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ABSTRACT: Chronic myelogenous leukemia (CML) is caused by the BCR-ABL1 fusion gene that encodes for a constitutively-active tyrosine kinase. Adults and children with CML are typically treated with imatinib mesylate, a BCR-ABL1 tyrosine kinase inhibitor (TKI), or a second-generation TKI. Several case reports have documented growth delay of unknown mechanism in children with CML treated with imatinib. We report a seven-year-old identical twin with CML who developed significant growth delay, as compared to her twin, during five years of TKI therapy. Detailed endocrine evaluation showed acquired growth hormone deficiency, a pathway potentially inhibited by TKIs.
Pediatric Blood & Cancer 04/2011; 56(4):671-3. · 1.89 Impact Factor
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Philip Zeitler
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ABSTRACT: The prevalence of both type 1 and type 2 diabetes among children and adolescents has been steadily increasing over the last few decades. However, as the general pediatric population becomes more obese and more ethnically diverse, reliance on phenotypic characteristics for distinguishing between these types of diabetes is becoming increasingly untenable. Yet, the recognition of differences in treatment strategies, associated disorders, and both short- and long-term diabetes and cardiovascular outcomes supports the importance of diagnostic efforts to make a distinction between diabetes types. An approach to determination of diabetes type is discussed, focused on the presence or absence of autoimmunity and assessment of β-cell function. At the time of diagnosis, it is generally not possible to be certain of diabetes type, and therefore, initial treatment decisions must be made based on aspects of the presenting physiology, with adjustments in treatment approach made as the individual's course proceeds and additional information becomes available. The apparent overlap between type 1 and type 2 diabetes that occurs in obese adolescents has resulted in some controversy regarding mixed forms of diabetes that are ultimately semantic, but this does raise interesting questions about the treatment of type 1 diabetes in the presence of an insulin-resistant phenotype. Finally, the lack of information about the efficacy of treatment of cardiovascular risk factors, such as dyslipidemia and hypertension, along with the well-documented challenges in adherence to chronic illness treatment in this population, creates substantial challenges.
The Journal of clinical endocrinology and metabolism 12/2010; 95(12):5163-70. · 6.50 Impact Factor
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The Journal of pediatrics 07/2010; 157(1):13-14.e1. · 4.02 Impact Factor
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Philip Zeitler
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ABSTRACT: The prevalence of diabetes among children and adolescents has been steadily increasing, making it even more important that diabetes be adequately managed in this patient population. A basic distinction between type 1 and type 2 diabetes has long been understood. Type 1 diabetes results from a primary loss of pancreatic insulin production, usually as a consequence of autoimmune destruction of pancreatic cells; in type 2 diabetes, insulin production continues and may even be exaggerated, but is insufficient to adequately compensate for resistance to insulin action, leading to the loss of glycemic control. Regardless of the type of diabetes, the treatment goal is to control hyperglycemia. However, the optimal treatment strategy depends on the underlying cause of hyperglycemia. It is therefore important to accurately diagnose whether a patient has type 1 or type 2 diabetes. Historically, this has been thought possible based on the different clinical presentations and age of onset of the conditions. More recently, with the increasing prevalence of type 2 diabetes among adolescents and the trend toward a more obese society, the distinction has become less clear. This has led to the need for the differential diagnosis of diabetes to be confirmed using biochemical and immunological testing. In addition, because the prevalence of type 2 diabetes in the pediatric population is a relatively new phenomenon, available treatments for type 2 diabetes have been studied predominantly in adult populations. With type 2 diabetes becoming increasingly common in pediatric centers, there is a need to evaluate the optimal treatments for children and adolescents.
Postgraduate Medicine 05/2010; 122(3):89-97. · 1.78 Impact Factor
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ABSTRACT: Background. Adrenal insufficiency is a life-threatening event. It is recommended that patients with known adrenal insufficiency and their families receive careful and repeated education on sick-day glucocorticoid management. We hypothesized that the electronic medical record (EMR) can be used to improve patient education through automated provider notification. Methods. We established an automated electronic alert in the EMR that triggered in the outpatient endocrine clinic. The alert asked if stress dose education was reviewed at the visit. The response to this alert was evaluated between July 15, 2009 and February 19, 2010. Results. 128 unique patients had visits both prior to and following the implementation of the EMR alert. The alert was acknowledged in 58 unique patient visits. After the alert was implemented, 87/128 (68%) of the patients had documentation in their record that stress dosing was reviewed. In the visit just prior to implementation of the alert, 48/128 (38%) of the patient encounters showed written documentation of stress dose review. Conclusion. This report documents that an automated alert in the EMR can promote improved provider adherence to recommendations regarding ongoing education of patients for stress dosing of glucocorticoids. Whether this translates into better outcomes for patients remains to be seen.
International Journal of Pediatric Endocrinology 01/2010; 2010.
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Philip Zeitler
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ABSTRACT: Over the last two decades, nonautoimmune-mediated type 2 diabetes mellitus (T2DM) has become a clinical entity of increasing importance among adolescents. Yet, research specific to adolescent T2DM is in its infancy. Our understanding of the epidemiology of T2DM among adolescents is complicated by variability in definition, incomplete knowledge of novel autoimmune epitopes, the presence of individuals with phenotypic overlap between type 1 and type 2 diabetes, and inadequate understanding of the contribution of common single-gene defects. Furthermore, a higher ratio of diagnosed to undiagnosed cases and a strong relationship with the onset of puberty suggest unique aspects of the pathophysiology in adolescents. Investigators have begun to address these areas while also identifying important relationships with the intrauterine development. Well-designed clinical studies are currently examining the adolescent-specific challenges in prevention and treatment of T2DM, whereas a number of associations struggle to provide screening and treatment guidelines to practitioners based on limited understanding of the phenomenon. Finally, there is growing understanding of medium- and long-term morbidity and mortality in early adulthood. Given the likelihood that early-onset T2DM will have important implications for future public health, continued attention to all aspects of this complex social, economic, and physiological disorder is critical.
The Journal of clinical endocrinology and metabolism 08/2009; 94(7):2215-20. · 6.50 Impact Factor
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Philip Zeitler
Journal of Clinical Endocrinology & Metabolism 03/2007; 92(2):422-4. · 6.50 Impact Factor
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ABSTRACT: GHRH, in addition to stimulating the release of growth hormone (GH) from the pituitary, is a trophic factor for pituitary somatotrophs. Growth hormone-releasing hormone is also expressed in the gonads, gastrointestinal tract, pancreas, thymus, and lymphocytes, as well as in tumors of the pancreas, lung, central nervous system, and breast. Since GHRH has mitogenic effects, we examined the hypothesis that GHRH is an autocrine/paracrine growth factor in neoplastic breast tissue. The effect of disrupting endogenous GHRH on cell growth and apoptosis of MDA231 cells was examined through the use of a competitive GHRH antagonist, [N-acetyl-Tyr1, D-Arg2] fragment 1-29Amide (GHRHa). Cell proliferation was determined by direct cell counting and tritiated thymidine incorporation. Apoptosis was analyzed by examination of DNA laddering and nuclear condensation. GHRHa resulted in a dose-dependent, transient, and reversible decrease in cell number, proliferation rate, and tritiated thymidine uptake. Conversely, GHRHa led to a marked and dose-dependent increase in both DNA laddering and nuclear condensation. These results indicate that disruption of endogenous GHRH action in MDA231 cells results in both decreased cellular proliferation and increased apoptosis. Taken together, the findings suggest that endogenous GHRH acts as an autocrine/paracrine factor in the regulation of growth of at least some breast cancer cell types.
Endocrine 07/2002; 18(1):85-90. · 1.42 Impact Factor
