Clinical Case Summary
Cronkhite-Canada Syndrome (CCS) is a rare, non-hereditary gastrointestinal polyposis syndrome characterized by gastrointestinal polyps, onychodystrophy, hyperpigmentation, and alopecia1. We report a case of CCS associated with primary hypothyroidism and elevated serum IgG-4 levels, which, while not a typical feature, has been sporadically reported in association with the syndrome2-6.
A male patient in his late 70s presented with a 1-month history of dysgeusia, asthenia, and a 4-month history of unexplained weight loss (15 kg). Medical history included type 2 diabetes, Crohn's disease (CD), chronic obstructive pulmonary disease, and chronic kidney disease. Physical examination showed onychodystrophy, hyperpigmentation, and bilateral pitting edema. Differential diagnoses were considered in relation to these multiple comorbidities, namely uncontrolled diabetes, CD flare-up, or worsening of kidney disease.
Laboratory tests revealed marked hypothyroidism (TSH: 230 mcg/L, FT4: <0.42 ng/dL), hypoalbuminemia (25.5 g/L), and elevated serum IgG-4 levels (151.26 mg/dL; normal range 3.92–86.4 mg/dL). Thyroid autoantibodies were negative. Colonoscopy showed diffuse adenomatous and hamartomatous-like sessile polyps with histology revealing eosinophilic inflammation and glandular hyperplasia. Gastroscopy with biopsies showed striking foveolar hyperplasia and marked edema of lamina propria, with normal duodenal mucosa.
The patient met clinical and endoscopic diagnostic criteria for CCS7, leading to the revocation of the prior CD diagnosis. Treatment included prednisone (50 mg/day) and levothyroxine (50 mcg/day) with nutritional support.
This case underscores the diagnostic challenges of CCS, particularly in the context of prior CD misdiagnosis. The association with hypothyroidism and elevated IgG-4 levels suggests a potential autoimmune component, emphasizing the need for a comprehensive evaluation and a multidisciplinary treatment approach.
References
1. Cronkhite, Canada. Generalized Gastrointestinal Polyposis: An Unusual Syndrome of Polyposis, Pigmentation, Alopecia and Onychotrophia. June 1955.
2. Størset, Ø, Todnem, K, Waldum, L, Burhol, P. G., Kearney, M. S. A Patient with Cronkhite-Canada Syndrome, Myxedema and Muscle Atrophy. 1979. doi:10.1111/j.0954-6820.1979.tb06060.x
3. Jones AF, Paone DB. Canada-Cronkhite syndrome in an 82-year-old woman. The American Journal of Medicine. 1984;77(3):555-557. doi:10.1016/0002-9343(84)90120-7
4. Dawra S, Sharma V, Dutta U. Clinical and Endoscopic Remission in a Patient With Cronkhite-Canada Syndrome. Clinical Gastroenterology and Hepatology. 2018;16(8):e84-e85. doi:10.1016/j.cgh.2017.09.023
5. Burnell RH. CRONKHITE‐CANADA SYNDROME. Medical Journal of Australia. 1976;1(11):347-348. doi:10.5694/j.1326-5377.1976.tb140664.x
6. Qiao Mei, Lei Zhange, Nai-Zhong Hu. Cronkhite-Canada Syndrome With Hypothyroidism. doi:10.1097/01.SMJ.0000157528.71614.C4
7. Hokari R, Hisamatsu T, eds. Atlas of Cronkhite-Canada Syndrome. Singapore: Springer Nature Singapore; 2022. doi:10.1007/978-981-19-0652-7
