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Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2007-1637
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The Journal of Clinical Endocrinology & Metabolism Vol. 92, No. 12 4706-4711
Copyright © 2007 by The Endocrine Society

Accuracy of [18F]Fluorodopa Positron Emission Tomography for Diagnosing and Localizing Focal Congenital Hyperinsulinism

Olga T. Hardy, Miguel Hernandez-Pampaloni, Janet R. Saffer, Joshua S. Scheuermann, Linda M. Ernst, Richard Freifelder, Hongming Zhuang, Courtney MacMullen, Susan Becker, N. Scott Adzick, Chaitanya Divgi, Abass Alavi and Charles A. Stanley

Division of Endocrinology (O.T.H., C.M., S.B., C.A.S.), Departments of Radiology (H.Z.), Pathology and Laboratory Medicine (L.M.E.), and Surgery (N.S.A.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; and the Department of Radiology (M.H.-P., J.R.S., J.S.S., R.F., C.D., A.A.), University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4283

Address all correspondence and requests for reprints to: Charles A. Stanley, M.D., Division of Endocrinology, The Children’s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, Pennsylvania 19104. E-mail: stanleyc{at}email.chop.edu.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Objectives: Focal lesions in infants with congenital hyperinsulinism (HI) represent areas of adenomatosis that express a paternally derived ATP-sensitive potassium channel mutation due to embryonic loss of heterozygosity for the maternal 11p region. This study evaluated the accuracy of 18F-fluoro-L-dihydroxyphenylalanine ([18F]DOPA) positron emission tomography (PET) scans in diagnosing focal vs. diffuse disease and identifying the location of focal lesions.

Design: A total of 50 infants with HI unresponsive to medical therapy were studied. Patients were injected iv with [18F]DOPA, and PET scans were obtained for 50–60 min. Images were coregistered with abdominal computed tomography scans. PET scan interpretations were compared with histological diagnoses.

Results: The diagnosis of focal or diffuse HI was correct in 44 of the 50 cases (88%). [18F]DOPA PET identified focal areas of high uptake of radiopharmaceutical in 18 of 24 patients with focal disease. The locations of these lesions matched the areas of increased [18F]DOPA uptake on the PET scans in all of the cases. PET scan correctly located five lesions that could not be visualized at surgery. The positive predictive value of [18F]DOPA in diagnosing focal adenomatosis was 100%, and the negative predictive value was 81%.

Conclusions: [18F]DOPA PET scans correctly diagnosed 75% of focal cases and were 100% accurate in identifying the location of the lesion. These results suggest that [18F]DOPA PET imaging provides a useful guide to surgical resection of focal adenomatosis and should be considered as a guide to surgery in all infants with congenital HI who have medically uncontrollable disease.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
CONGENITAL HYPERINSULINISM (HI) is the most common cause of persistent hypoglycemia in infants and children. This condition is most often associated with recessive mutations of the β-cell ATP-sensitive potassium (KATP) channel. The channel is composed of two subunits, SUR1 and Kir6.2, encoded by adjacent genes on chromosome 11p15.1, ABCC8, and KCNJ11. In cases of diffuse HI, infants have mutations of both KATP parental alleles resulting in dysregulation of insulin secretion from all β-cells (1, 2). Recessive KATP mutations may also cause focal HI, in which there is an area of β-cell adenomatosis due to embryonic loss of heterozygosity (LOH) for the maternal 11p region and expression of a paternally derived KATP mutation (3, 4). Because KATP mutations block diazoxide action, surgical intervention is often necessary to control hypoglycemia in both forms of KATP HI. Surgery is only palliative in diffuse HI but can be curative in the cases of focal adenomatosis if the lesion can be found.

The surgical management of infants with medically uncontrolled congenital HI depends on being able, first, to distinguish preoperatively between the focal and diffuse forms of the disease, and, second, to locate accurately the area of the focal lesion. Focal lesions are difficult to identify at surgery and cannot be detected using conventional imaging techniques (5). Interventional radiological techniques such as selective pancreatic arterial calcium stimulation with hepatic vein insulin sampling (ASVS) and transhepatic portal venous insulin sampling (THPVS), as well as functional tests of insulin responses to secretagogues, are unable to reliably distinguish focal vs. diffuse disease (6, 7, 8).

A preliminary report from Otonkoski et al. (9) suggested that 18F-fluoro-L-dihydroxyphenylalanine ([18F]DOPA) positron emission tomography (PET) scans could image focal lesions in congenital HI. This is based on the fact that neuroendocrine cells have an affinity for taking up amino acid precursors, such as L-dihydroxyphenylalanine, and decarboxylating them to dopamine through the action of aromatic amino acid decarboxylase (10, 11, 12, 13, 14). Neuroendocrine tumors such as carcinoids and pheochromocytomas have been successfully localized using [18F]DOPA PET (15, 16). Several studies have shown that normal pancreatic β-cells take up L-dihydroxyphenylalanine (13, 14). Two small series of cases successfully imaging focal HI lesions in infants have been recently reported (17, 18, 19). On the basis of the preliminary results of our study, the [18F]DOPA PET scan was 96% accurate in the diagnosis of focal HI and 100% accurate in localizing the focal lesion (20).

The purpose of the present study was to assess the reliability of [18F]DOPA PET scans in diagnosing focal adenomatosis preoperatively in infants with HI and also to determine its accuracy in localizing focal lesions to aid in their surgical excision. For this purpose, we studied a large group of infants who all required surgery for medically uncontrollable HI. This made it possible to determine the accuracy of the PET scan by comparison with histological diagnosis in all cases.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subjects

The infants included in this study were referred to the Hyperinsulinism Center at the Children’s Hospital of Philadelphia between December 2004 and March 2007. Only infants who required surgical intervention after failing trials of medical therapy with diazoxide and octreotide were considered eligible for the study. This ensured that the results of the [18F]DOPA PET scan could be correlated with a diagnosis based on permanent histological sections in all of the cases. Failure of medical therapy was defined as the inability to maintain plasma glucose levels greater than 70 mg/dl for at least a 6-h fasting period. In most cases, control of hypoglycemia before surgery required continuous dextrose infusions at rates greater than 10 mg/kg·min.

There were 11 additional infants with HI who were diazoxide unresponsive but considered to be stable on medical therapy with octreotide and tube feedings also evaluated with [18F]DOPA PET. Eight of these 11 underwent surgery electively after PET scan results were available, and their parents elected surgical intervention. These patients were not included in the analysis of study results.

The diagnosis of HI was based on previously described criteria (21, 22). Mutation analysis of KATP genes was performed by sequencing coding exons and flanking intronic regions of genomic DNA from peripheral blood leukocytes using a commercial laboratory (Athena Diagnostics, Inc., Worcester, MA). In most cases results of mutation analyses were not available for preoperative diagnosis. LOH in focal adenomatosis lesions was identified in paraffin-embedded surgical specimens by haplotype analysis using microsatellite markers and/or by absence of p57KIP2 immunostaining (3, 4, 23, 24).

PET imaging technique

The [18F]DOPA was administered under a Food and Drug Administration Investigational New Drug modified to allow inclusion of children. The study was approved by the institutional review boards of the Children’s Hospital of Philadelphia and the Hospital of the University of Pennsylvania. Written informed consent was obtained from the parents of the subjects. [18F]DOPA PET scans were performed at the University of Pennsylvania PET Imaging Facility. Medications that could potentially interfere with pancreatic β-cell function, such as diazoxide, octreotide, and glucagon, were discontinued 5 d, 2 d, and 12 h, respectively, before the PET scan. This step may be unnecessary because Ribeiro et al. (18) found no significant differences in [18F]DOPA uptake between PET scans performed with and without octreotide and diazoxide. Patients were intubated and sedated with general anesthesia. Rates of iv glucose infusion were adjusted to maintain plasma glucose levels greater than 70 mg/dl during the PET scan and to enhance urinary excretion of isotope. In one case a catheter was passed to facilitate bladder emptying. The [18F]DOPA was manufactured using established procedures (25) by the Cyclotron Facility of the University of Pennsylvania on the day of the test. Patients were injected iv with 3–6 MBq/kg (0.08–0.16 mCi/kg) of [18F]DOPA.

Scanning began within 10 min of injection, and five or six consecutive 10-min acquisitions were performed, followed by a measured transmission scan using a rotating Cs-137 source. The images were acquired on a PET camera based on Anger-logic gadolinium oxyorthosilicate detectors, designed and built by the Physics and Instrumentation Group at the University of Pennsylvania (26). This instrument, used clinically for brain PET, has both axial and transverse fields-of-view of 25 cm, suitable for imaging infants. An abdominal computed tomography (CT) with contrast was obtained separately to define the anatomy of the pancreas and adjacent tissue before surgery. To assist in defining the location of focal lesions, the CT image was coregistered with the PET scan using Syntegra software (Phillips Medical Systems, Bothell, WA).

Image interpretation

The image set for each patient was visually interpreted by a nuclear medicine physician (A.A. or C.D.) well versed in PET interpretation. Images were reviewed in all three planes as well as maximum intensity projection views. The presence and pattern of uptake in the pancreas were taken into consideration in generating final reports for these scans. The image was considered positive for focal adenomatosis when the uptake of the radiotracer in a part of the pancreas was visually higher than the uptake in the remaining pancreatic tissue. When there was nearly uniform [18F]DOPA uptake throughout the pancreas, the examination was considered to represent diffuse disease.

Surgical technique and intraoperative frozen section evaluation. During surgery, biopsies from the head, body, and tail of the pancreas were obtained and examined for islets containing one or more β-cells with enlarged nuclei, the histological marker for diffuse disease, as described by Suchi et al. (27) and Rahier et al. (28). The lack of nuclear enlargement in islets from all three regions indicated the absence of diffuse disease, prompting further biopsies to find the focal adenomatosis lesion. The results of the PET scan were made available to the surgeon to help in the localization of potential focal lesions. The final diagnosis of focal adenomatosis or diffuse disease was made by a pathologist who was masked to the results of the PET scan.

In addition to the typical focal and diffuse forms of HI, a third type of pancreatic lesion has been identified and termed "localized islet cell nuclear enlargement" (LINE) (27, 29). LINE is characterized histologically by regional confinement of islet cell nucleomegaly, with an absence of nuclear enlargement in islets outside the lesional area and lack of focal adenomatosis within the resected specimen.

Statistical analysis and sample size

The efficient-score method was used to calculate 95% confidence intervals (CIs) for proportions (30). Fisher’s exact probability test was used to determine associations between patient clinical characteristics and the form of HI. Probability values less than 0.05 were considered statistically significant.

On the basis of previous reports on ASVS and THPVS (18, 19), we assumed that 50% of surgical cases would have focal adenomatosis and that at least 70% of focal lesions would be correctly identified by the [18F]DOPA PET test. Sample size estimates based on these assumptions indicated that 50 total cases (25 focal cases) would provide an estimate of test accuracy between 50 and 87% (95% CI). Test accuracy was defined as the percentage of focal cases correctly identified with the PET scan.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Table 1Go summarizes the clinical features of the 50 infants who met the study criteria of requiring surgery for medically uncontrollable HI. There were 24 cases with focal adenomatosis, 24 with diffuse disease, and two with LINE. The infants with focal adenomatosis and diffuse disease exhibited typical features of severe congenital HI, including large birthweight and hypoglycemia during the first week of life. Infants with focal adenomatosis tended to have milder disease, consistent with previous reports (8). Neither of the LINE cases was large for gestational age, and only one presented during the first week of life. One patient had hypoglycemia during the PET procedure secondary to tenuous iv access. Otherwise, there were no adverse events.


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  		TABLE 1. Clinical features of 50 infants with HI studied preoperatively with [18F]DOPA PET scan

 
Figure 1Go illustrates an [18F]DOPA PET scan in an infant with diffuse disease. In an image obtained 10 min after injection of the isotope, uniform [18F]DOPA uptake was observed throughout the pancreas but was somewhat obscured by intense uptake in the kidneys due to isotope excretion in the urine (Fig. 1AGo). In a later image taken 30 min after injection of the isotope, kidney uptake was less intense, and the pancreas was easier to visualize (Fig. 1BGo). After injection of [18F]DOPA, the high uptake in the kidneys decreased with time, but uptake in the pancreas was consistently higher than uptake in the liver and remained constant during the entire 50-min scan.


Figure 1
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  		FIG. 1. [18F]DOPA PET of a patient with diffuse disease. A, Depth-weighted maximum intensity projection sagittal image done 10 min after injection. B, Maximum intensity projection sagittal image done 30 min after injection.

 
Figure 2Go illustrates an [18F]DOPA PET scan in an infant with a focal adenomatosis lesion in the head of the pancreas. There was an intense area of [18F]DOPA uptake in the head of the pancreas (Fig. 2AGo). The body and tail of the pancreas had less intense, diffuse uptake, demonstrating that the labeled DOPA is taken up by normal pancreatic tissue. Coregistration of the PET and CT scans (Fig. 2Go, B–D) confirmed that the location of the focal uptake was in the head of the pancreas. Throughout the 50-min scan, the uptake of isotope in the lesion was consistently higher than the uptake in the unaffected areas of the pancreas, indicating a greater concentration of endocrine cells.


Figure 2
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  		FIG. 2. [18F]DOPA PET of a patient with a focal adenomatosis in the head of the pancreas. A, Maximum intensity projection sagittal image done 50 min after injection. Transverse views show: focal uptake of [18F]DOPA in pancreatic head (B), confirmation of [18F]DOPA uptake in the pancreatic head with CT coregistration (C), and less intense uptake in normal neighboring pancreatic tissue (D).

 
Table 2Go compares the PET scan readings and final histological diagnoses in the 50 infants studied. In all of the 24 typical diffuse cases, the preoperative interpretation of the PET scan was the same as the histological diagnosis of diffuse disease. The two patients with LINE did not demonstrate focal uptake on the PET scan but had generalized pancreatic uptake and were correctly read as not having focal adenomatosis. There was no difference in PET images between the patients with LINE and those with typical diffuse disease. Because infants with LINE have no histological features of focal adenomatosis, LINE cases were included in the category of diffuse disease in the analysis. Thus, in all of these 26 cases, PET imaging correctly diagnosed the absence of focal adenomatosis. In 18 of the 24 cases of focal adenomatosis, the interpretation of the PET scan correctly diagnosed the presence of focal adenomatosis. Overall, [18F]DOPA PET was 88% accurate in distinguishing diffuse disease from focal adenomatosis (95% CI 75–95%). Two of these 18 patients with focal adenomatosis underwent ASVS testing before surgery and PET imaging. Although the ASVS test suggested focal adenomatosis in both cases, it was correct in localizing the lesion in only one of the two.


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  		TABLE 2. Results of preoperative [18F]DOPA PET scans in 50 infants with congenital HI

 
Of the cases with focal adenomatosis not recognized by [18F]DOPA PET scans, five had significantly smaller lesions when compared with the 18 lesions that were correctly identified (0.6 ± 0.2 vs. 1.3 ± 4.2 cm; P = 0.05). In one of these five, surgical exploration revealed a palpable lesion on the tail of the pancreas. A retrospective review of the PET scan indicated that the lesion was probably assumed to be part of the left kidney secondary to its location. In two others, a retrospective review of the PET images identified an area of focal uptake corresponding to the focal lesion. In the fourth and fifth cases, the focal lesion appeared to have been either too small to be revealed by the PET scan or too thin in shape to be detected. In the sixth case, diffuse uptake was observed throughout the pancreas consistent with diffuse disease, but the interpretation mentioned the possibility of an extensive focal lesion. The latter possibility was confirmed at surgery, in which an area of islet adenomatosis occupied 80–90% of the pancreas.

As shown in Table 3Go, among the 18 focal cases with focal adenomatosis identified by PET scan, 100% were correctly localized (13 pancreatic head, three pancreatic body, and two pancreatic tail). The surgeon was unable to detect 25% of these lesions at surgery using palpation and anatomical cues but was aided by the PET scan result in searching for the lesion by biopsies in the area suspected. Of the six focal lesions that were not detected on PET scan, five were visible to the surgeon, and all were found on initial biopsies; the sixth case with an extensive adenomatosis lesion was detected readily on the first exploratory biopsies.


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  		TABLE 3. Accuracy of [18F]DOPA PET for localizing focal lesions

 
Most of the patients with focal adenomatosis had limited pancreatectomy, and seven had less than 25% pancreatectomy (Table 4Go). Preoperative suspicion of focal adenomatosis in the tail of the pancreas allowed for laparoscopic excision of the focal lesion in two cases, which shortened the postoperative length of stay (average 20 d open surgery vs. 11.5 d laparoscopic; not significant). Preoperative identification of a focal lesion in the head of the pancreas in eight of the infants allowed the surgeon to perform a proximal pancreatectomy with Roux-en-Y, which preserved the tail of the pancreas. Compromised vascular supply to the small intestine necessitated a Whipple procedure in one patient. Two patients with focal adenomatosis required redo operations for persistent hypoglycemia after a laparoscopic resection and incomplete removal of the large focal adenomatosis.


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  		TABLE 4. Surgical procedures in 50 infants with preoperative [18F]DOPA PET scan

 
Of the 24 infants with focal adenomatosis, 22 were cured by surgery. The other two cases had residual areas of lesion that would have been dangerous to remove with redo surgery. Of the 24 infants with diffuse disease, 17 had improvement in glucose requirement but required continued medical therapy. Six infants required insulin therapy postoperatively; one infant with diffuse disease was able to be discharged without medical therapy.

Among the 22 focal cases in which mutation analysis was completed, 100% had a paternal-only KATP channel mutation. Mutation analysis of the KATP genes in diffuse cases identified two mutations in 67% of the cases in which mutation analysis was completed. In four diffuse cases, only one of the expected two mutations could be identified; two of these were paternally derived. These four cases may have a postzygotic mutation on the other allele that was not detectable in peripheral blood. In three diffuse cases and two LINE cases, no mutations were found.

Of the 11 infants considered to have medically controllable HI, [18F]DOPA PET scans were interpreted as focal in three and diffuse in eight. Four of the cases read as diffuse did not have surgery, and their histology is unknown. The three read as focal all had focal lesions. One of the other cases read as diffuse had a focal lesion; the other three had diffuse disease.


   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
The present study shows that [18F]DOPA PET is useful in infants with medically unresponsive congenital HI, not only for diagnosing focal vs. diffuse disease, but also for accurately identifying the location of the focal lesion to guide surgical resection. Diagnosis of focal vs. diffuse disease was accurate in 44 of 50 cases (88%; 95% CI 75–95%). The sensitivity of [18F]DOPA PET in diagnosing focal adenomatosis was 75% (95% CI 53–89%). The positive predictive value of [18F]DOPA in diagnosing focal adenomatosis was 100%, and the negative predictive value was 81%. Of the 18 focal lesions that were identified on PET scan, the location of the lesion was correctly defined in all of the cases (95% CI 78–100%).

We purposely limited our study population to infants with severe HI requiring surgery to be able to correlate the PET images with histological diagnosis in all of the cases. This selection criterion may have led to a selection bias for infants with the most severe disease and, therefore, possibly with the largest focal lesions. Some information on this point was obtained in a separate group of 11 infants with milder, medically controllable HI in whom surgery was elective. Although the number of cases was limited, it appeared that the success with [18F]DOPA PET scans in identifying focal lesions was similar in this group and in those with more severe cases. A recent report indicates that [18F]DOPA PET scans may also be used to localize insulinomas in adults with acquired HI (31).

The present data show that [18F]DOPA PET is more accurate than THPVS or ASVS in diagnosing focal vs. diffuse disease and, especially, in identifying the location of the focal lesion. In the Necker Hospital series of 45 cases, the sensitivity of THPVS for detecting a focal lesion was 89%, but the rate of false positives was 29% (4). In the Children’s Hospital series, ASVS correctly diagnosed diffuse disease in only four of 13 cases and localized the focal lesion in 73% of 33 cases (8). However, both of these procedures only grossly indicate the region of the pancreas containing a focal lesion and are unable to provide precise localization needed for surgical resection. In addition, although PET scans require general anesthesia and a small dose of radioactivity, the method is much less invasive than either THPVS or ASVS and does not require exposure to prolonged hypoglycemia or the removal of large volumes of blood.

Genetic analysis is a potentially attractive method for distinguishing focal from diffuse HI preoperatively because the focal form is expected to be associated with a single, paternally derived KATP mutation, whereas diffuse HI is expected to require mutations of both parental alleles. In the present series, consistent with this expectation, all of the focal cases had a single demonstrable KATP mutation that had been transmitted from the infant’s father, and all of the focal lesions in these cases showed evidence of maternal LOH. However, in the diffuse cases, direct sequencing of the KATP channel genes in genomic DNA from peripheral blood was able to find the expected two mutations only two thirds of the time, consistent with previously reported series (3, 8). Presumably, the remaining diffuse cases had mutations that escaped detection, possibly because they were in noncoding regions or possibly because of embryonic mutation events. Of note, among the diffuse cases with only one identifiable mutation, half had a paternal-only mutation that could be confused as indicating focal disease. Therefore, because of the possibility of undetected mutations, genetic analysis is reliable only for preoperatively diagnosing diffuse disease based on identifying at least one maternal ABCC8 or KCNJ11 mutation. Detection of a paternally derived mutation is compatible with but does not guarantee that an infant has a focal lesion.

The accuracy of [18F]DOPA PET in our series is consistent with previous reports of smaller series. Otonkoski et al. (19) and Ribeiro et al. (18) reported results in groups of nine subjects each in which [18F]DOPA PET scans also appeared useful in diagnosing focal congenital HI. PET scans accurately diagnosed five focal cases in both studies with no false positives or negatives. These patients were included in a compilation of PET scans in 94 children with HI at various European facilities, 48 of whom were surgically treated. This compilation gave a sensitivity of 94% and a specificity of 100% when comparing PET and histology (32). However, in all of these three reports, because some cases did not have surgery, the rate of false-negative PET scans is not known. The present study, in which histopathological diagnosis was ascertained for all cases, clearly demonstrates that not all focal lesions are detectable by PET scan.

In the present study, 20% of focal lesions were missed on the preoperative PET scan interpretation. This was due to the small size of the lesions in two of the cases. However, in three others, it appeared to be due to overly conservative interpretation of the PET image because postoperative reviews of the scans identified increased uptake in areas that corresponded to the location of the lesion. Thus, although conservative interpretation is appropriate in the diagnosis of focal vs. diffuse disease, once a commitment for surgery is made, efforts should be made to direct the attention of the surgeon to areas that might be suspicious. Subtle lesions may be easier to detect by evaluating scans from later time points after injection of isotope, when uptake by the kidneys is less intense. It should also be noted that the PET images from focal cases clearly show that normal, unaffected β-cells take up [18F]DOPA, confirming that uptake of isotope is related to the mass of β-cells and is not caused by the dysregulation of insulin secretion in areas of adenomatosis.

In summary, [18F]DOPA PET scan is highly accurate in the preoperative diagnosis of infants with focal HI. Of equal importance, [18F]DOPA PET scans were found to be 100% accurate in localizing the focal lesions and aiding in successful surgical resection. [18F]DOPA PET scans may also be useful in infants who are controllable medically but may have a curable focal lesion based on mutation analysis. There is a possibility that small focal lesions may escape detection by [18F]DOPA PET scan; therefore, identification and resection of such lesions depend on a well-experienced surgeon and surgical pathology team. The encouraging results of the present series of cases suggest that preoperative [18F]DOPA PET imaging should be strongly considered in all infants with congenital HI who require surgery.


   Acknowledgments
 
We thank the nursing team of the Hyperinsulinism Center and the General Clinical Research Center staff for their assistance with these studies.


   Footnotes
 
Supported in part by grants from the National Institutes of Health RO1-DK-56268 (to C.A.S.) and General Clinical Research Center MO1-RR-00240. O.T.H. was supported by National Institutes of Health training Grant T32-DK63688 (to C.A.S.) and by the Lawson Wilkins Pediatric Endocrine Society Research Fellowship Award.

Disclosure Statement: The authors have nothing to disclose.

First Published Online September 25, 2007

Abbreviations: ASVS, Selective pancreatic arterial calcium stimulation with hepatic vein insulin sampling; CI, confidence interval; CT, computed tomography; [18F]DOPA, 18F-fluoro-L-dihydroxyphenylalanine; HI, hyperinsulinism; KATP, ATP-sensitive potassium; LINE, localized islet cell nuclear enlargement; LOH, loss of heterozygosity; PET, positron emission tomography; THPVS, transhepatic portal venous insulin sampling.

Received July 23, 2007.

Accepted September 17, 2007.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

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