Short stature
What is the etiology of acquired GH deficiency?
Acquired GH deficiency causing late-onset growth failure suggests the possibility of a tumor of the hypothalamus or pituitary causing compression of the area. Malnutrition, medications (corticosteroids), or severe liver disease may cause acquired GH resistance because serum GH is elevated and IGF-1 is decreased.
What is Laron syndrome?
A very rare cause of growth failure is GH resistance or GH insensitivity, caused by abnormal number or function of GH receptors or by a postreceptor defect. Patients with the autosomal recessive Laron syndrome, involving mutations of the GH receptor, have a prominent forehead, hypoplastic nasal bridge, delayed dentition, sparse hair, blue sclerae, delayed bone maturation and osteoporosis, progressive adiposity, hypercholesterolemia, and low blood glucose.
What is the most common cause of short stature in children? A. Familial short stature B. Chromosomal abnormality C. Constitutional delay of growth D. Hypothyroidism E. Pituitary dwarfism
A. Familial short stature The most common cause of short stature in children is short parents. When a short child who is growing at a normal rate and has a normal bone age is found to have a strong family history of short stature, familial short stature is the most likely cause. Other causes of short stature include constitutional delay of growth, chromosomal abnormalities, intrauterine growth restriction, chronic diseases such as renal disease or inflammatory bowel disease, hypothyroidism, adrenal hyperplasia, growth hormone deficiency or resistance, psychosocial dwarfism, and idiopathic short stature.
How is growth measured after 2 years of age?
After 2 years of age, the height of a child should be measured in the standing position. Children measured in the standing position should be barefoot against a hard surface.
Bone age can sometimes be used to differentiate certain causes of short stature in children. With respect to bone age, which of the following statements is true? A. Bone age is normal in both familial short stature and constitutional delay of growth B. Bone age is normal in familial short stature and delayed in constitutional delay of growth C. Bone age is normal in constitutional delay of growth and delayed in growth hormone deficiency D. Bone age is delayed in both familial short stature and short stature caused by hypothyroidism E. Bone age is variable and cannot be used to differentiate familial short stature and constitutional delay
B. Bone age is normal in familial short stature and delayed in constitutional delay of growth Bone age determination can distinguish between the two most common causes of short stature: familial short stature and constitutional delay of growth. Children with familial short stature have normal bone ages. Constitutional delay of growth, which is really a delay in reaching ultimate height and sexual maturation, is manifested with delayed bone age and delayed sexual maturation. Hypothyroidism and growth hormone deficiency usually are manifested with a delayed bone age.
How is growth hormone secretion evaluated?
Because concentrations of GH are low throughout the day, except for brief secretory peaks in the middle of the night or early morning, the daytime ascertainment of GH deficiency or sufficiency on the basis of a single determination of a random GH concentration is impossible. Adequacy of GH secretion may be determined by a stimulation test to measure peak GH secretion. A normal response is a vigorous secretory peak after stimulation; the lack of such a peak is consistent with GH deficiency. However, there is a high false-positive rate. Indirect measurements of GH secretion, such as serum concentrations of IGF-1 and IGF-BP3, are considered better screens for GH deficiency.
What is bone age?
Bone age (AP x-ray of the left wrist) helps delineate familial short stature from constitutional delay -An advanced bone age ⇒ precocious puberty -A normal bone age ⇒ familial short stature -Delayed bone age ⇒ constitutional delay
What GH stimulatory test results are indicative of GH deficiency?
Classic GH-deficient patients do not show an increase in serum GH levels after stimulation. Tests for GH secretion are insensitive, not very specific, and fairly variable.
What is the epidemiology of congenital GH deficiency?
Classic congenital or idiopathic GH deficiency occurs in about 1 in 4000 children.
What is disproportionate short stature?
Disproportionate short stature is characterized by short limbs but an average-sized trunk -Rickets and achondroplasia (dwarfism).
How is GH deficiency treated?
GH deficiency is treated with biosynthetic recombinant DNA-derived GH. Dosage is titrated to the growth rate, weight of the patient and IGF-1 levels. Treatment with GH carries the low risk of an increased incidence of SCFE, especially in rapidly growing adolescents, and of pseudotumor cerebri. Psychological support of children with severe short stature is important.
What is genetic/familial short stature?
Genetic or familial short stature refers to the stature of a child of short parents, who is expected to reach lower than average height and yet normal for these parents.
What is growth failure?
Growth failure denotes a slow growth rate regardless of stature. Ultimately a slow growth rate leads to short stature, but a disease process is detected sooner if the decreased growth rate is noted before the stature becomes short. Plotted on a growth chart, growth failure appears as a curve that crosses percentiles downward and is associated with a height velocity below the 5th percentile of height velocity for age.
What is growth hormone?
Growth hormone (GH) secretion is pulsatile, stimulated by hypothalamic GH-releasing factor (GRF), and inhibited by GH release inhibitory factor (somatostatin, somatotropin release-inhibiting factor [SRIF]), which interact with their individual receptors on the pituitary somatotrope in a noncompetitive manner. GH is also stimulated by a number of factors (e.g. ghrelin, sex steroid hormones, clonidine, hypoglycemia, etc.) GH circulates bound to a GH-binding protein (GHBP); GHBP abundance reflects the abundance of GH receptors. GH has direct effects on tissue and also causes production and secretion of insulin-like growth factor-1 (IGF-1) in many tissues. GH stimulates IGF-1 production in the liver along with production of the acid-labile subunit and the IGF-binding protein (IGF-BP3); this forms the complex that delivers IGF-1 to tissue.
What is insulin-like growth factor-1 (IGF-1)?
IGF-1 acts primarily as a paracrine and autocrine agent and is most closely associated with postnatal growth. When IGF-1 attaches to its membrane-bound receptor, second messengers are stimulated to change the physiology of the cell and produce growth effects. IGF-1 production is influenced by disease states such as malnutrition, chronic renal and liver disease, hypothyroidism or obesity.
What is the etiology of congenital GH deficiency?
Idiopathic GH deficiency, of unidentified specific etiology, is the most common cause of both congenital and acquired GH deficiency. Less often, GH deficiency is caused by anatomical defects of the pituitary gland, such as pituitary aplasia or other midline defects, with variable degrees of deficiency of other pituitary functions. Hereditary forms of GH deficiency that affect pituitary differentiation are the result of heterogeneous defects of the gene for GH, GRF, or GH receptor. Classic GH deficiency refers to very reduced to absent secretion of GH; numerous short children may have intermediate forms of decreased GH secretion.
What are GH stimulatory tests?
If chronic disease or familial short stature are ruled out and routine laboratory testing is normal, two GH stimulatory tests are commonly performed. GH testing should be offered to a patient who is short (<5th percentile and usually >3.5 SDs below the mean), growing poorly (<5th percentile growth rate for age), or whose height projection, based on bone age, is considerably below the target height when corrected for family height.
What is the appropriate laboratory evaluation for GH deficiency?
If family or other medical history does not provide a likely diagnosis, screening tests should include a metabolic panel to evaluate kidney and liver function, a complete blood count (CBC) to rule out anemia, a celiac panel to rule out celiac disease, ESR, thyroid function testing, and IGF-1, IGFBP-3 for children under age 3 years. A urine study should be performed to assess renal function and evaluate for renal tubular acidosis. In girls, a karyotype to rule out Turner syndrome should be considered. A bone age will establish skeletal maturation.
How does congenital GH deficiency present clinically?
Infants with congenital GH deficiency achieve a normal or near-normal birth length and weight at term, but the growth rate slows after birth, most noticeably after age 2-3 years. These children become progressively shorter for age and tend to have an elevated weight-to-height ratio. Careful measurements in the first year of life may suggest the diagnosis, but most patients elude diagnosis until several years of age. A patient with classic GH deficiency has the appearance of a cherub (a chubby, immature appearance), with a high-pitched voice resulting from an immature larynx. The patient usually has normal intellectual growth and age-appropriate speech. Male neonates with isolated GH deficiency with or without gonadotropin deficiency may have a microphallus (a stretched penile length of <2 cm [normal is 3-5 cm]) and fasting hypoglycemia.
What is Laurence-Moon-Bardet-Biedl syndrome?
Laurence-Moon-Bardet-Biedl syndrome is characterized by retinitis pigmentosa, hypogonadism, and developmental delay with an autosomal dominant inheritance pattern. Laurence-Moon syndrome is associated with spastic paraplegia; Bardet-Biedl syndrome is associated with obesity and polydactyly.
When is arm span measured?
Measurement of the arm span is essential when the diagnoses of Marfan or Klinefelter syndrome, short-limbed dwarfism, or other dysmorphic conditions are considered. Arm span is measured as the distance between the tips of the fingers when the patient holds both arms outstretched horizontally while standing against a solid surface.
What is growth?
Normal growth is the final common pathway of many factors, including endocrine, environmental, nutritional, and genetic influences. A normal linear growth pattern is good evidence of overall health and can be considered a bioassay for the well-being of the whole child.
What is the most important factor affecting growth?
Nutrition is the most important factor affecting growth on a worldwide basis. Failure to thrive may develop in the infant as a result of maternal deprivation (nutritional deficiency or aberrant psychosocial interaction) or as a result of organic illness (anorexia, nutrient losses through a form of malabsorption, or hypermetabolism caused by hyperthyroidism or other causes).
How can height be suggestive of chromosomal abnormalities?
Phenotypic features suggesting an underlying chromosomal disorder can occur in many syndromes. These syndromes can be suspected by attending to arm spans and upper-to-lower segment ratios. Genetic syndromes often combine obesity and decreased height, whereas otherwise normal obese children are usually taller than average and have advanced skeletal development and physical maturation.
What is proportionate short stature?
Proportionate short stature (PSS) is when the person is small, but all the parts are in the usual proportions: -Prenatal etiologies include intrauterine growth retardation, placental dysfunction, intrauterine infections, teratogens, and chromosomal abnormalities (trisomy 21 and Turner's syndrome) -Postnatal causes include malnutrition, chronic systemic disease, psychosocial deprivation, drugs and endocrine disorders (hypothyroidism), GH deficiency, glucocorticoid excess, and precocious puberty
What is pseudohypoparathyroidism?
Pseudohypoparathyroidism leads to short stature and developmental delay with short fourth and fifth digits (Alright hereditary osteodystrophy phenotype), resistance to parathyroid hormone and resultant hypocalcemia, and elevated levels of serum phosphorus.
What is deprivation dwarfism?
Psychological difficulties also can affect growth, as in psychosocial or deprivation dwarfism, in which the child develops functional temporary GH deficiency and poor growth as a result of psychological abuse; when placed in a different, healthier psychosocial environemnt, GH physiology normalizes, and growth occurs.
What is short stature?
Short stature is defined as subnormal height relative to other children of the same gender and age, taking family heights into consideration. The CDC growth charts use the 3rd percentile of the growth curve as the demarcation of the lower limit.
What is Prader-Willi syndrome?
The Prader-Willi syndrome includes fetal and infantile hypotonia, small hands and feet, postnatal acquired obesity with an insatiable appetite, developmental delay, hypogonadism, almond-shaped eyes, and abnormalities on the snRNP portion of the 15th chromosome at 15q11-q13. Most cases have deletion of the paternal sequence, but about 20-25% have uniparental disomy, in which both chromosomes 15 derive from the mother.
What is constitutional delay?
The common condition known as constitutional delay in growth or puberty or both is considered a variation of normal growth, caused by a reduced tempo, or cadence, of physiological development. Usually a family member had delayed growth or puberty but achieved a normal final height. The bone age is delayed, but the growth rate remains mostly within the lower limits of normal. Constitutional delay usually leads to a delay in secondary sexual development.
How is growth measured in an infant?
The correct measurement of an infant's length requires one adult to hold the infant's head still and another adult to extend the feet with the soles perpendicular to the lower legs. A caliper-like device, such as an infantometer, or the movable plates on an infant scale are used so that the exact distance between the two calipers or plates can be determined.
What other hormones are necessary for postnatal growth?
The factors responsible for postnatal growth are not the same as the factors that mediate fetal growth. Thyroid hormone is essential for normal postnatal growth, although a thyroid hormone-deficient fetus achieves a normal birth length; similarly, a GH-deficient fetus has a normal birth length, although in IGF-1 deficiency resulting from GH resistance (Laron dwarfism), fetuses are shorter than control subjects. Adequate thyroid hormone is necessary to allow the secretion of GH. Hypothyroid patients may appear falsely to be GH deficient; with thyroid hormone repletion, GH secretion normalizes. Gonadal steroids are important in the pubertal growth spurt.
What is the upper-to-lower segment ratio?
The upper-to-lower segment ratio is the ratio of the upper segment (determined by subtraction of the measurement from the symphysis pubis to the floor [known as the lower segment] from the total height) to the lower segment. This ratio changes with age. A normal term infant has an upper-to-lower ratio of 1.7:1, a 1 year old has a ratio of 1.4:1, and a 10 year old has a ratio of 1:1. Conditions of hypogonadism, not commonly discerned or suspected until after the normal age for onset of puberty, lead to greatly decreased upper-to-lower ratio in an adult, whereas long-lasting and untreated hypothyroidism leads to a high upper to lower ratio in the child.
What is Turner syndrome?
Turner syndrome is characterized by a karyotype of 45,XO or by a mosaic karyotype and clinically presents with short stature, shield chest, wide-spaced nipples, wide-carrying angle of the upper extremities, high-arched palate, gonadal failure, kidney dysplasias with normal function, and aortic arch abnormalities. Affected girls are often susceptible to autoimmune disorders.
