Dipartment of Medicine

Slides:



Advertisements
Similar presentations
Group on Scientific Research into ME: Neuroendocrinology of CFS/ME Dr Anthony Cleare Reader, Kings College London, Institute of Psychiatry.
Advertisements

Chapter 85 Chapter 85 Parathyroid Hormone Treatment for Osteoporosis Copyright © 2013 Elsevier Inc. All rights reserved.
Addison’s, Cushing’s & Acromegaly
Calcium & phosphor disturbance CKD- MBD Dr. Atapour.
Clinical case 2003… A 30 year-old woman…...admitted to our hospital due to obesity and diabetes mellitus...
Is my thyroid making me fat? Justin Moore, MD, FACP Division Chief, Endocrinology and Metabolism Medical Director, Via Christi Weight Management.
Adrenal Gland.
VITAMEN D DEFICIENCY IN SAUDI ARABIA THE SILENT EPIDEMIC
OLSON, M.L., ET AL Vitamin D Deficiency in Obese Children an Its Relationship to Glucose Homeostasis J CLIN ENDOCRINOL METAB, 97, , 2012.
Adrenal gland. ? What is the adrenal gland The adrenal glands (also known as suprarenal glands) are the triangle-shaped and orange- colored endocrine.
Effect of Vitamin D Supplementation on Serum 25-Hydroxyvitamin D Levels in Children with Chronic Disease Primary investigators: Tania Vander Meulen, MEd,
Bone Mineral Density Testing March 29, Introduction Osteoporosis is a systemic skeletal disorder characterized by decreased bone mass and deterioration.
Treatment. Bisphosphonates Promotes bone formation and decreases bone resorption Mechanism of Action First line treatment for osteoporosis in both men.
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 60 Drugs for Disorders of the Adrenal Cortex.
Testosterone  Testosterone is a steroid hormone from the androgen group.  It is synthesized in the testes of males, the ovaries of females, and the adrenal.
Adrenal Insufficiency UNC Internal Medicine Morning Report June 28, 2010 Edward L. Barnes, MD.
1 Ipriflavone in the Treatment of Postmenopausal Osteoporosis Randomized placebo-controlled, 4-year study conducted Europe 475 postmenopausal white women,
A Comparison of the Effectiveness of Estrogen-Progesterone and Estrogen-Testosterone Combination Therapies in the Prevention of Osteoporosis in Postmenopausal.
The Adrenal Cortex. Basic principles of steroid endocrinology Steroid effects fall into 3 categories: –Mineralocorticoid –Glucocorticoid –Androgen/Estrogen.
Adrenal Insufficiency
END ‘Hot topic’ DHEAS miraculous potion or snake oil? © Dr S Nussey &  IOS.
Glucocorticoid-Induced Osteoporosis (GIO) Nguyen Thy Khue, MD, PhD Department of Endocrinology, HoChiMinh City University of Medicine and Pharmacy.
Some Current Issues in the Management of Prostate Cancer Suman Chatterjee MD.
OLSON, M.L., ET AL Vitamin D Deficiency in Obese Children an Its Relationship to Glucose Homeostasis J Clin Endocrinol Metab, 97, , 2012.
Pulmonary-Allergy Drugs Advisory Committee January 17, FLOVENT ® DISKUS ® NDA , S004 GlaxoSmithKline Pulmonary-Allergy Drugs Advisory Committee.
Human Physiology Endocrine Glands Chapter 8. Hypothalamus and Pituitary A 50 year-old and has a pituitary tumor that produces excess amounts of growth.
A Double-Blind, Randomized, Placebo-Controlled Trial of High- Dose Vitamin D Therapy on Musculoskeletal Pain and Bone Mineral Density in Anastrozole- Treated.
+ This lecture was conducted during the Nephrology Unit Grand Ground by Medical Student rotated under Nephrology Division under the supervision and administration.
OLSON, M.L., ET AL Vitamin D Deficiency in Obese Children an Its Relationship to Glucose Homeostasis J Clin Endocrinol Metab, 97, , 2012.
Endocrine Physiology The Adrenal Gland 2
Osteoporosis. Introduction  The word comes from osteon which means bone and porosis means holes.  The bone is made up of protein and calcium. The protein.
Adrenal insufficiency. Objectives At the end of this lecture, the student should be able to: Define adrenal insufficiency Recognize the causes of adrenal.
Weekly Alendronate Safe and Effective at Increasing Bone Mineral Density in HIV-Infected Persons on Antiretroviral Therapy Slideset on: McComsey GA, Kendall.
HYPOTHYROIDISM. INTRODUCTION  Hypothyroidism is defined as a deficiency in thyroid hormone secretion and action that produces a variety of clinical signs.
Steroid Therapy.
Introduction Addison’s Disease is a rare and chronic disease that is characterized by adrenal insufficiency There is a decrease in hormones in the adrenal.
Chapter ?? 23 Osteoporosis Nichols and Pavlovic C H A P T E R.
Osteopenia and Osteoporosis
Date of download: 9/17/2016 From: Dose Response to Vitamin D Supplementation in Postmenopausal Women: A Randomized Trial Ann Intern Med. 2012;156(6):
ADULT GROWTH HORMONE DEFICIENCY
Osteopenia in Sheehan’s Syndrome
Long-term follow up of patients with craniopharyngioma
Bill Lynch The St George Hospital Sydney
Acute Adrenal Insufficiency
x-squared= p= /10 patients had no pathology results
Therapeutic Implications
GLYPICAN-4 LEVELS IN RELATION WITH HORMONAL AND METABOLIC PROFILE IN PATIENTS WITH POLYCYSTIC OVARY SYNDROME Doç.Dr.Özlem ALTINKAYA.
Aromatase inhibitor-associated bone loss in breast cancer patients is distinct from postmenopausal osteoporosis  Peyman Hadji  Critical Reviews in Oncology.
Hypothyroidism management
Neal B, et al. Diabetes Care 2015;38:403–411
Advances in Vitamin D Therapeutics in CF Trang Le, M. D
Figure 1. TAK-448 structure (A) and effect on the hypothalamic-pituitary-gonadal axis (B). At the normal physiological state, GnRH pulses in the hypothalamus.
Presenter : For : Dr. Dhananjay Gupta API-DSC 2016
Figure 1. Height distribution for adults with AIS.
DISEASES OF THE ENDOCRINE SYSTEM SUPRARENAL GLAND
Managing Addison’s Disease
Relative Adrenal Insufficiency
Osteoporosis in Individuals with Spinal Cord Injury
Case for androgens Giorgio Arnaldi Clinica di Endocrinologia
Diabetes and Bone: the model of GIO
Primary Hyperparathyroidism and Bone
Adrenal Insufficiency (AI) in the Septic Patient
Shannon D. Sullivan, M. D. , Philip M. Sarrel, M. D. , Lawrence M
RAC-OST-POL Study population based Polish epidemiological study on postmenopausal osteoporosis prof. dr hab. n. med. Wojciech Pluskiewicz Medical University.
Potential diagnostic utility of intermittent administration of short-acting gonadotropin- releasing hormone agonist in gonadotropin deficiency  Carrie.
Major Hormone Secreting Glands of the Endocrine System
Diagnosis of Cortisol deficiency
Algorithm based on the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of polymyalgia.
Clinical responses to therapy from baseline to week 24 and end point with last observation carried forward (LOCF). Clinical responses to therapy from baseline.
Figure 1. Relative risks of vertebral, hip, and nonvertebral fractures (and 95% CIs) in response to the treatments for ... Figure 1. Relative risks of.
Presentation transcript:

Dipartment of Medicine Case for Addison’s disease and glucocorticoid replacement Alberto Falorni Dipartment of Medicine University of Perugia Conflict of interest: SANOFI VIROPHARMA Srl

Definition and forms of adrenal insufficiency (AI) Two main forms:1,2 Primary AI (Addison’s disease) Secondary AI (Hypopituitarism) Caused by adrenal gland destruction or dysfunction Prevalence: 93–140 per million Peak age at diagnosis: 4th decade Deficit in glucocorticoid and mineralocorticoid Caused primarily by hypothalamic/pituitary tumours Prevalence: 150–280 per million Peak age at diagnosis: 6th decade Deficit in glucocorticoid (not mineralocorticoid) May have multiple pituitary hormone deficiencies3 Tertiary/temporary AI may occur after a prolonged period of endogenous or exogenous pharmaceutical glucocorticoid exposure1 Arlt W. In: Harrison’s Principles of Internal Medicine, 18th ed. 2012. Chapter 342, pp. 2940–2961 Artl W and Allolio B. Lancet 2003;361:1881–1893 Regal M et al. Clin Endocrinol 2001;55:735–740 2 2

Recommended therapeutic approach to primary adrenal insufficiency Glucocorticoid replacement Immediate-release hydrocortisone dosing: Start on 15–25 mg hydrocortisone per 24 hours Administer in 2 or 3 divided doses Administer ⅔ or ½ the dose, respectively, immediately after waking Once-daily modified-release hydrocortisone dosing: Dose based on clinical response, 20–40 mg/day Administer once daily in the morning Mineralocorticoid replacement Not required if hydrocortisone dose is >50 mg per 24 hours Dosing: Start on 100 μg fludrocortisone as a single dose immediately after waking Optimised doses usually 50–250 μg/day Adrenal androgen replacement Consider in: Patients with impaired well-being and mood despite optimised glucocorticoid/ mineralocorticoid replacement therapy Women with symptoms and signs of androgen deficiency Dosing: DHEA 25–50 mg as a single morning dose In women, also consider transdermal testosterone

Late afternoon/evening peaks and troughs 2 Immediate-release hydrocortisone tablet TID1 90% CI healthy volunteers2 Elevated late afternoon or evening levels have been associated with: Alterations in glucose tolerance and insulin sensitivity3 Coronary artery calcification4 00.00 06.00 12.00 18.00 24.00 Clock time Figure derived from Johannsson et al. and healthy volunteer data based on Vgontzas AN et al. 1. Johannsson G et al. J Clin Endocrinol Metab 2012;97:473–481; 2. Vgontzas AN et al. J Clin Endocrinol Metab 2001;86:3787–3794; 3. Plat L et al. J Clin Endocrinol Metab 1999;84:3082–3092; 4. Matthews K et al. Psychos Med 2006;68:657–661; 4. García-Borreguero D et al. J Clin Endocrinol Metab 2000;85:4201–4206.

Potential negative outcomes associated with classical substitutive therapy of adrenal insufficiency Classical substitutive therapy with glucocorticoids Premature mortality High frequency of infections/ hospitalization Reduced well-being and quality of life Altered metabolic profile Reduced bone mineral density HIGHLY CONTROVERSIAL ?? Bergthorsdottir et al. JCEM 2006, Smans LCCJ et al. ECE 2011, Hahner et al. JCEM 2007, Filipsson et al. JCEM 2007, Zelissen et al. Ann Intern Med 1994; Lövås et al EJE 2009 5 5

Improved Serum Cortisol Profile with Dual-Release HC tablet Cortisol conc. (nM) Dual-release HC tablet 800 Immediate release hydrocortisone tablet 0-24 h (8 AM-8 AM) Total exposure 19% lower on Dual-release than TID 0-4 h (8 AM-12.00) Morning exposure 6% higher on Dual-release than TID 4-12 h (12.00-8 PM) Afternoon and early evening exposure 38% lower on Dual-release than TID 12-24 h (8 PM-8AM) Night exposure 41% lower on Dual-release than TID 600 400 200 00.00 06.00 12.00 18.00 24.00 Clock time Johannsson G et al. J Clin Endocrinol Metab 2012;97:473–481

ADDISON’S DISEASE and OSTEOPOROSIS: a controversial issue

MORBO DI ADDISON E OSTEOPOROSI: UN RAPPORTO CONTROVERSO

BMD and ADDISON’S DISEASE BMD males BMD females Devolagear et al. 1987 33 NS ↓ Florkowski et al. 1994 14 Zelissen et al. 1994 91 Valero et al. 1994 30 Braatvedt et al. 1999 29 Jodar et al. 2003 25 Arlt et al. 2006 15 Gurnell et al. 2008 100 Løvås et al. 2009 292 Koetz et al. 2012 86

Coefficients of Correlation between Bone Mineral Density and Plasma Concentrations of Androgens and Follicle-stimulating Hormone in Women with Addison Disease*. Coefficients of Correlation between Bone Mineral Density and Plasma Concentrations of Androgens and Follicle-stimulating Hormone in Women with Addison Disease* Zelissen P M J et al. Ann Intern Med 1994;120:207-210 ©1994 by American College of Physicians

Mean change in BMD in 100 Addison patients treated for 12 months with DHEA-supplementation or placebo Baseline: Lumbar spine: 39% males osteopenic 39% females “ 7% males osteoporotic 5% females “ Femoral neck: 39% females “ 2% females osteoporotic Gurnell M et al JCEM 2008

Bone Mineral Density in patients with long-term treated Addison’s disease (n=25 patients) Jodar et al Clinical Endocrinology 2003

JCEM 2012

BMD Z-scores in Addison’s disease patients from Norway (n=187) and UK and New Zealand (n=105) Løvås et al EJE 2009

Correlation of corticosteroid dose and duration of Addison’s disease with BMD (n=29 patients) Braatvedt et al Osteoporosis Internat 1999

Correlation between weight-adjusted glucocorticoid dose and femoral neck Z-scores in Norwegian patients Løvås et al EJE 2009

Z-score lumbar spine Z-score femoral neck Total males females Total males females T-score lumbar spine T-score femoral neck Box-plot of BMD Z-score and T-score subdivided according to gender in 73 pz with Addison’s disease (in treatment with 15-30 mg/d HC) Total males females Total males females

Correlation between disease duration and femoral or lumbar BMD Z-score Z-score lumbar spine Z-score femoral neck Disease duration (yrs) Disease duration (yrs) Correlation between disease duration and femoral or lumbar BMD Z-score

Follow-up of lumbar and femoral Z-score in patients with no specific treatment Z-score lumbar spine Z-score femoral neck Duration of follow- up (yrs) Duration of follow- up (yrs)

Follow-up of lumbar and femoral Z-score in patients for whom a BMD analysis was available since the first year after diagnosis Z-score femoral neck Z-score lumbar spine Duration of follow- up (yrs) Duration of follow- up (yrs)

Correlation between femoral Z-score and corrected daily dose of hydrocortisone in Addison patients Z-score femoral neck MALES Z-score femoral neck FEMALES Hydrocortisone (mg/kg/d) Hydrocortisone (mg/kg/d)

In our cohort of patients… baseline concentrations of 25OH-vitamin D were 18,65 ng/ml (range 4-57,99) with no significant differences between females (median 18,35, range 4-27,63) and males (median 22,12 range 7,51-57,99)

Recommended therapeutic approach to primary adrenal insufficiency Glucocorticoid replacement Immediate-release hydrocortisone dosing: Start on 15–25 mg hydrocortisone per 24 hours Administer in 2 or 3 divided doses Administer ⅔ or ½ the dose, respectively, immediately after waking Once-daily modified-release hydrocortisone dosing: Dose based on clinical response, 20–40 mg/day Administer once daily in the morning Mineralocorticoid replacement Not required if hydrocortisone dose is >50 mg per 24 hours Dosing: Start on 100 μg fludrocortisone as a single dose immediately after waking Optimised doses usually 50–250 μg/day Adrenal androgen replacement Consider in: Patients with impaired well-being and mood despite optimised glucocorticoid/ mineralocorticoid replacement therapy Women with symptoms and signs of androgen deficiency Dosing: DHEA 25–50 mg as a single morning dose In women, also consider transdermal testosterone + Cholecalciferol 25.000 UI every two weeks

In summary…. Most of studies indicate that patients with Addison’s disease have a significant lower BMD than expected If HC 15-30 mg/d treatment is carried on: 1. BMD is not influenced by disease duration and is not affected by treatment during the follow-up 2. High doses of HC (and other synthetic glucocorticoids) may reduce BMD 3. In our cohort almost every AD patient had a vitamin D deficiency 4. Loss of BMD seems to be more related to AD per se than to HC treatment 5. Causes of BMD loss in AD patients include: a. Cortisol deficiency b. Asthenia and reduced physical activity c. Anorexia and body weight loss d. Vitamin D deficiency e. Hyponatremia f. DHEA deficiency 6. No significant differences were observed between patients with isolated AD and patients with APS II