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Small adrenal incidentaloma becoming an aggressive adrenocortical carcinoma in a patient carrying a germline APC variant

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Abstract

Purpose

Recent guidelines on adrenal incidentalomas suggested in patients with an indeterminate adrenal mass and no significant hormone excess that follow up with a repeat noncontrast CT or MRI after 6–12 months may be an option.

Methods

We report the case of a 32-year-old woman who presented with a 2.9 × 1.9 cm left adrenal incidentaloma that was stable in size for 4 years. Ten years later the left adrenal mass was a stage IV adrenocortical carcinoma (ACC).

Results

In 2006, a 32-year-old French Canadian woman was referred to endocrinology for a left 2.9 × 1.9 cm incidentally discovered adrenal mass (31 HU). She had normal hormonal investigation. The patient was followed with adrenal imaging and hormonal investigation yearly for 4 years and the lesion stayed stable in size over the 4 years. Ten years later, in 2016, the patient presented with renal colic. Urological CT unexpectedly revealed that the left adrenal mass was now measuring 9 × 8.2 cm and 2 new hepatic lesions were found. Biochemical workup demonstrated hypercorticism and hyperandrogenemia: plasma cortisol after 1 mg overnight DST of 476 nmol/L and DHEA-S of 14.0 μmol/L (N 0.9–6.5). Twenty-four hour urine steroid profiling was consistent with an adrenocortical carcinoma (ACC) co-secreting cortisol, androgens and glucocorticoid precursors. The diagnosis of ACC with hepatic ACC metastases was confirmed at histology. Following genetic analysis, germline heterozygous variant of uncertain significance (VUS) was identified in the exon 16 of the APC gene (c.2414G > A, p.Arg805Gln). Immunohistochemical staining’s of the ACC was positive for IGF-2 and cytoplasmic/nuclear β-catenin staining.

Conclusions

This case illustrates that (1) small adrenal incidentaloma stable in size may evolve to ACC and (2) better genetic characterization of these patients may eventually give clues on this unusual evolution.

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Abbreviations

ACC:

adrenocortical carcinoma

DST:

dexamethasone suppression test

HBP:

high blood pressure

CT:

computed tomography

HU:

Hounsfield unit

LCMS:

liquid chromatography and mass spectrometry

MRI:

magnetic resonance imaging

PET:

positron emission tomography

N:

normal

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Funding

This research was supported in part by a salary grant to I. Bourdeau from Fonds de Recherche du Québec-Santé (FRQ-S) and the generous financial support from Fondation McAbbie for the laboratory work.

Author information

Authors and Affiliations

  1. Division of Endocrinology, Department of Medicine, Research Center, Centre hospitalier de l’Université de Montréal (CHUM), Montreal, QC, Canada

    Nadia Gagnon, Pascale Boily, Catherine Alguire, Gilles Corbeil, Catherine Beauregard, Katia Caceres & Isabelle Bourdeau

  2. Division of Endocrinology, Metabolism, Nutrition and Diabetes, Mayo Clinic, Rochester, MN, USA

    Irina Bancos

  3. Division of Pathology, Department of Medicine, Research Cente, Centre hospitalier de l’Université de Montréal (CHUM), Montreal, QC, Canada

    Mathieu Latour

  4. Division of Genetics, Department of Medicine, Centre hospitalier de l’Université de Montréal (CHUM), Montreal, QC, Canada

    Zaki El Haffaf & Isabelle Bourdeau

  5. Division of Urology, Department of Surgery, Research Center, Centre hospitalier de l’Université de Montréal (CHUM), Montreal, QC, Canada

    Fred Saad

  6. Division of Medical Oncology, Department of Medicine, Research Center, Centre hospitalier de l’Université de Montréal (CHUM), Montreal, QC, Canada

    Harold J. Olney

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  1. Nadia Gagnon
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Contributions

We thank the patient who kindly consents that we report her case. We thank Dr. Serge Nolet for technical assistance for leukocyte DNA. N.G. and I. Bourdeau contributed to literature search and writing of the manuscript. I. Bourdeau designed the study. I. Bancos provided the metabolomic profile. G.C. and K.C. contributed to technical laboratory work. I.B and all other co-authors contributed towards patient care and finalizing the draft.

Corresponding author

Correspondence to Isabelle Bourdeau.

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Gagnon, N., Boily, P., Alguire, C. et al. Small adrenal incidentaloma becoming an aggressive adrenocortical carcinoma in a patient carrying a germline APC variant. Endocrine 68, 203–209 (2020). https://doi.org/10.1007/s12020-020-02209-4

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