Evaluation and Management of Short Stature in Children

Authors:
Alexander K. C. Leung, MD, and Alexander A. C. Leung, MD

Citation: 
Leung AKC, Leung AAC. Evaluation and management of short stature in children. Consultant. 2018;58(8):195-208, 210.  

ABSTRACT: Short stature in children is a common problem. A child whose height falls below the third percentile for age- and sex-matched children—ideally compared within the same racial-ethnic group—generally is considered short. The most common causes of short stature are constitutional growth delay and familial short stature. This article reviews the many causes of short stature among children and the clinical challenge of distinguishing normal variants from abnormal growth patterns caused by pathologic processes. Familial short stature is usually reflected in most members of the extended family. Constitutional growth delay features delayed timing of all growth events and usually a family history of “late bloomers.” Bone age determination is useful in the differential diagnosis of the causes of short stature and also can be used to estimate the probable adult height of an individual. Most children with constitutional growth delay and familial short stature require no treatment other than reassurance. Growth hormone (GH) therapy is indicated for the treatment of GH deficiency. Children with severe short stature from GH insensitivity may benefit from insulinlike growth factor 1 therapy.

KEYWORDS: Short stature, constitutional growth delay, familial short stature, intrauterine growth retardation, growth hormone deficiency, genetic disorders

Short stature is a common problem in children and a frequent concern among parents.^1,2 In general, a child whose height falls below the third percentile for children of the same sex and chronological age, and ideally compared within the same racial-ethnic group, is considered short.^1-4 Some authors define short stature as a height that is 2 standard deviations or more below the mean height for children of the same sex, chronological age, and race.^5,6 This translates to a height that is below the 2.3rd percentile.⁵ The most common causes of short stature are constitutional growth delay and familial short stature. The clinical challenge is to distinguish these normal variants from a subset of abnormal growth patterns caused by pathologic processes. Some pathologic processes are amenable to treatment if started early.

NORMAL GROWTH

By definition, approximately 2.3% to 3% of children have short stature.^1-3,6 Size at birth appears to be related more to maternal size than to genetic factors.^1,7,8 Between birth and 2 years of age, children make adjustment for those maternal factors that influence birth length with corresponding increases or decreases in their growth velocity in relation to the norm to reach their genetic potential.^7,8 By the age of 2 years, the height percentile of a healthy child usually stabilizes and correlates with parental heights.^1,3

Growth velocity varies with age, sex, and race. At birth, white male and female infants average 50 cm long.¹ In both sexes, the normal growth increment in the first 6 months of life is 16 to 17 cm and in the second 6 months is approximately 8 cm.¹ Between 1 and 2 years of age, girls grow at least 11 cm and boys at least 10 cm. After the first 2 years of life, until puberty, the average growth rate for boys and girls is 6.25 cm per year with a range of 4 to 7.5 cm per year.¹ Ninety-five percent of children grow faster than 4 cm per year.^2,3 

During adolescence, girls begin their growth spurt 2 years earlier than boys but generally do not reach as high a peak height velocity. The peak yearly pubertal growth rate for girls is 5 to 10 cm and for boys is 6 to 12 cm.⁹ An average girl gains approximately 6 cm in height after menarche, but there is no such marker in boys.¹

Growth of different body regions is variable throughout childhood, and body proportions are important in evaluating abnormal growth rates. The upper to lower segment ratio (crown to pubis/pubis to heel) is one common measurement. At birth, the upper/lower segment ratio in white infants is approximately 1.7.² It reaches 1.0 at 10 years of age and then falls to 0.95 in adulthood.² Blacks have relatively long limbs. In adult black individuals, the upper/lower segment ratio is approximately 0.85 to 0.90.¹ Asian children have shorter limbs and therefore have a higher upper/lower segment ratio than their white counterparts.¹

NEXT: Measurements of Growth

MEASUREMENTS OF GROWTH

During measurements of growth, the child should stand erect, with the back of the head, back, buttocks, and heels touching a firm vertical structure such as the vertical bar of a stadiometer, with shoes off and interfering hair accessories removed.^2,3 The horizontal measuring bar of the stadiometer should be lowered to level with the child’s head to obtain the height measurement.³ Alternatively, a firm object can be placed at a right angle over the top of the head and against the wall above the head for the measurement to be made.² A child younger than 2 years of age should be measured on a firm horizontal platform that contains an attached yardstick, a fixed headboard, and a movable footplate.^4,10,11 The child’s feet should be held steady with the legs fully extended while the measurement is made.^4,12

The height and weight should be plotted on the growth chart that is appropriate for the child’s age and sex. The weight will provide information about the child’s nutritional status and in some cases clues to the underlying cause. The growth charts that have been widely used are those published by the Centers for Disease Control and Prevention’s National Center for Health Statistics (CDC/NCHS) as well as those published by the World Health Organization (WHO).⁹ The former are based on large surveys of multiethnic populations for children living in the United States, while the latter are based on a pooled sample from 6 participating countries (Brazil, India, Ghana, Oman, Norway, and the United states [California]) where children are raised under optimal environmental conditions (economically advantaged, breastfed infants and children of nonsmoking mothers).^9,13 The WHO standards define a pediatric population that is leaner and taller than that of the CDC/NCHS standards.⁹ Since there are significant differences in growth rates, adult heights, and age of onset of puberty among different ethnic groups, it would be of great advantage to use standards based on ethnic background for each child assessed.¹⁴ Nevertheless, such standard growth charts are not always available for different ethnic groups.

NEXT: Clinical Evaluation

CLINICAL EVALUATION

Careful historical reviews and systematic physical examinations are keystones to the evaluation process. In most cases, a diagnosis can be made with relative certainty from the history and physical examination alone. Familiarity with the growing process and the physiology of growth, as well as the clinical features of many diseases and syndromes associated with short stature, is definitely an asset, and in some cases a spot diagnosis can be made.

Table 1 highlights some historical events that may provide essential and even diagnostic clues. The pattern of growth is of utmost importance in the diagnosis. Hence, reviewing the growth chart to determine the growth velocity is critical in the evaluation of a child with short stature.¹⁵ A short child with a growth rate of greater than 4 cm per year likely has either familial short stature, or, more commonly, constitutional growth delay. Familial short stature is usually reflected in most members of the extended family. In constitutional growth delay, there is delayed timing of all growth events including puberty, and there is usually a family history of “late bloomers.”² An abnormality is not usually found in a short child who is growing at a normal rate. On the other hand, a growth rate of less than 4 cm per year suggests pathologic short stature. Particular emphasis should be placed on the history of events that occurred when growth first deviated from the normal curve. A thorough systems review should reveal most acquired systemic diseases.

Careful and precise measurement of height, weight, arm span (distance between tips of the middle fingers with the arms raised and stretched to a horizontal position)¹² and upper/lower segment ratio is the most useful exercise in the physical examination.¹⁶ The lower body segment can be determined by measuring the distance from the symphysis pubis to the floor with the child standing erect against a wall. The upper body segment value can be obtained by subtracting the lower body segment value from the child’s height. The upper-to-lower body segment ratio is then derived by dividing the upper body segment value by the lower segment value.

In general, the further away from the population mean the child’s height, the higher the chance that a pathologic cause can be found.¹⁷ Children with achondroplasia, hypochondroplasia, rickets, multiple epiphyseal dysplasia, osteogenesis imperfecta, chondrodysplasia punctata, metaphyseal chondrodysplasia, thanatophoric dwarfism, Ellis-van Creveld syndrome, or long-standing hypothyroidism have relatively short extremities and therefore a higher upper/lower segment ratio.^12,15,18 On the other hand, children with spondylodysplasia, mucopolysaccharidosis, severe scoliosis, hemivertebrae, or metatropic dwarfism have a lower upper/lower segment ratio.^12,15,19

Children with simple obesity are usually tall for age. The combination of obesity and short stature should suggest an organic disease.¹⁷ Short stature with very low weight (weight disproportionately low for height), on the other hand, should suggest a nutritional disturbance or chronic organic disease.¹⁶

The recording of vital signs is also important in the evaluation. Hypothermia and bradycardia may be signs of hypothyroidism. Abnormal blood pressure may be a clue to cardiovascular disease. An appraisal of the child’s general health and nutrition status is also very important. The stage of sexual development should also be recorded. A thorough physical examination should be performed targeting features of chronic illnesses and dysmorphic syndromes (Table 2). Chromosomal disorders usually manifest as a multiplicity of congenital abnormalities.²⁰ Familiarity with the dysmorphic features may allow a spot diagnosis to be made. Turner syndrome may initially present as isolated short stature, since the other associated manifestations may be quite subtle.⁸

NEXT: Laboratory Evaluation

LABORATORY EVALUATION

Investigation should be guided by history and physical examination findings. Indiscriminate testing should be avoided. The following laboratory tests may be useful in the evaluation of a child with short stature and a deficient growth rate: complete blood cell count with differential (anemia, infection, parasitic disease, malignancy); erythrocyte sedimentation rate or C-reactive protein level (infection, inflammatory bowel disease, collagen vascular disease, malignancy); urinalysis (urinary tract infection, renal disease); stool examination for occult blood (inflammatory bowel disease, malignancy); serum electrolytes (adrenal disease, renal disease); blood urea nitrogen (renal disease); serum calcium, phosphorus, and alkaline phosphatase (rickets, hypophosphatasia); serum thyrotropin, free thyroxine (hypothyroidism); serum insulinlike growth factor 1 (IGF-1), and bone age assessment.

Bone age determination not only is useful in the differential diagnosis of the various causes of short stature but also may be used to estimate the probable adult height of an individual.³ The most commonly used method to assess bone age is the use of the Greulich and Pyle atlas. In this method, the appearance of different epiphyseal centers on the left hand and wrist radiograph are compared with the standards in the atlas.¹⁹ If the bone age is delayed or advanced, then the projected height should be recalculated based on the bone age rather than on the chronological age.⁶

The clinician must then decide which laboratory tests to perform to confirm a presumptive diagnosis. Nondirected comprehensive screening is not warranted. Only tests aimed at confirming a suspected diagnosis as suggested by the history or physical examination findings should be ordered. For example, tissue transglutaminase immunoglobulin A and total IgA tests should be ordered if celiac disease is suspected. Chromosome analysis or karyotyping should be performed in the presence of dysmorphic features, especially with development delay and in girls with unexplained short stature, since some patients with Turner syndrome may have minimal dysmorphic features.^5,10,21 Fluorescence in situ hybridization can be used to detect small chromosomal abnormalities such as duplications and deletions.²¹ This approach is only useful when a clinician has a specific deletion or duplication for a differential diagnosis. Screening for mutations of the short stature homeobox gene (SHOX) should be reserved for short children with any combinations of the following physical findings: increased sitting height/height ratio, decreased arm span/height ratio, short or bowed forearm, above-average body mass index, muscular hypertrophy, Madelung deformity, cubitus valgus, and dislocation of the ulna at the elbow.²²

If growth hormone (GH) deficiency is suspected, high-quality contrast-enhanced magnetic resonance imaging of the hypothalamus and pituitary gland is an excellent modality for early diagnosis of a lesion in the central nervous system such as a craniopharyngioma.²³ Screening tests for the secretion of GH include postexercise or sleep sampling; a serum GH level of greater than 10 ng/mL by immunoradiometric assay rules out GH deficiency.^5,24 Definitive tests for the secretion of GH include provocative tests with a number of pharmacologic agents such as arginine, insulin, glucagon, l-dopa, and clonidine.^5,25 Because 10% to 20% of normal individuals may have abnormal responses to GH stimulation tests, provocative tests with 2 different medications my provide confidence for GH deficiency.^11,24 Nevertheless, screening tests for GH are not used these days, because measuring IGF-1 is sufficient for GH deficiency screening. Measurement of serum IGF-1 and IGF-binding protein 3 (IGFBP-3) should be considered in the evaluation of the GH-insulinlike growth factor axis.^24,26,27 Unlike GH, serum IGF-1 and IGFBP-3 have little to no circadian variation.²⁸ Serum IGFBP-3 concentration has greater specificity than serum IGF-1 concentration in the diagnosis of GH deficiency.¹¹

NEXT: Etiology

ETIOLOGY

Constitutional Growth Delay

Constitutional growth delay is the most common cause of short stature.¹ Characteristically, children with constitutional growth delay are of normal length and weight at birth, but during the first few years of life their growth velocity slows down.¹ By the time they enter school, their height and weight measurements decrease to near or below the third percentile on the standard growth curves.¹ This is followed by growth at a low-normal rate, paralleling a lower percentile curve throughout the prepubertal years.^1,29 The bone age usually is retarded but, in contrast to patients with hypothyroidism and hypopituitarism, not as retarded as the height age.^1,29 Onset of puberty is delayed: puberty develops when the bone age reaches about 10½ years in girls and 11 to 11½ years in boys.¹ Growth continues until the epiphyses fuse. Normally, this occurs around the age of 18 years in boys and 15 years in girls. As such, catch-up growth may continue into the early 20s in males and late teens in girls.¹ Adult height is usually within the normal range.²⁹ Constitutional growth delay is more common in males. There is often a family history of “late bloomers” in one or both parents.¹

Familial Short Stature

Familial (racial or genetic) short stature, the second most common cause of short stature, may occur as a genetically determined family trait based on polygenic inheritance of genes associated with growth.¹ At times, familial short stature may result from IGF-1 receptor gene mutations.^30-32 It is important that parental height be considered when evaluating children with familial short stature, since their ultimate height is related to the mid-parental height. The mid-parental height can be calculated by averaging the parents’ heights after first adding 13 cm to the mother’s height if the subject is a boy, or subtracting 13 cm from the father’s height if the subject is a girl.^3,6 Extrapolation of the child’s anticipated growth along his or her channel should yield an adult height within plus or minus 5 cm of the derived mid-parental height.² If the child’s bone age is advanced or delayed, then the projected height should be plotted based on the bone age rather than the chronological age.⁶

In familial short stature, height often crosses several percentiles in infancy and then parallels the third percentile. Growth velocity is low-normal during the growth period. Although bone age and puberty are usually not delayed, such delays may be observed. The ultimate adult height is often below the tenth percentile and usually within the range predicted by mid-parental height.²⁹

Intrauterine Growth Retardation

Etiopathogenetically, both endogenous (ie, chromosomal and genetic) factors and exogenous factors (eg, maternal illnesses, maternal drug and alcohol abuse, placental insufficiency) must be considered. In all of these disorders, there is probably a defect in cellular proliferation, and these children are small for age. Children who have catch-up growth usually do it in the first 2 years of life.^29,33 Catch-up growth may be delayed in children who are born prematurely.²⁹ Approximately 10% to 15% of affected children do not have catch-up growth and have persistent short stature.²⁹ Puberty is not delayed and bone age is normal in children affected by intrauterine growth retardation.

NEXT: GH Deficiency

GH Deficiency

GH deficiency may be either idiopathic or secondary to disease of the hypothalamus and/or pituitary gland. Pituitary dysgenesis may occur as an isolated abnormality or in association with midline developmental defects (eg, septo-optic dysplasia). Mutations of POU1F1, PROP1, LHX3, LHX4, HESX1, OTX2, TBX19, SOX2, SOX3, and GLI2 genes may result in GH deficiency.¹¹ Deletions and mutations of GH1, the gene encoding GH located on chromosome 17, as well as mutations in the GH receptor gene, GHR, may also result in short stature.^11,34 Acquired causes include tumor (eg, craniopharyngioma), infection, medications (eg, glucocorticoids, methylphenidate, cytotoxic drugs), trauma, surgical damage, vascular infarcts, and irradiation.^35-38

If GH deficiency is congenital, growth failure is usually evident by 12 to 18 months of age but may be present as early as 3 to 6 months of age.¹ When growth deficiency is acquired, the growth curve is typical of acquired growth failure. In the neonatal period, infants with GH deficiency may present with hypoglycemia, micropenis, hypoplasia of the scrotum, and cryptorchidism.³⁹ Children with GH deficiency have increased subcutaneous fat and tend to be overweight for their height. The head circumference is less retarded than height. With long-standing GH deficiency, the head shows frontal bossing, and the face is small. Together with the full cheeks, this appearance has been coined “angel-like” (cherubic) or “doll-like.” Hair growth is sparse and thin. The voice is often high-pitched or squeaky, caused by the small larynx. Bone age is markedly delayed. Dental age is also delayed, with late eruption of both deciduous and permanent teeth. In cases in which GH deficiency results from a brain tumor, headaches, polyuria, polydipsia and visual field defects may be present. If GH deficiency is diagnosed, concomitant insufficiency of other anterior hormones (thyrotropin, corticotropin, follicle-stimulating hormone, and luteinizing hormone) and posterior hormones (antidiuretic hormone) must be looked into.

Children with Kowarski syndrome have short stature due to bioinactive GH. Affected children have normal or slightly increased serum GH levels but low serum IGF-1 levels.¹¹ The bioinactive GH is due to a mutation of GH1.¹¹ Affected children respond to exogenous GH.¹¹ Children with Laron syndrome have normal or high levels of GH but low serum IGF-1 levels. The condition is due to mutations in the gene for the GH receptor, which prevents the production of IGF-1.¹¹ Affected children do not respond to administration of GH but respond to biosynthetic IGF-1. Peripheral resistance to GH and IGF-1 also has been documented in the African Pygmies.⁴⁰

Hypothyroidism

Infants born with congenital hypothyroidism may present with excessive sleeping, poor feeding, hypotonia, hoarse cry, constipation, prolonged jaundice, hypothermia, larger anterior fontanel, umbilical hernia, and macroglossia. Delayed treatment can lead to growth failure and permanent mental retardation. In juvenile hypothyroidism, there is marked growth retardation, and the bone age is usually more retarded than the height. The affected child is very short and has a higher upper/lower segment ratio.^1,2

Cushing Syndrome

The majority of Cushing syndrome cases are iatrogenic, secondary to chronic administration of glucocorticoids. Rarely, the condition may be the result of a corticotropin-producing pituitary tumor, bilateral adrenal hyperplasia, adrenal adenoma, adrenal carcinoma, or ectopic corticotropin production. The growth impairment results from suppression of endogenous GH secretion.²⁹ The cardinal features of Cushing syndrome include short stature, truncal obesity, moon facies, suprascapular fat pad (“buffalo hump”), muscle weakness, striae, hirsutism, and hypertension. The bone age is delayed. In contrast, children with simple or exogenous obesity are tall for their age, and the bone age is slightly advanced.

NEXT: Androgen Excess

Androgen Excess

Excess androgen endogenously produced or exogenously administered can lead to accelerating growth with advanced bone age and early epiphyseal closure. Androgen accelerates growth because it is converted to estrogen by aromatase. High levels of estrogen lead to accelerated growth with advanced bone age. As such, individuals with androgen excess are tall as children (prior to epiphyseal closure) and short as adolescents and adults.⁴¹

Chromosomal and Genetic Disorders

Most chromosomal disorders, with the exception of the multiple X and Y syndromes, result in prenatal as well as postnatal growth retardation. Examples of chromosomal and genetic disorders associated with short statures include Turner syndrome, Noonan syndrome, Down syndrome, Russell-Silver syndrome, Prader-Willi syndrome, skeletal dysplasias, and mutations in SHOX on the X chromosome.²⁹ The presence of dysmorphic features may suggest the diagnosis. A genetic consult would be in order if the diagnosis is not obvious. Note that in Turner syndrome, short stature may be the only presenting symptom. Hence, chromosome studies should be done on all girls whose short stature is otherwise unexplained.

Psychosocial Dwarfism

Poor growth may be associated with an unfavorable psychosocial situation. It is thought to represent functional hypopituitarism in which psychic factors have produced pituitary insufficiency through hypothalamic suppression.¹ Some children with psychosocial dwarfism may have end-organ resistance to IGF-1.¹ Caloric deprivation, anorexia, and malnutrition may coexist in an adverse environment. Confirmation of the diagnosis of psychosocial dwarfism is made when linear growth returns to normal when the child is removed from the home environment. Psychosocial dwarfism in its most severe form is readily diagnosable but represents just the tip of the iceberg; diagnosis of milder forms may be more difficult, requiring a high index of suspicion. In all cases, the underlying cause(s) should be looked into and properly treated.

Chronic Malnutrition

Chronic nutritional deprivation retards growth and is associated with reduced synthesis of IGF-1. Catch-up growth usually occurs when the malnutrition is corrected, although the catch-up is not always complete. With protein malnutrition such as occurs in kwashiorkor, resumption of growth requires essential amino acids as well as adequate caloric intake. The hallmark of chronic malnutrition is low weight for height.²⁹

Chronic Systemic Diseases

Almost any chronic systemic diseases (eg, celiac disease, cystic fibrosis, inflammatory bowel disease, immunodeficiency) may result in growth retardation.²⁹ Many patients with these conditions are in a state of negative nitrogen balance. After the disease has been under control or is cured, there is usually significant catch-up growth.

Skeletal Dysplasias

The skeletal dysplasias comprise a heterogeneous group of disorders associated with abnormalities in the size and shape of the limbs and skull, resulting in short stature. Children with skeletal dysplasias often have short extremities and an increased upper/lower segment ratio. There are exceptions: Proportionate short stature may occur in children with osteogenesis imperfecta.¹⁸

Idiopathic Short Stature

Idiopathic short stature is a diagnosis of exclusion. The etiology is deemed idiopathic if no cause can be found after a thorough history, complete physical examination, and appropriate laboratory investigations. Approximately 50% of children with idiopathic short stature remain short in adult life.⁴²

NEXT: Complications

COMPLICATIONS

Children with short stature may experience bullying, teasing, victimization, exclusion, and juvenilization.^43-46 Affected children may have low self-esteem.⁴⁰ Parents may have concerns and anxiety.⁴⁴ The psychosocial stress on the children and parents cannot be overemphasized. The condition may have an adverse effect on the quality of life of the child and parents.⁴⁶ Short stature may be a harbinger of an occult underlying chronic disorder.

PROGNOSIS

The prognosis varies, depending on the underlying etiology. Children with constitutional growth delay have an excellent prognosis.¹

MANAGEMENT

Treatment depends on the nature of the underlying disorder. When the cause is treatable, it is important to initiate treatment as early as possible to optimize the final adult height potential. Most children with constitutional growth delay and familial short stature do not require treatment apart from watchful observation.¹ If the cause does not require treatment or is untreatable, a frank and thorough explanation for the short stature should be given to the child and the family. Affected children should be encouraged to discuss the implications of the diagnosis so to minimize the psychological disturbances.^1,47 Psychological stress should not be overlooked, and psychological counseling may occasionally be necessary.¹

The treatment of GH deficiency or bioinactive GH (Kowarski syndrome) is GH replacement therapy, usually in the form of recombinant DNA-derived human GH (rhGH) given subcutaneously.⁴⁸ Somatropin, an rhGH produced via recombinant DNA technology in Escherichia coli, has been widely used since 1985. The recommended dose ranges from 20 to 40 µg/kg once daily based on serial measures of serum IGF-1 levels.⁴⁹

In 2003, the Food and Drug Administration (FDA) approved the use of GH for children with idiopathic short stature with a height more than 2.25 standard deviations (1.2nd percentile) below the mean, in whom the epiphyses are not closed, and whose predicted adult height without therapeutic intervention is less than 160 cm for males and less than 150 cm for females.⁵⁰ In spite of FDA approval, the decision about whether to use GH for such purposes should be made on a case-by-case basis after a thorough discussion with the family and the child.⁴⁹ The physical and psychosocial burdens as a result of short stature and the efficacy, potential adverse effects, and cost of the treatment should be taken into consideration.^5,51,52 The recommended dose ranges from 43 to 67 µg/kg once-daily by subcutaneous injection.⁴⁹ These doses are substantially higher than those recommended for children with GH deficiency, presumably because children with idiopathic short stature have relatively impaired sensitivity to GH.^42,49 Daily administration of GH is superior to less frequent administration.¹⁶ Treatment with GH is continued if the height velocity increases by at least 2.5 cm per year above the baseline height velocity when reassessed after 1 year of treatment or until the child grows to a height considered satisfactory to the family and clinician.⁴⁹ Although GH therapy does improve final height in patients with idiopathic short stature, treated individuals remain relatively short when compared with peers of normal stature.^53,54

In general, GH therapy at standard doses has an acceptable safety profile.^55-57 Adverse events are rare and include diabetes mellitus, benign intracranial hypertension (pseudotumor cerebri), increased intraocular pressure, scoliosis, arthralgias, slipped capital femoral epiphysis, cholestatic hepatitis, pancreatitis, and increased risk of malignancy in those with cancer-associated risk factors.^{42,51,55,56,58}

Adolescent boys with constitutional growth delay and puberty and moderate short stature (taller than -2.5 standard deviations) are more appropriately treated with low-dose testosterone rather than GH.^5,49 Testosterone can be given intramuscularly, orally, or topically (ie, patches or gels).⁵⁹ Oxandrolone, a testosterone derivative with fewer androgenic effects than testosterone and which does not aromatize, is the treatment of choice.^5,49 Aromatase inhibitors such as anastrozole and letrozole may also be used for such purposes. Aromatase inhibitors work by delaying closure of epiphyses and thereby prolonging the period of growth through inhibition of androgen to estrogen.^45,56 Available data suggest that aromatase inhibitors may improve short-term growth outcome, but final adult height data are scarce.^60-62

In adolescent girls with constitutional growth delay and puberty and moderate short stature, a short course of estrogen therapy may be considered. The use of aromatase inhibitors is not a treatment option, because aromatase inhibitors would slow growth by inhibiting estrogen production.

Children with severe short stature from GH insensitivity due to genetic defects in the GH receptor (eg, Laron syndrome) or postreceptor mechanisms or from the development of GH-inactivating antibodies may benefit from IGF-1 therapy.^28,42,49,51 Mecasermin, a recombinant human IGF-1 can be used in this regard. The main concern with recombinant human IGF-1 therapy is the increased risk of hypoglycemia.⁵¹ 

Alexander K. C. Leung, MD, is a clinical professor of pediatrics at the University of Calgary and a pediatric consultant at the Alberta Children’s Hospital in Calgary, Alberta, Canada.

Alexander A. C. Leung, MD, is an assistant professor in the Departments of Medicine, Community Health Sciences, and Oncology at the University of Calgary, in Calgary, Alberta, Canada.

NEXT: References

REFERENCES:

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