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Year : 2015  |  Volume : 11  |  Issue : 4  |  Page : 1027

Ectopic Cushing syndrome secondary to recurrent pancreatoblastoma in a child: Lessons learnt

1 Department of Pediatric Surgical Oncology, Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India
2 Department of Pediatric Oncology, Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India
3 Department of Radiology, Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India

Date of Web Publication15-Feb-2016

Correspondence Address:
Sajid S Qureshi
Department of Paediatric Surgical Oncology, Tata Memorial Hospital, Ernest Borges Road, Parel, Mumbai - 400 012, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.151854

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 > Abstract 

Although rare, pancreatoblastoma is the most common pancreatic tumor in children. Cushing syndrome secondary to ectopic secretion of adrenocorticotropic hormone (ACTH) from a pancreatoblastoma is very rare with only two previously reported cases. We present the management and the lesson learnt in a 3-year-old child with recurrent pancreatoblastoma with Cushing syndrome.

Keywords: Adrenocorticotropic hormone, cushing syndrome, ectopic, pancreatoblastoma

How to cite this article:
Qureshi SS, Bhagat M, Kurkure PA, Kembhavi SA. Ectopic Cushing syndrome secondary to recurrent pancreatoblastoma in a child: Lessons learnt. J Can Res Ther 2015;11:1027

How to cite this URL:
Qureshi SS, Bhagat M, Kurkure PA, Kembhavi SA. Ectopic Cushing syndrome secondary to recurrent pancreatoblastoma in a child: Lessons learnt. J Can Res Ther [serial online] 2015 [cited 2022 Jul 5];11:1027. Available from: https://www.cancerjournal.net/text.asp?2015/11/4/1027/151854

 > Introduction Top

Ectopic Cushing's syndrome represents 20% of adrenocorticotropic hormone (ACTH) dependent and 10% of all types of Cushing's syndrome. [1] The most prevalent tumors associated with ectopic Cushing's syndrome are bronchial, pancreatic, and thymic carcinoids; small cell lung carcinomas; medullary carcinomas of the thyroid; and phaeochromocytomas. However, ectopic Cushing's syndrome is very rare in children and pancreatic tumors as the source of ectopic ACTH secretion is even rarer. Hitherto only two reports of pancreatoblastoma with ectopic Cushing syndrome have been reported. [2],[3] We present a case of recurrent pancreatoblastoma with Cushing syndrome and describe the lessons learnt through management of this rare entity.

 > Case report Top

A 3-year-old boy was referred following surgery of pancreatic tumor elsewhere. Computed tomography (CT) showed irregularity in the region of the uncinate process suggestive of postoperative changes. The histopathology was indicative of pancreatoblastoma. All baseline blood investigations were normal except serum alpha fetoprotein (AFP), which was 604 ng/ml (normal range 0-15). The patient received three cycles of cisplatin and doxorubicin based chemotherapy. The earlier postoperative changes had remained unchanged after chemotherapy on imaging and the serum AFP had marginally lowered to 487 ng/ml, raising the suspicion of residual disease, therefore exploration was planned. On exploration, the pancreas and the uncinate process appeared normal and biopsy from the suspected residual disease did not reveal evidence of tumor on frozen section examination. In view of this it was decided not to pursue an extensive resection in the form of Whipple's surgery, and subsequently the child was kept on observation. At 3-month follow-up, the child presented with features of Cushing syndrome [Figure 1]. The child was normotensive with a blood pressure of 100/70 mmHg and hypokalemic (2.5 mmol/L). The serum phosphorus was marginally raised (5.1 mg/dl, normal range 2.7-4.5) and AFP had increased significantly (3,975 ng/ml). CT scan revealed a mass arising from the uncinate process of the pancreas [Figure 2]. A whole body flourodeoxyglucose positron emission tomography (FDG-PET) scan revealed abnormal uptake in the primary only. The plasma ACTH concentration was 85.20 pg/ml (normal range 5-20 pg/ml). The serum cortisol levels were elevated with loss of diurnal variation. The 24-h urinary cortisol levels were also markedly elevated (1,695.60 μg/day, normal range 2-27 μg/day).An magnetic resonance imaging (MRI) of the brain excluded a pituitary abnormality. Considering all this, a diagnosis of recurrent pancreatoblastoma with ectopic secretion of ACTH causing Cushing syndrome was made and a re-exploration was planned. On exploration, the tumor mass was found to be encasing the superior mesenteric artery and extended distally along its branches. Several mesenteric nodes were also present; hence, the tumor was considered unresectable. The patient had a turbulent postoperative course with hypokalemic episodes, hematuria, and hematochezia requiring prolonged intensive unit stay. The impoverished socioeconomic condition and overall poor prognosis of the child impelled the parents against pursuing further therapy. The patient expired at home, 2 weeks after discharge from the hospital.
Figure 1: Clinical image of the child at relapse showing typical Cushingoid features

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Figure 2: Axial (a) and sagittal (b) view of computed tomography images showing the lesion in the uncinate process of pancreas displacing the superior mesenteric artery

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 > Discussion Top

Pancreatic tumors are rare in children and amongst them pancreatoblastoma is the commonest. [4] Cushing syndrome in children due to ectopic secretion of ACTH is very rare. Pancreatic tumor as the cause of this ectopic secretion is even rarer. On comprehensive review of the existing literature we encountered only 12 instances where pancreatic tumors were associated with Cushing syndrome in children. [2],[3],[5],[6],[7],[8],[9],[10],[11],[12],[13] Only two of them were pancreatoblastoma, other being islet cell tumor and acinar cell carcinoma. [2],[3]

Passmore et al., reported the first patient with a recurrent and metastatic pancreatoblastoma and Cushing syndrome. [2] Kletter et al., reported the second patient with pancreatoblastoma and Cushing syndrome at the outset. [3] Although the Cushingoid features resolved after surgery in their patient, they reappeared at recurrence. Our patient developed Cushing's syndrome at disease relapse. Although the tumor-free interval was short, the absence of tumor in biopsy on exploration after a course of chemotherapy confirms it to be recurrent rather than residual disease. The role of chemotherapy in pancreatoblastoma is not clear, however, it has been used with variable results. [4] Pancreatoblastomas secrete AFP, but the relationship between tumor behavior and AFP is not fully understood. Conflicting results are available regarding correlation of AFP with disease activity, disease recurrence, or the presence of metastases. Hence, it is not recommended for monitoring response to therapy. [4] In contrast, the AFP initially was high in our patient that did not show significant decrease after chemotherapy and there was a substantial rise at recurrence.

Various medical and surgical options are available to relegate the morbidity due to Cushing's syndrome and improve quality of life. [3] Medical therapy to reduce cortisol production include mitotane, ketoconazole, aminogluthemide, etc.; however, an effective drug without significant adverse events is not available. These have also been used in build up for surgery. Matarazzo et al., had used oral ketoconazole preoperatively, which prevented postoperative complications in their patient with ectopic ACTH secretion. [13] The stormy postoperative course in our patient could have been avoided if medical therapy was initiated. Surgical cure of Cushing's syndrome can be achieved with bilateral adrenalectomies. This option also could have been exploited at exploration when the tumor was deemed unresectable.

In conclusion, Cushing syndrome secondary to ACTH secretion from pancreatoblastoma is rare with only few cases reported. Although it was fatal in all the previous patients including ours, symptom alleviation or boost up for surgery in case of resectable disease with various medical therapies available should be considered. In addition to the medical therapy, possibility of bilateral adrenalectomy at surgery for inoperable disease should also be considered and consent taken prior to exploration, especially if the medical therapy had failed preoperatively.

 > Acknowledgement Top

We wish to thank Mr. Mehboob Shah for data collection and images.

 > References Top

Alexandraki KI, Grossman AB. The ectopic ACTH syndrome. Rev Endocr Metab Disord 2010;11:117-26.  Back to cited text no. 1
Passmore SJ, Berry PJ, Oakhill A. Recurrent pancreatoblastoma with inappropriate adrenocorticotrophic hormone secretion. Arch Dis Child 1988;63:1494-6.  Back to cited text no. 2
Kletter GB, Sweetser DA, Wallace SF, Sawin RS, Rutledge JC, Geyer JR. Adrenocorticotropin-secreting pancreatoblastoma. J Pediatr Endocrinol Metab 2007;20:639-42.  Back to cited text no. 3
Qureshi SS, Shukla PJ, Shrikhande SV. Pediatric Pancreatic Tumors. In: Shrikhande S, Friess H, Buchler B, editors. Surgery of Pancreatic Tumours. New Delhi: BI Publications; 2008. p. 299-310.  Back to cited text no. 4
Sayle BA, Lang PA, Green WO Jr, Bosworth WC, Gregory R. Cushing's syndrome due to islet cell carcinoma of the pancreas. Report of two cases: One with elevated 5-hydroxyindole acetic acid and complicated by aspergillosis. Ann Intern Med 1965;63:58-68.  Back to cited text no. 5
Burkinshaw JH, O'Brien D, Pendower JE. Cushing's syndrome associated with an islet tumour of the pancreas in a boy aged two years. Arch Dis Child 1967;42:525-31.  Back to cited text no. 6
Imura H, Matsukura S, Yamamoto H, Hirata Y, Nakai Y. Studies on ectopic ACTH- producing tumours: Clinical and biochemical features of 30 cases. Cancer 1975;35:1430-7.  Back to cited text no. 7
Styne DM, Isaac R, Miller WL, Liesti S, Connors M, Conte FA, et al. Endocrine, histological and biochemical studies of adrenocorticotropin-producing islet cell carcinoma of the pancreas in corticotrophin with characterization of proopiomelanocortin. J Clin Endocrinol Metab 1983;57:723-31.  Back to cited text no. 8
Clark ES, Carney JA. Pancreatic islet cell tumours associated with Cushing's syndrome. Am J Surg Pathol 1984;76:729-33.  Back to cited text no. 9
Garg SK, Vashist R, Pathak IC, Dash RJ. Ectopic ACTH syndrome due to islet cell carcinoma in a 12 year old child. Indian J Pediatr 1988;55:155-60.  Back to cited text no. 10
Hinnie J, Gray CE, McNicol AM, Carter R, Thomson JA, White A, et al. Cushing's syndrome in a 16 year old girl due to ectopic ACTH precursor production from a pancreatic tumour. Clin Endocrinol 2000;53:539-40.  Back to cited text no. 11
Ilyes G, Luzcay A, Benyo G, Kalman A, Borka K, Köves K, et al. Cushing's syndrome in a child with pancreatic acinar cell carcinoma. Endocr Pathol 2007;18:95-102.  Back to cited text no. 12
Matarazzo P, Tuli G, Tessaris D, Verna F, Rabbone I, Lezo A, et al. Cushing syndrome due to ectopic adrenocorticotropic hormone secretion in a 3-year-old child. J Pediatr Endocrinol Metab 2011;24:219-22.  Back to cited text no. 13


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