A Masking Effect: A Case of Initial Presentation of Ulcerative Colitis After Discontinuation of Growth Hormone

Introduction: The inflammation and repair of the intestinal mucosa in IBD involve a complex interplay between innate, adaptive immune responses and hormones. Growth factors enhance or stimulate cellular differentiation, proliferation, and angiogenesis. We present the first reported case of a patient with no history of ulcerative colitis who presented her initial flare of IBD after discontinuing Growth hormone (GH) therapy and hence raises the question of whether growth factors can inhibit the development of IBD and, if so, may lead to additional adjuvant therapy for IBD. Case Description/Methods: A 13-year-old woman with a past medical history of GH deficiency presented with abdominal pain, bloody diarrhea for 8 weeks, and an abnormal fecal calprotectin of > 8000ug/g. She was treated with 1.8mg daily GH injection for 6 years, discontinued 2 weeks before the onset of symptoms as the patient had achieved her expected height. Lab results is as shown, Table 1. Colonoscopy showed a non-bleeding ulcerated mucosa in the rectum, sigmoid colon, descending colon, and splenic flexure, Figure 1. The biopsy result was positive for mild to moderate acute inflammation, crypt architectural distortion, and increased chronic inflammatory cells in the lamina propria, suggestive of ulcerative colitis, slide 1. Discussion: The apoptosis of colon epithelial cells (CEC) and activation of NF-kB has been reported to compromise the barrier function of the colon. Growth factors help maintain mucosal barrier integrity by promoting CEC survival and inhibiting NF-kB activation via the Signal transducer and activator of the transcription factor 5b (STAT5b) pathway. The onset of our patient’s first flare following discontinuation of GH may support previous studies on the anti-inflammatory effects of growth factors in IBD. A double-blind and placebo-controlled study by Slonim et al in patients with moderate to severe CD showed that the use of a GH dose of 5 mg/day subcutaneously for 1 week, followed by 1.5 mg/day maintenance dose for 4 months was superior to a placebo in reducing disease severity. In a randomized, double-blind control clinical trial by Sinha et al 10 out of 12 UC patients treated with epidermal growth factor enema and mesalamine were in remission after 2 weeks compared to 1/12 in the control group treated with only mesalamine. Despite the concern with GH-induced carcinogenesis, none of the study trials reported cancer development during its use. More research may need to be done in humans to support its efficacy in IBD.Figure 1.: Hematoxylin and Eosin (H&E) stains of colonoscopy biopsies from cecum [A], transverse colon [B], appendiceal orifice [C], splenic flexure [D], descending colon [E], sigmoid colon [F], rectum [G], splenic flexure higher power [H]. Panels [A, B] demonstrate unremarkable colonic mucosa. While panels [C-H] display biopsies from the appendiceal orifice, splenic flexure, descending colon, sigmoid colon, and rectal biopsies show superficial fragments of colonic mucosa with mild to moderate acute inflammation (black arrows), crypt architectural distortion (red arrows), and increased chronic inflammatory cells in the lamina propria (black boxes). There is no granulomatous inflammation, dysplasia, or malignancy. Panels [A-G] were taken at 10X magnification. Panel [H] was taken at 40X magnification. These histologic findings are consistent with inflammatory bowel disease. Ulcerated rectal mucosa (blue arrow) shown with colonoscopy. Table 1. - Laboratory tests Significant Laboratory tests Results WBC 14.3k/cm3 Hemoglobin 10gm/dl Platelets 506k/uL MCV 74.8fL CRP 2.68mg/dL Serum iron 9ug/dl Percent iron saturation 3% Ferritin 3ng/ml