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2012

Updates for physicians on practices, advances and research from Cleveland Clinic’s Endocrinology & Metabolism Institute

endocrine notes

Endocrine Notes | 2 | 2012

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Endocrine Notes

Chairman, Endocrinology & Metabolism Institute

James B. Young, MD

Managing Editor

Kimberley Sirk

Art Director

Mike Viars

Marketing

Bill Sattin, PhD

Mary Anne Connor

Endocrine Notes updates physicians on clinical prac-

tices, advances and research from Cleveland Clinic’s

Endocrinology & Metabolism Institute. It is written for

physicians and should be relied on for medical education

purposes only. It does not provide a complete overview of

the topics covered and should not replace the independent

judgment of a physician about the appropriateness or risks

of a procedure for a given patient.

© 2012 The Cleveland Clinic Foundation

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Endocrine Notes | 1 | 2012 800.223.2273, ext. 46568 | 1 | clevelandclinic.org/endonotes

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, MDChairman, 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


Texas, and they were published in Diabetes, Obesity and

Metabolism (see Suggested reading).

Robust data from a large patient population

We conducted this retrospective analysis using the Cleveland

Clinic Diabetes Registry, a repository comprising data on

patients with diabetes treated with oral anti-diabetic agents.

We identified 23,915 patients with type 2 diabetes who

were seen at Cleveland Clinic between 1998 and 2006 who

received monotherapy with metformin (n=12,774), glipizide

(n=4,325), glyburide (n=4,279) or glimepiride (n=2,537).

The patients were followed for mortality by documentation of

death within the enterprisewide electronic health record (EHR)

system and/or Social Security Death Index (SSDI) records.

There were a total of 2,546 deaths in 58,513 person years

of follow-up in the entire cohort, and 419 deaths in 5,980

person-years of follow-up in the subgroup with a history of

documented CAD (n=2,721). Multivariable Cox models with

propensity analysis were used to compare cohorts.

Cleveland Clinic is ideally suited to this type of study, given

our large patient population with type 2 diabetes and CAD

and our multidisciplinary approach in treating a high volume

of patients within the Endocrinology & Metabolism Institute

and the Sydell and Arnold Miller Family Heart & Vascular

Institute.

Practical clinical considerations

The precise reason why glimepiride may be safer than the

other sulfonylureas in patients with underlying CAD remains

unclear and requires further study.

In Cleveland Clinic’s Department of Endocrinology, Diabetes

and Metabolism, we have identified an increased risk of

overall mortality in patients with type 2 diabetes mellitus

treated with sulfonylurea vs. metformin monotherapy. In

patients who do receive a sulfonylurea, our research found

that glimepiride may be the preferred agent in patients with

underlying coronary artery disease (CAD).

We recently conducted a retrospective cohort study of nearly

24,000 patients with type 2 diabetes who were seen at

Cleveland Clinic, to assess the risk of overall mortality in

patients taking the most commonly prescribed sulfonyl-

ureas or metformin. In the entire population of our study,

which analyzed patients seen across eight years, glipizide,

glyburide and glimepiride were all associated with a statisti-

cally significant >50 percent increase in mortality risk vs.

metformin. However, in those patients with documented CAD,

a statistically significant increase in overall mortality risk

was observed with glipizide (41 percent) and glyburide (38

percent) vs. metformin — but not with glimepiride.

These results suggest that metformin is associated with a

substantial reduction in mortality risk vs. sulfonylureas; thus,

in the absence of contraindications, metformin should be

the preferred first-line agent. In addition, these study results

suggest that when a sulfonylurea is required to treat patients

with type 2 diabetes, particularly those with underlying CAD,

glimepiride may be the preferred/safer agent among the most

commonly used generic sulfonylureas available in the United

States (glipizide, glyburide and glimepiride).

We presented the results of our study at The Endocrine

Society’s 94th Annual Meeting, ENDO 2012, in Houston,

But Glimepiride May Be Safest Sulfonylurea

Cleveland Clinic Study Identifies Increased Mortality Risk with Sulfonylureas vs. Metformin

Kevin M. Pantalone, DO, and Robert Zimmerman, MD

800.223.2273, ext. 46568 | 3 | clevelandclinic.org/endonotes

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

the patient, it would seem inappropriate when no contrain-

dications 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 man-

age 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

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, espe-

cially 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

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, met-

formin, or sulfonylureas: a retrospective analysis. Acta Diabetol.

2009;46(2):145-154.

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

(A) Overall Mortality Entire Cohort

(B) Overall Mortality CAD Subgroup


By Judy Jin, MD

Differentiating Normocalcemic Primary Hyperparathyroidism and Secondary Hyperparathyroidism

Cleveland Clinic endocrine surgeons create mathematical model to clarify diagnosisWith awareness increasing about primary hyperpara-

thyroidism, clinicians are discovering that rather than

one disease entity of high calcium and high parathy-

roid 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 pri-

mary 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).

Overlapping biochemical presentation

NCPHP can at times be confused with secondary hyper-

parathyroidism. 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 diagno-

sis of NCPHP is suspected. This was a novel idea, so to test

how well the formula performs, we conducted a retrospec-

tive study at Cleveland Clinic.

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 bio-

chemical profiles and tested whether our formula would

have predicted primary hyperparathyroidism rather than

2° HPT.

Table 1

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

MaxPTH = 120 – 6 x Ca – 1/2 x VitD25 + 1/4 x Age

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.


In order to use the decision tree, we asked that all

patients undergo a comprehensive biochemical workup

(Figure 2). The protocol then takes the clinician through a

review of the patient’s ionized calcium and vitamin D lev-

els and the calculated maxPTH level to identify the next

management plan. This protocol clearly outlines when a

referral to the endocrine surgeon should be made.

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 devel-

oped 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 normocal-

cemic primary hyperparathyroidism.

About the author

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].

Patients should undergo this biochemical workup to help inform the primary clinician’s diagnosis,

treatment plan and possible referral to an endocrine surgeon.

SerumCalciumIonized CalciumIntact PTH25-Hydroxy Vitamin D1,25-Dihydroxyvitamin DPhosphorusMagnesiumAlbuminCreatinine

Urine24-hr Calcium24-hr Creatinine

Figure 2

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.

Figure 1

1

1

Our retrospective analysis 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

NCPHP. Even in patients with coexisting vitamin D

deficiency, the formula was able to sort these patients

into the NCPHP group and not the 2° HPT group.

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

management protocol to help clinicians effectively triage

patients to their correct disease group (Figure 1).


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

Clinical Endocrinology and Endocrine Practice concerning

the utility of IPSS and its interpretation in challenging cases of

ACTH-dependent Cushing syndrome (see Suggested reading).

Here we review the principles — referred to as the Five IPSS

Pillars — that are key to the appropriate use and

interpretation of IPSS. To illustrate how the pillars can be

used, we also share a report on a challenging case (see

sidebar article).

Inferior petrosal sinus sampling (IPSS) is the gold standard test

to determine the etiology of ACTH-dependent Cushing syndrome.

An inferior petrosal sinus to peripheral (IPS:P) ACTH ratio >2

before or >3 after corticotropin-releasing hormone (CRH) admin-

istration confirms a pituitary source of ACTH.

False-negative results, or the presence of Cushing disease

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,

the test suggests a pituitary source of ACTH when in fact the

source is ectopic or peripheral — is rare.

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


The Five IPSS PillarsBased on our experience at Cleveland Clinic, we believe clinicians

should adhere to the following principles for IPSS testing:

1 Do not perform IPSS before confirming the presence

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 angiogra-

phy 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 false-

negative 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 prolac-

tin ratio >1.8 as an indication of appropriate IPS venous

sampling. Currently, we have a dedicated interventional

neuroradiologist perform all IPSS procedures.

4 Note 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 ve-

nous 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.

5 Calculate prolactin-adjusted ACTH ratios. Prolactin-

adjusted ACTH ratios may help to lateralize a corticotroph

adenoma and may have an impact on surgical outcome.

While the utility of IPSS to diagnose pituitary-mediated

ACTH-dependent Cushing syndrome is well-established, to

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 gradi-

ent 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 measure-

ment 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 mi-

croadenoma 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 neurosur-

geon 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 administra-

tion 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.


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 drain-

age 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 postopera-

tively, 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 experi-

ence, guided us in diagnosing and treating the patient

discussed in this case.


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.

RPS LPS P ACTH ratio RPS LPS P PRL ratio

R/P L/P R/P L/P

-10 79 89 73 1.10 1.20 14.0 24.1 13.4 1.00 1.80 29.1

-5 77 85 76 1.00 1.10 13.1 28.6 12.5 1.00 2.20 28.5

+2 108 117 83 1.30 1.40 13.3 35.2 12.5 1.10 2.80 29.7

+5 196 267 210 0.93 1.30 13.6 38.8 11.8 1.20 3.30 31.6

+10 326 315 246 1.30 1.30 13.0 34.6 13.3 0.98 2.60 33.5

+15 383 370 288 1.30 1.30 13.7 34.9 12.7 1.10 2.70 36.5

Table 1

TIME min

CORT (µg/dL)

ACTH (pg/mL)

PRL (ng/mL)

About the authors

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.

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 pe-

trosal 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 sam-

pling 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.

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.

Machado MC, de Sa SV, Domenice S, Fragoso MC, Puglia P Jr,

Pereira MA, de Mendonça BB, Salgado LR. The role of desmopres-

sin 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.

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 in-

ferior 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.


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.

Based on this workup, we diagnosed the patient with

subclinical Cushing syndrome due to ACTH-independent

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.

Surgical technique

After intubation and administration of general anesthesia on

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 laparo-

scopic ultrasound. The robot surgical system was docked

(Figure 2), and we resected the mass. Then we turned

our attention to the other side. We made a 1-cm incision

below the right 12th rib and entered the retroperitoneal

space using an optical trocar. Then, we repeated the

same steps as on the contralateral side. The mass was

removed using a specimen retrieval bag inserted through

the 12-mm port site (Figure 3).

We performed a bilateral adrenalectomy with a skin-to-

skin operative time of 268 minutes (98 minutes for the

left side, and 170 minutes for the right side), including

the docking times of 12 and 6 minutes, respectively.

Estimated blood loss was 50 mL. The patient was

discharged uneventfully on steroid replacement on post-

operative 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-

ment therapy.

The choice of the posterior retroperitoneal approach was

helpful in this case, as this obviated the need to reposition

the patient to remove the mass on the contralateral side.

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 hospi-

tal. 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

Robotic Bilateral Posterior Adrenalectomy for ACTH-Independent Macronodular Adrenal Hyperplasia Causing Subclinical Cushing Syndrome


We believe that avoiding the abdominal cavity helped with

the patient’s quick recovery. Use of the robotic system

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 bilater-

al 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].

Suggested reading

Karabulut K, Agcaoglu O, Aliyev S, Siperstein A, Berber E. Comparison of intraoperative time use and perioperative out-comes for robotic versus laparoscopic adrenalectomy. Surgery. 2012;151(4):537-542.

Agcaoglu O, Aliyev S, Karabulut K, Siperstein A, Berber E. Robotic versus laparoscopic posterior retroperitoneal adrenalec-tomy. 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 out-comes 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.

Figure 2: Intraoperative photo depicting the position of the robotic system for the left side.

Figure 1: CT scan image showing bilateral adrenal masses. Figure 3: Intraoperative photo showing the final appearance of the incisions.

Grasping Forceps

30° Scope

Harmonic Scalpel


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 heri-table 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 syn-drome (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 muta-tion-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 impli-cations 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

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 dedi-cated 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 pathol-ogy 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-

Plus: Access Cleveland Clinic’s Online Calculator for Estimating a

Patient’s Risk for PTEN Mutation and Need for Genetics Consultation

Importance of Screening for Thyroid Cancer in Patients Diagnosed with Cowden Syndrome

Study Highlights

Figure 2By Rosemarie Metzger, MD, MPH, and Charis Eng, MD, PhD


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.

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 popula-tion 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 im-plications 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 mor-tality 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).

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

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


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 in-

dividuals 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.

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.


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.

Proposed Clinical Algorithm Targets the Management of Residual Diabetes Following Bariatric Surgery

Based on our experience, we have proposed a clinical

algorithm for the long-term management of residual diabetes

following bariatric surgery in the absence and presence of

weight regain. Our clinical approach, which is based on

established pathophysiological effects of these procedures

on diabetes remission, was published in Diabetes, Obesity

and Metabolism in 2012 (14:773-779).

Cleveland Clinic’s Bariatric & Metabolic Institute is fully

integrated within the broader Endocrinology & Metabolism

Institute. As such, the patient’s endocrinologist, as part

of a multidisciplinary obesity team, plays a key role in our

bariatric surgery center of excellence and other settings in

the long-term treatment, evaluation and monitoring of post-

bariatric surgery patients with type 2 diabetes. Of specific

importance is the need to monitor comorbidity status,

weight regain and nutritional deficiencies.

Diabetes nonremission or re-emergence

Residual diabetes occurs more commonly following gastric re-

strictive (i.e., laparoscopic adjustable gastric banding [LAGB]

and sleeve gastrectomy) procedures vs. intestinal bypass (i.e.,

Roux-en-Y gastric bypass [RYGB] and biliopancreatic diver-

sion [BPD]) surgeries. Patients who undergo gastric bypass

and BPD procedures improve sooner and maintain glucose

control for longer periods than do patients treated by banding

or sleeve gastrectomy procedures. Additionally, patients who

do not achieve biochemical remission or who experience a

re-emergence often have diabetes duration >10 years, are in

advanced stages of the disease, and experience inadequate

weight loss and regain weight. Other factors associated with

suboptimal diabetes control following bariatric procedures are

insulin use, male gender, lower preoperative BMI, severity of

preoperative ß-cell function (i.e., hyperglycemia) and poten-

tially inadequate incretin stimulation following surgery.

Therapies for residual diabetes

Nonremission of hyperglycemia is indicated by an HbA1c level

>7 percent or 53 mmol/mol that requires the use of anti-

diabetic medications. Targeting weight regain and poor residual

pancreatic ß-cell function with insulin may be indicated by du-

ration of diabetes >10 years, insulin use, poor glycemic control

on oral agents and microvascular complications.

Gastric restrictive procedures

In patients who have had gastric restrictive procedures,

nonremission is indicated when patients have inadequate

weight loss or weight regain and progressive ß-cell failure

without weight regain. The management of residual type 2

diabetes due to insulin resistance and/or insulin secretion

defects in these patients should focus on weight loss and

glycemic control with anti-diabetic medications that have

weight-negative or -neutral effects. Metformin remains the

first-line agent in this context due to its mechanism of ac-

tion that improves insulin sensitivity by suppressing hepatic

gluconeogenesis and increasing muscle/liver glucose uptake

through increased AMPK activity.

By Sangeeta Rao Kashyap, MD, and Philip R. Schauer, MD


Caution should be exercised in these patients when con-

sidering sulphonylureas in the early postoperative period,

because they may precipitate hypoglycemia and trigger

dumping syndromes. In patients who experience suboptimal

glycemic control several years after gastric restrictive surgery,

the addition of a sulphonylurea to metformin could enhance

insulin secretion and restore glycemic control by targeting

ß-cell failure. Patients who do not respond to this therapy

should be prescribed basal insulin; if glycemic control is not

adequate, then prandial insulin should be added.

Revisional bariatric surgery is indicated primarily for patients

with anatomical/mechanical issues or severe nutritional

deficiencies and patients whose comorbid conditions worsen

following LAGB or sleeve gastrectomy.

Intestinal bypass procedures

At our institution, we observed 12 months following RYGB

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

when they had significant weight loss.

In patients who have undergone gastric bypass surgery, the

re-emergence of hyperglycemia without weight regain is

likely related to ß-cell exhaustion. Pharmacologic interven-

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

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

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

bromocriptine in conjunction with lifestyle counseling.

Data regarding the use of alternative diabetes therapies

including incretin analogues (i.e., DPP4 inhibitors and

GLP-agonists) in bariatric patients is lacking. Studies have

demonstrated that these agents enhance glucose-dependent

insulin secretion and offer advantages for weight loss in

obese type 2 diabetes patients. Because incretin stimulation

of insulin secretion following gastric bypass helps improve

glucose levels, the role of GLP-1 analogues in post-bariatric

surgery patients must be further defined.

The pathophysiology underlying diabetes relapse following

various bariatric surgery procedures is complex. Enhancing

our understanding in this area will inform further research

and treatment options.

Continued monitoring of long-term diabetes complications

is essential following bariatric surgery, regardless of initial

remission status.

About the authors

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.

For more information, please contact Dr. Kashyap at

216.445.2679 or [email protected]. Dr. Schauer can be


Suggested reading

Kashyap SR, Schauer P. Clinical considerations for the

management of residual diabetes following bariatric surgery.

Diabetes, Obes Metab. 2012;14:773-779.

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.

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.

Nannipieri M, Mari A, Anselmino M, et al. The role of beta-

cell 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 as-

sociated with durable remission of diabetes after Roux-en-Y gastric

bypass. Surg Obes Relat Dis. 2010;6:254-259.

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.


Studies have demonstrated that the benefits of bariatric surgery

extend beyond durable weight loss and include significant im-

provements 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 preop-

erative 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.

Benefits of Bariatric Surgery in Type 2 Diabetes Extend to Improvement, Prevention of Nephropathy By Philip R. Schauer, MD


The presence of diabetic nephropathy, pre- and postop-

eratively, was determined by urinary albumin-creatinine

ratio (uACR). Patients’ current diabetes status (remission,

improvement or no change) was determined by biochemical

analyses and review of medications.

We presented our findings at the 29th Annual Meeting of

the American Society of Metabolic and Bariatric Surgery in

June 2012. The findings follow a study that I published with

colleagues earlier in 2012 in the New England Journal of

Medicine that showed bariatric surgery can cause remis-

sion of type 2 diabetes even before substantial weight loss

occurs.

Sustainable clinical benefits

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.

When my colleagues and I initiated this study, we hypoth-

esized that bariatric surgery may halt the progression of

diabetic nephropathy. Instead we found that over half of the

patients who had diabetic nephropathy prior to undergoing

bariatric surgery experienced remission.

No medical therapy has been as effective as bariatric sur-

gery in achieving an effect of this magnitude on diabetic

nephropathy. This is an important finding that warrants

further research and greater consideration of bariatric

surgery in this patient population.

About the author

Dr. Schauer, Professor of Surgery and Director of

Cleveland Clinic’s Bariatric & Metabolic Institute, can be


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.

“No medical therapy has been

as effective as bariatric surgery in

achieving an effect of this magni-

tude on diabetic nephropathy.”


Gastric Bypass Improves Glucose Homeostasis by Attenuating the Effect of Ghrelin on ß-cell Function

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.

Despite the known effects of surgery-induced diabetes

remission, the mechanism responsible for this improved

glycemic control remains unclear. Ghrelin is a fundus-derived

hormone that has glucoregulatory effects on ß-cell function

and insulin sensitivity.

In addition, ghrelin is an appetite-stimulating hormone that

plays a key role in body weight regulation. For example,

obese, insulin-resistant adults with type 2 diabetes mel-

litus have decreased abilities to suppress ghrelin following

food intake. This impaired response subsequently leads to

overeating and the development of poor insulin secretion.

Improving ghrelin suppression therefore represents an impor-

tant endocrine-related mechanism for diabetes remission.

In our recent substudy, 53 moderately obese adults with

poorly controlled diabetes were randomized to intensive

medical therapy alone vs. gastric bypass and sleeve gas-

trectomy. At baseline and 24 months, we measured ß-cell

function, insulin sensitivity (determined by mixed-meal toler-

ance testing), body fat and postprandial ghrelin levels.

Gastric bypass and sleeve gastrectomy decreased body fat

by approximately 12 percent at 24 months, while intensive

medical therapy had little effect (Table 1). Although fast-

ing glycemia improved in all three groups at 24 months

(P<0.05), insulin sensitivity and ß-cell function increased

most following gastric bypass compared with sleeve gastrec-

tomy or intensive medical therapy.

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.

By Sangeeta Rao Kashyap, MD; Steven K. Malin, PhD; and Aashish Samat, MD

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.


After 24 months, only gastric bypass improved ghrelin suppres-

sion (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 stud-

ies 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


Although follow-up studies

are required to understand

how ghrelin affects insulin

secretion, our data suggest a

role for ghrelin as a regulator

of glucose metabolism after

gastric bypass surgery.IMT, intensive medical therapy; SG, sleeve gastrectomy;

RYGB, Roux-en-Y gastric bypass

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

Ghr

elin

Sup

pres

sion

(pg

/mL)

*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)

* *̂Baseline24 months

Table 1


Journals

Below are peer-reviewed journal articles and

book chapters published within the past year by

Endocrinology & Metabolism Institute staff.

Academic Medicine

Young JB, Cosgrove DM. Change we must: Putting patients first

with the institute model of academic health center organization

[Commentary]. Acad Med. 2012;87(5):552-554.

American Journal of Cardiology

Heneghan HM, Meron-Eldar S, Brethauer SA, Schauer PR,

Young JB. Effect of bariatric surgery on cardiovascular risk pro-

file. Am J Cardiol. 2011;108(10):1499-1507.

American Journal of Otolaryngology

Makin V, Hatipoglu B, Hamrahian AH, Arrossi AV, Knott PD,

Lee JH, Sade B. Spontaneous cerebrospinal fluid rhinorrhea as

the initial presentation of growth hormone-secreting pituitary

adenoma. Am J Otolaryngol. 2011;32(5):433-437.

American Journal of Physiology – Endocrinology and

Metabolism

Haus JM, Solomon TPJ, Lu L, Jesberger JA, Barkoukis H, Flask

CA, Kirwan JP. Intramyocellular lipid content and insulin sen-

sitivity are increased following a short-term low-glycemic index

diet and exercise intervention. Am J Physiol Endocrinol Metab.

2011;301(3):E511-E516.

Annals of Surgical Oncology

Bohacek L, Milas M, Mitchell J, Siperstein A, Berber E.

Diagnostic accuracy of surgeon-performed ultrasound-guided

fine-needle aspiration of thyroid nodules. Ann Surg Oncol.

2012;19(1):45-51.

Sahin DA, Agcaoglu O, Chretien C, Siperstein A, Berber E. The

utility of PET/CT in the management of patients with colorectal

liver metastases undergoing laparoscopic radiofrequency thermal

ablation. Ann Surg Oncol. 2012;19(3):850-855.

Archives of Surgery

Agcaoglu O, Aliyev S, Karabulut K, Siperstein A, Berber E.

Robotic vs laparoscopic posterior retroperitoneal adrenalectomy.

Arch Surg. 2012;147(3):272-275.

Shin JJ, Milas M, Mitchell J, Berber E, Ross L, Siperstein A.

Impact of localization studies and clinical scenario in patients

with hyperparathyroidism being evaluated for reoperative neck

surgery. Arch Surg. 2011;146(12):1397-1403.

Bariatric Nursing and Surgical Patient Care

Calogeras E, Zeller M, Hoover C, Cooper K, Tuininga P, Ashton

K. Sleeve gastrectomy patients may be at increased risk post-

operatively for decline in vitamin B12 values — do they need

monitoring? Bariatr Nurs Surg Patient Care. 2012;7(1):21-24.

Best Practice & Research Clinical Endocrinology & Metabolism

Jin J, McHenry CR. Thyroid incidentaloma. Best Pract Res Clin

Endocrinol Metab. 2012;26(1):83-96.

Orija IB, Weil RJ, Hamrahian AH. Pituitary incidentaloma. Best

Pract Res Clin Endocrinol Metab. 2012;26(1):47-68.

Body Image

Coughlin JW, Schreyer CC, Sarwer DB, Heinberg LJ, Redgrave

GW, Guarda AS. Cosmetic surgery in inpatients with eating disor-

ders: Attitudes and experience. Body Image. 2012;9(1):180-183.

Canadian Journal of Anaesthesia

Abdelmalak B, Zimmerman R, Foss J. Diagnosing preoperative

hyperglycemia in non-diabetic patients: a challenge and an

opportunity [Reply]. Can J Anaesth. 2011;58(6):583.

Circulation: Heart Failure

Hsich EM, Naftel DC, Myers SL, Gorodeski EZ, Grady KL,

Schmuhl D, Ulisney KL, Young JB. Should women receive left

ventricular assist device support? Findings from INTERMACS.

Circ Heart Fail. 2012;5(2):234-240.

Publications


Cleveland Clinic Journal of Medicine

Albashir S, Olansky L, Sasidhar M. Progressive muscle

weakness: More there than meets the eye. Cleve Clin J Med.

2011;78(6):385-391.

Lansang MC, Hustak LK. Glucocorticoid-induced diabetes

and adrenal suppression: How to detect and manage them.

Cleve Clin J Med. 2011;78(11):748-756.

Lansang MC, Hustak LK. Glucocorticoid-induced

diabetes and adrenal suppression [Reply]. Cleve Clin J Med.

2012;79(4):237,242.

Newey CR, Sarwal A, Uchin J, Mulligan G. Necrotic skin lesions

after hemodialysis. Cleve Clin J Med. 2011;78(10):646-648.

Clinical Journal of the American Society of Nephrology

Thomas G, Sehgal AR, Kashyap SR, Srinivas TR, Kirwan JP,

Navaneethan SD. Metabolic syndrome and kidney disease: A

systematic review and meta-analysis. Clin J Am Soc Nephrol.

2011;6(10):2364-2373.

Diabetes Care

Pantalone KM, Kattan MW, Wells BJ, Zimmerman RS. The risk

of overall mortality in patients with type 2 diabetes receiving

glipizide, glyburide, or glimepiride monotherapy: A retrospective

analysis [Response to Comment on: Pantalone et al. Diabetes

Care. 2010;33:1224-1229]. Diabetes Care. 2011;34(8):E139.

Diabetes, Obesity and Metabolism

Olansky L, Reasner C, Seck TL, Williams-Herman DE, Chen M,

Terranella L, Mehta A, Kaufman KD, Goldstein BJ. A treatment

strategy implementing combination therapy with sitagliptin and

metformin results in superior glycaemic control versus metformin

monotherapy due to a low rate of addition of antihyperglycaemic

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

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.

Endocrine Practice

Alguraan Z, Agcaoglu O, El-Hayek K, Hamrahian AH, Siperstein

A, Berber E. Retroperitoneal masses mimicking adrenal tumors.

Endocr Pract. 2012;18(3):335-341.

Cheng V, Doshi KB, Falcone T, Faiman C. Hyperandrogenism

in a postmenopausal woman: diagnostic and therapeutic

challenges. Endocr Pract. 2011;17(2):E21-E25.

Harvey A, Hu M, Gupta M, Butler R, Mitchell J, Berber E,

Siperstein A, Milas M. A new, vitamin D-based, multidimension-

al nomogram for the diagnosis of primary hyperparathyroidism.

Endocr Pract. 2012;18(2):124-131.

Katznelson L, Atkinson JLD, Cook DM, Ezzat SZ, Hamrahian

AH, Miller KK. American Association of Clinical Endocrinologists

Medical Guidelines for Clinical Practice for the Diagnosis and

Treatment of Acromegaly — 2011 update: executive summary.

Endocr Pract. 2011;17(4):636-646.

Pantalone KM, Faiman C, Olansky L. Insulin glargine use during

pregnancy. Endocr Pract. 2011;17(3):448-455.

Pantalone KM, Faiman C, Olansky L. Use of insulin detemir

and insulin glargine during pregnancy: Are the data convincing?

Endocr Pract. 2011;17(5):830.

Expert Opinion on Pharmacotherapy

Subbarayan S, Kipnes M. Sitagliptin: a review. Expert Opin

Pharmacother. 2011;12(10):1613-1622.

Expert Review of Endocrinology and Metabolism

Kashyap SR, Louis ES, Kirwan JP. Weight loss as a cure for

type 2 diabetes? Fact or fantasy. Expert Rev Endocrinol Metab.

2011;6(4):557-561.

Heart Failure Clinics

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 vulner-

able myocardium in patients receiving chemotherapy: is it time

to change tracks? Heart Fail Clin. 2011;7(3):xiii-xxix.

continued on next page


Baliga RR, Young JB. Reducing the burden of stage B heart

failure and the global pandemic of cardiovascular disease:

time to go to war with the “barefoot” troops! Heart Fail Clin.

2012;8(2):ix-xiii.

Baliga RR, Young JB. Reducing the burden of stage B heart

failure will require connecting the dots between “knowns” and

“known unknowns.” Heart Fail Clin. 2012;8(1):xi-xv.

Hepatology

Zein CO, Yerian LM, Gogate P, Lopez R, Kirwan JP, Feldstein AE,

McCullough AJ. Pentoxifylline improves nonalcoholic steato-

hepatitis: A randomized placebo-controlled trial. Hepatology.

2011;54(5):1610-1619.

International Journal of Cancer

Nock NL, Patrick-Melin A, Cook M, Thompson C, Kirwan JP, Li

L. Higher bone mineral density is associated with a decreased

risk of colorectal adenomas. Int J Cancer. 2011;129(4):956-964.

International Journal of Obesity (London)

Eldar S, Heneghan HM, Brethauer SA, Schauer PR. Bariatric

surgery for treatment of obesity. Int J Obes (Lond).

2011;35(Suppl 3):S16-S21.

Issues in Science and Technology

Young JB. A better process for new medical devices.

Issues Sci Technol. 2011;27(4):10-12.

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.

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.

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

Transplant. 2012;31(2):117-126.

Journal of Medical Economics

Lamy A, Wang X, Gao P, Tong W, Gafni A, Dans A, Avezum A,

Ferreira R, Young J, Yusuf S, Teo K. The cost implications of the

use of telmisartan or ramipril in patients at high risk for vascular

events: the ONTARGET study. J Med Econ. 2011;14(6):792-797.

Journal of Nutrition and Metabolism

Sun G, Kashyap SR. Cancer risk in type 2 diabetes mellitus:

metabolic links and therapeutic considerations. J Nutr Metab.

2011;2011:708183.

Journal of Obesity

Cheng V, Kashyap SR. Weight considerations in pharmacothera-

py for type 2 diabetes. J Obes. 2011;2011:984245.

Medical Clinics of North America

Smith BR, Schauer P, Nguyen NT. Surgical approaches to the

treatment of obesity: bariatric surgery. Med Clin North Am.

2011;95(5):1009-1030.

Medicine and Science in Sports and Exercise

Kelly KR, Blaszczak A, Haus JM, Patrick-Melin A, Fealy CE,

Solomon TPJ, Kalinski MI, Kirwan JP. A 7-d exercise program

increases high-molecular weight adiponectin in obese adults.

Med Sci Sports Exerc. 2012;44(1):69-74.

Metabolic Syndrome and Related Disorders

Kennedy DJ, Kashyap SR. Pathogenic role of scavenger receptor

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

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,

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.

continuedPublications


The New England Journal of Medicine

Schauer PR, Kashyap SR, Wolski K, Brethauer SA, Kirwan JP,

Pothier CE, Thomas S, Abood B, Nissen SE, Bhatt DL. Bariatric

surgery versus intensive medical therapy in obese patients with

diabetes. N Engl J Med. 2012;366(17):1567-1576.

Obesity (Silver Spring)

Huang H, Kasumov T, Gatmaitan P, Heneghan HM, Kashyap SR,

Schauer PR, Brethauer SA, Kirwan JP. Gastric bypass surgery

reduces plasma ceramide subspecies and improves insulin

sensitivity in severely obese patients. Obesity (Silver Spring).

2011;19(11):2235-2240.

Obesity Surgery

Appachi S, Kelly KR, Schauer PR, Kirwan JP, Hazen S, Gupta

M, Kashyap SR. Reduced cardiovascular risk following bariatric

surgeries is related to a partial recovery from “adiposopathy.”

Obes Surg. 2011;21(12):1928-1936.

Wu J, You J, Yerian L, Shiba A, Schauer PR, Sessler DI.

Prevalence of liver steatosis and fibrosis and the diagnostic

accuracy of ultrasound in bariatric surgery patients. Obes Surg.

2012;22(2):240-247.

Pediatric Emergency Care

Horwitz SM, Heinberg LJ, Storfer-Isser A, Barnes DH, Smith M,

Kapur R, Findling R, Currier G, Wilcox HC, Wilkens K. Teaching

physicians to assess suicidal youth presenting to the emergency

department. Pediatr Emerg Care. 2011;27(7):601-605.

Pituitary

Cheng V, Faiman C, Kennedy L, Khoury F, Hatipoglu B, Weil

R, Hamrahian A. Pregnancy and acromegaly: a review. Pituitary.

2012;15(1):59-63.

Daud S, Hamrahian AH, Weil RJ, Hamaty M, Prayson RA,

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.

Grover V, Hamrahian AH, Prayson RA, Weil RJ. Rathke’s cleft

cyst presenting as bilateral abducens nerve palsy. Pituitary.

2011;14(4):395-399.

Psychiatric Annals

Maudlin S, Hatipoglu B. Is there a lack of communication

between endocrinologists and psychiatrists regarding metabolic

screening of second-generation antipsychotic users? Psychiatr

Ann. 2011;41(7):350.

Rheumatology (Oxford)

Knafo R, Haythornthwaite JA, Heinberg L, Wigley FM, Thombs

BD. The association of body image dissatisfaction and pain

with reduced sexual function in women with systemic sclerosis.

Rheumatology (Oxford). 2011;50(6):1125-1130.

Surgeon

Eldar S, Heneghan HM, Brethauer S, Schauer PR. A focus on

surgical preoperative evaluation of the bariatric patient — The

Cleveland Clinic protocol and review of the literature. Surgeon.

2011;9(5):273-277.

Surgery

Agcaoglu O, Sahin DA, Siperstein A, Berber E. Selection

algorithm for posterior versus lateral approach in laparoscopic

adrenalectomy. Surgery. 2012;151(5):731-735.

Karabulut K, Akyildiz HY, Lance C, Aucejo F, McLennan G,

Agcaoglu O, Siperstein A, Berber E. Multimodality treatment of

neuroendocrine liver metastases. Surgery. 2011;150(2):316-325.

Karabulut K, Agcaoglu O, Aliyev S, Siperstein A, Berber E.

Comparison of intraoperative time use and perioperative out-

comes for robotic versus laparoscopic adrenalectomy. Surgery.

2012;151(4):537-542.

Wallace LB, Parikh RT, Ross LV, Mazzaglia PJ, Foley C, Shin

JJ, Mitchell JC, Berber E, Siperstein AE, Milas M. The pheno-

type of primary hyperparathyroidism with normal parathyroid

hormone levels: How low can parathyroid hormone go? Surgery.

2011;150(6):1102-1112.

Surgery for Obesity and Related Diseases

Brethauer S. American Society for Metabolic and Bariatric

Surgery position statement on global bariatric healthcare.

Surg Obes Relat Dis. 2011;7(6):669-671.

Brethauer S. ASMBS position statement on preoperative

supervised weight loss requirements. Surg Obes Relat Dis.

2011;7(3):257-260.

continued on next page


continuedPublications Brethauer SA, Chand B, Schauer PR, Thompson CC. Transoral

gastric volume reduction as intervention for weight manage-

ment: 12-month follow-up of TRIM trial. Surg Obes Relat Dis.

2012;8(3):296-303.

Heinberg LJ, Ashton K, Coughlin J. Alcohol and bariatric

surgery: review and suggested recommendations for assessment

and management. Surg Obes Relat Dis. 2012;8(3):357-363.

Heneghan HM, Heinberg L, Windover A, Rogula T, Schauer PR.

Weighing the evidence for an association between obesity and

suicide risk. Surg Obes Relat Dis. 2012;8(1):98-107.

Schauer PR, Rubino F. International Diabetes Federation

position statement on bariatric surgery for type 2 diabetes: impli-

cations for patients, physicians, and surgeons. Surg Obes Relat

Dis. 2011;7(4):448-451.

Yimcharoen P, Heneghan HM, Tariq N, Brethauer SA, Kroh M,

Chand B. Endoscopic stent management of leaks and anas-

tomotic strictures after foregut surgery. Surg Obes Relat Dis.

2011;7(5):628-636.

Yimcharoen P, Heneghan H, Chand B, Talarico JA, Tariq N, Kroh

M, Brethauer SA. Successful management of gastrojejunal stric-

tures after gastric bypass: is timing important? Surg Obes Relat

Dis. 2012;8(2):151-157.

Surgical Clinics of North America

Brethauer SA. Sleeve gastrectomy. Surg Clin North Am.

2011;91(6):1265-1279.

Surgical Endoscopy

Brethauer SA, Heneghan HM, Eldar S, Gatmaitan P, Huang H,

Kashyap S, Gornik HL, Kirwan JP, Schauer PR. Early effects

of gastric bypass on endothelial function, inflammation, and

cardiovascular risk in obese patients [Erratum in: Surg Endosc.

2011;25(8):2660]. Surg Endosc. 2011;25(8):2650-2659.

Gould J, Ellsmere J, Fanelli R, Hutter M, Jones S, Pratt J,

Schauer P, Schirmer B, Schwaitzberg S, Jones DB. Panel report:

best practices for the surgical treatment of obesity. Surg Endosc.

2011;25(6):1730-1740.

Kroh M, El-Hayek K, Rosenblatt S, Chand B, Escobar P, Kaouk

J, Chalikonda S. First human surgery with a novel single-port

robotic system: cholecystectomy using the da Vinci Single-Site

platform. Surg Endosc. 2011;25(11):3566-3573.

Yimcharoen P, Heneghan HM, Singh M, Brethauer S, Schauer P,

Rogula T, Kroh M, Chand B. Endoscopic findings and outcomes

of revisional procedures for patients with weight recidivism after

gastric bypass. Surg Endosc. 2011;25(10):3345-3352.

Surgical Laparoscopy Endoscopy & Percutaneous Techniques

Berber E, Siperstein A. Robotic transaxillary total thyroidectomy

using a unilateral approach. Surg Laparosc Endosc Percutan

Tech. 2011;21(3):207-210.

Wallace LB, Berber E. Percutaneous and video-assisted ablation

of endocrine tumors: liver, adrenal, and thyroid. Surg Laparosc

Endosc Percutan Tech. 2011;21(4):255-259.

Thyroid

Cheng V, Brainard J, Nasr C. Co-occurrence of papillary

thyroid carcinoma and primary lymphoma of the thyroid in

a patient with long-standing Hashimoto’s thyroiditis. Thyroid.

2012;22(6):647-650.

McQuade C, Skugor M, Brennan DM, Hoar B, Stevenson

C, Hoogwerf BJ. Hypothyroidism and moderate subclinical

hypothyroidism are associated with increased all-cause mortality

independent of coronary heart disease risk factors: A PreCIS

database study. Thyroid. 2011;21(8):837-843.

Book ChaptersAshton K, Budur K. Scared to sleep: A Hurricane Katrina survi-

vor. In: Foldvary-Schaefer N, Krishna J, Budur K, eds. A Case a

Week: Sleep Disorders from the Cleveland Clinic. Oxford; New

York, NY: Oxford University Press; 2011. Chapter 3. p. 43-48.

Ashton K, Streem D. Smoking cessation. In: Carey WD, ed.

Current Clinical Medicine. 2nd ed. Philadelphia, PA: Saunders/

Elsevier; 2010. p. 977-980.

Babar T, Skugor M. Diabetes mellitus treatment. In: Carey

WD, ed. Current Clinical Medicine. 2nd ed. Philadelphia, PA:

Saunders/Elsevier; 2010. p. 358-363.


Brethauer S, Kashyap S, Schauer P. Obesity. In: Carey WD, ed.


Elsevier; 2010. p. 391-396.

Chikunguwo SM, Brethauer SA, Schauer PR. Bariatric surgery.

In: Cameron JL, Cameron AM, eds. Surgery of the Esophagus

and Stomach. London; New York, NY: Springer; 2011. Chapter

16. p. 217-232.

Chinnappa P, Mehta A. Hirsutism. In: Carey WD, ed. Current

Clinical Medicine. 2nd ed. Philadelphia, PA: Saunders/Elsevier;

2010. p. 376-379.

Diab DL, Hamrahian AH. Clinical detection and treatment of be-

nign and malignant pituitary diseases. In: Hunt JL, ed. Molecular

Pathology of Endocrine Diseases. New York, NY: Springer; 2010.

Chapter 17. p. 169-174.

Gatmaitan P, Brethauer SA, Schauer PR. Obesity and presenta-

tions after anti-obesity surgery. In: Talley NJ, Kane SV, Wallace

MB, eds. Practical Gastroenterology and Hepatology. Small

and Large Intestine and Pancreas. Chichester, West Sussex ;

Hoboken, NJ: Wiley-Blackwell; 2010. Chapter 24. p. 169-175.

Gopan T, Hamrahian A. Adrenal disorders. In: Camacho PM,

ed. Clinical Endocrinology and Metabolism (A Color Handbook).

London: Manson Publishing; 2011. Chapter 5. p. 113-147.

Harvey AM, Siperstein AE, Berber E. Clinical detection and

treatment of adrenal disease. In: Hunt JL, ed. Molecular

Pathology of Endocrine Diseases. New York, NY: Springer; 2010.

Chapter 19. p. 197-203.

Ioachimescu AG, Hamrahian AH. Diseases of the adrenal

gland. In: Carey WD, ed. Current Clinical Medicine. 2nd ed.

Philadelphia, PA: Saunders/Elsevier; 2010. p. 336-349.

Mitchell JC. Clinical detection and treatment of pancreatic

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.

Moustarah F, Brethauer SA, Schauer PR. Laparoscopic surgery

for severe obesity. In: Cameron JL, Cameron AM, eds. Current

Surgical Therapy. 10th ed. Philadelphia, PA: Saunders/Elsevier;

2011. p. 1304-1316.

Nasr C. Flushing. In: Carey WD, ed. Current Clinical Medicine.

2nd ed. Philadelphia, PA: Saunders/Elsevier; 2010. p. 369-375.

Reddy SSK. Hypothalamic-pituitary disorders. In: Camacho PM,

ed. Clinical Endocrinology and Metabolism (A Color Handbook).

London: Manson Publishing; 2011. Chapter 4. p. 91-112.

Schirmer B, Schauer PR. The surgical management of obesity.

In: Brunicardi FC, ed. Schwartz’s Principles of Surgery. 9th ed.

New York, NY: McGraw-Hill; 2010. Chapter 27. p. 949-978.

Skugor M. Section 4: Endocrinology [Section editor]. In: Carey

WD, ed. Current Clinical Medicine. 2nd ed. Philadelphia, PA:

Saunders/Elsevier; 2010. p. 335-420.

Skugor M. Hypocalcemia and hypercalcemia. In: Carey WD, ed.


Elsevier; 2010. p. 380-386.

Skugor M. Osteoporosis. In: Carey WD, ed. Current Clinical

Medicine. 2nd ed. Philadelphia, PA: Saunders/Elsevier; 2010.

p. 402-407.

Skugor M, Fleseriu M. Hypothyroidism and hyperthyroidism. In:

Carey WD, ed. Current Clinical Medicine. 2nd ed. Philadelphia,

PA: Saunders/Elsevier; 2010. p. 416-420.

Skugor M, Hamrahian AH. Pituitary disorders. In: Carey WD, ed.


Elsevier; 2010. p. 408-415.

Zimmerman R. Microvascular complications of diabetes. In:

Carey WD, ed. Current Clinical Medicine. 2nd ed. Philadelphia,

PA: Saunders/Elsevier; 2010. p. 355-357.


Thyroid Expo 2013Jan. 26, 2013

Lerner College of Medicine | NA5-08 Auditorium and Conference WingThis 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 2013May 31, 2013

Intercontinental Hotel and Bank of America Conference Center, ClevelandGet 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

Live and Online CME OpportunitiesCleveland 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.

Online CMEOnline webcasts and journal articles of interest to endocrinologists and approved for AMA PRA Category 1 Credits™ include:

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.

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

800.223.2273, ext. 46568 | 27 | clevelandclinic.org/endonotes 800.223.2273, ext. 46568 | 27 | clevelandclinic.org/endonotes

TITLE PI CONTACT/NUMBER

ACROSTUDY – A Multicenter, Post-Marketing Surveillance Study of Somavert® Therapy in Patients with Acromegaly in the USA and Europe

Amir Hamrahian, MDAndreea Mocanu216.444.9612

Somatuline® Depot (Lanreotide) Injection for Acromegaly (SODA): A Post-Marketing Observational Study Betul Hatipoglu, MDAndreea Mocanu216.444.9612

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, MDBob McCoy216.445.4029

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 Mocanu216.444.9612

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, MDBob McCoy216.445.4029

EXenatide Study of Cardiovascular Event Lowering Trial (EXSCEL) Robert Zimmerman, MDBob McCoy216.445.4029

The Diagnostic Accuracy of the Glucagon Stimulation Test for Evaluation of Adult Growth Hormone Deficiency and the Hypothalamic-Pituitary-Adrenal Axis

Amir Hamrahian, MDBob McCoy216.445.4029

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, MDAndreea Mocanu216.444.9612

Effect of a Portion-Controlled, Commercially Available Diet on Presurgical Weight Loss and Metabolic Outcomes in Patients Undergoing Laparoscopic Bariatric Surgery

Leslie Heinberg, PhD, MAChytaine Hall216.445.3983

Effect of Bariatric Surgery on Mechanisms of Type 2 Diabetes: The B2D Trial John Kirwan, PhDChytaine Hall216.445.3983

Gastric Plication for the Treatment of Obesity and Related Conditions Philip Schauer, MDJanice Kakish216.444.7551

Parathyroidectomy – Effect of Parathyroidectomy in Reducing Coronary Artery Calcification and Improving Vascular Compliance in Patients with Primary and Secondary Hyperparathyroidism

Eren Berber, MDLinda Heil216.444.2262

Randomized, Double-Blind, Phase II Trial of Radiofrequency Ablation +/- Lyso-Thermosensitive Liposomal Doxorubicin (ThermoDox®) for Colorectal Liver Metastases ≥2 cm Maximum Diameter

Allan Siperstein, MDLinda Heil 216.444.2262

Prospective Randomized Comparison of Bilateral vs. Focal Neck Exploration for Sporadic Hyperparathyroidism

Allan Siperstein, MDLinda Heil 216.444.2262

Current Clinical Trials

Department of Endocrinology, Diabetes and Metabolism

Revital Gorodeski Baskin, MDSpecialty Interest(s): Endocrinology, thyroid disorders, thyroid cancerLocation(s): Independence Family Health CenterOffice: 216.986.4000 | Fax: 216.986.4995Appointments: 216.986.4000

Kevin Borst, DOSpecialty Interest(s): Endocrine disorders in pregnancy, general endocrinology, diabetesLocation(s): Lakewood Hospital Professional BuildingOffice: 216.529.5300 | Fax: 216.529.5301Appointments: 216.444.6568

Krupa Doshi, MDSpecialty Interest(s): General endocrinology, diabetes, parathyroid and calcium disorders, hirsutism, thyroid disorders, adrenal disordersLocation(s): Main campusOffice: 216.445.0741 | Fax: 216.445.1656Appointments: 216.444.6568

Marwan Hamaty, MDSpecialty Interest(s): General endocrinology, diabetesLocation(s): Main campus; Strongsville Family Health and Surgery CenterOffice: 216.445.7568 | Fax: 216.445.1656Appointments: Main campus, 216.444.6568; Strongsville, 440.878.2500

Amir Hamrahian, MDSpecialty Interest(s): Pituitary and adrenal disordersLocation(s): Main campusOffice: 216.445.8538 | Fax: 216.445.1656Appointments: 216.444.6568

James Young, MDInstitute Chairman Endocrinology & Metabolism Institute216.444.2333

Laurence (Ned) Kennedy, MDChairman, Department of Endocrinology, Diabetes and Metabolism 216.445.8645

Allan Siperstein, MDChairman, Department of Endocrine Surgery216.444.5664

Philip Schauer, MDChairman, Bariatric & Metabolic Institute 216.444.4794

Betul Hatipoglu, MDSpecialty Interest(s): Diabetes, thyroid disorders, pituitary disorders, adrenal disorders, alternative medicineLocation(s): Main campusOffice: 216.445.6709 | Fax: 216.445.1656Appointments: 216.444.6568

Suman Jana, MDSpecialty Interest(s): General endocrinology, diabetes, thyroid disease, thyroid cancerLocation(s): Main campus; Medina Office: 216.444.0567 | Fax: 216.445.1656Appointments: Main campus, 216.444.6568; Medina, 330.725.3713

Sangeeta Kashyap, MDSpecialty Interest(s): Endocrinology, diabetes, insulin resistance and cardiovascular risk prevention, obesity, metabolic syndrome and diseases, hyperlipidemiaLocation(s): Main campusOffice: 216.445.2679 | Fax: 216.445.1656Appointments: 216.444.6568

Laurence (Ned) Kennedy, MDDepartment ChairSpecialty Interest(s): General endocrinology, diabetes, pituitary disorders, hyperthyroidism, hypothyroidism, thyroiditisLocation(s): Main campus; Ashtabula County Medical Center; Cleveland Clinic Florida, WestonOffice: 216.445.8645 | Fax: 216.445.1656Appointments: Main campus, 216.444.6568; Ashtabula, 440.997.6910; Florida, 954.659.6038

Leila Khan, MDSpecialty Interest(s): General endocrinology, diabetes, calcium/bone disordersLocation(s): Main campus; Willoughby Hills Family Health CenterOffice: 216.445.1598 | Fax: 216.445.1656Appointments: Main campus, 216.444.6568; Willoughby Hills, 440.943.2500

Endocrinology & Metabolism Institute

Staff Directory

Visit clevelandclinic.org/EndoStaff for the most current staff listings and locations.

E N D O C R I N O L O G Y & M E T A B O L I S M I N S T I T U T E L E A D E R S H I P

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M. Cecilia Lansang, MD, MPHSpecialty Interest(s): General endocrinology, diabetesLocation(s): Main campusOffice: 216.445.5246 | Fax: 216.445.1656Appointments: 216.444.6568

Melissa Li-Ng, MDSpecialty Interest(s): General endocrinology, diabetesLocation(s): Main campusOffice: 216.444.1949 | Fax: 216.445.1656Appointments: 216.444.6568

Vinni Makin, MDSpecialty Interest(s): General endocrinology, diabetes, hirsutism, acne, thyroid disordersLocation(s): Main campus; Solon Family Health CenterOffice: 216.444.0539 | Fax: 216.445.1656 Appointments: Main campus, 216.444.6568; Solon, 440.519.6800

Adi Mehta, MDSpecialty Interest(s): Diabetes, thyroid disorders, endocrine complications of pregnancy, menopause, lipid disorders, general and adolescent endocrinologyLocation(s): Main campus; Beachwood Family Health Center (reproductive endocrinology only)Office: 216.445.5312 | Fax: 216.445.7261Appointments: Main campus, 216.444.6568; Beachwood, 216.839.3000

Guy Mulligan, MDSpecialty Interest(s): General endocrinology, diabetesLocation(s): Main campus; Independence Family Health Center; Twinsburg Family Health and Surgery CenterOffice: 330.888.4000 | Fax: 330.963.4561Appointments: Independence, 216.986.4000; Main campus, 216.444.6568; Twinsburg, 330.888.4000

Christian Nasr, MDSpecialty Interest(s): Thyroid nodules, thyroid cancers, flushing syndromesLocation(s): Main campus; Lorain Family Health and Surgery Center (thyroid cancer only)Office: 216.445.1788 | Fax: 216.445.1656Appointments: Main campus, 216.444.6568; Lorain, 440.204.7400

Leann Olansky, MDSpecialty Interest(s): Diabetes and diabetes complications, gestational diabetes, general endocrinologyLocation(s): Main campus; Stephanie Tubbs Jones Health CenterOffice: 216.444.2642 | Fax: 216.445.1656Appointments: 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 disordersLocation(s): Main campus; Twinsburg Family Health and Surgery CenterOffice: 330.888.4000 | Fax: 216.445.1656Appointments: Main campus, 216.444.6568; Twinsburg, 330.888.4000

Endocrinology & Metabolism Institute | Staff directory

Seenia Peechakara, MDSpecialty Interest(s): Endocrine disorders in pregnancy, thyroid disorders, thyroid cancer, diabetes, calcium and parathyroid disorders, lipid disorders, pituitary and adrenal disorders, general endocrinologyLocation(s): Lakewood Hospital Professional BuildingOffice: 216.529.5300 | Fax: 216.529.5301Appointments: 216.444.6568

Richard Shewbridge, MDSpecialty Interest(s): Endocrinology, diabetes, thyroid disorders, hyperlipidemia, osteoporosisLocation(s): Medina Medical Office BuildingOffice: 330.725.3713 | Fax: 330.725.2141Appointments: 330.725.3713

David Shewmon, MDSpecialty Interest(s): General endocrinology, diabetes, high cholesterol, osteomalacia, osteoporosis, pituitary tumors, thyroid conditions, thyroid cancerLocation(s): Lakewood Hospital Professional BuildingOffice: 216.529.5300 | Fax: 216.529.5301Appointments: 216.444.6568

Mario Skugor, MDAssociate Director, Endocrinology Fellowship ProgramSpecialty Interest(s): Osteoporosis and calcium metabolism, obesity and diabetes, multiple endocrine neoplasia syndromes, thyroid disorders, thyroid cancerLocation(s): Main campusOffice: 216.445.0739 | Fax: 216.445.1656Appointments: 216.444.6568

Mariam Stevens, MDSpecialty Interest(s): Diabetes, gestational diabetes, goiter, Graves disease, Hashimoto disease, hirsutism, hyperthyroidism, hypoglycemia, hypothyroidism, polycystic ovary syndrome, thyroid disease, Location(s): Independence Family Health CenterOffice: 216.986.4000 | Fax: 216.986.4995Appointments: 216.986.4000

Mary Vouyiouklis, MD Specialty Interest(s): Thyroid disorders, thyroid cancer, parathyroid and calcium disorders, adrenal disorders, diabetesLocation(s): Main campus; Solon Family Health Center; Willoughby Hills Family Health Center Office: 216.444.6568 | Fax: 216.445.1656Appointments: Main campus, 216.444.6568; Solon, 440.519.6908; Willoughby Hills, 440.943.2500

Susan Williams, MDSpecialty Interest(s): Bone and mineral metabolism, metabolic bone disease, calcium disorders, malabsorption and malnutrition in adults, medical bariatricsLocation(s): Main campusOffice: 216.444.5665 | Fax: 216.445.1656Appointments: 216.444.6568

Robert Zimmerman, MDDirector, Cleveland Clinic Diabetes CenterDepartment Vice ChairProgram Director, Endocrinology Training ProgramSpecialty Interest(s): Diabetes, thyroid disorders, growth hormone in adultsLocation(s): Main campusOffice: 216.444.9428 | Fax: 216.445.1656Appointments: 216.444.6568

Department of Endocrine Surgery

Eren Berber, MDDirector, Robotic Endocrine SurgerySpecialty Interest(s): Endocrine surgery (thyroid andparathyroid), laparoscopic radiofrequencyablation of liver tumors, pancreatic neuroendocrinetumors, robotic thyroid and parathyroid surgery,laparoscopic and robotic adrenalectomy and liver surgeryLocation(s): Main campusOffice: 216.445.0555 | Fax: 216.636.0662Appointments: 216.444.6568

Judy Jin, MDSpecialty Interest(s): Endocrine surgery (thyroid and parathyroid), advanced laparoscopic surgery, laparoscopic adrenalectomy, laparoscopic radiofrequency ablation of liver tumorsLocation(s): Main campusOffice: 216.445.3411 | Fax: 216.636.0662Appointments: 216.444.6568

Rosemarie Metzger, MDSpecialty Interest(s): Endocrine surgery (thyroid, parathyroid and adrenal) Location(s): Main campusOffice: 216.445.3695 | Fax: 216.636.0662Appointments: 216.444.6568

Jamie Mitchell, MDSpecialty Interest(s): Endocrine surgery (thyroid, parathyroid and adrenal), laparoscopic solid organ surgery, advanced laparoscopic surgery, laparoscopic radiofrequency ablation of liver tumorsLocation(s): Main campus; Independence Family Health Center; Solon Family Health CenterOffice: 216.445.9713 | Fax: 216.636.0662Appointments: Main campus, 216.444.6568; Independence, 216.986.4000; Solon, 440.519.6800

Joyce J. Shin, MDSpecialty 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 tumorsLocation(s): Main campus; Willoughby Hills Family Health CenterOffice: 216.636.9365 | Fax: 216.636.0662Appointments: Main campus, 216.444.6568; Willoughby Hills, 440.943.2500

Allan Siperstein, MD Department ChairSpecialty Interest(s): Endocrine surgery (thyroid and parathyroid), advanced laparoscopic surgery, laparoscopic thermal ablation of liver tumors, pancreatic endocrine tumorsLocation(s): Main campusOffice: 216.444.5664 | Fax: 216.636.0662Appointments: 216.444.6568

Bariatric & Metabolic Institute

Stacy Brethauer, MDDepartment Vice ChairSpecialty Interest(s): Bariatric surgery, laparoscopic surgery, gastrointestinal surgery, hernia repair, endoscopy, surgery for GERD, hiatal hernia, solid-organ endoluminal surgery, single-incision laparoscopic surgeryLocation(s): Main campus; Richard E. Jacobs Health CenterOffice: 216.444.9244 | Fax: 216.445.1586Appointments: Main campus, 216.445.2224; Richard E. Jacobs, 440.695.4000

Derrick Cetin, DOSpecialty Interest(s): Bariatric medicine, medical weight management, nutrition sciences, obesity management, preoperative evaluation, diabetes careLocation(s): Main campusOffice: 216.445.4255 | Fax: 216.636.1588Appointments: 216.445.2224

Karen Cooper, DOSpecialty Interest(s): Bariatric medicine, family medicine, kinesiology and nutrition sciences, exercise instructionLocation(s): Main campusOffice: 216.445.1114 | Fax: 216.445.1586Appointments: 216.445.2224

Matthew Kroh, MDSpecialty Interest(s): Advanced laparoscopic surgery, bariatric surgery, gastrointestinal surgery, endoscopy, single-incision laparoscopic surgeryLocation(s): Main campus Office: 216.445.9966 | Fax: 216.444.2153Appointments: 216.445.2224

Tomasz Rogula, MD, PhDSpecialty Interest(s): Advanced laparoscopic surgery, bariatric surgery, gastrointestinal surgery, endoscopy, single-incision laparoscopic surgeryLocation(s): Main campus; Strongsville Family Health and Surgery CenterOffice: 216.445.0255 | Fax: 216.445.1586Appointments: Main campus, 216.445.2224; Strongsville, 440.878.2500

Philip Schauer, MDDepartment ChairSpecialty Interest(s): Bariatric surgery, laparoscopic surgery, gastrointestinal surgery, colon surgery, weight management, hernia surgery, biliary surgery, surgery for GERDLocation(s): Main campusOffice: 216.444.4794 | Fax: 216.445.1586Appointments: 216.445.2224

Visit clevelandclinic.org/EndoStaff for the most current staff listings and locations.


C l e v e l a n d C l i n i C R e S O U R C e G U i d e

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Resources for Patients

Resources for PhysiciansReferring Physician Center and HotlineCleveland 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.

Physician DirectoryView all Cleveland Clinic staff online atclevelandclinic.org/staff.

Track Your Patient’s Care OnlineDrConnect 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.

Critical Care Transport WorldwideCleveland 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).

Outcomes DataView clinical Outcomes books from all Cleveland Clinic institutes at clevelandclinic.org/outcomes.

Clinical TrialsWe offer thousands of clinical trials for qualifying patients. Visit clevelandclinic.org/clinicaltrials.

CME Opportunities: Live and OnlineThe 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.

Executive EducationCleveland 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.

Same-Day AppointmentsCleveland 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).

Medical Concierge For complimentary assistance for out-of-state patients and families, call 800.223.2273, ext. 55580, or email [email protected].

Global Patient ServicesFor 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 healthcaremanagement tool that connects patients to their medical record.Patients can register for MyChart through their physician’s officeor by going online to clevelandclinic.org/mychart.

MyConsultCleveland 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.

24/7 ReferralsReferring Physician Hotline855.REFER.123 (855.733.3712)

Hospital Transfers800.553.5056On the Web at clevelandclinic.org/Refer123

Stay Connected with Us on …

about Cleveland ClinicCleveland 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.


The Cleveland Clinic Foundation Endocrinology & Metabolism Institute Endocrine Notes 9500 Euclid Ave. / AC311 Cleveland, OH 44195

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: 2 Cleveland Clinic Study Identifies Increased Mortality Risk with Sulfonylureas vs. Metformin

4 differentiating normocalcemic Primary Hyperparathyroidism and Secondary Hyperparathyroidism

6 Five 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

12 Study Highlights importance of Screening for Thyroid Cancer in Patients diagnosed with Cowden Syndrome

14 Proposed Clinical Algorithm Targets the Management of Residual diabetes Following Bariatric Surgery

16 Benefits of Bariatric Surgery in Type 2 Diabetes Extend to improvement, Prevention of nephropathy

18 Gastric Bypass improves Glucose Homeostasis by attenuating the effect of Ghrelin on ß-cell Function

20 Publications

26 Live and Online CME Opportunities

27 Current Clinical Trials

28 Staff directory

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