Supported by a grant from The Genentech Foundation for Growth and Development. Thesematerials may be freely reproduced, but may not be modified without written consent of theauthors.

Timmy and the "Big Kids"Facilitator’s Guide

Case Authors: Case Advisors:Laurie E. Cohen, MD S. Jean Emans, MDJohn R. Knight MD Joan Mansfield, MDHarvard Medical School Harvard Medical SchoolChildren’s Hospital, Boston Children’s Hospital, Boston

Topic: Constitutional Short Stature

Abstract:Pediatricians and other primary care clinicians are commonly consulted when childrenare shorter than their peers. These children often worry about their height and may sufferfrom diminished self-confidence. Parents also are often anxious and look to the primarycare clinician for answers. Very often, their presenting question is “Isn’t there some kindof medicine that will make my child grow more?” Pediatricians should know how toevaluate a child with short stature, diagnose and treat any underlying illness, anddiscriminate between those children who require hormonal therapy and those needingreassurance alone. Proper management will have an enormous effect on a child’s life.

Goal:To provide clinicians with a basic understanding of how to manage short stature in theprimary care medical office.

Objectives:By the end of this session, trainees will be able to:1. List an appropriate differential diagnosis for short stature.2. Accurately calculate mid-parental height and target height.3. List appropriate assessments and diagnostic studies for a child who is short.4. Understand the concept of bone age.5. Describe the office management of short stature.

Prerequisite Cases:“Normal vs. Abnormal Patterns” (Understanding Growth)

Related Cases: “The Shortest in the Class” (Turner’s Syndrome and Short Stature) “Will I Ever Get My Period?” (Growth and Chronic Disease)

Themes:Growth in Children and Adolescents

Key Words: short stature, bone age, constitutional delay, asthma, growth velocity,growth hormone deficiency, growth chart, target height, mid-parental height

Bright Futures Core Concepts:While all of the Core Concepts are included in each case, this particular case can be usedto highlight communication, partnership, advocacy, and prevention/healthy promotion.

Materials Provided:• Facilitator’s Guide• 3-part case narrative: Part I, Part II, and Epilogue• Handout #1: Timmy’s Growth chart• Handout #2a & 2b: Bayer and Bayley height and weight growth curves• Handout #3: Upper:lower Segment Ratios• Handout #4: 9 Year Old Hand and Wrist Radiograph for Bone Age• Bibliography

Facilitator Preparation:Facilitators should thoroughly review this guide and the other materials provided.Facilitators should locate a copy of Greulich WW and Pyle S. Radiographic Atlas ofSkeletal Development of the Hand and Wrist. Stanford, CA: Stanford University Press,1959. If possible this text should be borrowed from the Radiology Department for theconference. If this is not possible, photocopy the radiograph of the hand and wriststandard for a nine-year-old boy and the chart of estimated mature heights for delayedboys.

At the end of the guide we have included a section entitled, “IndependentLearning/Prevention Exercises,” that will further stimulate group and individualeducation on this topic.

Suggested Format for a One Hour Session:We anticipate that case facilitators will modify implementation of the case session tobest fit their educational setting and learners. For detailed recommendations on casefacilitation, please see the previous chapter entitled, “A Brief Guide to FacilitatingCase Discussion.”

Introduction: Short stature is defined as two standard deviations below the mean forheight age (or below the third percentile). Of these children, approximately 20% have apathological cause for their short stature, with the rest having familial short stature orconstitutional delay. The United States standards are based on a sampling of NorthAmerican children and may not be valid for all ethnic groups (e.g., Asian children tend tobe shorter on average, African-American and Hispanic children tend to enter puberty atan earlier age).

Chronic diseases may affect growth by decreased caloric intake and increased energyexpenditure. Mild asthma is not associated with poor growth. Growth delay associatedwith asthma has been related to severe disease, onset before age 3 years, and malegender. However, final height is not compromised in the absence of steroid use. Oralsteroid use is associated with poor growth. There have also been some reports of growth

failure with normal-dose long-term inhaled steroids (see references), although moststudies report no adverse influence on growth associated with inhaler use.

The primary care clinician can monitor the growth of most children with short stature.Referral to an endocrinologist is indicated if there is:• Abnormal growth velocity• Abnormal physical exam• Abnormal screening

Open the Discussion: Introduce the case title and the session goal. Explain that thiswill be an interactive case discussion and not a lecture. Distribute Part I of the caseand ask one or more of the participants to read it aloud.

Part I

Timmy is an 11 year and 10 month old boy who comes to your office with his mother and father. He hasalways been short for his age. Over the past 1 to 2 years, his mother has noticed that he seems even smallercompared to his peers.

Review of the clinic medical record reveals that Timmy was born after a full term pregnancy at a weight of3kg (6 lb 10 oz). The delivery was spontaneous and vaginal and without complications. He achieved all ofhis early developmental milestones on time and has always done well in school. Timmy has a history ofmoderate asthma. He has required hospitalization on five different occasions, and has been givenprescriptions for short courses of oral prednisone at least twice yearly. He has multiple environmentalallergies. His current treatment consists of a cromolyn sodium metered-dose-inhaler (MDI), 2 inhalationsTID; a beclomethasone MDI, 2 inhalations TID; and an albuterol MDI, 1 or two inhalations prn forwheezing.

"How are things going in school ," you ask.Timmy replies that “school is OK except when I get teased by the bigger kids.”He states that he has many friends outside of school, and he enjoys bicycling, soccer, and basketball.

Physical examination reveals a well-nourished male who appears small for his chronological age. Hisheight is 132.75cm (52¼ in) and his weight is 30kg (66 lb.) (see Growth chart). His sexual maturity ratingfor pubertal development is Tanner I. Hearing and vision screens are normal. The remainder of his exam isunremarkable.

Timmy’s father wants to know if growth hormone therapy would help his son to be taller. “We have someclose friends whose son was short. He got hormone shots and he’s grown about 6 inches in the last year.Wouldn’t that stuff help Timmy, too? You know, doctor, Timmy's a good hoops player, but unless he growsa lot more he’ll never get to play on the varsity squad .”

Distribute Handout #1 (NCGS Growth Chart). Following this reading, ask allparticipants “So what do you think about this case? What would you like to focus onduring our discussion today?” List agenda items on a blackboard or flipchart. Thenuse the questions below to guide the discussion. Remember that the key tosuccessfully leading a small group is facilitation of the discussion rather thanlecture. Draw as many participants as possible into the discussion. Allow silenceswhile group members think about questions. Present material from the discussionguide only when needed to complement or redirect the group discussion.

Guiding Questions and Discussion: Based on the history and physical examination, what is the differential diagnosis forTimmy’s short stature? Although most children with short stature but normal growthvelocity do not have a pathologic cause, the differential diagnosis should be considered: Systemic Disorders Affecting Growth:

• Malnutrition• Renal disease: secondary to rickets, acidosis, and nutritional failure• Diabetes: poor control, with significant acidosis, will result in significant

growth retardation• Cardiac: due to cyanosis and hypoxia, and other unclear underlying mechanisms• Hematologic diseases, such as chronic anemias• Gastrointestinal disorders (inflammatory bowel disease, chronic liver disease,

celiac disease, other causes of malabsorption)• Respiratory disease (cystic fibrosis, asthma)

Endocrine disorders• Hypothyroidism• Glucocorticoid excess• Growth hormone deficiency or resistance

Congenital Disorders• Intrauterine growth retardation• Skeletal dysplasias• Other genetic syndromes

Special inhibited growth patterns• Constitutional delay of growth and puberty• Familial and genetic short stature

Other• Idiopathic short stature• Psychosocial short stature

Facilitators may want to have the group generate this list through discussion,recording it on a blackboard or flip chart. Which diagnostic possibilities are most likely? Least likely? How do you thinkTimmy’s asthma and/or its treatment have affected his growth? The most likely possibilities are:

• Special inhibited growth patterns (normal variants)• Constitutional delay• Familial short stature• Asthma (although Timmy’s asthma is probably not severe enough to cause short

stature and the clinician would expect him to be underweight for height due toincreased energy expenditure)

• Steroid use (discuss small possibility that high dose inhaled steroids couldsuppress growth but that Timmy is on a low dose)

• Endocrine causes (these children tend to be overweight for height)− Hypothyroidism− Growth hormone deficiency

• Skeletal dysplasia (may not notice skeletal disproportion on visual inspection) andthese proportions may be measured (arm span, U/L ratio), as noted below.

The least likely possibilities are malnutrition or systemic diseases, as Timmy is notunderweight for height, and he does not have any other abnormalities on physical exam(e.g., cyanosis or heart murmur as evidence for cardiac disease, history of polydipsia andpolyuria as evidence of diabetes). What is a normal growth rate? For a child from 3 years until onset of puberty, thenormal growth rate is 5-6.5 cm/year (2-2.5 inches/year). Linear growth stabilizes withmost children establishing a pattern of growth by 3 years of age and not deviating fromthis pattern until the onset of puberty. Just prior to the onset of puberty, the growth ratemay dip to 4 cm/year.

Separate National Center for Health Statistics (NCHS) charts, based on a largesampling of North American children, have been created to track growth in boys andgirls. These charts provide normative curves + 2 standard deviations for both height andweight parameters. There is potential variation based on ethnic and racial influences, aswell as other cultural and environmental factors that can influence growth or growthvelocity. The NCHS growth charts are derived from cross-sectional data and tend toflatten out the variability of the pubertal growth spurt. New growth charts have beenrecently released by the CDC (http://www.cdc.gov/growthcharts/).

Distribute Handout #2a & 2b (Bayer and Bayley growth charts). The Bayer andBayley growth charts or the North American growth charts (Tanner and Davies) areparticularly useful for tracking pubertal development in an individual child who may beshowing an abnormality of growth. These growth charts are derived from longitudinaldata and contain curves for early and late developers. What further information do you need from Timmy’s parents? The most helpfulinformation would be parental heights. (Note to Facilitator-This information will begiven in Part 2 of the narrative.) You should also ask about parental pubertal pattern. What additional measurements might be performed as part of the physicalexamination? (Optional question for advanced groups of learners.)

Abnormal body proportions are often detected by casual visual assessments butadditional measurements may be helpful. Consider measuring Timmy’s arm span andlower segment. Arm span is measured from middle fingertip to middle fingertip. Lower segment is measured from the top of the pubic symphysis to floor. To getthe upper segment, the lower segment is subtracted from the height, and then the ratio ofupper/lower segments ratio is calculated. Distribute Handout #3: Upper:Lower Segment Ratios

In the child with normal body proportion, the arm span should be approximately equal toheight. There are normative data for upper:lower segment ratios. For a Caucasian 10-14year old, the mean ratio is ~0.95. In children with a skeletal dysplasia, the arms and legsare short, giving a short arm span and reduced lower segment. In children with delayedpuberty, the arms and legs are often proportionally long. Distribute Part II of the case and have participant(s) read it aloud.

Part II

At your visit, you obtain family history, additional measurements, and a hand and wrist x-ray for bone age.

Timmy’s father is 174 centimeters (68 ½ in), and his mother is 161.3 centimeters (63 ½ in). Timmy’s fatherremembers still changing clothes sizes late in high school, and his mother had menarche at age 15 years.

On physical examination, Timmy appears to have normal body proportions, but to be sure you measure hisarm span from middle fingertip to middle fingertip and his lower segment from top of his pubic symphysisto the floor. His arm span is 133.3 cm (52 ½ in) and this should be approximately equal to his height if hehas normal proportions. His lower segment is 67cm (26 3/8 in) which you subtract from his height tocalculate a ratio of upper to lower segment (.99).

His bone age is read as 9 years. What is Timmy’s mid-parental height? Timmy’s father is 174 centimeters (68 ½in), and his mother is 161.3cm (63 ½in). This information is then used to calculate mid-parental height and target height: (Facilitator’s note: The following calculation is presented in inches. If metric units arepreferred, convert into centimeters by multiplying inches by 2.54.) mid-parental height = (mother's height + 5in) + (father's height) for boys 2 mid-parental height = (father's height –5in) + (mother's height) for girls 2 target height: mid-parental height + 2 SD (1 SD =2 in) • This calculation provides a target mean height and range for the genetic potential of a

child based upon the biologic parents' heights• This calculation alone is not sufficient to predict final height; it only calculates a

reference range for assessing growth Timmy’s mid-parental height = (63½ + 5 in) + (68½)

2 = 137 in 2 = 68½ inches

Tommy’s target height = 64½ inches to 72½ inches Considering Timmy’s mid-parental height, what is the most likely etiology of hisshort stature? The child who has been paralleling the mean growth curve within + 1 to 3 SD is probablygrowing along his or her genetically predetermined growth curve. Timmy may be shortbecause of genetic or familial short stature or because he has a delay in the onset ofpuberty. Typical features associated with genetic or familial short stature are:

• Family history of short stature• Birth weight > 2.5 kg if full-term infant• Height < 3rd percentile for chronologic age• Growth curve parallel but at or below 3rd percentile• Predicted adult height <3rd percentile• No organic or emotional cause for growth failure• Normal annual growth rate and bone age• Normal pubertal onset and maturation

Typical features associated with constitutional delay are:

• Family history of similar pattern of growth and pubertal development• Height at or below 3rd percentile for age, but normal annual growth rate• Delayed puberty• Delayed bone age, appropriate for height age• Normal predicted adult height in context of family pattern• No organic or emotional cause for growth failure• More common in boys

What further diagnostic studies are indicated? Consider the following laboratorystudies: • Complete blood cell count (CBC) to screen for infection, anemia, other hematologic abnormalities • Erythrocyte sedimentation rate (ESR) to screen for evidence of chronic inflammation, e.g., inflammatory bowel disease • Electrolytes and chemistry panel to screen for abnormalities of the kidneys, liver, bones, and adrenal glands • Urinalysis to screen for kidney disease• Thyroxine (T4) and thyrotropin (TSH) to screen for hypothyroidism• IGF-1 and IGFBP-3 to screen for growth hormone deficiency.

Distribute Handout #4: 9 Year Old Hand and Wrist Radiograph for Bone age.

Clinicians should also obtain a bone age. The x-ray of the hand and wrist is ameasurement of how far the growth centers of the bones in the left wrist and hand haveprogressed towards maturity in shape and relative to other bones. Skeletal changesinclude the calcification, growth, and shaping of the epiphyseal centers of the bones, andthe eventual fusion with the long bones. The bone age is compared to the standards ofGreulich and Pyle; or the Tanner-Whitehouse scoring system is used for each bone.Experience in determination is essential; not all radiologists may have adequate expertisein assessing bone age. Many etiologies of short stature are associated with a delayedbone age, i.e., with bone age lagging behind chronologic age (constitutional delay,malnutrition, hypothyroidism, growth hormone deficiency). Using the growth chart, onecan also determine a so-called “height age”- the age of a child who is at the 50thpercentile for that height. In this case, Timmy’s height age is 9 years, consistent with hisbone age and therefore suggesting constitutional delay. The bone age determination alsoallows the clinician to estimate final adult height using tables in Radiographic Atlas ofSkeletal Development of the Hand and Wrist (Greulich WW and Pyle S. Stanford, CA:Stanford University Press, 1959). In this case the predicted height is 168-170 centimeters(66 to 67 in).

What further evaluation would you do? Obtaining a follow up height in 4-6 monthsis important to determine if the growth velocity is within normal limits. The genitalexamination should be repeated, as there should not be onset of puberty at that time witha bone age of 9 years at the time of initial evaluation.

What would you like to tell Timmy? How can you improve his feelings of self worthand attitude about school? What will you say to his father? Unfortunately, oursociety often places too much emphasis on height. Timmy’s father needs to come toterms with Timmy’s size. Timmy’s parents should focus on his strengths to build hisself-esteem. If Timmy appears depressed or is acting socially immature, he wouldbenefit from professional counseling.

Although treatment with recombinant human growth hormone would increase growthvelocity and improve the height standard deviation in the short-term, it does not appear toimprove final height. Therefore, healthy children who have a normal growth velocity andwhose predicted heights are in keeping with their genetic potential, should not be treatedwith recombinant human growth hormone.

If Timmy has not started pubertal development at age 14 years and is distressed about hisimmature sexual development at that time, a pediatric endocrinologist could treat himwith a short course of low dose testosterone enanthate. This would result in penileenlargement and pubic hair development without compromise of final adult height.Spontaneous pubertal development would be expected within one year after treatment.

Distribute the Epilogue and Bibliography page. Ask someone to read the Epiloguealoud.

Epilogue

Timmy’s x-ray for bone age allows you to predict his final height of 168 to 170 centimeters (66 to 67 in).Based on your findings and recommendations, Timmy does not receive any medical treatment for hisgrowth. At age 14 years, he has testicular enlargement. At age 14 ½ years, he has developed pubic hair.At age 15 years, his growth rate accelerates and continues to increase at age 16 years.

He also sees the school psychologist weekly to work on family conflicts and self-esteem. At age 16 ½years, he is reasonably comfortable with his stature, has good peer relationships, and is on the soccer team.

Refer back to group’s learning agenda and summarize the key teaching points thatwere made. This will give the group a sense of accomplishment and emphasize theimportant messages. Suggest further sources of reading or other information ifthere are agenda items that were not covered in the discussion.

Independent Learning/Prevention Exercises: Facilitators may wish to assign“Independent Learning/Prevention Exercises” to the group, particularly if timeconstraints hinder the completion of the case. For example, learners can volunteer to givea talk to coaches and/or parents on the differences in growth rates and pubertaldevelopment in boys and girls. If the exercise is done in the absence of the facilitator,learners should take notes on their experience, then discuss with a faculty member forfeedback.

Timmy and the “Big Kids”

Case Authors:Laurie E. Cohen, MDJohn R. Knight MDHarvard Medical SchoolChildren’s Hospital, Boston

Case Advisors:S. Jean Emans, MDJoan Mansfield, MDHarvard Medical SchoolChildren’s Hospital, Boston

Part I

Timmy is an 11 year and 10 month old boy who comes to your office with his mother andfather. He has always been short for his age. Over the past 1 to 2 years, his mother hasnoticed that he seems even smaller compared to his peers.

Review of the clinic medical record reveals that Timmy was born after a full termpregnancy at a weight of 3kg (6 lb 10 oz). The delivery was spontaneous and vaginal andwithout complications. He achieved all of his early developmental milestones on timeand has always done well in school. Timmy has a history of moderate asthma. He hasrequired hospitalization on five different occasions, and has been given prescriptions forshort courses of oral prednisone at least twice yearly. He has multiple environmentalallergies. His current treatment consists of a cromolyn sodium metered-dose-inhaler(MDI), 2 inhalations TID; a beclomethasone MDI, 2 inhalations TID; and an albuterolMDI, 1 or two inhalations prn for wheezing.

"How are things going in school," you ask.Timmy replies that “school is OK except when I get teased by the bigger kids.”He states that he has many friends outside of school, and he enjoys bicycling, soccer, andbasketball.

Physical examination reveals a well-nourished male who appears small for hischronological age. His height is 132.75cm (52¼ in) and his weight is 30kg (66 lb.) (seeGrowth chart). His sexual maturity rating for pubertal development is Tanner I. Hearingand vision screens are normal. The remainder of his exam is unremarkable.

Timmy’s father wants to know if growth hormone therapy would help his son to be taller.“We have some close friends whose son was short. He got hormone shots and he’sgrown about 6 inches in the last year. Wouldn’t that stuff help Timmy, too? You know,doctor, Timmy's a good hoops player, but unless he grows a lot more he’ll never get toplay on the varsity squad.”

Timmy and the “Big Kids”

Part II

At your visit, you obtain family history, additional measurements, and a hand and wristx-ray for bone age.

Timmy’s father is 174 centimeters (68 ½ in), and his mother is 161.3 centimeters (63 ½in). Timmy’s father remembers still changing clothes sizes late in high school, and hismother had menarche at age 15 years.

On physical examination, Timmy appears to have normal body proportions, but to besure you measure his arm span from middle fingertip to middle fingertip and his lowersegment from top of his pubic symphysis to the floor. His arm span is 133.3 centimeters(52 ½ in) and this should be approximately equal to his height if he has normalproportions. His lower segment is 67 centimeters (26 ? in) which you subtract from hisheight to calculate a ratio of upper to lower segment (.99).

His bone age is read as 9 years.

Timmy and the “Big Kids”

Epilogue

Timmy’s x-ray for bone age allows you to predict his final height of 168 to 170centimeters (66 to 67 in). Based on your findings and recommendations, Timmy does notreceive any medical treatment for his growth. At age 14 years, he has testicularenlargement. At age 14 ½ years, he has developed pubic hair. At age 15 years, hisgrowth rate accelerates and continues to increase at age 16 years.

He also sees the school psychologist weekly to work on family conflicts and self-esteem.At age 16 ½ years, he is reasonably comfortable with his stature, has good peerrelationships, and is on the soccer team.

97

Timmy and the “Big Kids”Handout #1: Timmy’s Growth Chart

Timmy and the "Big Kids"Handout #2a: Bayer & Bayley Growth Curves of Height

Timmy and the "Big Kids"Handout #2b: Bayer & Bayley Growth Curve of Weight

Timmy and the "Big Kids" Handout #3: Upper:lower Segment Ratios

Timmy and the "Big Kids"Handout #4: 9 Year Old Hand and Wrist Radiograph for Bone Age

Timmy and the “Big Kids”

Bibliography:

Growth rates and monitoring growth1. Monitoring and Assessment of Growth, The Primary Care Perspective [slide series], Genentech, Inc.2. Greulich WW and Pyle S. Radiographic Atlas of Skeletal Development of the Hand and Wrist.

Stanford, CA: Stanford University Press; 1959.3. Rosenfield RG. Skeletal Maturation (Bone Age). In Sperling MA, editor. Pediatric Endocrinology.

Philadelphia: W.B. Saunders Co; 1996. p.120-121.

Short stature4. Cowell CT. Short Stature. In Brook CGD, editor. Clinical Paediatric Endocrinology. Oxford:

Blackwell Science LTD; 1995. p. 136-172.5. Linder B, Cassoria F. Short stature, etiology, diagnosis, and treatment. Journal of the American

Medical Association 1988;260:3171-3175.6. Mahoney CP. Evaluating the child with short stature. Pediatric Clinics of North America

1987;34:825-849.7. Shulman DI, Bercu BB. Growth hormone therapy: An update. Contemporary Pediatrics 1998;

15:95-110.

Inhaled steroids and growth8. Crowley S, Hindmarsh PC, Matthews DR, Brook CGD. Growth and the growth hormone axis in

prepubertal children with asthma. Journal of Pediatrics 1995;126:297-303.9. Doull IJM, Freezer NJ, Holgate ST. Growth of prepubertal children with mild asthma treated with

inhaled beclomethasone dipropionate. American Journal of Respiratory Critical Care and Medicine1995;151:1715-1719.

Use of growth hormone in non-growth hormone deficient short children10. Lawson Wilkins Pediatric Endocrine Society. Guidelines for the Use of Growth Hormone in Children.

1995.11. Loche S, Cambiaso P, Setzu S, Carta D, Marini R, Borrelli P, Cappa M. Final height after growth

hormone therapy in non-growth-hormone deficient children with short stature. Journal of Pediatrics1994;125:196-200.

12. Moore WV, Moore KC, Gifford R, Hollowell JG, Donaldson DL. Long-term treatment of childrenwith short stature and normal growth hormone secretion. Journal of Pediatrics 1992;120:702-708.

Suggested Readings: Amer K and Brill M. (Illustrations by L. Amer). Short Mort and the Big Bully. Bethesda, MD:Association for the Care of Children’s Health; 1996. This is a story about an 11 year old boy who isshort. It is a wonderful resource to recommend to young patients and includes material on how toconstructively deal with teasing, and how to build one’s self-confidence. The reading level isapproximately 5th grade. Copies may be obtained by calling 301-654-6549.

Mahoney CP. Evaluating the child with short stature. Pediatric Clinics of North America 1987;34:825-849. A timeless review article which describes normal growth patterns, the evaluation of shortstature, and diseases causing short stature.

Shulman DI, Bercu BB. Growth hormone therapy: An update. Contemporary Pediatrics 1998;15:95-110. This article discusses when treatment with recombinant growth hormone is appropriate.

Educational Resources on the World Wide WebThe National Center for Health Statisticshttp://www.cdc.gov/nchs/ (Home page); http://www.cdc.gov/growthcharts/ (Growth charts)