EVALUATION AND MANAGEMENT OF SHORT STATURE.pptx

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1. Evaluation and management of short stature Dr Umesh Kumar Garg MBBS, MD, DM (Endocrinology) June 30, 2024, Jabalpur

2. Disclosure No Conflict of interest to disclose. Ardent Cricket Fan (Since childhood, not since last night) Not a Football Freak Yet

3. It is often challenging to identify children with abnormal growth patterns and distinguish normal growth variants from pathologic variants

4. Preface Short stature is defined as a height 2 SD below the mean/ < 3 rd centile Growth velocity <25 th centile or crossing down centile line Short for MPH (Mid-parental height) by 1.5 SD severe short stature being defined as a height >3 SD below the mean AGE SEX REFERENCE POPULATION

5. Why Present to you Shorter than their younger sibling Shortest in their class Gets teased ,Bullied / treated differently in school Height not meet expectations/ Want to be sure nothing WRONG Impediment to sports/Job Short stature causing DISTRESS

6. TO DO LIST---CHILD BROUGHT WITH CONCERN FOR HEIGHT Accurate height measurement * Assessment of height velocity if available Relevant history taking Assessment of body proportions Comparison with population norms Comparison with child’s own genetic potential Sexual maturity rating Bone Age Laboratory investigations

7. Why Present to you Shorter than their younger sibling Shortest in their class Gets teased ,Bullied / treated differently in school Height not meet expectations/ Want to be sure nothing WRONG Impediment to sports/Job Short stature causing DISTRESS

8. Height measurement Supine Length: – From birth to 2 years old – on Infantometer Measurement of stature is the cheapest procedure available in the pediatric office the one often incorrectly performed if even performed at all – Denis Styne “Pediatric Endocrinology”

9. Height measurement On Stadiometer preferably Without footwear & Heels & back touching the wall Lower border of the eye socket in the same horizontal plane as external auditory meatus (Frankfurt Plane) Gentle but firm pressure upwards applied to the mastoids from underneath Record to last 0.1 cm S ame time of day by a trained individual

10. Basic calculations MPH ( cms ) (boys) = Father’s Ht + Mother’s Ht + 13 2 MPH ( cms ) (girls) = Father’s Ht + Mother’s Ht – 13 2 Target height range ( cms ) = MPH +/- 8 cm

11. Growth Charts- IAP+WHO Plot height, weight, MPH, Target height range in appropriate growth charts, Calculate height age and weight age

12. Normal Growth rates First year- 25 cm Second year – 12 cm 3 rd and 4 th year – 6-7 cm >4 yr till puberty- 4-6 cm/ yr Puberty – boys -9-11cm/ yr Puberty – girls -7-9 cm/ yr

13. Anthropo-metrics HEIGHT AGE- Age at which the current height is at 50 th centile WEIGHT AGE- Age at which the current weight is at 50 th centile GROWTH VELOCITY- Growth over a period of time expressed in cm/year BONE AGE- Age corresponding to Level of maturation CHRONOLOGICAL AGE- Age in Calander year HT SDS- (Actual Height – Mean Height at same age & sex)/ SD for Height at same age & Sex WT SDS- (Actual weight – Mean weight at same age & sex)/ SD for weight at same age & Sex

14. Body proportion The lower body segment --distance from the symphysis pubis to the floor The upper body segment -- Height minus the lower body segment Normal US/LS = 1.7:1 at birth, 1.3:1 at 3 yr , 1.1:1 at 7 yr , 0.9:1 at 10 yr Children with achondroplasia, hypochondroplasia, rickets, hypothyroidism have relatively short extremities and therefore a higher US/LS On the other hand, children with spondylodysplasia , mucopolysaccharidosis, hemivertebrae, or metatropic dwarfism have a lower US/LS

15. Causes of short stature Normal Variants : Constitutional delay in growth, Familial short stature Idiopathic Short stature (ISS) : Endocrine Caus es : Hypothyroidism, Cushing Syndrome, Rickets, Psuedo -hypoparathyroidism, Poorly controlled diabetes, Untreated DI, CAH & PP GH-IGF-1 AXIS GHD = Congenital – (Isolated/MPHD/Genetic), Acquired - (Trauma, tumor, irradiation, etc ) Functional GHD – Psychosocial Dwarfism GH Resistance/(Primary IGF-1 Deficiency) = (Laron Syndrome, Pygmies), Acquired IGF-1 Resistance Modified from - Brook,s Clinical Pediatric endocrinology 7 th ed

16. Causes of short stature Syndromes of short stature - Turner syndrome, Noonan Syndrome, SHOX Deficiency, Trisomy 13,18,21, Prader Willi Syndrome, Bardet Biedl Syndrome Dysmorphic Syndromes- Russell silver, Cornelia de Lange, 3M Storage Diseases – Mucopolysaccharidoses, Muco-lipidoses Osteo-chondrodysplasias and OI Malabsorption syndromes & Malnutrition – incl. Coeliac disease, PCM, Micronutr Systemic disorders/ Chronic illnesses- Cardiac, Pulmonary, Hematological, Immunological, Renal and infections Modified from - Brook,s Clinical Pediatric endocrinology 7 th ed

17. ETIOLOGY OF SHORT STATURE Courtesy - Sperling Pediatric Endocrinology 5 th ed .

18. Clues on history and examination CLUES POSSIBLE ETIOLOGY Underweight Nutrition, Infection, SGA, Malabsorbtion Overweight Hypothyroidism, Cushing`s, GH def., IGF-1 def Pallor Nutrition, Thalassemia Frontal Bossing, Mid facial hypoplasia GH def/ resistance Macrocephaly Birth asphyxia, symmetric SGA, Sotos ’ syndrome Hypertension Renal disease, Cushings, Turner Micropenis Hypopituitarism/GHD Pubertal stage Precocious/ delayed Hepatosplenomegaly Metabolic disease/ Thalassemia Signs of neglect or abuse Psychosocial deprivation

19. Lab Evaluation Investigation should be guided by history and physical examination findings. Indiscriminate and unstructured testing should be avoided Tier 1 investigation- All with SS CBC, ESR, Blood Biochemistry - renal function test, calcium, phosphate, alkaline phosphatase, venous gas, fasting sugar, albumin, transaminases Urine analysis, stool analysis X ray for bone age (IgA TTG antibody, FT4, TSH, IGF-1) *

20. Lab Evaluation If previous investigations are normal and height between -2 to -3 SD, then observe height velocity for 6-12 months IGF-1 is used for screening due to stable levels * • If height <3 SD, proceed to Further Evaluation for GH Stimulation test Karyotype in each girl with unexplained short stature Other Investigation as per clinical Features incl Genetic study/MRI Pituitary

21. Bone Age Calculation Tanner and Whitehouse (TW-II/III) / Bone X Pert or Gruelich -Pyle method OR Roche- Wainer -Thissen (RWT) (Rarely) X-ray of non dominant hand-AP view. Compared with the standard of the same sex and nearest age with match to both older and younger to get the closest match. The difference between bone age and chronological age is an estimation of remaining growth potential

22. Delayed Bone Age ❖ Bone age <2SD or < 2yr of chronological age » Hypothyroidism » GH deficiency » Constitutional short stature » Corticosteroid Rx » Celiac disease

23. Traditional way of d/d on clustering Intrinsic shortness Delayed Growth Attenuated Growth BA = CA>HA BA = HA<CA HV ~ Normal BA = HA<CA HV: Subnormal Familial short stature Syndromic short stature Skeletal Dysplasias CDGP Mild-Moderate chronic illness Mild-Moderate malnutrition Endocrinopathies - GH deficiency - Hypothyroidism - Cushing syndrome Severe chronic illness Severe malnutrition

24. When GHD IS MORE LIKELY Severe short stature (Height SDS <-3 SD) Severe growth deceleration (height velocity SDS <-2 SD over 12 months) Height <-2 SD and Height velocity <-1.0 SD over 12 months Height <-1.5 SD and height velocity <-1.5 SD over 2 years Risk factors for GHD Modified from - Brook,s Clinical Pediatric endocrinology 7 th ed

25. GH Stimulation tests Random GH assays of no use due to pulsatile secretion Endocrine diagnostic principle – Suspecting Deficiency – Stimulation test and Suppression test in suspected excess Provocative GH testing is non-physiologic Arbitrary definitions of “subnormal” response to provocative tests • Expense, discomfort, and risks of provocative GH testing • Poor reproducibility/specificity of provocative tests, at least 2 test to be done *

26. GH Stimulation test Insulin tolerance test is “Gold Standard” Clonidine stimulation test and Glucagon stimulation test --- Most Commonly used In the past GH > 10 ng/ml was considered pass or normal Newer assay – Now > 7 ng/ml is considered Normal

27. GH Stimulation test Courtesy - Sperling Pediatric Endocrinology 5 th ed .

28. Sex Steroid Priming or not Not universally agreed upon for sex steroid priming - 1) No priming Sex steroid priming for any children with pubertal delay (prepubertal at 13–14 years in boys and 11–12 years in girls). Sex steroid priming for all peri‐pubertal children (boys >9 years, girls >8 years based on chronological or bone age). Sex steroid priming before provocative GH testing augments the ability of the secretagogues to elicit a GH response and improves test specificity Reduces False Positive test (Esp CDGP)

29. Constitutional delay in growth and puberty (CDGP) Often presents in adolescence More prevalent in boys Normal length at birth, start falling <5th centile in 1st 3 yrs of life Delayed puberty Parents stature: average Family history: delayed puberty Height velocity: normal Bone age = Height age <Chronological age GH secretion is usually normal Final height: normal

30. Management Specific management of disorders Gluten Free Diet- Coeliac Disease Levo -thyroxin Replacement in hypothyroidism Appropriate Management for RTA, Rickets Vosoritide for Achondroplasia Optimal management for chronic illness and other disorders

31. Management Growth Hormone Only When Growth Hormone deficiency proven or other valid indications Weight based daily sc Injection is preferred Now weekly SC formulation available

32. approval For GH IN CHILDREN WITH SS Growth hormone deficiency 1985 Chronic renal insufficiency 1993 Turner syndrome 1997 Prader–Willi syndrome 2000 Small for gestational age 2001 Idiopathic short stature 2003 SHOX gene deficiency 2007 Noonan syndrome 2008 Sperling pediatric endocrinology 5th ed

33. Various GH Dosing Regimen-SS 1 mg 3 u Indication Daily dose (U/Kg/d) Growth hormone deficiency 0.08-0.12 Prader Willi syndrome .24-0.72 Chronic kidney disease .1 SHOX gene haploinsufficiency 0.1 Turner syndrome 0.1-0.15 SGA children who fail to catch up .1-0.2 Idiopathic short stature 0.1-0.2 Noonan syndrome .12-0.15

34. Monitoring At 1 month – Technique, compliance and side effects At 3 month look for subclinical AI, Hypothyroidism which may manifest Every 3-6 month Anthropometry IGF-1 to keep it in target

35. Potential side effects OF GH Oedema Arthralgia Benign intracranial hypertension Impaired insulin sensitivity Slipped femoral epiphysis Worsened scoliosis ??

36. When to stop

37. Practice pearls Use of growth charts and interpretation with MPH is of utmost importance in each case Growth velocity is a more valuable indicator to monitor linear growth and detect growth faltering Chronic illness/ Malnutrition is a common disregarded cause of SS esp. in our country • Growth hormone testing and treatment should be reserved and undertaken by a trained endocrinologist

38. TAKE HOME MESSAGE With a proper background knowledge, careful history, meticulous physical examination and targeted investigations, an exact diagnosis of a short child can be arrived at!”

39. Gratitude My Teachers – Prof S K Mathur, Prof Balram Sharma (SMS MC Jaipur)- For everything Team Endo-Brigade and Friends- for their constant motivation and supports ( Dr Mohan T Shenoy, Dr Ameya Joshi, Dr Kaushik Biswas, Dr Om J Lakhani, Dr Rama Mohan M V, Dr Basav Raj G S, Dr Karthik B C, Dr Rajesh Moganti ) Dr P K Jabbar Sir, Dr Santosh R, Dr Saptarishi Bhattacharya, Dr Vrind K Bhardwaj and Dr Vikram Singh Chauhan for providing me the opportunity

40. THANK YOU ALL