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Growth Retardation

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This translates into being below the third percentile for height. ... Idiopathic short stature ... Such children are considered to have idiopathic short stature. ... – PowerPoint PPT presentation

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Title: Growth Retardation


1
Growth Retardation
  • 96/10/12
  • Data from Up To Date
  • ???

2
INTRODUCTION
  • Short stature is not a disease it is a term
    applied to a child who is 2 standard deviations
    (SD) or more below the mean height for children
    of that sex and chronologic age (and ideally of
    the same racial-ethnic group).
  • This translates into being below the third
    percentile for height.
  • A single measurement of height is much less
    useful in assessing growth than is the pattern of
    growth over a period of time.

3
  • Growth curve in a male with intrinsic shortness.
    The growth velocity is normal from age 5 onward
    with the height being below, but parallel to, the
    third percentile.

4
  • To define any growth point, one must measure
    children accurately and plot each point (height,
    weight, and head circumference) precisely.
  • One of the more common causes of apparent growth
    failure (and short stature) is mismeasurement or
    aberrant plotting of the data.

5
Prediction of height potential
  • Somatic growth and biologic maturation are
    influenced by many factors that act independently
    or in concert to modify a child's genetic
    potential for growth.
  • Although the precise contribution of heredity
    cannot be quantitated, an estimate of a child's
    adult height potential can be obtained by
    calculation of the midparental height, adjusted
    for the sex of the child
  •   For girls, 13 cm is subtracted from the
    father's height and averaged with the mother's
    height.
  • For boys, 13 cm is added to the mother's height
    and averaged with the father's height.

6
VARIATIONS OF NORMAL GROWTH
  • A normal pattern of growth is evidence that the
    general health of a child or adolescent is good.
  • On the other hand, children with just about any
    subacute or chronic illness may grow slowly.
  • Statural growth is a continuous but not linear
    process. There are three phases of postnatal
    growth infantile, childhood, and pubertal.
  • Each has its own distinctive pattern.

7
  • The infantile phase is characterized by rapid but
    decelerating growth during the first two years of
    life overall growth during this period is about
    30 to 35 cm.
  • Infants often cross percentile lines in the first
    24 months as they grow toward their genetic
    potential and get further away from the excesses
    or constraints of the intrauterine environment.

8
  • The childhood phase is characterized by growth at
    a relatively constant velocity of 5 to 7 cm per
    year there is often slight slowing later in
    childhood.
  • The pubertal phase is characterized by a growth
    spurt of 8 to 14 cm per year because of the
    synergistic effects of increasing gonadal steroid
    and growth hormone secretion.

9
Idiopathic short stature
  • There are certain children whose stature falls
    below 2 SD of the mean for age, and for whom no
    endocrine, metabolic or other diagnosis can be
    made.
  • Such children are considered to have idiopathic
    short stature.

10
  • They have normal (often at the lower limit)
    growth velocity, no biochemical or other evidence
    for a specific growth retarding condition, normal
    serum concentrations of insulin-like growth
    factor-I (IGF-I) and IGF binding protein-3, and
    normal growth hormone responses to pharmacologic
    agents that lead to growth hormone release.

11
PATTERNS OF ABNORMAL GROWTH
  • The most common causes of short stature beyond
    the first year or two of life are familial
    (genetic) short stature and delayed
    (constitutional) growth.
  • The latter may have a genetic basis, because
    there is often another close family member in
    whom growth was delayed.
  • The shortest children often have both of these
    variants of normal growth.

12
  • Although there is considerable individual
    variability, the size at birth in children with
    these disorders is usually normal.
  • However, a downward shift in growth begins at
    three to six months that is often
    indistinguishable from that in normal children
    (lag-down growth) but tends to be more severe and
    more prolonged .
  • Many of these children have normal growth
    velocity by the third or fourth year, and then
    continue to grow below, but parallel to, the
    third percentile .

13
  • There are multiple ways in which to categorize
    slow growth and the resulting short stature, but
    it is the abnormal growth rate (the trajectory
    along the growth chart) that is more relevant
    than the issue of whether a child is short or not
    (see above).
  • I use a classification based upon the
    relationship between chronologic age, height age,
    weight age, bone age, and growth rate.

14
  • Intrinsic shortness Intrinsic shortness is
    characterized by inherent limitations of bone
    growth and predicts adult short stature.
  • Delayed growth Delayed growth is defined as a
    bone age closer to height age than chronologic
    age and predicts "normal" adult stature.

15
  • Attenuated growth Attenuated growth is
    characterized by a growth rate that is so slow
    that the child progressively deviates from a
    previously defined growth channel (or
    percentile).
  • Because the height age approximates the bone age,
    adult height potential is often normal, but only
    after remedial action is taken for one of the
    many possible causes.

16
DISEASES THAT MAY CAUSE GROWTH FAILURE AND SHORT
STATURE
  • Renal disease
  • Metabolic acidosis
  • Cancer
  • Glucocorticoid therapy
  • Pulmonary disease
  • Cardiac disease
  • Gastrointestinal disease
  • Immunologic disease
  • Metabolic and endocrine diseases

17
  • Renal disease Growth failure in children with
    renal disease is multifactorial.
  • Implicated factors include metabolic acidosis,
    uremia, poor nutrition secondary to dietary
    restrictions, anorexia of chronic illness,
    anemia, calcium and phosphorus imbalance, renal
    osteodystrophy and potential adverse effects on
    the serum concentrations of growth factors and
    their binding proteins.

18
  • Metabolic acidosis alone can also impair growth,
    as occurs in children with renal tubular acidosis
    .
  • Alkali therapy may lead to attainment and
    maintenance of normal stature.

19
  • Cancer Children with cancer may grow poorly
    before diagnosis because of poor food intake,
    nausea, vomiting, and increased caloric
    utilization.
  • After diagnosis, anorexia, nausea, and vomiting
    induced by chemotherapy and radiotherapy also can
    contribute to impaired growth.
  • These effects of treatment often subside by one
    to two years, and some children then have
    catch-up growth.

20
  • Late growth failure is common in children who
    received cranial radiotherapy (and perhaps
    chemotherapy), because it causes growth hormone
    (GH), gonadotropin, and sometimes thyrotropin
    deficiency .
  • In younger children, especially girls, cranial
    radiotherapy can cause precocious puberty and
    adult short stature.
  • Primary hypothyroidism also can occur if the
    thyroid gland was in the radiation field. Spinal
    irradiation may result in slow growth of the
    spine, with relative sparing of limb growth.

21
  • Glucocorticoid therapy Glucocorticoids exert
    multiple growth-suppressing effects, interfering
    with endogenous growth hormone secretion, bone
    formation, nitrogen retention, and collagen
    formation .
  • The impairment in growth is most pronounced with
    daily therapy, may be less pronounced with an
    alternate-day regimen, and even can occur with
    inhaled glucocorticoids .

22
  • As an example, one report evaluated the effect of
    seven months of relatively low-dose inhaled
    beclomethasone dipropionate (400 mcg/day) in 7-
    to 9-year-old children with mild asthma .
  • Treatment had no effect on overnight urinary
    cortisol excretion, but did reduce growth
    velocity (0.79 versus 1.14 mm/week).
  • At the end of the seven months of therapy,
    children receiving beclomethasone had grown 1 cm
    less than those in the placebo group.

23
  • The growth-impairing effects of glucocorticoids
    may persist after therapy is discontinued.
  • In a study of 224 children with cystic fibrosis
    who previously had been treated for up to four
    years with either alternate-day prednisone or
    placebo, mean height after age 18 years (on
    average six to seven years after cessation of
    therapy) was significantly lower in boys who had
    received either high- or low-dose prednisone
    (170.5 and 170.7 versus 174.6 cm with placebo p
    0.03) .
  • This effect was most pronounced in boys who had
    started taking prednisone at 6 to 8 years of age.
  • In contrast, there was no persistent growth
    impairment in girls treated similarly.

24
  • Pulmonary disease Asthma is the most common
    chronic pulmonary disease in children. Severe
    asthma alone probably results in slow growth, but
    it is slowed more by treatment, especially with
    glucocorticoids.
  • Cystic fibrosis is both a pulmonary and
    gastrointestinal disease. Growth failure is
    multifactor in this disorder as poor food intake,
    increased fecal losses becuase of maldigestion or
    malabsorption, chronic infection, and increased
    energy requirements (work of breathing) can all
    contribute.

25
  • Cardiac disease Growth failure is common in
    children with severe heart disease of any cause.
    The major pathogenetic factors are thought to be
    anorexia and increased basal energy requirements
    .

26
  • Gastrointestinal disease Celiac disease is a
    prime example of a remediable cause of short
    stature, especially in younger children .
  • Children with growth failure resulting from
    gastrointestinal disease have a greater deficit
    in weight than height (ie, they are
    underweight-for-height) in contrast to those with
    endocrine disorders who are often
    overweight-for-height .
  • Older children with inflammatory bowel disease,
    especially Crohn's disease, may present with
    growth failure before the onset of
    gastrointestinal symptoms.

27
  • Immunologic disease Renewed interest in
    immunologic causes of growth retardation has come
    with the AIDS epidemic. However, it is difficult
    to attribute growth failure to the infection or
    its immunologic consequences, because anorexia,
    malabsorption, diarrhea, severe infections, and
    failure of one or more organ systems are so
    common in these patients .
  • Growth failure also can occur with other
    immunological deficiencies such as the severe
    combined immunodeficiency syndrome. As with HIV
    infection, multiple factors are probably
    involved.

28
  • Metabolic and endocrine diseases Growth failure
    is common in children and adolescents with many
    of the inborn disorders of metabolism.
  • Among acquired metabolic diseases, the most
    common is autoimmune diabetes mellitus.
  • Diabetes was, in the past, an important cause of
    short stature and attenuated growth because of
    caloric deficit resulting from severe glucosuria
    .
  • However, it is now rare because of improvements
    in therapy.
  • Although children with fair-to-good metabolic
    control have some decrease in insulin-like growth
    factor-1 (IGF-1) production or action, their
    growth is usually normal.

29
  • Any disorder associated with vitamin D deficiency
    or decreased vitamin D action can cause
    hypophosphatemia and rickets, which is
    characterized by abnormal epiphyseal development,
    bowing of the extremities, and poor growth.
  • Other common endocrine causes of growth failure
    and short stature are hypothyroidism,
    hypopituitarism (isolated GH deficiency or
    multiple anterior pituitary hormone
    deficiencies), and hypercortisolism (Cushing's
    syndrome, exogenous and endogenous).

30
  • GH deficiency usually results from deficiency of
    growth hormone-releasing hormone (GHRH), but can
    be because of sellar and parasellar tumors (eg,
    germinoma ) that destroy the pituitary gland
    itself.
  • These children can have striking catch-up growth
    after surgical treatment or during GH replacement
    therapy .
  • A rare cause is an inactivating mutation of the
    GHRH receptor that is inherited in an autosomally
    recessive manner .

31
  • Hypothyroidism is a well-recognized cause of
    growth failure that may be an early or the major
    manifestation of hypothyroidism in children.
  • The skeletal age is usually as delayed as the
    height age as a result, many children with
    hypothyroidism have a reasonably normal growth
    potential.

32
  • Cushing's syndrome in children is most often
    iatrogenic, because of glucocorticoid therapy for
    asthma, inflammatory bowel disease, or
    immunologic renal disease.
  • Endogenous Cushing's syndrome is uncommon in
    children, but should be considered if the child
    has both weight gain and growth retardation, ie,
    is overweight-for-height .

33
DIAGNOSIS OF ENDOCRINE CAUSES OF GROWTH FAILURE
  • Hypothyroidism Thyroid function should always
    be evaluated, because growth failure may be the
    first or even the only manifestation of
    hypothyroidism.
  • The evaluation should include measurements of
    both serum thyrotropin (TSH) and thyroxine both
    primary and central hypothyroidism can cause
    growth failure, and measurement of serum TSH
    alone will not detect central hypothyroidism.

34
  • Cushing's syndrome Cushing's syndrome is rare
    in children except when due to the toxicity of
    glucocorticoid therapy.
  • It is initially a clinical diagnosis that is
    suggested by the clinical findings and then
    confirmed by biochemical and imaging tests.
  • The following findings were noted in a review of
    59 patients with Cushing's syndrome who were
    between the ages of 4 and 20 years

35
  • A corticotropin (ACTH)-secreting pituitary
    adenoma (Cushing's disease) is by far the most
    common cause, accounting for 50 cases.
  • The two major findings are weight gain (90
    percent) and growth retardation (83 percent)
    bone age was normal at diagnosis in most
    patients.

36
  • Growth hormone deficiency If growth hormone
    deficiency is congenital and complete, the
    diagnosis is relatively easy to confirm.
  • Affected children present with severe growth
    failure, delayed bone age, and very low serum
    concentrations of growth hormone, IGF-I, and its
    major binding protein, IGF-binding protein-3.

37
  • The rare children with growth hormone
    insensitivity have high serum growth hormone
    concentrations but low serum IGF-I and IGF
    binding-protein-3 concentrations.
  • In its complete form, this condition is called
    Laron-type dwarfism (complete growth hormone
    insensitivity).

38
Treatment of growth hormone deficiency in
children
  • PREPARATIONS OF GROWTH HORMONE FOR THERAPY
    Seven pharmacologic preparations are approved for
    treatment of growth hormone deficiency in
    children, and others are still being tested

39
  • Aqueous solutions of growth hormone for
    subcutaneous administration.
  • Several brands of growth hormone have been
    available for subcutaneous administration for
    many years, and most information about growth
    hormone treatment comes from these preparations.
  • Most are available in multiple-dose pen devices
    that materially aid in administration.
  • Daily therapy is more effective than three times
    a week at the same dose .
  • The recommended dose of growth hormone in
    children with growth hormone deficiency is 0.04
    mg/kg per day.
  • Children with chronic kidney disease or Turner's
    syndrome are given slightly higher doses because
    they have a degree of growth hormone resistance.

40
  • Growth hormone encapsulated in biodegradable
    glycolide microspheres for deep subcutaneous
    administration.
  • This formulation was approved by the United
    States Food and Drug Administration in January
    2000.
  • In a study of 74 children with growth hormone
    deficiency, either 1.5 mg/kg body weight once a
    month or 0.75 mg/kg twice a month significantly
    increased linear growth compared with the
    pretreatment rate, but this formulation was not
    compared with a subcutaneous formulation .
  • Local reactions at the injection site were
    common 60 percent of injections resulted in
    subcutaneous nodules and 36 percent in
    postinjection pain.
  • This product has been removed from the market.

41
  • Synthetic growth hormone-releasing hormone
    (sermorelin, Geref) is an approved treatment for
    children whose pituitaries are capable of
    releasing growth hormone .
  • It is about one-half as expensive as growth
    hormone but, in the recommended doses, may be
    somewhat less effective .
  • This product has been removed from the market.

42
  • Several growth hormone-releasing peptides (GHRP)
    or nonpeptide analogs (some active orally) are
    being evaluated in growth hormone-deficient
    children and adults .
  • It is too early to determine their long-term
    efficacy and safety.

43
The End
  • Thank for your attention.
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