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Endocrine Notes
Updates for physicians on practices, advances and research
from Cleveland Clinic’s Endocrinology & Metabolism Institute
2012
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Endocrine Notes
Chairman, Endocrinology & Metabolism Institute
James B. Young, MD
Endocrine Notes updates physicians on clinical practices, advances and research from Cleveland Clinic’s
Managing Editor
Kimberley Sirk
Endocrinology & Metabolism Institute. It is written for
physicians and should be relied on for medical education
Art Director
Mike Viars
purposes only. It does not provide a complete overview of
the topics covered and should not replace the independent
Marketing
Bill Sattin, PhD
Mary Anne Connor
Endocrine Notes
Cleveland Clinic Willoughby
Hills Family Health Center
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Willoughby Hills, OH 44094
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judgment of a physician about the appropriateness or risks
of a procedure for a given patient.
© 2012 The Cleveland Clinic Foundation
| 2 |2012
Dear Colleagues,
I am pleased to present the 2012 edition of Endocrine Notes, in which you can read about the
latest clinical innovations, emerging research and new treatment modalities within Cleveland Clinic’s
Endocrinology & Metabolism Institute.
The Endocrinology & Metabolism Institute is a part of Cleveland Clinic’s group practice model
that brings related specialties together to provide integrated, patient-centered care. Collaboration
among endocrinology; endocrine surgery; bariatrics, including bariatric surgery; and cardiology
allows us to offer exceptional integrative, multidisciplinary patient care and novel discoveries.
In this issue, you will learn more about our leading-edge innovation and research, including:
• Details of a Cleveland Clinic study that identified increased mortality risk with sulfonylureas
vs. metformin, while also demonstrating that glimepiride may be the preferred sulfonylurea
for patients with underlying coronary artery disease
• A mathematical model developed by our endocrine surgeons that can help differentiate
normocalcemic primary hyperparathyroidism and secondary hyperparathyroidism
• Five inferior petrosal sinus sampling (IPSS) pillars to adhere to when ordering and interpreting
IPSS in patients with ACTH-dependent Cushing syndrome
• Robotic bilateral posterior adrenalectomy for ACTH-independent macronodular adrenal
hyperplasia causing subclinical Cushing syndrome
• Highlights of our study that sheds light on the importance of screening for thyroid cancer in
patients diagnosed with Cowden syndrome, including an online calculator that estimates a
patient’s risk for PTEN mutation and the need for genetics consultation
• Our study that found gastric bypass improves glucose homeostasis by attenuating the effect of
ghrelin on ß-cell function
• A proposed clinical algorithm targeting the management of residual diabetes following bariatric
surgery
• Our groundbreaking study, known as STAMPEDE, that continues to provide a wealth of
information about our field, including the story we bring you here about how the benefits of
bariatric surgery in type 2 diabetes extend to the improvement and prevention of nephropathy
Throughout the Endocrinology & Metabolism Institute, our staff remains committed to Cleveland
Clinic’s core ideology: Patients First. Our institute comprises:
• The Department of Endocrinology, Diabetes and Metabolism, which manages specialized centers
of care for patients with diabetes, thyroid disorders and pituitary disorders
• The Department of Endocrine Surgery, which performs the highest number of surgical procedures
in the region
• The Bariatric & Metabolic Institute, which has been designated as a Bariatric Surgery Center of
Excellence by the American Society for Metabolic and Bariatric Surgery
Your comments and questions about Endocrine Notes articles are always welcome. Please feel free
to contact me at 216.444.6568 or 800.223.2273, ext. 46568.
Sincerely,
James B. Young, MD
Chairman, Endocrinology & Metabolism Institute
Professor of Medicine and Executive Dean,
Cleveland Clinic Lerner College of Medicine of Case Western Reserve University
George and Linda Kaufman Chair
Physician Director, Institutional Relations and Development
800.223.2273,
Endocrine Notesext. 46568
| 1 |clevelandclinic.org/endonotes
2012
Cleveland Clinic Study Identifies
Increased Mortality Risk with
Sulfonylureas vs. Metformin
Kevin M. Pantalone, DO, and Robert Zimmerman, MD
But Glimepiride May Be Safest Sulfonylurea
In Cleveland Clinic’s Department of Endocrinology, Diabetes
Texas, and they were published in Diabetes, Obesity and
and Metabolism, we have identified an increased risk of
Metabolism (see Suggested reading).
overall mortality in patients with type 2 diabetes mellitus
treated with sulfonylurea vs. metformin monotherapy. In
Robust data from a large patient population
patients who do receive a sulfonylurea, our research found
We conducted this retrospective analysis using the Cleveland
that glimepiride may be the preferred agent in patients with
Clinic Diabetes Registry, a repository comprising data on
underlying coronary artery disease (CAD).
patients with diabetes treated with oral anti-diabetic agents.
We identified 23,915 patients with type 2 diabetes who
We recently conducted a retrospective cohort study of nearly
were seen at Cleveland Clinic between 1998 and 2006 who
24,000 patients with type 2 diabetes who were seen at
received monotherapy with metformin (n=12,774), glipizide
Cleveland Clinic, to assess the risk of overall mortality in
(n=4,325), glyburide (n=4,279) or glimepiride (n=2,537).
patients taking the most commonly prescribed sulfonyl-
The patients were followed for mortality by documentation of
ureas or metformin. In the entire population of our study,
death within the enterprisewide electronic health record (EHR)
which analyzed patients seen across eight years, glipizide,
system and/or Social Security Death Index (SSDI) records.
glyburide and glimepiride were all associated with a statistically significant >50 percent increase in mortality risk vs.
There were a total of 2,546 deaths in 58,513 person years
metformin. However, in those patients with documented CAD,
of follow-up in the entire cohort, and 419 deaths in 5,980
a statistically significant increase in overall mortality risk
person-years of follow-up in the subgroup with a history of
was observed with glipizide (41 percent) and glyburide (38
documented CAD (n=2,721). Multivariable Cox models with
percent) vs. metformin — but not with glimepiride.
propensity analysis were used to compare cohorts.
These results suggest that metformin is associated with a
Cleveland Clinic is ideally suited to this type of study, given
substantial reduction in mortality risk vs. sulfonylureas; thus,
our large patient population with type 2 diabetes and CAD
in the absence of contraindications, metformin should be
and our multidisciplinary approach in treating a high volume
the preferred first-line agent. In addition, these study results
of patients within the Endocrinology & Metabolism Institute
suggest that when a sulfonylurea is required to treat patients
and the Sydell and Arnold Miller Family Heart & Vascular
with type 2 diabetes, particularly those with underlying CAD,
Institute.
glimepiride may be the preferred/safer agent among the most
commonly used generic sulfonylureas available in the United
Practical clinical considerations
States (glipizide, glyburide and glimepiride).
The precise reason why glimepiride may be safer than the
We presented the results of our study at The Endocrine
Society’s 94th Annual Meeting, ENDO 2012, in Houston,
Endocrine Notes
other sulfonylureas in patients with underlying CAD remains
unclear and requires further study.
| 2 |2012
(A) Overall Mortality Entire Cohort
Figures A and B. Overall mortality in the entire cohort
(A) and subgroup with a documented history of coronary
artery disease (CAD) (B), treated with sulfonylurea or
metformin monotherapy
the patient, it would seem inappropriate when no contraindications exist and adequate glucose control is not an issue
to prescribe those medications that are associated with a
higher risk of mortality.
The results of this retrospective study are clinically significant
for endocrinologists and primary care physicians who manage this patient population, especially in light of the fact that
prospective, randomized controlled clinical trials comparing
the mortality risk of these agents may not be a high priority
given that the drugs are all available at bargain-basement
pricing at local pharmacies. However, the sulfonylurea drug
(B) Overall Mortality CAD Subgroup
class remains a mainstay of therapy for patients with type
2 diabetes and is recommended as a tier-1, well-validated
core therapy in the American Diabetes Association/European
Association for the Study of Diabetes Consensus Treatment
Algorithm. Therefore, randomized controlled clinical trials
examining the mortality risk of various sulfonylureas, especially in patients with CAD, would provide endocrinologists
and other physicians with evidence-based data — beyond
expert opinion — to guide us in this area.
About the authors
Dr. Pantalone is an endocrinologist who specializes in the
evaluation and management of diabetes mellitus, with a particular
focus on type 2 diabetes. Dr. Zimmerman is Vice Chairman of the
Department of Endocrinology, Diabetes and Metabolism and
Director of the Diabetes Center.
For more information, please contact Dr. Pantalone at
216.445.9060 or [email protected]. Dr. Zimmerman can
Over the past few decades, research has suggested that the
individual sulfonylureas differ considerably in terms of their
pharmacologic properties, including:
• Hypoglycemic risk
• Sulfonylurea receptor selectivity
• Effects on myocardial ischemic preconditioning
(a cardioprotective phenomenon in which short periods
of nonlethal ischemia help protect the myocardium from
subsequent damage in the setting of recurrent ischemia)
Some reports that have suggested that glimepiride, unlike
other sulfonylureas, may be a mild insulin sensitizer. These
differences in pharmacologic properties may translate into
differences in clinical outcomes, including mortality risk.
Because glipizide, glyburide, glimepiride and metformin are
all readily available as generic agents at a similar cost to
800.223.2273, ext. 46568
be reached at 216.444.9428 or [email protected].
Suggested reading
Pantalone KM, Kattan MW, Yu C, Wells BJ, Arrigain S, Jain
A, Atreja A, Zimmerman RS. Increase in overall mortality risk in
patients with type 2 diabetes receiving glipizide, glyburide, or
glimepiride monotherapy vs. metformin: a retrospective analysis.
Diabetes Obes Metab. 2012;14(9):803-809.
Pantalone KM, Kattan MW, Yu C, Wells BJ, Arrigain S, Jain
A, Atreja A, Zimmerman RS. The risk of overall mortality in
patients with type 2 diabetes receiving glipizide, glyburide, or
glimepiride monotherapy: a retrospective analysis. Diabetes Care.
2010;33(6):1224-1229.
Pantalone KM, Kattan MW, Yu C, Wells BJ, Arrigain S, Jain A,
Atreja A, Zimmerman RS. The risk of developing coronary artery
disease or congestive heart failure, and overall mortality, in type
2 diabetic patients receiving rosiglitazone, pioglitazone, metformin, or sulfonylureas: a retrospective analysis. Acta Diabetol.
2009;46(2):145-154.
| 3 |clevelandclinic.org/endonotes
Differentiating Normocalcemic
Primary Hyperparathyroidism and
Secondary Hyperparathyroidism
Cleveland Clinic endocrine
surgeons create mathematical
model to clarify diagnosis
With awareness increasing about primary hyperparathyroidism, clinicians are discovering that rather than
one disease entity of high calcium and high parathyroid hormone (PTH), primary hyperparathyroidism
presents across a wide spectrum. Just one year ago,
endocrine surgeons at Cleveland Clinic described the
new parathyroid disease entity normohormonal primary hyperparathyroidism (www.clevelandclinic.org/
endonotes2011). This is a presentation in which the
patient’s calcium level is elevated but his/her PTH
level is within normal range.
In this article, I describe a new mathematical model
developed by clinicians in Cleveland Clinic’s Department
of Endocrine Surgery that can help clarify the diagnosis
of another challenging disease presentation: normal
calcium level with elevated PTH, or normocalcemic
primary hyperparathyroidism (NCPHP).
By Judy Jin, MD
Overlapping biochemical presentation
NCPHP can at times be confused with secondary hyperparathyroidism. Patients with 2° hyperparathyroidism
(HPT) caused by vitamin D deficiency can present with
a biochemical profile similar to patients with NCPHP:
normal calcium level, elevated PTH level and low or
low-normal vitamin D level. Because of the overlapping
biochemical presentation, many patients with NCPHP
may be diagnosed initially with 2° HPT; then, worsening
osteoporosis despite treatment or recurrent kidney stones
brings them back to the attention of endocrine surgeons.
To facilitate the initial diagnosis of NCPHP, Cleveland Clinic’s
endocrine surgeons proposed a mathematical formula that
allows the calculation of a maximally expected normal PTH
(maxPTH) level when taking into account the patient’s age
and serum calcium and vitamin D levels (Table 1). When the
serum PTH is higher than the calculated maxPTH, a diagnosis of NCPHP is suspected. This was a novel idea, so to test
how well the formula performs, we conducted a retrospective study at Cleveland Clinic.
Table 1
MaxPTH = 120 – 6 x Ca – 1/2 x VitD25 + 1/4 x Age
Patient #
Age
Calcium
VitD25
PTH
maxPTH
PTH>maxPTH
Diagnosis
1
57
12.8
26
202
44
Yes
1°HPT
2
54
10.5
23
89
59
Yes
1°HPT
3
69
9.9
11
139
72
Yes
1°HPT
4
55
9.7
45
47
54
No
2°HPT
This mathematical formula developed by Cleveland Clinic’s Department of
Endocrine Surgery calculates the maximally expected normal PTH level when
taking into account the patient’s age and serum calcium and vitamin D levels.
When the serum PTH is higher than the calculated maxPTH, a diagnosis of
normocalcemic primary hyperparathyroidism is suspected.
Endocrine Notes
We identified 477 patients diagnosed between 2007 and
2010 with primary hyperparathyroidism who underwent
surgery and were found to have abnormal parathyroid
glands. Of these 477 patients, 66 were diagnosed with
NCPHP. We reviewed these 66 patients’ preoperative biochemical profiles and tested whether our formula would
have predicted primary hyperparathyroidism rather than
2° HPT.
| 4 |2012
Figure 1
Figure 2
Serum
Calcium
Ionized Calcium
Intact PTH
25-Hydroxy Vitamin D
1,25-Dihydroxyvitamin D
Phosphorus
Magnesium
Albumin
Creatinine
1
1
Urine
24-hr Calcium
24-hr Creatinine
This Cleveland Clinic-developed management protocol can help clinicians effectively triage patients to their correct disease
group so that patients with secondary hyperparathyroidism aren’t inadvertently sorted into the normocalcemic primary
hyperparathyroidism group based on the results of the mathematical formula.
Patients should undergo this biochemical workup to
help inform the primary clinician’s diagnosis,
treatment plan and possible referral to an
endocrine surgeon.
Our retrospective analysis found that if the formula
In order to use the decision tree, we asked that all
developed by Cleveland Clinic’s endocrine surgeons had
patients undergo a comprehensive biochemical workup
been used as another diagnostic tool prior to surgery, it
(Figure 2). The protocol then takes the clinician through a
would have correctly identified all 66 patients to have
review of the patient’s ionized calcium and vitamin D lev-
NCPHP. Even in patients with coexisting vitamin D
els and the calculated maxPTH level to identify the next
deficiency, the formula was able to sort these patients
management plan. This protocol clearly outlines when a
into the NCPHP group and not the 2° HPT group.
referral to the endocrine surgeon should be made.
Furthermore, we found that even though patients with
NCPHP had calcium levels in the normal range, they
were often in the high-normal range, whereas patients
with 2° HPT usually had mid- to low-normal-range
calcium levels. The PTH levels in patients with NCPHP
were significantly higher than those in patients with 2°
HPT, despite similar vitamin D levels.
Clinical management and referrals
One drawback of the formula was that while it was
very sensitive, it also sorted some patients with 2° HPT
into the NCPHP group. Therefore, we have proposed a
We are currently in the process of implementing this
protocol in the offices of the primary care physicians
and endocrinologists at Cleveland Clinic so that we may
prospectively evaluate the efficacy of the management
protocol when incorporating the maxPTH calculation.
Our retrospective study found that if the formula developed by Cleveland Clinic’s endocrine surgeons had been
used as another diagnostic tool prior to surgery, it would
have correctly identified all 66 patients to have normocalcemic primary hyperparathyroidism.
management protocol to help clinicians effectively triage
About the author
patients to their correct disease group (Figure 1).
Dr. Jin serves as associate staff in the Department of
Endocrine Surgery.
For more information, please contact Dr. Jin at
216.445.3411 or at [email protected].
800.223.2273, ext. 46568
| 5 |clevelandclinic.org/endonotes
Five Important Pillars
to Adhere to When Ordering and Interpreting IPSS in
Patients with ACTH-Dependent Cushing Syndrome
By Amir H. Hamrahian, MD; Ferdinand Hui, MD; Robert Weil, MD;
and Laurence Kennedy, MD
Although a pituitary adenoma is the most
common cause of adrenocorticotropic
hormone (ACTH)-dependent Cushing
syndrome, the distinction from ectopic ACTH
production can be difficult. This is because
approximately 25 to 40 percent of pituitary
microadenomas causing Cushing syndrome are
too small to be detected by MRI, and also
because about 10 percent of adults have (usually
nonfunctional) microadenomas that are
incidentally found on MRI screening.
In the past two years, we have published two reports in
Inferior petrosal sinus sampling (IPSS) is the gold standard test
to determine the etiology of ACTH-dependent Cushing syndrome.
Clinical Endocrinology and Endocrine Practice concerning
An inferior petrosal sinus to peripheral (IPS:P) ACTH ratio >2
the utility of IPSS and its interpretation in challenging cases of
before or >3 after corticotropin-releasing hormone (CRH) admin-
ACTH-dependent Cushing syndrome (see Suggested reading).
istration confirms a pituitary source of ACTH.
Here we review the principles — referred to as the Five IPSS
Pillars — that are key to the appropriate use and
False-negative results, or the presence of Cushing disease
interpretation of IPSS. To illustrate how the pillars can be
in the absence of a diagnostic IPS:P ACTH ratio, may occur
in up to 10 percent of patients and can be a source of confusion.
In contrast, the presence of a false-positive IPSS — that is,
used, we also share a report on a challenging case (see
sidebar article).
the test suggests a pituitary source of ACTH when in fact the
source is ectopic or peripheral — is rare.
Endocrine Notes
| 6 |2012
The Five IPSS Pillars
5 Calculate prolactin-adjusted ACTH ratios. Prolactin-
Based on our experience at Cleveland Clinic, we believe clinicians
adjusted ACTH ratios may help to lateralize a corticotroph
should adhere to the following principles for IPSS testing:
adenoma and may have an impact on surgical outcome.
While the utility of IPSS to diagnose pituitary-mediated
1 Do not perform IPSS before confirming the presence
ACTH-dependent Cushing syndrome is well-established, to
of ACTH-dependent hypercortisolemia. The result of IPSS
in a healthy volunteer or a patient with pseudo-Cushing may
mimic the result in a patient with Cushing disease.
2 Confirm hypercortisolemia at the time of IPSS. Patients
with cyclic Cushing syndrome may have a false-positive
or false-negative IPSS result, depending on where the tumor
is located and the degree and duration of eucortisolemia or
hypocortisolemia between the hypercortisolemia episodes. We
obtain a stat cortisol level in the morning the day that IPSS is
planned and do not proceed with the IPSS if serum cortisol is
<10 µg/dL.
3 Confirm catheter placement. Radiological confirmation of
catheter tip placement during IPSS using venous angiography to demonstrate retrograde flow into the
cavernous sinuses before sampling and by intermittent
fluoroscopy during sampling may not be reliable, especially
in centers with less experience with this procedure. At the
same time, since there are collateral vessels draining to the
inferior petrosal sinus (IPS), the aspirated venous sample
from a properly placed catheter may occasionally come
from a collateral vessel and may not accurately represent
true pituitary venous efflux. We recently confirmed that
the prolactin measurement during IPSS can reduce falsenegative results. Based on our data, if the IPS:P prolactin
ratio is <1.3 and the corresponding IPS:P ACTH ratio is
negative (i.e., <2 and <3 for pre- and post-CRH samples,
respectively), the clinician cannot be sure that the negative
result is valid. Others have recommended an IPS:P prolactin ratio >1.8 as an indication of appropriate IPS venous
sampling. Currently, we have a dedicated interventional
neuroradiologist perform all IPSS procedures.
4N
ote that proper unilateral IPS venous sampling does not
rule out a corticotroph adenoma in the contralateral side.
As is illustrated in the accompanying case study, the patient
had a tumor on the right side yet had appropriate IPS venous sampling only on the left side. Based on the presence
or absence of collateral venous plexus to the contralateral
side, the IPS on the contralateral side may not show a
significant IPS:P ACTH ratio.
800.223.2273, ext. 46568
date the technique does not appear reliable for predicting
precisely where within the pituitary — right, left, center
— a microadenoma will be localized. A proposed criterion
for localization indicates that an intersinus ACTH gradient of ≥1.4 before or after CRH stimulation is accurate in
approximately 50 to 70 percent of cases. Variable patterns
of venous drainage and catheter misplacement or improper
venous sampling during IPSS are important factors that can
lead to inaccuracy in lateralization of the tumor.
We have demonstrated that the prolactin-adjusted ACTH ratio
may be particularly useful when there is proper bilateral IPS
venous sampling based on concurrent IPS:P prolactin ratios.
In fact, no patient in our initial series of 14 patients — with
the number now extending to about 20 patients — had a
dominant prolactin-adjusted ACTH ratio (≥1.4) and a lesion
on the opposite side of the pituitary gland. Such measurement could not be applied to the patient in the case study
presented here because she had successful IPS sampling only
on one side. We have encountered cases in which a pituitary
adenoma has been found at neurosurgery contralateral to the
side suggested by the prolactin-adjusted ACTH ratio; however,
further meticulous pituitary exploration on the other side,
prompted by the IPSS result, has uncovered a very small microadenoma on the side predicted by the ratio. If our data are
confirmed by additional studies, the IPSS prolactin-adjusted
ACTH ratio may conceivably be used to guide the neurosurgeon if hemi-hypophysectomy is to be performed.
Finally, desmopressin has been used successfully in place of
CRH in centers around the world, with similar diagnostic
accuracy. Desmopressin is given as a 10-µg IV push; an IPS:P
ACTH ratio >2 before and >3 after desmopressin administration is usually used to confirm a pituitary source. Considering
that CRH cannot be obtained in this country at the present
time, the use of desmopressin seems a reasonable option
until CRH again becomes clinically available.
In conclusion, IPSS is best performed by experienced hands,
and adherence to the Five IPSS Pillars outlined here will
increase the likelihood of successful localization and treatment
of pituitary adenomas causing Cushing disease.
| 7 |clevelandclinic.org/endonotes
SIDEBAR:
A Challenging Case:
Applying the Five IPSS
Pillars in ACTH-Dependent
Cushing Syndrome
A 30-year-old woman with progressive weight gain,
fatigue, muscle weakness and skin changes suggestive
of hypercortisolism was found to have the following
biochemical results: cortisol after 1-mg dexamethasone
suppression test, 44.8 µg/dL; 24-hour UFC, 824 and
3,515 µg (0-50); ACTH, 80 and 102 pg/mL (8-24). The
pituitary MRI failed to reveal a pituitary adenoma. She
was referred for IPSS, during which the neuroradiologist
believed that he had achieved successful bilateral IPS
catheter placement.
The patient’s IPS:P ACTH ratio was <2 and <3 in all
pre- and post-CRH samples, respectively (Table 1). The
IPS:P prolactin levels indicated that the right IPS was
not successfully catheterized or that the venous drainage did not represent IPS venous flux, as all the IPS:P
prolactin ratios on the right side were <1.3. This, taken
along with the robust ACTH response to CRH, which
is reported in similar cases, suggested that the IPSS
results were falsely negative and that the source of the
ACTH was more likely pituitary than ectopic. The patient
subsequently was found to have a right-sided pituitary
adenoma, developed adrenal insufficiency postoperatively, and the tumor was stained positive for ACTH.
The application of our Five IPSS Pillars for ordering and
interpreting IPSS results, along with our clinical experience, guided us in diagnosing and treating the patient
discussed in this case.
Endocrine Notes
| 8 |2012
Table 1
TIME
min
ACTH
(pg/mL)
RPS
LPS
P
PRL
(ng/mL)
ACTH ratio
RPS
LPS
P
CORT
(µg/dL)
PRL ratio
R/P
L/PR/P
L/P
-10 79 89 73 1.101.2014.024.113.41.001.8029.1
-5
77 85 76 1.001.1013.128.612.51.002.2028.5
+2 108 117 83 1.301.4013.335.212.51.102.8029.7
+5 196 267 210 0.931.3013.638.811.81.203.3031.6
+10326 315 246 1.301.3013.034.613.30.982.6033.5
+15383 370 288 1.301.3013.734.912.71.102.7036.5
ACTH, corticotropin; PRL, prolactin; CORT, cortisol; RPS, right petrosal sinus; LPS, left petrosal sinus;
P, peripheral; R/P, right petrosal sinus to peripheral ratio; L/P, left petrosal sinus to peripheral ratio
Source: Mulligan et al. Endocrine Practice. 2011;17:1-17.
About the authors
Castinetti F, Morange I, Dufour H, Jaquet P, Conte-Devolx B, Girard
N, Brue T. Desmopressin test during petrosal sinus sampling: a
valuable tool to discriminate pituitary or ectopic ACTH-dependent
Cushing’s syndrome. Eur J Endocrinol. 2007;157(3):271-277.
Dr. Hamrahian specializes in pituitary and adrenal disorders in
the Department of Endocrinology, Diabetes and Metabolism.
Dr. Hui is a neurointerventional surgeon and neuroradiologist
in the Cerebrovascular Center. Dr. Weil is Section Head of
Neuro-Endocrine Surgery. Dr. Kennedy is Chair of the
Department of Endocrinology, Diabetes and Metabolism and
has a special interest in pituitary conditions.
Machado MC, de Sa SV, Domenice S, Fragoso MC, Puglia P Jr,
Pereira MA, de Mendonça BB, Salgado LR. The role of desmopressin in bilateral and simultaneous inferior petrosal sinus sampling for
differential diagnosis of ACTH-dependent Cushing’s syndrome. Clin
Endocrinol (Oxf). 2007;66(1):136-142.
For more information, please contact Dr. Hamrahian at
216.445.8538 or [email protected]. Dr. Kennedy can be
reached at 216.445.8645 or [email protected].
Suggested reading
Mulligan GB, Faiman C, Gupta M, Kennedy L, Hatipoglu B, Hui F,
Weil RJ, Hamrahian AH. Prolactin measurement during inferior petrosal sinus sampling improves the localization of pituitary adenomas
in Cushing’s disease. Clin Endocrinol. 2012;77(2):268-274.
Mulligan GB, Eray E, Faiman C, Gupta M, Pineyro MM, Makdissi
A, Suh JH, Masaryk TJ, Prayson R, Weil RJ, Hamrahian AH.
Reduction of false-negative results in inferior petrosal sinus sampling with simultaneous prolactin and corticotropin measurement.
Endocr Pract. 2011;17(1):33-40.
Sharma ST, Raff H, Nieman LK. Prolactin as a marker of successful
catheterization during IPSS in patients with ACTH-dependent Cushing’s
syndrome. J Clin Endocrinol Metab. 2011;96(12):3687-3694.
800.223.2273, ext. 46568
Findling JW, Kehoe ME, Raff H. Identification of patients with
Cushing’s disease with negative pituitary adrenocorticotropin
gradients during inferior petrosal sinus sampling: prolactin as
an index of pituitary venous effluent. J Clin Endocrinol Metab.
2004;89(12):6005-6009.
Swearingen B, Katznelson L, Miller K, Grinspoon S, Waltman
A, Dorer DJ, Klibanski A, Biller BM. Diagnostic errors after inferior petrosal sinus sampling. J Clin Endocrinol Metab. 2004
Aug;89(8):3752-63.
Yanovski JA, Cutler GB Jr, Doppman JL, Miller DL, Chrousos GP,
Oldfield EH, Nieman LK. The limited ability of inferior petrosal
sinus sampling with corticotropin-releasing hormone to distinguish
Cushing’s disease from pseudo-Cushing states or normal physiology.
J Clin Endocrinol Metab. 1993;77(2):503-509.
| 9 |clevelandclinic.org/endonotes
Robotic Bilateral Posterior Adrenalectomy for
ACTH-Independent Macronodular Adrenal Hyperplasia
Causing Subclinical Cushing Syndrome
Our patient was a 60-year-old man with bilateral macronodular adrenal masses These masses were
incidentally identified on a CT scan ordered for abdominal pain in December 2011 in an outside hospital. He was referred to Cleveland Clinic’s Department of Endocrine Surgery within the Endocrinology &
Metabolism Institute on February 15, 2012. At his office visit, the patient’s only complaint was a weight
gain of 20 pounds over the past six months without any change in his dietary habits.
By Eren Berber, MD
On physical exam, the patient did not have any signs of
Cushing syndrome. His BMI was 32.8. A CT scan showed
bilateral adrenal masses with a macronodular
appearance. The right adrenal measured 2 cm, and the
left was 4 cm (Figure 1). The patient’s medical history
was significant for hypertension and smoking.
The preoperative laboratory workup was significant for
ACTH-independent Cushing syndrome. The patient’s blood
cortisol was 13.8 µg/dL, and his ACTH was less than 5
pg/mL (normal 8-42 pg/mL). His 24-hour urine cortisol
was 104.8 µg/dL (normal <50) with a creatinine of 2.2
grams. Further dexamethasone suppression testing also
supported an ACTH-independent adrenal pathology.
same steps as on the contralateral side. The mass was
Based on this workup, we diagnosed the patient with
removed using a specimen retrieval bag inserted through
subclinical Cushing syndrome due to ACTH-independent
the 12-mm port site (Figure 3).
macronodular adrenal hyperplasia. He provided consent for
bilateral robotic PR adrenalectomy and was admitted to the
hospital on the day of the surgery, May 29, 2012.
We performed a bilateral adrenalectomy with a skin-toskin operative time of 268 minutes (98 minutes for the
left side, and 170 minutes for the right side), including
Surgical technique
the docking times of 12 and 6 minutes, respectively.
After intubation and administration of general anesthesia on
Estimated blood loss was 50 mL. The patient was
the gurney, the patient was flipped on a Wilson frame to
the prone position on the operating room table. Initially,
on the left side, we used three incisions placed below the
12th rib. We identified the adrenal mass using laparoscopic ultrasound. The robot surgical system was docked
discharged uneventfully on steroid replacement on postoperative day 1, on May 30, 2012. The final pathology
revealed bilateral adrenal cortical hyperplasia. The patient
was seen for follow-up at two weeks with no evidence of
complications. He continues to receive steroid replace-
(Figure 2), and we resected the mass. Then we turned
ment therapy.
our attention to the other side. We made a 1-cm incision
The choice of the posterior retroperitoneal approach was
below the right 12th rib and entered the retroperitoneal
helpful in this case, as this obviated the need to reposition
space using an optical trocar. Then, we repeated the
the patient to remove the mass on the contralateral side.
Endocrine Notes
| 10 |2012
Harmonic Scalpel
30° Scope
Grasping Forceps
Figure 2: Intraoperative photo depicting the position of the robotic system for the left side.
Figure 3: Intraoperative photo showing the final appearance of the incisions.
Figure 1: CT scan image showing bilateral adrenal masses.
We believe that avoiding the abdominal cavity helped with
Suggested reading
the patient’s quick recovery. Use of the robotic system
Karabulut K, Agcaoglu O, Aliyev S, Siperstein A, Berber E.
Comparison of intraoperative time use and perioperative outcomes for robotic versus laparoscopic adrenalectomy. Surgery.
2012;151(4):537-542.
facilitated the procedure by providing a three-dimensional
view and wristed instrumentation in a small space. This
case also takes its place in the literature as the first bilateral posterior adrenalectomy that was performed robotically.
About the author
Dr. Berber is an Associate Professor of Surgery and Director of
Robotic Endocrine Surgery in the Department of Endocrine Surgery,
Endocrinology & Metabolism Institute. His specialty interests include
minimally invasive and robotic endocrine and liver surgery.
For more information, please contact Dr. Berber at
216.445.0555 or [email protected].
800.223.2273, ext. 46568
Agcaoglu O, Aliyev S, Karabulut K, Siperstein A, Berber E.
Robotic versus laparoscopic posterior retroperitoneal adrenalectomy. Surgery. 2012;151(4):537-542.
Agcaoglu O, Aliyev S, Karabulut K, Mitchell J, Siperstein A,
Berber E. Robotic versus laparoscopic resection of large adrenal
tumors. Ann Surg Oncol. 2012;19(7):2288-2294.
Karabulut K, Agcaoglu O, Aliyev S, Siperstein A, Berber E.
Comparison of intraoperative time use and perioperative outcomes for robotic versus laparoscopic adrenalectomy. Surgery.
2012;151(4):537-542.
Berber E, Mitchell J, Milas M, Siperstein A. Robotic posterior
retroperitoneal adrenalectomy: operative technique. Arch Surg.
2010;145(8):781-784.
| 11 |clevelandclinic.org/endonotes
Study Highlights
Importance of Screening for Thyroid Cancer
in Patients Diagnosed with Cowden Syndrome
Plus: Access Cleveland Clinic’s Online Calculator for Estimating a
Patient’s Risk for PTEN Mutation and Need for Genetics Consultation
By Rosemarie Metzger, MD, MPH, and Charis Eng, MD, PhD
At Cleveland Clinic, where endocrinologists and endocrine
surgeons from the Endocrinology & Metabolism Institute
work collaboratively with geneticists, researchers and
other clinicians, referrals for thyroid screening are frequent
among those with inherited cancer syndromes. One such
example is Cowden syndrome (CS), a rare, dominantly heritable disorder that typically falls beyond routine recognition.
Traditional aspects of care for CS patients have focused
on the treatment of breast and thyroid cancer, both of
which demonstrate increased incidence among CS patients.
However, there has been evolution in the way that genetics
professionals diagnose CS — and subsequently, a broader
understanding of its associated disease spectrum, including
CS-related cancers.
Housed under the umbrella diagnosis of PTEN hamartoma
tumor syndrome (PHTS), CS is one of several genetic
syndromes, including Bannayan-Riley-Ruvalcaba syndrome (BRRS) and Proteus-like syndrome, characterized
by germline mutations of the tumor suppressor PTEN. These
mutations predispose patients to benign hamartomatous
changes (Figure 1) as well as malignant transformation
of epithelial tissues, including breast, thyroid, kidney,
intestine and endometrium. Although being PTEN mutation-positive imparts the ultimate diagnostic confirmation
of CS, diagnosis can also be made on clinical grounds, as
outlined by the International Cowden Consortium (ICC)
Diagnostic Categories.
Recognizing patients with CS is especially important given
the frequency of associated cancers and the inherent implications for screening. Until recently, the exact magnitude
and proportion of lifetime cancer risks in these patients
were not fully appreciated. New data indicate that the
lifetime risks in PTEN mutation-positive patients for breast,
thyroid, endometrial, colorectal and kidney cancer, as well as
melanoma, are elevated beyond those expected in the general
Endocrine Notes
Figure 2
population. Moreover, the lifetime risk of differentiated thyroid
cancer for this group of patients is 35 percent.
Given the importance of recognizing patients who potentially
have CS and initiating appropriate cancer screening, a dedicated thyroid screening program was developed at Cleveland
Clinic in 2007. Recently, we evaluated the outcomes of our
thyroid screening program in PTEN mutation-positive CS
patients and delineated the characteristics of both malignant
and benign thyroid disease in this population.
Study results
The patient population for this study was derived from a large
database of CS and CS-like patients that is part of a national
multi-institutional study that is centrally coordinated at
Cleveland Clinic by Charis Eng, MD, PhD, Chair and Founding
Director of the Genomic Medicine Institute.
For the purpose of our investigation, we looked at only those
patients with a known germline pathogenic PTEN mutation
(n=225). From the cohort of 225 patients, we identified 32
individuals (14 percent) with differentiated thyroid cancer.
The median age at cancer diagnosis for the overall group was
35 years. Tumors were multifocal in 54 percent of patients
and generally small (mean size, 1.4 cm). Distant (n=1) and
cervical (n=2) metastases were rare. At the time of surgery
for thyroid cancer, 25/32 patients (78 percent) had clinical
and histologic evidence of goiter, and 16/32 (50 percent) had
a background of Hashimoto thyroiditis noted on the pathology report. In patients with benign disease only, goiter was
present in more than 70 percent, and Hashimoto thyroiditis
in nearly 30 percent.
Twenty-five of the 225 patients were seen and screened at
Cleveland Clinic. Sixteen of these 25 patients underwent their
first formal ultrasound screening or second opinion evaluation
by endocrine surgeons at Cleveland Clinic. Nine (56 percent)
of these 16 patients had ultrasound-evident thyroid abnor-
| 12 |2012
These are examples of physical features characteristic of Cowden syndrome. Figures 1a represent trichilemmomas, flesh-colored hamartomas of the outer sheath of the follicle.
They are typically found nearer to hairlines. Figures 1b show papillomatous papules: mucocutaneous lesions found on the face, oral mucosa and acral surfaces. Pictured here
are papillomas of the gum and the tongue that represent benign epithelial lesions. The skin and gastrointestinal tract are the most common sites of hamartomatous change, but
mucocutaneous features, including trichilemmomas and papillomatous papules, are estimated to have a 99 percent penetrance in CS by the third decade of life.
malities consisting of multinodular goiter (n=6), Hashimoto
thyroiditis (n=2) or both (n=1). Seven patients (44 percent)
required thyroid nodule fine-needle aspiration biopsy at the
first office visit, which was abnormal in three patients
(19 percent), leading to total thyroidectomy. Two of these
(12.5 percent of the group of 16) were diagnosed with
thyroid cancer, unsuspected prior to screening.
We recently developed a risk calculator at Cleveland Clinic
to estimate the possibility of CS. You can access this
clinical tool online at lerner.ccf.org/gmi/ccscore/ to facilitate
identifying patients who will benefit from
genetics consultation.
About the authors
Clinical applications
Based on our findings, PTEN mutation-positive patients with
CS have an increased prevalence of thyroid disease, both
malignant and benign, and it occurs much sooner than is
widely appreciated. Data from the Surveillance Epidemiology
and End Results (SEER) cancer registry indicate that the
median age at thyroid cancer diagnosis in the general population is 49 years. The onset of thyroid cancer by the middle of
the third decade in this PTEN mutation-positive population
is striking in comparison. Screening for thyroid disease is
therefore advisable at the time of diagnosis, regardless of age,
and preferably by dedicated thyroid specialists.
Thyroid surgery, if needed, should be a total thyroidectomy. This
makes sense biologically, since the hereditary process places
the entire thyroid tissue at risk. Furthermore, this approach
avoids multiple partial resections and repeat surgeries, which
are riskier procedures.
Although CS may be somewhat difficult to recognize, the implications are so valuable that it is a worthwhile investment of
effort and vigilance. PTEN mutation-positive patients are at
risk for multiple cancer diagnoses, and increased screening is
recommended to decrease the resultant morbidity and mortality from disease. The challenge is to notice the subtleties
and hints of something unusual — the recognition of kidney
and endometrial cancers, for instance. Unfortunately, skin
findings can be difficult to recognize, and biopsy is needed to
properly identify a trichilemmoma (Figure 1). Oral papillomas
may be more discernible and certainly can be incorporated
into a head and neck exam, as could measurement of head
circumference (Figure 2).
800.223.2273, ext. 46568
Dr. Metzger is an endocrine surgeon in the Department of Endocrine
Surgery who specializes in the thyroid and parathyroid. Dr. Eng is
Chair and Founding Director of the Genomic Medicine Institute.
For more information, please contact Dr. Metzger at
216.445.3695 or [email protected].
Suggested reading
Eng C. Will the real Cowden syndrome please stand up: revised
diagnostic criteria. J Med Genet. 2000;37:828-830.
Tan MH, Mester JL, Ngeow J, Rybicki LA, Orloff MS, Eng C. Lifetime
cancer risks in individuals with germline PTEN mutations. Clin
Cancer Res. 2012;18(2):400-407.
Ngeow J, Mester J, Rybicki LA, Ni Y, Milas M, Eng C. Incidence and
clinical characteristics of thyroid cancer in prospective series of individuals with Cowden and Cowden-like syndrome characterized by
germline PTEN, SDH, or KLLN alterations. J Clin Endocrinol Metab.
2011;96(12):E2063-E2071.
Milas M, Mester J, Metzger R. Should patients with Cowden
syndrome undergo prophylactic thyroidectomy? Surgery. 2012;
152(6):1201-1210.
National Cancer Institute Web site. Surveillance Epidemiology and End
Results (SEER) cancer statistics. Available at: http://seer.cancer.gov.
Tan MH, Mester J, Peterson C, Yang Y, Chen JL, Rybicki LA. A
clinical scoring system for selection of patients for PTEN mutation
testing is proposed on the basis of a prospective study of 3042
probands. Am J Hum Genet. 2011;88(1):42-56.
| 13 |clevelandclinic.org/endonotes
Proposed Clinical Algorithm Targets
the Management of Residual Diabetes
Following Bariatric Surgery
By Sangeeta Rao Kashyap, MD, and Philip R. Schauer, MD
Numerous observational studies have documented the positive metabolic
effects of bariatric surgery in morbidly obese patients with type 2 diabetes.
However, despite initial weight loss, 25 to 40 percent of bariatric surgery
patients improve glycemic control but do not necessarily achieve “biochemical
remission” of hyperglycemia. Some achieve normal glycemic control (HbA1c
<6 percent or <42 mmol/mol) initially but relapse later while others never
quite reach normal blood sugar levels.
Based on our experience, we have proposed a clinical
advanced stages of the disease, and experience inadequate
algorithm for the long-term management of residual diabetes
weight loss and regain weight. Other factors associated with
following bariatric surgery in the absence and presence of
suboptimal diabetes control following bariatric procedures are
weight regain. Our clinical approach, which is based on
insulin use, male gender, lower preoperative BMI, severity of
established pathophysiological effects of these procedures
preoperative ß-cell function (i.e., hyperglycemia) and poten-
on diabetes remission, was published in Diabetes, Obesity
tially inadequate incretin stimulation following surgery.
and Metabolism in 2012 (14:773-779).
Therapies for residual diabetes
Cleveland Clinic’s Bariatric & Metabolic Institute is fully
Nonremission of hyperglycemia is indicated by an HbA1c level
integrated within the broader Endocrinology & Metabolism
>7 percent or 53 mmol/mol that requires the use of anti-
Institute. As such, the patient’s endocrinologist, as part
diabetic medications. Targeting weight regain and poor residual
of a multidisciplinary obesity team, plays a key role in our
pancreatic ß-cell function with insulin may be indicated by du-
bariatric surgery center of excellence and other settings in
ration of diabetes >10 years, insulin use, poor glycemic control
the long-term treatment, evaluation and monitoring of post-
on oral agents and microvascular complications.
bariatric surgery patients with type 2 diabetes. Of specific
importance is the need to monitor comorbidity status,
Gastric restrictive procedures
weight regain and nutritional deficiencies.
In patients who have had gastric restrictive procedures,
Diabetes nonremission or re-emergence
nonremission is indicated when patients have inadequate
Residual diabetes occurs more commonly following gastric re-
weight loss or weight regain and progressive ß-cell failure
strictive (i.e., laparoscopic adjustable gastric banding [LAGB]
without weight regain. The management of residual type 2
and sleeve gastrectomy) procedures vs. intestinal bypass (i.e.,
diabetes due to insulin resistance and/or insulin secretion
Roux-en-Y gastric bypass [RYGB] and biliopancreatic diver-
defects in these patients should focus on weight loss and
sion [BPD]) surgeries. Patients who undergo gastric bypass
glycemic control with anti-diabetic medications that have
and BPD procedures improve sooner and maintain glucose
weight-negative or -neutral effects. Metformin remains the
control for longer periods than do patients treated by banding
first-line agent in this context due to its mechanism of ac-
or sleeve gastrectomy procedures. Additionally, patients who
tion that improves insulin sensitivity by suppressing hepatic
do not achieve biochemical remission or who experience a
gluconeogenesis and increasing muscle/liver glucose uptake
re-emergence often have diabetes duration >10 years, are in
through increased AMPK activity.
Endocrine Notes
| 14 |2012
Caution should be exercised in these patients when con-
GLP-agonists) in bariatric patients is lacking. Studies have
sidering sulphonylureas in the early postoperative period,
demonstrated that these agents enhance glucose-dependent
because they may precipitate hypoglycemia and trigger
insulin secretion and offer advantages for weight loss in
dumping syndromes. In patients who experience suboptimal
obese type 2 diabetes patients. Because incretin stimulation
glycemic control several years after gastric restrictive surgery,
of insulin secretion following gastric bypass helps improve
the addition of a sulphonylurea to metformin could enhance
glucose levels, the role of GLP-1 analogues in post-bariatric
insulin secretion and restore glycemic control by targeting
surgery patients must be further defined.
ß-cell failure. Patients who do not respond to this therapy
The pathophysiology underlying diabetes relapse following
should be prescribed basal insulin; if glycemic control is not
various bariatric surgery procedures is complex. Enhancing
adequate, then prandial insulin should be added.
our understanding in this area will inform further research
Revisional bariatric surgery is indicated primarily for patients
and treatment options.
with anatomical/mechanical issues or severe nutritional
Continued monitoring of long-term diabetes complications
deficiencies and patients whose comorbid conditions worsen
is essential following bariatric surgery, regardless of initial
following LAGB or sleeve gastrectomy.
remission status.
Intestinal bypass procedures
About the authors
At our institution, we observed 12 months following RYGB
Dr. Kashyap is an endocrinologist in the Endocrinology &
Metabolism Institute and Assistant Professor of Medicine at
Cleveland Clinic Lerner College of Medicine. Dr. Schauer is
Professor of Surgery and Director of Cleveland Clinic’s
Bariatric & Metabolic Institute.
that obese patients with type 2 diabetes experienced a
greater than fourfold improvement in insulin sensitivity and
a 10-fold increase in ß-cell function with mixed meal testing
(unpublished data). These improvements were not seen in
patients who underwent gastric-restrictive procedures, even
For more information, please contact Dr. Kashyap at
when they had significant weight loss.
216.445.2679 or [email protected]. Dr. Schauer can be
reached at 216.444.4794 or [email protected].
In patients who have undergone gastric bypass surgery, the
re-emergence of hyperglycemia without weight regain is
Suggested reading
likely related to ß-cell exhaustion. Pharmacologic interven-
Kashyap SR, Schauer P. Clinical considerations for the
management of residual diabetes following bariatric surgery.
Diabetes, Obes Metab. 2012;14:773-779.
tions in these patients should target ß-cell failure with a trial
of sulphonylureas and the subsequent addition of insulin.
However, due to the insulin-sensitizing and incretin-related
effects of gastric bypass in patients with diabetes, these
Schauer PR, Kashyap SR, Wolski K, et al. Bariatric surgery versus
intensive medical therapy in obese patients with diabetes. N Engl J
Med. 2012;366:1567-1576.
agents should be used cautiously due to the potential for
hypoglycemia. Revisional bariatric surgery in these patients
should be considered only for select surgical failure cases as
Pories WJ, Swanson MS, MacDonald KG, et al. Who would have
thought it? An operation proves to be the most effective therapy for
adult-onset diabetes mellitus. Ann Surg. 1995;222:339-350.
it is associated with additional morbidity.
Looking forward
With an estimated 350,000 bariatric operations performed
worldwide each year, additional research is needed regarding
the adjunctive use of medications for long-term diabetes
control. Safety and efficacy trials are warranted in this
patient population to define the potential roles of alternative
diabetes agents such as GLP-agonists, acarbose and
Nannipieri M, Mari A, Anselmino M, et al. The role of betacell function and insulin sensitivity in the remission of type 2
diabetes after gastric bypass surgery. J Clin Endocrinol Metab.
2011;96:E1372-E1379.
Chikunguwo SM, Wolfe LG, Dodson P, et al. Analysis of factors associated with durable remission of diabetes after Roux-en-Y gastric
bypass. Surg Obes Relat Dis. 2010;6:254-259.
bromocriptine in conjunction with lifestyle counseling.
Data regarding the use of alternative diabetes therapies
including incretin analogues (i.e., DPP4 inhibitors and
800.223.2273, ext. 46568
Schauer PR, Burguera B, Ikramuddin S, et al. Effect of
laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus.
Ann Surg. 2003;238:467-484.
| 15 |clevelandclinic.org/endonotes
Benefits of Bariatric Surgery
in Type 2 Diabetes Extend to Improvement,
Prevention of Nephropathy By Philip R. Schauer, MD
Studies have demonstrated that the benefits of bariatric surgery
extend beyond durable weight loss and include significant improvements in glycemic control and a sustainable improvement
in diabetes. The results of a study that we conducted recently
at the Bariatric & Metabolic Institute take that concept one step
further: Bariatric surgery also can improve or even prevent
microvascular complications such as diabetic nephropathy.
Our study included obese diabetic patients who had undergone
bariatric surgery at our institution and who had completed a five-year
follow-up (n=52; 75 percent female). The patients’ average preoperative BMI was 49, and the primary bariatric surgery performed was
gastric bypass. The mean length of time patients had been diagnosed
with diabetes was 8.5 years, HbA1c was 7.9±1.3 percent and 35
percent had diabetic nephropathy.
We hypothesized that improving diabetes control may have positive
effects on end-organ complications of the disease, including diabetic
nephropathy. Remarkably, we found that 55 percent of patients with
diabetic nephropathy prior to their bariatric surgery had a resolution
of the disease at a mean follow-up of 66 months.
Among those patients with no evidence of diabetic nephropathy prior
to bariatric surgery, only 25 percent proceeded to develop albuminuria
five years later. Additionally, the five-year remission and improvement
rates for diabetes were 22 percent and 55 percent, respectively.
Endocrine Notes
| 16 |2012
“No medical therapy has been
as effective as bariatric surgery in
achieving an effect of this magnitude on diabetic nephropathy.”
The presence of diabetic nephropathy, pre- and postop-
When my colleagues and I initiated this study, we hypoth-
eratively, was determined by urinary albumin-creatinine
esized that bariatric surgery may halt the progression of
ratio (uACR). Patients’ current diabetes status (remission,
diabetic nephropathy. Instead we found that over half of the
improvement or no change) was determined by biochemical
patients who had diabetic nephropathy prior to undergoing
analyses and review of medications.
bariatric surgery experienced remission.
We presented our findings at the 29th Annual Meeting of
No medical therapy has been as effective as bariatric sur-
the American Society of Metabolic and Bariatric Surgery in
gery in achieving an effect of this magnitude on diabetic
June 2012. The findings follow a study that I published with
nephropathy. This is an important finding that warrants
colleagues earlier in 2012 in the New England Journal of
further research and greater consideration of bariatric
Medicine that showed bariatric surgery can cause remis-
surgery in this patient population.
sion of type 2 diabetes even before substantial weight loss
occurs.
About the author
Sustainable clinical benefits
Dr. Schauer, Professor of Surgery and Director of
Cleveland Clinic’s Bariatric & Metabolic Institute, can be
reached at 216.444.4794 or [email protected].
Studies have shown that patients may lose as much as 60
percent of their excess weight six months after bariatric/
metabolic surgery and 77 percent of excess weight as early
as 12 months after surgery.
In addition to remission or improvement in type 2 diabetes
and its complications, the patients in our study were able
to maintain 50 percent of their excess weight loss after five
years and also achieved significant improvements in blood
pressure and cholesterol levels.
800.223.2273, ext. 46568
Suggested reading
Heneghan HM, Orzech N, Bencsath K, Cetin D, Brethauer SA,
Schauer PR. Effects of bariatric surgery on diabetic nephropathy
after 5 years of follow-up. Abstract PL-116. Presented at the 29th
Annual Meeting of the American Society of Metabolic & Bariatric
Surgery, San Diego, Calif., June 17-22, 2012.
Schauer PR, Kashyap SR, Wolski K, et al. Bariatric surgery versus
intensive medical therapy in obese patients with diabetes. N Engl
J Med. 2012;366:1567-1576.
| 17 |clevelandclinic.org/endonotes
Gastric Bypass
Improves Glucose Homeostasis by Attenuating
the Effect of Ghrelin on ß-cell Function
By Sangeeta Rao Kashyap, MD; Steven K. Malin, PhD; and Aashish Samat, MD
STAMPEDE (Surgical Therapy and Medications
Potentially Eradicate Diabetes Efficiently) was
a single-center prospective, randomized,
controlled trial conducted at Cleveland Clinic’s
Endocrinology & Metabolism Institute. We
designed this metabolic substudy to determine
the impact of intensive medical therapy
combined with either Roux-en-Y gastric bypass
or sleeve gastrectomy on glycemic control in
obese adults with type 2 diabetes mellitus.
As a continuation of the STAMPEDE trial, we are now
looking at the effects of two bariatric surgery procedures
on ghrelin as a mediator of glucose regulation and will be
presenting related substudy results at the American Diabetes
Association’s 73rd Scientific Sessions (2013), June 21-25,
2013, Chicago, Ill.
A healthy insulin response, illustrated here, is one result of gastric bypass.
Insulin secretion increases most following gastric bypass compared with
sleeve gastrectomy or intensive medical therapy.
Despite the known effects of surgery-induced diabetes
In our recent substudy, 53 moderately obese adults with
remission, the mechanism responsible for this improved
poorly controlled diabetes were randomized to intensive
glycemic control remains unclear. Ghrelin is a fundus-derived
medical therapy alone vs. gastric bypass and sleeve gas-
hormone that has glucoregulatory effects on ß-cell function
trectomy. At baseline and 24 months, we measured ß-cell
and insulin sensitivity.
function, insulin sensitivity (determined by mixed-meal tolerance testing), body fat and postprandial ghrelin levels.
In addition, ghrelin is an appetite-stimulating hormone that
Gastric bypass and sleeve gastrectomy decreased body fat
plays a key role in body weight regulation. For example,
obese, insulin-resistant adults with type 2 diabetes mel-
by approximately 12 percent at 24 months, while intensive
litus have decreased abilities to suppress ghrelin following
medical therapy had little effect (Table 1). Although fast-
food intake. This impaired response subsequently leads to
ing glycemia improved in all three groups at 24 months
overeating and the development of poor insulin secretion.
(P<0.05), insulin sensitivity and ß-cell function increased
Improving ghrelin suppression therefore represents an impor-
most following gastric bypass compared with sleeve gastrec-
tant endocrine-related mechanism for diabetes remission.
tomy or intensive medical therapy.
Endocrine Notes
| 18 |2012
Although follow-up studies
Ghrelin Suppression (pg/mL)
Table 1
0.0
-0.5
-1.0
-1.5
-2.0
-2.5
-3.0
-3.5
-4.0
-4.5
-5.0
IMT
SG
RYGB
are required to understand
how ghrelin affects insulin
secretion, our data suggest a
*
*^
role for ghrelin as a regulator
Baseline
24 months
of glucose metabolism after
*IMT vs. SG vs. RYGB at 24 months (P<0.001)
^Change from 0-24 months RYGB vs. SG (P=0.03) and IMT (P=0.09)
gastric bypass surgery.
IMT, intensive medical therapy; SG, sleeve gastrectomy;
RYGB, Roux-en-Y gastric bypass
After 24 months, only gastric bypass improved ghrelin suppression (P<0.05 vs. sleeve gastrectomy; P=0.09 vs. intensive
medical therapy). Lower ghrelin levels correlated with enhanced
ß-cell function (r=-0.29, P=0.03) and decreased abdominal fat
(r=0.37, P=0.006). Improved insulin secretion correlated with
reduced fasting glucose levels (r=-0.39, P<0.01).
Together, these findings suggest that gastric bypass restores
normal glucose homeostasis by attenuating the negative
effect of ghrelin on ß-cell function. Although follow-up studies are required to understand how ghrelin affects insulin
secretion, our data suggest a role for decreased abdominal
body fat.
About the authors
Dr. Kashyap is an endocrinologist in the Department of Endocrinology,
Diabetes and Metabolism and is a co-lead investigator in the
STAMPEDE trial. Dr. Malin is a postdoctoral fellow in Pathobiology
at Cleveland Clinic Lerner Research Institute. Dr. Samat is an
endocrinology fellow in the Department of Endocrinology, Diabetes
and Metabolism.
For more information, please contact Dr. Kashyap at
216.445.2679 or [email protected].
800.223.2273, ext. 46568
| 19 |clevelandclinic.org/endonotes
Publications
Below are peer-reviewed journal articles and
Archives of Surgery
book chapters published within the past year by
Agcaoglu O, Aliyev S, Karabulut K, Siperstein A, Berber E.
Endocrinology & Metabolism Institute staff.
Robotic vs laparoscopic posterior retroperitoneal adrenalectomy.
Arch Surg. 2012;147(3):272-275.
Journals
Shin JJ, Milas M, Mitchell J, Berber E, Ross L, Siperstein A.
Academic Medicine
Impact of localization studies and clinical scenario in patients
Young JB, Cosgrove DM. Change we must: Putting patients first
with hyperparathyroidism being evaluated for reoperative neck
with the institute model of academic health center organization
surgery. Arch Surg. 2011;146(12):1397-1403.
[Commentary]. Acad Med. 2012;87(5):552-554.
Bariatric Nursing and Surgical Patient Care
American Journal of Cardiology
Calogeras E, Zeller M, Hoover C, Cooper K, Tuininga P, Ashton
Heneghan HM, Meron-Eldar S, Brethauer SA, Schauer PR,
K. Sleeve gastrectomy patients may be at increased risk post-
Young JB. Effect of bariatric surgery on cardiovascular risk pro-
operatively for decline in vitamin B12 values — do they need
file. Am J Cardiol. 2011;108(10):1499-1507.
monitoring? Bariatr Nurs Surg Patient Care. 2012;7(1):21-24.
American Journal of Otolaryngology
Best Practice & Research Clinical Endocrinology & Metabolism
Makin V, Hatipoglu B, Hamrahian AH, Arrossi AV, Knott PD,
Jin J, McHenry CR. Thyroid incidentaloma. Best Pract Res Clin
Lee JH, Sade B. Spontaneous cerebrospinal fluid rhinorrhea as
Endocrinol Metab. 2012;26(1):83-96.
the initial presentation of growth hormone-secreting pituitary
Orija IB, Weil RJ, Hamrahian AH. Pituitary incidentaloma. Best
adenoma. Am J Otolaryngol. 2011;32(5):433-437.
Pract Res Clin Endocrinol Metab. 2012;26(1):47-68.
American Journal of Physiology – Endocrinology and
Metabolism
Body Image
Haus JM, Solomon TPJ, Lu L, Jesberger JA, Barkoukis H, Flask
Coughlin JW, Schreyer CC, Sarwer DB, Heinberg LJ, Redgrave
CA, Kirwan JP. Intramyocellular lipid content and insulin sen-
GW, Guarda AS. Cosmetic surgery in inpatients with eating disor-
sitivity are increased following a short-term low-glycemic index
ders: Attitudes and experience. Body Image. 2012;9(1):180-183.
diet and exercise intervention. Am J Physiol Endocrinol Metab.
Canadian Journal of Anaesthesia
2011;301(3):E511-E516.
Abdelmalak B, Zimmerman R, Foss J. Diagnosing preoperative
Annals of Surgical Oncology
hyperglycemia in non-diabetic patients: a challenge and an
Bohacek L, Milas M, Mitchell J, Siperstein A, Berber E.
opportunity [Reply]. Can J Anaesth. 2011;58(6):583.
Diagnostic accuracy of surgeon-performed ultrasound-guided
Circulation: Heart Failure
fine-needle aspiration of thyroid nodules. Ann Surg Oncol.
Hsich EM, Naftel DC, Myers SL, Gorodeski EZ, Grady KL,
2012;19(1):45-51.
Schmuhl D, Ulisney KL, Young JB. Should women receive left
Sahin DA, Agcaoglu O, Chretien C, Siperstein A, Berber E. The
ventricular assist device support? Findings from INTERMACS.
utility of PET/CT in the management of patients with colorectal
Circ Heart Fail. 2012;5(2):234-240.
liver metastases undergoing laparoscopic radiofrequency thermal
ablation. Ann Surg Oncol. 2012;19(3):850-855.
Endocrine Notes
| 20 |2012
Cleveland Clinic Journal of Medicine
Endocrine Practice
Albashir S, Olansky L, Sasidhar M. Progressive muscle
Alguraan Z, Agcaoglu O, El-Hayek K, Hamrahian AH, Siperstein
weakness: More there than meets the eye. Cleve Clin J Med.
A, Berber E. Retroperitoneal masses mimicking adrenal tumors.
2011;78(6):385-391.
Endocr Pract. 2012;18(3):335-341.
Lansang MC, Hustak LK. Glucocorticoid-induced diabetes
Cheng V, Doshi KB, Falcone T, Faiman C. Hyperandrogenism
and adrenal suppression: How to detect and manage them.
in a postmenopausal woman: diagnostic and therapeutic
Cleve Clin J Med. 2011;78(11):748-756.
challenges. Endocr Pract. 2011;17(2):E21-E25.
Lansang MC, Hustak LK. Glucocorticoid-induced
Harvey A, Hu M, Gupta M, Butler R, Mitchell J, Berber E,
diabetes and adrenal suppression [Reply]. Cleve Clin J Med.
Siperstein A, Milas M. A new, vitamin D-based, multidimension-
2012;79(4):237,242.
al nomogram for the diagnosis of primary hyperparathyroidism.
Endocr Pract. 2012;18(2):124-131.
Newey CR, Sarwal A, Uchin J, Mulligan G. Necrotic skin lesions
Katznelson L, Atkinson JLD, Cook DM, Ezzat SZ, Hamrahian
after hemodialysis. Cleve Clin J Med. 2011;78(10):646-648.
AH, Miller KK. American Association of Clinical Endocrinologists
Clinical Journal of the American Society of Nephrology
Medical Guidelines for Clinical Practice for the Diagnosis and
Thomas G, Sehgal AR, Kashyap SR, Srinivas TR, Kirwan JP,
Treatment of Acromegaly — 2011 update: executive summary.
Navaneethan SD. Metabolic syndrome and kidney disease: A
Endocr Pract. 2011;17(4):636-646.
systematic review and meta-analysis. Clin J Am Soc Nephrol.
Pantalone KM, Faiman C, Olansky L. Insulin glargine use during
2011;6(10):2364-2373.
pregnancy. Endocr Pract. 2011;17(3):448-455.
Diabetes Care
Pantalone KM, Faiman C, Olansky L. Use of insulin detemir
Pantalone KM, Kattan MW, Wells BJ, Zimmerman RS. The risk
and insulin glargine during pregnancy: Are the data convincing?
of overall mortality in patients with type 2 diabetes receiving
Endocr Pract. 2011;17(5):830.
glipizide, glyburide, or glimepiride monotherapy: A retrospective
Expert Opinion on Pharmacotherapy
analysis [Response to Comment on: Pantalone et al. Diabetes
Care. 2010;33:1224-1229]. Diabetes Care. 2011;34(8):E139.
Subbarayan S, Kipnes M. Sitagliptin: a review. Expert Opin
Pharmacother. 2011;12(10):1613-1622.
Diabetes, Obesity and Metabolism
Olansky L, Reasner C, Seck TL, Williams-Herman DE, Chen M,
Expert Review of Endocrinology and Metabolism
Terranella L, Mehta A, Kaufman KD, Goldstein BJ. A treatment
Kashyap SR, Louis ES, Kirwan JP. Weight loss as a cure for
strategy implementing combination therapy with sitagliptin and
type 2 diabetes? Fact or fantasy. Expert Rev Endocrinol Metab.
metformin results in superior glycaemic control versus metformin
2011;6(4):557-561.
monotherapy due to a low rate of addition of antihyperglycaemic
Heart Failure Clinics
agents. Diabetes Obes Metab. 2011;13(9):841-849.
Rhoads GG, Dain MP, Zhang Q, Kennedy L. Two-year glycaemic
control and healthcare expenditures following initiation of insulin
glargine versus neutral protamine Hagedorn insulin in type 2
diabetes. Diabetes Obes Metab. 2011;13(8):711-717.
Diabetes Research and Clinical Practice
Baliga RR, Young JB. Clinical trials to “real-world” heart failure:
applying risk stratification to deliver personalized care. Heart Fail
Clin. 2011;7(4):xi-xiv.
Baliga RR, Young JB. Early detection and monitoring of vulnerable myocardium in patients receiving chemotherapy: is it time
to change tracks? Heart Fail Clin. 2011;7(3):xiii-xxix.
Pantalone KM, Agarwal S, Faiman C. Glargine vs. NPH insulin
therapy in pregnancies complicated by diabetes: An observational
cohort study [Comment on Negrato et al]. Diabetes Res Clin
Pract. 2011;93(1):E9-E10.
continued on next page
800.223.2273, ext. 46568
| 21 |clevelandclinic.org/endonotes
Publications
continued
Journal of Medical Economics
Baliga RR, Young JB. Reducing the burden of stage B heart
failure and the global pandemic of cardiovascular disease:
Lamy A, Wang X, Gao P, Tong W, Gafni A, Dans A, Avezum A,
time to go to war with the “barefoot” troops! Heart Fail Clin.
Ferreira R, Young J, Yusuf S, Teo K. The cost implications of the
2012;8(2):ix-xiii.
use of telmisartan or ramipril in patients at high risk for vascular
events: the ONTARGET study. J Med Econ. 2011;14(6):792-797.
Baliga RR, Young JB. Reducing the burden of stage B heart
failure will require connecting the dots between “knowns” and
Journal of Nutrition and Metabolism
“known unknowns.” Heart Fail Clin. 2012;8(1):xi-xv.
Sun G, Kashyap SR. Cancer risk in type 2 diabetes mellitus:
Hepatology
metabolic links and therapeutic considerations. J Nutr Metab.
Zein CO, Yerian LM, Gogate P, Lopez R, Kirwan JP, Feldstein AE,
McCullough AJ. Pentoxifylline improves nonalcoholic steato-
2011;2011:708183.
Journal of Obesity
hepatitis: A randomized placebo-controlled trial. Hepatology.
Cheng V, Kashyap SR. Weight considerations in pharmacothera-
2011;54(5):1610-1619.
py for type 2 diabetes. J Obes. 2011;2011:984245.
International Journal of Cancer
Medical Clinics of North America
Nock NL, Patrick-Melin A, Cook M, Thompson C, Kirwan JP, Li
L. Higher bone mineral density is associated with a decreased
Smith BR, Schauer P, Nguyen NT. Surgical approaches to the
risk of colorectal adenomas. Int J Cancer. 2011;129(4):956-964.
treatment of obesity: bariatric surgery. Med Clin North Am.
2011;95(5):1009-1030.
International Journal of Obesity (London)
Eldar S, Heneghan HM, Brethauer SA, Schauer PR. Bariatric
Medicine and Science in Sports and Exercise
surgery for treatment of obesity. Int J Obes (Lond).
Kelly KR, Blaszczak A, Haus JM, Patrick-Melin A, Fealy CE,
2011;35(Suppl 3):S16-S21.
Solomon TPJ, Kalinski MI, Kirwan JP. A 7-d exercise program
increases high-molecular weight adiponectin in obese adults.
Issues in Science and Technology
Young JB. A better process for new medical devices.
Issues Sci Technol. 2011;27(4):10-12.
Med Sci Sports Exerc. 2012;44(1):69-74.
Metabolic Syndrome and Related Disorders
Kennedy DJ, Kashyap SR. Pathogenic role of scavenger receptor
The Journal of Clinical Endocrinology & Metabolism
Zeiger MA, Siegelman SS, Hamrahian AH. Medical and
surgical evaluation and treatment of adrenal incidentalomas.
J Clin Endocrinol Metab. 2011;96(7):2004-2015.
CD36, metabolic syndrome and diabetes. Metab Syndr Relat
Disord. 2011;9(4):239-245.
Minerva Endocrinologica
Milas Z, Shin J, Milas M. New guidelines for the management
Journal of Gastrointestinal Surgery
Bencsath KP, Falk G, Morris-Stiff G, Kroh M, Walsh RM,
Chalikonda S. Single-incision laparoscopic cholecystectomy:
do patients care? J Gastrointest Surg. 2012;16(3):535-539.
of thyroid nodules and differentiated thyroid cancer. Minerva
Endocrinol. 2011;36(1):53-70.
Neurology
Busch RM, Frazier T, Chapin JS, Hamrahian AH, Diehl B,
The Journal of Heart and Lung Transplantation
Kirklin JK, Naftel DC, Kormos RL, Stevenson LW, Pagani FD,
Miller MA, Baldwin JT, Young JB. The Fourth INTERMACS
Annual Report: 4,000 implants and counting. J Heart Lung
Alexopoulos A, Unnwongse K, Naugle RI, Kubu CS,
Tesar GE, Najm IM. Role of cortisol in mood and memory in
patients with intractable temporal lobe epilepsy. Neurology.
2012;78(14):1064-1068.
Transplant. 2012;31(2):117-126.
Endocrine Notes
| 22 |2012
The New England Journal of Medicine
Psychiatric Annals
Schauer PR, Kashyap SR, Wolski K, Brethauer SA, Kirwan JP,
Maudlin S, Hatipoglu B. Is there a lack of communication
Pothier CE, Thomas S, Abood B, Nissen SE, Bhatt DL. Bariatric
between endocrinologists and psychiatrists regarding metabolic
surgery versus intensive medical therapy in obese patients with
screening of second-generation antipsychotic users? Psychiatr
diabetes. N Engl J Med. 2012;366(17):1567-1576.
Ann. 2011;41(7):350.
Obesity (Silver Spring)
Rheumatology (Oxford)
Huang H, Kasumov T, Gatmaitan P, Heneghan HM, Kashyap SR,
Knafo R, Haythornthwaite JA, Heinberg L, Wigley FM, Thombs
Schauer PR, Brethauer SA, Kirwan JP. Gastric bypass surgery
BD. The association of body image dissatisfaction and pain
reduces plasma ceramide subspecies and improves insulin
with reduced sexual function in women with systemic sclerosis.
sensitivity in severely obese patients. Obesity (Silver Spring).
Rheumatology (Oxford). 2011;50(6):1125-1130.
2011;19(11):2235-2240.
Surgeon
Obesity Surgery
Eldar S, Heneghan HM, Brethauer S, Schauer PR. A focus on
Appachi S, Kelly KR, Schauer PR, Kirwan JP, Hazen S, Gupta
surgical preoperative evaluation of the bariatric patient — The
M, Kashyap SR. Reduced cardiovascular risk following bariatric
Cleveland Clinic protocol and review of the literature. Surgeon.
surgeries is related to a partial recovery from “adiposopathy.”
2011;9(5):273-277.
Obes Surg. 2011;21(12):1928-1936.
Surgery
Wu J, You J, Yerian L, Shiba A, Schauer PR, Sessler DI.
Agcaoglu O, Sahin DA, Siperstein A, Berber E. Selection
Prevalence of liver steatosis and fibrosis and the diagnostic
algorithm for posterior versus lateral approach in laparoscopic
accuracy of ultrasound in bariatric surgery patients. Obes Surg.
adrenalectomy. Surgery. 2012;151(5):731-735.
2012;22(2):240-247.
Karabulut K, Akyildiz HY, Lance C, Aucejo F, McLennan G,
Pediatric Emergency Care
Agcaoglu O, Siperstein A, Berber E. Multimodality treatment of
Horwitz SM, Heinberg LJ, Storfer-Isser A, Barnes DH, Smith M,
neuroendocrine liver metastases. Surgery. 2011;150(2):316-325.
Kapur R, Findling R, Currier G, Wilcox HC, Wilkens K. Teaching
Karabulut K, Agcaoglu O, Aliyev S, Siperstein A, Berber E.
physicians to assess suicidal youth presenting to the emergency
Comparison of intraoperative time use and perioperative out-
department. Pediatr Emerg Care. 2011;27(7):601-605.
comes for robotic versus laparoscopic adrenalectomy. Surgery.
2012;151(4):537-542.
Pituitary
Cheng V, Faiman C, Kennedy L, Khoury F, Hatipoglu B, Weil
Wallace LB, Parikh RT, Ross LV, Mazzaglia PJ, Foley C, Shin
R, Hamrahian A. Pregnancy and acromegaly: a review. Pituitary.
JJ, Mitchell JC, Berber E, Siperstein AE, Milas M. The pheno-
2012;15(1):59-63.
type of primary hyperparathyroidism with normal parathyroid
Daud S, Hamrahian AH, Weil RJ, Hamaty M, Prayson RA,
2011;150(6):1102-1112.
hormone levels: How low can parathyroid hormone go? Surgery.
Olansky L. Acromegaly with negative pituitary MRI and no
evidence of ectopic source: the role of transphenoidal pituitary
exploration? Pituitary. 2011;14(4):414-417.
Surgery for Obesity and Related Diseases
Brethauer S. American Society for Metabolic and Bariatric
Grover V, Hamrahian AH, Prayson RA, Weil RJ. Rathke’s cleft
Surgery position statement on global bariatric healthcare.
cyst presenting as bilateral abducens nerve palsy. Pituitary.
Surg Obes Relat Dis. 2011;7(6):669-671.
2011;14(4):395-399.
Brethauer S. ASMBS position statement on preoperative
supervised weight loss requirements. Surg Obes Relat Dis.
2011;7(3):257-260.
continued on next page
800.223.2273, ext. 46568
| 23 |clevelandclinic.org/endonotes
Publications
continued
Brethauer SA, Chand B, Schauer PR, Thompson CC. Transoral
Kroh M, El-Hayek K, Rosenblatt S, Chand B, Escobar P, Kaouk
gastric volume reduction as intervention for weight manage-
J, Chalikonda S. First human surgery with a novel single-port
ment: 12-month follow-up of TRIM trial. Surg Obes Relat Dis.
robotic system: cholecystectomy using the da Vinci Single-Site
2012;8(3):296-303.
platform. Surg Endosc. 2011;25(11):3566-3573.
Heinberg LJ, Ashton K, Coughlin J. Alcohol and bariatric
Yimcharoen P, Heneghan HM, Singh M, Brethauer S, Schauer P,
surgery: review and suggested recommendations for assessment
Rogula T, Kroh M, Chand B. Endoscopic findings and outcomes
and management. Surg Obes Relat Dis. 2012;8(3):357-363.
of revisional procedures for patients with weight recidivism after
Heneghan HM, Heinberg L, Windover A, Rogula T, Schauer PR.
Weighing the evidence for an association between obesity and
gastric bypass. Surg Endosc. 2011;25(10):3345-3352.
Surgical Laparoscopy Endoscopy & Percutaneous Techniques
suicide risk. Surg Obes Relat Dis. 2012;8(1):98-107.
Berber E, Siperstein A. Robotic transaxillary total thyroidectomy
Schauer PR, Rubino F. International Diabetes Federation
using a unilateral approach. Surg Laparosc Endosc Percutan
position statement on bariatric surgery for type 2 diabetes: impli-
Tech. 2011;21(3):207-210.
cations for patients, physicians, and surgeons. Surg Obes Relat
Wallace LB, Berber E. Percutaneous and video-assisted ablation
Dis. 2011;7(4):448-451.
of endocrine tumors: liver, adrenal, and thyroid. Surg Laparosc
Endosc Percutan Tech. 2011;21(4):255-259.
Yimcharoen P, Heneghan HM, Tariq N, Brethauer SA, Kroh M,
Chand B. Endoscopic stent management of leaks and anastomotic strictures after foregut surgery. Surg Obes Relat Dis.
Thyroid
2011;7(5):628-636.
Cheng V, Brainard J, Nasr C. Co-occurrence of papillary
Yimcharoen P, Heneghan H, Chand B, Talarico JA, Tariq N, Kroh
M, Brethauer SA. Successful management of gastrojejunal strictures after gastric bypass: is timing important? Surg Obes Relat
thyroid carcinoma and primary lymphoma of the thyroid in
a patient with long-standing Hashimoto’s thyroiditis. Thyroid.
2012;22(6):647-650.
Dis. 2012;8(2):151-157.
McQuade C, Skugor M, Brennan DM, Hoar B, Stevenson
Surgical Clinics of North America
hypothyroidism are associated with increased all-cause mortality
Brethauer SA. Sleeve gastrectomy. Surg Clin North Am.
independent of coronary heart disease risk factors: A PreCIS
2011;91(6):1265-1279.
database study. Thyroid. 2011;21(8):837-843.
Surgical Endoscopy
Brethauer SA, Heneghan HM, Eldar S, Gatmaitan P, Huang H,
Book Chapters
Kashyap S, Gornik HL, Kirwan JP, Schauer PR. Early effects
Ashton K, Budur K. Scared to sleep: A Hurricane Katrina survi-
C, Hoogwerf BJ. Hypothyroidism and moderate subclinical
of gastric bypass on endothelial function, inflammation, and
vor. In: Foldvary-Schaefer N, Krishna J, Budur K, eds. A Case a
cardiovascular risk in obese patients [Erratum in: Surg Endosc.
Week: Sleep Disorders from the Cleveland Clinic. Oxford; New
2011;25(8):2660]. Surg Endosc. 2011;25(8):2650-2659.
York, NY: Oxford University Press; 2011. Chapter 3. p. 43-48.
Gould J, Ellsmere J, Fanelli R, Hutter M, Jones S, Pratt J,
Ashton K, Streem D. Smoking cessation. In: Carey WD, ed.
Schauer P, Schirmer B, Schwaitzberg S, Jones DB. Panel report:
Current Clinical Medicine. 2nd ed. Philadelphia, PA: Saunders/
best practices for the surgical treatment of obesity. Surg Endosc.
Elsevier; 2010. p. 977-980.
2011;25(6):1730-1740.
Babar T, Skugor M. Diabetes mellitus treatment. In: Carey
WD, ed. Current Clinical Medicine. 2nd ed. Philadelphia, PA:
Saunders/Elsevier; 2010. p. 358-363.
Endocrine Notes
| 24 |2012
Brethauer S, Kashyap S, Schauer P. Obesity. In: Carey WD, ed.
Moustarah F, Brethauer SA, Schauer PR. Laparoscopic surgery
Current Clinical Medicine. 2nd ed. Philadelphia, PA: Saunders/
for severe obesity. In: Cameron JL, Cameron AM, eds. Current
Elsevier; 2010. p. 391-396.
Surgical Therapy. 10th ed. Philadelphia, PA: Saunders/Elsevier;
2011. p. 1304-1316.
Chikunguwo SM, Brethauer SA, Schauer PR. Bariatric surgery.
In: Cameron JL, Cameron AM, eds. Surgery of the Esophagus
Nasr C. Flushing. In: Carey WD, ed. Current Clinical Medicine.
and Stomach. London; New York, NY: Springer; 2011. Chapter
2nd ed. Philadelphia, PA: Saunders/Elsevier; 2010. p. 369-375.
16. p. 217-232.
Reddy SSK. Hypothalamic-pituitary disorders. In: Camacho PM,
Chinnappa P, Mehta A. Hirsutism. In: Carey WD, ed. Current
ed. Clinical Endocrinology and Metabolism (A Color Handbook).
Clinical Medicine. 2nd ed. Philadelphia, PA: Saunders/Elsevier;
London: Manson Publishing; 2011. Chapter 4. p. 91-112.
2010. p. 376-379.
Schirmer B, Schauer PR. The surgical management of obesity.
Diab DL, Hamrahian AH. Clinical detection and treatment of be-
In: Brunicardi FC, ed. Schwartz’s Principles of Surgery. 9th ed.
nign and malignant pituitary diseases. In: Hunt JL, ed. Molecular
New York, NY: McGraw-Hill; 2010. Chapter 27. p. 949-978.
Pathology of Endocrine Diseases. New York, NY: Springer; 2010.
Chapter 17. p. 169-174.
Skugor M. Section 4: Endocrinology [Section editor]. In: Carey
WD, ed. Current Clinical Medicine. 2nd ed. Philadelphia, PA:
Gatmaitan P, Brethauer SA, Schauer PR. Obesity and presentations after anti-obesity surgery. In: Talley NJ, Kane SV, Wallace
Saunders/Elsevier; 2010. p. 335-420.
Skugor M. Hypocalcemia and hypercalcemia. In: Carey WD, ed.
MB, eds. Practical Gastroenterology and Hepatology. Small
Current Clinical Medicine. 2nd ed. Philadelphia, PA: Saunders/
and Large Intestine and Pancreas. Chichester, West Sussex ;
Elsevier; 2010. p. 380-386.
Hoboken, NJ: Wiley-Blackwell; 2010. Chapter 24. p. 169-175.
Skugor M. Osteoporosis. In: Carey WD, ed. Current Clinical
Gopan T, Hamrahian A. Adrenal disorders. In: Camacho PM,
Medicine. 2nd ed. Philadelphia, PA: Saunders/Elsevier; 2010.
ed. Clinical Endocrinology and Metabolism (A Color Handbook).
p. 402-407.
London: Manson Publishing; 2011. Chapter 5. p. 113-147.
Skugor M, Fleseriu M. Hypothyroidism and hyperthyroidism. In:
Harvey AM, Siperstein AE, Berber E. Clinical detection and
Carey WD, ed. Current Clinical Medicine. 2nd ed. Philadelphia,
treatment of adrenal disease. In: Hunt JL, ed. Molecular
Pathology of Endocrine Diseases. New York, NY: Springer; 2010.
Chapter 19. p. 197-203.
PA: Saunders/Elsevier; 2010. p. 416-420.
Skugor M, Hamrahian AH. Pituitary disorders. In: Carey WD, ed.
Current Clinical Medicine. 2nd ed. Philadelphia, PA: Saunders/
Ioachimescu AG, Hamrahian AH. Diseases of the adrenal
Elsevier; 2010. p. 408-415.
gland. In: Carey WD, ed. Current Clinical Medicine. 2nd ed.
Philadelphia, PA: Saunders/Elsevier; 2010. p. 336-349.
Zimmerman R. Microvascular complications of diabetes. In:
Carey WD, ed. Current Clinical Medicine. 2nd ed. Philadelphia,
Mitchell JC. Clinical detection and treatment of pancreatic
PA: Saunders/Elsevier; 2010. p. 355-357.
neuroendocrine tumors. In: Hunt JL, ed. Molecular Pathology of
Endocrine Diseases. New York, NY: Springer; 2010. Chapter 22.
p. 229-235.
Mitchell JC, Milas M. Clinical detection and treatment of thyroid
diseases. In: Hunt JL, ed. Molecular Pathology of Endocrine
Diseases. New York, NY: Springer; 2010. Chapter 4. p. 27-35.
800.223.2273, ext. 46568
| 25 |clevelandclinic.org/endonotes
Live and Online
CME Opportunities
Cleveland Clinic’s Center for Continuing Education offers
convenient, complimentary learning opportunities, from
webcasts and podcasts to a host of medical publications,
in addition to live CME symposia.
Thyroid Expo 2013
Jan. 26, 2013
Lerner College of Medicine | NA5-08 Auditorium and Conference Wing
This one-day course will highlight recent advances in the management of thyroid
diseases. In 2012, these included molecular pathogenesis and prognostication in
thyroid cancer. More so than ever before, innovations of new surgical technologies,
thyroid cancer diagnostic tests, and new therapies for thyroid cancer are influencing
patient care options. The format of the course is designed to address the key concepts
of these advancements during lectures and panel discussions.
Diabetes Day 2013
May 31, 2013
Intercontinental Hotel and Bank of America Conference Center, Cleveland
Get up to date on the mechanisms of complications for patients with diabetes.
This event is designed to increase your competency and performance when
caring for this patient population, ultimately improving patient outcomes.
For more information on these events, visit our website:
clevelandclinic.org/endonotes
Online CME
Online webcasts and journal articles of interest to endocrinologists and approved for AMA PRA Category 1 Credits™ include:
Online Webcast
“The Next Generation of Therapies
for Type 2 Diabetes”
Estimated Time: 45 minutes
Online Journal Article
“Glucocorticoid-Induced Diabetes and
Adrenal Suppression: How to Detect
and Manage Them”
Estimated Time: 1 hour
Online Journal Article
“Does Lack of Sleep Cause
Diabetes?”
Estimated Time: 1 hour
For a full list of all Cleveland Clinic CME opportunities, please visit ccfcme.org; to manage your CME credits,
use the myCME.com Web portal, available 24/7.
Endocrine Notes
| 26 |2012
Current Clinical Trials
T I T LE
PI
CONTAC T / N U M B E R
ACROSTUDY – A Multicenter, Post-Marketing Surveillance Study of Somavert® Therapy in Patients with
Acromegaly in the USA and Europe
Amir Hamrahian, MD
Andreea Mocanu
216.444.9612
Somatuline® Depot (Lanreotide) Injection for Acromegaly (SODA): A Post-Marketing Observational Study
Betul Hatipoglu, MD
Andreea Mocanu
216.444.9612
DiaPep277® – A Phase III, Multinational, Randomized, Double-Blind, Placebo-Controlled,
Parallel-Group Study to Investigate the Clinical Efficacy and Safety of DiaPep277 in Newly Diagnosed
Type 1 Diabetes Subjects
Leann Olansky, MD
Bob McCoy
216.445.4029
A Randomized, Double-Masked, Placebo-Controlled, Multicenter, Phase 2 Study to Evaluate the Safety and
Renal Efficacy of LY2382770 in Patients with Diabetic Kidney Disease Due to Type 1 or Type 2 Diabetes
Leann Olansky, MD
Andreea Mocanu
216.444.9612
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate Cardiovascular
Outcomes During Treatment with Lixisenatide in Type 2 Diabetic Patients After an Acute Coronary Syndrome
Robert Zimmerman, MD
Bob McCoy
216.445.4029
EXenatide Study of Cardiovascular Event Lowering Trial (EXSCEL)
Robert Zimmerman, MD
Bob McCoy
216.445.4029
The Diagnostic Accuracy of the Glucagon Stimulation Test for Evaluation of Adult Growth Hormone
Deficiency and the Hypothalamic-Pituitary-Adrenal Axis
Amir Hamrahian, MD
Bob McCoy
216.445.4029
The CAROLINA Trial – A Multicentre, International, Randomized, Parallel Group, Double-Blind Study to
Evaluate Cardiovascular Safety of Linagliptin vs. Glimepiride in Patients with Type 2 Diabetes Mellitus at
High Cardiovascular Risk
Leann Olansky, MD
Andreea Mocanu
216.444.9612
Effect of a Portion-Controlled, Commercially Available Diet on Presurgical Weight Loss and Metabolic
Outcomes in Patients Undergoing Laparoscopic Bariatric Surgery
Leslie Heinberg, PhD, MA
Chytaine Hall
216.445.3983
Effect of Bariatric Surgery on Mechanisms of Type 2 Diabetes: The B2D Trial
John Kirwan, PhD
Chytaine Hall
216.445.3983
Gastric Plication for the Treatment of Obesity and Related Conditions
Philip Schauer, MD
Janice Kakish
216.444.7551
Parathyroidectomy – Effect of Parathyroidectomy in Reducing Coronary Artery Calcification and Improving
Vascular Compliance in Patients with Primary and Secondary Hyperparathyroidism
Eren Berber, MD
Linda Heil
216.444.2262
Randomized, Double-Blind, Phase II Trial of Radiofrequency Ablation +/- Lyso-Thermosensitive
Liposomal Doxorubicin (ThermoDox®) for Colorectal Liver Metastases ≥2 cm Maximum Diameter
Allan Siperstein, MD
Linda Heil
216.444.2262
Allan Siperstein, MD
Linda Heil
216.444.2262
Prospective Randomized Comparison of Bilateral vs. Focal Neck Exploration for
Sporadic Hyperparathyroidism
800.223.2273, ext. 46568
| 27 |clevelandclinic.org/endonotes
Endocrinology & Metabolism Institute
Staff Directory
ENDOCRINOLOGY & METABOLISM INSTITUTE LEADERSHIP
James Young, MD
Institute Chairman
Endocrinology & Metabolism Institute
216.444.2333
Allan Siperstein, MD
Chairman, Department of Endocrine
Surgery
Laurence (Ned) Kennedy, MD
Chairman, Department of Endocrinology,
Diabetes and Metabolism
Philip Schauer, MD
Chairman, Bariatric & Metabolic
Institute
216.445.8645
216.444.4794
216.444.5664
Department of Endocrinology, Diabetes and Metabolism
Revital Gorodeski Baskin, MD
Specialty Interest(s): Endocrinology,
thyroid disorders, thyroid cancer
Location(s): Independence Family Health Center
Office: 216.986.4000 | Fax: 216.986.4995
Appointments: 216.986.4000
Betul Hatipoglu, MD
Specialty Interest(s): Diabetes, thyroid
disorders, pituitary disorders, adrenal disorders,
alternative medicine
Location(s): Main campus
Office: 216.445.6709 | Fax: 216.445.1656
Appointments: 216.444.6568
Kevin Borst, DO
Specialty Interest(s): Endocrine disorders
in pregnancy, general endocrinology, diabetes
Location(s): Lakewood Hospital Professional Building
Office: 216.529.5300 | Fax: 216.529.5301
Appointments: 216.444.6568
Suman Jana, MD
Specialty Interest(s): General endocrinology,
diabetes, thyroid disease, thyroid cancer
Location(s): Main campus; Medina
Office: 216.444.0567 | Fax: 216.445.1656
Appointments: Main campus, 216.444.6568;
Medina, 330.725.3713
Krupa Doshi, MD
Specialty Interest(s): General endocrinology,
diabetes, parathyroid and calcium disorders,
hirsutism, thyroid disorders, adrenal disorders
Location(s): Main campus
Office: 216.445.0741 | Fax: 216.445.1656
Appointments: 216.444.6568
Marwan Hamaty, MD
Specialty Interest(s): General endocrinology, diabetes
Location(s): Main campus; Strongsville Family
Health and Surgery Center
Office: 216.445.7568 | Fax: 216.445.1656
Appointments: Main campus, 216.444.6568;
Strongsville, 440.878.2500
Amir Hamrahian, MD
Specialty Interest(s): Pituitary and adrenal disorders
Location(s): Main campus
Office: 216.445.8538 | Fax: 216.445.1656
Appointments: 216.444.6568
Visit clevelandclinic.org/EndoStaff for the most current staff listings and locations.
Sangeeta Kashyap, MD
Specialty Interest(s): Endocrinology, diabetes,
insulin resistance and cardiovascular risk
prevention, obesity, metabolic syndrome and
diseases, hyperlipidemia
Location(s): Main campus
Office: 216.445.2679 | Fax: 216.445.1656
Appointments: 216.444.6568
Laurence (Ned) Kennedy, MD
Department Chair
Specialty Interest(s): General endocrinology,
diabetes, pituitary disorders, hyperthyroidism,
hypothyroidism, thyroiditis
Location(s): Main campus; Ashtabula County
Medical Center; Cleveland Clinic Florida, Weston
Office: 216.445.8645 | Fax: 216.445.1656
Appointments: Main campus, 216.444.6568;
Ashtabula, 440.997.6910; Florida, 954.659.6038
Leila Khan, MD
Specialty Interest(s): General endocrinology,
diabetes, calcium/bone disorders
Location(s): Main campus; Willoughby Hills
Family Health Center
Office: 216.445.1598 | Fax: 216.445.1656
Appointments: Main campus, 216.444.6568;
Willoughby Hills, 440.943.2500
Endocrinology & Metabolism Institute | Staff Directory
M. Cecilia Lansang, MD, MPH
Specialty Interest(s): General endocrinology, diabetes
Location(s): Main campus
Office: 216.445.5246 | Fax: 216.445.1656
Appointments: 216.444.6568
Melissa Li-Ng, MD
Specialty Interest(s): General endocrinology, diabetes
Location(s): Main campus
Office: 216.444.1949 | Fax: 216.445.1656
Appointments: 216.444.6568
Vinni Makin, MD
Specialty Interest(s): General endocrinology,
diabetes, hirsutism, acne, thyroid disorders
Location(s): Main campus; Solon Family Health Center
Office: 216.444.0539 | Fax: 216.445.1656
Appointments: Main campus, 216.444.6568;
Solon, 440.519.6800
Adi Mehta, MD
Specialty Interest(s): Diabetes, thyroid disorders,
endocrine complications of pregnancy, menopause,
lipid disorders, general and adolescent endocrinology
Location(s): Main campus; Beachwood Family
Health Center (reproductive endocrinology only)
Office: 216.445.5312 | Fax: 216.445.7261
Appointments: Main campus, 216.444.6568;
Beachwood, 216.839.3000
Guy Mulligan, MD
Specialty Interest(s): General endocrinology, diabetes
Location(s): Main campus; Independence Family Health
Center; Twinsburg Family Health and Surgery Center
Office: 330.888.4000 | Fax: 330.963.4561
Appointments: Independence, 216.986.4000; Main
campus, 216.444.6568; Twinsburg, 330.888.4000
Christian Nasr, MD
Specialty Interest(s): Thyroid nodules, thyroid
cancers, flushing syndromes
Location(s): Main campus; Lorain Family Health and
Surgery Center (thyroid cancer only)
Office: 216.445.1788 | Fax: 216.445.1656
Appointments: Main campus, 216.444.6568;
Lorain, 440.204.7400
Leann Olansky, MD
Specialty Interest(s): Diabetes and diabetes complications,
gestational diabetes, general endocrinology
Location(s): Main campus; Stephanie Tubbs Jones
Health Center
Office: 216.444.2642 | Fax: 216.445.1656
Appointments: Main campus, 216.444.6568;
Stephanie Tubbs Jones Health Center, 216.767.4242
Kevin Pantalone, DO
Specialty Interest(s): Type 2 diabetes mellitus;
male hypogonadism (low testosterone); thyroid,
pituitary and adrenal disorders
Location(s): Main campus; Twinsburg Family Health
and Surgery Center
Office: 330.888.4000 | Fax: 216.445.1656
Appointments: Main campus, 216.444.6568;
Twinsburg, 330.888.4000
Seenia Peechakara, MD
Specialty Interest(s): Endocrine disorders in pregnancy, thyroid
disorders, thyroid cancer, diabetes, calcium and parathyroid
disorders, lipid disorders, pituitary and adrenal disorders,
general endocrinology
Location(s): Lakewood Hospital Professional Building
Office: 216.529.5300 | Fax: 216.529.5301
Appointments: 216.444.6568
Richard Shewbridge, MD
Specialty Interest(s): Endocrinology, diabetes, thyroid
disorders, hyperlipidemia, osteoporosis
Location(s): Medina Medical Office Building
Office: 330.725.3713 | Fax: 330.725.2141
Appointments: 330.725.3713
David Shewmon, MD
Specialty Interest(s): General endocrinology, diabetes, high
cholesterol, osteomalacia, osteoporosis, pituitary tumors,
thyroid conditions, thyroid cancer
Location(s): Lakewood Hospital Professional Building
Office: 216.529.5300 | Fax: 216.529.5301
Appointments: 216.444.6568
Mario Skugor, MD
Associate Director, Endocrinology Fellowship Program
Specialty Interest(s): Osteoporosis and calcium metabolism,
obesity and diabetes, multiple endocrine neoplasia syndromes,
thyroid disorders, thyroid cancer
Location(s): Main campus
Office: 216.445.0739 | Fax: 216.445.1656
Appointments: 216.444.6568
Mariam Stevens, MD
Specialty Interest(s): Diabetes, gestational diabetes,
goiter, Graves disease, Hashimoto disease, hirsutism,
hyperthyroidism, hypoglycemia, hypothyroidism, polycystic
ovary syndrome, thyroid disease,
Location(s): Independence Family Health Center
Office: 216.986.4000 | Fax: 216.986.4995
Appointments: 216.986.4000
Mary Vouyiouklis, MD
Specialty Interest(s): Thyroid disorders, thyroid cancer,
parathyroid and calcium disorders, adrenal disorders, diabetes
Location(s): Main campus; Solon Family Health Center;
Willoughby Hills Family Health Center
Office: 216.444.6568 | Fax: 216.445.1656
Appointments: Main campus, 216.444.6568; Solon,
440.519.6908; Willoughby Hills, 440.943.2500
Susan Williams, MD
Specialty Interest(s): Bone and mineral metabolism, metabolic
bone disease, calcium disorders, malabsorption and
malnutrition in adults, medical bariatrics
Location(s): Main campus
Office: 216.444.5665 | Fax: 216.445.1656
Appointments: 216.444.6568
Robert Zimmerman, MD
Director, Cleveland Clinic Diabetes Center
Department Vice Chair
Program Director, Endocrinology Training Program
Specialty Interest(s): Diabetes, thyroid disorders, growth
hormone in adults
Location(s): Main campus
Office: 216.444.9428 | Fax: 216.445.1656
Appointments: 216.444.6568
Department of Endocrine Surgery
Bariatric & Metabolic Institute
Eren Berber, MD
Director, Robotic Endocrine Surgery
Specialty Interest(s): Endocrine surgery (thyroid and
parathyroid), laparoscopic radiofrequency
ablation of liver tumors, pancreatic neuroendocrine
tumors, robotic thyroid and parathyroid surgery,
laparoscopic and robotic adrenalectomy and liver surgery
Location(s): Main campus
Office: 216.445.0555 | Fax: 216.636.0662
Appointments: 216.444.6568
Stacy Brethauer, MD
Department Vice Chair
Specialty Interest(s): Bariatric surgery, laparoscopic surgery,
gastrointestinal surgery, hernia repair, endoscopy, surgery
for GERD, hiatal hernia, solid-organ endoluminal surgery,
single-incision laparoscopic surgery
Location(s): Main campus; Richard E. Jacobs Health Center
Office: 216.444.9244 | Fax: 216.445.1586
Appointments: Main campus, 216.445.2224; Richard E.
Jacobs, 440.695.4000
Judy Jin, MD
Specialty Interest(s): Endocrine surgery (thyroid
and parathyroid), advanced laparoscopic surgery,
laparoscopic adrenalectomy, laparoscopic radiofrequency
ablation of liver tumors
Location(s): Main campus
Office: 216.445.3411 | Fax: 216.636.0662
Appointments: 216.444.6568
Derrick Cetin, DO
Specialty Interest(s): Bariatric medicine, medical weight
management, nutrition sciences, obesity management,
preoperative evaluation, diabetes care
Location(s): Main campus
Office: 216.445.4255 | Fax: 216.636.1588
Appointments: 216.445.2224
Rosemarie Metzger, MD
Specialty Interest(s): Endocrine surgery
(thyroid, parathyroid and adrenal)
Location(s): Main campus
Office: 216.445.3695 | Fax: 216.636.0662
Appointments: 216.444.6568
Jamie Mitchell, MD
Specialty Interest(s): Endocrine surgery (thyroid,
parathyroid and adrenal), laparoscopic solid organ
surgery, advanced laparoscopic surgery, laparoscopic
radiofrequency ablation of liver tumors
Location(s): Main campus; Independence Family Health
Center; Solon Family Health Center
Office: 216.445.9713 | Fax: 216.636.0662
Appointments: Main campus, 216.444.6568;
Independence, 216.986.4000; Solon, 440.519.6800
Joyce J. Shin, MD
Specialty Interest(s): Endocrine surgery (thyroid and
parathyroid), advanced laparoscopic surgery, laparoscopic
adrenalectomy, neuroendocrine tumors, thyroid/parathyroid
ultrasound, intra-abdominal ultrasound, laparoscopic
radiofrequency thermal ablation of liver tumors
Location(s): Main campus; Willoughby Hills
Family Health Center
Office: 216.636.9365 | Fax: 216.636.0662
Appointments: Main campus, 216.444.6568;
Willoughby Hills, 440.943.2500
Allan Siperstein, MD
Department Chair
Specialty Interest(s): Endocrine surgery (thyroid
and parathyroid), advanced laparoscopic surgery,
laparoscopic thermal ablation of liver tumors, pancreatic
endocrine tumors
Location(s): Main campus
Office: 216.444.5664 | Fax: 216.636.0662
Appointments: 216.444.6568
Visit clevelandclinic.org/EndoStaff for the most current staff listings and locations.
Karen Cooper, DO
Specialty Interest(s): Bariatric medicine, family medicine,
kinesiology and nutrition sciences, exercise instruction
Location(s): Main campus
Office: 216.445.1114 | Fax: 216.445.1586
Appointments: 216.445.2224
Matthew Kroh, MD
Specialty Interest(s): Advanced laparoscopic surgery,
bariatric surgery, gastrointestinal surgery, endoscopy,
single-incision laparoscopic surgery
Location(s): Main campus
Office: 216.445.9966 | Fax: 216.444.2153
Appointments: 216.445.2224
Tomasz Rogula, MD, PhD
Specialty Interest(s): Advanced laparoscopic surgery,
bariatric surgery, gastrointestinal surgery, endoscopy,
single-incision laparoscopic surgery
Location(s): Main campus; Strongsville Family Health
and Surgery Center
Office: 216.445.0255 | Fax: 216.445.1586
Appointments: Main campus, 216.445.2224;
Strongsville, 440.878.2500
Philip Schauer, MD
Department Chair
Specialty Interest(s): Bariatric surgery, laparoscopic surgery,
gastrointestinal surgery, colon surgery, weight management,
hernia surgery, biliary surgery, surgery for GERD
Location(s): Main campus
Office: 216.444.4794 | Fax: 216.445.1586
Appointments: 216.445.2224
Cle vel and Clinic RESOURCE Guide
24/7 Referrals
About Cleveland Clinic
Referring Physician Hotline
855.REFER.123 (855.733.3712)
Cleveland Clinic is an integrated healthcare delivery system with local, national and
international reach. At Cleveland Clinic, 2,800 physicians represent 120 medical
specialties and subspecialties. We are a main campus, 18 family health centers,
eight community hospitals, Cleveland Clinic Florida, Cleveland Clinic Lou Ruvo
Center for Brain Health in Las Vegas, Cleveland Clinic Canada, Sheikh Khalifa
Medical City and Cleveland Clinic Abu Dhabi.
In 2012, Cleveland Clinic was ranked one of America’s top 4 hospitals in
U.S. News & World Report’s annual “America’s Best Hospitals” survey. The survey
ranks Cleveland Clinic among the nation’s top 10 hospitals in 14 specialty areas,
and the top hospital in three of those areas.
Hospital Transfers
800.553.5056
On the Web at clevelandclinic.org/Refer123
Stay Connected with Us on …
Resources for Physicians
Referring Physician Center and Hotline
Cleveland Clinic’s Referring Physician Center has established a
24/7 hotline — 855.REFER.123 (855.733.3712) — to
streamline access to our array of medical services. Contact the
Referring Physician Hotline for information on our clinical
specialties and services, to schedule and confirm patient
appointments, for assistance in resolving service-related issues,
and to connect with Cleveland Clinic specialists.
Outcomes Data
View clinical Outcomes books from all Cleveland Clinic institutes
at clevelandclinic.org/outcomes.
Clinical Trials
We offer thousands of clinical trials for qualifying patients. Visit
clevelandclinic.org/clinicaltrials.
Physician Directory
View all Cleveland Clinic staff online at
clevelandclinic.org/staff.
CME Opportunities: Live and Online
The Cleveland Clinic Center for Continuing Education’s website
offers convenient, complimentary learning opportunities. Visit
ccfcme.org to learn more, and use Cleveland Clinic’s myCME
portal (available on the site) to manage your CME credits.
Track Your Patient’s Care Online
DrConnect is a secure online service providing real-time
information about the treatment your patient receives at
Cleveland Clinic. Establish a DrConnect account at
clevelandclinic.org/drconnect.
Executive Education
Cleveland Clinic has two education programs for healthcare
executive leaders — the Executive Visitors’ Program and the
two-week Samson Global Leadership Academy immersion
program. Visit clevelandclinic.org/executiveeducation.
Critical Care Transport Worldwide
Cleveland Clinic’s critical care transport teams and fleet
of vehicles are available to serve patients across the globe.
To arrange for a critical care transfer, call 216.448.7000 or
866.547.1467 (see clevelandclinic.org/criticalcaretransport).
For STEMI (ST elevated myocardial infarction), acute stroke, ICH
(intracerebral hemorrhage), SAH (subarachnoid hemorrhage) or
aortic syndrome transfers, call toll-free 877.379.CODE (2633).
Same-Day Appointments
Cleveland Clinic offers same-day appointments to help your
patients get the care they need, right away. Have your patients
call our same-day appointment line, 216.444.CARE (2273) or
800.223.CARE (2273).
Resources for Patients
Medical Concierge
For complimentary assistance for out-of-state patients and
families, call 800.223.2273, ext. 55580, or email
[email protected].
Global Patient Services
For complimentary assistance for national and international
patients and families, call 001.216.444.8184 or visit
clevelandclinic.org/gps.
MyChart®
Cleveland Clinic MyChart® is a secure, online personal healthcare
management tool that connects patients to their medical record.
Patients can register for MyChart through their physician’s office
or by going online to clevelandclinic.org/mychart.
MyConsult
Cleveland Clinic offers online medical second opinions for more
than 1,000 life-threatening and life-altering diagnoses. For more
information, visit clevelandclinic.org/myconsult or call
800.223.2237, ext. 43223.
12-END-382
Endocrine Notes
| 5 |2012
The Cleveland Clinic Foundation
Endocrinology & Metabolism Institute
Endocrine Notes
9500 Euclid Ave. / AC311
Cleveland, OH 44195
HOSPITALS
NATIONAL
DIABETES & ENDOCRINOLOGY
Cleveland Clinic’s Diabetes and Endocrinology Program is
ranked No. 2 in the nation in the annual U.S. News & World
Report “America’s Best Hospitals” survey.
In This Issue:
2Cleveland Clinic Study Identifies Increased Mortality
Risk with Sulfonylureas vs. Metformin
4
Differentiating Normocalcemic Primary Hyperparathyroidism
and Secondary Hyperparathyroidism
6Five Important Pillars to Adhere to When Ordering and Interpreting IPSS in
Patients with ACTH-Dependent Cushing Syndrome
10 Robotic Bilateral Posterior Adrenalectomy for ACTH-Independent
Macronodular Adrenal Hyperplasia Causing Subclinical Cushing Syndrome
12Study Highlights Importance of Screening for Thyroid Cancer
in Patients Diagnosed with Cowden Syndrome
14
roposed Clinical Algorithm Targets the Management of
P
Residual Diabetes Following Bariatric Surgery
of Bariatric Surgery in Type 2 Diabetes Extend
16 Btoenefits
Improvement, Prevention of Nephropathy
Bypass Improves Glucose Homeostasis by Attenuating
18Gastric
the Effect of Ghrelin on ß-cell Function
800.223.2273, ext. 46568
20 Publications
26 Live and Online CME Opportunities
27 Current Clinical Trials
28 Staff Directory
| 4 |clevelandclinic.org/endonotes