 1981; 50: 4-16PubMed Google Scholar We considered the ischemic colitis as a secondary event that compounded the myxedema megacolon. We treated our patient with orally administered thyroxine. Reports in the literature describe the use of intravenous infusions of triiodothyronine30Batalis T Muers M Royle GT Treatment with intravenous triiodothyronine of colonic pseudo-obstruction caused by myxoedema.Br J Surg. 1981; 68: 439Crossref PubMed Scopus (9) Google Scholar for managing myxedema megacolon; however, with regard to our patient's age and duration of the hypothyroidism and megacolon,31Borrie MJ Cape RDT Troster MM Fung ST Myxedema megacolon after external neck irradiation.J Am Geriatr Soc. 1983; 31: 228-230PubMed Google Scholar we thought we should proceed with caution. The fact that our patient's symptoms resolved after thyroid hormone replacement supports our hypothesis that myxedema was the primary diagnostic consideration. Myxedema megacolon is rare. Usually, it manifests with abdominal distention, flatulence, and constipation; however, we report a possible case associated with diarrhea. One explanation is that gross dilatation of the colon was followed by intestinal ischemia and complicated by recurrent episodes of pseudomembranous colitis.