Intestinal Perforation in ACTH-Dependent Cushing’s Syndrome

Abstract

Previous studies have linked systemic glucocorticoid use with intestinal perforation. However, the association between intestinal perforation and endogenous hypercortisolism has not been well described, with only 14 previously published case reports. In this study, we investigated if intestinal perforation occurred more frequently in patients with ectopic ACTH syndrome and in those with a greater than 10-fold elevation of 24-hour urinary free cortisol level. Of 110 patients with ACTH-dependent Cushing’s syndrome followed in two clinics in Canada, six cases with intestinal perforation were identified over 15 years. Age of patients ranged from 52 to 72, five females and one male, four with Cushing’s disease and two with ectopic ACTH production, one from a pancreatic neuroendocrine tumor and one from medullary carcinoma of the thyroid. Five had diverticular perforation and one had intestinal perforation from a stercoral ulcer. All cases had their lower intestinal perforation when the cortisol production was high, and one patient had diverticular perforation 15 months prior to the diagnosis of Cushing’s disease. As in previously reported cases, most had hypokalemia and abdominal pain with minimal or no peritoneal symptoms and this occurred during the active phase of Cushing’s syndrome. Whereas all previously reported cases occurred in patients with 24-hour urinary free cortisol levels greater than 10-fold the upper limit of normal when measured and 11 of 14 patients had ectopic ACTH production, only one of our patients had this degree of hypercortisolism and four of our six patients had Cushing’s disease. Similar to exogenous steroid use, patients with endogenous hypercortisolism also have a higher risk of intestinal, in particular diverticular, perforation and should be monitored closely for its occurrence with a low threshold for investigation and surgical intervention. Elective colonoscopy probably should be deferred until Cushing’s syndrome is under control.

MANAGEMENT OF ENDOCRINE DISEASE: Cushing’s syndrome due to ectopic ACTH secretion: an expert operational opinion

“…In the presence of an unexplained septic state, physicians should also be aware of cortisol-induced gut perforation responsible for peritonitis that can occur without 'contracture' and prescribe abdominal imaging (121,122,123).…”

A challenging case of Cushing’s disease complicated with multiple thrombotic phenomena following trans-sphenoidal surgery; a case report

“…There is a well-known association between the treatment with exogenous corticosteroids and intestinal perforation. It was also previously observed that there is an association between intestinal perforation and endogenous glucocorticoid excess due to ACTH dependent CS [ 9 , 10 ]. Interestingly, most of these patients did not have a history of pre-existing diverticular disease.…”

“…Several mechanisms are responsible for the diverticular perforation associated with hypercortisolism, including reduced collagen turnover leading to weakened colonic wall integrity, reduction of prostacyclin formation and impaired wound healing. Glucocorticoid-induced activation of tumour necrosis factor alpha receptors may play a role [ 9 ]. Cortisol excess is also known to cause a delay in diagnosis of bowel perforation by masking typical symptoms.…”

Adrenocorticotropic Hormone-Dependent Cushing's Syndrome Complicated With Gastric Ulcer Perforation in a 30-Year-Old Saudi Female: A Case Report and a Review of the Literature

“…However, there is limited information on gastrointestinal complications associated with endogenous hypercortisolemia [3,4]. Thus far, only 23 instances have been published addressing the co-occurrence of gastrointestinal perforation with endogenous Cushing's syndrome [5][6][7][8][9][10][11][12][13][14][15][16][17]. To the best of our knowledge, this is the first case reporting gastric perforation in an ACTH-dependent Cushing's syndrome, while the vast majority reported diverticular, sigmoid, or duodenal perforation with Cushing's syndrome [5][6][7][8][9][10][11][12][13][14][15][16][17].…”