Insulin Like growth factor (IGF-1)

Views:
 
Category: Entertainment
     
 

Presentation Description

No description available.

Comments

Presentation Transcript

PowerPoint Presentation:

Insulin-like Growth Factor-1 (IGF-1) The First line Test for Assessing Growth Hormone Dr.Hussam Elmouzi Clinical Pathologist Alborg Laboratory

PowerPoint Presentation:

Regulation of the GH/IGF-1 axis

Factors affecting GH release :

Factors affecting GH release GH is released in 10-20 pulses throughout the day instead of in a steady stream. The largest daily pulse of GH takes place during the beginning stages of sleep. Fasting , exercise, protein intake increase the release of GH. GH in circulation has a half-life of 20 minutes and IGF-1 has a half-life of 22 hours.

Factors affecting IGF-1 release :

Factors affecting IGF-1 release IGF-1 levels are lower in children, peak at puberty, and gradually decline throughout adulthood. IGF-1 reference ranges must therefore always be interpreted within the context of the patient’s age. Puberty and pregnancy may be associated with abnormally high IGF-1levels Malnutrition of any kind , estrogens, hypothyroidism or liver diseases may lower IGF-1 even in patients with acromegaly. Most (approximately 80%) circulating IGF-1 is bound to IGFBP 3, <1% is unbound, and the remainder is bound to other IGF binding proteins

PowerPoint Presentation:

Growth Hormone Deficiency

Causes of Growth hormone deficiency:

Causes of Growth hormone deficiency Gene mutations (GH, GH receptor, GH binding protein) Congenital malformations involving the pituitary Idiopathic ( most common cause in children ) Damage to the pituitary ( most common cause in Adults ) Radiation therapy Tumor Severe head trauma Ischmic damage Autoimmune inflamation

Growth Hormone Insensitivity:

Growth Hormone Insensitivity Growth hormone insensitivity disorders are usually characterized by elevated levels of growth hormone, accompanied by decreased levels of IGF-1, IGFBP-3 The most common form of growth hormone insensitivity is Laron syndrome , and fewer than 300 cases have been reported worldwide

Symptoms of Growth hormone deficiency:

The primary symptom of growth hormone deficiency is a noticeable slow growth (less than two inches per year), although the body has normal proportions. The child with growth hormone deficiency may also have: 1- An immature face, meaning he/she looks much younger than his/her peers 2- A chubby body build Symptoms of Growth hormone deficiency

Symptoms of Growth hormone deficiency:

Symptoms of Growth hormone deficiency Severe GH deficiency in children Extreme low stature Retardation of growth Delayed physical maturation Delayed bone age Low levels of IGF-1 Severe GH deficiency in adults higher amount of body fat Subnormal bone density Diminished muscle strength Higher cholesterol levels Low levels of IGF-1 produces significantly different problems at various ages and degree of disease

Differential diagnoses by short stature :

Differential diagnoses by short stature Constitutional Growth Delay Family Short Stature Nutritional Hypocaloric Chronic inflamatory bowel disease Malabsorption , Coeliac disease Endocrine Hypothyroidism Growth Hormone Deficiency Hypopituitarism Excessive cortisol Precosious puberty Chromosome defects Turner Syndrome Low birth weight Small for gestagional age Prematurity Fetal alcohol syndrome Bone development disorders Rickets Sceletal dysplasias Metabolic Kidney failure Hypoxic, Cardiac Liver diseases Inborn errors of metabolism

Growth Hormone Deficiency Testing Algorithm For Pediatric Patients :

Growth Hormone Deficiency Testing Algorithm For Pediatric Patients Suspect growth hormone deficiency IGF-1 and IGFBP-3 Testing Below age-matched reference range Normal Supports diagnosis of GHD Does not support diagnosis of GHD; consider GHST

IGF-1 and IGFBP-3 Testing with GHD:

IGF-1 and IGFBP-3 Testing with GHD Direct testing of growth hormone production is difficult because growth hormone secretion is pulsatile, with the most consistently elevated surges occurring during deep sleep. In contrast, IGF-1 and IGFBP-3 serum levels are much more stable and they correlate closely with secreted growth hormone levels. Minimal diurnal variation of IGF-1 and IGFBP-3 allows reliable assessment from a single random blood sample. IGFBP-3 levels are not significantly affected by malnutrition and the normal range varies only modestly with age. IGF-1 is more sensitive while IGFBP-3 is more specific , when combined the predication value is more than 95% in GHD diagnosis

Growth Hormone Deficiency Testing Algorithm For Adults Patients :

Growth Hormone Deficiency Testing Algorithm For Adults Patients Suspect growth hormone deficiency IGF-1 Testing Normal Below age-matched reference range Supports diagnosis of GHD GHST testing Subnormal peak GHST result Normal Does not support diagnosis of GHD

Growth Hormone Stimulation :

Growth Hormone Stimulation Insulin Tolerance Test (ITT) – “Gold Standard” GHRH-Arginine Arginine L-DOPA Clonidine

Insulin Tolerance Test :

Insulin Tolerance Test 0 30 60 90 120 minutes Insulin (0.1 – 0.15 u/kg) Measure Growth Hormone and Glucose Children: Normal GH > 10 mcg/L Adults: Normal GH > 5 mcg/L

Limitations of Growth Hormone Stimulation Testing:

The GHST test is expensive, uncomfortable, and potentially hazardous to the patient. Patients undergoing GHST must be carefully monitored by the health care team. False-negatives are high, as GHST often correctly identifies only GHD children with the lowest responses. Normal prepubertal children have false-positive results, because the peak growth hormone concentrations can overlap between normal children and those with less severe GHD. While insulin stimulation has been considered the gold standard, it can cause serious complications in people with diabetes, seizure disorders, cardiovascular disease, or even some healthy people. Limitations of Growth Hormone Stimulation Testing

GHD Treatment Monitoring Algorithm :

GHD Treatment Monitoring Algorithm Growth hormone therapy IGF-1 testing every 1 to 2 months during dose titration Within age-matched reference range Above age-matched reference range Below age-matched reference range Adjust GH dosage accordingly Monitor at 6-month intervals with IGF-1 testing

PowerPoint Presentation:

Excess Growth Hormone

PowerPoint Presentation:

Gigantism • Condition of Excessive Growth Human Growth Hormone during childhood Acromegaly • Condition of Excessive Growth Human Growth Hormone in adults

Causes of Excess Growth Hormone :

Causes of Excess Growth Hormone Most cases are secondary to pituitary adenomas Rare causes – growth hormone secretion from tumors (carcinoid or small cell lung cancer) Genetic diseases associated with acromegaly – MEN1, McCune-Albright syndrome, Carney complex

Symptoms of Excess Growth hormone:

Symptoms of Excess Growth hormone Pituitary mass expansion symptoms • Headaches • Visual field defects • Cranial nerve palsies GH excess symptoms • Carpal tunnel syndrome • Coarse facial features • Spade-shaped hands • Enlarged feet • Growth of mandible • Hypertension – about 30% of patients • Cardiomyopathy • Arrhythmias

Excess GH Testing Algorithm :

Excess GH Testing Algorithm Suspect excess growth hormone IGF-1 Testing > 25% above the age adjusted reference range < 25% above the age adjusted reference range Oral Glucose Tolerance Test with Measurement of GH Suppression (OGTT GH) GH suppressed < 1 ng /ml GH not suppressed > 1 ng /ml Does not support diagnosis of Excess GH support diagnosis of Excess GH Pituitary imaging MRI/CT

GH Testing with excess growth Hormone:

GH Testing with excess growth Hormone Random GH testing is not recommended for the diagnosis of acromegaly. Nearly 30% of acromegaly patients will have random GH levels within the normal reference range. Of these 20% to 50% will, however, have elevated IGF-1 levels. The 24-hour mean integrated GH test impractical because it is costly, requires an inpatient hospital stay, generates >70 samples to be tested, and is time consuming for the patient and medical staff

IGF-1 Testing with excess growth Hormone:

IGF-1 Testing with excess growth Hormone The best initial screening test for all patients suspected of having acromegaly IGF-1 is consistently elevated in acromegaly patients, less variable serum concentration than GH. it also is a very sensitive indicator of minimal chronic increases in GH secretion IGF-1 also is the best indicator of clinical disease activity both during initial assessment and later to assess and monitor treatment. Measurement of IGF-1 requires only a random blood specimen.

OGTT GH tests:

OGTT GH tests Glucose suppresses insulin, which in turn suppresses GH OGTT GH is performed by giving 75 g of glucose orally and sampling for glucose and GH levels at 0, 30, 60, 90, and 120 minutes after administration of glucose IGF-1 and OGTT GH tests are employed together to diagnose acromegaly, they have a predictive value of 95% OGTT GH suppression testing should primarily be used as an adjunct to IGF-1 measurements, as approximately 20% of patients with acromegaly will have a normal OGTT GH suppression test, while their IGF-1 is elevated Additionally, several factors can cause false-positive OGTT GH test results, including adolescence, diabetes mellitus, liver disease, renal disease, and anorexia nervosa

IGFBP-3 Testing with excess growth Hormone:

IGFBP-3 Testing with excess growth Hormone IGFBP-3 testing is not as sensitive as IGF-1 at detecting GH in excess. In acromegaly patients, IGFBP-3 levels do not increase as much as IGF-1 levels, and they sometimes overlap with normal patient values. Thus IGFBP-3 is not recommended for routine use, but in cases where OGTT GH and IGF tests are discordant, it may be a useful adjuvant test

Excess GH Treatment Monitoring Algorithm :

Excess GH Treatment Monitoring Algorithm Monitor with IgF-1 Testing < lower 1/3 of age adjusted reference range > lower 1/3 of age adjusted reference range Above age adjusted reference range Oral Glucose Tolerance Test with Measurement of GH Suppression (OGTT GH) GH suppressed < 1 ng /ml GH not suppressed > 1 ng /ml Consider additional treatment Curried Monitor annually with IGF-1 testing

The battle of aging:

After age 35 the amount of body fat expands by 50%, while the lean body mass (LBM) that forms muscles, bones, and the vital organs actually shrinks by 30%. The battle of aging

Somatopause:

Somatopause Declines 14% per decade after age 25 due to decline in nocturnal pulses ( this means that HGH in the body is reduced by half at age 60 ) Both GH and IGF-1 decline with age due to : 1 - Loss of hypothalamus sensitivity 2- Decreased liver function 3- Lack of deep sleep 4- High blood sugar levels

Marketing of HGH in the Media :

Marketing of HGH in the Media In 1990, a study by Rudman, D. was published titled, “Effects of Human Growth Hormone on Men Over 60 Years Old” The study involved 21 men aged 61 to 81 who were apparently healthy but with IGF-1 levels below those found in normal young men 12 men were given HGH injections, 9 received placebo for a treatment period of 6 months Results were decrease in adipose tissue, increase in lean body mass and lumbar spine density in the treatment group (P < 0.05) The study became the “Gold Standard” referenced as the study supporting most claims by marketed by manufactures

Real future of anti-aging medicine lies with IGF-1:

Real future of anti-aging medicine lies with IGF-1 IGF-1 is 10 times more potent than HGH and some researchers and clinicians believe that it can be more effective when used as a therapy than human growth hormone. By taking IGF-1 directly the pituitary gland and liver are bypassed, which is good if they are damaged .

IGF 1 has been shown to have numerous benefits regarding anti-aging:

IGF 1 has been shown to have numerous benefits regarding anti-aging Improve Energy Improve Sex Life Lowers cholesterol level Improve Mood Extend life span in people that use it Reduce inflammation Stimulate glucose transport in human muscle tissue Diminish the rate of protein breakdown Shift fuel utilization from carbohydrates to fat, permitting the body to burn more fat Improve nitrogen retention and increase sodium excretion Improve parathyroid/Vitamin D interaction, producing denser bone

IGF-1 the dark side:

IGF-1 the dark side Several studies have shown powerful associations between blood levels of insulin-like growth factor-I (IGF-1) and the risk of colon cancer, prostate cancer, and premenopausal breast cancer. They suggest that IGF-1 may increase both cell turnover and the susceptibility of cells to become cancerous. They also point to recent evidence that indicates that IGF-1 prevents the programmed death (apoptosis) of cancer cells. GH and IGF-1 have been approved by the FDA for growth hormone deficiency in youngs and adults but not yet for ant aging purposes

IGF-1 Normal Ranges:

IGF-1 Normal Ranges According to Age and sex Anti-aging medicine believe that aging adults are better off having an IGF-1 level at the higher end of their normal range rather than at the lower end.

Conclusion:

Conclusion IgF-1 is the best indicator of GHD in children and adults IgF-1 is the best indicator of Excess GH in children and adults IgF-1 is the best indicator of treatment response in both GHD and Excess GH IgF-1 is 10 times more potent than GH as anti aging treatment

References:

References WWW.MAYOREFERENCESERVICES.ORG/COMMUNIQUE/ • MARCH 2006 WWW.MAYOREFERENCESERVICES.ORG/COMMUNIQUE/ • MAY 2007 Casanueva FF, Castro AI, Micic D, Kelestimur F, Dieguez C. New guidelines for the diagnosis of growth hormone deficiency in adults.Horm Res. 2009; 71 Suppl 1 :112-115. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. The Endocrine Society - Disease Specific Society. 2006. Federico G, Street ME, Maghnie M, Caruso-Nicoletti M, Loche S, Bertelloni S, Cianfarani S. Assessment of serum IGF-I concentrations in the diagnosis of isolated childhood-onset GH deficiency: a proposal of the Italian Society for Pediatric Endocrinology and Diabetes (SIEDP/ISPED).J Endocrinol Invest. 2006; 29 (8) :732-737. Bidlingmaier M, Strasburger CJ. Growth hormone assays: current methodologies and their limitations.Pituitary. 2007; 10 (2) :115-119. Cordero RA, Barkan AL. Current diagnosis of acromegaly.Rev Endocr Metab Disord. 2008; 9 (1) :13-19. Bidlingmaier M, Strasburger CJ. What endocrinologists should know about growth hormone measurements.Endocrinol Metab Clin North Am. 2007; 36 (1) :101-108. Ballard F, Wallace J, Francis G, Read L, Tomas F.  Des (1-3) IGF-1: a truncated form of insulin-like growth factor-1. International Journal of Cellular Biology. 28:1085-1087 (1996). Des (1-3) . Smith, George Davey, et al. Cancer and insulin-like growth factor-I. British Medical Journal, Vol. 321, October 7, 2000, pp. 847-48 (editorial)

PowerPoint Presentation:

Thank you for your attention

authorStream Live Help