Turkish Journal of Oncology Turkish Society for Radiation Oncology
Article Open Access Volume 23 · Issue 2 · 2008 pp. 096–099

Adrenal insufficiency caused by bilateral adrenal macrometastases: a rare case with metastatic colon cancer

İrfan ÇİÇİN1
1 Trakya Üniversitesi Tıp Fakültesi, Medikal Onkoloji Anabilim Dalı, Edirne
2 Trakya Üniversitesi Tıp Fakültesi, Patoloji Anabilim Dalı, Edirne
3 Trakya Üniversitesi Tıp Fakültesi, Radyoloji Anabilim Dalı, Edirne
Published: 2008 Pubmed: 77011 Article ID: 693
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Abstract
A 42-year-old male with symptoms of weight loss, fatigue,
hyponatremia, hypoglycemia, hypotension and fever was
referred to our hospital. A computed tomographic scan of the
abdomen and pelvis showed multiple solid masses in the liver,
thickened wall of sigmoid colon and bilateral solid adrenal masses,
7x5x3 cm on the right side and 6x4.5x3.5 cm on the left side.
A colonoscopic examination showed tumoral mass originating
from the sigmoid colon. A biopsy was performed and adenocarcinoma
was diagnosed. The patient was suspected of having primary
adrenal insufficiency due to bilateral adrenal macrometastases.
The diagnosis of adrenal insufficiency was confirmed by
levels of ACTH serum, cortisol and ACTH stimulation test.
Adrenal metastases are well-recognized, but compared with the
prevalence of adrenal metastases, adrenocortical insufficiency in
patients with cancer seems to be rare. We report the case of a
patient with both bilateral surrenal macrometastases, which is
rare in colorectal cancer, and subsequent adrenal insufficiency.

Keywords: Adrenal insufficiency; colon cancer; macrometastases

Full text

Introduction

Metastases of the adrenal gland are a frequent finding in patients with advanced solid tumors. In autopsy series, the prevalence of adrenal metastases was 36-44% in bronchiogenic carcinoma, 20-58% in breast cancer, 50-60% in malignant melanoma, 11-21% in gastric cancer, and 4.8-14% in colorectal cancer.[] The common occurrence of this adrenal lesion is related to its rich sinusoidal blood supply.[] In most of these patients, the metastases remained clinically silent and did not require specific therapy. Compared with the prevalence of adrenal metastases, clinically apparent adrenocortical insufficiency in these patients seems to be rare, since about 90% of the adrenal gland must be destroyed before an adrenal insufficiency is detectable. Although the adrenal insufficiency rate has been reported as high as 20-80% in some prospective and retrospective studies, most of these studies lack clear laboratory proofs. Most data on patients with adrenal insufficiency due to adrenal metastases have been reported as case reports. Fewer than 100 cases have been reported in the literature, and only a few of them concern patients with colorectal cancer.[],[]

We report the case of a patient with both bilateral surrenal macrometastases, which is rare in colorectal cancer, and a subsequent adrenal insufficiency.

Case Presentation

A 42-year-old male with weight loss (>15 kg in last 3 months) and fatigue was admitted to our medical polyclinic. Laboratory tests were performed (Table 1). An abdominal ultrasonographic examination showed multiple masses in liver, bilateral adrenal masses and a thickened wall of sigmoid colon. After one week, the patient was admitted for an advanced evaluation and treatment in the gastroenterology department. The colonoscopic examination showed an annular tumoral mass originating from sigmoid colon, and biopsy was performed. A computed tomographic (CT) scan of the abdomen (Fig. 1), which was obtained after oral administration of contrast material, showed multiple solid masses in liver, a thickened wall of sigmoid colon and bilateral solid adrenal masses, 7x5x3 cm on the right side and 6x4.5x3.5 cm on the left side. The spleen, kidneys, pancreas, gallbladder, omentum, and other sites of gastrointestinal tract were normal. Three weeks later, the patient began to pass four or more loose stools daily, without bleeding, and diarrhea developed, with an abdominal pain and temperature of 37.8°C. Test for Clostridium difficile toxin in stool specimen was negative. Blood culture was also negative. A physician prescribed ciprofloxacin and metronidazole for the treatment of gastroenteritis. On the 30th day, hypoglycemia, lower hyponatremia, tachycardia and hypotension developed (Table 2). In the meantime, a pathologist diagnosed adenocarcinoma (Fig. 2). The patient was transferred to the medical oncology department.

Table 1: Hematologic laboratory values and blood chemical values

Table 2: Clinical signs and symptoms

Fig 1: (a) Axial contrast-enhanced CT image showing bilateral adrenal masses, 7x5x3 cm on the right side and 6x4.5x3.5 cm on the left side, and multiple small liver metastatic lesions. (b) CT image shows severe wall thickening of the sigmoid colon with fat stranding

Fig 2: Tumoral development formed of epithelial cells, with eccentric nucleus, and which are irregular, hyperchromatic, huge, atypic, spreading separately, and completely eliminating the mucosa (H-E x 100).

This patient was suspected of having a primary adrenal insufficiency. His anorexia, fever, fatigue, and weight loss were consistent with this diagnosis, although they could also be explained by the presence of a malignant tumor or an infectious disease. Additional findings that supported the diagnosis of adrenal insufficiency were anemia, hypotension, hypoglycemia, a low serum sodium level, and bilateral adrenal masses. The levels of ACTH serum and cortisol were examined. ACTH stimulation test was performed (Table 3). On the basis of these laboratory results, the patient was diagnosed with adrenal insufficiency due to bilateral macrometastases and was initially treated with intravenous hydrocortisone 200 mg followed by oral hydrocortisone 20 mg daily and fludrocortisone 0.1 mg daily. The patient rejected the adrenal biopsy. A dramatic improvement in clinical and laboratory findings was observed within days (Tables 1, 2). He was then given 2000 mg/m2 capecitabine on the 1st-14th days and 135 mg/m2 oxaliplatin on the 1st day and at 21 day-intervals.

Table 3: Diagnostic tests for adrenal insufficiency

Discussion

Adrenocortical insufficiency is a rare but potentially lethal disease. Autoimmune adrenalitis is the most frequent cause, accounting for 70% of the cases, followed by adrenal tuberculosis (15%). Adrenal metastases are well-recognized, but compared with the prevalence of adrenal metastases, adrenocortical insufficiency in these patients seems to be rare. Particularly, adrenal insufficiency due to metastasis of colorectal cancer is rarer than in others cancer such as lung cancer and lymphoma according to the literature.[] The low incidence of adrenocortical insufficiency in adrenal metastases may be attributed to the fact that over 90% of the adrenal glands must be destroyed before there is a functional adrenal cortical loss. The prevalence of adrenal insufficiency in patients with adrenal metastases as reported in the literature ranges from 0 to 80%. These differences seem to be mainly due to the preselection of patients and variable criteria for the diagnosis of adrenal insufficiency.[] However, there is not a systematic, prospective evaluation of the prevalence of adrenal insufficiency.

Clinically, patients with cancer frequently have signs and symptoms suggestive of adrenal insufficiency. These symptoms are more likely due to the underlying malignancy than caused by a relative glucocorticoid deficit. Clinical assessment of adrenal insufficiency, therefore, is of little value in these patients, and the prevalence of adrenal impairment will be overestimated if the diagnosis of adrenal insufficiency is based only on features like weakness, fatigue, anorexia, weight loss, and vomiting.[,] Recently, Lutz et al. showed that adrenal insufficiency was only found in a patient with large (>4 cm) bilateral adrenal metastases.[]

Consequently, in a patient with cancer, symptoms and signs such as anorexia, fever, fatigue, weight loss, hypotension, anemia, hypoglycemia and low serum sodium level, which are consistent with a malignant tumor or an infectious disease, can also be explained by the presence of adrenal insufficiency. Therefore, as was the case with our patient, adrenal insufficiency should be taken into consideration in patients suffering from bilateral surrenal macrometastases and showing these symptoms and findings.

References

Lutz A, Stojkovic M, Schmidt M, Arlt W, Allolio B, Reincke M. Adrenocortical function in patients with macrometastases of the adrenal gland. Eur J Endocrinol 2000;143(1):91-7. Kung AW, Pun KK, Lam K, Wang C, Leung CY. Addisonian crisis as presenting feature in malignancies. Cancer 1990;65(1):177-9. Redman BG, Pazdur R, Zingas AP, Loredo R. Prospective evaluation of adrenal insufficiency in patients with adrenal metastasis. Cancer 1987;60(1):103-7. Seidenwurm DJ, Elmer EB, Kaplan LM, Williams EK, Morris DG, Hoffman AR. Metastases to the adrenal glands and the development of Addison's disease. Cancer 1984;54(3):552-7. Oelkers W. Adrenal insufficiency. N Engl J Med 1996;335(16):1206-12. Cedermark BJ, Sjöberg HE. The clinical significance of metastases to the adrenal glands. Surg Gynecol Obstet 1981;152(5):607-10.
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