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Unusual Patterns of Hepatic Steatosis Caused by the Local Effect of Insulin Revealed on Chemical Shift MR Imaging

¹ Department of Radiology, University of Pennsylvania Medical School, First Floor Silverstein, 3400 Spruce St., Philadelphia, PA 19104-4283.
² Department of Radiology, Hackensack University Medical Center, 30 Prospect St., Hackensack, NJ 07601.

Received May 30, 2000; accepted after revision July 26, 2000.

 
Address correspondence to E. S. Siegelman.

Abstract

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OBJECTIVE. We reveal the chemical shift MR findings of unusual patterns of hepatic steatosis caused by the local effect of insulin.

CONCLUSION. Unusual patterns of hepatic steatosis can be seen on MR imaging. Such patterns result from localized high concentrations of insulin. A rim of hepatic steatosis surrounding insulinoma metastases and a subcapsular distribution of hepatic steatosis in patients with diabetes treated with peritoneal dialysis are two such patterns that can be revealed on chemical shift imaging.

Introduction

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Diffuse and focal fatty infiltration of the liver (hepatic steatosis) has been described in association with chemotherapy, alcohol abuse, diabetes mellitus, obesity, exogenous steroids, and IV hyperalimentation [1, 2]. Focal hepatic steatosis can be mistaken for other focal lesions such as abscesses, metastases, and infiltrative primary liver neoplasms [3]. MR imaging with chemical shift gradient-echo pulse sequences can reveal and characterize fatty infiltration of the liver [4]. We present two unusual patterns of focal hepatic steatosis caused by insulin and revealed on chemical shift imaging.

Pattern 1
A 27-year-old man with a history of distal pancreatectomy for insulinoma presented with recurrent symptoms of hypoglycemia. His fasting serum glucose level was 27 mg/dL (reference range, 70-110 mg/dL), and his serum insulin level was 86 IU/mL (reference range, 5-25 IU/mL). Abdominal MR imaging was performed at 1.5 T (Signa; General Electric Medical Systems, Milwaukee, WI) to evaluate for recurrent tumor or metastatic disease. In-phase gradient-echo images showed a 12-mm hypointense liver mass (Fig. 1A). On the corresponding opposed-phase image, a peripheral 3- to 7-mm rim of low signal intensity was revealed, indicating peritumoral hepatic steatosis (Fig. 1B). The mass revealed on in-phase imaging, but not the rim of steatosis, showed early enhancement on dynamic contrast-enhanced imaging (Fig. 1C).

View larger version (87K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A. —Focal rim of hepatic steatosis surrounding an insulinoma metastasis in 27-year-old man. Axial breath-hold spoiled in-phase gradient-echo image (TR/TE, 250/4.2) shows 12-mm liver mass (straight arrow). Note phase-encoding artifact from aorta (curved arrow).

View larger version (88K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B. —Focal rim of hepatic steatosis surrounding an insulinoma metastasis in 27-year-old man. Opposed-phase image (250/2.1) corresponding to A reveals rim of signal loss surrounding lesion indicating focal hepatic steatosis (arrow).

View larger version (87K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1C. —Focal rim of hepatic steatosis surrounding an insulinoma metastasis in 27-year-old man. Fat-saturated opposed-phase image (250/2.1) shows that central tumor (arrow) but not surrounding rim of steatosis shows enhancement.

The patient underwent surgical reexploration with intraoperative sonography of the liver. A lesion in the dome of the right lobe of the liver, corresponding to the lesion revealed on MR imaging, showed a peripheral rim of increased echogenicity (Fig. 1D). This lesion was treated with radiofrequency ablation. Another superficial lesion in the anterior right lobe was excised, which revealed an islet cell metastasis with surrounding hepatic steatosis (Fig. 1E).

View larger version (132K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1D. —Focal rim of hepatic steatosis surrounding an insulinoma metastasis in 27-year-old man. Intraoperative sonogram reveals same lesion as that in C with peripheral echogenic rim (arrow).

View larger version (109K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1E. —Focal rim of hepatic steatosis surrounding an insulinoma metastasis in 27-year-old man. Photomicrograph of histologic specimen shows three zones: insulinoma metastasis (T), adjacent focal hepatic steatosis without tumor infiltration (asterisk), and normal hepatic parenchyma (L). (H and E, x20)

Pattern 2
A 35-year-old woman with end-stage renal disease caused by diabetes mellitus presented with epigastric pain and persistent nausea. Unenhanced abdominal CT revealed an irregular peripheral rim of low attenuation in the liver (Fig. 2A). Abdominal MR imaging was performed for further characterization. In-phase gradient-echo images showed an irregular, scalloped peripheral subcapsular rim of higher signal intensity relative to adjacent hepatic parenchyma (Fig. 2B), which revealed loss of signal intensity on the corresponding opposed-phase image (Fig. 2C), indicating the presence of microscopic lipid and cellular water.

View larger version (110K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2A. —Subcapsular rim of hepatic steatosis in 35-year-old woman with diabetes mellitus who had insulin in peritoneal dialysate. Unenhanced CT scan reveals irregular peripheral rim of low attenuation in liver (asterisks).

View larger version (126K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2B. —Subcapsular rim of hepatic steatosis in 35-year-old woman with diabetes mellitus who had insulin in peritoneal dialysate. Axial breath-hold spoiled in-phase gradient-echo MR image (TR/TE, 250/4.2) reveals irregular peripheral subcapsular rim of higher signal intensity relative to adjacent hepatic parenchyma (arrows).

View larger version (111K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2C. —Subcapsular rim of hepatic steatosis in 35-year-old woman with diabetes mellitus who had insulin in peritoneal dialysate. Opposed-phase image (250/2.1) corresponding to B shows signal loss in subcapsular rim indicating peripheral hepatic steatosis (asterisks).

Discussion

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Focal hepatic steatosis can have a variable appearance depending on the amount of lipid deposited, the distribution of lipids within the liver, and the presence of associated hepatic disease. General imaging features include a lack of mass effect, a characteristic distribution or location, and a rapid change over time. A common location of both focal fatty infiltration and focal fatty sparing is in the medial segment of the left lobe of the liver, anterior to the porta hepatis or adjacent to the falciform ligament [5]. Focal hepatic steatosis can have a nodular or segmental distribution [2], which can mimic malignant disease.

Chemical shift MR imaging with in-phase and opposed-phase gradient-echo pulse sequences has been shown to be sensitive in revealing microscopic fatty change of the liver [4]. Loss of signal intensity of hepatic parenchyma between the in-phase and opposed-phase images indicates the presence of microscopic lipid.

The subcapsular pattern of hepatic steatosis shown in pattern 2 has been described in the pathology literature in patients undergoing peritoneal dialysis [6]. Wanless et al. [6] reported 10 cases with a discontinuous subcapsular rim of hepatic steatosis ranging from 0.05 to 2 mm in thickness. The deep margin of the steatosis was usually scalloped. This pattern was present only in patients whose dialysate contained insulin. The subcapsular steatosis tended to be more severe in patients with a longer duration of peritoneal dialysis, higher intraperitoneal insulin dose, greater obesity, or higher serum triglycerides.

In those patients with severe steatosis, the subcapsular hepatocytes are exposed to high concentrations of insulin and glucose from the hyperosmolar dialysate bathing the hepatic surface. Insulin and glucose diffuse through the hepatic capsule and are absorbed by the subcapsular hepatocytes [6].

Insulin has been shown to be important in the pathogenesis of hepatic steatosis [6, 7]. In the fasting state (low insulin), free fatty acids in the liver are preferentially oxidated to ketone bodies. In the fed state, high insulin levels inhibit oxidation of free fatty acids and promote the esterification of free fatty acids into triglycerides, which then accumulate in hepatocytes. Focal deposition of fat, mostly in the form of triglycerides, occurs when hepatic triglyceride synthesis exceeds secretion. Thus, the peripheral subcapsular pattern of hepatic steatosis could be explained by the higher insulin concentration in the periphery of the liver.

Similarly, this theory can explain the pattern of peritumoral hepatic steatosis seen in our patient with metastatic insulinoma. The focal rim of fatty infiltration surrounding the insulinoma metastasis is likely a result of local insulin production by the tumor. Higher local insulin levels can promote the synthesis and accumulation of lipid in hepatocytes adjacent to the metastasis. A wedge-shaped region of fatty infiltration has been described peripheral to an insulinoma metastasis on CT and is hypothesized to be related to decreased portal flow and focal metabolic changes [8]. This prior report supports the role of localized insulin in focal fatty infiltration. It is important to recognize that the metastasis is confined to the central portion without extension into the adjacent hepatic steatosis, so that the size of the metastasis is not overestimated.

The peritumoral and subcapsular segments of hepatic steatosis were isointense to hyperintense to normal liver on in-phase imaging. This finding has increased specificity for hepatocellular tissue and thus can exclude a diagnosis of metastatic insulinoma or peritoneal-based metastatic disease, respectively.

In conclusion, focal hepatic steatosis caused by the local effects of insulin can present in the patterns of a focal rim surrounding insulinoma metastases and a subcapsular distribution related to insulin-rich peritoneal dialysate. Chemical shift MR imaging can reveal and characterize these unusual patterns of fatty infiltration.

References

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3. Yates CK, Streight RA. Focal fatty infiltration of the liver simulating metastatic disease. Radiology 1986;159:83 -84[Abstract/Free Full Text]
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