Recurrent Cushing Syndrome From Metastatic Adrenocortical Carcinoma With Fumarate Hydratase Allelic Variant

Emily Silverman, MD; Noor Addasi, MD; Muaataz Azzawi, MD; Ernesto Martinez Duarte, MD, MPH; Dali Huang, MD; Benjamin Swanson, MD, PhD; Apar Kishor Ganti, MD; Gwen Reiser, MS; Abbey L. Fingeret, MD; Anupam Kotwal, MD

AACE Clinical Case Reports (Nov 2022)

Recurrent Cushing Syndrome From Metastatic Adrenocortical Carcinoma With Fumarate Hydratase Allelic Variant

Emily Silverman, MD,
Noor Addasi, MD,
Muaataz Azzawi, MD,
Ernesto Martinez Duarte, MD, MPH,
Dali Huang, MD,
Benjamin Swanson, MD, PhD,
Apar Kishor Ganti, MD,
Gwen Reiser, MS,
Abbey L. Fingeret, MD,
Anupam Kotwal, MD

Affiliations

Emily Silverman, MD: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska
Noor Addasi, MD: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska
Muaataz Azzawi, MD: Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska
Ernesto Martinez Duarte, MD, MPH: Department of Pathology, University of Nebraska Medical Center, Omaha, Nebraska
Dali Huang, MD: Department of Pathology, University of Nebraska Medical Center, Omaha, Nebraska
Benjamin Swanson, MD, PhD: Department of Pathology, University of Nebraska Medical Center, Omaha, Nebraska
Apar Kishor Ganti, MD: Division of Oncology and Hematology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska
Gwen Reiser, MS: Department of Genetic Medicine, University of Nebraska Medical Center, Omaha, Nebraska
Abbey L. Fingeret, MD: Division of Surgical Oncology, Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska
Anupam Kotwal, MD: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska; Address correspondence to Dr Anupam Kotwal, Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, University of Nebraska Medical Center, 984120 Nebraska Medical Center, Omaha, NE 68102.

Journal volume & issue: Vol. 8, no. 6
pp. 259 – 263

Abstract

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Background: Adrenal Cushing syndrome (CS) is usually benign in etiology; however, although rarely, it can be due to adrenocortical carcinoma (ACC); in which case, diagnosis and management are quite complicated. Case Report: A 34-year-old woman presented with worsening confusion, weight gain, new-onset diabetes, and hypertension. Her history was significant for a 7.4-cm left adrenal mass and CS, which were treated with left adrenalectomy 2 years ago. She received hydrocortisone replacement therapy after the surgery, which was discontinued on admission when evaluation showed hypokalemia, hypercortisolemia, and undetectable adrenocorticotropic hormone. Subsequent testing included 1-mg and 8-mg dexamethasone suppression tests, which did not suppress cortisol; late-night salivary cortisol measurement, which yielded a very high salivary cortisol level; and 24-hour urinary cortisol measurement. The level of 11-deoxycortisol was elevated. A computed tomography scan revealed multiple hepatic lesions, which were fluorodeoxyglucose avid, and a biopsy confirmed metastatic ACC. She received treatment with mitotane, metyrapone (later changed to mifepristone), doxorubicin, cisplatin, and etoposide. Over 8 weeks, mitotane levels became therapeutic at 20 mcg/mL, the hepatic masses decreased in size, and she transitioned to adrenal insufficiency and improved glycemic control. Next-generation sequencing of liver biopsy and germline testing revealed a frameshift loss-of-function allelic variant in the FH gene that encodes the protein fumarate hydratase. Discussion: We report a case of recurrent CS due to metastatic ACC in a patient with a previously resected adrenal adenoma and FH allelic variant. Conclusion: Metastatic ACC presenting with severe CS presents a diagnostic and management challenge where combination therapy guided by a multidisciplinary team is essential. FH allelic variant may contribute to ACC progression.

Published in AACE Clinical Case Reports

ISSN: 2376-0605 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the endocrine glands. Clinical endocrinology
Website: https://www.journals.elsevier.com/aace-clinical-case-reports

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