Hypoglycemia The Major Barrier to Good Glycemic Control

Mon, 06 Jun 2011 23:47:47 +0000

Risk factors have been identified for iatrogenic hypoglycemia, and physiologic studies have revealed the mechanisms of many of these risk factors. Predictors of severe (requiring assistance) hypoglycemia identified through the DCCT include prior history of severe hypoglycemia, longer duration of diabetes, higher baseline glycosylated hemoglobin (HbA1c), and lower treatment HbA1c in type 1 diabetes. The strongest predictor of future episodes of hypoglycemia was the number of prior episodes.

Abstract:

Approximately 20.8 million Americans (14.6 million diagnosed and 6.2 million undiagnosed) have diabetes mellitus (diabetes) and in 2002 it was the sixth leading cause of death, emphasizing the need for improved treatment. However, iatrogenic hypoglycemia precludes reaching and maintaining euglycemia. During the Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS), outcomes of diabetes improved while hypoglycemia worsened with intensive therapy. The consequence was that hypoglycemia became the major obstacle to achieving the stated glycemic targets in these studies. As a result, hypoglycemia becomes a major barrier in improving outcomes in type 1 and type 2 diabetes. This has considerable financial implications as at least US$40 billion is spent each year in the US on complications of diabetes. Understanding the mechanisms and impact of hypoglycemia in diabetes is vital so that it can be addressed clinically. Furthermore, newer pharmacologic agents offer the clinician options to reduce iatrogenic hypoglycemia.

Author:

Stephen N Davis

Julia P Dunn

Edition:

US Endocrine Disease 2006 - Issue 2

The Problem of the Aggressive Pituitary Tumor

Mon, 06 Jun 2011 23:47:50 +0000

Invasion, proliferation, and metastatic ability are three ways in which tumors take root, grow, and advance. Although proliferative tumors can be invasive, and invasion is a prerequisite to metastasis, none of these qualities automatically links to the others in a given tumor.Thus, each should be considered as sufficient, but not necessary, for a tumor to qualify as aggressive.

Invasion

Abstract:

Truly aggressive pituitary tumors are uncommon, representing no more than 2% of the lesions encountered in any large pituitary clinic. Such tumors prove their atypical behavior by invading adjacent tissues, by proliferating rapidly (compared with the slow or absent growth seen in standard benign adenomas), and/or by showing metastasis to distant sites. Difficulty achieving complete removal at surgery, leading to a strong tendency to recur, is the expected result. Such tumors thus pose a challenge to surgeon and endocrinologist alike, and control rather than cure may be the more realistic therapeutic goal.

Author:

Ian E McCutcheon

Edition:

US Endocrine Disease 2006 - Issue 2

Pharmacological Treatment of Painful Diabetic Neuropathy

Mon, 06 Jun 2011 23:47:53 +0000

Stabilisation of glycaemic control is the cornerstone of neuropathy management. In the Diabetes Control and Complications Trial (DCCT), improved metabolic control achieved by intensive insulin therapy resulted in a 60% overall reduction of risk of neuropathic complications. It should be emphasised, however, that slower progression, not improvement of neuropathy, had been achieved. According to the result of the EURODIAB IDDM (insulin-dependent diabetes mellitus) Complications Study, the development and progression of neuropathy is strongly related to cardiovascular risk factors.

Abstract:

To know diabetes is to know all aspects of neuropathy."This sentence by Professor Philip Low clearly summarises the unique complexity of diabetic neuropathy. Autonomic and sensory neuropathy are progressive complications of diabetes and are associated with poor prognosis. High mortality is observed among patients with cardiac autonomic neuropathy and foot ulcers, considered to be neuropathic complications, are associated with a one-year amputation rate of 15%. Nevertheless, neuropathy is still considered to be a stepbrother among diabetic complications and often represents the unattended borderline between diabetology and neurology. Neuropathy affects approximately 30–60% of all diabetic patients, while 10–20% of patients with diabetes may have pain due to neuropathy. It should be noted that pain and loss of sensation frequently co-exist. Pain usually represents the top of the neuropathy pyramid.

Author:

Tamás Várkonyi

Peter Kempler

The Impact of Treatment of Obstructive Sleep Apnoea Syndrome on Glycaemic Control in Patients with Diabetes Mellitus

Mon, 06 Jun 2011 23:47:56 +0000

These findings suggest a significant overlap between the two diseases, but this clinic-based sample of obese patients (body mass index (BMI) 30.6±0.2) had been selected on the basis of presentation with typical symptoms of OSAS.

Abstract:

Obesity is, typically, a common feature of both type 2 diabetes mellitus and of obstructive sleep apnoea syndrome (OSAS). Thus, it seems reasonable to be suspicious of some overlap between the two disease entities. For example, in a French study, 595 males with suspected OSAS underwent both nocturnal polysomnography and a two-hour ora glucose-tolerance test. OSAS was confirmed in 494 patients; type 2 diabetes was present in 30.1% and impaired glucose tolerance (IGT) was diagnosed in 20.0% of the patients.¹

Author:

Anne-Katrin Schober

Eckhart G Hahn

Igor A Harsch

Edition:

European Endocrine Disease 2007 Issue 1

Oxidative Stress, Diabetes, and Its Complications

Mon, 06 Jun 2011 23:47:58 +0000

On this basis it is not surprising that oxidative stress has been implicated in involved in diabetic complications entails the intracellular formation of AGEs. The augmented presence of glucose inside the cell originates reactive dicarbonyl molecules such as glyoxal, methylglyoxal, and 3- deoxyglucosone, which react with the aminic groups of proteins to form AGEs. The modification process does not require the presence of an enzyme and the two-step reaction is not reversible.

Abstract:

Our evolution as complex aerobic organisms with high energy demands is tightly linked to the acquisition of mitochondria in our cells. This passage gave us the ability to use oxygen, harnessing its power in the respiratory chain, but also the fundamental function to compartmentalize this process, protecting the cytosol from its potentially harmful side effects.¹ In fact, even being scarcely reactive this molecule has the tendency to ‘radicalize,’ forming incompletely reduced molecules characterized by an uncoupled electron. This highly reactive and short-living class of molecules is known as reactive oxygen species (ROS). ROS production is a side effect of the normal metabolism of the cell, which developed a series of enzymes able to disarm them. Superoxide dismutase, catalase, and glutathione peroxidase are powerful weapons that act together with antioxidant molecules introduced with diet to protect the organism. In healthy subjects there is a balance between ROS formation and elimination. Every time this balance is lost due to an augmented production of reactive species or due to a reduction in antioxidant production or activity there is a condition of oxidative stress. Losing control of ROS is very harmful and almost all the constituents of the cell can be targets of these molecules. DNA, proteins, and lipids can be involved in chain reactions that entail their modification and, in the worst case, the loss of their functionality. Genetic degeneration and physiological dysfunction can lead to cell death and aging of the organism.

Author:

Ludovica Piconi

Antonio Ceriello

Edition:

US Endocrine Disease 2007 - Issue 1

Epidemiology and Classification of Chronic Kidney Disease and Management of Diabetic Nephropathy

Mon, 06 Jun 2011 23:48:01 +0000

The Burden of ESRD and CKD
In the UK, the incidence of ESRD has doubled over the last ten years and has now reached 101 patients per million of population (pmp).3 This is below the European and US averages of approximately 135pmp and 336pmp, respectively.4 Studies that have supplied data on the prevalence of CKD provide the opportunity to plan nephrology service requirements and develop stronger working relationships with the primary care teams in the community.

Abstract:

The number of patients with chronic kidney disease (CKD) and the subsequent need for renal replacement therapy (RRT) has reached epidemic proportion and is anticipated to rise further. Worldwide, it is estimated that over 1.1 million patients with end-stage renal disease (ESRD) currently require maintenance dialysis, and this number is increasing at a rate of 7% per year.1 If the trend continues, the number will exceed 2 million by 2010.2 This figure excludes developing countries, where there is less availability of and access to dialysis services, and is therefore an underestimate of the true demand. The most common cause of chronic renal failure is diabetic nephropathy. This article examines the epidemiology and classification of CKD and the management of diabetic nephropathy.

Author:

Althea Mahon

Investigation, Treatment and Monitoring of Late-onset Hypogonadism

Mon, 06 Jun 2011 23:48:04 +0000

Demographics clearly indicate that the population of the world is ageing, with life expectancy rapidly increasing by three months every year in the developed world. In Europe, the percentage of the population over 60 years represented approximately 20% in 2000 and will represent more than 30% in 2025. Data support the concept that testosterone levels fall progressively with age and that a significant percentage of men over the age of 60 years have serum testosterone levels that are below the lower limits.

Abstract:

Androgen deficiency in the ageing male (ADAM) has become a topic of much interest and debate. With an increasing percentage of the male population now falling into the older age bracket, the principal questions raised are whether older hypogonadal men affected by late-onset hypogonadism (LOH) will benefit from testosterone treatment and what will be the risks associated with such intervention.

Author:

Claude Schulman

Jean-Marc Kaufman

Fibrates - The Other Life-saving Lipid Drugs

Mon, 06 Jun 2011 23:48:07 +0000

However, statin-based interventions are unlikely to correct problems of triglycerides and HDL, whereas the use of fibrates has a stronger effect on the atherogenic dyslipidemia and might even produce significant LDL reduction in some patients.

Abstract:

The main controversy in the area of lipid management today is related to the usefulness of ‘non-statin’ agents to maximize cardiovascular risk reduction in particular patient types, such as those with diabetes and metabolic syndrome. Fibrate drugs, such as gemfibrozil (Lopid) and fenofibrate (TriCor), are undoubtedly the best tools to address the condition characterized by high triglycerides, low high-density lipoprotein (HDL), and small dense low-density lipoprotein (LDL) (atherogenic dyslipidemia), but the most recent guidelines from both the American Diabetes Association (ADA) and the National Cholesterol Education Panel continue to focus on LDL control as the target of therapy.

Author:

Sergio Fazio

Edition:

US Endocrine Review 2005

Inhaled InsulinA New Insulin Delivery System

c.halagiera — Wed, 04 Apr 2012 23:48:10 +0000

The inhaled insulin, Exubera^®, was recently approved for the treatment of type 1 and type 2 diabetes. This article will review the delivery systems for inhaled insulin, the kinetics of inhaled insulin, clinical trials in type 1 and type 2 diabetes, and safety considerations for inhaled insulin.

Delivery of Inhaled Insulin

Author:

Martin J Abrahamson

Laura Zemany

Edition:

US Endocrine Disease 2006

Diabetes and Depression – A Burdensome Co-morbidity

Mon, 06 Jun 2011 23:48:12 +0000

In clinical care settings this means that out of 100 patients with diabetes, approximately 11–12 meet the diagnostic criteria for clinical depression and another 20 have mild or subthreshold depression. Thus, approximately every third patient with diabetes is affected by depression or elevated depressive symptoms. The reasons for this close association between diabetes and depression are not yet fully understood. Below we will discuss three possible explanations. First, diabetes could be a consequence of depression.

Abstract:

Diabetes and Depression
Depression is a frequent co-morbid condition in people with diabetes. A meta-analysis of 42 studies demonstrated that 31% of patients with diabetes described themselves as having elevated depressive symptoms compared with 14% of those without diabetes. A clinical depression diagnosis based on standardised criteria defined by the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) or the Diagnostic and Statistical Manual of Mental Disorders (DSM IV) occurred in 11.4% of patients with diabetes, whereas the prevalence in people without diabetes was 5%.¹

Author:

Norbert Hermanns

Bernhard Kulzer

Edition:

European Endocrinology Volume 4 Issue 2

Advances in the Diagnosis and Management of Differentiated Thyroid Cancer

Mon, 06 Jun 2011 23:48:15 +0000

Despite an increasing incidence, the mortality from thyroid cancer in general and from papillary thyroid cancer in particular remained stable (0.5 deaths per 100,000 in both 1973 and 2002).¹

Abstract:

The incidence of thyroid cancer (mainly differentiated) is one of the most rapidly increasing among human cancers, at least in the US.¹This phenomenon is mainly due to an increase in the papillary histotype, which showed a 2.9-fold increase per year. The increase is attributable to better detection of small papillary carcinomas as a result of improved diagnostic accuracy (neck ultrasound and fine-needle aspiration cytology [FNAC]). It is a common experience in thyroid cancer referral centres that nearly 60–80% of thyroid carcinomas detected nowadays are micropapillary thyroid carcinomas (less than 1cm in size) carrying an excellent long-term prognosis.^2,3

Author:

Grazia Castagna Maria

Brilli Lucia

Pacini Furio

Edition:

US Endocrinology Volume 4 Issue 2

Dilemmas Associated with Hormone Therapy for Post-menopausal Women

Mon, 06 Jun 2011 23:48:19 +0000

The most effective treatment is estrogen, which may be given alone to women without a uterus or combined with a progestogen in women with a uterus. As with any medicine, these hormone treatments are not trouble-free, but alternatives such as herbal remedies, natural foods, and neuroactive drugs are less effective. Given that estrogen with or without progestogen is the best therapy, the challenge lies in finding ways to optimize the benefits and minimize the risks of hormone treatment.

Optimizing the Benefits—When and What to Prescribe

Abstract:

More than 50% of women going through the menopause experience hot flashes, which may cause sleep disturbances and lethargy. The symptoms are due to estrogen deficiency, which may also cause urogenital atrophy and vaginal dryness. In 25% of women, symptoms of the menopause are severe enough to seek relief. In women who do not undergo treatment, the proportion with hot flashes decreases to about 30% within three years.¹

Author:

Collins John

Edition:

US Endocrinology Volume 4 Issue 1

The Management of Post-prandial Glucose

Mon, 06 Jun 2011 23:48:21 +0000

Post-prandial blood glucose levels are generally <120mg/dl in healthy nondiabetic subjects and rarely exceed 140mg/dl, which reflects the World Health Organization (WHO) definition.² Post-prandial hyperglycemia is defined as a plasma glucose level exceeding 140mg/dl.³ Development of post-prandial hyperglycemia coincides with an impairment or absence of the first-phase insulin response, a decrease in insulin sensitivity in the peripheral tissues, and decreased suppression of hepatic glucose output after meals due to insulin deficiency.⁴Post-prandial hyperglycem

Abstract:

Recently there has been considerable debate regarding the importance of post-prandial glucose (PPG) levels in patients with diabetes. Previously, therapeutic intervention focused on optimizing overall glycemic control as assessed by glycated hemoglobin (HbA_1c) levels, with a strong emphasis on fasting plasma glucose (FPG). There was concern in some quarters that setting PPG goals could be unrealistic and even unsafe because they carry an increased risk for hypoglycemia.1 However, a growing body of evidence suggests that reducing PPG is as important, or even more important, for achieving HbA_1c goals.

Author:

Antonio Ceriello

Edition:

US Endocrinology Volume 4 Issue 2

La Glucemia y el Peso Corporal en la Diabetes Tipo 2: ¿Son éstos Objetivos de Tratamiento Compatibles?

Mon, 06 Jun 2011 23:48:24 +0000

La Importancia de Controlar el Peso en la Diabetes Tipo 2

Abstract:

Author:

David Russell-Jones

Familial Isolated Pituitary Adenomas

Mon, 06 Jun 2011 23:48:27 +0000

Pituitary adenomas are common intracranial tumours, and clinically relevant pituitary adenomas have been estimated to occur in about one in every 1,000 of the population. The vast majority of these adenomas are sporadic; however, there is increasing recognition that pituitary adenomas may also occur in a familial setting, and a recent estimate suggests that 5% of pituitary adenomas are familial in origin. Familial pituitary adenomas can form part of the classic syndromes of multiple endocrine neoplasia type 1 (MEN1) and Carney complex.

Abstract:

Abstract
Over the last century several families have been described with familial isolated pituitary adenomas (FIPAs). Most commonly, family members have acromegaly or prolactinoma, but other types of pituitary adenomas can also occur. Recently, mutations in the AIP (aryl hydrocarbon receptor interacting protein) gene have been found to occur in 30–50% of FIPA patients, while for the rest of the patients the gene causing the disease is currently unknown and is a topic of intense research. Tumours in patients with AIP mutations are diagnosed at significantly younger ages and tend to be larger. Often the response to medical therapy in these patients is poor. This article discusses the clinical and genetic characteristics of this relatively recently recognised disease.

Keywords
Pituitary tumour, familial disease, AIP, tumour suppressor gene

Disclosure: The authors have no conflicts of interest to declare.
Acknowledgements: We are very grateful for the helpful advice on the manuscript from one of our patients with familial isolated pituitary adenoma.
Received: 25 April 2009 Accepted: 6 July 2009
Correspondence: Márta Korbonits, Department of Endocrinology, Barts and The London School of Medicine and Dentistry, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, UK. E: m.korbonits@qmul.ac.uk

Author:

VK Ajith Kumar

Márta Korbonits

Harvinder S Chahal

Edition:

US Endocrinology - Volume 5

Children and Diabetes—The Second Campaign Year, No Time to Lose

Mon, 06 Jun 2011 23:48:30 +0000

Celebrated every year on November 14, World Diabetes Day is now an official UN World Health Day as a result of the successful Unite for Diabetes campaign. This year sees the second of a two-year World Diabetes Day campaign. The theme for the 2008 campaign is ‘Diabetes in Children and Adolescents.’ In this article, we explain why children are the focus of the campaign and what can be done to change the lives of all of those, particularly children, who are living with diabetes.

Diabetes Is Different for Children

Author:

Henk-Jan Aanstoot

Edition:

US Endocrinology Volume 4 Issue 1

Advances in Our Understanding of Pituitary Adenoma

Mon, 06 Jun 2011 23:48:33 +0000

Pituitary adenomas are common benign monoclonal neoplasms— accounting for 15% of intracranial neoplasms—that may be clinically silent or secrete anterior pituitary hormones such as prolactin, growth hormone (GH), adrenocorticotrophic hormone (ACTH), or, rarely, thyroid-stimulating hormone (TSH) or gonadotrophins.

Author:

Sandra Pekic

Vera Popovic-Brkic

Edition:

US Endocrinology Volume 4 Issue 1

Doing More with What We Already Know—Prevention and Improved Coverage of Healthcare for Diabetes

Mon, 06 Jun 2011 23:48:35 +0000

The International Diabetes Federation (IDF) launched the fourth edition of the IDF Diabetes Atlas at its 20th World Diabetes Congress in Montreal, Canada in October 2009.¹ Based on conservative modeling assumptions, this edition estimates that the global prevalence of diabetes in 2010 has risen to 285 million people, representing 6.6% of the world's adult population. Far from being a condition of higher-income countries, 70% of those with diabetes live in low- and middle-income countries.

Abstract:

Abstract
Diabetes now affects 285 million people, representing 6.6% of the world’s adult population. It disproportionately affects the developing world, with four of five people with diabetes living in low- and middle-income countries (LMCs). Diabetes is expected to cost the world at least $376 billion (11.6% of total healthcare expenditure) in 2010, according to the IDF Diabetes Atlas. This means that LMCs will also bear the economic brunt of the disease, which affects far more people of working age than previously believed. In many of these countries, essentials for good basic care for diabetes are scarce. The International Diabetes Federation (IDF) believes that where care for diabetes is scarce or limited, improving the coverage of prevention measures and basic care for diabetes will improve outcomes and quality of life. Good basic care can be highly cost-effective or even cost-saving. Even if costs are higher, the number of people affected by diabetes is now so large that it is no longer acceptable to ignore it.

Author:

David Whiting

Edition:

European Endocrinology - Volume 6

Osteoporosis in Men

Mon, 06 Jun 2011 23:46:31 +0000

But a decade ago, endocrinologist Sundeep Khosla, M.D., made another profound discovery: Estrogen regulates bone metabolism in men as well as women. Moreover, declining estrogen levels can lead to osteoporosis in aging men just as in postmenopausal women. [J. Clin. Invest. (2000)106(12), 1553-1560]. Dr. Khosla’s finding that men need estradiol, the primary form of estrogen, drew attention to male osteoporosis.

Abstract:

When it comes to bones and what makes them break, Mayo Clinic researchers have a habit of shattering conventional wisdom. It was Mayo investigators who, in the early 1970s, first identified osteoporosis as a preventable and treatable disorder, not an inevitable consequence of aging. Subsequent osteoporosis research focused on women and estrogen, the hormone that regulates female bone metabolism. Testosterone, the primary male sex hormone, was assumed to regulate bone metabolism in men.

Non-alcoholic Fatty Liver Disease in Children

Mon, 06 Jun 2011 23:48:40 +0000

Since non-alcoholic fatty liver disease (NAFLD) was first described in children in the early 1980s by Moran and colleagues,¹ a number of case series have been reported. Awareness of the disease has been growing among healthcare providers in the last few years, and nowadays NAFLD represents the most common cause of chronic liver disease in youth.

Abstract:

Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of paediatric liver disease. It is the hepatic component of the metabolic syndrome (MetS), being almost always associated with obesity and insulin resistance, and frequently with abnormal triglyceride and/or cholesterol levels, abnormal blood pressure and impaired glucose tolerance. Its increasing prevalence among children and adolescents has been attributed to the obesity epidemic and the modern western lifestyle, with excessive consumption of refined carbohydrates and saturated fats in combination with low levels of physical activity. Key questions need to be answered concerning the potential progression of NAFLD towards more severe forms of liver derangement, the worth of performing biopsies in children with suspected NAFLD and the role played by the disease in promoting and anticipating the onset of cardiovascular disease (CVD) at an unexpectedly early age. The clinical relevance of these questions is undoubted, as NAFLD may cause significantly increased morbidity and mortality in adulthood.

Keywords
Insulin resistance (IR), metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), paediatric obesity

Disclosure: The author has no conflicts of interest to declare.
Received: 12 May 2009 Accepted: 17 August 2009 Citation: European Endocrinology, 2010;6(1):60–63
Correspondence: Melania Manco, Scientific Directorate, ‘Bambino Gesù’ Children’s Hospital, S Onofrio 4 Square, 00165 Rome, Italy. E: melaniamanco@tiscali.it

Author:

Melania Manco

Edition:

European Endocrinology - Volume 6

Advances in the Understanding of Adult Growth Hormone Deficiency Syndrome – Diagnosis, Epidemiology and Management

Mon, 06 Jun 2011 23:48:43 +0000

Growth hormone (GH) therapy was introduced in the 1950s, but the initial GH preparations extracted from human cadaver pituitaries were reserved the treatment of GH deficiency (GHD) children.¹ Since 1985, only recombinant DNA-derived biosynthetic human GH free from, for example, Creutzfeldt-Jakob prions has been used.²

Abstract:

Abstract
In patients with hypopituitarism, growth hormone (GH) deficiency is almost always present. Lack of other pituitary hormones may require prompt replacement, but lack of GH is also associated with several abnormalities, which can be improved by GH treatment. The aberrations include low bone mass and increased risk of fractures, abnormal body composition, e.g. increased fat mass and reduced lean body mass resulting in reduced muscle mass and strength. Decreased exercise capacity may be influenced by impaired cardiac performance and heat intolerance. Increased abdominal fat results in metabolic disturbancies, such as reduced insulin sensitivity and hyperlipidaemia, increasing the risk of cardiovascular diseases. Patients with hypopituitarism replaced with relevant hormones except GH have increased mortality due to cardiovascular diseases and increased morbidity. Thus, it is important to diagnose GH deficiency, which requires precise diagnostic criteria and methods. Dynamic testing of GH secretion with an insulin tolerance test or arginine plus GH-releasing hormone can be used.

Keywords
Growth hormone, growth hormone deficiency, hypopituitarism, diagnosis, epidemiology

Disclosure: The author has no conflicts of interest to declare.
Received: 6 August 2010 Accepted: 20 September 2010 Citation: European Endocrinology, 2010;6(2):45–50
Correspondence: Torben Laursen, Department of Pharmacology, Bartholin Building, Vilhelm Meyers allé 4, University of Aarhus, DK-8000 Aarhus C, Denmark. E: tl@farm.au.dk

Author:

Torben Laursen

Edition:

European Endocrinology - Volume 6 Issue 2

Specialty Drugs for the Treatment of Short Stature in Children— Pros, Cons, and Perspectives for the Future

Mon, 06 Jun 2011 23:48:46 +0000

Specialty Drugs— Evolving Terminology and Context

Abstract:

Abstract
Specialty drugs are generally defined as medications that involve special drug handling and/or parenteral administration and are typically used to treat complex medical conditions. They are typically biologicals, often very expensive, and generally prescribed by specialists. The recent surge in use of specialty pharmaceuticals has placed these drugs in the spotlight as policy-makers struggle to contain healthcare costs. Specialty drugs are central to discussions about optimal ways to manage childhood short stature; recombinant human growth hormone (rhGH) and recombinant human insulin-like growth factor-1 (rhIGF-1)—specialty drugs with annual prices of $20,000 to $30,000 per child—are available to treat childhood short stature from specific causes. rhGH and rhIGF-1 revolutionized treatment of severe short stature resulting from growth hormone deficiency and growth hormone insensitivity, respectively. Over the past 20 years, use of rhGH has expanded to other conditions. Expanded use of the newer rhIGF-1 may occur in an analogous manner. This article reviews the background, current status, and potential for these drugs in view of current evidence and policies.

Keywords
Growth hormone (GH), insulin-like growth factor-1 (IGF-1), specialty drugs, biologicals, short stature

Disclosure: The authors have no conflicts of interest to declare.
Acknowledgement: This work was supported in part by grants from the NIH and an award by the Rainbow Babies and Children’s Hospital Foundation.
Received: October 1, 2010 Accepted: November 5, 2010 Citation: US Endocrinology, 2010;6:78–83
Correspondence: Michaela B Koontz, MD, Division of Pediatric Endocrinology, Diabetes, and Metabolism, Rainbow Babies and Children’s Hospital, Room 737, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, Ohio 44106. E: michaela.koontz@uhhospitals.org

Author:

Michaela B Koontz

Leona Cuttler

Edition:

US Endocrinology - Volume 6

Advances in the Evaluation and Treatment of Osteoporosis— Is There an Optimal Regimen?

charmaine.kisting — Wed, 26 Oct 2011 20:36:07 +0000

Osteoporosis is skeletal disorder characterized by microarchitectural deterioration of bone and compromised bone strength, which predisposes to fractures.¹ It is estimated that 33.6 million Americans have bone loss, and of these 10 million have established osteoporosis.² At an annual rate of 1.5 million fractures, the incidence of vertebral fractures is greater than that of breast cancer, stroke, and heart attack.^2–4 The majority of afflicted persons are women, who have a 50% risk for fracture throughout their lifetime.⁵ However, approximately 20% of

Author:

Pauline M Camacho

Edition:

US Endocrinology Volume 4 Issue 1

Antioxidants, Diabetes, and Endothelial Dysfunction

charmaine.kisting — Tue, 08 Nov 2011 07:29:17 +0000

A substantial amount of evidence has demonstrated that diabetes is highly associated with oxidative stress and endothelial dysfunction.^1–3 It is also well recognised that endothelial dysfunction, which is present even in people at risk of developing diabetes, is strongly connected with oxidative stress and considered as a preliminary risk factor for the development of atherosclerosis and cardiovascular disease.^4,5

Author:

John Doupis

Aristidis Veves

Edition:

US Endocrine Disease 2007 - Issue 2

Familial Isolated Pituitary Adenomas

charmaine.kisting — Tue, 08 Nov 2011 19:56:11 +0000

Abstract:

Author:

VK Ajith Kumar

Márta Korbonits

Harvinder S Chahal

Edition:

European Endocrinology - Volume 5

Introduction of New Recombinant Insulin-like Growth Factor - Current and Future Perspectives

charmaine.kisting — Wed, 16 Nov 2011 18:32:46 +0000

The past 50 years have seen extraordinary developments, from the somatomedin hypothesis¹ to a broad understanding of the insulin-like growth factor (IGF) system with its varied components and diverse actions.² At the centre of the system is IGF-1, the insulin-like peptide with major effects on metabolism and cellular function.

Author:

Michael B Ranke

Edition:

European Endocrinology Volume 4

Advances in Our Understanding of Hyperthyroidism-associated Bone Loss

charmaine.kisting — Fri, 18 Nov 2011 13:57:02 +0000

Hyperthyroidism is an important cause of secondary osteoporosis²and the relationship between the hypothalamic–pituitary– thyroid (HPT) axis and bone is an important factor to consider in the management of sub-clinical hyperthyroidism and differentiated thyroid cancer. This article discusses animal models that provide insight into the underlying mechanisms that result in hyperthyroidism-associated bone loss. It will then review the clinical data investigating effects of hyperthyroidism on the skeleton.

Abstract:

Osteoporosis is characterised by low bone mass and deterioration of bone micro-architecture associated with increased bone fragility and susceptibility to fracture. In 2005 the incidence of osteoporotic fracture in the US was over two million, at a cost of nearly US$17 billion. By 2025, annual fractures and costs are projected to rise by almost 50%, making this a major healthcare priority.¹

Author:

Jane Brassill Mary

R Williams Graham

Edition:

European Endocrinology Volume 4 Issue 2

Thyroid Nodules—Management Dilemmas and Theraputic Considerations

charmaine.kisting — Fri, 18 Nov 2011 18:32:06 +0000

Thyroid nodules are very common in clinical practice, with an overall prevalence that varies from 4% by palpation to 67% by ultrasonography. The annual incidence by palpation has been estimated at 0.09% by the Framingham study,¹ which translates into approximately 300,000 new nodules in the US in 2005. Despite their high frequency, only a small fraction (~5%) of thyroid nodules harbor cancer. Because only malignant or large, symptomatic nodules will require surgical excision, a systematic approach to their evaluation is important to avoid unnecessary surgery.

Author:

M Regina Castro

Edition:

US Endocrine Review 2005

No More Heart Disease— Addressing Major Modifiable Risk Factors in Type 2 Diabetes

lata.ravichander — Tue, 20 Mar 2012 14:20:30 +0000

Individuals with diabetes have twice the incident myocardial infarction (MI) rate as the general population, and survival rates are lower among individuals with diabetes once they have an adverse cardiovascular event.¹ Women with diabetes and cardiovascular disease (CVD), regardless of menopausal status, have a four- to sixfold increase in the risk of developing CVD, whereas men with diabetes have a two- to threefold increased risk of CVD compared to women and men without diabetes.² Women with diabetes also have poorer prognosis after an MI, have higher risk of death from

Abstract:

Cardiovascular disease (CVD) is the leading cause of death among people with type 2 diabetes, yet much of the population remains unaware of the risk. People with diabetes are two to four times more likely to develop CVD due to a variety of risk factors. Large studies have shown that 85–90 % of patients with CVD have one or more of the traditional modifiable risk factors. Important modifiable risk factors include obesity, physical exercise, nutritional factors, alcohol consumption, tobacco smoking, vitamin D, psychosocial factors, dyslipidemia, hypertension, albuminuria, and dysglycemia. This article will review the impact that each of these modifiable factors has on CVD risk. The importance of aspirin therapy will also be addressed in light of the results of a number of studies that failed to demonstrate a convincing cardioprotective benefit of low-dose aspirin in patients with type 2 diabetes. Gene polymorphisms are also emerging as important contributors to CVD development, but will not be addressed in this article.

Author:

Claude K Lardinois

Edition:

US Endocrinology - Volume 7

Rituximab for the Treatment of Graves’ Orbitopathy

lata.ravichander — Tue, 20 Mar 2012 16:26:32 +0000

Functions of B Cells and Their Role in Autoimmune Disease

Abstract:

The contribution of B-cells to human autoimmune disease has recently been underscored because of the therapeutic benefit of B-cell depleting therapies. B-cells are involved in the production of autoantibodies, and in CD4+ T-cell activation, control of T-cell function, and inflammation through cytokine production. B-cells are also important antigen-presenting cells. Rituximab (RTX) has been used off-label in various autoimmune disorders and has been shown to effectively deplete mature and memory CD20+ B-cells, but not long-lived plasma cells. The rationale behind the use of RTX in Graves’ disease (GD) and Graves’ orbitopathy (GO) relies on its putative effect on pathogenic autoantibodies causing hyperthyroidism. RTX in patients with active GO has been shown to have a significant effect on the inflammatory activity and severity of GO. However, caution is suggested before proposing RTX as a novel therapeutic tool in this disease until randomized controlled trials are available. Should preliminary observations be confirmed, an optimal strategy for controlling the progression of GO would be to pursue B-cell depletion shortly after diagnosis, rather than only as an alternative therapeutic option when standard immunosuppression has failed.

Author:

Mario Salvi

Guia Vannucchi

Paolo Beck-Peccoz

Edition:

US Endocrinology - Volume 7 Issue 2