Cronkhite-Canada syndrome with hypothyroidism.

Abstract: Cronkhite-Canada syndrome is a rare, noninherited gastrointestinal polyposis syndrome associated with characteristic ectodermal abnormalities. This report describes a 60-year-old female who was diagnosed with Cronkhite-Canada syndrome with hypothyroidism after presenting with chronic diarrhea, alopecia, intermittent abdominal pain, generalized gastrointestinal polyposis, hyperpigmentation, and nail dystrophy. Endoscopic examination of the stomach and duodenum showed multiple sessile polyps and mucosal erosion associated with evidence of chronic inflammation. Colonoscopy also revealed mucosal edema and diffuse polyposis.

Key Words: Cronkhite-Canada syndrome, hypothyroidism, polyp

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Cronkhite-Canada syndrome (CCS) is an acquired, nonfamilial syndrome characterized by diffuse gastrointestinal polyposis with alopecia, nail dystrophy, and hyperpigmentation. (1,2) The underlying cause of this syndrome remains obscure. The optimal therapy for CCS is not known, but several treatment options such as nutritional support, antibiotics, corticosteroids, anabolic steroids, histamine-receptor antagonists, and surgical treatment have all been used, with varying degrees of success. (3,4)

Case Report

We report the case of a 60-year-old female who presented with chronic diarrhea, alopecia, intermittent abdominal pain, generalized gastrointestinal polyposis, hyperpigmentation, nail dystrophy, and a 10-kg weight loss over a 6-month period. She had a history of chronic coronary heart disease for 10 years and hyperlipidemia for 4 years. Her family history was noncontributory. Physical examination revealed her face, palms, and the back of her hands and soles of her feet to be deeply hyperpigmented with small, dark brown spots, and her nails revealed dystrophy. Generalized hair loss was noted on the scalp, eyebrows, face, axilla, and groin.

Laboratory values included complete blood count, serum electrolytes, urea nitrogen, creatinine, cholesterol, triglycerides, alpha fetoprotein, carcinoembryonic antigen, carbohydrate 19-9, and routine tests of urine and feces, which were all normal. Serum total protein was 5.39 g/dL, with 3.23 g/dL of albumin. Tests for thyroid and adrenal function, serum thyroxine ([T.sub.3]), thyroid-stimulating hormone, and adrenocorticotropic hormone were elevated, and free tri-iodothyronine ([T.sub.4]) was decreased. Serum cortisol and urine 17-hydroxycorticosteroid, 17-ketosteroid, and titers of serum antithyroglobulin antibodies and antibodies to thyroid peroxidase were also normal. Endoscopic examination of the stomach showed multiple sessile polyps throughout the entire stomach and duodenum, varying in size from 2 to 10 mm (Fig. 1). Histopathologic examination of these polyps revealed mucosal erosion associated with evidence of chronic inflammation. Colonoscopy also revealed mucosal edema and diffuse polyposis; most polyps measured less than 25 mm, and the polyps were typically nonneoplastic inflammation (Fig. 2). A computed tomography scan of the adrenal gland and ultrasound sonography of the abdominal cavity revealed no abnormal findings.

The combination of symptoms and findings led to a diagnosis of CCS. Because so little is known regarding the cause of the disorder, treatment is symptomatic, and therapeutic regimens have included vitamin supplementation and nutritional support to correct fluid, electrolyte, and protein loss. Corticosteroid drugs were not used for reducing intestinal inflammation in this case because of patient refusal. A proton pump inhibitor was used to inhibit the acid secretion and provide gastric mucosal protection. Antibiotics were given to suppress bacterial overgrowth in the intestines. One week later, the patient's diarrhea decreased in severity. Her appetite improved, and her dermatologic manifestations gradually resolved.

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Discussion

In 1955, Cronkhite and Canada described the syndrome that bears their names. (1) CCS is characterized by the presence of diffuse gastrointestinal (GI) polyposis, dystrophic changes in the fingernails, alopecia, cutaneous hyperpigmentation, diarrhea, weight loss, abdominal pain, and other GI complications such as protein-losing enteropathy and malnutrition.

Conclusion

The exact cause of CCS is not known, although it is not thought to be genetic in origin. CCS affects more females than males, with a ratio of approximately 1.5:1, and the age of onset is during middle to old age. Worldwide, about 200 cases of CCS have been reported in the medical literature. Of these, more than 100 cases were reported from Japan. (5) CCS has rarely been reported in China, especially in association with hypothyroidism, (6,7) so supplementation with L-[T.sub.4] was scheduled to improve the symptoms of hypothyroidism. A partial recovery after administration of prednisolone suggests that it may be effective in preventing leakage of plasma protein into the GI tract, but randomized placebo-controlled trials are needed to prove the efficacy of these therapies. Further investigation of the histopathologic features of the associated alopecia may determine its cause.

Accepted November 18, 2004.

References

1. Zugel N, Tannapfel A, Lembcke O. Cronkhite-Canada syndrome: epidemiology, symptoms, morphology and therapy based on a case report and literature review. Chirurg 1997;68:710-714.

2. Ward EM, Wolfsen HC. Review article: the non-inherited gastrointestinal polyposis syndromes. Aliment Pharmacol Ther 2002;16:333-342.

3. Ward EM, Wolfsen HC. Pharmacological management of Cronkhite-Canada syndrome. Expert Opin Pharmacother 2003;4:385-389.

4. Chadalavada R, Brown DK, Walker AN, et al. Cronkhite-Canada syndrome: sustained remission after corticosteroid treatment. Am J Gastroenterol 2003;98:1444-1446.

5. Goto A. Cronkhite-Canada syndrome: epidemiological study of 110 cases reported in Japan. Nippon Geka Hokan 1995;64:3-14.

6. Pal A, Sen S, Ghosh S, et al. Cronkhite-Canada syndrome with hypothyroidism. Indian J Gastroenterol 1990;9:229-230.

7. Storset O, Todnem K, Waldum HL. A patient with Cronkhite-Canada syndrome, myxedema and muscle atrophy. Acta Med Scand 1979;205:343-346.

RELATED ARTICLE: Key Points

* Cronkhite-Canada syndrome is a rare and noninherited gastrointestinal polyposis syndrome associated with characteristic ectodermal abnormalities.

* This report describes a 60-year-old female who was diagnosed with Cronkhite-Canada syndrome with hypothyroidism.

* Endoscopic examination showed multiple sessile polyps in the stomach, duodenum, and colon.

* Treatment is symptomatic and to effectively improve the patient's diarrhea and dermatologic manifestations.

* The cause and pathogenic features of this syndrome needed to be investigated gradually.

Mei Qiao, PhD, Zhang Lei, MD, Hu Nai-Zhong, MD, and Xu Jian-Ming, PhD

From the Digestive Department, The First Affiliated Hospital of Anhui Medical University, Heifei, China.

Reprint requests to Prof. Xu Jian-Ming, Post Code 230032, 281 Jixi Road, Digestive Department of The First Affiliated Hospital Anhui Medical University, Hefei City, Anhui Province, China. Email: [e-mail]