HUMAN GROWTH HORMONE DEFICIENCY PPT.pptx

APPROACH TO GH DEFICIENCY

1. GROWTH HORMONE DEFICIENCY

2. 191–amino acid, single- chain polypeptide. Synthesized, stored and secreted by somatotropes in the pituitary. Secreted in pulsatile fashion under regulation of hypothalamic hormones. GH- releasing hormone (GHRH)- Stimulates GH release. Somatostatin - Inhibits GH release.

3. Effects of GH: Increases: Linear growth Bone thickness Soft tissue growth Protein synthesis Fatty acid release from adipose tissue Insulin resistance Blood glucose Mediated through IGF-1

4. Etiology Congenital : Genetic defects - Isolated GH deficiency: Defect in GH1 gene:type 1 –autosomal recessive type 2 –AD type 3- AR Defect in GHRHR gene –type 4 -Multiple pituitary hormone deficiency Type1-AR Type 2-XLR

5. Developmental defects: Pituitary aplasia /hypoplasia Holoprosencephaly Septo -optic dysplasia Anencephaly

6. Acquired: Tumors – hypothalamic, pituitary other intracranial tumors Irradiation Infections- encephalitis, meningitis, tuberculosis, toxoplasmosis Infiltration – histiocytosis , hemochromatosis, sarcoidosis Injury – perinatal insult(breech),head injury, surgery Vascular- aneurysm, infarction

7. Clinical Features Normal growth at birth Growth retardation apparent at 1 year Body proportion: Normal Overweight over height with markedly increased subcutaneous fat Teeth development delayed Doll like facial appearance Delayed bone age: Height age < Bone age and Chronological age

8. Mid-facial crowding Round facies Mild Obesity Immature facial appearance Depressed nasal bridge Frontal bossing Prominent philtrum

9. High pitched voice Increased skin fold thickness Truncal obesity Single central incisor Hypoplastic penis and scrotum

10. Resistance to growth hormone action –Growth hormone insensitivity or Laron syndrome Severe growth retardation and elevated baseline GH levels

11. History Perinatal history, birth weight and length Early indicators of GHD – History of birth asphyxia, breech presentation, neonatal hypoglycemia and prolonged jaundice Features of chronic illness - CVS , pulmonary problems , malnutrition and chronic raised intracranial tension Rule out other causes: Diabetes, Renal tubular acidosis , Hypothyroidism Family history: Familial Short Stature,CDGP

12. Examination Anthropometry : Weight, height,weight for height, BMI,head circumference Body Proportion Lower Segment (LS) : Symphysis pubis to feet Upper Segment (US) : Length – LS

13. US : LS Increased -> hypothyroidism,rickets , achondroplasia , Turner’s syndrome US : LS Decreased -> Morquio syndrome, spondyloepiphyseal dysplasia US : LS Normal -> Growth hormone deficiency Dysmorphism and deformities Sexual maturity rating

14. Investigations Stepwise approach Step 1 : r/o malnutrition,chronic diseases,recurrent infections Bone age Step 2 : r/o hypothyroidism,celiac disease,Turner syndrome Step 3: GH-IGF axis GH stimulation test : insulin,glucagon,clonidine,GHRH GH deficiency:<7ng/ml IGF-1,IGFBP-3

15. Look for other pituitary hormone deficiencies in GHD MRI of hypothalamic and pituitary region- r/o developmental/acquired neurological lesions

16. Management General measures : Correct underlying cause & provide adequate nutrition Nonspecific – High protein & calorie diet – Increase physical activity – Correct iron & vitamin deficiencies

17. Specific therapy : Thyroxine -hypothyroidism Gluten free diet- celiac disease Bicarbonate supplements-renal tubular acidosis Testosterone -CDGP

18. Growth hormone – Subcutaneous i njection 25-50 microgram/kg/day at night-time till epiphyseal closure – Increase in final height by 20-30 cm – Very expensive, given for at least 2 years Short course of testosterone in boys with constitutional delay of puberty and growth

19. Indications of GH GH deficiency in children and adults Turner syndrome Noonan syndrome Prader – Willi syndrome Russel –Silver syndrome Chronic renal insufficiency SGA failing to catchup growth by 2-3yrs Idiopathic short stature SHOX gene mutation,Leri -Weill dyschondrosteosis

20. Monitoring : Growth velocity and bone age IGF-1 levels :if response suboptimal /on high dose

21. THANKYOU