Case Files Pediatrics, (LANGE Case Files) 4th Ed.

CASE 21

The parents of a healthy 8-year-old boy are concerned that he is the shortest child in his class. His height and weight growth curves are shown in Figure 21-1 (see next page). He was a full-term infant, has experienced no significant medical problems, and is developmentally appropriate. Other than being small, his examination is normal. His upper and lower body segment measurements demonstrate normal body proportions. His father is 6 ft 4 in tall; he began pubertal development at 13 years of age. His mother is 5 ft 11 in tall; she had her first menstrual cycle at the age of 14 years.

image

Figure 21-1. Childhood growth curve. (Reproduced from the Centers for Disease Control and Prevention.) Available at http://www.cdc.gov/growthcharts/clinical_charts.htm. Accessed on April 19, 2012.

Image What is the most likely diagnosis?

Image What is the best diagnostic test?

Image What is the best therapy?

ANSWERS TO CASE 21: Growth Hormone Deficiency

Summary: An 8-year-old boy with no significant medical history and a normal examination presents with failure to grow.

• Most likely diagnosis: Growth hormone (GH) deficiency.

• Best diagnostic test: Screening tests might include a complete blood count (CBC) and erythrocyte sedimentation rate (ESR); electrolytes and general health chemistry panel; urinalysis; serum for thyroid function studies, insulin-like growth factor-1 (IGF-1), and insulin-like growth factor–binding protein-3 (IGF-BP3); bone age radiograph; and, if this were a girl, possibly chromosomal karyotype.

• Best therapy: Replace GH via injection.

ANALYSIS

Objectives

1. Understand the common causes of growth delay in children.

2. Appreciate the evaluation strategies for the various forms of growth failure.

3. Learn treatment options for common causes of childhood growth delay.

Considerations

This patient has essentially stopped growing (or is growing at a rate less than expected). He has no medical problems and a normal examination. His parents are tall, and their pubertal development was not delayed. An evaluation to determine the reason for his growth failure is appropriate.

APPROACH TO:

Growth Hormone Deficiency

DEFINITIONS

BONE AGE: Childhood bone development occurs in a predictable sequence. Left wrist radiographs on children older than 2 years (or the knee in those younger) are compared to “normals” to determine how old the bones appear compared to chronologic age, thus providing an estimate of the remaining growth potential of the bones.

CONSTITUTIONAL GROWTH DELAY: A condition in which a healthy child’s growth is slower than expected but for whom one or more parents demonstrated a pubertal development delay and ultimately normal adult height. In this case, the “bone age” equals the “height age.”

FAMILIAL SHORT STATURE: A condition in which a short child is born to short parents who had normal timing of their pubertal development.

HEIGHT AGE: The age at which a child’s measured height is at the 50th percentile.

IDIOPATHIC SHORT STATURE: A condition in which a short stature diagnosis cannot be reached.

CLINICAL APPROACH

Many parents become concerned if their child is noticeably shorter than their child’s peers. Many conditions can result in short stature; a growth and social history (to identify psychosocial growth failure), physical examination, and selected screening tests usually help to identify the problem’s etiology.

In the first year of life, children grow at a rate of approximately 23 to 28 cm per year. This rate drops to approximately 7.5 to 13 cm per year for children aged 1 to 3 years. Until puberty, they grow approximately 4.5 to 7 cm per year. At puberty, growth increases to 8 to 9 cm per year for girls and to 10 to 11 cm per year for boys. By approximately 24 months of age, most children settle into a percentile growth channel, remaining there for the remainder of their childhood. Significant deviations from these expectations alert the clinician to potential growth problems (ie, “fall off their curve”).

Constitutional growth delay is a common cause of short stature. These children have no history or examination abnormalities. In contrast to children with GH deficiency, children with constitutional delay have a growth rate that is normal. Their family history is positive, however, for one or more parents with pubertal development delays (“late bloomers”) who developed normal adult height. A short child in a family with a classic history of “late bloomers” often requires no laboratory or radiographic evaluation. Sometimes a bone age is helpful to reassure the patient and family that much bone growth remains and normal height will be achieved. For some of these children, testosterone injections will hasten pubertal changes (which eventually will begin on their own without treatment); consultation with a pediatric endocrinologist can be helpful.

The child born to short parents often is short (familial short stature). The growth curve shows growth parallel to a growth line at or just below the third to fifth percentile. Laboratory and radiographic testing usually are not necessary; a bone age equals the chronologic age, indicating no “extra” growth potential. An estimate of a child’s ultimate height potential is calculated using the parents’ heights. A boy’s final height can be predicted as follows: (Father’s height in cm + [Mother’s height in cm + 13])/2. A girl’s final height can be predicted as follows: (Mother’s height in cm + [Father’s height in cm + 13])/2. Reassurance is indicated for children with familial short stature.

Growth hormone (GH) deficiency occurs in approximately 1 in 4000 school-age children. These children demonstrate a growth rate that is slow, usually falling away from the normal growth curve (in contrast to constitutional delay where growth parallels the third to fifth percentile curve). On examination these children often appear younger than their stated age and frequently appear chubby (weight age > height age). Bone ages are delayed, indicating catch-up growth potential. GH screening tests include serum IGF-1 or somatomedin C and IGF-BP3. Confirmation often requires GH stimulation testing and interpretation by a pediatric endocrinologist. Replacement therapy involves recombinant GH injections several times per week until the child reaches full adult height.

Clues that growth failure may be caused by an underlying condition not already mentioned include poor appetite, weight loss, abdominal pain or diarrhea, unexplained fevers, headaches or vomiting, weight gain out of proportion to height, or dysmorphic features. Screening tests might include a CBC (anemia), ESR (chronic inflammatory diseases), electrolytes (acidosis or renal abnormalities), general health chemistry panel (hepatitis, liver dysfunction), urinalysis (infection, renal disease), thyroid function tests (hypothyroidism), IGF-1 and IGF-BP3 (GH deficiency), and, for girls, possibly chromosomal analysis (Turner syndrome). Children with growth failure who do not fall into another, more appropriate category are classified as having idiopathic short stature.

COMPREHENSION QUESTIONS

21.1 An 8-year-old boy has short stature. He has begun to gain quite a bit of weight over the last year, has little or no energy, sleeps more than normal, and complains of being cold. His growth curve demonstrates that he has fallen from the 50th percentile to the 5th percentile for height, but his weight has increased to the 90th percentile. On examination, he is obese and has an immature facies, thin hair, and slow reflexes. Which of the following is the most appropriate course of action for this child?

A. Order Epstein-Barr virus titers.

B. Measure thyroid function.

C. Reassure the mother that the child has normal prepubertal development.

D. Determine bone age.

E. Order a somatomedin C level.

21.2 A 16-year-old boy complains that he is the shortest boy in his class. He has a normal past medical history, and although always a bit small for age, he has really noticed that he has fallen behind his peers in the last 2 years. He is Tanner stage 3 and is at the 5th percentile for height. His father began puberty at the age of 16 and completed his growth at the age of 19; he is now 6 ft 2 in tall. His mother began her pubertal development at the age of 10 and had her first menstrual period at the age of 13; her height is 5 ft 4 in. Which of the following is the single most appropriate first intervention?

A. Chromosomal analysis

B. Liver function studies

C. Measurement of bone age

D. Measurement of somatomedin C

E. Pediatric endocrinology referral

21.3 A 17-year-old girl is 4 ft 10 in tall. Her father is 5 ft 10 in tall and her mother is 5 ft 5 in tall. Her past medical history is significant for lifelong short stature and cardiac surgery at the age of 1 year. She has never had a menstrual period. Which of the following is the most appropriate first action?

A. Chromosomal analysis

B. Referral to a pediatric endocrinologist

C. Serum testosterone levels

D. Thyroid function studies

E. Ultrasonogram of the abdomen

21.4 You see a 14-year-old boy in the juvenile detention center where he is currently living for arson to an abandoned building. He is tall, slim, underweight, and appears to have especially long legs. His testes are small for age, and his phallus seems somewhat undersized. His mother reports that he had difficulty with reading, spelling, and mathematics early on, but now he has difficulty in all classes. Which of the following diagnostic tests is most likely to identify his problem?

A. Chromosomal analysis

B. Referral to pediatric endocrinology

C. Serum testosterone levels

D. Thyroid function studies

E. Ultrasonogram of the abdomen

ANSWERS

21.1 B. This child has classic symptoms of acquired hypothyroidism. A bone age would be delayed, but thyroid function studies are needed to make the diagnosis. Thyroid hormone replacement therapy should resolve these symptoms, and growth should resume normally.

21.2 C. This boy likely has constitutional growth delay, similar to that of his father. Bone age would be delayed, indicating potential growth. He eventually will enter puberty, but the psychosocial ramifications of remaining shorter and appearing more immature than his peers may warrant treatment. Monthly testosterone injections “jump start” the pubertal process without altering final growth potential; a pediatric endocrinologist might be required to assist.

21.3 A. Chromosomal analysis is likely to show Turner syndrome (TS) in this child with parents of normal height. The surgery might have been for coarctation of the aorta. Common TS features include female phenotype, short stature, sexual infantilism, streak gonads, broad chest, low hairline, webbed neck, and congenital lymphedema of the hands and feet. Some TS children benefit from GH therapy.

21.4 A. Boys with Klinefelter syndrome are tall for their age; the testes are smaller than normal and feel firm and fibrotic. Examination can reveal eunuchoid body habitus and reduced upper body-lower body segment ratio (a long lower segment). Diagnosis is established by karyotyping.


CLINICAL PEARLS

Image Constitutional growth delay is a condition in which a healthy child’s growth is slower than expected and for whom at least one parent demonstrated a pubertal development delay but normal adult height (“late bloomers”). Growth parallels the 3rd or 5th percentile growth curve; bone age is delayed.

Image Familial short stature is a condition in which a short child is born to short parents who had normal timing of their pubertal development. Growth parallels the 3rd or 5th percentile growth curve; bone age is normal.

Image Idiopathic short stature includes children with short stature for whom a more appropriate diagnosis cannot be found.

Image Growth hormone (GH) deficiency is a condition in which inadequate GH secretion results in growth failure, delayed bone age, and catch-up growth upon GH replacement.


REFERENCES

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Moshang T, Grimberg A. Neuroendocrine disorders. In: McMillan JA, Feigin RD, DeAngelis CD, Jones MD, eds. Oski’s Pediatrics: Principles and Practice. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006:2097-2103.

Parks JS, Felner EI. Hypopituitarism. In: Kleigman RM, Stanton BF, St. Geme JW, Schor NF, Behrman RE, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: WB Saunders; 2011:1876-1881.

Plotnick LP, Miller RS. Growth, growth hormone, and pituitary disorders. In: McMillan JA, Feigin RD, DeAngelis CD, Jones MD, eds. Oski’s Pediatrics: Principles and Practice. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006:2084-2092.

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Reiter EO. Disorders of the anterior pituitary gland. In: Rudolph CD, Rudolph AM, Lister G, First LR, Gershon AA, eds. Rudolph’s Pediatrics. 22nd ed. New York, NY: McGraw-Hill; 2011:2009-2012.

Thilo EH, Rosenberg AA. Disturbances of growth. In: Hay WW, Levin MJ, Sondheimer JM, Deterding RR. Current Diagnosis & Treatment: Pediatrics. 20th ed. New York, NY: McGraw-Hill; 2011:944-951.