DOCSLIB.ORG

How to Manage Steroid Diabetes in the Patient with Cancer David S

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
How to Manage Steroid Diabetes in the Patient with Cancer David S HOW WE DO IT How to Manage Steroid Diabetes in the Patient With Cancer David S. Oyer, MD, FACE, Ajul Shah, BS, and Susan Bettenhausen, APRN, CDE lucocorticosteroids (steroids) have profound perglycemic nonketotic hyperosmolar coma may effects on glucose metabolism, particularly even ensue. Increased steroid levels are not the G on postprandial hyperglycemia. Patients with only factor promoting diabetes in cancer patients; Dr. Oyer is Assistant cancer often receive steroids as a component of infection, inactivity, emotional stress, intravenous Professor of Clinical Medicine, Division their chemotherapy, as a measure to treat or pre- glucose, and high carbohydrate diets also increase of Endocrinology, vent nausea, or as adjuvant therapy following neu- the tendency toward hyperglycemia. Feinberg School of rosurgical procedures. The oncology caregiver may Multiple reviews have emphasized the impor- Medicine, Northwestern not notice steroid-induced hyperglycemia, either tance of intensive insulin therapy in hospitalized University, Chicago, Illinois. Mr. Shah is a 2–5 because it is not considered or because steroids af- patients, and several studies reinforce the im- medical student, the fect post-meal glucose much more so than morning portance of tight glucose control in this patient University of Texas fasting sugars. A recent study suggests that even a population. Furnary et al1,6,7 showed that aggres- Southwestern Medical School, Dallas. Ms. few days of hyperglycemia have deleterious effects sive control of postoperative blood glucose levels Bettenhausen is a 1 on the immune system. The current trend for in diabetic patients who had undergone a coronary Clinical Nurse Specialist maintaining near-euglycemia in hospitalized pa- artery bypass graft reduced sternal wound infec- and Certified Diabetes tients is the use of intensive insulin therapy in hy- tions and also improved morbidity and mortality. Educator, Associates in Internal Medicine, perglycemic patients with or without diabetes. This The Diabetes Mellitus, Insulin-Glucose Infusion Ltd., Chicago, Illinois. article will discuss steroid effects on glucose metab- in Acute Myocardial Infarction (DIGAMI) study8 olism, recommend levels at which therapy should showed that, compared with conventional therapy, be considered, and discuss the options available for 48 hours of tight glucose control in patients with treating hyperglycemia caused by steroids. At this acute myocardial infarction reduced mortality. time, there are no official guidelines for the cancer The Van den Berghe study9 may be relevant to patient with steroid diabetes, but the guidelines for steroid-induced hyperglycemic patients, since the diabetes care in general will be reviewed. study population consisted largely of patients in the intensive care unit (ICU) not known to be dia- Pathophysiology betic who developed hyperglycemia in the hospital. Steroids induce a state of relative insulin re- This response may have been related to the infused sistance. Steroid effects on glucose metabolism glucose and the stress-induced endogenous steroid include down-regulation of glucose transporter 4 production. Patients who had a glucose reading (GLUT-4) in the muscle so that more insulin is above 110 mg/dL were randomized to receive in- needed for the uptake of glucose into cells. Ste- tensive insulin therapy or conventional therapy. roids may also promote glucose production in the Patients in the intensive insulin group received in- liver, reduce binding of insulin to the insulin recep- sulin infusions set to reduce their glucose level to tor on cells, and decrease insulin secretion from 80–110 mg/dL, whereas those in the conventional the islet cell. In patients known to have diabetes, therapy group received insulin treatment only if the steroids will worsen the hyperglycemia, whereas glucose level went above 215 mg/dL and mainte- non-diabetic patients, depending on the state of nance of glucose at a level between 180 and 200 their islet cell reserve, may experience hyperglyce- mg/dL. The final glucose averages of the intensive mia or even overt diabetes. In rare instances, hy- and conventional groups were 103 mg/dL and 153 mg/dL, respectively. The benefits of tight glucose control in the intensive insulin group included a re- Correspondence to: David S. Oyer, MD, 211 E. Chicago Av- enue, Suite 1050, Chicago, IL 60611; telephone: (312) 944- duction in overall mortality, particularly in patients 6677; fax: (312) 944-3346; e-mail: [email protected] who remained in the ICU > 5 days, and a reduced J Support Oncol 2006;4:479–483 © 2006 Elsevier Inc. All rights reserved. risk of sepsis, transfusions, renal failure, and ICU VOLUME 4, NUMBER 9 ■ OCTOBER 2006 www.SupportiveOncology.net 479 Steroid Diabetes in the Patient With Cancer glucose levels; the most sensitive time to test for hypergly- Table 1 cemia is 2 hours after lunch. The normal range for fasting Preparations of Glucocorticosteroids glucose is below 100 mg/dL, and the normal level for the GLUCOCORTICOID MINERALOCORTICOID 2-hour postprandial reading is below 140 mg/dL. Diabetic PREPARATION POTENCY EFFECT HALF-LIFE levels are 127 mg/dL or more for fasting glucose and 200 mg/ Cortisone 1.0 ++ 4–6 h dL or more for the 2-hour postprandial level. Glucose values Prednisone 4.0 + 6–12 h between 100 and 126 mg/dL represent impaired fasting glu- Methylprednisolone 4.8 +/– 6–12 h cose, and postprandial glucose levels of 141–199 mg/dL rep- Dexamethasone 20.0 0 1–2 d resent impaired glucose tolerance. There is no way to predict whether glucose values will return to normal after cessation of steroids, since steroids may have unmasked a pre-exist- neuropathy. ing tendency toward diabetes. Current glucose monitors for In a more recent study, Van den Berghe et al10 achieved home use are accurate to within ± 10%, and there are few reduced morbidity, but not reduced mortality, using an in- drugs that interfere with the current monitoring strips. Se- tensive insulin therapy protocol in a medical ICU (MICU). vere anemia may cause false meter readings. A1C testing is Mortality was reduced only in those in the MICU for longer not indicated to monitor short-term hyperglycemia, since it than 3 days. Hyperglycemic patients not known to be diabetic represents a 90-day summation of all the glucose variations suffered greater morbidity from hyperglycemia than known but should be done at least once whenever hyperglycemia diabetics with the same degree of hyperglycemia. A 2005 is noted. A high A1C would indicate undetected previous study11 showed less morbidity postoperatively if the glucose diabetes. It should be noted that the A1C test is only valid was controlled during surgery to a level < 140 mg/dL by in- if the life of the red cell is normal; in transfused or anemic sulin infusions compared with a control group that averaged patients, false low A1C readings may be seen. 180 mg/dL during surgery. In all of these studies, insulin was used for glycemic control, so it is unknown if the benefits re- When to Treat sult from the lower glucose or possibly from direct effects of For outpatients with only a few days of mild steroid hy- the insulin itself.12,13 In vitro studies have shown that insulin perglycemia, therapy may not be needed. Treatment would can reduce many of the factors elicited in stress and infection, require patients to learn to test their glucose, take pills, or such as nuclear-factor kappa B,14 and these factors may be as give insulin, all with no proven benefit. In the hospital, how- important in the cancer patient as they are in the ICU patient, ever, this type of management is possible and should be con- which is one reason to prefer insulin therapy over oral therapy. sidered for even brief episodes of hyperglycemia. If the patient The aforementioned studies were all performed on inpatients, has only a few days of steroid therapy, and hyperglycemia is so we can only assume that outpatients might benefit as well. not causing symptoms, no therapy is indicated. However, pa- There is no proof that the benefits of intensive glucose control tients in the hospital for 3 days or more with a fasting glucose will extrapolate to hyperglycemic cancer patients on steroids, level over 110 mg/dL or a postprandial glucose level over 140 and prospective studies targeting this group are needed. mg/dL would be candidates for therapy. Preparations of Glucocorticosteroids Options for Therapy Steroid diabetes is related to the dose of steroids used but The first steps in the management of steroid diabetes are diet not the type. Insulin resistance causes primarily postprandial and exercise. The appropriate diet is low in carbohydrates to hyperglycemia. This causal relationship is particularly evident minimize postprandial hyperglycemia, but if the cancer patient with morning doses of prednisone and could be partially related has anorexia or cachexia, limiting the choices of food is not de- to the steroid effect wearing off overnight, but the improvement sirable. In these cases, nutritional consultation is recommended. in glucose overnight is also seen with the longer-acting dexa- Avoidance of other medications that may promote hyperglyce- methasone. A typical patient will have elevated glucose values mia, such as hydrochlorothiazide (> 12.5 mg/d), niacin, and after breakfast, lunch, dinner, and at bedtime but will have a some selective serotonin reuptake inhibitors, might be helpful. significant drop toward normal glucose overnight. Therefore, hyperglycemia is greatest 1–2 hours after a meal, with persis- ORAL AGENTS tent elevation until the following meal, followed by a return to The role of oral agents in the oncology patient with steroid normal between 4:00 am and 7:00 am. Table 1 shows different diabetes is limited because of potential side effects, slow onset preparations of glucocorticosteroids; it is not clear that the hy- of action, and lack of flexibility. Oral secretagogues (Table 2) perglycemic effects will differ despite the different half-lives.
Load more

Recommended publications
  • Safety and Efficacy of Metformin for Therapy-Induced Hyperglycemia in Children with Acute Lymphoblastic Leukemia
    ORIGINAL ARTICLE Safety and Efficacy of Metformin for Therapy-induced Hyperglycemia in Children With Acute Lymphoblastic Leukemia Bruce Bostrom, MD,* Priya Uppal, BA,* Julie Chu, MD,* Yoav Messinger, MD,* Laura Gandrud, MD,w and Robert McEvoy, MDw insulin secretion in response to hyperglycemia and possibly Background: Hyperglycemia during corticosteroid and aspar- reduced number of insulin receptors from asparaginase.2,3 aginase therapy for acute lymphoblastic leukemia is a significant Treatment with either single agent corticosteroids or sin- side effect that is usually treated with insulin. Metformin is an oral gle agent asparaginase causes significant hyperglycemia in antidiabetic biguanide that may cause metabolic acidosis and liver about 1% of patients and the combination synergistically enzyme abnormalities of possible concern in patients receiving chemotherapy. increases glucose intolerance. Risk factors for hyperglycemia included age over 10 years, Down syndrome, obesity, and a Procedure: We reviewed patients with acute lymphoblastic leuke- family history of diabetes mellitus. The frequency of hyper- mia treated with corticosteroids and asparaginase who received glycemia increases when there is >1 risk factor.1 Pui et al metformin for control of hyperglycemia. observed hyperglycemia during remission induction in 41 Results: Seventeen patients received metformin, including 4 who (9.7%) of 421 pediatric patients who received the combination received insulin before starting metformin therapy. Twelve were of prednisone and asparaginase for ALL.4 In 39 of the 41 treated during initial induction therapy and 5 during relapse rein- patients, hyperglycemia developed within a week of the first duction. Corticosteroids included dexamethasone in 11, prednisone dose of asparaginase. Koltin et al5 observed a 15.7% incidence in 5, and megesterol in 1.
    [Show full text]
  • Feline Diabetes Mellitus
    Feline diabetes mellitus Aspects on epidemiology and pathogenesis Malin Öhlund Faculty of Veterinary Medicine and Animal Science Department of Clinical Sciences Uppsala Doctoral thesis Swedish University of Agricultural Sciences Uppsala 2017 Acta Universitatis agriculturae Sueciae 2017:88 Cover: Portrait of a cat and a rat (Photo: S. Yuliia, photo ID 601890158, Shutterstock) ISSN 1652-6880 ISBN (print version) 978-91-7760-066-4 ISBN (electronic version) 978-91-7760-067-1 © 2017 Malin Öhlund, Uppsala Print: SLU Service/Repro, Uppsala 2017 Feline diabetes mellitus. Aspects on epidemiology and pathogenesis Abstract Feline diabetes mellitus (DM) is strikingly similar to human type 2 diabetes. Cats and humans share many risk factors for the disease, including an association with insulin resistance coupled to obesity and a sedentary lifestyle. There are also pathophysiological resemblances, with β-cell loss and amyloid deposition in the islets of Langerhans in the pancreas. In people, ethnicity has been associated with an increased risk of DM, and in cats, a breed predisposition has been identified, with the Burmese breed at increased risk. The aims of this thesis were to identify risk factors for DM in cats and to increase under- standing of disease pathogenesis. We used insurance data from Agria Pet Insurance to determine the general incidence of DM in Swedish cats, and the incidence in relation to age, sex and breed. We found that incidence rates peaked when cats were 13 years old. Male cats developed DM twice as often as female cats. The Burmese breed, along with the Russian Blue, Abyssinian, and Norwegian Forest cat breeds, showed an increased risk of DM, while several breeds showed a lower risk.
    [Show full text]
  • 11Β-HSD1 Plays a Critical Role in Trabecular Bone Loss Associated with Systemic Glucocorticoid Therapy C
    Fenton et al. Arthritis Research & Therapy (2019) 21:188 https://doi.org/10.1186/s13075-019-1972-1 RESEARCH ARTICLE Open Access 11β-HSD1 plays a critical role in trabecular bone loss associated with systemic glucocorticoid therapy C. G. Fenton1,2, C. L. Doig1, S. Fareed2, A. Naylor1, A. P. Morrell3, O. Addison4,5, C. Wehmeyer1, C. D. Buckley1, M. S. Cooper6, G. G. Lavery2, K. Raza1,7 and R. S. Hardy1,2* Abstract Background: Despite their efficacy in the treatment of chronic inflammation, the prolonged application of therapeutic glucocorticoids (GCs) is limited by significant systemic side effects including glucocorticoid-induced osteoporosis (GIOP). 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a bi-directional enzyme that primarily activates GCs in vivo, regulating tissue-specific exposure to active GC. We aimed to determine the contribution of 11β-HSD1 to GIOP. Methods: Wild type (WT) and 11β-HSD1 knockout (KO) mice were treated with corticosterone (100 μg/ml, 0.66% ethanol) or vehicle (0.66% ethanol) in drinking water over 4 weeks (six animals per group). Bone parameters were assessed by micro-CT, sub-micron absorption tomography and serum markers of bone metabolism. Osteoblast and osteoclast gene expression was assessed by quantitative RT-PCR. Results: Wild type mice receiving corticosterone developed marked trabecular bone loss with reduced bone volume to tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N). Histomorphometric analysis revealed a dramatic reduction in osteoblast numbers. This was matched by a significant reduction in the serum marker of osteoblast bone formation P1NP and gene expression of the osteoblast markers Alp and Bglap.In contrast, 11β-HSD1 KO mice receiving corticosterone demonstrated almost complete protection from trabecular bone loss, with partial protection from the decrease in osteoblast numbers and markers of bone formation relative to WT counterparts receiving corticosterone.
    [Show full text]
  • Steroid Induced Diabetes Mellitus in Patients Receiving Prednisolone for Haematological Disorders
    Steroid induced diabetes mellitus in patients receiving prednisolone for haematological disorders Kotila TR1, Olutogun T1, *Ipadeola A2 1. Department of Haematology, College of Medicine, University of Ibadan, Ibadan, Nigeria 2. Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria Abstract Introduction: Steroids are a useful component of combination chemotherapy or as a single agent in the treatment of haematological disorders even though there are adverse effects associated with its use. Methods: We report four patients who developed diabetes mellitus (DM) during treatment with steroids for haematological disorders despite a negative history of DM. Results: The mean age of the patients was 55yrs and DM was diagnosed by fasting plasma glucose (FPG) after a cumulative steroid dose of 500-1800mg. Conclusion: It is necessary to have a baseline and frequent FPG in patients who are considered for combination chemotherapy which include steroid since the development of DM does not appear to be dose dependent or related to history of DM in the patient or family. Key words: Steroid, Diabetes Mellitus, Haematological malignancy, Chemotherapy, Adverse effect African Health Sciences 2013; 13(3): 842 - 844 http://dx.doi.org/10.4314/ahs.v13i3.45 Introduction Combination chemotherapy is useful in the glucose tolerance, there are reports on these adverse management of haematological malignancies and this effects in its use in the treatment of many disease evolved from the use of single agents in order to conditions4-6 but we are not aware of any report on overcome drug resistance. Attention was drawn to the side effects of steroids in combination the benefit of steroids in the treatment of lymphoid chemotherapy for haematological disorders.
    [Show full text]
  • Systemic Corticosteroid Therapy—Side Evects and Their Management
    704 Br J Ophthalmol 1998;82:704–708 PERSPECTIVE Br J Ophthalmol: first published as 10.1136/bjo.82.6.704 on 1 June 1998. Downloaded from Systemic corticosteroid therapy—side eVects and their management Rosalyn M Stanbury, Elizabeth M Graham Corticosteroids have been used in ophthalmology for Haematological almost 50 years. Hench, in 1949,1 was the first to report on Polycythaemia is a feature of Cushing’s syndrome but does the beneficial eVects of ACTH and cortisone. His work not appear to be a feature of corticosteroid therapy. was with rheumatoid arthritis and since 1929 he had The total white blood count is increased in patients on noticed that rheumatoid arthritis improved in pregnancy corticosteroids. The various classes of white blood cells are and jaundice. He conjectured that an adrenal hormone aVected in the following ways: might be the common agent causing this improvement. In + Polymorphonuclear leucocytes increased 1948 he managed to acquire the necessary hormones and + Lymphocytes decreased; T cells are reduced to a greater found clinical improvement in the rheumatoid arthritis and extent than B cells although immunoglobulin synthesis a reduction of the erythrocyte sedimentation rate on treat- is also decreased4 ment with the hormones and relapse when they were + Monocytes decreased stopped. His article concluded that theoretically these + Eosinophils decreased agents may be of benefit in other conditions which can be Corticosteroid use promotes blood coagulation and relieved by pregnancy and jaundice. Very soon after this alters the patient’s response to anticoagulants and hence steroids were used, both systemically and topically, to treat frequent checks on the extent of anticoagulation are neces- inflammation of the eye.
    [Show full text]
  • Reversal of Corticosteroid-Induced Diabetes Mellitis with Supplemental Chromium
    L Reversal of corticosteroid-induced diabetes mellitis with supplemental chromium A. Ravina*, L. Slezak*, N. Mirsky*, N. A. Bryden² and R. A. Anderson² Abstract *Department of Diabetes, The Linn Clinic, Haifa, Aims To determine if the stress of corticosteroid treatment increases chromium Department of, Biology, Oranim University of (Cr) losses and if corticosteroid-induced diabetes (steroid diabetes) can be reversed Haifa, Israel by supplemental chromium. ² Nutrient Requirements and Functions Laboratory, Beltsville Human Nutrition Research Methods The effects of corticosteroid treatment on chromium losses of 13 patients Center, Beltsville, MD, USA 2 days prior to steroid administration and the ®rst 3 days following treatment were determined. Since steroid-induced diabetes was associated with increased Received 20 May 1998; revised 3 August 1998; accepted 18 August 1998 chromium losses and insuf®cient dietary chromium is associated with glucose intolerance and diabetes, we treated three patients with steroid-induced diabetes with 600 mg per day of chromium as chromium picolinate. Results Urinary chromium losses following corticosteroid treatment increased from 155 6 28 ng/d before corticosteroid treatment to 244 6 33 ng/d in the ®rst 3 days following treatment. Chromium supplementation of patients with steroid- induced diabetes resulted in decreases in fasting blood glucose values from greater than 13.9 mmol/l (250 mg/dl) to less than 8.3 mmol/l (150 mg/dl). Hypoglycaemic drugs were also reduced 50% in all patients when given supplemental chromium. Conclusions These data demonstrate that corticosteroid treatment increases chromium losses and that steroid-induced diabetes can be reversed by chromium supplementation. Follow-up, double-blind studies are needed to con®rm these observations.
    [Show full text]
  • Incidence and Risk Factors of Steroid-Induced Diabetes in Patients with Respiratory Disease
    ORIGINAL ARTICLE Respiratory Diseases DOI: 10.3346/jkms.2011.26.2.264 • J Korean Med Sci 2011; 26: 264-267 Incidence and Risk Factors of Steroid-induced Diabetes in Patients with Respiratory Disease Seo Yun Kim1, Chul-Gyu Yoo1, Glucocorticoids are effective for treating several respiratory diseases. However, they can Chun Taeg Lee2, Hee Soon Chung3, cause hyperglycemia. This study determined the incidence and risk factors of steroid- Young Whan Kim1, Sung Koo Han1, induced diabetes mellitus (S-DM) in patients treated with glucocorticoid for respiratory Young-Soo Shim1, and Jae-Joon Yim1 diseases. A retrospective study examined patients with respiratory diseases treated with a prednisolone-equivalent glucocorticoid dose exceeding 20 mg/day for at least 4 weeks 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Lung Institute between January 2003 and December 2008. Patients whose initial random glucose level of Medical Research Center, Seoul National exceeded 200 mg/dL or who had pre-existing diabetes were excluded. S-DM was defined University College of Medicine, Seoul; 2Division of as a fasting glucose concentration exceeding 126 mg/dL or a random glucose concentration Pulmonary and Critical Care Medicine, Department exceeding 200 mg/dL at least twice after beginning steroid treatment. A total of 231 of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University Bundang patients with respiratory diseases met the inclusion criteria. Their median age was 55 yr, Hospital, Seongnam; 3Division of Pulmonary and and 139 were female. The median cumulative prednisolone-equivalent glucocorticoid dose Critical Care Medicine, Department of Internal was 4,965 mg, and the median duration of steroid treatment was 193 days.
    [Show full text]
  • Empagliflozin Compared to NPH Insulin for Steroid Diabetes
    Klarskov et al. BMC Endocrine Disorders (2020) 20:86 https://doi.org/10.1186/s12902-020-00561-0 STUDY PROTOCOL Open Access Study rationale and design of the EANITIATE study (EmpAgliflozin compared to NPH Insulin for sTeroId diAbeTEs) - a randomized, controlled, multicenter trial of safety and efficacy of treatment with empagliflozin compared with NPH-insulin in patients with newly onset diabetes following initiation of glucocorticoid treatment Carina Kirstine Klarskov1* , Helga Holm Schultz2, Frederik Persson3, Tomas Møller Christensen4, Thomas Peter Almdal5, Ole Snorgaard6, Katrine Bagge Hansen3, Ulrik Pedersen-Bjergaard1,7 and Peter Lommer Kristensen1 Abstract Background: A well-known metabolic side effect from treatment with glucocorticoids is glucocorticoid-induced diabetes mellitus (GIDM). Guidelines on the management of GIDM in hospitalized patients (in the non-critical care setting), recommend initiation of insulin therapy. The scientific basis and evidence for superiority of insulin therapy over other glucose lowering therapies is however poor and associated with episodes of both hypo- and hyperglycaemia. There is an unmet need for an easier, safe and convenient therapy for glucocorticoid-induced diabetes. Methods: EANITIATE is a Danish, open, prospective, multicenter, randomized (1:1), parallel group study in patients with new-onset diabetes following treatment with glucocorticoids (> 20 mg equivalent prednisolone dose/day) with blinded endpoint evaluation (PROBE design). Included patients are randomized to either a Sodium-Glucose- Cotransporter 2 (SGLT2) inhibitor or neutral protamin Hagedorn (NPH) insulin and followed for 30 days. Blinded (Continued on next page) * Correspondence: [email protected] 1Department of Endocrinology and Nephrology, Nordsjaellands Hospital, Dyrehavevej 29, DK-3400 Hilleroed, Denmark Full list of author information is available at the end of the article © The Author(s).
    [Show full text]
  • Adrenocortical Hormones BIMM118 Adrenocortical Hormones
    Steroid-based Drugs • Adrenocortical Hormones BIMM118 Adrenocortical Hormones Adrenal gland: • Medulla: – produces Epinephrine (stimulated by sympathetic impulse) • Cortex: – Zona glomerulosa – produces Aldosterone (stimulated by Angiotensin II and ACTH) – Zona fasciculata – produces Glucocorticoids (stimulated by ACTH = Corticotropin) – Zona reticularis – produces Androgens (physiological role unclear) BIMM118 Adrenocortical Hormones Steroid hormone synthesis: • Pregnenolone synthesis is rate-limiting step • C21 hydroxylase: – Prevents hydroxylation of C17 (-> c) => Only mineralocorticoids • C17 hydroxylase: – Hydroxylation of C17 (-> f, g) can be followed by hydroxylation of C11 and C21 (-> h, j, k) => Sex hormones and glucocorticoids • P450C17α hydroxylase: – Produces 17-Keto-steroids (-> l) => Sex hormones BIMM118 Adrenocortical Hormones Steroid hormone classification: • Progesterone: – C21 – C 3: =O – C17: -OH or =O • Mineralocorticoids: – C21 – C21: -OH – C3: =O • Glucocorticoids : – C21 – C21, C17: -OH – C 3: =O – C11: -OH or =O • Estrogens : – C18 – C17: -OH or =O – C 3: -OH • Androgens : – C19 – C17: -OH – C 3: =O BIMM118 Adrenocortical Hormones Glucocorticoids (GC): • Inhibit all phases of inflammatory reaction • Promote fetal development (lungs) • Inhibit NFκB nuclear translocation => transcription of proinflammatory mediators is prevented • Upregulate lipocortin => inhibits PLA2 => no PG and LT synthesis • Undesirable effects of increased GC: – Immune suppression – Increased glucose release (=> “steroid diabetes”) – Glucose
    [Show full text]
  • Investigation and Management of Steroid Diabetes
    Diabetes Clinical Guideline INVESTIGATION AND MANAGEMENT OF STEROID DIABETES SETTING Oxford Children’s Hospital. Oxford University Hospitals Trust FOR STAFF Clinical staff in the Paediatric Haematology/Oncology departments, and others _____________________________________________________________________________ GUIDANCE This guidance is recommended for use by staff looking after children with or at risk of Steroid Induced Diabetes, for example oncology patients. We recommend that the ward staff monitor and commence treatment according to the following guidelines, but also contact the diabetes team via the registrar (bleep 1775) to inform them of the patient details at an early stage. The diabetes specialist nurses should also be contacted to arrange teaching for the patient and family regarding injections and blood glucose (BG) monitoring (telephone 28737 or 28736). Out of hours and at weekends (but not in the middle of the night) please telephone the out of hours mobile 07823 533466. DIAGNOSING STEROID DIABETES (S-DM): There are no clear guidelines in the literature about the timing or diagnosis of S-DM. It is known that S- DM can start at any point after commencing steroid treatment, and is more likely in the first week of treatment with high-dose steroid protocols. Studies have also shown that steroids affect post-prandial BG levels more than fasting levels. It is therefore important to measure BG levels through-out the day in addition to fasting levels. RECOMMENDATIONS for DIAGNOSIS: All children on high-dose steroid treatment should have BG levels monitored. Fasting BG and pre-evening meal BG levels should be measured twice a day. If not feasible in an individual patient, glucose in the urine will indicate whether the threshold of around 10 mmol/l has been reached and after that BG levels should be monitored.
    [Show full text]
  • Serum Lipid Levels During Oral Contraceptive and Glucocorticoid Administration'
    J. clin. Path., 23, suppl. (Ass. Clin. Path.), 3, 55-61 Serum lipid levels during oral contraceptive and glucocorticoid administration' J. W. H. DOAR AND V. WYNN From the Alexander Simpson Laboratory for Metabolic Research, St Mary's Hospital Medical School, London SYNOPSIS The effects of oral contraceptives on fasting serum lipid levels have been studied longitudinally in two groups of women. One hundred and twenty-eight subjects (group A) were tested before and during therapy; 52 subjects (group B) were tested initially during therapy and again after this had been discontinued. In both groups oral contraceptive therapy was associated with significantly raised mean serum triglyceride and cholesterol levels. No relation was found between the magnitude of change of serum triglyceride levels and the nature of oestrogen-progestogen combination, age, parity, degree of obesity, family history of diabetes, or duration of therapy. A significant elevation of the mean fasting serum triglyceride level was also found in a group of 19 women receiving low-dose glucocorticoid therapy, though the percentage increase (16%) was less than that in the wemen receiving oral contra- ceptives (49 %). Studies carried out in the decade 1950-59 showed that the relative impairment of oral glucose that oestrogen therapy was associated with a tolerance commonly found during oral contra- reduction in serum cholesterol and low density ceptive therapy is 'steroid diabetes' (Wynn et al, lipoprotein levels in postmenopausal women and 1966, 1969) caused by elevation of both the free men, many of whom had ischaemic heart disease and protein-bound plasma cortisol levels (Burke, (Russ, Eder, and Barr, 1951; Oliver and Boyd, 1969).
    [Show full text]
  • Implications for Glucose Homeostasis, Insulin Resistance and Diabetes
    ARAFACHO and others Glucocorticoids and pancreatic 223:3 R49–R62 Review endocrine cells Glucocorticoid treatment and endocrine pancreas function: implications for glucose homeostasis, insulin resistance and diabetes Alex Rafacho1, Henrik Ortsa¨ter2, Angel Nadal3 and Ivan Quesada3 Correspondence 1Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina (UFSC), should be addressed 88040-900, Floriano´ polis, SC, Brazil to A Rafacho or I Quesada 2Department of Clinical Science and Education, So¨ dersjukhuset, Karolinska Institutet, SE-11883 Stockholm, Sweden Emails 3Institute of Bioengineering and the Biomedical Research Center in Diabetes and Associated Metabolic Disorders [email protected] or (CIBERDEM), Miguel Herna´ ndez University, University Avenue s/n, 03202, Elche, Spain [email protected] Abstract Glucocorticoids (GCs) are broadly prescribed for numerous pathological conditions because Key Words of their anti-inflammatory, antiallergic and immunosuppressive effects, among other " glucocorticoids actions. Nevertheless, GCs can produce undesired diabetogenic side effects through " insulin resistance interactions with the regulation of glucose homeostasis. Under conditions of excess and/or " insulin sensitivity long-term treatment, GCs can induce peripheral insulin resistance (IR) by impairing insulin " insulin secretion Journal of Endocrinology signalling, which results in reduced glucose disposal and augmented endogenous glucose " glucagon secretion production. In addition, GCs can promote abdominal obesity, elevate plasma fatty acids and " glucose tolerance triglycerides, and suppress osteocalcin synthesis in bone tissue. In response to GC-induced " diabetes peripheral IR and in an attempt to maintain normoglycaemia, pancreatic b-cells undergo several morphofunctional adaptations that result in hyperinsulinaemia. Failure of b-cells to compensate for this situation favours glucose homeostasis disruption, which can result in hyperglycaemia, particularly in susceptible individuals.
    [Show full text]