Nuclear medicine helps localize tumor in ectopic Cushing's syndrome

By Will Boggs MD

Nuclear medicine imaging significantly improves the ability to localize the tumor in ectopic Cushing's syndrome, according to a new systematic review.

"Localization of the source of ectopic ACTH can be very difficult," Dr. Andrea M. Isidori from Sapienza University of Rome and Dr. Rosario Pivonello from Università degli Studi di Napoli Federico II in Naples, Italy, told Reuters Health in a joint email.

"In up to 30% of patients, it takes several months and a number of different investigations during which the patients remains exposed to the risks of hypercortisolism, anti-steroidal drugs, and tumor growth," they said. "In some of the cases we reviewed it took more than one year to find these tumors that can be hidden anywhere in the body: from the rectum to the olfactory bulb."

Ten to 15% of Cushing's syndrome cases result from ectopic Cushing's caused by various extrapituitary tumors. Between 9% and 27% of the primary lesions responsible for these ectopic Cushing's syndrome cases remain unidentified even after long-term follow-up.

Drs. Isidori and Pivonello and colleagues in the ABC Study Group reviewed reports on the diagnostic performance of simultaneous conventional and nuclear medicine imaging in the identification of ectopic Cushing's syndrome based on individual data for 231 patients.

Tumors were localized by CT in 66.2% of cases, MRI in 51.5%, (111)inpentetreotide (OCT) in 48.9%, FDG-PET in 51.7%, F-DOPA-PET in 57.1%, (131)/(123)I-metaiodobenzylguanidine (MIBG) in 30.8%, and (68)gallium-PET/CT in 81.8%, the researchers report in The Journal of Clinical Endocrinology & Metabolism, online July 7.

Lung lesions were most commonly identified by CT; thymus-mediastinum tumors by OCT; adrenal gland tumors by CT, MRI, and FDG-PET; gastrointestinal tract tumors by CT; thymus tumors by CT; and rare abdominal tumors by MRI.

Based on these results, the researchers developed a flowchart that illustrates the most efficient diagnostic approach:

- Total body CT should be done first.

- Positive CT should be confirmed by OCT, and treatment (normally surgery) should be treated if the latter test is confirmatory.

- Negative OCT should be followed by FDG-PET; if the latter is positive, treatment should be started; if it is negative, it should be followed by gallium-PET, but treatment may also be considered.

- Negative initial CT should be followed by MRI.

- Negative CT and MRI should be followed by gallium-SSTR-PET/CT.

- Patients with unclear or discordant findings should be reevaluated with gallium-SSTR-PET/CT.

"It should be emphasized that imaging alone, even when including molecular, anatomical, biological and endoscopic imaging, is not sufficient for a correct diagnosis - a process that needs additional information, including clinical characteristics, to be integrated in a broad discussion within a multidisciplinary team," the researchers note.

"Whole-body scanning often reveal incidental lesions that are not sustaining the ectopic Cushing's syndrome, exposing to the risk of ineffective surgical procedures," Dr. Isidori and Dr. Pivonello said. "For this reason we recommend that at least two different imaging modalities confirm the diagnosis of ectopic Cushing's syndrome, combining conventional radiology scanning with functional nuclear medicine imaging using (the) most sensitive radiolabeled tracers. We provided data to help the physicians to choose which combinations are the most appropriate according to the tumor site."

They reiterate, "The source of ectopic ACTH (or CRH) can be anywhere and remain occult for long. The physician should not give up, with repeated scanning performed using a rational and rigorous approach whilst taking all necessary measures to control hypercortisolemia and related complications."

SOURCE: http://bit.ly/1LunlTZ

J Clin Endocrinol Metab 2015.

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