An Unusual Case of Ectopic ACTH Syndrome

Abstract

Ectopic ACTH-syndrome is a rare cause of Cushing’s disease. Despite extensive diagnostic procedures the source of ACTH secretion often remains occult.

This case describes a 45-year old woman with an ectopic Cushing’s syndrome. Extensive imaging procedures including CT scan of chest and abdomen, octreotide scan and MRI of the chest and pituitary did not reveal the source of ACTH secretion.

In consideration of an occult source of ACTH secretion we started a therapeutic trial with cabergoline (0.5 mg/d), a dopamine receptor agonist, which has been shown to be effective in ectopic Cushing’s syndrome. 2 months after cabergoline treatment had been initiated, ACTH and cortisol levels normalized in association with significant improvement of the clinical symptoms.

During follow-up a [⁶⁸Ga-DOTA-dPhe¹, Tyr³]-octreotate ([⁶⁸Ga-DOTA]-TATE) PET-CT was performed revealing a somatostatin receptor positive lesion in the right sphenoidal sinus suggesting the source of ACTH secretion. The patient was cured by transnasal resection of the polypoid lesion, which was immunohistochemically characterized as an ACTH-positive neuroendocrine tumor.

This case report demonstrates the management of ectopic ACTH-syndrome by molecularly ­targeted therapy with dopamine receptor ­agonists as well as improved detection of the ectopic ACTH source by novel imaging modalities, such as [⁶⁸Ga-DOTA]-TATE PET specifically targeting somatostatin receptor subtype-2 with high affinity.

Key words

pituitary adenoma - glucocorticoids - cabergoline - DOTA-TATE-PET

• Literature

• 1 Bethge H, Arlt W, Zimmermann U et al. Cushing’s syndrome due to an ectopic ACTH-secreting pituitary tumour mimicking occult paraneoplastic ectopic ACTH production. Clin Endocrinol (Oxf) 1999; 51: 809-814
• 2 Biller BM, Grossman AB, Stewart PM et al. Treatment of adrenocorticotropin-dependent Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab 2008; 93: 2454-2462
• 3 de Bruin C, Pereira AM, Feelders RA et al. Coexpression of dopamine and somatostatin receptor subtypes in corticotroph adenomas. J Clin Endocrinol Metab 2009; 94: 1118-1124
• 4 Findling JW, Raff H. Cushing’s Syndrome: important issues in diagnosis and management. J Clin Endocrinol Metab 2006; 91: 3746-3753
• 5 Gabriel M, Decristoforo C, Kendler D et al. 68Ga-DOTA-Tyr3-octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT. J Nucl Med 2007; 48: 508-518
• 6 Hamon M, Coffin C, Courtheoux P et al. Case report: cushing disease caused by an ectopic intracavernous pituitary microadenoma: case report and review of the literature. J Comput Assist Tomogr 2003; 27: 424-426
• 7 Haug A, Auernhammer CJ, Wangler B et al. Intraindividual comparison of 68Ga-DOTA-TATE and 18F-DOPA PET in patients with well-differentiated metastatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2009; 36: 765-770
• 8 Hori A. Suprasellar peri-infundibular ectopic adenohypophysis in fetal and adult brains. J Neurosurg 1985; 63: 113-115
• 9 Kayani I, Bomanji JB, Groves A et al. Functional imaging of neuroendocrine tumors with combined PET/CT using 68Ga-DOTATATE (DOTA-DPhe1,Tyr3-octreotate) and 18F-FDG. Cancer 2008; 112: 2447-2455
• 10 McGrath P. Volume and histology of the human pharyngeal hypophysis. Aust NZ J Surg 1967; 37: 16-27
• 11 Miyoshi T, Otsuka F, Takeda M et al. Effect of cabergoline treatment on Cushing’s disease caused by aberrant adrenocorticotropin-secreting macroadenoma. J Endocrinol Invest 2004; 27: 1055-1059
• 12 Nieman LK, Biller BM, Findling JW et al. The diagnosis of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2008; 93: 1526-1540
• 13 Orth DN. Cushing’s syndrome. N Engl J Med 1995; 332: 791-803
• 14 Petrossians P, Ronci N, Valdes Socin H et al. ACTH silent adenoma shrinking under cabergoline. Eur J Endocrinol 2001; 144: 51-57
• 15 Pivonello R, De Martino MC, Cappabianca P et al. The medical treatment of Cushing’s disease: effectiveness of chronic treatment with the dopamine agonist cabergoline in patients unsuccessfully treated by surgery. J Clin Endocrinol Metab 2009; 94: 223-230
• 16 Pivonello R, Ferone D, de Herder WW et al. Dopamine receptor expression and function in corticotroph ectopic tumors. J Clin Endocrinol Metab 2007; 92: 65-69
• 17 Pivonello R, Ferone D, Lamberts SW et al. Cabergoline plus lanreotide for ectopic Cushing’s syndrome. N Engl J Med 2005; 352: 2457-2458
• 18 Rocheville M, Lange DC, Kumar U et al. Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity. Science 2000; 288: 154-157
• 19 Suzuki J, Otsuka F, Ogura T et al. An aberrant ACTH-producing ectopic pituitary adenoma in the sphenoid sinus. Endocr J 2004; 51: 97-103
• 20 Wajchenberg BL, Mendonca BB, Liberman B et al. Ectopic adrenocorticotropic hormone syndrome. Endocr Rev 1994; 15: 752-787