Endocrine

https://doi.org/10.1007/s12020-018-1633-1

ENDOCRINE SURGERY

Incidence and management of postoperative hyperglycemia in

patients undergoing insulinoma resection
Pavel Nockel1,2 Amit Tirosh1,3 Mustapha El Lakis1 Apostolos Gaitanidis4 Roxanne Merkel1 Dhaval Patel1
● ● ● ● ● ●

Naris Nilubol1 Samira M. Sadowski5 Craig Cochran6 Phillip Gorden6 Electron Kebebew7
● ● ● ●

Received: 17 January 2018 / Accepted: 10 May 2018

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Abstract
Purpose It has been proposed that rebound hyperglycemia after resection of insulinoma indicates a biochemical cure. However,
there is scant objective data in the literature on the rate and need for intervention in hyperglycemia in patients undergoing
resection of insulinoma. The goal of our study was to evaluate the rate of postoperative hyperglycemia, any predisposing factors,
and the need for intervention in a prospective cohort study of all patients undergoing routine glucose monitoring.
Methods A retrospective analysis of 33 patients who had an insulinoma resected and who underwent routine postoperative
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monitoring of blood glucose (every hour for the first six hours then every four hours for the first 24 h) was performed.
Hyperglycemia was defined as glucose greater than 180 mg/dL (10 mmol/l).
Results Twelve patients (36%) developed hyperglycemia within 24 h (range 1–16 h). In patients with hyperglycemia, the
mean maximum plasma glucose level was 221.5 mg/dL (range 97–325 mg/dL) (12.3 mmol/l), and four (33%) patients were
treated with insulin. There was no significant difference in age, gender, body mass index (BMI), tumor size, biochemical
profile, or surgical approach and extent of pancreatectomy between patients who developed hyperglycemia and those who
did not. Pre-excision and post-excision intraoperative insulin levels were evaluated in 14 of 33 patients. The percentage
decrease of the intraoperative insulin levels was not significantly different between patients who developed hyperglycemia
and those who did not. All patients with postoperative hyperglycemia had normalization of their glucose levels, and none
were discharged on anti-hyperglycemic agents.
Conclusions Hyperglycemia is common after insulinoma resection, and a subset of patients require transient treatment with
insulin.
Keywords Insulinoma Pancreatic neuroendocrine tumor Hyperglycemia Surgery
● ● ●

Introduction patients have an inherited predisposition. Most insulinomas

Insulinomas are the most common functional pancreatic
neuroendocrine tumor, with a reported incidence of 0.1–0.3
cases per 100,000 individuals per year [1, 2]. Approximately
90% of insulinomas are sporadic, while the remaining 10% of
are solitary lesions and benign tumors [2, 3]. The median age
of presentation in patients with sporadic insulinoma is 50
years, and insulinoma has a slightly higher female pre-
ponderance. Patients with multiple endocrine neoplasia
(MEN) type 1 syndrome have a predisposition to developing

* Electron Kebebew 4
Second Department of Surgery, University General Hospital of
kebebew@stanford.edu Alexandroupoli, Democritus University of Thrace Medical School,
Alexandroupoli, Greece
1
Endocrine Oncology Branch, National Cancer Institute, National 5
Thoracic and Endocrine Surgery, University Hospitals of Geneva,
Institutes of Health, Bethesda, MD, USA
Geneva, Switzerland
2
Presbyterian Medical Group, Endocrine Surgery, 6
The National Institute of Diabetes and Digestive and Kidney
Albuquerque, NM, USA
Diseases, National Institutes of Health, Bethesda, MD, USA
3
NET service, Sheba MC, and Sackler Faculty of Medicine, Tel 7
Department of Surgery, Surgery and Cancer Center, Stanford
Aviv University, Tel Aviv, Israel
University School of Medicine, Stanford, CA, USA

insulinoma, which typically manifests in them at an earlier
age and is more likely to be multifocal [3]. Hyperinsulinemic
hypoglycemia and the resultant autonomic overactivity are the
predominant clinical manifestations, often presenting with the
features of Whipple’s triad, namely hypoglycemic symptoms,
low blood glucose, and relief of symptoms after glucose
administration [4]. The diagnosis is established by an inap-
propriately elevated level of insulin and proinsulin, along with
hypoglycemia [less than 50 mg/dL (2.77 mmol/l)], during a
48-h supervised fast [5, 6].
Postoperative rebound hyperglycemia has long been
known to manifest after insulinoma resection and has been
attributed to the atrophy of the remaining pancreatic islet
cells, as well as the hormonal effects of the glucagon,
growth hormone, and glucocorticoids that prevail during the
immediate postoperative period [7, 8]. Some investigators
have reported that elevations in blood glucose eventually
occur, to some extent, in all patients after surgery [9–11],
and it has been proposed that postoperative hyperglycemia
can be used as a marker of complete resection or even as an
intraoperative guide for appropriate resection [12]. How-
ever, others have questioned its clinical utility, noting that a
significant proportion of patients display delayed elevations
in blood glucose, thus limiting its use as an intraoperative
guide for complete resection [11, 13–15]. Blood glucose
levels may also be influenced by multiple other factors, such
as anesthetic agents and intraoperative fluid management,
and, hence, some patients may not display hyperglycemia in
the postoperative period [16].
The duration and significance of postoperative hyper-
glycemia in patients who have insulinoma resection is
unknown. Most studies suggest hyperglycemia is transient,
taking anywhere from 3 to 4 days [7] to more than 9 days to
resolve [11]. In addition, there are reports of previously
unknown diabetes mellitus that manifested after insulinoma
resection, leading to persistent postoperative hyperglycemia
and requiring permanent treatment [17, 18]. Currently, there
is no high-quality data on the rate of hyperglycemia
(defined as plasma glucose ≥ 180 mg/dL (10 mmol/L)) and
the need for intense glucose monitoring and treatment after
insulinoma resection.
In this study, we determined the rate of hyperglycemia
after insulinoma resection, potential clinical and intrao-
perative factors associated with it, and the natural history of
hyperglycemia in a prospective cohort observational study
of patients undergoing intense glucose monitoring.
Materials and methods
Patients with suspected or confirmed insulinoma were
enrolled in a prospective clinical protocol at the National
Institutes of Health (NIH) Clinical Center after giving
Endocrine
written informed consent (NCT00001276, NCT01005654).
The studies were approved by the institutional review
boards of the National Institute of Diabetes and Digestive
and Kidney Diseases and the National Cancer Institute.
The biochemical diagnosis of an insulinoma was made
based on a patient’s glucose, insulin, proinsulin, and C-
peptide levels during a 48-h supervised fast, as previously
described [19]. Patients underwent multimodal imaging,
including pancreatic protocol contrast-enhanced computed
tomography (CT) and magnetic resonance imaging (MRI),
selective arterial calcium stimulation testing, endoscopic
ultrasound, 111In-pentetreotide single-photon emission
68
computed tomography (SPECT)/CT, and Ga-
DOTATATE positron emission tomography/computed
tomography (PET/CT).
Preoperative insulin levels were obtained via peripheral
venous or arterial puncture prior to the start of the operation
and postoperative insulin levels were obtained twenty
minutes after the resection of insulinoma. The specimens
were analyzed with Roche cobas® e601 blood analyzer
(Pleasanton, CA).
Postoperative monitoring included routine measurement
of blood glucose at a minimum of once every hour for the
first six hours and every four hours for the first 24 h after
surgery. Hyperglycemia was defined as plasma glucose ≥
180 mg/dL (10 mmol/l) [20]. Serum glucose was collected
with a finger stick and processed with a StatStrip GLU
Meter glucometer (Nova Biomedical UK, Runcorn, Che-
shire, UK). All patients with resolution of hypoglycemic
symptoms and normalization of glucose levels on post-
operative evaluation were included in the study. Routinely,
patients had the dextrose infusion stopped at the time of the
operation when a neuroendocrine tumor was diagnosed on
frozen section and intraoperative glucose was normal
(within 20 min of insulinoma resection). Only two patients
received fluids containing 10% dextrose solution during the
first 24 h after the operation.
The statistical analysis of patient demographics, clinical
characteristics, and laboratory data was performed using t-
test, Mann Whitney test and Fisher’s Exact tests, where
appropriate. A p value < 0.05 was considered statistically
significant. IBM SPSS Statistics Data Editor (New York,
NY) and Microsoft Excel (Redmond, WA) were used for
statistical analyses.
Results
The clinical and laboratory characteristics are summarized
in Table 1. Twenty-eight patients had sporadic insulinoma,
and five patients had MEN1-associated insulinoma. Nine-
teen patients underwent tumor enucleation (57.6%), 13
underwent distal pancreatectomy (41.9%), and one
Endocrine

Table 1 Demographic
Postoperative hyperglycemia No postoperative hyperglycemia P value
characteristics of patients based
(n = 12) [mean ± SD] (n = 21) [mean ± SD]
on postoperative hyperglycemia
Age (years) 56.8 ± 15.1 50.5 ± 14.5 0.24
BMI (kg/m2) 33.7 ± 8.3 30.3 ± 8 0.26
Size (cm) 1.42 ± 0.49 1.56 ± 0.76 0.57
Hospital stay (days) 11.2 ± 8.2 7.5 ± 3.6 0.16
Pre-op Insulin (mcU/mL) 40.9 ± 31.6 39.2 ± 38.1 0.90
C-peptide (ng/mL) 5.6 ± 4.2 5.4 ± 3.4 0.89
Proinsulin (pmol/L) 257 ± 262 242 ± 335 0.90
Duration of fast (h) 14.7 ± 9.0 12.6 ± 9.2 0.53
Duration of operation 275 ± 83.3 233.3 ± 82.7 0.18
(min)
Intraoperative insulin 66 ± 17.8 (n = 4) 53.7 ± 44.4 (n = 8) 0.61
drop (%)
Gender (female) 8/12 13/21 1
Family history of diabetes 3/12 9/21 0.70
mellitus
Sporadic vs. MEN1 Sporadic 9 Sporadic 19 0.30
MEN1 3 MEN1 2
Extent of resection Enucleation 5 Enucleation 14 0.33
Distal Pancreatectomy 6 Distal Pancreatectomy 7
Whipple 1 Whipple 0
Type of operation Open 8 Open 7 0.27
Laparoscopic 1 Laparoscopic 7 0.30
Laparoscopic/hand-assisted 3 Laparoscopic/hand-assisted 7
SD standard deviation, BMI body mass index, MEN1 multiple endocrine neoplasia type 1 syndrome

underwent a Whipple procedure (3.2%). In 13 patients, an
open resection was performed, while 20 patients underwent
a laparoscopic resection, ten of whom had a hand-assisted
laparoscopic procedure performed.
Postoperative hyperglycemia
Twelve of 33 patients (36.3%) had postoperative hyper-
glycemia (glucose level ≥ 180 mg/dL [>10 mmol/l]) in the
first 24 h after insulinoma resection (range 1–16 h), and two
patients remained hyperglycemic after 24 h (Fig. 1). Two
other patients manifested hyperglycemia more than 24 h
after surgery. Eight out of 12 patients developed hyper-
glycemia in the first 4 h, while four patients developed it in
the first 8 h. The median peak blood glucose level during
the first 24 h for all patients was 171 mg/dL (9.5 mmol/l,
range 126–325 mg/dL [7–18 mmol/l]). Sixteen of 33
patients (48.48%) reached the peak of their post-excision
blood glucose levels on postoperative day zero, and most
patients (17/33, 51.5%) reached their peak levels by the end
of the first postoperative day (Table 2). One patient had a
history of insulin resistance, and 11 patients (35.5%) had a
family history of diabetes mellitus. None of the other
patients had a personal history of diabetes mellitus or glu-
cose intolerance. Among patients with no postoperative
hyperglycemia we did not find a time dependent trend in
plasma glucose levels.
No patient required insulin intraoperatively. Four patients
received insulin within 24 h of surgery for blood glucose
levels greater than 180 mg/dL (10 mmol/l), and two of those
patients received insulin for blood glucose levels greater
than 200 mg/dL (11.1 mmol/l). None of the two patients who
received 10% Dextrose solution in their postoperative fluid
developed hyperglycemia. The average postoperative length
of hospital stay was 9 days and prior to discharge, every
patient’s hyperglycemia resolved, and none of the patients
were discharged on anti-hyperglycemic medications.
The patients’ characteristics, such as BMI, age, gender,
biochemical profile, duration of the supervised fast, and pre-
sence of predisposing germline mutations, did not have any
statistically significant association with the development of
post-resection hyperglycemia. Furthermore, hyperglycemia
was not associated with the tumor’s location in the pancreas,
the operative approach, or the duration of the operation.
Intraoperative insulin level
Insulin levels before and after excision were measured in 14
patients. The mean pre-excision insulin was 36.06 ±
39.9 mIU/L, while the mean post-excision levels were 9.35
 Endocrine

A Mean Glucose and Standard Deviaon

250

200
Mean Glucose Level mg/dL

150

100

50

0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Time (hour)

B Range of Glucose Levels in Paents During the First 24 Hours Aer Insulinoma Resecon
350

325

300

260
250

230
221
211
202
Glucose mg/dL

200 198 196

189 192
187
172 175 172 171 173 171
167 166 165 167
158 156 160 158 156
150 155
148 145 147 149
138 138
125 124 125 126 128
118 117 118 118 115
112 110 110 107 112 109 111
107 104
100 98 102
97 97
89 89 91 88 92
85 83 83
76
59
50

0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33
Paent

Maximum Minimun

Fig. 1 Postoperative glucose levels after insulinoma resection. a Average glucose levels by hour (error bars: standard deviation). b Minimum and
maximum glucose levels after insulinoma resection

± 7.20 mIU/L, with a mean percent drop of 59.3% ± 34.6. Discussion

Ten of 14 (71%) patients had a drop in insulin levels greater
than 50% twenty minutes after tumor excision (Table 3). Hyperglycemia has long been known to manifest post-
The percentage post-excision insulin drop was not sig- operatively in patients after resection of insulinoma, but the
nificantly different between patients who developed incidence of hyperglycemia and the resultant requirements
hyperglycemia in the first 24 h and those who did not (P = in insulin therapy have not been comprehensively evaluated
0.61). to determine if close glucose monitoring is justified. Our
Endocrine

Table 2 Postoperative day when maximum plasma glucose levels results [11, 13–16]. Postoperative hyperglycemia is a sig-
were reached
nificant, clinically important issue that may result in patients
Postoperative day Patients who had maximal plasma glucose levels requiring short-term insulin treatment. In our study, 12 of 33
n (%) patients developed hyperglycemia in the first 24 h following
0 16 (48.5) resection, but only four patients required short-term insulin
1 3 (9.7) therapy. The hyperglycemia eventually resolved in all cases,
2 4 (12.9) and none of the patients required glucose-lowering medica-
3 4 (12.9)
tions upon discharge. Chang et al. reported that, out of a
4 2 (6.5)
cohort of 10 patients, two were diagnosed with diabetes after
insulinoma resection; however, both patients had impaired
5 2 (6.5)
oral glucose tolerance tests prior to the operation [10]. Given
7 2 (6.5)
these data, we believe close blood glucose monitoring is
important, as one-third of patients develop hyperglycemia and
Table 3 Insulin levels pre and post-resection of insulinoma require transient administration of insulin.
Pre-resection insulin Post-resection insulin Percent change Postoperative elevations in blood glucose levels have
level (mIU/L) level (mIU/L) (%) been attributed to the suppression, atrophy, and degranula-
tion of the remaining beta pancreatic cells [8], as well as the
34.30 10.80 −68.51
hyperglycemic hormonal effects of glucagon, glucocorti-
31.40 6.70 −78.66
coids, and growth hormone in the immediate postoperative
12.70 18.50 45.67
period [7]. Additional factors that may contribute toward
6.40 3.30 −48.44 blood glucose elevations include large pancreatic resections
23.90 10.80 −54.81 and the coexistence of diabetes mellitus or insulin resistance
35.80 4.80 −86.59 [21]. Our study did not identify any clinical factors asso-
57.60 8.70 −84.90 ciated with postoperative hyperglycemia, including
3.80 2.70 −28.95 increasing age and BMI, which could be related to insulin
5.60 1.50 −73.21 resistance, tumor size, and intraoperative insulin drop after
36.00 9.40 −73.89 resection. We also found no association between the extent
71.20 8.80 −87.64 of pancreatic resection and postoperative hyperglycemia.
151.00 29.00 −80.79 These data suggest that there is no reliable, usable predictor
10.00 4.40 −56.00 of hyperglycemia and that patients should have routine
blood glucose monitoring postoperatively. The absence of
plasma glucose level trend among patients with no post-
results demonstrate that there were no predictive factors operative hyperglycemia, may be explained by the short
associated with hyperglycemia and that, within 24 h of half-life time of insulin in the blood [22].
insulinoma resection, 36.3% of patients were found to have One patient had a history of insulin resistance and
glucose levels greater than 180 mg/dL (10 mmol/l). A short- developed postoperative hyperglycemia. Given the scarcity
term insulin treatment was administered in four patients of patients with diabetes mellitus or insulin resistance in our
with hyperglycemia. cohort we cannot confidently conclude that it is not a risk
A glucose level of 180 mg/dL (10 mmol/l) or greater was factor for hyperglycemia after insulinoma resection, how-
used to define hyperglycemia based on the 2009 recom- ever, this should be taken into consideration based on pre-
mendations by Finfer and colleagues [20]. The authors vious reports [23].
showed improvement in mortality with a less stringent Based on our data, in patients after insulinoma resection,
glucose control in critically ill patients [20]. Whether this with a normal plasma glucose levels post operatively, we
threshold is appropriate in patients undergoing insulinoma would suggest to monitor plasma glucose levels for hyper-
resection is unclear, but we believe the clinical scenario is glycemia hourly in the first 4 h after surgery, every 2–3 h in
applicable to patients undergoing pancreatectomy. the next 8 h, and every 6–12 h until the end of postoperative
Postoperative elevations in blood glucose both in humans day 4. This suggestion should be validated in an independent
and animals after resection of insulin-hypersecreting tissue cohort before implemented in clinical practice.
have been reported [9–11]. However, cases where patients did This study has several limitations. The sample size is
not develop hyperglycemia after insulinoma resection have small, so a type II error cannot be excluded, and intrao-
also been reported [16]. The clinical utility of blood glucose perative insulin levels were not measured in all cases.
elevations is not a reliable marker of a curative resection of However, insulinomas are rare and a small difference or
insulinoma due to both false positive and false negative association with hyperglycemia likely would not result in a

clinically meaningful change in management. We are a
referral center, but that did not appear to considerably
influence our cohort since MEN1-associated insulinoma
accounted for 16.1% of the cases, similar to the reported
incidence [3]. One of the patients showed an increase in the
intraoperative insulin level. Pathologic diagnosis confirmed
that pancreatic lesion was insulinoma, and the patient
remained euglycemic postoperatively, and did not require
dextrose supplementation. Given the retrospective nature of
this study it is difficult to explain the mechanism behind this
result and lab error cannot be excluded.
In conclusion, patients require close glucose monitoring
after insulinoma resection during the first 24 h. Hyperglycemia
may require short-term insulin management, but it is self-
limiting in patients without a prior history of impaired glucose
tolerance.
Funding Intramural Research Program, National Cancer Institute,
National Institutes of Health.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
Ethical approval All procedures performed in studies involving human
participants were in accordance with the ethical standards of the insti-
tutional and/or national research committee and with the 1964 Helsinki
declaration and its later amendments or comparable ethical standards.
Informed consent Informed consent was obtained from all individual
participants included in the study.
References
1. J. Zhou, L. Enewold, A. Stojadinovic et al. Incidence rates of
exocrine and endocrine pancreatic cancers in the United States.
Cancer Causes Control. 21, 853–861 (2010). http://www.ncbi.
nlm.nih.gov/pubmed/20182788
2. C.W. Anderson, J.J. Bennett, Clinical presentation and diagnosis
of pancreatic neuroendocrine tumors. Surg. Oncol. Clin. N. Am.
25, 363–374 (2016). http://www.ncbi.nlm.nih.gov/pubmed/
27013370
3. G.W. Krampitz, J.A. Norton, Pancreatic neuroendocrine tumors.
Curr. Probl. Surg. 50, 509–545 (2013). http://linkinghub.elsevier.
com/retrieve/pii/S0011384013002062
4. A.O. Whipple, V.K. Frantz, Adenoma of islet cells with hyper-
insulinism: a review. Ann. Surg. 101, 1299–1335 (1935). http://
www.ncbi.nlm.nih.gov/pubmed/17856569
5. J.M. Guettier, A. Lungu, A. Goodling, C. Cochran, P. Gorden,
The role of proinsulin and insulin in the diagnosis of insulinoma: a
critical evaluation of the endocrine society clinical practice
guideline. J. Clin. Endocrinol. Metab. 98, 4752–4758 (2013).
https://academic.oup.com/jcem/article-lookup/doi/10.1210/
jc.2013-2182
6. B. Hirshberg, A. Livi, D.L. Bartlett et al. Forty-eight-hour fast: the
diagnostic test for insulinoma. J. Clin. Endocrinol. Metab. 85,
3222–3226 (2000). https://academic.oup.com/jcem/article-lookup/
doi/10.1210/jcem.85.9.6807
Endocrine
7. P. Chari, S.K. Pandit, R.N. Kataria, H. Singh, D.K. Baheti, J. Wig,
Anaesthetic management of insulinoma. Anaesth. 32, 261–264
(1977). http://www.ncbi.nlm.nih.gov/pubmed/192099
8. W.L. Chick, S. Warren, R.N. Chute, A.A. Like, V. Lauris, K.C.
Kitchen, A transplantable insulinoma in the rat. Proc. Natl Acad.
Sci. USA 74, 628–632 (1977). http://www.ncbi.nlm.nih.gov/
pubmed/191819
9. S.S. Schwartz, D.L. Horwitz, B. Zehfus, B.G. Langer, E. Kaplan,
Continuous monitoring and control of plasma glucose during
operation for removal of insulinomas. Surg. 85, 702–707 (1979).
http://www.ncbi.nlm.nih.gov/pubmed/222000
10. H.Y. Chang, H.S. Huang, J.D. Lin, B.Y. Huang, M.J. Huang, L.B.
Jeng, Insulinoma--clinical experience in ten cases. Chang. yi xue za
zhi 17, 28–38 (1994). http://www.ncbi.nlm.nih.gov/pubmed/8205495
11. J.C. Yu, Continuous monitoring for blood glucose after surgery of
insulinoma and the use of insulin. Zhonghua Wai Ke Za Zhi 31,
352–354 (1993). http://www.ncbi.nlm.nih.gov/pubmed/8313754
12. N. Schnelle, G.D. Molnar, D.O. Ferris, J.W. Rosevear, E.A.
Moffitt, Circulating glucose and insulin in surgery for insulomas.
JAMA 217, 1072–1078 (1971). http://www.ncbi.nlm.nih.gov/
pubmed/4327740
13. J.J. Muir, S.M. Endres, K. Offord, J.A. van Heerden, J.H. Tinker,
Glucose management in patients undergoing operation for insu-
linoma removal. Anesthesiology 59, 371–375 (1983). http://www.
ncbi.nlm.nih.gov/pubmed/6314850
14. G.O. Tutt, A.J. Edis, F.J. Service, J.A. van Heerden, Plasma
glucose monitoring during operation for insulinoma: a critical
reappraisal. Surgery 88, 351–356 (1980). http://www.ncbi.nlm.
nih.gov/pubmed/6251575
15. J. Puig la Calle, P. Clavé, G. Capella, C. Fidal, J.M. Pou, F. Lluis,
Rebound hyperglycemia and peroperative normalization of insu-
linemia. Complet. excision Insul? Chirurgie 118, 284-8-91 (1992)
16. Y. Matsumoto, K. Tashiro, S. Ohmura, T. Kobayashi, [Lack of
hyperglycemic rebound after insulinoma removal: two case
reports]. Masui 46, 664–668 (1997). http://www.ncbi.nlm.nih.
gov/pubmed/9185465
17. J. Ahn, S.E. Lee, Y.S. Choi, A.H.K. Tan, J. Kim, Y.J. Chung,
Overtly manifested diabetes mellitus after resection of insulinoma.
Intern. Med. 48, 2105–2107 (2009). http://www.ncbi.nlm.nih.gov/
pubmed/20009401
18. E. Ademoğlu, U. Ünlütürk, K. Ağbaht, A. Karabork, D. Çorapçıoğlu,
Type 2 diabetes mellitus in a patient with malignant insulinoma
manifesting following surgery. Diabet. Med. 29, e133–e137 (2012).
http://doi.wiley.com/10.1111/j.1464-5491.2012.03603.x
19. P. Nockel, B. Babic, C. Millo et al. Localization of Insulinoma
Using 68Ga-DOTATATE PET/CT Scan. J. Clin. Endocrinol.
Metab. 102, 2016–3445 (2016). http://www.ncbi.nlm.nih.gov/
pubmed/27805844
20. NICE-SUGAR Study Investigators for the Australian and New
Zealand Intensive Care Society Clinical Trials Group and the
Canadian Critical Care Trials Group, S. Finfer, D. Chittock et al.
Intensive versus conventional glucose control in critically ill
patients with traumatic brain injury: long-term follow-up of a
subgroup of patients from the NICE-SUGAR study. Intensive
Care Med. 41, 1037–1047 (2015). http://www.ncbi.nlm.nih.gov/
pubmed/26088909
21. D.G. Watson, Insulinoma: anesthetic implications. AANA J. 55,
539–543 (1987). http://www.ncbi.nlm.nih.gov/pubmed/2827425
22. D.R. Matthews, A.S. Rudenski, M.A. Burnett, P. Darling, R.C.
Turner, The half-life of endogenous insulin and C-peptide in man
assessed by somatostatin suppression. Clin. Endocrinol. 23, 71–79
(1985). http://www.ncbi.nlm.nih.gov/pubmed/2863015
23. M. Toaiari, M.V. Davì, L. Dalle Carbonare et al.. Presentation,
diagnostic features and glucose handling in a monocentric series
of insulinomas. J. Endocrinol. Invest. 36, 753–758 (2013). http://
www.ncbi.nlm.nih.gov/pubmed/23608735