Growth Failure or Just Short Stature?

Transcription

1 Growth Failure or Just Short Stature? Amy Chartoff, APN The Molly Center for Children with Diabetes and Endocrine Disorders May 21,2014

2 I have no disclosures

3 Chapter 1, Worrisome Growth; Pediatric Endocrinology, 5 th Edition, volume 2, Fima Lifshitz, Editor Growth can be worrisome along two variables: height (short stature) and velocity (growth failure)

4

5

6

7

8

9

10

11

12

13

14

15 Why discuss short stature/growth failure? Growth is the # 1 reason for referral to pediatric endocrinology Growth failure may be a sign of underlying disease 1 in 3,500 children may have growth hormone deficiency # of girls should be equal to # boys The earlier a problem is identified, the earlier treatment is started, the better the outcome

16 Definition of short stature >2 SD below the mean length or height for sex and chronological age (<2.3%ile) Substantially below the predicted height based on biological parents height (target height) (to calculate target height, add 6.5 cm to mother s height for boys, subtract 6.5 cm from dad s height for girls. Midpoint between same sex parent s height and opposite sex s corrected height is target, +/- 10 cm for expected range) Nichol et al. Pediatric Practice: Endocrinology:2010; 23-76

17 Definition of growth failure Growth velocity below normal for age (Growth that crosses over percentiles in a downward fashion, regardless of the percentile the child is on.) ie: dropping from 75%ile to 25%ile is growth failure, even though the child is still on the normal curve. Ref: Pediatric Endocrinology, 5 th Edition, volume 2, Fima Lifshitz, Editor

18 Measurement caveats Minimum of 3 mo interval needed to accurately calculate GV. 6 mo interval is preferable. There can be seasonal variation in height velocity Marshal WA (1971) Evaluation of growth rate in height over periods of less than one year. Arch Dis Child 46:414

19 Growth velocity calculation (cm/yr) Height (cm) measured at time 1 --Height (cm) measured at time 2 Number of months between time 1 and time 2 X 12 (months/yr)

20 What is the importance of monitoring growth? Growth is an excellent measure of the health and wellbeing of a child Lack of growth could be a sign of underlying health issues: chronic illness, IBD, celiac, hypothyroidism, GHD Stature is height, growth is the rate at which you increase your size Growth failure is abnormal, short stature may not be

21 Childhood is a time for growth Children usually grow in a very predictable manner Deviation from a normal growth pattern can be the first manifestation of both endocrine and non-endocrine disorders

22 From conception through the first year of life, growth is almost entirely dependant upon nutrition. Congenital GHD, congenital thyroid disease, sex hormone deficiency: all these babies are near normal size at birth and may grow well for 6 months 1 year.

23 What do we need to grow? Malnutrition is still the leading cause of short stature in the world Consequence of malnutrition is weight loss & decreased GV, leading to short stature Conversely Over nutrition leads to obesity and tall stature

24 How do children become short? It is important to know when the child started to fall off the growth curve If SGA with no catch up, there may be defects related to growth plates (chromosomal anomalies, skeletal dysplasia) SGA with catch-up growth postnatally (by 2 yr of age) probably related to maternal factors (placental factors, in-utero infections)

25 Tall children become tall by growing at a rate that is (consistently) slightly greater than that of their peers ie: A child growing at the 95%ile needs to grow 6.5 cm/yr vs a child at the 5%ile who grows 5 cm/yr, in order to maintain the percentile they are on

26 Was baby AGA but started to fall off curve soon after birth? Consider congenital defect in organs whose function was not necessary or was modified in utero. (kidney, lung, GI, liver/metabolic, thyroid, cardiac)

27 AGA growing well for ~ 6 mo and then falls off growth curve Re-evaluate at 18 mo: If they HAVE NOT resumed normal growth rate, consider hormone deficiency or nonendocrine causes If they HAVE resumed a normal rate, can be genetic short stature or constitutional delay

28 Is growth failure uniform among all growth plates? If not, think of skeletal dysplasia, rickets Is bone age delayed? If yes, think of factors unrelated to growth plates (hormone deficiency, malabsorption), or constitutional delay

29 Is growth failure an isolated symptom, or is there evidence of underlying disease process? (abd distention, bowed legs, murmur, stigmata of a syndrome) Some children may be asymptomatic or the family is used to the symptoms ( my child has always been the smallest )

30 What do I need to know? Is there a family history of short stature, constitutional delay of growth and/or delayed puberty? If yes, probably Genetic Short Stature (GSS) and/or Constitutional Delay of Growth (CDG) make sure there is no herditary disease related to short stature (GHD, dysplasia)

31 Important to know the parent heights, in order to make an estimation of the target range for the child Can use reported parental heights But guess what? They (may) over estimate their height, so MEASURE THEM when possible

32 What is normal growth? Up to 3 years of age, and then again during puberty, crossing percentiles could be normal Any child between 3 yr and start of puberty should grow at least 5 cm/yr

33 Plot measurements at exact age (ie 3 y 3 mo) Growth charts available at

34 How accurate are measurements? Measurement errors can occur (not easy measuring a squirming child) Short term growth velocity is not always accurate: (ie 6 mo rate is better than 3 mo rate) There can be seasonal differences in growth velocity

35 -2SD to +2 SD includes 94% of all children -2 SD to -3 SD: ~8% will have organic reason for short stature -3 SD to-4 SD: 50% have organic reason for short stature

36 The art of measurement Sounds simple enough, but good measuring technique, as well as plotting the measurements appropriately, is essential to knowing how well the child is growing. So how do you measure?

37 Measurement guidelines A & B: Recumbent stadiometer with fixed foot board and moveable head board. C: Standing wall mounted stadiometer

38 Measuring technique Infants should be measured lying down on a length board. Feet at fixed end, 2 people are needed for an accurate measurement. (use up to 3 yrs) Children > 3 yr old should be measured on a wall mounted stadiometer. 2 people should be used. (to prevent tippie-toes or bent knees) No shoes, no hair ornaments, high pony tails, buns, hats, etc.

39 Child should stand with heels, knees straight, buttocks & upper back touching the stadiometer. Feet should be together Arms hanging relaxed at sides of body Line of vision parallel to floor (Frankfort plane) DO NOT USE: exam table paper, height rod on scale, ruler or book, no carpeting under feet, pencil marking on wall

40 Measure to the nearest 1 mm 3 measurements, averaged, is ideal Plot measurement at the exact age (ie: not 5 y but 5 yr 3 mo) If measurement doesn t seem correct when plotted, (GV too fast, too slow) remeasure the child If GV is abnormal, re-measure in 3-4 months

41 Screening All diseases impair growth, so a child who is growing slowly needs a diagnosis and appropriate treatment CMP, CBC, U/A, CRP/ESR Screen for thyroid disease (TFT s + antibodies, based on family hx), celiac, adrenal insufficiency, karyotype as well as array CGH in select cases, (all short girls need karyotype), gonadotropins (based on age and presentation)

42 Which labs are most helpful? Free T4 and TSH (no T3 or T4 uptake) IGF-1 & IGF BP3 (IGF-1 can be low due to poor weight gain) Anti-thyroglobulin ab & antitpo ab (family hx) Total IGA, Anti-transglutaminase IGA/IGG ab Antigliadin IGA/IGG ab Cortisol, (+/-ACTH) **prior to 9 am Vitamin D 25 OH +/- LH, FSH, Estradiol or Testosterone (age dependant) Bone age x-ray (left hand and wrist)

43 Growth Hormone Growth Hormone is secreted in pulses, mostly at night so. Random growth hormone levels are useless. (unless it is high: that would be abnormal) Best screening test for GH is IGF-1 and IGF BP3 (IGF-1 can be affected by nutritional status)

44 It is important to know the baseline screening results before going forward, as we may uncover the reason for poor growth and begin treatment, which may address the poor growth. ie: hypothyroidism, celiac, adrenal insufficiency, abnormal karyotype (Turner syndrome, Noonan syndrome, etc.)

45 Some abnormalities/diseases we uncover may also require growth hormone to assist in achieving the best possible adult height Depending upon age at diagnosis, & if much ground has been lost, we may consider growth hormone to help improve outcome Turner syndrome, Noonan syndrome, SGA without catch-up by 2 y of age are all FDA approved indications for growth hormone treatment, without GHD

46 What next? After careful re-measurement in 3-4 months from initial consult, & based on the screening labs, Growth Hormone stimulation testing may be considered, along with Lupron stimulation test (to assess pubertal status if early or no pubertal signs and/or age is appropriate) & ACTH stimulation to assess adrenal function

47 Review of some growth charts Can you guess the diagnosis?

48 GHD, started 9 y 9m

49 Acquired hypothyroidism: (TSH>500) 5 y 4 m; Puberty started < 8 y old, tx d with Lupron, GV decreased, tx d with Gh at 8 y 4 m, Dc d Lupron and GH at 11 y

50 Hashimoto s hypothyroidism, TSH >500, Levoxyl started at 13 y, Started puberty rapidly, tx d with Lupron starting at 13 y 7 m, d/c d at ~ 16 y. Also GHD, familial polyposis. Unable to treat with GH due to FP.

51 GHD, Tx d with Lupron Depot PED & Growth hormone starting at 10.5 y, Discontinued treatment at ~ 14 y, per patient request. She was happy with her height at that time.

52 Hashimoto s hypothyroidism; dx d after seeing GI for facial puffiness and belly pain. TSH Ttg IGA ab elevated. Started on lthyroxine to normalize TFT s prior to endoscopy. Biopsy confirmed celiac disease.

53 ISS. GH stim test peak GH 16 Started GH 11 y 2 m, discontinued GH 13 y 6 m per patient request. She was happy with her height at that time.

54 ISS. GH stim test peak GH 13 Started GH 6 y 6 m.

55 ISS. GH stim test peak GH 10.8, waiting for approval to start GH

56 Interrupted pituitary stalk: GHD, hypothyroid, hypogonadism

57 Turner syndrome, dx d at 7 y. 46 x/ 46xx; Started GH at 8 y.

58 Prolactinoma

59 References Pediatric Endocrinology.:The Requisites in Pediatrics; Edited by Thomas Moshang, Jr., MD, Mosby, 2005 Pediatric Endocrinology, Fifth Edition, Volume 2, Growth, Adrenal, Sexual, Thyroid, Calcium and Fluid Balance Disorders; Edited by Fima Lifshitz, Informa Healthcare, USA, 2009 Pediatric Endocrinology, Third Edition, Edited by Mark A. Sperling, MD, Saunders, 2008

60 Nichol et al. Pediatric Practice: Endocrinology:2010; Marshal WA (1971) Evaluation of growth rate in height over periods of less than one year. Arch Dis Child 46:414