A Young Patient With Diabetes and Liver Tumors
Tom J. Harryvan and Maarten E. Tushuizen
Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
Question: A 21-year old woman was referred to our tertiary center for follow-up and treatment of multiple adenomas in the liver. Her medical history revealed a giant cell hepatitis at the age of 6 months. She was diagnosed with insulin- dependent diabetes mellitus at the age of 13 years. Her family history was positive for diabetes mellitus and hepatocel- lular carcinoma (FigureA). She developed multiple liver adenomas at age 16 years, which were previously monitored with magnetic resonance imaging every 6 months at an affiliated center. Owing to progression of some of the lesions, with several adenomas growing>5 cm in diameter, selective arterial embolization was chosen to treat the larger adenomas.
Despite this treatment, the most recent magnetic resonance imaging still showed extensive hepatic adenomatosis (Figure B), with the largest adenoma, located in the right lobe, being >8 cm (FigureC). Furthermore, a previous magnetic resonance imaging study showed signs of bleeding in one of these adenomas (data not shown). Currently, this patient has no active symptoms and physical examination only revealed hepatomegaly. Laboratory results show elevated alkaline phosphatase 626 U/L (normal range, 0-115 U/L) and gamma-glutamyl transferase 208 U/L (normal range, 0-55 U/L), with mild dis- turbances in aminotransferases (alanine aminotransferase, 77 U/L; aspartate aminotransferase, 51 U/L [normal range, 0-40 U/L]) and glycemic control (hemoglobin A1c 7.7%). Bilirubin, albumin, and the International Normalized Ratio are normal.
On referral, the patient expressed a strong desire to have children in the near future.
What is your diagnosis? What treatment should be given to this patient?
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Conflicts of interest
The authors disclose no conflicts.
© 2018 by the AGA Institute 0016-5085/$36.00
https://doi.org/10.1053/j.gastro.2017.12.031
CLINICAL CHALLENGES AND IMAGES IN GI
Gastroenterology 2018;155:25–26
Answer to: Image 6 (Page 25): Maturity-Onset Diabetes of the Young-Type III Associated Hepatic Adenomatosis
This patient had a family history of both insulin-dependent diabetes at a young age and hepatocellular carcinoma, which prompted further genetic investigation. The diagnosis maturity-onset diabetes of the young type III was made based on the identification of a pathogenic duplication in the hepatic nuclear factor 1a (HNF1a) gene (c130dup,pLeu44fs). Further genetic analysis also revealed this mutation to be present in the patient’s mother (diabetes) and a sibling (no symptoms).
No other family members could be tested, but it was assumed that this genetic trait was also present in her grandfather (diabetes) and his siblings (diabetes and hepatocellular carcinoma; FigureA). Expression of HNF1a is confined to tissues with an endodermal origin and plays a role in the transcription of genes associated with glucose homeostasis. Furthermore, HNF1a also functions as a tumor suppressor gene, shown by loss of function of this gene in pancreatic cancer and hepa- tocellular carcinoma.1Mutations in this gene have an autosomal-dominant inheritance pattern and clinical suspicion should arise when there is a family history of diabetes and liver adenoma/hepatocellular carcinoma. The clinical management of patients with maturity-onset diabetes of the young-type III associated hepatic adenomatosis is challenging, with regard to the prevention of adenoma bleeding as well as the prevention of malignant transformation (18% and 4%, respectively).2,3 Owing to the diffuse nature of this disease, surgical intervention is often not possible. Selective arterial embolization can be chosen to target the larger adenomas, but this treatment was not successful in this patient. In this patient, liver trans- plantation is now considered because of the risk of bleeding and a history of previous malignant transformation in one of her family members. Furthermore, her wish to have children might increase the risk of bleeding owing to the effect of pregnancy on hepatic adenomas. Finally, screening of affected family members is recommended in this disease and consists of biennial abdominal ultrasound examination and yearly fasting glucose monitoring.
References
1. Bluteau O, Jeannot E, Bioulac-Sage P, et al. Bi-allelic inactivation of TCF1 in hepatic adenomas. Nat Genet 2002;
32:312–315.
2. Clinical Guidelines. EASL Clinical Practice Guidelines on the management of benign liver tumours. J Hepatol 2016;
65:386–398.
3. Nault JC, Couchy G, Balabaud C, et al. Molecular classification of hepatocellular adenoma associates with risk factors, bleeding, and malignant transformation. Gastroenterology 2017;152:880–894.
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