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Diagnostic utility of Gallium-68-somatostatin receptor PET/CT in ectopic ACTH-secreting tumors: a systematic literature review and single-center clinical experience

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Abstract

Purpose

Tumors causing ectopic Cushing’s syndrome (ECS) are often not visible with conventional imaging. Gallium-68-DOTATATE, DOTATOC, and DOTANOC positron emission tomography/computed tomography (68Ga-SSTR PET/CT) reportedly exhibits greater sensitivity in identifying an ECS source, however, evidence is limited to mainly case reports and a few small retrospective studies. Previous systematic ECS imaging review has shown 68Ga-SSTR PET/CT sensitivity is similar to CT (81.8%) in histologically-proven cases and is 100% in covert-cases, however, the number of patients was small and no occult cases were reported.

Methods

We performed a systematic literature review of 68Ga-SSTR PET/CT use in ECS patients. We also report 6 consecutive patients with confirmed active and occult ECS who underwent 68Ga-DOTATATE PET/CT and were followed at our institution between 2014 and 2019.

Results

We identified 33 articles (23 case-reports, 4 case-series, 5 retrospective studies and 1 prospective study) detailing 68Ga-SSTR PET/CT in 69 ECS patients. Overall 68Ga-SSTR PET/CT sensitivity was 64.0%, while in histologically confirmed cases (67 lesions), sensitivity was 76.1%. There were two false-positives cases, both in the adrenal glands. In covert cases, 68Ga-SSTR PET/CT identified 50% of lesions. There were ten occult cases where all imaging failed to identify an adrenocorticotropic hormone source; source remains unknown. In our case series, 68Ga-DOTATATE PET/CT showed decreased uptake in pancreatic neuroendocrine tumor in one patient and did not help identify an ECS source in 5 patients.

Conclusion

Both this systematic literature review, the largest to date, and our single- center experience demonstrate a lower than previously reported 68Ga-SSTR PET/CT sensitivity for ECS, especially in occult lesions. We suggest that the data on 68Ga-SSTR PET/CT in ECS is subject to publication bias, and false-negatives are likely underreported; it’s diagnostic value for ECS needs further study.

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Acknowledgements

The authors thank Shirley McCartney, PhD, for editorial assistance.

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Authors and Affiliations

  1. Department of Medicine, Division of Endocrinology, Diabetes and Clinical Nutrition, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Road, L607, Portland, OR, USA

    Elena Varlamov & Maria Fleseriu

  2. Department of Neurological Surgery, Oregon Health & Science University, 3303 SW Bond Ave, Mail Code CH8N, Portland, OR, USA

    Elena Varlamov, José Miguel Hinojosa-Amaya & Maria Fleseriu

  3. Northwest Pituitary Center, Oregon Health & Science University, 3303 SW Bond Ave, Mail Code CH8N, Portland, OR, USA

    Elena Varlamov, José Miguel Hinojosa-Amaya, Madeleine Stack & Maria Fleseriu

  4. Endocrinology Division, Department of Medicine, Hospital Universitario “Dr. José E. González”, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico

    José Miguel Hinojosa-Amaya

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  1. Elena Varlamov
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Correspondence to Maria Fleseriu.

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Maria Fleseriu disclosures—Principal Investigator with research funding to OHSU from Novartis, Millendo, Strongbridge and has received occasional scientific consulting fee from Novartis, Strongbridge, and declares no conflict of interest. All other authors declare that they have no disclosures and no conflict of interest

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Varlamov, E., Hinojosa-Amaya, J.M., Stack, M. et al. Diagnostic utility of Gallium-68-somatostatin receptor PET/CT in ectopic ACTH-secreting tumors: a systematic literature review and single-center clinical experience. Pituitary 22, 445–455 (2019). https://doi.org/10.1007/s11102-019-00972-w

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