68Ga DOTATOC positron emission tomography (PET) signal intensity is positively correlated with somatostatin receptor (ssr) 2 expression in an ACTH-producing thymic carcinoid tumor causing severe Cushing's syndrome in an adolescent boy

Background: The majority of patients with ectopic ACTH syndrome have malignant neuroendocrine tumors, some of which cannot be detected using standard radiological techniques, due to small size and/or poor resolution from other anatomical structures. ⁶⁸Ga DOTATOC binds to somatostatin receptors (ssr) and can be used in PET to visualize ssr-expressing tumors. Clinical case: Over 2 months, a 15-year old boy had developed severe acne, truncal obesity (BMI 35,5kg/m²), hypertension (>180/120mmHg), and diabetes mellitus requiring insulin therapy. Concentrations of serum cortisol ranged from 2730–4056 nmol/l (nl. <630), of ACTH from 249–560 pg/ml (nl. <46) with loss of circadian periodicity. Concentrations were not increased by CRH, and did not suppress in a low and high dose DEX test. Central catheterization revealed highest ACTH concentrations in the left brachiocephalic venous outflow (521 pg/ml vs. 326–428 pg/ml in other regions). Imaging Methods: With standard X-ray, CT scan and MRI techniques, a tumor could not be clearly delineated, although suspect mediastinal and intrapulmonary lesions were seen. Total body PET using the somatostatin analogue ⁶⁸Ga-DOTATOC (75 MBq) showed focal nuclide accumulation in the left ventral mediastinum only. Treatment: A mediastinal tumor (5.5cm length) was excised. Histopathologically, it was a highly differentiated thymic carcinoid with low proliferative activity (<5%). After tumor resection, the features of Cushing syndrome resolved, ACTH and cortisol returned to normal. Receptor Studies: Presence of ssr types 1–5 in tumor tissue was examined by immunostaining. Tissue was positive for ssr1 and 2, strongly positive for ssr3 and negative for ssr4 and ssr5. Conclusions: PET CT with ⁶⁸Ga DOTATOC binding to ssr2 is highly specific to discern ssr-expressing neuroendocrine tumors from neighbouring structures. In tumors like this one, expressing large amounts of ssr3, use of ssr3-specific agents as ligands (e.g. SOM32) could even enhance sensitivity of tumor detection.