Clinical Anatomy_ Applied Anatomy for Students and Junior Doct.pdf

Grant’s Dissector.pdf

ANESTHESIOLOGY
Barash Clinical Anesthesia 5th ed.pdf
Miller’s Anesthesia.pdf

BIOCHEMISTRY
Harper’s illustrated biochemistry 26ed.pdf
Harper’s illustrated biochemistry 27th edition.chm
Color Atlas of Biochemistry 2nd Ed J.Koolman K-H. Roehm Thieme 2005.pdf

CARDIOLOGY
ABC of Interventional Cardiology.pdf
Advanced Interventional Cardiology.pdf
Gulizia – Emerging Pathologies in Cardiology.pdf
Cannon – Critical Pathways in Cardiology 2001.pdb
Cardiology cd.exe
Wagner – Marriott’s Practical Electrocardiography 10th ed.pdb

CLINICAL EPIDEMIOLOGY
Basic Epidemiology – Beaglehole , Bonita.pdf
Clinical_Epidemiology__Robert_Fletcher.pdf
Pinciples of Epidemiology, An Introduction to Applied

evidence_base_of_clinical_diagnosis.pdf

Evidence-Based Imaging – Optimizing Imaging in Patient Care.pdf

Evidence-based Medicine Workbook.pdf

Evidence Based Practice in Primary Care [ILLUSTRATED].pdf

DERMATOLOGY
Atlas of Dermatology Schering Co USAss.pdf
Fitzpatrick – Dermatology 5th ed 2005.CHM
Fitzpatrick’s Dermatology In General Medicine 6th ed.pdb
Hall – Sauer’s Manual of Skin Diseases 8th ed.pdb

Handbook of Skin Diseases.pdf

EMERGENCY MEDICINE & ICU
Wolfson – The Clinical Practice of Emergency Medicine 3rd ed.pdb
Pediatric Emergency Medicine. (a comperhensive study guide). 2nd eition,2007.CHM
An Introduction to Clinical Emergency Medicine.pdf
Cline – Emergency Medicine – A Comprehensive Study
Intensive and Critical Care Medicine.pdf
Irwin and Rippe’s Intensive Care Medicine 5th ed.pdb
Noble – Textbook of Primary Care Medicine 3rd ed
Field Guide to Bedside Diagnosis, 2e 2006.CHM.part
Rosen’s Emergency Medicine.chm

ENDOCRINOLOGY
Williams Textbook of Endocrinology 10ed.pdf
Handbook of Diagnostic Endocrinology.pdf

FAMILY MEDICINE & GERIATRICS
CURRENT Diagnosis & Treatment in Family Medicine.chm
Evans – Oxford Textbook of Geriatric Medicine.pdb
Geriatric Medicine An Evidence-based Approach.pdf

HEMATOLOGY & IMMUNOLOGY
Modern Hematology Biology and Clinical Management 2nd ed.pdf
Oxford Handbook of Hematology.pdf
Color Atlas of Hematology.pdf
Wintrobe’s Clinical Hematology 11th.pdb
Adelman – Manual of Allergy and Immunology Diagnosis.pdb
World of Microbiology and Immunology.pdf
HISTOLOGY
Histology Image Review.CHM
Junqueira Carneiro – Basic Histology Text and Atlas 11ed.chm
Kuehnel – color atlas of cytology, histology and microscopic anatomy.pdf

INTERNAL MEDICINE

Harrison’s principles of internal medicine 17ed.chm
Harrison’s principles of internal medicine 16ed.pdf
Harrison_s_Manual_of_Medicine_16th_Edition.pdf
Cecil – Textbook of Medicine.pdf
Kelly’s Textbook of Medicine.pdb
Mayo Clinic Internal Medicine Concise Textbook.pdf
Lippincott.Wilkins.&.Williams.Yamada’s.Textbook.of.Gastroenterology.pdf
Schrier – Manual of Nephrology Diagnosis and Therapy 5th ed.pdb
Bates guide to physical examination+MCQs.pdf

Clinical Interviewing.pdf

Clinical Medicine – 6th edition.pdf

LR – Pocket Medicine 3rd Edition.pdf

Problem Solving in Clinical Medicine.pdf

MICROBIOLOGY
Jawetz, Melnick, & Adelberg’s Medical Microbiology, 24th Ed 2007 McGraw Hill.chm
Laboratory Exercises In Microbiology.pdf
Clinical Microbiology made simple.pdf
The Desk Encyclopedia Microbiology.pdf
Lippincott Illustrated Reviews_Microbiology
Essential Microbiology.pdf
Glazer Microbial Biotechnology – Fundamentals of Applied Microbiology 2nd ed.pdf

World of Microbiology and Immunology.pdf

NEUROANATOMY & NEUROLOGY
Snell’s clinical neuroanatomy
Neuroanatomy An Atlas of Structures, Sections, and Systems – Duane E. Haines.pdf
Adams and Victor’s Principles of Neurology 8th.pdf
Atlas of functional neuroanatomy 2nd ed.pdf

Cranial Nerves Functional Anatomy (2005).pdf

Differential Diagnosis in Neurology and Neurosurgery.pdf

Goetz textbook of neurology.pdb
The Clinical Science of Neurologic Rehabilitation (Contemporary Neurology Series, 66) (2003).pdf
Neuroanatomy – Atlas of Structures Sections Systems 6ed.pdf
Neuroscience – D.Purves, et al.pdf
Merritt – Merritt’s Neurology 10th Ed.pdb
Handbook of Neurology.CHM

Nervous System and Sensory Organs – Color Atlas and Textbook of Human Anatomy – Volume 3.pdf

OBSTETRICS-GYNECOLOGY
Benson Pernolls Handbook of Obstetrics-Gynecology.pdf
Williams Obstetrics 22nd Edition.pdf
Berek & Novak’s Gynecology 14th ed.pdf
Novak’s Gynecology 13ed.pdb
Obstetrics And Gynecology At A Glance.pdf
Stenchever – Comprehensive Gynecology 4th ed – Big Images.pdb
Havens – Manual of Outpatient Gynecology 4ed.pdb
The Johns Hopkins Manual of Gynecology and Obstetrics 2nd ed.pdb

Obstetrics and Gynecology An Illustrated Colour Text.pdf

ONCOLOGY

Weinstein Pediatric Oncology – Pediatric_Lymphomas.pdf

Manual of Pediatric Hematology and Oncology.pdf

Berek Practical Gynecologic Oncology 3ed.pdb

Rosenberg – Cancer – Principles and Practice of Oncology 6th.pdb

Pizzo – Principles and Practice of Pediatric Oncology 4th Ed.pdb

ORTHOPEDICS & RHEUMATOLOGY
MILLER’S_REVIEW_OF_ORTHOPEDICS.pdf
Manual of Rheumatology and Outpatient Orthopedic Disorders Diagnosis and Therapy 4th ed.pdb
Kelley’s Textbook of Rheumatology 6th Edition, 2-Volume Set – ISBN.pdb
DeLee and Drez’s – Orthopaedic Sports Medicine. Editor DeLee (2nd Ed. 2003).pdb
Current Diagnosis & Treatment in Orthopedics 3rd ed.pdb

Pediatric Orthopedics for Primary Care Physicians.pdf

Pediatric Orthopedics in Practice.pdf

PARASITOLOGY
Gillespie & Pearson – Principles and Practice of Clinical Parasitology 2001
Clinical Parasitology.pdf
Dictionary of Parasitology.pdf

PATHOLOGY
Robbins Pathologic Basis of Disease 7th ed 2005.pdf
stedmans Pathology&Lab medicine
Scott_Tietz’s Applied Laboratory Medicine 2nd ed.pdf
Ravel – Clinical Laboratory Medicine – Clinical Applications.pdb

PATHOPHYSIOLOGY OF DISEASE.pdf

PEDIATRICS
Nelson Textbook of Pediatrics 17th ed.pdf
Nelson Essentials of PEDIATRICS.CHM
Current Strategies in Pediatrics 2004.pdf

Pediatric.Musculoskeletal.Disease.pdf

Pediatric.Radiography.3HAXAP.pdf

Treatment.of.Pediatric.Neurologic.Disorders.3HAXAP.pdf

PHARMACOLOGY
Katzung basic clinical pharmacology 10ed.pdf
Katzung basic clinical pharmacology 9ed.pdf
Basic Clinical Pharmacology – 10th Ed.chm
Color Atlas of Pharmacology 3rdEd.pdf

Color Atlas of Pharmacology.pdf
Color Atlas Of Pharmacology,2Nd Ed (By H Lullmann Et Al ,Thieme 2000,Isbn 0865778434).pdf
Lippincott Illustrated Reviews_Pharmacology 2nd ed 2000
Edwards – Principles and Practice of Pharmaceutical Medicine 2nd ed.pdf
Goodman Gilman’s – The Pharmacological Basis of Therapeutics 11th Edition

PHYSIOLOGY
Review of Medical Physiology 21 Edition -William F. Ganong.chm
Physiology – Berne and Levy – 5th Edition.chm
physiology – Guyton.pdf

PSYCHIATRY
Kaplan & Sadock’s Comprehensive Textbook of Psychiatry (2 Volume Set) 7th Ed (Lippincott Williams & Wilkins).pdf
Lewis – Child and Adolescent Psychiatry A Comprehensive Textbook 4th Edition

RADIOLOGY
Dahnert – radiology review manual 4th ed.pdf
Getting Started in Clinical Radiology – from Image to Diagnosis.pdf
Emergency Radiology.pdf
WHO manuals of diagnostic imaging – Radiographic Anatomy and Interpretation of the Musculoskeletal System.pdf
Churchill Livingstone – 2001 – Grainger & Allison’s Diagnostic Radiology. A Textbook of Medical I.pdb

SURGERY
Schwartz Manual of Surgery 8ed.pdf
Oxford Textbook of Surgery (2ed).pdf
Clinical Surgery in General R.M.Kirk 4th Ed 2004.pdf
Wilmore – ACS Surgery – Principles and Practice 2nd ed.zip
Morris – Oxford Textbook of Surgery 2nd ed.pdb
Sabiston Textbook of Surgery, 16th Edition.pdf

Current Surgical Diagnosis and Treatment 11ed With images.pdb
MANUALS, DICTIONARIES, ATLAS
Current Clinical Strategies. Physicians’ Drug Manual. Side Effects, Drug Interactions, and Newly Approved Drugs. 2003 Ed.pdf
Dale – Infectious Diseases The Clinician’s Guide to Diagnosis, Treatment, and Prevention – Big Images.pdb
Bennett and Brachman’s Hospital Infections (Lippincott, 2007).chm
LR – Pocket Medicine 3rd Edition.pdf
Lippincott Williams Wilkins 2003 Medical Terminology An Illustrated Guide 4th Ed.pdf
Merck Manual 17th.Ed.pdb
Pocket Atlas of Radiographic Anatomy 2nd ed, 2000.pdf
Pocket Guide to Diagnostic Tests-0838581358.pdf
Pocket.Guide.to.Musculoskeletal.Diagnosis.3HAXAP.pdf
Oxford Textbook Of Rheumatology, 2nd ed (1998).pdb
Oxford_textbook_of_public_health_4th_ed.pdb
Manual of Clinical Problems In Pediatrics 5th Edition (2000).pdb
Manual of Family Practice 2nd ed.pdb
Ferri’s Clinical Advisor 2004 – Instant Diagnosis and Treatment. 6th edition.pdb
Pocket Atlas of Echocardiography.pdf
Pocket Atlas Of Radiographic Anatomy 2d ed – Torsten B. Moller, Emil Reif.pdf
Pocket_Atlas_of_Human_Anatomy__H._Feneis__W._Dauber._4th_Ed._2000_.pdf
Pocket guide to diagnostic tests.chm
Stedman’s Electronic Medical Dictionary 6th Edition.pdf
Colour Atlas of Anatomical Pathology.pdf
Glossary of Biotechnology Terms, Third Edition.pdf
Clinical Neuropathology Text and Color Atlas.pdf
An Atlas Of Back Pain.pdf
An Atlas of Headache.maxiwarez.pdf
Atlas of Clinical Diagnosis 2nd Ed (2003).pdf
Henry Clinical Diagnosis and Management by Laboratory Methods 21st ed.chm

FLASH CARDS
- ANATOMY (NETTER)
- ANATOMY (ROHEN’S)
- PATHOLOGY
- PHARMACOLOGY

ABC SERIES

ABC of AIDS.pdf
ABC of Antenatal Care.pdf
ABC of Antithrombotic Therapy.pdf
ABC of Arterial and Venous Disease.pdf
ABC of Burns.pdf
ABC of Clinical Electrocardiography.pdf
ABC of Clinical Genetics.pdf
ABC of Clinical Haematology.pdf
ABC of Colorectal Cancer.pdf
ABC of Conflict and Disaster.pdf
ABC of Dermatology.pdf
ABC of Diabetes.pdf
ABC of Eyes.pdf
ABC of First Year.pdf
ABC of Heart failure.pdf
ABC of Intensive Care.pdf
ABC of Interventiona Cardiology 2004.pdf
ABC of Learning Teaching Medicine.pdf
ABC of Nutrition, 4th Edition.pdf
ABC of Occupational and Environmental Medicine.pdf
ABC of Preterm Birth.pdf
ABC of Psychological Medicine.pdf
ABC of Resuscitation.pdf
ABC of Sexually Transmitted Infections.pdf
ABC of Spinal Cord Injury 4th Ed.pdf
ABC of Subfertility.pdf
ABC of the Liver Pancreas and Gall Bladder.pdf
ABC of the Upper Gastrointestinal.pdf

—————————————————————
US MLE REVIEW SERIES

anatomy.pdf
basic epidemiology -beaglehole,bonita.pdf
behavioral sciences.pdf
beyond basic resp.pdf
biochemistry.pdf
clinical anatomy 11ed.pdf
clinical epidimiology -robert fletcher.pdf
kaplan lecture notes.pdf
lecture on visuals.pdf
microbiology,immunology.pdf
pathology.pdf
pharmacology.pdf
physiology.pdf
principles of epidemiology.pdf
Qbook.pdf
upper extremities cadaver pics.pdf
kaplan medical timeline.pdf

OTHERS:

1. Journal Medical Passwords 2003.pdf
——————————————————
1. Anatomy.tv – Anatomy Study Guides.chm
2. Cranial_Nerves_Functional_Anatomy.pdf
3. Outline of Biology – Fried, George H..pdf
——————————————————
1. Gray’s Anatomy for Students.chm
2. Chest Radiology The Essentials, 2nd Edition.CHM
3. Clinical Anatomy by Regions – 8th Ed.CHM
4. Grant’s Dissector.pdf
5. Clinical Radiology Made Ridiculously Simple (MedMaster Series 2003 Ed
6. Clinical Anatomy_ Applied Anatomy for Students and Junior Doct.pdf
7. The Medical Student’s Guide to the Plain Chest Film.pdf
——————————————————
1. Clinical Interviewing 3rd edition.pdf
2. What They Didnt Teach You at Medical School.pdf
3. Medical English.pdf
4. Medical Law and Moral Rights (Springer, 2005).pdf
5. Neuroethics.pdf
——————————————————
1. Ferri’s Clinical Advisor 2008_ Instant Diagnosis and Treatment.CHM
2. Current Medical Diagnosis & Treatment 2007, 46th Ed.chm
3. Handbook of Neurology.CHM
4. Professional Guide to Signs and Symptoms – 5th Ed.chm
5. Colour Atlas of Anatomical Pathology.pdf
6. Glossary of Biotechnology Terms, Third Edition.pdf
7. Clinical Neuropathology Text and Color Atlas.pdf
8. An Atlas Of Back Pain.pdf
9. An Atlas of Headache.maxiwarez.pdf
10. Atlas of Clinical Diagnosis 2nd Ed (2003).pdf
11. Atlas of functional neuroanatomy 2nd ed.pdf
12. Kahle, Color Atlas of Human Anatomy, vol 3 (2003).pdf
13. Neuroanatomy An Atlas of Structures, Sections, and Systems – Duane E. Haines.pdf
14. Pocket Atlas of Echocardiography.pdf
15. Pocket Atlas Of Radiographic Anatomy 2d ed – Torsten B. Moller, Emil Reif.pdf
16. Pocket_Atlas_of_Human_Anatomy__H._Feneis__W._Dauber._4th_Ed._2000_.pdf
17. Stedman’s Electronic Medical Dictionary 6th Edition.pdf
——————————————————
1. Skill 01[1].Temperature..pdf
2. Skill 02[1]..Pulse.pdf
3. Skill 03[1]..Respiration.pdf
4. Skill 04[1]..Blood Pressure.pdf
5. Skill 05[1]..Pulse Oximetry.pdf
6. Skill 06[1]..Capillary Blood Draw.pdf
7. Skill 07[1]..Venipuncture.pdf
8. Skill 08[1]..Blood Draw from a Central Venous Catheter.pdf
9. Skill 09[1]..Nasopharyngeal Swab.pdf
10. Skill 10[1]..Throat Culture.pdf
11. Skill 11[1]..Collection of Stool Specimen.pdf
12. Skill 12[1]..Collection of Urine Specimen.pdf
13. Skill 13[1]..Collection of a Midstream.pdf
14. Skill 14[1]..Assisting with Child during Bone Marrow.pdf
15. Skill 15[1]..Assisting with Child during Lumbar Puncture.pdf
16. Skill 16[1]..Assisting with Collection of Cerebrospinal.pdf
17. Skill 17[1]..Sponge Bath.pdf
18. Skill 18[1]..Insertion of a Peripheral IV Line.pdf
19. Skill 19[1]..Dressing Change Central Venous Line.pdf
20. Skill 20[1]..Insertion of a Nasogastric Tube.pdf
21. Skill 21[1]..Management of Gastrointestinal Suction.pdf
22. Skill 22[1]..Nasogastric Tube Irrigation.pdf
23. Skill 23[1]..Nasogastric Tube Lavage.pdf
24. Skill 24[1]..Administration of a Bolus Feeding.pdf
25. Skill 25[1]..Administration of NG, NJ, Gastrostomy and.pdf
26. Skill 26[1]..Changing a Fecal Ostomy Appliance.pdf
27. Skill 27[1]..Emptying an Ostomy Pouch.pdf
28. Skill 28[1]..Administration of Enemas.pdf
29. Skill 29[1]..Urinary Catheterization.pdf
30. Skill 30[1]..Petaling a Cast.pdf
31. Skill 31[1]..Pin Site Care.pdf
32. Skill 32[1]..Care of the Child in an External Fixation.pdf
33. Skill 33[1]..Pin Care, External Fixation Device.pdf
34. Skill 34[1]..EVD Maintaining System at Correct Level and Functioning.pdf
35. Skill 35[1]..EVD Client Assessment.pdf
36. Skill 36[1]..EVD Monitoring Cerebrospinal Fluid (CSF).pdf
37. Skill 37[1]..EVD Changing the Drainage Bag.pdf
38. Skill 38[1]..EVD General Nursing Care and Safety.pdf
39. Skill 39[1]..Assisting with Chest Tube Insertion.pdf
40. Skill 40[1]..Preparing the Chest Tube Drainage System.pdf
41. Skill 41[1]..Care of the Child with a Chest Tube.pdf
42. Skill 42[1]..Assisting with Removal of Chest Tube.pdf
43. Skill 43[1]..Oxygen Administration.pdf
44. Skill 44[1]..Bulb Suctioning.pdf
45. Skill 45[1]..Nasotracheal Suctioning.pdf
46. Skill 46[1]..Tracheostomy Monitoring.pdf
47. Skill 47[1]..Tracheostomy Tube Change.pdf
48. Skill 48[1]..Tracheostomy Tube.pdf
49. Skill 49[1]..Tracheostomy Suctioning.pdf
50. Skill 50[1]..Endotracheal Tube Monitoring (ETT).pdf
——————————————————

Churchill Livingstone – 2001 – Grainger & Allison’s Diagnostic Radiology. A Textbook of Medical I.pdb
Classifications and Scores of the Shoulder – Habermeyer.pdf
Clinical Examination of Musculoskeletal System – Assessing Rheumatic Conditions.pdf
Clinical Interviewing.pdf
Clinical Orthopaedic Examination, Fifth Edition (2004).pdf
Clinical Tests for the Musculoskeletal System.pdf
Clinical.Anatomy.11ed.1405138041.Oct.2006.pdf
Clinical.Knowledge.Management.Opportunities.and.Challenges.pdf
clinical_evidence_vol_10.pdb
clinical_evidence_vol_9.pdb
clinical_laboratory_medicine_-_clinical_applications.pdb
Clinician’s Pocket Reference_0838515525.pdf
Color Atlas of Pharmacology.pdf
Color Atlas of Physiology.pdf
Common Symptom Answer Guide.pdf
Complementary Therapies in Neurology.pdf
Comprehensive Management of Chronic Obstructive Pulmonary Disease (2002) – COPD.iso
Core Topics in Pain.pdf
Cranial Nerves Functional Anatomy (2005).pdf
Current Diagnosis & Treatment in Orthopedics 3rd ed.pdb
Current Medical Diagnosis & Treatment, 2005 full pic.pdb
DeLee and Drez’s – Orthopaedic Sports Medicine. Editor DeLee (2nd Ed. 2003).pdb
Differential Diagnosis in Neurology and Neurosurgery.pdf
Drawing the Line. Art Therapy with the Difficult Client.pdf
Dynamics_of_Human_Gait.pdf
Electrodiagnosis in Diseases of Nerve and Muscle – Principles and Practice.chm
Elsevier’s Medical Terminology for the Practicing Nurse (1998).pdf
Encyclopedia of Infectious Diseases.pdf
Essentials of Complementary and Alternative Medicine.pdf
Essentials_of_Physical_Medicine_and_Rehabilitation.pdb
Evaluation of the Low Back Pain Practice Guideline Implementation in the Army.pdf
Evidence Based Practice in Primary Care [ILLUSTRATED].pdf
Evidence-Based Imaging – Optimizing Imaging in Patient Care.pdf
Evidence-based Medicine Workbook.pdf
evidence_base_of_clinical_diagnosis.pdf
Exercise Leadership in Cardiac Rehabilitation – An Evidence-based Approach – 0470019719.pdf
Ferri’s Clinical Advisor 2004 – Instant Diagnosis and Treatment. 6th edition.pdb
Foundations of Sport-Related Brain Injuries.pdf
Fractures_Classification_in_Clinical_Practice__2006_.pdf
Fractures_in_children_5ed.pdb
Functional Neuroanatomy of Pain.pdf
General Practice, 3rd Edition (J. Murtagh).pdb
Geriatric Medicine An Evidence-based Approach.pdf
Hand Bone Age.pdf
Handbook of couples therapy.pdf
Healing or Stealing. Medical Charlatans in the New Age.pdf
Healing_Back_Pain_The_Mind.pdf
How to Present at Meetings 2001.pdf
How to Read a Paper.pdf
Human Biology_0071218068.pdf
Human Body Dynamics – classical mechanics and human movement – A.Tozeren.pdf
Image-guided spine interventions.pdf
Information Technologies in Medicine – Volume I.pdf
Instant Pain Control – Using the Body’s Trigger Points.djvu
Interpretation of Diagnostic Tests 7th ed.pdb
Interviewing And Diagnostic Exercises For Clinical And Counseling Skills Building – ISBN 08058464.pdf
Kelley’s Textbook of Rheumatology 6th Edition, 2-Volume Set – ISBN.pdb
Lab Notes Guide to Lab and Diagnostic Tests (2005).pdf
Learning_Medicine_An_Informal_Guide_to_a_Career_in_Medicine.pdf
Living well with Parkinson’s.pdf
Lovell_and_winter_s_pediatric_orthopaedics_3rd_ed.pdb
Managing the symptoms of multiple sclerosis.pdf
Managing Your Multiple Sclerosis.pdf
Manual of Clinical Problems In Pediatrics 5th Edition (2000).pdb
Manual of Family Practice 2nd ed.pdb
Manual of Rheumatology and Outpatient Orthopedic Disorders Diagnosis and Therapy 4th ed.pdb
Marketing health services.pdf
Massage For Dummies.pdf
MCQ.Companion.to.Applied.Radiological.Anatomy.3HAXAP.pdf
Means Ends and Medical Care.pdf
Medical and Psychosocial Aspects of Chronic Illness and Disability, Third Edition (2005).pdf
Medical Malpractice – A Physician’s Sourcebook.pdf
Medical_Physiol_2nd_Ed.pdf
Merritt – Merritt’s Neurology 10th Ed.pdb
MILLER’S_REVIEW_OF_ORTHOPEDICS.pdf
Modern Neuromuscular Techniques (Modern Neuromuscular Techniques (WCD)) (2003).ISO
MP Van De Graaff Human Anatomy.pdf
Musculoskeletal.Diseases.DIAGNOSTIC IMAGING AND INTERVENTIONAL TECHNIQUES.pdf
Nelson.Textbook.of.Pediatrics.17th.ed – Behrman.pdb
Nervous System and Sensory Organs – Color Atlas and Textbook of Human Anatomy – Volume 3.pdf
Neuroanatomy – Atlas of Structures Sections Systems 6ed.pdf
Neuroscience – D.Purves, et al.pdf
Neurotransmitters, Drugs and Brain Function Wiley (2001).pdf
Nurses manual of laboratory and diagnostic tests 4th Ed 2003.pdf
Nursing practice in multiple sclerosis – a core curriculum.pdf
Occupational Health Practice – Arnold.Publishers.Fourth.EditionISBN0750627204.pdf
Opportunities in Physician Careers_0071438483.pdf
Outpatient and Primary Care Medicine, 2005 Edition (2004).pdf
Oxford Textbook Of Rheumatology, 2nd ed (1998).pdb
Oxford_Dictionary_of_Medical_Quotations.pdf
Oxford_textbook_of_public_health_4th_ed.pdb
Pediatric Musculoskeletal Diseases.pdf
Pediatric Radiography.pdf
Pain and Depression – An Interdisciplinary Patient-centered Approach.pdf
Pain.Medicine.and.Management.Just.the.Facts.pdf
Pain.Psychological.Perspectives.eBook-DDU.pdf
PATHOPHYSIOLOGY OF DISEASE.pdf
Pediatric Orthopedics for Primary Care Physicians.pdf
Pediatric Orthopedics in Practice.pdf
Physical Medicine and Rehabilitation Board Review.pdf
Pocket Atlas of Radiographic Anatomy 2nd ed, 2000.pdf
Pocket Guide to Diagnostic Tests-0838581358.pdf
Pocket.Guide.to.Musculoskeletal.Diagnosis.3HAXAP.pdf
Primary_care_medicine_office_evaluation_and_managem.pdb
Principles.and.Practice.of.Burn.Surgery.3HAXAP.pdf
Quick reference dictionary for massage therapy and bodywork.pdf
Robbins Pathologic Basis of Disease (with pictures).pdb
Rosen’s Emergency Medicine.chm
Scientific Writing Easy When You Know How (2002).pdf
Screening Notes Rehabilitation Specialists Pocket Guide (Davis Notes S) ISBN0803615736.pdf
Soft Tissue Rheumatology.CHM
Sports Injuries – Mechanisms, Prevention, Treatment. 2nd edition.pdb
SPORTS MEDICINE Just the Facts.pdf
strength training anatomy.pdf
Stretching – anderson bob.pdf
Super Joints Russian Longevity Secrets for Pain-Free Movement, Maximum Mobility & Flexible Strength (2001).pdf
Symptoms of Unknown Origin.pdf
T’Ai Chi for Seniors. How to Gain Flexibility, Strength, and Inner Peace .pdf
Textbook of Clinical Trials Wiley (2004).pdf
Textbook of Medical Physiology.pdf
Textbook Of Physical Diagnosis History – Examination Swartz.djvu
The Aging Spine.pdf
The A-Z Medical Writing.pdf
The Circuitry of the Human Spinal Cord_Its Role in Motor Control and Movement Disorders_0521825814.pdf
The Clinical Drug Therapy Rationales for Nursing Practice (Field Guide Series) (2006).pdf
The Clinical Science of Neurologic Rehabilitation (Contemporary Neurology Series, 66) (2003).pdf
The Coiled Spring.pdf
The Handbook of Brain Theory and Neural Networks – ISBN 0262511029.pdf
The healthcare quality book- vision, strategy, and tools.pdf
The Massage connection – ANATOMY AND PHYSIOLOGY.pdf
The Trigger Point Therapy Workbook – Your Self-Treatment Guide for Pain Relief – Clair Davies.pdf
The.Ultimate.New.York.Body.Plan.eBook-TLFeBOOK.pdf
TMJ Disorders and Orofacial.doc
Toward.Replacement.Parts.for.the.Brain.Implantable.Biomimetic.Electronics.PDF.eBook-YYePG.pdf
Trauma.E.Moore, et al – 5th edition.pdb
Treating Pediatric Bed-wetting With Acupuncture & Chinese Medicine.pdf
Treatment of Osteoarthritic Change in the Hip – Joint Preservation or Joint Replacement.pdf
Treatment.of.Pediatric.Neurologic.Disorders.3HAXAP.pdf
Tyranny of Health Doctors and the Regulation of Lifestyle.pdf
Understanding Human Anatomy and Physiology 5th edition.pdf
Using Alternative Therapies – A Qualitative Analysis.pdf
Visions of the Future. Chemistry and Life Science.pdf
Weight Training Basics.pdf
What They Didn’t Teach You at Medical School.pdf
What’s Wrong With Me – The Frustrated Patients’ Guide to Getting an Accurate Diagnosis.pdf
When.Walking.Fails.eBook-DDU.pdf
WHO manuals of diagnostic imaging – Radiographic Anatomy and Interpretation of the Musculoskeletal System.pdf
Who s who in orthopedics.pdf
World of Microbiology and Immunology.pdf
Writing Skills in Practice (Health Professionals).pdf

Supported  by
CLINICAL PEDIATRIC ONLINE 

Yudhasmara Foundation 

email : judarwanto@gmail.com, 

http://clinicalpediatric.wordpress.com/

Copyright © 2009, Clinical Pediatric Online Information Education Network. All rights reserved.

Supported  by
CLINICAL PEDIATRIC ONLINE

Yudhasmara Foundation

JL Taman Bendungan Asahan 5 Jakarta Indonesia 102010

phone : 62(021) 70081995 – 5703646

email : judarwanto@gmail.com,

http://clinicalpediatric.wordpress.com/

Clinical and Editor in Chief :

DR WIDODO JUDARWANTO

Copyright © 2009, Clinical Pediatric Online Information Education Network. All rights reserved.

In the 1950s, growth hormone isolated from the pituitaries of humans and anthropoid apes was discovered to stimulate growth in children who had growth hormone deficiency. From 1958-1985, a limited supply of cadaver-derived pituitary growth hormone was used to treat 8000 children who had growth hormone deficiency in the United States. In 1985, these preparations of cadaver-derived pituitary growth hormone were implicated in several cases of Creutzfeldt-Jakob disease (CJD), and the Food and Drug Administration (FDA) ceased distribution of the cadaver-derived growth hormone. In an analysis of patients treated with cadaver-derived growth hormone, Mills et al have reported 26 subjects who died from CJD.¹

The somatotroph cells of the anterior pituitary gland produce growth hormone. The hormone’s secretion is stimulated by growth hormone – releasing hormone (GHRH) and is inhibited by somatostatin, both of which are produced by the hypothalamus.

The clinical manifestations of growth hormone deficiency (GHD) are variable, depending on the age of onset.¹ Children usually present with short stature, while adults have reduced physical performance and impaired psychological well-being.

The goals of growth hormone therapy differ in children and adults. In children, therapy promotes linear growth and restores body composition; in adults, the goals are to improve conditioning and strength, to restore normal body composition, and to improve the quality of life.

Since 1985, recombinant DNA–produced human growth hormone has assured a safe and unlimited supply for uninterrupted therapy at doses adequate to restore normal growth. Growth hormone deficiency may be isolated (isolated growth hormone deficiency) or associated with other pituitary deficiencies. Multiple pituitary hormone deficiency involving growth hormone deficiency is caused by genetic defects in pituitary stem cells or by anatomic problems that may be congenital or acquired (eg, from tumor, trauma, radiation, infection).

Pathophysiology

Pituitary growth hormone secretion is stimulated by growth hormone–releasing hormone (GHRH) from the hypothalamus and possibly by another signal, which may be stimulated by certain growth hormone–releasing peptides (GHRPs). Receptors for the GHRPs have been identified, and the natural ligand for these receptors has been determined to be ghrelin. Somatostatin secreted by the hypothalamus inhibits growth hormone secretion. When growth hormone pulses are secreted into the systemic circulation, insulinlike growth factor 1 (IGF-1) is released, either locally or at the site of growing bone. Growth hormone binds to a specific growth hormone–binding protein (GHBP) and circulates. This GHBP is the extracellular portion of the growth hormone receptor. IGF-1 binds to one of several IGF-binding proteins (IGFBPs) and circulates almost entirely (>99%) in the bound state. IGFBP-3 accounts for most of the IGF-I binding and this binding protein directly depends on growth hormone.

Growth hormone deficiency may result from disruption of the growth hormone axis in the higher brain, hypothalamus, or pituitary. This dysfunction can be congenital or acquired.

In 1992, a patient was described with a mutation in a transcription factor (POUF-1, also known as PIT-1), which resulted in familial growth hormone deficiency.² As many as 14 different mutations have been described. In addition to growth hormone deficiency, affected individuals have had prolactin deficiencies and variable thyroid-stimulating hormone (TSH) deficiencies. Imaging of the pituitary gland usually reveals a hypoplastic or ectopic posterior pituitary.

Growth hormone deficiency with other hypopituitarism associated with inactivating mutations of the PROP1 (Prophet of PIT-1) transcription factor gene have been documented in reports. Patients with this mutation usually do not produce luteinizing hormone (LH) or follicle-stimulating hormone (FSH), and thus, do not spontaneously progress into puberty. They may also have TSH deficiency. Imaging of the pituitary gland of patients with PROP1 mutations may show either a small anterior pituitary or an intrapituitary mass.

Congenital growth hormone deficiency may be associated with an abnormal pituitary gland (seen on MRI) or may be part of a syndrome such as septooptic dysplasia (SOD) (de Morsier syndrome), which may include other pituitary deficiencies, optic nerve hypoplasia, and absence of the septum pellucidum; it occurs with an incidence of about 1 in 50,000 births. SOD may be associated with a mutation in the gene for another transcription factor, HESX1.

Acquired growth hormone deficiency may result from trauma, infections (eg, encephalitis, meningitis), cranial irradiation (somatotrophs appear to be the most radiation-sensitive cells in the pituitary), and other systemic diseases (particularly histiocytosis). Although most instances of isolated growth hormone deficiency are idiopathic, specific etiologies cause most growth hormone deficiency associated with other pituitary deficiencies. A reported 12-86% of children with apparent isolated growth hormone deficiency have sellar developmental defects.

Frequency

United States

A study of 80,000 children in Salt Lake City, Utah, reported that 555 children were below the third height percentile and had growth rates less than 5 cm/y; of these children, 33 had growth hormone deficiency, an incidence rate of 1 case per 3,500 children. Of more than 20,000 children receiving growth hormone in the National Cooperative Growth Study (a database of patients receiving growth hormone therapy), approximately 25% of the patients with growth hormone deficiency had an organic etiology. These etiologies included the following:^3,4,5

• CNS tumor, including craniopharyngioma – 47%
• CNS malformation – 15%
• SOD – 14%
• Leukemia – 9%
• CNS radiation – 9%
• CNS trauma – 3%
• Histiocytosis – 2%
• CNS infection – 1%

International

Frequency of isolated growth hormone deficiency has been reported to range from 1 case per 1,800 children in Sri Lanka (a probable overestimate due to liberal diagnostic criteria) to 1 case per 30,000 children in Newcastle, United Kingdom (a probable underestimate due to its reliance on referral rates to a growth clinic).

Mortality/Morbidity

Mortality in children with growth hormone deficiency is due almost entirely to other pituitary hormone deficiencies. These children have an increased relative risk of death in adulthood from cardiovascular causes resulting from altered body composition and dyslipidemia.

• Most morbidity in children with growth hormone deficiency relates to short stature. Average adult height for untreated patients with severe isolated growth hormone deficiency is 143 cm in men and 130 cm in women. Approximately 5% of children with growth hormone deficiency also have episodes of hypoglycemia, particularly in infancy, which resolve with growth hormone therapy.
• Adults with untreated growth hormone deficiency have altered body composition (eg, excess body fat, lower lean body mass), decreased bone mineralization, cardiovascular risk factors (in particular, altered blood lipids), and decreased exercise tolerance. In addition, these patients may be socially isolated.

Race

Although no racial difference in the incidence of growth hormone deficiency is apparent, the rate at which patients receive growth hormone therapy appears to differ by race. Among nearly 9000 patients with idiopathic growth hormone deficiency in a large North American database of patients treated with growth hormone, 85% were white, only 6% were black, and 2% were of Asian descent.^3,4,5 An almost identical distribution is seen for patients with organic growth hormone deficiency. The racial difference may reflect a possible ascertainment bias, a notion supported by the observation that patients from other racial groups are shorter than their white counterparts at diagnosis.

Sex

The sex distribution of patients with idiopathic growth hormone deficiency in the National Cooperative Growth Study is 73% male and 27% female.^3,4,5 Among patients with organic growth hormone deficiency, in which no sex difference should be present, the ratio is 62% male to 38% female.

When growth hormone deficiency is diagnosed as part of SOD, sex distribution is nearly equal (male-to-female ratio is 1.3:1). Referral bias may explain this distribution (ie, greater concern for short stature in boys). This referral bias is absent when reasons other than stature result in diagnosis (eg, in patients with SOD). However, close examination of the Utah study data reveals twice the number of boys than girls in the group with heights less than the third height percentile and with growth rates less than 5 cm/y.⁶ Furthermore, the group diagnosed with growth hormone deficiency had about 3 times the number of boys as girls. Given the approximately equal number of boys and girls in the Utah school system, the observed difference may not be due to referral bias. 

However, several recent studies have tried to determine the point at which gender bias is introduced. Cuttler et al published results of a survey of pediatric endocrinologists that growth hormone treatment was 1.3 times more common in boys than in girls.⁷  Furthermore, Grimburg et al examined a large worldwide database of children treated with growth hormone and found a male predominance of treated patients in Asia, the United States, Europe, Australia, and New Zealand, but not in the rest of the world.⁸ These authors speculate that the bias may be introduced by parents and referring physicians and is a reflection of the culture in those countries in which the bias is observed.

Age

In children, the age of presentation varies with respect to the time of onset and the degree of GHD. Children with complete absence of growth hormone secretion usually present before reaching the age of 3 years, whereas those with lesser degrees of deficiency present at older ages.

Although most cases of idiopathic growth hormone deficiency are thought present at birth, diagnosis is often delayed until concern is raised about short stature. Diagnosis of growth hormone deficiency is made during 2 broad age peaks. The first age peak occurs at 5 years, a time when children begin school and the height of short children is probably compared with that of their peers. The second age peak occurs in girls aged 10-13 years and boys aged 12-16 years. This second peak possibly relates to the delay in puberty associated with growth hormone deficiency. Children with growth hormone deficiency may seem to grow at a slower rate than their peers because their peers are in the midst of the pubertal growth spurt, whereas children with growth hormone have not yet entered this phase.

Clinical

History

Short stature history should focus on the following issues:

• Birth weight and length: Intrauterine growth retardation is an issue in the differential diagnosis and should be apparent from the birth history.
• Height of parents
  • Calculation of the sex-adjusted midparental height, also termed the “target height,” helps evaluate a child’s genetic potential.
  • For boys, calculate the sex-adjusted midparental height by adding 2.5 in or 6.5 cm from the mean of the parents’ heights. For girls, subtract 2.5 in or 6.5 cm from the mean of the parents’ heights.
  • This sex-adjusted midparental height represents the statistically most probable adult height for the child, based on parental contribution.
• Timing of puberty in parents
  • Constitutional delay in growth and maturation may have a family history. Most mothers can remember their age at menarche (average age is 12-12.5 y).
  • Although pubertal age is more difficult to establish for fathers because no precise landmark is recognized, recall is generally good for development later than other boys, for always looking younger than peers, for continuing to grow after high school, and for delayed beard appearance.
• Previous growth points
  • The child’s growth pattern is an important part of the workup for short stature. Previous growth data may be obtained from physicians’ offices, schools, or heights plotted on a door at home.
  • If the growth rate is normal (about 2 in/y [5 cm/y] from age 3 y to puberty), the child’s short stature most likely is caused by a normal variant, such as familial short stature or constitutional delay in growth and maturation. If the growth rate is slow, a pathological cause for short stature is more likely.
• General health of child: Exclusion of chronic disease as the cause of short stature is imperative.
• Nutritional history: Malnutrition is the most common cause of short stature worldwide.

Physical

The following items should be targeted in a workup of short stature.

•  
  • The standing height standard deviation score is usually below -2.
  • Growth velocity is below the 10-25th percentile, which reflects growth deceleration.
  • Increased subcutaneous fat is present, especially around the trunk.
  • The face is immature, with a prominent forehead and depressed midfacial development.
  • Dentition is delayed.
  • The average age of pubertal onset is delayed in males and females.
  • In males, the phallus may be small.

• Height and weight measurement
  • The best way to evaluate height or weight measurements is to plot the points on a growth chart. A growth chart depicts the child’s growth over time, allows comparison of the height or weight to other children, and graphically depicts changes in growth or growth velocity.
  • Although weight is not difficult to determine, height measurement requires care. The following points help provide accurate measurements:
    • Children should be either barefoot or in stocking feet upon measurement. The heels, buttocks, and shoulders should be in contact with the wall or the measuring device.
    • Have the child stand with feet slightly spread but with heels together.
    • Instruct the child to look straight ahead. This positions the head in the Frankfort horizontal plane (ie, the plane represented in the profile by a line between the lowest point on the margin of the orbit and the highest point on the margin of the auditory meatus).
    • Instruct the child to hold a deep breath at the time of measurement.
    • Use proper equipment. The ideal device for height measurement is a wall-mounted stadiometer with an arm that moves vertically. The arm is placed on the head; the height can be read from a counter or from a ruler on the wall. If a stadiometer is unavailable, good height measurements may be obtained from a yardstick (or meterstick) attached to the wall, combined with a device creating a right angle with the wall and the child’s head. Floppy-arm devices mounted on weight scales are inherently inaccurate and frequently yield poor measurements. A child’s height can be determined using this device, but accurate measurement requires even more attention.
    • For precise height determinations, measure the child 2-3 times and calculate the mean. If the first 2 measurements agree, consider them accurate.
    • Measure the child at the same time of day to minimize diurnal variation in height.
• Proportionality: Inspect the child for proportionality of limbs and trunk. The following measurements may be taken if disproportionality is suspected:
  • Arm span: Measure outstretched arms from fingertip to fingertip. The arm span should approximate the height, although this depends on genetic background. In comparisons of people of Asian, European, and African heritage, Asians have proportionally shorter arms, Europeans have intermediate arm length, and Africans have significantly longer arms.
  • Lower segment (LS): Measure from the symphysis pubis to the floor.
  • Upper segment (US): Calculate by subtracting the lower segment measurement from the height.
  • US/LS ratio: Calculate by dividing US by LS. For people of European origin, the US/LS ratio at birth is approximately 1.7:1 and decreases to 1:1 at age 10 years, a ratio that lasts throughout adulthood. In comparisons of people of Asian, European, and African heritage, Asians have proportionally shorter legs (and, therefore, larger US/LS ratios), Europeans have intermediate length legs, and Africans have significantly longer legs.
• Pubertal status
  • Calculate stage of puberty using the Tanner staging system.⁹
  • Constitutional and many other pathological causes of short stature, including growth hormone deficiency (GHD), delayed puberty.
• Evidence of specific syndromes: Many syndromes include short stature as follows:
  • Turner syndrome
  • Noonan syndrome
  • Russell-Silver syndrome
• Children
  • Growth failure after a period of normal growth is a characteristic feature of GHD that presents during childhood. Children present with short stature and low growth velocity for age and pubertal stage.⁸
  • Consider the possibility of hypopituitarism in patients with neonatal hypoglycemia, prolonged jaundice, septo-optic dysplasia, midline facial defects (eg, cleft palate, solitary central incisor), male micropenis (not necessarily related to gonadotropin deficiency), histiocytosis X, previous cranial irradiation, and symptoms of a mass lesion in the hypothalamic-pituitary region (eg, headaches, visual disturbances).

Causes

Most instances of growth hormone deficiency are idiopathic. Other causes include the following:

Causes

• Causes of GHD in children can be divided into 3 categories.
  • Congenital conditions
    • Defective pituitary development that leads to pituitary aplasia
    • Empty sella
    • Encephalocele
    • Midline defects
    • Septo-optic dysplasia
    • Panhypopituitarism
    • Genetic abnormalities, including autosomal-recessive, autosomal-dominant, or X-linked defects or a mutation or deletion in the growth hormone gene or in the GHRH.
  • Acquired conditions
    • Tumors of the hypothalamic-pituitary region – Craniopharyngioma is the most common tumor.
    • Cranial irradiation
    • Infiltrative diseases, including sarcoidosis, tuberculosis, histiocytosis X, hemochromatosis, and lymphocytic hypophysitis
    • Trauma
    • Hypoxic insult
  • Idiopathic - In many cases, no clear etiology can be identified.
• Causes of GHD in adults
  • Pituitary disease – More than 90% of patients have pituitary disease, which is usually caused by a pituitary tumor, by surgery, or by radiation therapy for the tumor.
  • Other causes – These include trauma, tuberculosis, histiocytosis X, hemochromatosis, lymphocytic hypophysitis, and infiltrative diseases, such as sarcoidosis.
  • Idiopathic – In rare instances, no cause can be found.

• Organic causes
  • Brain tumors, especially craniopharyngioma
  • CNS surgery
  • CNS radiation
  • Anatomical abnormalities (eg, septooptic dysplasia, empty sella syndrome signified by ectopic bright spot on MRI)
• Genetic causes

Differential Diagnoses

Other Problems to Be Considered

Familial (genetic) short stature
Constitutional delay of growth
Short stature accompanying systemic disease
Short stature as part of a genetic syndrome
Short stature related to endocrinopathy (eg, hypothyroidism, Cushing syndrome)
Short stature related to a metabolic abnormality (ie, renal tubular acidosis, poorly controlled diabetes mellitus)
Short stature from abuse and neglect

Workup

Laboratory Studies

• Thyroxine and thyroid-stimulating hormone: Hypothyroidism should be excluded as a cause of growth failure and short stature.
• Serum electrolytes: A low bicarbonate level may indicate renal tubular acidosis, which can result in growth failure. Abnormal electrolytes may indicate renal failure.
• CBC count and sedimentation rate: These studies may be helpful if inflammatory bowel disease is suspected.
• IGF-1 and IGFBP-3
  • Both IGF-1 and IGFBP-3 are growth hormone–dependent.
  • Low values of IGF-1 and IGFBP-3 suggest growth hormone deficiency (GHD). However, a low value alone is not diagnostic because IGFs are sensitive to other factors such as nutritional state and chronic systemic disease.
• Karyotype
  • Girls with otherwise unexplained short stature should have a karyotype study to rule out Turner syndrome.
  • Although many girls with Turner syndrome are diagnosed from signs upon physical examination, the only recognizable feature of many girls with the condition is short stature.
  • In particular, girls with mosaic karyotypes or karyotypes with isochromosomes tend to exhibit fewer signs specific to Turner syndrome.
  • Many girls with Turner syndrome, and particularly those with mosaic karyotypes and karyotypes other than 45,X, do not demonstrate the striking stigmata associated with Turner syndrome.

Imaging Studies

• MRI of the head
  • Patients diagnosed with growth hormone deficiency should undergo an MRI of the head to exclude a brain tumor (eg, craniopharyngioma).
  • Approximately 15% of patients with growth hormone deficiency have an abnormality of the pituitary gland (eg, ectopic bright spot, empty or small sella).

Other Tests

• Bone age determination
  • Comparison of a left hand and wrist radiograph to standards can be used to estimate skeletal maturation.
  • With familial short stature, bone age is comparable to chronological age. Bone age is usually delayed in children with constitutional growth delay, malnutrition, and endocrine causes of short stature (eg, hypothyroidism, cortisol excess, growth hormone deficiency).
  • Bone age also allows determination of growth potential as adult stature may be estimated from the Bayley-Pinneau tables.
• Growth hormone provocative testing
  • Growth hormone response to insulin is the most reliable test for growth hormone deficiency.
  • Before accepting growth hormone deficiency diagnosis, many insurance companies require a documented failure to demonstrate a growth hormone response (with a growth hormone level >10 ng/mL) after presentation of 2 provocative stimuli.
  • Provocative stimuli include insulin-induced hypoglycemia, arginine, levodopa (L-dopa), clonidine, and glucagon.

Treatment

Surgical Care

Pituitary tumors and some of the congenital anomalies that occur in children may require surgical resection.

Consultations

• Consult with an endocrinologist as early as possible.
• Consult with a neurosurgeon for evaluation of pituitary tumors.

Medication

The goals of pharmacotherapy are to restore normal growth hormone levels and to reduce morbidity. The main therapeutic goal of growth hormone treatment in children with growth hormone deficiency are to enable short children to achieve normal height, with early improvement of the psychosocial problems related to short stature.

Growth hormones

Treatment requires recombinant growth hormone.

Human growth hormone (Humatrope, Genotropin, Nutropin)

Currently widely available in subcutaneous injection form. Adjust dose gradually based on clinical and biochemical responses assessed at monthly intervals, including body weight, waist circumference, serum IGF-1, IGFBP-3, serum glucose, lipids, thyroid function, and whole body dual-energy x-ray absorptiometry. In children, assess response based on height and growth velocity. Continue treatment until final height, epiphysial closure, or both have been recorded.

• Dosing  Interactions   Contraindications           Precautions

Adult

2-5 mcg/kg/d SC, usual starting dose, or approximately 100-300 mcg/d; increase q1-2 mo by 100-200 mcg to achieve clinical response and an IGF-1 level in upper half of age-adjusted reference range and to avoid side effects

Pediatric

0.04-0.05 mg/kg/d SC initially, given qd or 6 times/wk

Although growth hormone is normally secreted in multiple peaks during the day and mostly at night, a single daily injection of recombinant growth hormone can provide physiologic replacement. In order for growth hormone replacement to be effective, other pituitary deficiencies should be treated. Response to growth hormone therapy is measured (every 3-6 mo) by sequential height determinations and by occasional bone age determinations.

Consultations

Pediatric endocrinologists see almost all children with growth hormone deficiency (GHD).

Medication

Growth hormone replacement is used to treat growth hormone deficiency (GHD).

Growth hormones

These agents are used for physiologic replacement.

Somatropin (Genotropin, Humatrope, Norditropin, Nutropin, Saizen, TevTropin)

Purified polypeptide hormone of recombinant DNA origin. In children whose epiphyses are not yet fused, GH replacement usually causes significant increase in growth velocity (averaging 10-11 cm/y during first y of therapy). Response wanes each y, but growth velocity continues at faster than pretreatment rates. A long-acting depot preparation designed for monthly or bimonthly SC injection was available but is not off the market. Other long-acting preparations are currently under investigation.

• Dosing              Interactions           Contraindications               Precautions

Adult

0.05-0.1 mg/kg/wk SC divided into 7 injections one sixth to one fourth of childhood dose

Pediatric

0.18-0.3 mg/kg/wk SC divided into 6-7 injections; not to exceed 0.7 mg/kg/wk during puberty
Depot: 1.5 mg/kg/month or 0.75 mg/kg SC q2wk

Further Outpatient Care

Most pediatric endocrinologists see patients who are receiving growth hormone therapy 2-4 times per year. The most important reasons for follow-up are to monitor growth progress and to adjust growth hormone dosage. Growth rate usually increases most during the first year of treatment, with an average increase of 8-10 cm/y (often called “catch-up” growth). Progressive growth slows over the next several years (ie, waning effect). A growth rate appearing to slow more than expected should prompt investigation for a medical cause (eg, hypothyroidism) or another diagnosis (eg, inflammatory bowel disease). Follow-up may also be needed to assure patient compliance with the growth hormone injections.

Complications

Although few patients experience adverse events from growth hormone therapy, the following complications have been recognized:

• Carbohydrate metabolism: Growth hormone has an anti-insulin effect, and carbohydrate metabolism has been monitored in many clinical studies of growth hormone therapy. A review of large databases containing more than 35,000 patients on growth hormone and more than 75,000 patients with years of exposure indicates no greater incidence of type 1 diabetes than would be expected in the general population of age-matched children. One study of an increased incidence of type 2 diabetes in children undergoing growth hormone therapy with risk factors for diabetes suggests that growth hormone may cause earlier expression of this condition.
• Benign intracranial hypertension (pseudotumor cerebri): A clear association between intracranial hypertension and growth hormone therapy is observed. The incidence appears to be about 0.001 (21 cases reported out of 19,000 patients receiving growth hormone, or 50,000 patient-years). Usually, severe headache symptoms (occasionally with vomiting) develop during the first 4 months of therapy. The risk of this complication increased in children receiving growth hormone for chronic renal insufficiency. In most cases, cessation of growth hormone therapy resolved the intracranial hypertension; the growth hormone then could be restarted at a lower dose and slowly titrated back to the usual dose.
• Fluid homeostasis: Growth hormone affects fluid homeostasis, which may lead to edema and even carpal tunnel syndrome. These problems are more common in adults receiving growth hormone. When these occurrences become sufficiently serious to require action, stopping the growth hormone provides resolution. Restarting the growth hormone at a lower dose and slowly titrating it back to the usual dose is usually possible.
• Skeletal and joint problems: Children receiving growth hormone therapy are more susceptible to slipped capital femoral epiphysis (SCFE). Yet children with growth hormone deficiency (GHD), hypothyroidism, or renal disease seem to have increased risk for SCFE, even without growth hormone therapy. When a child receiving growth hormone therapy complains of hip or knee pain, a careful physical examination is vital, and, if warranted, hip radiography. Scoliosis progression is another skeletal-related complication of growth hormone therapy. Scoliosis relates to the rapid growth that occurs with therapy and is not a direct effect of the growth hormone Patients with scoliosis who are treated with growth hormone should have their scoliosis monitored during therapy.
• Prepubertal gynecomastia: Although adolescent gynecomastia is common, prepubertal gynecomastia occurs less frequently. Such cases have been reported in association with growth hormone therapy, although whether the gynecomastia is related to the growth hormone is unclear. Prepubertal gynecomastia is a benign condition that resolves without sequelae.
• Leukemia: Several worldwide databases have been examined in response to sporadic reports of leukemia in patients undergoing growth hormone therapy. When patients with other risk factors (eg, previous history of leukemia, radiation, chemotherapy) are excluded, no increased risk of leukemia has been demonstrated. No evidence suggests an association between growth hormone therapy and leukemia in otherwise healthy children.

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phone : 62(021) 70081995 – 5703646

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DR WIDODO JUDARWANTO

Copyright © 2009, Clinical Pediatric Online Information Education Network. All rights reserved.

Supported  by
CLINICAL PEDIATRIC ONLINE

Yudhasmara Foundation

JL Taman Bendungan Asahan 5 Jakarta Indonesia 102010

phone : 62(021) 70081995 – 5703646

email : judarwanto@gmail.com,

http://clinicalpediatric.wordpress.com/

Clinical and Editor in Chief :

DR WIDODO JUDARWANTO

Copyright © 2009, Clinical Pediatric Online Information Education Network. All rights reserved.

Supported  by
CLINICAL PEDIATRIC ONLINE

Yudhasmara Foundation

JL Taman Bendungan Asahan 5 Jakarta Indonesia 102010

phone : 62(021) 70081995 – 5703646

email : judarwanto@gmail.com,

http://clinicalpediatric.wordpress.com/

Clinical and Editor in Chief :

DR WIDODO JUDARWANTO

Copyright © 2009, Clinical Pediatric Online Information Education Network. All rights reserved.

Supported  by
CLINICAL PEDIATRIC ONLINE

Yudhasmara Foundation

JL Taman Bendungan Asahan 5 Jakarta Indonesia 102010

phone : 62(021) 70081995 – 5703646

email : judarwanto@gmail.com,

http://clinicalpediatric.wordpress.com/

Clinical and Editor in Chief :

DR WIDODO JUDARWANTO

Copyright © 2009, Clinical Pediatric Online Information Education Network. All rights reserved.

Supported  by
CLINICAL PEDIATRIC ONLINE 

Yudhasmara Foundation

JL Taman Bendungan Asahan 5 Jakarta Indonesia 102010

phone : 62(021) 70081995 – 5703646

email : judarwanto@gmail.com,

http://clinicalpediatric.wordpress.com/

Clinical and Editor in Chief :

DR WIDODO JUDARWANTO

Copyright © 2009, Clinical Pediatric Online Information Education Network. All rights reserved.

Supported  by
CLINICAL PEDIATRIC ONLINE

Yudhasmara Foundation

JL Taman Bendungan Asahan 5 Jakarta Indonesia 102010

phone : 62(021) 70081995 – 5703646

email : judarwanto@gmail.com,

http://clinicalpediatric.wordpress.com/

Clinical and Editor in Chief :

DR WIDODO JUDARWANTO

Copyright © 2009, Clinical Pediatric Online Information Education Network. All rights reserved.

Supported  by
CLINICAL PEDIATRIC ONLINE

Yudhasmara Foundation

JL Taman Bendungan Asahan 5 Jakarta Indonesia 102010

phone : 62(021) 70081995 – 5703646

email : judarwanto@gmail.com,

http://clinicalpediatric.wordpress.com/

Clinical and Editor in Chief :

DR WIDODO JUDARWANTO

Copyright © 2009, Clinical Pediatric Online Information Education Network. All rights reserved

Coppack SW.Proc Nutr Soc. 2001 Aug;60(3):349-56

PMID: 11681809 [PubMed - indexed for MEDLINE]

Academic Medical Unit, St Bartholomew’s and The Royal London School of Medicine, Whitechapel, UK. s.w.coppack@mds.qmw.ac.uk

Cytokines appear to be major regulators of adipose tissue metabolism. Therapeutic modulation of cytokine systems offers the possibility of major changes in adipose tissue behaviour. Cytokines within adipose tissue originate from adipocyte, preadipocyte and other cell types. mRNA expression studies show that adipocytes can synthesise both tumour necrosis factor alpha (TNF-alpha) and several interleukins (IL), notably IL-1beta and IL-6. Other adipocyte products with ‘immunological’ actions include complement system products and macrophage colony-stimulating factor. Cytokine secretion within adipocytes appears similar to that of other cells. There is general agreement that circulating TNF-alpha and IL-6 concentrations are mildly elevated in obesity. Most studies suggest increased TNF-alpha mRNA expression or secretion in vitro in adipose tissue from obese subjects. The factors regulating cytokine release within adipose tissue appear to include usual ‘inflammatory’ stimuli such as lipopolysaccaride, but also the size of the fat cells per se and catecholamines. There is conflicting data about whether insulin and cortisol regulate TNF-alpha. The effects of cytokines within adipose tissue include some actions that might be characterised as metabolic. TNF-alpha and IL-6 inhibit lipoprotein lipase, and TNF-alpha additionally stimulates hormone-sensitive lipase and induces uncoupling protein expression. TNF-alpha also down regulates insulin-stimulated glucose uptake via effects on glucose transporter 4, insulin receptor autophosphorylation and insulin receptor substrate-1. All these effects will tend to reduce lipid accumulation within adipose tissue. Other effects appear more ‘trophic’, and include the induction of apoptosis, regulation of cell size and induction of de-differentiation (the latter involving reduced peroxisome proliferator-activated receptor gamma). Cytokines are important stimulators and repressors of other cytokines. In addition, cytokines appear to modulate other regulatory systems. Examples of the latter include effects on leptin secretion (probably stimulation followed by inhibition) and reduction of beta3-adrenoceptor expression. There seems to be no clear agreement as to which cytokines derived from adipose tissue act as remote regulators, i.e. hormones. Leptin, which is structurally a cytokine, is also a hormone. IL-6 appears to be released systemically by adipose tissue, but TNF-alpha is probably not. Both leptin and IL-6 appear to act on the hypothalamus, IL-6 acts on the liver, while leptin may have actions on the pancreas. The importance of the immune system in whole-body energy balance provides a rationale for the links between cytokines and adipose tissue. It seems clear that TNF-alpha is a powerful autocrine and paracrine regulator of adipose tissue. Other cytokines, notably leptin, and possibly IL-6, have lesser actions on adipose tissue. These cytokines act as hormones, reporting the state of adipose tissue stores throughout the body.

Related Links

• Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells. [Vitam Horm. 2006]
• Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-alpha, overexpressed in human fat cells from insulin-resistant subjects. [J Biol Chem. 2003]
• Recent advances in the relationship between obesity, inflammation, and insulin resistance. [Eur Cytokine Netw. 2006]
• Pro-inflammatory delipidizing cytokines reduce adiponectin secretion from human adipocytes without affecting adiponectin oligomerization. [J Endocrinol. 2007]
• Cooperation of liver cells in health and disease. [Adv Anat Embryol Cell Biol. 2001]

Supported  by
CLINICAL PEDIATRIC ONLINE

Yudhasmara Foundation

JL Taman Bendungan Asahan 5 Jakarta Indonesia 102010

phone : 62(021) 70081995 – 5703646

email : judarwanto@gmail.com,

http://clinicalpediatric.wordpress.com/

Clinical and Editor in Chief :

DR WIDODO JUDARWANTO

Copyright © 2009, Clinical Pediatric Online Information Education Network. All rights reserved.