|  Home  |  Doctors  |  Students  |  Organizations  |  Health & Fitness  |  News  |  Message Boards  |  About Us  |

 


















































 






 











Patrons Doctor
     
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Back to List
Short Stature
INTRODUCTION

Background: Longitudinal assessment of growth is essential child care. Prompt recognition of the short child can occur only with accurate measurements of growth and critical analysis of the growth data.

Short stature optimally is defined relative to the genetic endowment of the individual. Short stature is recognized by comparing the individual child to a large population with a similar genetic background and, more particularly, to the mid-parental target height.

Growth failure (GF) often is confused with short stature. By definition, GF is a pathologic state, whereas short stature is often a normal variant. Regardless of the genetic background, short stature may be a sign of a wide variety of pathologic conditions or inherited disorders. Thus, accurate longitudinal assessment of growth is a fundamental aspect of health maintenance in children. Review of the patient's growth chart is critical to the evaluation of short stature. Deviation from a prior growth pattern appropriate for the genetic background often heralds new pathology. In addition, analysis of the prior growth pattern helps distinguish normal from pathologic variants of short stature.

Compared to a well-nourished, genetically relevant population, short stature is defined as standing height more than 2 standard deviations below the mean (or below the 2.5 percentile) for gender. Skeletal maturation typically is determined by the bone age obtained from an anteroposterior radiograph of the left hand and wrist. Gender-specific reference data for standing height, head circumference, and weight have been published for most developed countries, most ethnic subpopulations (including Asians and African Americans), and the most common genetic disorders (eg, Down syndrome, Ullrich-Turner syndrome, achondroplasia).

The causes of short stature can be divided into 3 broad categories: chronic disease (including undernutrition genetic disorders), familial short stature, and constitutional delay of growth and development. Endocrine diseases are rare causes of short stature. The hallmark of endocrine disease is linear GF occurring to a greater degree than weight loss. Most short children evaluated by clinicians in developed countries have familial short stature and/or constitutional delay of growth, both of which are diagnoses of exclusion.

The hallmarks of familial short stature (also referred to as genetic short stature) include bone age appropriate for chronologic age, normal growth velocity, and predicted adult height appropriate to the familial pattern (using the Bayley-Pinneau or Tanner-Goldstein-Whitehouse tables). By contrast, constitutional delay is characterized by delayed bone age, normal growth velocity, and predicted adult height appropriate to the familial pattern. Patients with constitutional delay typically have a first-degree or second-degree relative with constitutional delay (eg, menarche reached when older than 15 y, adult height attained in male relatives when older than 18 y).

Pathophysiology: Short stature may be normal. Obtaining the family history of growth patterns and direct measurement of the parents is crucial to determine the genetic potential for growth in the child.

Short stature also can be the sign of a wide variety of pathologic conditions or inherited disorders when it results from GF or premature closure of the epiphysial growth plates. Therefore, pathophysiology depends on the underlying cause. For detailed discussions of the disorders in the differential diagnosis of short stature.

Frequency:

  • Internationally: Worldwide, malnutrition unfortunately remains the most common cause of GF. Supporting lay and professional efforts to reverse this preventable cause of short stature in besieged communities must be a high priority of all governments and health care professionals.

Race: Normal variations in stature often are related to ethnic background. For example, tall for a Cambodian may be short for a Norwegian. However, the major causes of short stature (ie, malnutrition, recurrent illness, parasites) are not race specific.

Sex:

  • Unfortunately, short boys are more likely to come to medical attention than short girls. Notwithstanding the legitimate debate regarding this ascertainment bias, boys do appear more likely to have idiopathic GHD or constitutional delay of growth and development.
  • Ullrich-Turner syndrome (ie, TS) affects only females. The evaluation of a short female mandates a karyotype to exclude this disorder.

Age: Any age can be affected.

CLINICAL

History:

  • Key data to obtain for the evaluation of short stature include the child's weight and length at birth; prior growth pattern; and the final (or current) heights and weights of parents, siblings, and grandparents.
    • Whenever possible, obtain the original birth records to document length, weight, and fronto-occipital circumference at birth.
    • Assessing the heights of both parents is absolutely essential.

       

      • Generally, men overreport their height, and women underreport their weight.

         

      • Ideally, measure the height of each parent in the clinic for optimal calculation of the mid-parental target height, according to 1 of several formulae, among which the author prefers the following:

      Target height in cm for a girl = [mother's height in cm (father's height in cm - 13)]/2

      Target height in cm for a boy = [(mother's height in cm + 13) + father's height in cm)]/2
  • Document pubertal timing in first-degree relatives.
    • At a minimum, determine the age at onset of menarche for the child's mother and the age of adult height attainment for the father.
    • These 2 milestones usually can be recalled by most parents and have proven reliable predictors of pubertal timing and tempo in parent-child pair studies of puberty.
  • Review of symptoms by organ system provides additional clues to the etiology underlying short stature.
    • Gastrointestinal
      • Diarrhea, flatulence, or borborygmi (frequent, discomforting, or even audible peristalsis) suggest malabsorption.
      • Vomiting can suggest an eating disorder or a central nervous system (CNS) disorder (eg, dysgerminoma).
      • Consider dietary intake and composition. In particular, ask about intake of carbonated beverages, juices, and other casual intake.
      • Pain or abdominal discomfort suggests inflammatory bowel diseases.
    • Cardiac disease: Signs include peripheral edema, murmurs, and cyanosis.
    • Chronic infections: Poor wound healing and opportunistic infections are signs of potential immune deficiency.
    • Pulmonary
      • Sleep apnea can be a cryptic cause of short stature.
      • Other chronic diseases that may result in short stature include severe asthma associated with chronic steroid use and cystic fibrosis (CF).
    • Neurologic
      • Visual field deficits often herald pituitary neoplasms.
      • Vomiting, early morning nausea, polyuria, or polydipsia often is associated with masses of the CNS.
    • Renal
      • Polyuria and polydipsia are important symptoms of hypothalamic and/or pituitary disorders.
      • Chronic renal disease is a common cause of GF.
    • Social
      • Participation in sports requiring weight control (eg, wrestling, crew, gymnastics) may uncover anorexia nervosa or bulimia induced by the patient, peers, or coaches.
      • Growth often is impaired in refugees and in children emerging from foster care or certain international adoption settings.
      • The growth pattern with adequate nutrition in a loving environment over time is critical to distinguish pathologic GF from normal variant short stature in such patients.

Physical: Endocrinologists rely heavily upon accurate and reliable height assessment.

  • Measure standing height in triplicate using a calibrated wall-mounted stadiometer.
    • In infants, length is determined in triplicate using a tabletop recumbent stadiometer.
    • The mean value of the triplicate data serves as the true measurement.
  • For children who cannot stand or recline completely (eg, those with spina bifida, those with contractures), arm span provides a reliable alternative for longitudinal assessment of long bone growth.
    • Ascertain arm span by facing the child against a flat firm surface (usually the wall), fully extending the arms, and measuring the maximal distance between the tips of the middle fingers.
    • If this positioning is impossible physically, a flexible tape measure may be rolled along the dorsal aspect of the arms and upper back to determine arm span.
  • Documenting growth velocity over time complements the initial height assessment.
    • Calculate growth velocity as the change in standing height over at least 6 months (for children) or in length over at least 4 months (for infants).
    • Poor linear growth is defined as linear growth velocity more than 2 SDs below the mean for gender, genetic composition, and chronologic age.
  • Weigh all patients.
  • In infants, determine the fronto-occipital circumference.
  • With suspicion of short-limb dwarfism, the sitting height can be obtained by measuring the upper body segment, or crown to pelvis, as the child sits upright on a platform-mounted stadiometer (or on the floor with a wall-mounted stadiometer).
    • Alternatively, the lower segment can be determined by measuring from the superior midline brim of the symphysis pubis to the floor, with the child standing (feet placed together).
    • The upper-to-lower segment ratio (US/LS) should be close to 1.
    • The ratio is greater than 1 in children with shortened limbs, as it is in individuals with hypochondroplasia or achondroplasia.
  • Palpate for thyroid enlargement and firmness, which can be associated with Hashimoto thyroiditis, the most common cause of acquired hypothyroidism.
  • Test visual fields for signs of pituitary and/or hypothalamic tumors, initially by gross confrontation.
  • Inspect fourth metacarpals, which are shortened in persons with pseudohypoparathyroidism, Ullrich-Turner syndrome, and Albright hereditary osteodystrophy.
  • Inspect mucous membranes for ulcerative stomatitis, typical of Crohn disease and various trace mineral and vitamin deficiencies.
    • Pretibial ulcerations also are observed in persons with Crohn disease and ulcerative colitis.
    • Rectal tags and clubbing are also typical in individuals with Crohn disease.
  • Confirm the history with direct measurements whenever possible. For example, measure both biologic parents’ heights during the clinic visit.
  • Both the arm span and US/LS ratio can be informative regarding the cause of short stature. Patients with short limb dwarfism usually have an US/LS ratio less than 0.4.
  • Arm span also detects a decrement in growth, which otherwise is indiscernible in a child with spinal deformation (eg, myelomeningocele).
  • Carefully examine the midface.
    • A single, central, maxillary incisor reflects a defect in midline facial development.
    • Similarly, a bifid uvula suggests the possibility of a submandibular cleft palate, which may be palpable, yet not visible on inspection.
    • Associated anomalies of midline structures, such as the pituitary gland, are common in patients with major midline facial anomalies.
    • Growth hormone deficiency or panhypopituitarism should be considered as a cause of short stature in such patients.

Causes:

  • The nonendocrine causes of short stature can be divided into 3 major categories as follows:
    • Constitutional delay of growth and sexual development
    • Familial short stature
    • Chronic diseases of childhood: Among the chronic conditions, malnutrition remains the leading cause of short stature worldwide.
  • Genetic causes of short stature are as follows:
    • Down syndrome (trisomy 21)
    • Ullrich-Turner syndrome (45,XO)
    • Lerí-Weill dyschondrosteosis (SHOX gene)

Other Problems to be Considered:

Causes of growth failure in children (partial list)

Gastrointestinal
Protein or caloric deprivation
Inflammatory bowel disease - Crohn disease, ulcerative colitis
Cystic fibrosis
Sprue (gluten intolerance)
Protein-losing enteropathy

Endocrine
Hypothyroidism
Primary - Hashimoto thyroiditis, Pendred syndrome
Secondary - Thyrotropin (thyroid-stimulating hormone [TSH]) deficiency
Tertiary - Thyrotropin-releasing hormone (TRH) deficiency
Other - Iatrogenic or environmental radioablation, neoplasm
GHD (complete absence) or insufficiency (partial absence)
Neurosecretory GHD
Panhypopituitarism (combined anterior pituitary hormone deficiencies)
Growth hormone-releasing hormone (GHRH) deficiency
Poorly controlled type 1 diabetes mellitus - Mauriac syndrome
Chronic hypernatremia - Hypothalamic adipsia, diabetes insipidus
Hypercortisolism - Cushing syndrome, iatrogenic glucocorticoid administration
Hypocortisolism - DAX1 gene mutation, autoimmune adrenalitis (Addison disease) (However, note that adrenocorticotropic hormone deficiency alone has been associated with tall stature; short stature results from hypocortisolism only in persons with salt wasting.)
 

Normal variant short stature (also called familial short stature)

Genetic (known defect)
Down syndrome (trisomy 21)
Silver-Russell syndrome
Hypochondroplasia
SHOX gene mutations
TS
Leri-Weill dyschondrosteosis
Growth hormone (GH) receptor gene mutations (Laron syndrome)
IGF-1 gene mutation
IGF-1 receptor gene mutation
PROP1 gene mutations
Pit1 gene mutations
GHRH gene mutations
GH gene mutations
Insulin receptor gene mutations (leprechaunism)

Genetic (unknown defect)
Silver-Russell syndrome
Shwachman-Diamond syndrome

Pulmonic
Cystic fibrosis
Severe asthma
Chronic obstructive pulmonary disease
Restrictive lung disease

Cardiac
Hypoxemia
Congestive heart failure
Low cardiac output states
Precocious puberty

Renal
Chronic renal insufficiency
Renal failure
Renal tubular acidosis

Psychosocial dwarfism
Chronic neglect
Starvation

WORKUP

Lab Studies:

  • Laboratory studies to look for the major causes of poor linear growth in children include the following:
    • Serum levels of insulinlike growth factor-1 (IGF-I), formerly named somatomedin C, and insulinlike growth factor-binding protein-3 (IGFBP-3)
      • These are useful tests for GHD, except in patients with brain tumors or during puberty.
      • Patients with certain CNS neoplasms, particularly during puberty, may have normal serum growth factor levels despite GHD.
      • Consider provocative tests of pituitary function in any euthyroid patient suspected to be GH deficient.
      • Interpret a low serum IGF-I concentration cautiously since poor nutrition is associated with low serum IGF-I concentration.
      • Thus, the serum IGFBP-3 concentration has greater specificity than serum IGF-I for the diagnosis of GH deficiency.
    • Karyotype by G-banding
      • The 45,XO pattern defines patients with Ullrich-Turner syndrome.
      • Because 10% of patients with Ullrich-Turner syndrome possess a mosaic karyotype (eg, 45,XO; 46,XX), counting at least 30 cells reduces the possibility of missing a patient with mosaic TS.
    • Cautionary note about measuring serum levels of GH
      • Beyond the first months of life, endogenous GH is secreted in a pulsatile fashion. These intermittent peaks are greatest after exercise, after meals as blood glucose falls, and during deep sleep.
      • Therefore, measuring a single, random serum GH value is of no use in the evaluation of the short child.
      • Beyond the neonatal period, values obtained during the daytime are unlikely to be detectable.
      • While a random serum GH value greater than 10 mg/dL generally excludes GHD, a random low serum GH concentration does not confirm the diagnosis of GHD.
  • Useful tests include the following:
    • Complete blood count for hematologic disease
    • Wintrobe sedimentation rate for inflammatory bowel disease
    • Antiendomysial immunoglobulin A (IgA) and immunoglobulin G (IgG), transglutaminase IgG, and antigliadin IgG titers for sprue (gluten enteropathy): For sprue, antiendomysial IgA is more sensitive, and IgG is more specific.
    • Serum total thyroxine (total T4) and thyrotropin (TSH) levels to test for hypothyroidism
      • Determination of serum free T4 concentration is necessary with suspicion of TSH deficiency, TRH deficiency, or thyroxine-binding globulin (TBG) deficiency.
      • Assay free T4 levels directly by equilibrium dialysis.
      • Many reference laboratories report a value termed the free thyroxine index, which is calculated by multiplying the total T4 by an internal standard; however, if free T4 assessment is needed, measure it directly.
    • Sweat chloride testing: Consider in short patients with a history of meconium ileus or pulmonary symptoms to exclude CF.
    • Serum transferrin and pre-albumin concentrations for undernutrition

Imaging Studies:

  • Anteroposterior radiograph of left hand and wrist to assess bone age. Chondrodysplasia of the distal radial epiphysis (Madelung deformity) suggests Leri-Weill dyschondrosteosis.
  • Perform renal and cardiac ultrasounds in all patients with Ullrich-Turner syndrome. The most commonly associated anomalies are horseshoe kidney and bicuspid aortic valve.

Other Tests:

  • Perform hearing tests in all patients with Ullrich-Turner syndrome.
  • Use Bayley-Pinneau or Tanner-Goldstein-Whitehouse methods.
    • These methods often are used to predict final adult height and become more accurate with advancing bone age.
    • Within 5 years of epiphyseal closure, the predicted height may fall within ± 5 cm of the final adult height with 95% confidence.
    • The Bayley-Pinneau method can be used with a bone age as young as 6 years; however, the prediction is less accurate at the younger ages.

Procedures:

  • Several provocative tests have been developed for the evaluation of suspected GHD.
    • Insulin-induced hypoglycemia is the most powerful stimulus for GH secretion; however, this test also carries the greatest potential for harm and is the only GH provocative test that has been associated with fatalities.
    • Alternate GH secretagogues used successfully in combination as 2 serial tests include arginine, levodopa, propranolol with glucagon, exercise, clonidine, or epinephrine.
    • Perform all GH provocative testing under the supervision of a pediatric endocrinologist.

TREATMENT

Medical Care: Medical care depends on the etiology of the short stature.

  • Recombinant human growth hormone (rhGH) administration has not been proven to improve final adult height remarkably in children with normal variant short stature.
    • Nine inconclusive clinical studies that focused on this particular issue have been published to date.
    • Published studies were flawed variously by the following:
      • Selection bias due to high drop out rates from treatment regimens (presumably due, in part, to the parents' or health care provider's dissatisfaction with results of therapy in these individuals)
      • Lack of key design elements for a proper clinical trial (eg, placebo controls, double blinding, randomization)
      • Inadequate follow-up study to final adult height
    • A recent study from the National Institutes of Health was double-blinded randomly and suggests a small effect of GH on adult height in children with normal short stature if they are treated with GH injections for many years.
    • In the absence of better clinical outcomes, do not use rhGH therapy to treat children with normal variant short stature.

Surgical Care:

  • Surgical care depends on the underlying cause of short stature.
  • Brain tumors causing hyposomatotropism may require neurosurgical intervention, depending on the tumor type and location.
  • Limb-lengthening procedures have been performed but carry enormous morbidity and mortality and are not recommended.

Consultations:

  • Consult a pediatric cardiologist, radiologist, and audiologist for patients with Ullrich-Turner syndrome.
  • Consult a psychologist for patients with eating disorders.

Diet:

  • Optimize nutrition in patients with GI disease.
  • Obtain psychologic or psychiatric consultation for patients with eating disorders.
  • Forced energy intake in children with normal variant short stature has not been demonstrated to improve short-term growth or final adult height.

Activity:

  • Do not restrict activity in children with normal variant short stature.

MEDICATION

Medication administered depends on etiology of the short stature.
 

Drug Category: Growth hormone -- Improve symptoms associated with growth hormone deficiency.

Drug Name
 		 Somatotropin (Humatrope, Nutropin, Genotropin, Saizen) -- hGH produced via recombinant DNA technology in Escherichia coli; widely available since 1985. Currently, only 1 of 10 largest reported clinical studies has demonstrated that therapy can increase final adult height in patients with normal variant short stature. This most recent NIH-funded study was randomized, placebo controlled, and took place over 14 y. Investigators demonstrated average gain in height did not exceed 4 cm when rhGH treatment of normal variant short stature began prior to puberty and continued through completion of puberty. They did not identify any clinical feature that, prior to start of therapy, could predict whether an individual patient would respond to rhGH and to what degree. It remains a personal and individual decision involving patient, patient's family, and physician whether several years of daily injections are worth the potential, but not promised, relatively small increase in final adult height.
Pediatric Dose Regimens vary according to product, the following example is for somatotropin analogs (Humatrope, Nutropin, Nutropin AQ, Saizen)
0.05 mg/kg/d SC hs for classic GHD
0.08 mg/kg/d SC hs for TS or chronic renal insufficiency
Contraindications Documented hypersensitivity; active neoplasm; critical illness related to respiratory failure (critical illness due to burns has not been established as contraindication)
Interactions None known
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Monitor growth and IGF-I levels at least every 6 mo during therapy

FOLLOW-UP

Further Inpatient Care:

  • While many hospitalized patients are short, therapy directed at the illness underlying their short stature is the best course in the inpatient setting.

Further Outpatient Care:

  • The proper evaluation of short stature is conducted in the outpatient setting where the calibrated stadiometer is available.
    • The most useful information in the evaluation of a child with short stature is the child's growth pattern.
    • In children younger than 3 years, track length and weight at 3-month intervals.
    • Standing height and weight can be tracked at 6-month intervals in older children.

Deterrence/Prevention:

  • Growth evaluation is a useful means of detecting chronic disease in children.

Complications:

  • Short stature may be the harbinger of an occult chronic disease of childhood. Normal variant short stature may be associated with lower bone mineral density relative to the remainder of the (taller) population. Whether this healthy subset of the population is at higher risk of osteoporosis remains unclear.

Prognosis:

  • Individuals with normal variant short stature carry an excellent prognosis.
  • Treatment of persons with classic GHD with rhGH can be expected to yield a height consistent with genetic potential as long as therapy is initiated at least 5 years prior to the onset of puberty. Whether cotreatment with rhGH and a gonadotropin-releasing hormone analog (eg, leuprolide) to inhibit puberty results in greater adult height in patients with classic GHD remains controversial.
  • Treatment of hypothyroidism at least 5 years before the onset of puberty is essential to attain a height consistent with the genetic potential.
  • Any chronic illness can reduce the adult height achieved if treatment of the condition is initiated late.

Patient Education:

  • Superb resources prepared by health care professionals for lay audiences include the following:
  • In addition, the following are examples of informative web sites for specific diseases bring parents and researchers together in the ongoing effort to improve care:

Back to List