Challenges in the localization of ectopic ACTH-secreting tumors

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 29-49-Congenital Adrenal Hyperplasia & Ectopic Cushing's
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-49
Sandi-Jo Galati*1, Gillian Goddard2, Eliza B. Geer3 and Alice C Levine4
1Mount Sinai Medical Ctr, New York, NY, 2Mount Sinai Medical Ctr, 3Mt Sinai School of Medicine, New York, NY, 4Mt Sinai Med Ctr, New York, NY
Introduction: Ectopic adrenocorticotropin syndrome (EAS) is a rare cause of Cushing’s syndrome (CS).  Distinguishing the source of EAS is difficult and imparts a significant obstacle to treatment. Most ACTH-secreting tumors express somatostatin receptors (sst), therefore 111In-octreotide scintingraphy (octreoscan) may be a useful localization tool.  In practice, however, octreoscan has widely variable diagnostic yields in detecting these tumors, ranging from 8-80%.

Case: A 27 year-old man complained of fatigue, bruising, weight loss, decreased muscle mass and increased facial fullness for 3 months. Exam: BP 158/80, round face with flushing, supraclavicular and dorsocervical fat, hyperpigmented striae and bruising.  Data: ACTH 100 pg/mL and cortisol 30 mcg/dL after 1mg of dexamethasone, midnight free salivary cortisol values of 57.3 and 55.4 nmol/L (reference: 0.3-4.3) and urinary free cortisol 1554 mcg/24 hours (reference: < 50), confirming ACTH-dependent CS.  Pituitary MRI was normal.  Inferior petrosal sinus sampling did not demonstrate a step-up from pituitary to periphery.  Blood ACTH and cortisol levels following an 8 mg dexamethasone suppression test were 51 and 20, respectively.  Neuroendocrine and carcinoid markers were normal. CT demonstrated a 6mm left upper lobe (LUL) lung nodule. A discrete focus of uptake was seen in the left hilum on octreoscan, but there was no uptake in the lung nodule noted on CT.  Pulmonary venous sampling did not demonstrate an ACTH gradient.  Clinical Course: Ketoconazole therapy was initiated with reduction in blood ACTH and cortisol to 65 and 25, respectively. Due to rising liver function tests, he was switched to octreotide LAR. His clinical status continued to deteriorate, so bilateral adrenalectomy was planned.  Octreoscan was repeated and demonstrated unchanged left hilar uptake and new uptake in the LUL lesion identified on CT.  He underwent LUL wedge resection and hilar dissection, final pathology revealed bronchial carcinoid with two metastatic lymph nodes.  Postoperatively he received octreotide LAR, capecitabine and temozolomide for 4 months. He required glucocorticoid (GC) replacement for 13 months and is now disease free off GCs for 3 years. 

Discussion: We present a patient with EAS and conflicting localization studies at the time of diagnosis.  A pulmonary lesion was detected on CT that was not octreotide-avid initially, and became avid possibly because GC concentrations were reduced with therapy. The mechanism of altered sensitivity to 111In-octreotide is not entirely clear, although decreased sst expression, particularly the sst2 subtype is seen in a subset of neuroendocrine tumors due to GC-mediated down-regulation. Reduction of GC concentrations with cortisol biosynthesis inhibitors or blockade of the GC receptor with mifepristone may be useful tools for localization by unmasking previously non-octreotide-avid tumors.

Nothing to Disclose: SJG, GG, EBG, ACL

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