SHORT STATURE MZ.Zamanpour MD

Normal Growth  Normal growth: A good evidence of overall health  Endocrine, Environmental, Nutritional, and Genetic factors 2

Growth Hormone Physiology  Pulsatile secretion  GH-releasing factor (GRF)  Somatostatin, somatotropin release-inhibiting factor [SRIF]  Ghrelin  GHBP  IGF-1 Influenced by malnutrition, chronic renal and liver disease  hypothyroidism, or obesity  Acid-labile subunit  IGF-BP3 Less influenced by nutrition and age 3

Measurement of Growth  Length→ infants  Height→ After 2 years of age  A decrease of roughly 1.25 cm in height measurement may occur when the child is measured in the standing position rather than in the lying position  arm span Marfan or Klinefelter syn, short-limbed dwarfism, dysmorphic conditions  upper-to-lower segment ratio Term infant → 1.7:11-year → 1.4:110-year → 1:1 Adult → ↑ in hypothyroidism↓ in hypogonadism 4

Endocrine Evaluation of Growth- Hormone Secretion  191–amino  Under the control of GRF and SRIF  ↑ -adrenergic stimulation, hypoglycemia, starvation, exercise, early stages of sleep, stress  ↓ β-adrenergic stimulation and hyperglycemia  Pulsatile secretion  Peaks in the middle of the night or early morning  Provocative(stimulation) tests high false-positive rate  Indirect measurements of GH secretion IGF-1 and IGF-BP3 5

Hormonal Effects on Growth 6

Short Stature 7

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Short Stature of Nonendocrine Causes  Nutrition : the most important factor affecting growth worldwide  Maternal deprivation nutritional deficiency aberrant psychosocial interaction  Organic illness Anorexia nutrient losses through a form of malabsorption hypermetabolism by hyperthyroidism or other causes  Psychosocial or deprivation dwarfism Functional temporary GH deficiency and poor growth when placed in a different, healthier psychosocial environment, GH physiology normalizes, and growth occurs 10

Short Stature of Nonendocrine Causes Cont  Constitutional delay in growth or puberty or both A common condition A variation of normal Reduced tempo, or cadence, of physiologic development Usually a family member had delayed growth or puberty Normal final height Bone age is delayed Growth rate remains mostly within the lower limits of normal Usually leads to a delay in secondary sexual development 11

Short Stature of Nonendocrine Causes Cont 12  Genetic or familial short stature Short parents Reach a lower than average height If the parents were malnourished as children, grew up in a zone of war, or suffered famine, the heights of the parents are less predictive the most significant difference in stature between ethnic groups is the result of nutrition  Syndromes of short stature Abnormal arm spans and upper-to-lower segment ratios Combined obesity and decreased height

Short Stature of Nonendocrine Causes Cont 13 Prader-Willi syndrome Fetal and infantile hypotonia Small hands and feet (acromicria) Postnatal acquired obesity Insatiable appetite Developmental delay Hypogonadism Almond-shapedeyes Abnormalities of the snRNP portion of the 15q11-q13

Short Stature of Nonendocrine Causes Cont 14 Laurence-Moon-Bardet-Biedl syndrome Retinitis pigmentosa Hypogonadism Developmental delay Autosomal dominant Spastic paraplegia Obesity and polydactyly

Short Stature of Nonendocrine Causes Cont 15 Pseudohypoparathyroidism Short stature Developmental delay Short fourth & fifth digits (albright hereditary osteodystrophy phenotype) Resistance to parathyroid hormone Hypocalcemia, and elevated levels of serum phosphorus

Short Stature of Nonendocrine Causes Cont 16 Turner syndrome 45XO or mosaic karyotype Short stature Shield chest Widespaced nipples Wide-carrying angle of the upper extremities High-arched palate Gonadal failure Kidney dysplasias with normal function Aortic arch abnormalities Susceptibility to autoimmune disorders

Patterns of linear growth A, Constitutional delay of growth and adolescence (short stature with normal growth rate for bone age, delayed pubertal growth spurt, and eventual achievement of normal adult stature). B, Familial short stature(short stature in childhood and as an adult). C, Acquired pathologic growth failure (e.g., acquired untreated primary hypothyroidism) 17

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Short Stature Caused by Growth Hormone Deficiency  1 in 4000 to 1 in 10,000 children  Idiopathic GH deficiency The most common cause of both congenital and acquired GH deficiency  Classic congenital GH deficiency Anatomic defects of the pituitary gland ( aplasia, midline defects, with variable degrees of deficiency of other pituitary functions) Very reduced to absent secretion of GH  Acquired GH deficiency Late-onset growth failure suggests Possibility of a tumor of the hypothalamus or pituitary 19

Clinical Manifestations  Normal or near-normal birth length and weight at term  Growth rate slows after birth, most noticeably after age 2 to 3 years  Elevated weight-to-height ratio  Most patients elude diagnosis until several years of age  Appearance of a cherub (a chubby, immature appearance)  High-pitched voice  Normal intellectual growth and age-appropriate speech  Microphallus (a stretched penile length of <2 cm  Fasting hypoglycemia 20

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GH Resistance or GH Insensitivity  Laron syndrome Utosomal recessive prominent forehead hypoplastic nasal bridge delayed dentition sparse hair blue sclerae delayed bone maturation and osteoporosis progressive adiposity, hypercholesterolemia low blood glucose ↑GH, ↓ IGF1 & IGFBP3  Acquired GH resistance Malnutrition, medications (corticosteroids), or severe liver disease 22

Diagnosis  family or other medical history  Screening Lab tests  Karyotype  Bone Age  R/o Chronic Diseas  R/O familial short stature  GH stimulatory (provocative) test *2 Height 3.5 SDs below the mean Height velocity below the 5th percentile for age Height below the target height corrected for MPH  IGF1, IGFBP3 ??? 23

Treatment  biosynthetic recombinant DNA–derived GH ( mg/w)  Dosage is titrated to the growth rate  Side effects slipped capital femoral epiphysis pseudotumor cerebri  Ididpathiv short stature <  Turner Syndrome  chronic renal failure  Prader-Willi syndrome  SGA with no catch-up growth by 2 years of age 24