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Horm Metab Res 2021; 53(01): 24-31
DOI: 10.1055/a-1268-8301
Endocrine Care

Predicitve Value of FDG Uptake in the Remaining Adrenal Gland Following Adrenalectomy for Adrenocortical Cancer

Ruben Loewe‡
1   Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany
,
Natalie Rogowski-Lehmann‡
1   Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany
,
Thomas Pfluger
2   Klinik und Poliklink für Nuklearmedizin, Klinikum der Universität München, Munich, Germany
,
Martin Reincke
1   Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany
,
Stefanie Hahner
3   Department of Medicine, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany
,
Christina Bluemel
4   Department of Nuclear Medicine, University Hospital, University of Würzburg, Würzburg, Germany
,
Martin Fassnacht
3   Department of Medicine, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany
5   Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany
,
Felix Beuschlein
1   Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany
6   Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, Universitätsspital Zürich, Zürich, Switzerland
› Author Affiliations Funding Information This study was supported by the Deutsche Forschungsgemeinschaft within the CRC/Transregio 205/1 (“The Adrenal: Central Relay in Health and Disease) to FB, MF, SH, and MR.
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Abstract

Following initial surgery, patients with adrenocortical carcinoma (ACC) are commonly treated with the adrenolytic substance mitotane in an adjuvant or therapeutic setting. Treatment responses, however, are variable. The objective of the study was to investigate a possible correlation between FDG-PET activity of the remaining adrenal gland and therapeutic response of mitotane treatment. This is a retrospective study enrolling patients from two German centers with operated ACC and minimal information on PET-CT scanning. Eighty-two ACC patients after adrenalectomy were included (66 treated with mitotane and 16 without medical therapy). FDG uptake of the contralateral adrenal gland, liver and mediastinum was analyzed from a total of 291 PET/CT scans (median 4 scans per patient) and correlated with clinical annotations including overall and recurrence free survival. The majority of patients (81%) displayed a temporary increase in adrenal FDG uptake within the first 18 months following surgery, which was not associated with a morphological correlate for potential malignancy. This increase was mainly present in patients treated with mitotane (51/61, 84%) but less frequent in the control group (4/7, 57%). No direct correlation with mitotane plasma levels were evident. Patients following R0 resection with high adrenal uptake showed a tendency towards better clinical outcome without reaching a significance value (HR 1.41; CI 0.42–4.75; p=0.059). FDG update of the contralateral adrenal gland may not be misinterpreted as sign of malignancy but might be rather associated with a trend towards better clinical outcome.

Key words

adrenocortical cancer - FDG-PET - prognostic value - mitotane

Supplementary Material



Publication History

Received: 29 May 2020

Accepted after revision: 29 May 2020

Article published online:
21 October 2020

© 2020. Thieme. All rights reserved.

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  • References

  • 1 Else T, Kim AC, Sabolch A. et al. Adrenocortical carcinoma. Endocr Rev 2014; 35: 282-326
    CrossrefPubMedGoogle Scholar
  • 2 Fassnacht M, Dekkers OM, Else T. et al. European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol 2018; 179: G1-G46
    CrossrefPubMedGoogle Scholar
  • 3 Terzolo M, Angeli A, Fassnacht M. et al. Adjuvant mitotane treatment for adrenocortical carcinoma. N Engl J Med 2007; 356: 2372-2380
    CrossrefPubMedGoogle Scholar
  • 4 Fassnacht M, Terzolo M, Allolio B. et al. Combination chemotherapy in advanced adrenocortical carcinoma. N Engl J Med 2012; 366: 2189-2197
    CrossrefPubMedGoogle Scholar
  • 5 Beuschlein F, Weigel J, Saeger W. et al. Major prognostic role of Ki67 in localized adrenocortical carcinoma after complete resection. J Clin Endocrinol Metab 2015; 100: 841-849
    CrossrefPubMedGoogle Scholar
  • 6 Assie G, Letouze E, Fassnacht M. et al. Integrated genomic characterization of adrenocortical carcinoma. Nat Genet 2014; 46: 607-612
    CrossrefPubMedGoogle Scholar
  • 7 Zheng S, Cherniack AD, Dewal N. et al. Comprehensive pan-genomic characterization of adrenocortical carcinoma. Cancer Cell 2016; 30: 363
    Google Scholar
  • 8 Deandreis D, Leboulleux S, Caramella C. et al. FDG PET in the management of patients with adrenal masses and adrenocortical carcinoma. Horm Cancer 2011; 2: 354-362
    CrossrefPubMedGoogle Scholar
  • 9 Takeuchi S, Balachandran A, Habra MA. et al. Impact of (1)(8)F-FDG PET/CT on the management of adrenocortical carcinoma: Analysis of 106 patients. Eur J Nucl Med Mol Imaging 2014; 41: 2066-2073
    CrossrefPubMedGoogle Scholar
  • 10 Maurea S, Mainolfi C, Bazzicalupo L. et al. Imaging of adrenal tumors using FDG PET: Comparison of benign and malignant lesions. AJR Am J Roentgenol 1999; 173: 25-29
    CrossrefPubMedGoogle Scholar
  • 11 Yun M, Kim W, Alnafisi N. et al. 18F-FDG PET in characterizing adrenal lesions detected on CT or MRI. J Nucl Med 2001; 42: 1795-1799
    PubMedGoogle Scholar
  • 12 Leboulleux S, Dromain C, Bonniaud G. et al. Diagnostic and prognostic value of 18-fluorodeoxyglucose positron emission tomography in adrenocortical carcinoma: A prospective comparison with computed tomography. J Clin Endocrinol Metab 2006; 91: 920-925
    CrossrefPubMedGoogle Scholar
  • 13 Cistaro A, Niccoli Asabella A. et al. Diagnostic and prognostic value of 18F-FDG PET/CT in comparison with morphological imaging in primary adrenal gland malignancies - a multicenter experience. Hellenic. J Nucl Med 2015; 18: 97-102
    PubMedGoogle Scholar
  • 14 Leboulleux S, Deandreis D, Escourrou C. et al. Fluorodesoxyglucose uptake in the remaining adrenal glands during the follow-up of patients with adrenocortical carcinoma: Do not consider it as malignancy. Eur J Endocrinol 2011; 164: 89-94
    CrossrefPubMedGoogle Scholar
  • 15 Mpanaka I, Lyra VD, Kaltsas G. et al. High (18)F-FDG uptake by the remaining adrenal gland four months after surgery and initiation of mitotane treatment in two patients with adrenocortical carcinoma. Hellenic. J Nucl Med 2011; 14: 168-172
    PubMedGoogle Scholar
  • 16 Engeland WC, Ennen WB, Elayaperumal A. et al. Zone-specific cell proliferation during compensatory adrenal growth in rats. Am J Physiol Endocrinol Metab 2005; 288: E298-E306
    CrossrefPubMedGoogle Scholar
  • 17 Beuschlein F, Mutch C, Bavers DL. et al. Steroidogenic factor-1 is essential for compensatory adrenal growth following unilateral adrenalectomy. Endocrinology 2002; 143: 3122-3135
    CrossrefPubMedGoogle Scholar
  • 18 Bicknell AB, Lomthaisong K, Woods RJ. et al. Characterization of a serine protease that cleaves pro-gamma-melanotropin at the adrenal to stimulate growth. Cell 2001; 105: 903-912
    CrossrefPubMedGoogle Scholar
  • 19 Waszut U, Szyszka P, Dworakowska D. Understanding mitotane mode of action. J Physiol Pharmacol 2017; 68: 13-26
    PubMedGoogle Scholar
  • 20 Paragliola RM, Torino F, Papi G. et al. Role of mitotane in adrenocortical carcinoma - review and state of the art. Eur Endocrinol 2018; 14: 62-66
    CrossrefPubMedGoogle Scholar
  • 21 Else T. Association of adrenocortical carcinoma with familial cancer susceptibility syndromes. Mol Cell Endocrinol 2012; 351: 66-70
    CrossrefPubMedGoogle Scholar
  • 22 Bagheri B, Maurer AH, Cone L. et al. Characterization of the normal adrenal gland with 18F-FDG PET/CT. J Nucl Med 2004; 45: 1340-1343
    PubMedGoogle Scholar
  • 23 Wang Y, Chiu E, Rosenberg J. et al. Standardized uptake value atlas: Characterization of physiological 2-deoxy-2-[18F]fluoro-D-glucose uptake in normal tissues. Mol Imag Biol 2007; 9: 83-90
    CrossrefPubMedGoogle Scholar
  • 24 Boellaard R, Delgado-Bolton R, Oyen WJ. et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imag 2015; 42: 328-354
    CrossrefPubMedGoogle Scholar
  • 25 Fassnacht M, Johanssen S, Quinkler M. et al. Limited prognostic value of the 2004 International Union Against Cancer staging classification for adrenocortical carcinoma: proposal for a Revised TNM Classification. Cancer 2009; 115: 243-250
    CrossrefPubMedGoogle Scholar
  • 26 Kleitman N, Holzwarth MA. Compensatory adrenal cortical growth is inhibited by sympathectomy. Am J Physiol 1985; 248: E261-E263
    PubMedGoogle Scholar
  • 27 Di Dalmazi G, Berr CM, Fassnacht M. et al. Adrenal function after adrenalectomy for subclinical hypercortisolism and Cushing’s syndrome: A systematic review of the literature. J Clin Endocrinol Metab 2014; 99: 2637-2645
    CrossrefPubMedGoogle Scholar