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How Does Cushing's Lead To Diabetes?

Pathophysiology Of Diabetes Mellitus In Cushing's Syndrome.

Pathophysiology Of Diabetes Mellitus In Cushing's Syndrome.

Pathophysiology of diabetes mellitus in Cushing's syndrome. Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, Naples, Italy. [email protected] Neuroendocrinology. 2010;92 Suppl 1:77-81. doi: 10.1159/000314319. Epub 2010 Sep 10. Cushing's syndrome is commonly complicated with an impairment of glucose metabolism, which is often clinically manifested as diabetes mellitus. The development of diabetes mellitus in Cushing's syndrome is both a direct and indirect consequence of glucocorticoid excess. Indeed, glucocorticoid excess induces a stimulation of gluconeogenesis in the liver as well as an inhibition of insulin sensitivity both in the liver and in the skeletal muscles, which represent the most important sites responsible for glucose metabolism. In particular, glucocorticoid excess stimulates the expression of several key enzymes involved in the process of gluconeogenesis, with a consequent increase of glucose production, and induces an impairment of insulin sensitivity either directly by interfering with the insulin receptor signaling pathway or indirectly, through the stimulation of lipolysis and proteolysis and the consequent increase of fatty acids and amino acids, which contribute to the development of insulin resistance. Moreover, the peculiar distribution of adipose tissue throughout the body, with the predominance of visceral adipose tissue, significantly contributes to the worsening of insulin resistance and the development of a metabolic syndrome, which participates in the occurrence and maintenance of the impairment of glucose tolerance. Finally, glucocorticoid excess is able to impair insulin secretion as well as act at the level of the pancreatic beta cells, where it inhibits different steps of the insulin secretion proce Continue reading >>

Hypercortisolism - Other Types Of Diabetes Mellitus - Diapedia, The Living Textbook Of Diabetes

Hypercortisolism - Other Types Of Diabetes Mellitus - Diapedia, The Living Textbook Of Diabetes

Hypercortisolism refers to a range of conditions characterised by an excess of circulating corticosteroids. Endogenous hypercortisolism is known as Cushing's syndrome, and may arise from the adrenal cortex, e.g. because of an adrenal tumour, or may be secondary to overproduction of pituitary adrenocorticotrophic hormone (ACTH). The most common cause of hypercortisolism is, however, steroid therapy. Harvey CushingCushing's syndrome was first described in 1912 when the neurosurgeon Harvey Cushing described a patient known as Minnie G. She showed all the characteristic signs and symptoms of the syndrome, including hyperglycaemia. Since cortisone and adrenocorticotrophic hormone (ACTH) were unknown at the time, Cushing suggested a polyglandular disorder. The term Cushing's syndrome was coined by Fuller Albright in 1943 to designate the consequences of overproduction of a hormone affecting carbohydrate metabolism by the adrenal cortex. [1] In 1948 Lewis Sarett synthesised cortisone, which was then widely used without understanding of its potential adverse consequences. Two years later Van Seters demonstrated that Cushing's syndrome could also be induced by chronic treatment with glucocorticoids. [2] [3] Chronic treatment with glucocorticoids is the most common cause of hypercortisolism, whereas endogenous hypercortisolism (Cushing's syndrome) is a rare disease with an incidence of 1015 per million people per year. [4] Cushing' syndrome is usually due to a pituitary adenoma and is three to five times more common in women than in men. Hypercortisolism is associated with diabetes, obesity and hypertension, and should be considered in patients with these conditions, and in all those on steroid therapy. Some 20% of patients with Cushing's syndrome have a diagnosis of diabetes, b Continue reading >>

A Big Picture Look At Cushings Disease And Diabetes

A Big Picture Look At Cushings Disease And Diabetes

There are some diseases I just despise. It’s not that I like any disease, but some just make me want to crawl in a hole. Cushings disease is one of them. Cushings is short for hyperadrenocortisism, a state where the body makes too much steroid, either from a pituitary tumor or from an adrenal tumor. The tumor can be benign or malignant, but regardless the excess steroid can wreak havoc on the pet. It’s usually a forever treatment for the life of the pet (except for the less common adrenal mass that sometimes can be surgically removed), and it’s very expensive to treat. If you think treating diabetes is expensive, you should see the bills that pile up with Cushings disease! The initial and ongoing blood tests are expensive. The medication is expensive. And the vast majority of pets affected will be a ‘Cushingoid’ for life, requiring the medication for life. You see why I despise this disease! Why am I going on about one of my least favorite diseases? Because there is a link between Cushings disease and diabetes. Cushings patients produce too much steroid. Steroids cause insulin resistance. Some diabetic pets actually became diabetic secondary to having Cushings disease from the insulin resistance caused by steroids. It is difficult to regulate a diabetic pet that is also Cushingoid. There are a few things you should know about this disease if your pet is diabetic. Cushings can affect both dogs and cats, but it is better understood and much more common in our canine friends than our feline friends. Personally, I think it is often more affordable for families to go straight to an internist rather than have their regular veterinarian diagnose and treat this disease. Additionally, treatment of this Cushingoid state can result in a crisis situation and requires very Continue reading >>

Glucocorticoids And Type 2 Diabetes: From Physiology To Pathology

Glucocorticoids And Type 2 Diabetes: From Physiology To Pathology

Journal of Nutrition and Metabolism Volume 2012 (2012), Article ID 525093, 9 pages Division of Endocrinology, Department of Medical and Surgical Science, S. Orsola-Malpighi Hospital, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, Italy Academic Editor: Peter M. Clifton Copyright © 2012 Guido Di Dalmazi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Type 2 diabetes mellitus is the result of interaction between genetic and environmental factors, leading to heterogeneous and progressive pancreatic β-cell dysfunction. Overweight and obesity are major contributors to the development of insulin resistance and impaired glucose tolerance. The inability of β cells to secrete enough insulin produces type 2 diabetes. Abnormalities in other hormones such as reduced secretion of the incretin glucagon-like peptide 1 (GLP-1), hyperglucagonemia, and raised concentrations of other counterregulatory hormones also contribute to insulin resistance, reduced insulin secretion, and hyperglycaemia in type 2 diabetes. Clinical-overt and experimental cortisol excess is associated with profound metabolic disturbances of intermediate metabolism resulting in abdominal obesity, insulin resistance, and low HDL-cholesterol levels, which can lead to diabetes. It was therefore suggested that subtle abnormalities in cortisol secretion and action are one of the missing links between insulin resistance and other features of the metabolic syndrome. The aim of this paper is to address the role of glucocorticoids on glucose homeostasis and to explain the relationship between hypercortisolism and type 2 d Continue reading >>

Management Of Hyperglycaemia In Cushings Disease: Experts Proposals On The Use Of Pasireotide - Em|consulte

Management Of Hyperglycaemia In Cushings Disease: Experts Proposals On The Use Of Pasireotide - Em|consulte

Received:3September2012; accepted:23October2012 Management of hyperglycaemia in Cushings disease: Experts proposals on the use of pasireotide Prise en charge de lhyperglycmie au cours de la maladie de Cushing: propositions dexperts pour lutilisation de pasirotide , J.Bertherat b , F.Borson-Chazot c , d , T.Brue e , P.Chanson f , C.Cortet-Rudelli g , B.Delemer h , A.Tabarin i , S.Bisot-Locard j , B.Vergs k aService endocrinologie, CHU Cte-de-Nacre, 14033 Caen, France bService des maladies endocriniennes et mtaboliques, hpital Cochin, 75014 Paris, France cHospices civils de Lyon, universit Lyon1, Lyon, France dInserm U 1052 CRCL, fdration dendocrinologie, groupement hospitalier Est, Lyon, France eService dendocrinologie, diabte et maladies mtaboliques, centre de rfrence des maladies rares dorigine hypophysaire DEFHY, CNRS, CRN2M UMR 7286, Aix-Marseille universit, hpital Timone, APHM, 13385 cedex 15 Marseille, France fService dendocrinologie et des maladies de la reproduction, hpitaux universitaires Paris-Sud, Assistance PubliqueHpitaux de Paris, 94270 Le Kremlin-Bictre, France gClinique Linquette, CHRU de Lille, 59037 Lille, France hService dendocrinologie-diabte-nutrition, hpital Robert-Debr, 51092 Reims, France iDpartement endocrinologiediabtologie et maladies mtaboliques, CHU de Bordeaux, USN du Haut-Lvque, 33604 Pessac, France jNovartis Pharma S.A.S, 92500 Rueil-Malmaison, France kService dendocrinologie, diabtologie et maladies mtaboliques, hpital du Bocage, CHU, 21000 Dijon, France Corresponding author. Tel.: +33 2 31 06 45 86; fax: +33 2 31 06 48 54. Cushings disease causes considerable morbidity and mortality, including cardiovascular, metabolic, respiratory and psychiatric complications, bone demineralization and increased susceptibility to infections. Metabolic Continue reading >>

Cushing's Syndrome - Symptoms, Causes, Diagnosis & Treatment

Cushing's Syndrome - Symptoms, Causes, Diagnosis & Treatment

Using corticosteroids is the most common cause of Cushing's syndrome Cushings syndrome is a condition in which can occur if you have high levels of the stress hormone, cortisol, in your blood. Cortisol increases our blood pressure and blood glucose levels and diabetes is one complication which can result from untreated Cushings syndrome. Physical signs of Cushings syndrome may include: Fatty tissue building up typically around the waist, upper back, between the shoulders and the face. Slim arms and legs contrasting significantly with fat deposits around your middle Striae - red or purple stretch marks, which may resemble tiger stripes, commonly found on the abdomen, near the armpits or around the breasts and thighs Women may experience thicker than normal facial and body hair (hirsutism) and missed or irregular periods. Men may experience a loss of libido , difficulty achieving erections and loss of fertility. High blood pressure and high blood glucose levels ( hyperglycemia ) may commonly be experienced with Cushings syndrome. Usage of corticosteroids is the most common cause of Cushings syndrome. Corticosteroids are used to treat illnesses including: Doctors will prescribe the lowest effective dose to reduce the likelihood of complications, such as Cushings syndrome, developing. When Cushings syndrome results from steroid usage, this is known as iatrogenic Cushings syndrome. A less common reason for Cushings syndrome developing is known as endogenous Cushings syndrome, which is caused by the development of a tumour in the pituitary gland, one of your adrenal glands or one your lungs. Talk about Cushing's Syndrome in the Diabetes Forum A tumour in the pituitary gland is the more common cause for endogenous Cushings syndrome, accounting for about 7 out of 10 cases, and Continue reading >>

I Also Was Diagnosed With Cushings Disease

I Also Was Diagnosed With Cushings Disease

I also was diagnosed with Cushings Disease I was diagnosed with type one diabetes two or three years ago. At that time they said that I had Cushings Disease also. I need to find out any information on Cushings in adults I have looked and I find it is more common in dogs. Can someone please help me?? Hi Janie001 ~ thank you for coming to our site in search of answers to your question regarding type 1 diabetes and Cushings disease.The volunteers at this site are parents of type 1 or themselves diabetic and none of us are medical professionals, simply people who collectively have many years experience dealing with this disease. I have very little knowledge of Cushings myself, so I, too, did a search and found much more on Cushings in dogs as did you.I did come across a site, though, that had a lot of good information about the syndrome; its causes, treatment and current research.The link is: I wish I had more information for you, but hopefully others will come to our site and post comments to your question.Please visit often and let us know how things are going for you.Best wishes! Continue reading >>

Cushing Syndrome Can Cause Diabetes Mellitus

Cushing Syndrome Can Cause Diabetes Mellitus

Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians . A 67-year-old woman is evaluated for a 2-day history of severe muscle weakness. The patient experienced significant weight gain and developed hypertension and type 2 diabetes mellitus 2 years ago. She also reports developing muscle weakness of the lower extremities 6 months ago. Her diabetes is only partially controlled by metformin; her blood glucose measurements at home are usually greater than 250 mg/dL (13.9 mmol/L). Other medications are hydrochlorothiazide, lisinopril, amlodipine, and metoprolol. Physical examination shows a woman who appears chronically ill. Blood pressure is 154/92 mm Hg, and other vital signs are normal; BMI is 40. Skin examination is notable for facial hirsutism. Central obesity, mild proximal muscle weakness, and 2+ peripheral edema are noted. Results of laboratory studies show a serum creatinine level of 1.3 mg/dL (115 mol/L), a plasma glucose level of 144 mg/dL (8.0 mmol/L), and a serum potassium level of 2.9 mEq/L (2.9 mmol/L). Which of the following tests should be performed to reveal the cause of her diabetes? C) Glutamic acid decarboxylase antibody titer The correct answer is E) 24-Hour urine free cortisol excretion. This item is available to MKSAP 16 subscribers as item 6 in the Endocrinology and Metabolism section. Measurement of the 24-hour excretion of urine free cortisol is the most appropriate next test in this patient to determine the cause of her diabetes mellitus. Various secondary causes of diabetes exist, most involving other endocrinopathies, effects of medications, pancreatic diseases, or genetic conditions. Cushing syndrome is one of these secondary causes of diabetes. The most common cause of Cushing syndrome i Continue reading >>

Cushing's Syndrome

Cushing's Syndrome

What is Cushing's syndrome? Cushing's syndrome is a hormonal disorder caused by prolonged exposure of the body's tissues to high levels of the hormone cortisol. Sometimes called hypercortisolism, Cushing's syndrome is relatively rare and most commonly affects adults aged 20 to 50. People who are obese and have type 2 diabetes, along with poorly controlled blood glucose-also called blood sugar-and high blood pressure, have an increased risk of developing the disorder. What are the signs and symptoms of Cushing's syndrome? Signs and symptoms of Cushing's syndrome vary, but most people with the disorder have upper body obesity, a rounded face, increased fat around the neck, and relatively slender arms and legs. Children tend to be obese with slowed growth rates. Other signs appear in the skin, which becomes fragile and thin, bruises easily, and heals poorly. Purple or pink stretch marks may appear on the abdomen, thighs, buttocks, arms, and breasts. The bones are weakened, and routine activities such as bending, lifting, or rising from a chair may lead to backaches and rib or spinal column fractures. Women with Cushing's syndrome usually have excess hair growth on their face, neck, chest, abdomen, and thighs. Their menstrual periods may become irregular or stop. Men may have decreased fertility with diminished or absent desire for sex and, sometimes, erectile dysfunction. Other common signs and symptoms include severe fatigue weak muscles high blood pressure high blood glucose increased thirst and urination irritability, anxiety, or depression a fatty hump between the shoulders Sometimes other conditions have many of the same signs as Cushing's syndrome, even though people with these disorders do not have abnormally elevated cortisol levels. For example, polycystic ovary s Continue reading >>

Diabetes In Cushing Syndrome: Basic And Clinical Aspects - Sciencedirect

Diabetes In Cushing Syndrome: Basic And Clinical Aspects - Sciencedirect

Volume 22, Issue 12 , December 2011, Pages 499-506 Author links open overlay panel GherardoMazziotti12 CarmineGazzaruso34 AndreaGiustina1 Get rights and content Diabetes mellitus is a frequent complication of Cushing syndrome (CS) which is caused by chronic exposure to glucocorticoid excess, either endogenous or exogenous, and that is characterized by several clinical symptoms such as central obesity, purple striae, proximal muscle weakness, acne, hirsutism and neuropsychological disturbances. Diabetes occurs as a consequence of an insulin-resistant state together with impaired insulin secretion which are induced by glucocorticoid excess. The management of patients with CS and diabetes mellitus includes the treatment of hyperglycemia and, when possible, the correction of glucocorticoid excess. This review focuses on the disorders of glucose metabolism in patients exposed to glucocorticoid excess, addressing both the pathophysiological aspects and the clinical and therapeutic implications. Continue reading >>

Management Of Diabetes Mellitus In Cushings Syndrome

Management Of Diabetes Mellitus In Cushings Syndrome

Management of Diabetes Mellitus in Cushings Syndrome Academic Unit of Diabetes and Endocrinology, University of Sheffield Room OU142, Floor O, Royal Hallamshire Hospital Active Cushings syndrome is associated with insulin resistance induced by the high and prolonged circulating level of glucocorticoids. In endogenous Cushings syndrome the overall incidence of diabetes mellitus and insulin resistance is very likely to be under-reported as not all patients are actively investigated with glucose tolerance tests. Whilst it is common clinical experience that management of diabetes mellitus is necessary in patients with Cushings syndrome there is a dearth of literature-based evidence to support which regimes are the most effective. Therefore, a pragmatic approach is necessary on an individualized patient basis, whereby patients are stratified according to the severity of their impaired glucose homeostasis. The most effective means of control of diabetes mellitus in a patient with active Cushings syndrome is to lower the levels of circulating cortisol. This may initially be achieved by using adrenal steroidogenesis blockade with drugs including metyrapone, ketaconazole, or, on occasion, mitotane. The rapid action of metyrapone is particularly suitable in this circumstance. Despite this, diabetes-specific therapy is often necessary and metformin and PPAR- agonists may be of use, but in the acute setting insulin therapy is frequently needed. Definitive management directed against source driving Cushings syndrome is often highly effective at either reducing the severity of diabetes, or allowing its complete resolution. Patients experiencing diabetes mellitus in the context of exogenously administered glucocorticoids may well require insulin therapy for the period that the high l Continue reading >>

Cushing's Syndrome

Cushing's Syndrome

Not to be confused with Cushing's triad, due to increased intracranial pressure. Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to cortisol.[3][8] Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, a round red face, a fat lump between the shoulders, weak muscles, weak bones, acne, and fragile skin that heals poorly.[2] Women may have more hair and irregular menstruation.[2] Occasionally there may be changes in mood, headaches, and a chronic feeling of tiredness.[2] Cushing's syndrome is caused by either excessive cortisol-like medication such as prednisone or a tumor that either produces or results in the production of excessive cortisol by the adrenal glands.[9] Cases due to a pituitary adenoma are known as Cushing's disease.[3] It is the second most common cause of Cushing's syndrome after medication.[3] A number of other tumors may also cause Cushing's.[3][10] Some of these are associated with inherited disorders such as multiple endocrine neoplasia type 1 and Carney complex.[7] Diagnosis requires a number of steps.[4] The first step is to check the medications a person takes.[4] The second step is to measure levels of cortisol in the urine, saliva or in the blood after taking dexamethasone.[4] If this test is abnormal, the cortisol may be measured late at night.[4] If the cortisol remains high, a blood test for ACTH may be done to determine if the pituitary is involved.[4] Most cases can be treated and cured.[6] If due to medications, these can often be slowly stopped.[5] If caused by a tumor, it may be treated by a combination of surgery, chemotherapy, and/or radiation.[5] If the pituitary was affected, other medications may be required to replace its lost fun Continue reading >>

Occult Cushings Syndrome In Type-2 Diabetes

Occult Cushings Syndrome In Type-2 Diabetes

Subclinical Cushings syndrome (SCS) caused by adrenal incidentalomas is frequently associated with overweight and insulin resistance. Metabolic syndrome X may therefore be a clue to the presence of CS. However, the incidence of CS in this situation remains unknown. We have conducted a prospective study to evaluate the prevalence of occult CS in overweight, type-2 diabetic patients devoided of specific clinical symptoms of CS. Two hundred overweight, type-2 diabetic patients, consecutively referred for poor metabolic control (HbA1C > 8%), were studied as inpatients. A first screening step was performed with the 1-mg overnight dexamethasone suppression test (DST) using a revised criterion for cortisol suppression (60 nmol/liter) to maximize the sensitivity of the procedure. A second confirmatory step of biochemical investigations (midnight plasma cortisol concentration, plasma cortisol circadian rhythm, morning plasma ACTH concentration, 24-h urinary free cortisol, and 4-mg iv DST) was performed in patients with impaired 1-mg DST. A third step of imaging studies was performed according to the results of second-step investigations. Fifty-two patients had impaired 1-mg DST. Among these, 47 were further evaluated. Thirty were considered as false positives of the 1-mg DST, whereas 17 displayed at least one additional biological abnormality of the hypothalamic-pituitary-adrenal axis. Definitive occult CS was identified in four patients (2% of the whole series) with Cushings disease (n = 3) and surgically proven adrenal adenoma (n = 1). Definitive diagnosis remains to be established in seven additional patients (3.5%) with mild occult CS associated with unsuppressed plasma ACTH concentrations and a unilateral adrenal tumor of 1029 mm in size showing prevalent uptake at radioch Continue reading >>

Pathophysiology Of Diabetes Mellitus In Cushings Syndrome

Pathophysiology Of Diabetes Mellitus In Cushings Syndrome

Cushings syndrome is a rare clinical entity resulting from pathologic hypercortisolemia [1]. Patients may present along a spectrum of severity from classical signs and symptoms of cortisol excess to subclinical or entirely asymptomatic disease [13]. The most common endogenous causes are ACTH-producing pituitary adenomas, cortisol-secreting adrenal adenomas, and ectopic ACTH-secreting tumors [4, 5]. Arriving at an accurate diagnosis of the underlying etiology and initiating appropriate treatment in a timely manner are essential to preventing morbidity and mortality [6, 7]. Diagnostic evaluation requires a systematic approach and significant expertise [2, 4]. Although surgery is often the primary treatment modality, multispecialty care is often necessary for optimal outcomes [8]. The hormones produced by the adrenal gland have important effects on the bone both in physiological and pathological conditions. The role of cortisol secretion on the bone physiology during growth is not fully understood. During the adult life, the degree of the cortisol secretion, still in the normal range, seems to directly correlate with the bone mineral density in elderly individuals and in osteoporotic women. The overt and subclinical cortisol excess leads to an increased risk of fracture partially independent of the bone mineral density reduction and possibly related to a reduced bone quality. The individual sensitivity to cortisol due to the different polymorphisms of the glucocorticoid receptor (GR) or of the 11-hydroxysteroid dehydrogenase may modulate the effect of glucocorticoids (GCs) on the bone, thus explaining, at least in part, the wide interindividual variability of the skeletal consequences of the hypercortisolism. The adrenal androgens excess in congenital adrenal hyperplasia Continue reading >>

When To Think Cushings Syndrome In Type 2 Diabetes

When To Think Cushings Syndrome In Type 2 Diabetes

When to think Cushings syndrome in type 2 diabetes By Bruce Jancin, Family Practice News Digital Network ESTES PARK, COLO. Diabetes mellitus, osteoporosis, and hypertension are conditions that should boost the index of suspicion that a patient with some cushingoid features may in fact have endogenous Cushing's syndrome, Dr. Michael T. McDermott said at a conference on internal medicine sponsored by the University of Colorado. An estimated 1 in 20 patients with type 2 diabetes has endogenous Cushing's syndrome. The prevalence of this form of hypercortisolism is even greater estimated at up to 11% among individuals with osteoporosis. In hypertensive patients, the figure is 1%. And among patients with an incidentally detected adrenal mass, it's 6%-9%, according to Dr. McDermott, professor of medicine and director of endocrinology and diabetes at the University of Colorado. "Endogenous Cushing's syndrome is not rare. I suspect I've seen more cases than I've diagnosed," he observed. "I've probably missed a lot because I failed to screen people, not recognizing that they had cushingoid features. Not everyone looks classic." There are three screening tests for endogenous Cushing's syndrome that all primary care physicians ought to be familiar with: the 24-hour urine cortisol test, the bedtime salivary cortisol test, and the overnight 1-mg dexamethasone suppression test. "I think if you have moderate or mild suspicion, you should use one of these tests. If you have more than moderate suspicion if a patient really looks like he or she has Cushing's syndrome then I would use at least two screening tests to rule out endogenous Cushing's syndrome," the endocrinologist continued. The patient performs the bedtime salivary cortisol test at home, obtaining samples two nights in a row Continue reading >>

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