Publications by authors named "Betul Hatipoglu"

61 Publications

The Association of Smoking and Alcohol Abuse on Anxiety and Depression in Patients With Recurrent Acute or Chronic Pancreatitis Undergoing Total Pancreatectomy and Islet Autotransplantation: A Report From the Prospective Observational Study of TPIAT Cohort.

Pancreas 2021 Jul;50(6):852-858

Division of Pediatric Endocrinology, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN.

Objectives: Smoking and alcohol use are risk factors for acute and chronic pancreatitis, and their role on anxiety, depression, and opioid use in patients who undergo total pancreatectomy and islet autotransplantation (TPIAT) is unknown.

Methods: We included adults enrolled in the Prospective Observational Study of TPIAT (POST). Measured variables included smoking (never, former, current) and alcohol abuse or dependency history (yes vs no). Using univariable and multivariable analyses, we investigated the association of smoking and alcohol dependency history with anxiety and depression, opioid use, and postsurgical outcomes.

Results: Of 195 adults studied, 25 were current smokers and 77 former smokers, whereas 18 had a history of alcohol dependency (of whom 10 were current smokers). A diagnosis of anxiety was associated with current smoking (P = 0.005), and depression was associated with history of alcohol abuse/dependency (P = 0.0001). However, active symptoms of anxiety and depression at the time of TPIAT were not associated with smoking or alcohol status. Opioid use in the past 14 days was associated with being a former smoker (P = 0.005).

Conclusions: Active smoking and alcohol abuse history were associated with a diagnosis of anxiety and depression, respectively; however, at the time of TPIAT, symptom scores suggested that they were being addressed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPA.0000000000001850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373657PMC
July 2021

Evaluation of FKBP5 as a cortisol activity biomarker in patients with ACTH-dependent Cushing syndrome.

J Clin Transl Endocrinol 2021 Mar 6;24:100256. Epub 2021 Jun 6.

Corcept Therapeutics, 149 Commonwealth Drive, Menlo Park, CA 94025, USA.

Purpose: To evaluate the performance of FKBP5 as a cortisol activity biomarker in patients with ACTH-dependent Cushing syndrome (CS).

Methods: This was a prospective, multicenter, nonrandomized, noninterventional study of a cortisol activity biomarker in adult patients (≥18 years) with documented ACTH-dependent, endogenous CS. The impact of surgery on FKBP5 mRNA expression levels in these patients and the difference in expression levels between these patients and healthy controls were evaluated. Cortisol and biomarker samples were collected before and immediately after surgery. A custom NanoString assay was used to quantify FKBP5 mRNA expression levels. The same method was used to analyze healthy volunteer samples collected from a different study.

Results: Surgery was considered successful in 14/24 patients (58.3%) and changes from baseline in serum cortisol were -92.6% ( = 0.0005) and -43.8% (not significant) in patients with successful and unsuccessful surgeries, respectively. A strong positive correlation between FKBP5 and cortisol levels was observed (before surgery: r = 0.72,  = 0.0002; after surgery: r = 0.85,  < 0.0001). After successful surgery, FKBP5 expression levels were similar to those of healthy subjects. In patients without surgical success, FKBP5 levels remained unchanged from baseline and distinct from healthy subjects ( = 0.0025).

Conclusions: Our findings confirm that FKBP5 levels are higher in the presence of excess cortisol exposure in patients with CS and decrease to normal baseline levels after successful surgery. These findings suggest that FKBP5 can serve as a measure of biological cortisol activity and set the stage for the development of an FKBP5 mRNA expression assay as a biomarker of cortisol activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcte.2021.100256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260880PMC
March 2021

Circulating miRNA in Patients Undergoing Total Pancreatectomy and Islet Autotransplantation.

Cell Transplant 2021 Jan-Dec;30:963689721999330

University of Minnesota Medical School, Minneapolis, MN, USA.

Circulating microRNAs (miRNAs) can be biomarkers for diagnosis and progression of several pathophysiological conditions. In a cohort undergoing total pancreatectomy with islet autotransplantation (TPIAT) from the multicenter Prospective Observational Study of TPIAT (POST), we investigated associations between a panel of circulating miRNAs (hsa-miR-375, hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-216a-5p, hsa-miR-320d, hsa-miR-200c, hsa-miR-125b, hsa-miR-7-5p, hsa-miR-221-3p, hsa-miR-122-5p) and patient, disease and islet-isolation characteristics. Plasma samples ( = 139) were collected before TPIAT and miRNA levels were measured by RTPCR. Disease duration, prior surgery, and pre-surgical diabetes were not associated with circulating miRNAs. Levels of hsa-miR-29b-3p ( = 0.03), hsa-miR-148a-3p ( = 0.04) and hsa-miR-221-3p ( = 0.01) were lower in those with genetic risk factors. Levels of hsa-miR-148a-3p ( = 0.04) and hsa-miR-7-5p ( = 0.04) were elevated in toxic/metabolic disease. Participants with exocrine insufficiency had lower hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-320d, hsa-miR-221-3p ( < 0.01) and hsa-miR-375, hsa-miR-200c-3p, and hsa-miR-125b-5p ( < 0.05). Four miRNAs were associated with fasting C-peptide before TPIAT (hsa-miR-29b-3p, = 0.18; hsa-miR-148a-3p, = 0.21; hsa-miR-320d, = 0.19; and hsa-miR-221-3p, = 0.21; all < 0.05), while hsa-miR-29b-3p was inversely associated with post-isolation islet equivalents/kg and islet number/kg ( = -0.20, = 0.02). Also, hsa-miR-200c ( = 0.18, = 0.03) and hsa-miR-221-3p ( = 0.19, = 0.03) were associated with islet graft tissue volume. Further investigation is needed to determine the predictive potential of these miRNAs for assessing islet autotransplant outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0963689721999330DOI Listing
April 2021

Reply.

Pancreas 2021 01;50(1):e4-e5

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPA.0000000000001701DOI Listing
January 2021

Preoperative ERCP has no impact on islet yield following total pancreatectomy and islet autotransplantation (TPIAT): Results from the Prospective Observational Study of TPIAT (POST) cohort.

Pancreatology 2021 Jan 24;21(1):275-281. Epub 2020 Nov 24.

University of Minnesota Minneapolis, MN, USA.

Background And Aims: Many patients undergoing total pancreatectomy with islet autotransplant (TPIAT) for severe, refractory chronic pancreatitis or recurrent acute pancreatitis have a history of endoscopic retrograde cholangiopancreatography (ERCP). Using data from the multicenter POST (Prospective Observational Study of TPIAT) cohort, we aimed to determine clinical characteristics associated with ERCP and the effect of ERCP on islet yield.

Methods: Using data from 230 participants (11 centers), demographics, pancreatitis history, and imaging features were tested for association with ERCP procedures. Logistic and linear regression were used to assess association of islet yield measures with having any pre-operative ERCPs and with the number of ERCPs, adjusting for confounders.

Results: 175 (76%) underwent ERCPs [median number of ERCPs (IQR) 2 (1-4). ERCP was more common in those with obstructed pancreatic duct (p = 0.0009), pancreas divisum (p = 0.0009), prior pancreatic surgery (p = 0.005), and longer disease duration (p = 0.004). A greater number of ERCPs was associated with disease duration (p < 0.0001), obstructed pancreatic duct (p = 0.006), and prior pancreatic surgery (p = 0.006) and increased risk for positive islet culture (p < 0.0001). Mean total IEQ/kg with vs. without prior ERCP were 4145 (95% CI 3621-4669) vs. 3476 (95% CI 2521-4431) respectively (p = 0.23). Adjusting for confounders, islet yield was not significantly associated with prior ERCP, number of ERCPs, biliary or pancreatic sphincterotomy or stent placement.

Conclusions: ERCP did not appear to adversely impact islet yield. When indicated, ERCP need not be withheld to optimize islet yield but the risk-benefit ratio of ERCP should be considered given its potential harms, including risk for excessive delay in TPIAT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pan.2020.11.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924984PMC
January 2021

Prolactin-to-Testosterone Ratio Predicts Pituitary Abnormalities in Mildly Hyperprolactinemic Men with Symptoms of Hypogonadism.

J Urol 2021 Mar 20;205(3):871-878. Epub 2020 Oct 20.

Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio.

Purpose: We aimed to identify predictor variables associated with pituitary abnormalities in hypogonadal men with mild hyperprolactinemia. We also sought to develop a decision-making aid to select patients for evaluation with pituitary magnetic resonance imaging.

Materials And Methods: We retrospectively examined men with mild hyperprolactinemia (15.1-50.0 ng/ml) who presented with symptoms of hypogonadism and underwent pituitary magnetic resonance imaging. Demographics, laboratory values and clinical data were obtained from the electronic medical record. Selected predictor variables were included in multivariable logistic regression and partitioning models. Cost avoidance analysis was performed on models achieving sensitivities ≥90%.

Results: A total of 141 men were included in the study, of whom 40 (28%) displayed abnormalities on pituitary magnetic resonance imaging. Patients with pituitary abnormalities exhibited higher prolactin (p=0.01), lower testosterone (p=0.0001) and lower luteinizing hormone (p=0.03) levels than those with normal anatomy, as well as higher prolactin-to-testosterone ratios (p <0.0001) and lower luteinizing hormone-to-follicle-stimulating hormone ratios (p=0.0001). These serological variables were identified as the best performing predictor variables. The partition incorporating a prolactin-to-testosterone ratio cutoff of 0.10 and prolactin cutoff of 25 ng/ml achieved 90% sensitivity and 48% specificity, and reduced diagnostic expenses by 28%.

Conclusions: Hypogonadal men presenting with mild hyperprolactinemia and pituitary abnormalities declare themselves via endocrine studies routinely ordered to evaluate these conditions. The prolactin-to-testosterone ratio is the best independent predictor of finding a pituitary abnormality on magnetic resonance imaging, although sensitivity improves by referencing additional serological parameters. Significant cost avoidance may result from screening this population prior to ordering pituitary magnetic resonance imaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JU.0000000000001431DOI Listing
March 2021

Acromegaly: a clinical perspective.

Clin Diabetes Endocrinol 2020 20;6:15. Epub 2020 Aug 20.

Department of Endocrinology, Diabetes and Metabolism, Cleveland Clinic, 9500 Euclid Ave. F-20, Cleveland, OH 44195 USA.

Background: To examine the clinical and hormonal profiles, comorbidities, treatment patterns, surgical pathology and clinical outcomes of patients diagnosed with acromegaly at the Cleveland Clinic over a 15-year period.

Methods: A retrospective chart review of patients with acromegaly who underwent surgical resection between 2003 and 2018.

Results: A total of 136 patients (62 men; mean age 48.1 years) with biochemical evidence of acromegaly were analyzed. Median insulin-like growth factor 1 (IGF-1) level at diagnosis was 769.0 ng/mL and most patients had a macroadenoma (82.2%). Immunoreactivity to growth hormone (GH) was noted in 124 adenomas, with co-staining in 89 adenomas. Complete visible tumor resection during initial surgery was achieved in 87 patients (64.0%). In this cohort, complete response to surgery alone was observed in 61 patients (70.1%), while 31 out of 65 patients (47.7%) who received additional post-surgical medications and/or radiation therapy achieved complete response. At most recent follow-up, 92 patients achieved eventual complete response by documented normalization of IGF-1 levels. Higher IGF-1 level at diagnosis ( = 0.024) and cavernous sinus invasion ( = 0.028) were predictors for failure to respond to surgery.

Conclusion: In this study, the majority of tumors were macroadenoma, plurihormonal, and treated effectively with surgery alone or surgery with adjuvant medical or radiation therapy. More studies are needed to identify additional molecular biomarkers, tumor characteristics and imaging findings to individualize treatment and better predict treatment outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40842-020-00104-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441684PMC
August 2020

Pancreatic Islet Cell Transplantation: Graft Stability and Metabolic Outcomes.

OBM Transplant 2020 7;4(3):1-9. Epub 2020 Jul 7.

Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, OH, USA.

Pancreatic islet transplantation is a rapidly evolving field. It has been increasingly regarded as a promising approach for the correction of dysglycemia associated with type 1 diabetes mellitus (allogenic islet transplantation), or the prevention of surgical diabetes in chronic pancreatitis subjects undergoing total pancreatectomy (autologous islet transplantation). In this review, we discuss the latest literature pertaining to metabolic outcomes of autologous and allogenic islet transplantation, shedding close light on our own latest experience in the autologous islet transplantation setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21926/obm.transplant.2003115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409867PMC
July 2020

Change in Functional Beta Cell Capacity With Time Following Autologous Islet Transplantation.

Pancreas 2019 May/Jun;48(5):656-661

From the Endocrinology and Metabolism Institute and.

Objectives: Autologous islet transplantation (AIT) is performed to preserve insulin secretory function in chronic pancreatitis patients undergoing total pancreatectomy (TP). No data exist on the effect of time lapse on beta cell function post TP-AIT. We aimed to investigate the factor of time lapse on beta cell function following TP-AIT.

Methods: Retrospectively, we identified 31 adult patients with chronic pancreatitis who underwent TP-AIT between 2008 and 2016. Changes in beta cell function were assessed using (1) BETA-2 scores and (2) analysis of posttransplant mixed-meal tolerance testing.

Results: Significant decrease in functional beta cell capacity expressed by BETA-2 scores was seen in the first 2 years following TP-AIT, with an annual decrease of 6.3 points in median BETA-2 score (interquartile range, 4.6-11.6; P = 0.002). In the mixed-meal tolerance testing analysis, nonsignificant trends toward higher glucose, lower insulin, and lower C-peptide were seen with time lapse. Additionally, higher hemoglobin A1c values (P = 0.033) and higher insulin requirements (P = 0.04) were seen with longer follow-up after AIT.

Conclusions: A steady drop in functional beta cell capacity was observed in the 2 years following TP and AIT. To our knowledge, to date this is the first report of the BETA-2 score applicability in the AIT setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPA.0000000000001315DOI Listing
February 2020

Beta Cell Stress in Insulin Independent Subjects Following Total Pancreatectomy and Autologous Islet Transplantation.

Turk Klin Immunol Alerji 2019 12;2019:39-44. Epub 2019 Apr 12.

Cleveland Clinic, Endocrinology and Metabolism Institute, Cleveland, OH, USA.

In patients with chronic pancreatitis (CP), autologous islet transplantation (AIT) is often coupled with total pancreatectomy (TP) in aims to preserve patients' insulin secretory function. Despite a third of patients achieving insulin independence post-total pancreatectomy and autologous islet transplantation (TPAIT), many will require the addition of insulin therapy for maintenance of glycemic control overtime. We aimed through this study to investigate the early metabolic profile signature of insulin independent subjects post-TPAIT, specifically exploring markers of beta cell stress in this cohort. In a prospective study design, we identified 37 subjects who underwent TPAIT between 2008 and 2017. Metabolic parameters were assessed using mixed meal tolerance test data (MMTT), and the insulin-to-proinsulin index ratio, a marker of beta cell stress. Assessments between metabolic variables were evaluated using the Wilcoxon signed rank test. A significance level of 0.05 was assumed for all comparisons. At a mean (±standard deviation) follow up duration of 37.7±17 months post-TPAIT, 11 patients (30%) were insulin independent with a mean HbA1C of 5.85±0.42%. Despite adequate glycemic control in the latter cohort, we observed significantly higher median peak glucose (180.5 versus 115.0 mg/dL; p=0.031), and lower median fasting C-peptide (0.95 versus 1.5 ng/mL; p=0.008) on post-TPAIT MMTT compared to pre-TPAIT MMTT. Additionally, significantly lower insulin-to-proinsulin index AUC ratio was seen post-TPAIT compared to pre-TPAIT (p=0.022). A decline in the proinsulin processing capacity, expressed by a lower insulin-to-proinsulin index ratio was seen in insulin independent subjects post-TPAIT. Further studies exploring the pathophysiology underlying these findings should be attained.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182349PMC
April 2019

Islet cell autotransplantation update.

CellR4 Repair Replace Regen Reprogram 2019 18;7. Epub 2019 Apr 18.

Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, OH, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059780PMC
April 2019

Beta-cell therapies for type 1 diabetes: Transplants and bionics.

Cleve Clin J Med 2018 12;85(12):931-937

Department of Endocrinology, Diabetes, and Metabolism, Cleveland Clinic, Cleveland, OH, USA.

Research continues toward the goal of treating type 1 diabetes by replacing insulin-producing beta cells. Ideally, such treatment would be safe and long-lasting and would eliminate the need for subcutaneous insulin replacement. This article reviews the current state of beta-cell replacement through transplant of the whole pancreas or of islet cells. It also looks at the "bionic" pancreas and other future challenges.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3949/ccjm.85a.17088DOI Listing
December 2018

Postural Orthostatic Tachycardia Syndrome and Its Unusual Presenting Complaints in Women: A Literature Minireview.

Cureus 2018 Apr 5;10(4):e2435. Epub 2018 Apr 5.

Neurology, Cleveland Clinic, Ohio.

Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous disorder of the autonomic nervous system that is defined by symptoms of orthostatic intolerance. According to the current criteria for adults, currently, POTS is defined as a heart rate increment of 30 beats/minute or more after 10 minutes of standing in the absence of orthostatic hypotension. There is a vast majority that remains misdiagnosed due to the heterogeneity of the disorder. Due to a lack of Food and Drug Administration (FDA) approved therapy, alternative therapies and over the counter medications are used to alleviate the symptoms. This is an uncommon presentation observed primarily in women, as it is more prevalent in females.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7759/cureus.2435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988200PMC
April 2018

Total pancreaticoduodenectomy with autologous islet transplantation 14 years after liver-contained composite visceral transplantation.

Am J Transplant 2018 08 14;18(8):2068-2074. Epub 2018 May 14.

Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA.

Chronic pancreatitis (CP) is a severely disabling disorder with potential detrimental effects on quality of life, gut function, and glucose homeostasis. Disease progression often results in irreversible morphological and functional abnormalities with development of chronic pain, mechanical obstruction, and pancreatic insufficiency. Along with comprehensive medical management, the concept of total pancreatectomy and islet autotransplantation (TP-AIT) was introduced 40 years ago for patients with intractable pain and preserved beta-cell function. With anticipated technical difficulties, total excision of the inflamed-disfigured gland is expected to alleviate the incapacitating visceral pain and correct other associated abdominal pathology. With retrieval of sufficient islet-cell mass, the autologous transplant procedure has the potential to maintain an euglycemic state without exogenous insulin requirement. The reported herein case of CP-induced recalcitrant pain and foregut obstruction is exceptional because of the technical challenges in performing native pancreaticoduodenectomy in close proximity to the composite visceral allograft with complex vascular and gut reconstructions. Equally novel is transplanting the auto-islets in the liver-contained visceral allograft. Despite intravenous nutrition shortly after birth, liver transplantation at age 13, retransplantation with liver-contained visceral allograft at age 17 and TP-AIT at age 31, the 38-year-old recipient is currently pain free with full nutritional autonomy and normal glucose homeostasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.14880DOI Listing
August 2018

Autoimmunity in Autologous Islet Transplantation.

OBM Transplant 2018 3;2(3). Epub 2018 Jul 3.

Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, USA.

Total pancreatectomy (TP) is increasingly being utilized for definitive treatment in patients with debilitating chronic pancreatitis (CP). In an effort to prevent surgical diabetes, the procedure can be performed in conjunction with transplantation of islets of Langerhans recovered from the patients' own resected pancreas (autologous islet transplantation, AIT). Given that patients undergoing TP and AIT are traditionally assumed not to be at risk for the development of beta-cell autoimmunity, it is possible that the presence of autoimmune islet graft failure has been overlooked and underreported in this patient population. Herein, we describe two cases who underwent TP and AIT and later developed new-onset beta-cell autoimmunity (as evidenced by de novo glutamic acid decarboxylase antibody positivity), accompanied by complete insulin-dependent states. These cases emphasize the need for considering a possible autoimmune phenomenon in the workup of TP and AIT patients who manifest with unexpected and rapid deterioration in their glycemic control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21926/obm.transplant.1803014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039533PMC
July 2018

Coronary artery calcium may stabilize following islet cell transplantation in patients with type 1 diabetes.

Clin Transplant 2017 Oct 19;31(10). Epub 2017 Aug 19.

Division of Transplant Surgery, University of Illinois at Chicago, Chicago, IL, USA.

Islet cell transplantation can functionally cure type 1 diabetes and also improve carotid intima-media thickness. This study provides a preliminary description of changes in coronary artery calcium following islet transplantation, and associated factors. Coronary artery calcium was measured in 14 patients with type 1 diabetes (11 had measures both pre- and post-transplant [mean 2.3 years]) in the University of Illinois at Chicago's clinical trial. Multivariable mixed-effects linear regression of repeated measures was used to quantify calcium change and determine if this change was longitudinally associated with risk/protective factors. Thirteen of the patients were female, with mean baseline age, diabetes duration, and BMI of 47.6 and 28.7 years, and 23.1, respectively. Over half (57%) had detectable coronary artery calcium pre-transplant. Minimal change (0.39 mm /y, P = .02) occurred in coronary artery calcium levels pre- to post-transplant. No patient met criteria for calcium progression. Coronary artery calcium was positively associated with total and small VLDL particles (P ≤ .02), statin dose (P = .02), and urine albumin-to-creatinine ratio (P = .04) and negatively associated with free fatty acids (P = .03), total HDL (P = .03), large HDL particles (P = .005), and tacrolimus dose (P = .02). Islet transplant may stabilize coronary artery calcium, with optimal management of lipids and kidney function remaining key therapeutic targets. [NCT00679041].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ctr.13059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5633499PMC
October 2017

Surgical outcomes in patients with Cushing's disease: the Cleveland clinic experience.

Pituitary 2017 Aug;20(4):430-440

Department of Neurosurgery, the Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.

Context: Transsphenoidal surgery (TSS) to resect a pituitary adenoma is considered first-line treatment for patients with Cushing's disease (CD). Early, post-operative remission rates >80% are expected for patients with a microadenoma (≤ 10 mm) visible on magnetic resonance (MR) imaging.

Objective: To report surgical outcomes and predictors of remission in a specialist center for patients with CD.

Patients And Methods: Clinical data was obtained from a prospective CD database in addition to review of all electronic medical, laboratory and surgical patient records. Patients who underwent their first TSS by one neurosurgeon between 2004 and 2013, and had a minimum 1 year follow up, were evaluated.

Results: One hundred and one consecutive patients with CD (73F, 28M) underwent TSS. Median (range) age and follow-up were 47 (15-87) and 4.33 (1-9.8) years, respectively. At surgery, 74 (73.2%) patients had a microadenoma, 27 a macroadenoma; six of the latter patients had a planned, subtotal resection to control neurological signs due to mass effect. Initial remission rates were: microadenoma, 89% (66/74); macroadenoma, 63% (17/27); and 81% (17/21) in those macroadenomas where complete surgical removal was anticipated. Initial non-remission occurred in 18 patients, ten macro- and eight microadenoma; six of 18 had residual disease on most recent follow up. Six (2 macro, 4 micro) of the 83 patients with initial remission have had late (>12 months) recurrence of hypercortisolism that required either repeat TSS or adjunctive therapy, three of whom have persistent hypercortisolism. Macroadenoma (p = 0.003) and tumor invasion beyond the pituitary and sella (p < 0.001) were associated with failure to obtain remission with the initial TSS and greater likelihood of late recurrence. Patients in whom no lesion was seen on neuroimaging had rates of initial remission (21/25 or 84%) and a similar late recurrence rate of 4% (1/25) in comparison with those with MR-visible microadenomas (3/49, or 6%).

Conclusions: A team-based approach, in a specialized pituitary center, can lead to initial and durable, long-term remission in patients with CD. The presence of a macroadenoma and tumor extension beyond the pituitary and sella were predictive of initial non-remission as well as risk of late recurrence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11102-017-0802-1DOI Listing
August 2017

Long-Term Glycemic Control in Adult Patients Undergoing Remote vs. Local Total Pancreatectomy With Islet Autotransplantation.

Am J Gastroenterol 2017 04 7;112(4):643-649. Epub 2017 Feb 7.

Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.

Objectives: Total pancreatectomy with islet autotransplantation (TPIAT) is increasingly performed with remote islet cell processing and preparation, i.e., with islet cell isolation performed remotely from the primary surgical site at an appropriately equipped islet isolation facility. We aimed to determine whether TPIAT using remote islet isolation results in comparable long-term glycemic outcomes compared with TPIAT performed with standard local isolation.

Methods: We performed a retrospective cohort study of adult patients who underwent TPIAT at three tertiary care centers from 2010 to 2013. Two centers performed remote isolation and one performed local isolation. Explanted pancreata in the remote cohort were transported ∼130 miles to and from islet isolation facilities. The primary outcome was insulin independence 1 year following transplant.

Results: Baseline characteristics were similar between groups except the remote cohort had higher preoperative hemoglobin A1c (HbA1c; 5.43 vs. 5.25, P=0.02) and there were more females in the local cohort (58% vs. 76%, P=0.049). At 1 year, 27% of remote and 32% of local patients were insulin independent (P=0.48). Remote patients experienced a greater drop in fasting c-peptide (-1.66 vs. -0.64, P=0.006) and a greater rise in HbA1c (1.65 vs. 0.99, P=0.014) at 1-year follow-up. A preoperative c-peptide >2.7 (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.6-14.3) and >3,000 islet equivalents/kg (OR 11.0, 95% CI 3.2-37.3) were associated with one-year insulin independence in the local group.

Conclusions: At 1 year after TPIAT, patients undergoing remote surgery have equivalent rates of long-term insulin independence compared with patients undergoing TPIAT locally, but metabolic control is superior with local isolation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ajg.2017.14DOI Listing
April 2017

Islet Cell Yield Following Remote Total Pancreatectomy With Islet Autotransplant is Independent of Cold Ischemia Time.

Pancreas 2017 03;46(3):380-384

From the Sections of *Gastroenterology and Hepatology and †General Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH; ‡Section of Gastroenterology and Hepatology, Digestive Disease Institute, §Department of Endocrinology, Endocrinology and Metabolism Institute, and ∥Department of General Surgery, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, OH; and Sections of ¶Transplant Surgery and #Endocrinology, Dartmouth-Hitchcock Medical Center, Lebanon, NH.

Objectives: Total pancreatectomy with islet autotransplantation is increasingly being performed remotely, that is, removing the pancreas in 1 location, isolating the islet cells in another location, then returning the islets to the original location for reimplantation into the patient. We determined the influence of extended cold ischemia time on key clinical outcomes in remote islet autotransplantation.

Methods: We evaluated patients who underwent remote islet autotransplantation at 2 centers from 2011 to 2014. Patients were divided into 2 groups: those with and those without a decrease in C-peptide greater than 50% from baseline. The primary clinical outcome was the quantity of isolated islet equivalents per kilogram body weight (IEQs/kg).

Results: Twenty-five patients met inclusion criteria; 15 had a decrease in C-peptide greater than 50% from baseline and had lower corresponding IEQs/kg compared with those without a decrease greater than 50% (4045 vs 6654 IEQs/kg, P = 0.01). There was no difference in cold ischemia time between the 2 groups (664 vs 600 minutes, P = 0.25). Daily insulin use at 1 year nearly met statistical significance (25.3 vs 8 U, P = 0.06), as did glycated hemoglobin (8.07 vs 6.69 mmol/L, P = 0.06).

Conclusions: Cold ischemia time does not influence islet yield in patients undergoing pancreatectomy with remote isolation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPA.0000000000000792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308539PMC
March 2017

Islet Cell Transplantation and Alternative Therapies.

Authors:
Betul Hatipoglu

Endocrinol Metab Clin North Am 2016 12 28;45(4):923-931. Epub 2016 Sep 28.

Endocrinology and Metabolism Institute, Cleveland Clinic, 9500 Euclid Avenue, F20, Cleveland, OH 44195, USA. Electronic address:

Even though type 2 diabetes rates plateaued, type 1 diabetes continues to increase. Pancreas transplantation is a treatment modality for patients who suffer hypoglycemic unawareness or complications from diabetes. Islet cell transplantation success rates have improved with modification and advances in isolation, transplantation, and new immunosuppression regimens. The new cell sources as well as delivery ways are explored and being tested in human trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecl.2016.06.004DOI Listing
December 2016

Correction: Pancreatectomy and islet cell autotransplantation.

Cleve Clin J Med 2016 Sep;83(9):644

Department of Endocrinology, Diabetes, and Metabolism, Cleveland Clinic, Cleveland, OH, USA. E-mail:

The article "Total pancreatectomy and islet cell autotransplantation: Definitive treatment for chronic pancreatitis" (Arce KM, Lin YK, Stevens T, Walsh RM, Hatipoglu BA. Cleve Clin J Med 2016; 83:435-442) incorrectly stated that Paul Lacy and David Scharp performed research at the University of Washington at Seattle. They did their work at Washington University in St. Louis, Missouri.
View Article and Find Full Text PDF

Download full-text PDF

Source
September 2016

Spontaneous Hypoglycemia After Islet Autotransplantation for Chronic Pancreatitis.

J Clin Endocrinol Metab 2016 10 22;101(10):3669-3675. Epub 2016 Aug 22.

Department of Endocrinology, Diabetes, and Metabolism (Y.K.L., C.F., P.C.J., B.A.H.), Endocrinology and Metabolism Institute, Departments of General Surgery (R.M.W.) and Gastroenterology and Hepatology (T.S.), Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio 44195; and Islet Isolation Laboratory (R.B.), Institute of Cellular Therapeutics, Allegheny Health Network, Pittsburgh, Pennsylvania 15212.

Context: Spontaneous hypoglycemia has been reported in patients after total pancreatectomy (TP) and islet autotransplantation (IAT) with maintained insulin independence. Details surrounding these events have not been well described.

Objective: The objective of the study was to determine the frequency and characteristics of spontaneous hypoglycemia in patients undergoing TP-IAT and/or to ascertain predictive or protective factors of its development.

Design: This was an observational cohort study in 40 patients who underwent TP-IAT from August 2008 to May 2014, with a median follow-up of 34 months.

Setting: The study was conducted at a single institution (Cleveland Clinic).

Patients: Patients included recipients of TP-IAT.

Intervention: The intervention included small, frequent meals in those patients who developed spontaneous hypoglycemia.

Main Outcome Measures: Incidence of spontaneous hypoglycemia development, characteristics of the patients developing hypoglycemia, and their response to small, frequent meals were measured.

Results: Six of 12 patients, who maintained insulin independence, developed spontaneous hypoglycemia. The episodes could be fasting, postprandial, and/or exercise associated, with the frequency ranging from two to three times daily to once every 1-2 weeks. All patients experienced at least one episode that required external assistance, glucagon administration, and/or emergent medical attention. Patients who developed hypoglycemia had a lower median age and tended to have a lower median islet equivalent/kg body weight but a higher median total islet equivalent, body mass index, and homeostatic model assessment for insulin resistance score. All patients who received small, frequent meal intervention had improvement in severity and/or frequency of the hypoglycemic episodes.

Conclusions: Spontaneous hypoglycemia is prevalent after TP-IAT. Although the underlying pathophysiology responsible for these hypoglycemia events remains to be elucidated, small, frequent meal intervention is helpful in ameliorating this condition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/jc.2016-2111DOI Listing
October 2016

Total pancreatectomy and islet cell autotransplantation: Definitive treatment for chronic pancreatitis.

Cleve Clin J Med 2016 06;83:435-42

Department of Endocrinology, Diabetes, and Metabolism, Cleveland Clinic, Cleveland, OH, USA. E-mail:

In appropriately selected patients, total pancreatectomy and islet cell autotransplant controls pain and improves quality of life while often minimizing the development of overt diabetes. Multidisciplinary management and lifelong follow-up help to maximize the benefit of this procedure. This review highlights its history, indications, metabolic outcomes, and future directions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3949/ccjm.83a.15056DOI Listing
June 2016

Measurement of Serum Free Thyroxine Index May Provide Additional Case Detection Compared to Free Thyroxine in the Diagnosis of Central Hypothyroidism.

Case Rep Endocrinol 2015 8;2015:965191. Epub 2015 Dec 8.

Endocrinology and Metabolism Institute, Cleveland Clinic, Desk F-20, 9500 Euclid Avenue, Cleveland, OH 44195, USA; Department of Endocrinology, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE.

The diagnosis of central hypothyroidism is often suspected in patients with hypothalamic/pituitary pathology, in the setting of low, normal, or even slightly elevated serum TSH and low free thyroxine (FT4). We present four cases of central hypothyroidism (three had known pituitary pathology) in whom central hypothyroidism was diagnosed after the serum free thyroxine index (FTI) was found to be low. All had normal range serum TSH and free thyroxine levels. This report illustrates that the assessment of the serum FTI may be helpful in making the diagnosis of central hypothyroidism in the appropriate clinical setting and when free T4 is in the low-normal range, particularly in patients with multiple anterior pituitary hormone deficiencies and/or with symptoms suggestive of hypothyroidism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2015/965191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686635PMC
January 2016

Pancreas transplant for diabetes mellitus.

Cleve Clin J Med 2015 Nov;82(11):738-44

Department of Urology, Cleveland Clinic, Cleveland, OH, USA.

Pancreas transplant is an option for patients with type 1 diabetes and for some patients with type 2 diabetes and advanced diabetic kidney disease. The procedure has a high success rate, and performing it earlier in the course of diabetes could help prevent or reverse the long-term complications of diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3949/ccjm.82a.14090DOI Listing
November 2015

Diagnostic accuracy of circulating thyrotropin receptor messenger RNA combined with neck ultrasonography in patients with Bethesda III-V thyroid cytology.

Surgery 2016 Jan 9;159(1):113-7. Epub 2015 Oct 9.

Department of Endocrine Surgery, Cleveland Clinic, Cleveland, OH. Electronic address:

Background: The aim of this study was to analyze the usefulness of thyrotropin receptor messenger RNA (TSHR-mRNA) combined with neck ultrasonography (US) in the management of thyroid nodules with Bethesda III-V cytology.

Methods: Cytology slides of patients with a preoperative fine needle aspiration (FNA) and TSHR-mRNA who underwent thyroidectomy between 2002 and 2011 were recategorized based on the Bethesda classification. Results of thyroid FNA, TSHR-mRNA, and US were compared with the final pathology. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated.

Results: There were 12 patients with Bethesda III, 112 with Bethesda IV, and 58 with Bethesda V cytology. The sensitivity of TSHR-mRNA in predicting cancer was 33%, 65%, and 79 %, and specificity was 67%, 66%, and 71%, for Bethesda III, IV, and V categories, respectively. For the same categories, the PPV of TSHR-mRNA was 25%, 33%, and 79%, respectively; whereas the NPV was 75%, 88%, and 71%, respectively. The addition of neck US to TSHR-mRNA increased the NPV to 100% for Bethesda III, and 86%, for Bethesda IV, and 82% for Bethesda V disease.

Conclusion: This study documents the potential usefulness of TSHR-mRNA for thyroid nodules with Bethesda III-V FNA categories. TSHR-mRNA may be used to exclude Bethesda IV disease. A large sample analysis is needed to determine its accuracy for Bethesda category III nodules.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.surg.2015.06.063DOI Listing
January 2016

The utility of peripheral thyrotropin receptor mRNA in the management of differentiated thyroid cancer.

Surgery 2015 Oct 23;158(4):1089-93; discussion 1093-4. Epub 2015 Jul 23.

Department of Endocrine Surgery, Cleveland Clinic, Cleveland, OH. Electronic address:

Background: Our aim was to analyze the utility of peripheral thyrotropin receptor (TSHR) messenger RNA (mRNA) in predicting and detecting the recurrence of differentiated thyroid cancer.

Methods: Peripheral blood TSHR-mRNA was obtained in 103 patients before and after total thyroidectomy. An analysis was performed to correlate peripheral blood TSHR-mRNA concentration with oncologic outcomes.

Results: Tumor types were papillary (n = 92), follicular (n = 9) and Hürthle cell (n = 2) cancer. Preoperative TSHR-mRNA was ≥1.02 ng/μg in 85% (88/103). On follow-up (median 48 months), 10 patients (10 %) developed recurrence. Recurrence rate in patients with a preoperative TSHR-mRNA ≥ 1.02 ng/μg was 11% versus 0% in those with a lesser concentration. TSHR-mRNA correctly diagnosed 7 (70%) of 10 recurrences. Of 19 patients with positive thyroglobulin (Tg) antibodies, TSHR-mRNA confirmed disease-free status in 12 (63%) and recurrence in 1 (5%). For Tg, TSHR-mRNA and whole-body radioactive iodine scan, sensitivity was 70%, 70%, and 75%; specificity 94%, 76%, 97%; PPV 54%, 24%, and 67%; and NPV 97%, 96%, and 98%, respectively, in detecting recurrent disease.

Conclusion: This study shows that patients with preoperative TSHR-mRNA ≥1.02 ng/μg may be at a greater risk for recurrence compared with those with a lesser concentration. In the presence of Tg antibodies, TSHR-mRNA accurately predicted disease status in 68% of patients. Its overall performance in detecting recurrence was similar to Tg and whole-body radioactive iodine scan, albeit with lower specificity and PPV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.surg.2015.06.023DOI Listing
October 2015

PITUITARY MRI FINDINGS IN PATIENTS WITH PITUITARY AND ECTOPIC ACTH-DEPENDENT CUSHING SYNDROME: DOES A 6-MM PITUITARY TUMOR SIZE CUT-OFF VALUE EXCLUDE ECTOPIC ACTH SYNDROME?

Endocr Pract 2015 Oct 29;21(10):1098-103. Epub 2015 Jun 29.

Objective: Expert opinion and a consensus statement on Cushing syndrome (CS) indicate that in a patient with a clinical presentation and biochemical studies consistent with a pituitary etiology, the presence of a pituitary tumor ≥6 mm is highly suggestive of Cushing disease (CD). The purpose of the present study was to determine the optimal pituitary tumor size that can differentiate between patients with CD and ectopic adrenocorticotrophic hormone (ACTH) secretion (EAS) and obviate the need for inferior petrosal sinus sampling (IPSS).

Methods: We performed a retrospective study of 130 patients seen between 2000 and 2012 including 104 patients with CD and 26 patients with EAS.

Results: A pituitary lesion was reported in 6/26 (23%) patients with EAS and 71/104 (68.3%) patients with CD, with median (range) sizes of 5 mm (3-14) and 8 mm (2-31), respectively. All tumors in the EAS group measured ≤6 mm except for 1 that measured 14 mm. The presence of a pituitary tumor >6 mm in size had 40% sensitivity and 96% specificity for the diagnosis of CD. ACTH levels >209 pg/mL and serum potassium <2.7 mmol/L were found in patients with EAS. All patients with EAS had a 24-hour urine free cortisol (UFC) >3.4 times the upper limit of normal (×ULN) Conclusion: Pituitary incidentalomas as large as 14 mm in size can be seen in patients with EAS. However, the 6-mm tumor size cut-off value provided 96% specificity and may be a reasonable threshold to proceed with surgery without the need for IPSS when the biochemical data support a pituitary etiology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4158/EP15662.ORDOI Listing
October 2015

Chronic Pancreatitis and Diabetes Mellitus.

Curr Treat Options Gastroenterol 2015 Sep;13(3):319-31

Department of Endocrinology, Diabetes and Metabolism, Cleveland Clinic Foundation, 9500 Euclid Avenue Desk F20, Cleveland, OH, 44195, USA.

Opinion Statement: Patients with chronic pancreatitis should be screening at least annually for diabetes. Lifestyle modifications remain to be an important part of treatment for diabetic control. Unless contraindicated or not tolerated, metformin can be initiated and continued concurrently with other anti-diabetic agents or insulin. All anti-diabetic agents should be used based on their physiology and adverse effect profiles, along with the metabolic status of patients. Insulin therapy should be initiated without delay for any of the following: symptomatic or overt hyperglycemia, catabolic state secondary to uncontrolled diabetes, history of diabetic ketoacidosis, hospitalization or acute exacerbation of pancreatitis, or hyperglycemia that cannot be otherwise controlled. Dose adjustment should be done conservatively as these patients are more likely to be insulin sensitive and have loss of counter regulatory hormones. Insulin pump and continuous glucose monitoring should be considered early during therapy in selected patients. For patients undergoing total pancreatectomy or extensive partial pancreatectomy, evaluations to determine the eligibilities for islet cell autotransplantation should be considered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11938-015-0055-xDOI Listing
September 2015
-->