Ileal perforation in a patient with Crohn’s disease while receiving recombinant human growth hormone therapy

Abstract

Dear Editor: Crohn’s disease manifests systemically and is commonly followed by a chronic catabolic state. Treatment with glucocorticoids might disguise the catabolic state in the majority of patients, while muscle wasting and osteoporosis can be perceived more easily. Attempts to counteract the metabolic effects and the activity of the disease by the use of proteinor amino acid-based formula and nonelemental diets were partially successful in some patients but are reportedly not as effective as glucocorticoid treatment. Thus, the treatment of wasting in patients with Crohn’s diseases remains a challenge to the clinician. Growth hormone (GH) therapy was suggested to improve body composition and counterbalance wasting. GH is a peptide hormone of the pituitary gland. The GH axis and GH signaling in the liver is impaired through IL1, IL6, and TNF-α and might account for GH deficiency in patients with Crohn’s disease and the observed changes in body composition. GH induces an anabolic state mainly due to its mediator IGF-I. The positive effects of GH on intestinal mucosal function and structure have received increasing attention. Moreover, a study by Slonim et al. (2000) verified suggestions that GH treatment in adult patients with Morbus Crohn has beneficial effects on the Crohn’s Disease Activity Index (CDAI). We report on a patient with fistulizing Crohn’s disease with low body mass index (BMI) and GH deficiency who experienced spontaneous free ileal perforation while receiving recombinant human GH. Crohn’s disease of the terminal ileum was diagnosed in our 22-yearold female patient after 2 weeks of severe diarrhea in June 1999. Erythema nodosa, lactose intolerance, and iron deficiency accompanied the acute inflammation; the last one mentioned is still present. After budesonide and prednisone failure, she received azathioprine 2 years after onset and was in stable remission. Three years after onset, an uncomplicated transsphincteral fistula appeared, which resolved after intermittent administration of metronidazole and ciprofloxacin. Recombinant human GH (Genotropin, Pfizer, Erlangen, Germany) treatment was started because of the persistent low BMI of 16.8 kg/m and her low IGF-I and IGF-binding protein at level three (87 ng/ml, i.e., below 5th percentile and 3,170 ng/ml, i.e., below 25th percentile). The GH therapy was applied in a randomized controlled trial, which was approved by the Ethics committee of Dresden University (EK80052001). The trial was stopped in July 2003 due to insufficient patient recruitment. To minimize any adverse effect, the GH treatment was initiated at a dose of 0.4 U/day (0.13 mg/day). The daily G. W. Wolkersdorfer (*) . S. Miehlke . R. Schneider . G. Ehninger Medical Department I, Faculty of Medicine, Carl Gustav Carus, Technical University of Dresden, Fetscherstrasse 74, 01307 Dresden, Germany e-mail: wolkersdoerfer@mk1.med. tu-dresden.de Tel.: +49-351-4582627 Fax: +49-351-4584394