Ectopic adrenocorticotropic hormone syndrome in a case of duodenal neuroendocrine tumor presenting with liver metastasisJ Khare1, S Daga2, S Nalla1, P Deb1
1 Department of Endocrinology, Krishna Institute of Medical Sciences, Hyderabad, Telangana, India
2 Department of Surgical Gastroenterology, Krishna Institute of Medical Sciences, Hyderabad, Telangana, India
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/jpgm.JPGM_772_16
Source of Support: None, Conflict of Interest: None
Keywords: Cushing syndrome, duodenal neuroendocrine tumor, ectopic adrenocorticotropic hormone syndrome
Ectopic adrenocorticotropic hormone (ACTH) syndrome is an uncommon disorder and comprises about 15% of all patients with Cushing's syndrome (CS). Duodenal carcinoids are rare and are indolent tumors usually associated with a benign progression. ACTH-producing carcinoid tumors most commonly originate in the lung or thymus. We hereby report a rare case of CS resulting from ectopic ACTH secretion from a duodenal neuroendocrine tumor (NET) presenting with liver metastasis.
A 37-year-old female presented to the Surgical Gastroenterology Department with abdominal discomfort and dyspepsia of 1-month duration. Ultrasound abdomen suggested a well-defined hypoechoic space occupying lesion in the left lobe of the liver, suggestive of neoplasia.
She had recent onset diabetes and hypertension on treatment but inadequate control. On clinical examination, she had Cushingoid features and persistent hypokalemia. Midnight ACTH and cortisol levels were grossly elevated at 1027 pg/ml (n < 46 pg/ml) and 87.56 μg/dl (n < 7.5 μg/dl), respectively. Both overnight and high-dose dexamethasone suppression test confirmed nonsuppressed cortisol levels - 86.04 and 84.42 μg/dl (n < 1.8 μg/dl), respectively. Magnetic resonance imaging brain showed a structurally normal pituitary gland. Computed tomography scan of the abdomen revealed hepatic lesion [Figure 1]a with bilateral adrenal enlargement [Figure 1]b. Based on above findings, a diagnosis of ectopic ACTH-dependent CS was made.
She was started on spironolactone 100 mg and ketoconazole 600 mg daily, following which hypokalemia, blood sugars, and blood pressure control improved. She was scheduled for surgical resection of the liver lesion.
Intraoperatively, a lesion of 0.5 cm × 0.5 cm size in the first part of the duodenum [Figure 1]c was identified alongside an 8 cm × 6 cm exophytic lesion in segment IV of the liver. Frozen section of the duodenal lesion was positive for NET. A Whipple's surgery with cholecystectomy and left hepatic lobectomy was performed. The patient received bolus of 100 mg hydrocortisone intravenous infusion perioperatively, and postoperatively, hydrocortisone was tapered over the course of 3 days. Repeat serum cortisol and serum ACTH levels on midnight of the 5th postoperative day dropped to 7 μg/dl and 25.30 pg/ml, respectively, suggesting normal functioning of hypothalamic–pituitary–adrenal axis. Hence, steroid replacement was not restarted. Other biochemical parameters also showed remarkable improvement as shown in [Table 1].
Gross examination showed 0.5 cm × 0.5 cm gray-white nodule in the first part of the duodenum along with the specimen of liver lesion, pancreas, lymph nodes, bile duct, gallbladder, proximal resected margin (stomach), and distal resected margin (duodenum). Histopathology for both the hepatic and duodenal masses showed intermediate-grade NET without perineural invasion, lymphovascular emboli, or muscular invasion as depicted in scanner view of lesion [Figure 1]d. Immunohistochemistry was strongly positive for synaptophysin and chromogranin, and 6% of tumor cell nuclei showed strong positivity for MIB 1 [Figure 2]. Immunohistochemistry staining for ACTH was not done due to cost constraint which was the major limitation in the study. This would have helped to further establish the diagnosis of ectopic ACTH-secreting duodenal NET. Gross pathologic and histopathologic examination of the pancreas and other postoperative specimens received were normal and negative for NET. Histopathology identified tumor-free margins around the lesion.
On subsequent follow-up, she was weaned off antidiabetic and antihypertensive medications. Repeat electrolytes were normal. Three weeks postoperatively, she was clinically well. Morning (8:00 am) serum cortisol level was 17 μg/dl (n = 6.5–22.6 μg/dl). Clinically, the patient is currently in remission suggesting success of surgery.
Ectopic ACTH production accounts for about 15% of all cases of CS and is usually due to small cell lung carcinomas (50%), nonsmall cell lung carcinomas (5%), lung carcinoids (10%), thymic tumors (5%), pancreatic tumors (10%), pheochromocytoma (3%), medullary thyroid cancers (5%), and other carcinoids (2%). Rare association with carcinoma of the prostate, breast, ovary, gallbladder, and colon (10%) has also been reported.
Carcinoid tumors represent 1.2%–1.5% of all gastrointestinal tract neoplasms. Within the gastrointestinal tract, carcinoid tumors are most commonly found in the appendix, followed by the ileum, rectum, and stomach. Duodenal carcinoids are extremely rare, and their characteristics and biological behavior have not been fully elucidated. Duodenal carcinoid tumors are most commonly found on the first part of the duodenum. These tumors are usually indolent, especially when they are small and limited to the submucosa, and the symptoms are generally nonspecific. The ideal treatment for duodenal carcinoids is an endoscopic or a radical surgical excision.
Burke et al. identified three pathological characteristics of duodenal carcinoid tumors that are independent risk factors for metastases: invasion of the muscular layer, a size >2.0 cm, and the presence of more than two mitotic figures per high-power field. In our case, size of the duodenal carcinoid was about 0.5 cm × 0.5 cm, without any invasion to muscular layer, and tumor was of intermediate grade with 2–20 mitotic figures per high-power field but had metastasized.
In cases of liver metastases, a surgical resection and/or cytoreductive techniques, such as radiofrequency ablation and chemoembolization, may improve carcinoid syndrome symptom that are mediated by hormones produced by the tumor, to improve the quality of life and increase survival. Somatostatin analogs may induce symptomatic and biochemical responses that stabilize the disease and reduce the growth of metastases through cytostatic effects. In our patient, there were no carcinoid syndrome symptoms.
The largest series of ectopic ACTH-producing tumors was reported by Aniszewski et al., but no case of duodenal carcinoid was described. To date, only two cases of duodenal carcinoid with ectopic ACTH have been reported: one in Japanese and one in English literature. In our patient, preoperative imaging did not identify the duodenal carcinoid.
Herewith, we report the third case of duodenal carcinoid tumor presenting as ectopic ACTH syndrome and the first with liver metastasis, which was successfully treated with surgical resection.
The authors would like to acknowledge Dr. K. Sujatha and Dr. Kashif, Consultant Pathologists, in our hospital for gross and histopathological support.
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Conflicts of interest
There are no conflicts of interest.
[Figure 1], [Figure 2]