Abstract
We report a case of perforated colonic diverticulum in Cushing's disease. Although perforated diverticuli have been described in patients with Cushing's syndrome secondary to exogenous glucocorticoids, this complication has not been described in patients with Cushing's disease. Patients with hypercortisolism, from either exogenous or endogenous sources, should be monitored for diverticular perforation.
Keywords: Cushing's disease, Diverticulitis, Ruptured diverticulum, Hypercortisolism, Sepsis, Pituitary adenoma
1. Introduction
There is a strong association between systemic glucocorticoid therapy and a number of gastrointestinal complications including gastritis, gastroduodenal ulcers and gastric perforation.1 Patients receiving high dose glucocorticoids, for rheumatological or autoimmune disease are at increased risk for lower gastrointestinal tract abscesses and perforation; however lower gastrointestinal complications in Cushing's disease have not been reported.2
2. Presentation of case
A 71-year-old female with a 10-year history of refractory hypertension, hypokalemia, and diabetes mellitus presented with abdominal pain and distension. She was hospitalized multiple times over the past ten years for hypertension and hypokalemia. Over the last nine months the patient gained 30 pounds, developed extensive bruising of the extremities, and experienced psychiatric symptoms consistent with depression.
On presentation the patient had a blood pressure of 202/97 mmHg and a potassium level of 2.1 mequiv./L. Her physical exam was significant for a moon face, dorsocervical fat pad, large pannus, and skin thinning with several large areas of ecchymosis. Bowel sounds were absent. A 4/5 peripheral myopathy with mild muscular atrophy and a right nasal superior quandrantopia were present. A computed tomography scan of her abdomen and pelvis identified a number of dilated loops of the distal small bowel with no focal transition zone. Diverticulosis and bilateral enlargement of the adrenal glands were also noted (Fig. 1). The patient received intravenous potassium over the next 24 h and her abdominal pain and ileus resolved.
Fig. 1.
CT of the abdomen with contrast shows bilateral hypertrophy of the adrenal glands, identified by white arrows. There was also evidence of a small bowel obstruction, most likely due to the patent's chronic hypokalemia.
Following the administration of 8 mg dexamethaxone at 12 AM, the 8 AM cortisol was 94 μg/dL and ACTH 100 pg/mL. An MRI of the brain showed an area of tissue in the right lobe of the pituitary that had decreased uptake of contrast on early dynamic screening, suggesting a pituitary lesion.
Bilateral inferior petrosal sinus sampling showed a post-CRH petrosal to peripheral ratio of 7.7 on the right and 5.1 on the left. (Table 1) A transphenoidal hypophysectomy was performed. No discrete ACTH secreting adenoma was found on pathological examination and the patient continued to have elevated cortisol and ACTH levels. An octreotide scan failed to reveal a neuroendocrine tumor and the patient was started on ketoconazole, which normalized her cortisol concentration and corrected her hypokalemia.
Table 1.
Sampling of the petrosal sinus after CRH was administered revealed pituitary overproduction of ACTH.
| Time | Right inferior petrosal | Left inferior petrosal | Peripheral |
|---|---|---|---|
| −5″ pre-CRH | 95 | 66 | 80 |
| 0 | 188 | 110 | 69 |
| +2 | 525 | 349 | 68 |
| +5 | 439 | 313 | 69 |
| +10 | 252 | 196 | 69 |
Twelve days following surgery, the patient presented with sepsis. Laparotomy revealed a large intra-abdominal abscess and extensive colonic diverticulitis with evidence of perforation. A sigmoid colectomy with end colostomy and Hartmann's pouch was performed. She was treated with antibiotics during the hospital stay and discharged on Levaquin on the 13th postoperative day. Six days after discharge she developed hypotension and refused further treatment. An autopsy was performed.
Pertinent postmortem findings consisted of multiple intra-abdominal, pelvic and retroperitoneal abscesses, colonic mesenteric atrophy, loss of the normal colonic luminal architecture, and numerous large thin-walled diverticula, one of which was perforated. There was an absence of intrasellar pituitary tissue consistent with a recent hypophysectomy. Detailed examination of the parasellar region identified residual ACTH secreting cells consistent with an adenoma attached to the superior aspect of the pituitary stalk (Fig. 2).
Fig. 2.
Examination of the parasellar region identified residual ACTH-secreting cells consistent with an adenoma attached to the superior aspect of the pituitary stalk.
3. Discussion
Patients with Cushing's syndrome have a mortality rate four times higher than age and gender matched subjects, due primarily to an increase in cardiovascular complications such as hypertension, obesity, diabetes mellitus, and hyperlipidemia.3 Diverticular disease is very common after age 50 and perforation is a well-recognized complication. There has not, however, been a published report of lower gastrointestinal tract morbidity secondary to Cushing's disease. Possible pathophysiological mechanisms include inhibition of epidermal cell division and decreased collagen synthesis.4,5 Glucocorticoids excess can impair the cellular immune response and mask signs of acute inflammation. Additionally, hypokalemia decreases bowel motility and the resultant constipation also increases the risk of diverticular disease.
4. Conclusion
This case illustrates the potential for fulminant diverticular disease complications in patients with Cushing's disease. Multiple elements contribute to the increased risk of diverticular perforation and abscess formation in association with hypercortisolism. Surgeons and endocrinologists should be aware of this potentially fatal complication when caring for patients with Cushing's disease.
Conflict of interest
Neither author reports financial or personal relationships with people or organizations that could inappropriately influence this work.
Funding
None.
Ethical approval
Written informed consent was obtained from the patient's next-of-kin for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.
Author contributions
Drs. de Havenon and Ehrenkranz both contributed to the data collection, writing, and editing of this manuscript.
Acknowledgement
We would like to thank Dr. J. Wallace Graham for his assistance with the pathology.
References
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