A 10 year old girl presents to your clinic for evaluation of short stature. Parents report that she has always been the shortest girl in her class, but they have become concerned because the patient's 8 year old sister is now the same height as she is. The patient has not yet attained menarche and her mother reports no breast development. She has been well with no chronic medical problems, no hospitalizations, and no surgeries. She lives with her mother, father, and sister and she is currently a straight A student in the fifth grade. Her mother is 173 cm (5'8") and weighs 68 kg (150 pounds). She had menarche at age 12. The patient's father is 185 cm (6'1") and weighs 95 kg (210 pounds). He started shaving at age 15. There is no family history of any medical problems. On further history, you find that your patient was 43 cm (17 inches) long at term (average is 49.5 cm, 19.5 inches).
Exam: VS T 37.0, P 90, R 18, BP 100/60. Height 120 cm (<5%), weight 23 kg (slightly <5%). She is an alert, small appearing girl who is in no apparent distress. HEENT exam is normal. Neck is supple with webbed appearance. Heart regular rate, no murmurs. Lungs are clear. Abdomen is soft without masses. Tanner 1 breasts with wide-spaced nipples are evident. The carrying angle is increased. Tanner 1 pubic hair is noted.
Her growth chart is reviewed which demonstrates an average growth velocity of 3 cm per year. She is sent for a bone age that is read by the pediatric radiologist as 8 years and 6 months. CBC, ESR, TFT's, UA, and serum electrolytes are normal. Chromosomes are obtained revealing a 45XO pattern. The diagnosis of Turner Syndrome is made. You refer her for a renal ultrasound, cardiology evaluation, and a hearing screen. She is also seen by the pediatric endocrinologist and is started on growth hormone.
Growth is an important task for infants and children to accomplish. Short stature is a common pediatric problem with potential long-term sequelae if a pathologic cause remains undiagnosed. Physicians though, can be reassured that the majority of cases of short stature have a nonpathologic cause and by obtaining a thorough history, physical exam, and screening tests, short stature can be readily evaluated.
Growth is primarily controlled by the hypothalamus and pituitary gland. The pituitary gland has two lobes, the anterior lobe (adenohypophysis) and the posterior lobe (neurohypophysis). Growth hormone is secreted in a pulsatile fashion from the anterior lobe of the pituitary in response to two hypothalamic hormones, GH-releasing hormone (GHRH) and somatostatin. GHRH stimulates and somatostatin inhibits the secretion of growth hormone. GH stimulates the production of insulin-like growth factors (IGFs), especially IGF-1, mainly in the liver. These proteins then circulate and stimulate tissues to grow. GH can also directly act on growth plates to stimulate growth. IGF-1 and GH then feed back to the hypothalamus to inhibit secretion of GHRH and stimulate secretion of somatostatin.
Obtaining a complete and precise history in the work-up of a short child is crucial. It is important to inquire about prenatal history, gestational age at birth, weight and length at birth, and neonatal medical history. Adjustments must be made when plotting the weight, height, and head circumference of a former premature infant. In general, weight, height, and head circumference should be corrected until the child is about 24 months of age, unless the child's birthweight was less than 1500 grams in which case, correction until three years of age is recommended. Healthy, premature infants do display catch-up growth. Term infants can have intrauterine growth retardation (IUGR) that can affect the infant's weight, length, and even head circumference. Many causes of IUGR have been identified, including pregnancy-induced hypertension and maternal infections. Potential for future growth in infants with IUGR is variable and depends on the etiology. A neonatal history that includes hypoglycemia, prolonged jaundice, or microphallus should raise suspicions of hypopituitarism. Midline defects such as cleft palate may also be associated with panhypopituitarism or specific deficits in growth hormone or thyroid hormone production.
The medical history should also include the patient's past medical problems and current medications. Long-term corticosteroids, like those used in the treatment of asthma, can affect a child's height. Catch-up growth can be seen when the medication is discontinued, but this is also dependent on the underlying disease. Children with ADHD who are treated with stimulants are at risk of growth retardation. There often is a noticeable growth spurt when the medication is discontinued. Gastrointestinal, renal, hematologic, or cardiopulmonary disease can cause growth failure. In a patient with Crohn's or celiac disease, linear growth failure may even be the presenting complaint.
The family history is important information that can aid in determining potential reasons for short stature, as well as the child's expected height. One measure that is used for comparison is the adjusted mid-parental height (AMPH). The AMPH in a girl is the average of the father's height minus 13 cm and the mother's height. The AMPH in a boy is the average of the mother's height plus 13 cm and the father's height. Most children achieve their AMPH within approximately 5 cm. The two most common reasons for short stature in otherwise healthy children are familial short stature and constitutional delay. In both conditions, children are normal size at birth, but gradually fall across growth percentiles to resume a normal growth velocity at or below the bottom of the linear growth curve by age two or three. A short child with a normal growth velocity and a less than average mid-parental height can be diagnosed with familial short stature. Parents should also be asked when they entered puberty. A family history of delayed puberty in a short child with a normal growth velocity can help make the diagnosis of constitutional delay of growth and puberty, which means that the child is likely to enter puberty later than his/her peers and finish growing later, ending up with a height that is roughly normal.
A thorough physical exam should be completed on a child with short stature. Time should be spent obtaining accurate growth measurements. Weight, height, and head circumference should be plotted on the appropriate chart. A length (supine measurement) should be plotted on an infant (0-36 month) growth chart. A standing height should be plotted on a growth chart for children 2-18 years. Using prior height measurements, the child's growth velocity should be calculated. A clinician should become concerned if a child's growth velocity is less than 5 cm per year between the ages of 4-10 years. A height age can be determined by drawing a horizontal line from the patient's height to the 50th percentile line for height and then dropping a vertical line to the baseline to determine the height-equivalent age. Arm span should be measured and the upper-to-lower extremity ratio (pubis to crown of head compared to pubis to floor measurements) should be calculated. If these are abnormal, a skeletal dysplasia such as hypochondroplasia should be contemplated and evaluated with further x-rays. Determining a child's weight-to-height ratio also has some diagnostic value. In a child with short stature secondary to endocrine pathology, the child's weight will continue to progress normally or even increase relative to his or her height. Physical characteristics that might indicate a short statured syndrome should be sought. Turner Syndrome, for instance is associated with short stature, and stigmata on physical exam can include webbed neck, low posterior hairline, edema of the hands and feet, and wide-spaced nipples. Of note, these findings may be subtle or even absent in a girl with Turner Syndrome. Chromosomes should be obtained if Turner Syndrome is suspected or if all other causes of growth failure are ruled out in a short girl. A complete physical exam in a short child might detect a heart murmur that could lead a clinician to the diagnosis of significant cardiovascular disease, which can affect a patient's height, or an enlarged thyroid gland, which might indicate hypothyroidism-induced growth failure. (Hypothyroidism can, however, be present with a normal thyroid exam.)
Growth hormone deficiency is a pathologic cause of short stature that should be suspected in a boy with micropenis or any child with a midline abnormality (e.g., cleft palate, septo-optic dysplasia, or holoprosencephaly). Physical findings may also include a childlike appearance (excess fat relative to lean mass) and excess downy hair on the back.
Following a complete history and physical exam, a clinician can use ancillary tests to screen for potential causes of a child's short stature. A bone age can help determine a child's skeletal maturation. This test is performed by obtaining a radiograph of a child's left hand and wrist. The epiphyseal centers seen on the radiograph are compared to age-appropriate standards to determine a bone age. In children less than 2 years, a hemiskeleton bone age should be obtained. This test is performed by obtaining radiographs of the child's entire left upper and lower extremity. The number of ossification centers is determined and again compared to age-appropriate standards to determine the bone age. It is very helpful in the classification of short stature to compare chronologic age, bone age, and height age. In familial short stature, the patient's chronologic age and bone age are equivalent and both are older than the patient's height age. In constitutional delay and malnutrition, the patient's bone age and height age are equivalent and both are younger than the patient's chronologic age. A patient with hypothyroidism can present with a chronologic age older than height age, and bone age much younger than both.
Commonly, thyroid function tests (free T4 and TSH), a complete chemistry profile to include LFT's, a urinalysis and urine culture, and a CBC with ESR are carried out to look for occult causes of poor growth. In the child with delayed bone age and poor linear growth velocity but normal weight, low serum IGF-1 and IGF-BP3 (insulin-like growth factor and IGF binding protein 3) measurements may give clues to the presence of growth hormone deficiency. These patients should be referred to a pediatric endocrinologist for further testing. Random determination of serum growth hormone is not useful. Growth hormone stimulation tests are generally carried out by endocrinologists using agents which cause growth hormone release (e.g., insulin, arginine, L-dopa, clonidine) to determine "provocative" growth hormone levels which are more diagnostic.
A child's growth hormone secretory capacity is not always clear, even after extensive evaluation and testing. If growth hormone deficiency is suspected, a six to twelve month trial of growth hormone therapy may be carried out after an MRI of the sella is obtained. Recombinant growth hormone has been available since 1985 and there are numerous completed and ongoing studies attempting to evaluate its effectiveness in many different clinical settings. Short stature alone is not sufficient criteria to begin a child on growth hormone, as it is not only expensive and not without serious potential side effects, but also there may be no ultimate height benefit. Outside of accepted indications, e.g., GH deficiency, Turner Syndrome, and chronic renal failure, GH should only be administered in a research setting. Recently, GH has been gaining acceptance as an intervention in Prader Willi Syndrome and in some cases of IUGR.
In summary, short stature is a complaint that pediatricians commonly encounter in the outpatient setting. The key to diagnosing a cause is a detailed history, thorough physical exam, and meticulous height measurements over time. Ancillary tests can be of benefit, but a differential diagnosis should be contemplated prior to ordering additional information. The therapeutic goal is to allow children to grow as tall as their genetic potential.
1. What is the AMPH of a girl whose mother is 175 cm (5'9") and father is 193 cm (6'4")?
2. A) How should height be measured on a 22 month old boy? B) How should height be measured on a 39 month old girl?
3. You are evaluating a boy with a height below the 5% for age and weight is at the 50% for age. You are concerned that his growth is secondary to an endocrine cause. Should you order a serum growth hormone level in your work-up?
4. How do you obtain a bone age on a 20 month old child?
5. What is the cause of short stature in a 14 year old boy with a normal growth velocity and Tanner 2 genitalia on physical exam?
1. Brunader RE, Moore DC. Evaluation of the child with growth retardation. Am Fam Phys 1987;35(2):165-176.
2. Vogiatzi MG, Copeland KC. The short child. Pediatr Rev 1998;19(3):92-99.
3. Rosenfeld RG. Chapter 7 - Disorders of Growth Hormone and Insulin-like Growth Factor Secretion and Action. In: Sperling MA (ed). Pediatric Endocrinology. 1996, Philadelphia: W.B. Saunders Company, pp. 117-169.
4. Aceto TJ, Garibaldi L, Meyers SE, et al. Chapter 192 - Short Stature and Slow Growth in the Infant and Child. In: Becker KL(ed). Principles and Practice of Endocrinology and Metabolism, second edition. 1995, Philadelphia: J.B. Lippincott Company, pp. 1644-1661.
Answers to questions
1. 177.5 cm (5'10")
2. A) supine B) standing
3. No, random serum growth hormone levels are generally unhelpful in the work-up of short stature.
5. constitutional delay of growth and adolescence