of growth and puberty - Archives of Disease in Childhoodadc.bmj.com/content/archdischild/63/9/1104.full.pdf · Archives of Disease in Childhood, 1988, 63, 1104-1110 Personal practice

Archives of Disease in Childhood, 1988, 63, 1104-1110

Personal practice

Management of constitutional delay of growthand pubertyR STANHOPE AND M A PREECE

Department of Growth and Development, Institute of Child Health, London

Constitutional delay of growth and puberty (CDGP)is not a disease but a common condition in whichpuberty and its associated growth spurt occur at anage which is near the extreme of the normal range.Growth at puberty is intimately related to the stageof pubertal development and this is why, quiteappropriately, both growth and puberty are implicitin the name, although it could be argued that theyoccur in an incorrect order. It is an importantcondition to recognise as many such children onlyneed reassurance although some will require, if onlyfor psychological reasons, therapeutic interventionto improve their short term growth. There is muchinformation available about the anthropometricprogress of children with constitutional delay ofgrowth and puberty and we have attempted tocorrelate this with our more recent understanding ofpossible options for the manipulation of the endocri-nology of puberty.

Definition

Constitutional delay of growth and puberty isdefined by Prader as: 'constitutional delay of growthoccurring in otherwise healthy adolescents withstature reduced for chronological age but generallyappropriate for bone age and stage of pubertaldevelopment, both of which are usually delayed'.1As growth potential is related to the degree of

epiphyseal maturation, it is this delay in bone agewhich permits a final stature within the normalrange. It is the 'tempo' of growth (and puberty)which is significantly delayed.2 In this article, weshall use the terms 'constitutional delay' and 'growthdelay' as synonymous with CDGP as they are almostcertainly manifestations of the same condition,although presenting at different ages (see below).CDGP is more common in boys than girls and tendsto have a familial pattern. The anthropometric, aswell as the psychological, sequelae of delayed

puberty are more dramatic in boys on whom weshall concentrate most of our discussion.

Endocrinology of puberty

The initial endocrine event of puberty is highamplitude pulsatile gonadotrophin secretion fromthe pituitary gland in response to pulsatile gonado-trophin releasing hormone (GnRH) secretion fromthe hypothalamus.3 These events occur predomi-nantly at night, as does growth hormone secretion.It is interesting that the secretion of these hormonesis intimately related to the night during pubertyand that this relationship continues throughoutreproductive function; the onset of the luteinisinghormone surge in women, which is an essentialprerequisite to ovulation, occurs in the early hoursof the morning. The diurnal secretion of thesehormones during early puberty has important im-plications for their therapeutic administration4; oes-trogen in girls should be administered in themorning, oral testosterone in boys as well as growthhormone in both sexes are usually given during theevening.There is a sex difference in the pituitary response

to GnRH which may explain the characteristicdifferences between the timing of the onset ofpuberty in girls and boys; girls more readily releasegonadotrophins to a given GnRH stimulus.5 Thismay explain why the onset of puberty is earlier ingirls than boys, why central precocious puberty ismore common in girls, and why constitutional delayof growth and puberty is more common in boys.Although both sex steroids and growth hormone

are required for the growth spurt of puberty, thepattern of secretion of sex steroids alone does notexplain the growth acceleration of puberty. In girls,oestrogen secretion is at its peak just beforemenarche, when the growth spurt is waning. Inboys, sex steroid secretion increases progressively

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Management of constitutional delay of growth and puberty 1105

throughout puberty and yet initially growth deceler-ates and the onset of the growth spurt occursrelatively late between genitalia stage 3 and 4. Bothsex steroids and growth hormone are synergisticduring the growth spurt and it has been appreciatedfor many years that boys with delayed pubertybefore the onset of the growth spurt, as well as girlsin late prepuberty, have physiological growth hor-mone insufficiency,6 which can be reversed byexogenous administration ('priming') with sexsteroids.7 We have recently appreciated, however,that growth hormone pulse amplitude and not sexsteroid secretion correlates with changes in growthvelocity during puberty in both girls and boys.8Short term use of sex steroid 'priming' in boys inearly. puberty temporarily increases growth hor-mone secretion, and the administration of sexsteroids for greater than three months induces asustained increase in both growth hormone secre-tion and growth that continues after the cessation oftreatment. This is the principle for short coursetreatment with anabolic and sex steroids for boys inearly puberty with CDGP.Data from postmortem examination,9 pelvic

ultrasound,'( and hormone profiles5 have suggestedthat the endocrine events which we associate withpuberty probably have their origin very much earlierin childhood. Gonadotrophin secretion progres-sively increases throughout childhood and whensufficient sex steroids are secreted to induce secon-dary sexual characteristics, then phenotypic pubertybegins. These low concentrations of sex steroidssecreted during early childhood, however, may havegreat significance for the physiology of growthdelay. After the second year of life, when growthhas become dependent on growth hormone ,6 lowconcentrations of sex steroids may result insecondary growth hormone insufficiency and lowgrowth velocity but with contemporaneous retarda-tion of epiphyseal maturation; this is the exactscenario observed in growth delay.

Pubertal developmentIt is important to distinguish puberty that is normal,except that the onset is delayed, from absentpubertal development or arrested puberty (no pro-gress for 18 months or more). In contrast to CDGP,hypogonadotrophic hypogonadism is a spectrumwhich may present clinically as absent puberty,arrested puberty, or failure to attain reproductivefunction depending on the degree of GnRH insuffi-ciency. Thus children who have no signs of pubertyat 2-5 SD or greater from the mean (14.0 years in agirl and 14-5 years in a boy) require appropriateendocrine and radiological investigation of thehypothalamo-pituitary axis.

Progress through puberty can take a considerablelength of time; 3% of normal girls and boys takelonger than five years to progress from genitalia/breast stage 2 to 5.11 12 For example, a boy whoenters puberty at 14 years may not complete hispuberty (and therefore his growth) until 19 yearsand perhaps considerably later as children who enterpuberty later tend to progress through puberty moreslowly. I

Pattern of growth

CDGP is more common in boys than girls forreasons we have discussed. Even when this becomesa clinical problem in a girl, it is self limiting becauseas soon as the onset of puberty occurs (breastdevelopment) and they commence their growthspurt, girls will attain peak height velocity betweenbreast stage 2 and 3. By contrast, the problem isexaggerated in boys because their growth spurt onlyoccurs towards the end of puberty. The growth spurtcommences at 10 ml testicular volume (genitaliastage 3 to 4) and attains a peak velocity at 12 ml(genitalia stage 4 to 5). Thus the growth of a boywho enters puberty at 14 will continue to deceleratefor many years, until the growth spurt starts atperhaps 17 or 18 years of age, by which time he isconsiderably shorter than his peers. The later thegrowth spurt occurs, the lower the peak heightvelocity that is attained, as final height attainment isnot dependent on the timing of the onset of puberty(except in precocious sexual development). 1 14 Thisdictum has recently been affirmed as the use of aGnRH analogue to delay the puberty of shortnormal children does not improve final heightprognosis.An example of a boy with CDGP is shown in fig 1.

Although he entered puberty at 14 years, his growthcontinued to decelerate at an extended 50th centilevelocity. This may imply a growth velocity of onlyabout 2-4 cm/year by the age of 16 years, andalthough this may induce considerable concern in hismedical attendants it is important to appreciate thatthis is normal for chronological age and stage ofpuberty. By the age of 16 years, at the commence-ment of the growth spurt, his height was 15 cmbelow the 3rd centile on the 'distance' chart.

Diagnosis of constitutional delay of growth andpuberty

The characteristic feature of normal puberty is thatthere is a relationship between the pattern ofacquisition of the various stages of sexual matura-tion and the growth spurt. Loss of this normal har-mony of growth and puberty points to an



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*97 The distinction between CDGP and partial hypo-................... gonadotrophic hypogonadism can be difficult as

both show the normal consonance of growth and,.',, -. development. In order to distinguish between these

,. t wo' two conditions puberty may have to be induced (see.............. .3 below) for a period of two to three years and then

/ ,. ......j:;~progress observed after the cessation of treatment...' o'......./Congenital growth hormone insufficiency is not

,' , ,/-. usually confused with CDGP because by this agechildren with the former are very much shorter thanthe latter. Acquired growth hormone insufficiency

/ ' secondary to an intracranial tumour, however, mustalways be considered. In girls, Turner's syndromeand its variants should be excluded by a karyotype.Children with primary hypothyroidism usually havea growth rate that is inappropriately low for their

* ', age and stage of puberty, and moreover may haveinappropriate sexual maturation.'6 Children withmild skeletal dysplasias, such as spondyloepiphysealdysplasia seldom have a delayed bone age and

50 """"''''"" /'' '' \\'' usually exhibit limb-trunk disproportion. TheI,-___''' % \diagnosis is confirmed by skeletal survey.

3 - If pharmacological tests of the hypothalamo--- ~ : \pituitary axis are carried out these usually require

sex steroid 'priming' (see above) and, in the clinicalsituation of delayed puberty, are difficult to inter-pret. In our experience the anthropometric data aremore reliable. If sex steroid 'priming' is required,

8 10 12 14 16 18 20 2 however, then it is appropriate to use stilboestrol (1mg twice a day for three days), which can be used in

Age (years) either sex and does not interfere with the anthro-istance (above) and velocity (below) charts from a pometric data.

boy with constitutionally delayed puberty. The onset ofpuberty was at 14 years and he continued to grow at anextended 50th centile velocity until the onset ofthe growthspurt at 16 years. The typical pattern ofgrowth is shown onthe 'distance' chart.

endocrinopathy.'6 The absence of a growth spurtassociated with the acquisition of a 10 ml testicularvolume; a growth velocity of 2 cm/year in a boy inearly puberty that is appropriate at 17 years but notat 13 years; and a large testicular volume in relationto inadequate virilisation are all examples of loss ofthe normal harmony of growth and puberty andnecessitate investigation. In contrast, the normalconsonance of growth and puberty is usual inchildren with CDGP and this mitigates againstspecial investigations.Growth delay often occurs in children with severe

systemic disease such as asthma, renal disease,coeliac disease, inflammatory bowel disease, orafter the chronic use of corticosteroids. It is impor-tant not to overlook these possibilities as they canmimic some of the features of CDGP.'7

Psychological sequelae

The delay of both growth and puberty can haveconsiderable psychological sequelae, especially be-cause this is such a critical time for social, emo-tional, and educational development and, im-portantly, the onset of relationships with the oppo-site sex. At no other time during life is peer grouppressure so important and influential than at ado-lescence. In an analogous way to facial acne, there islittle consolation in the advice that all will be well ifthe boy waits long enough and that growth will becomplete in his early 20s. This is highlighted by thefollowing extracts from a letter written by an intelli-gent 17 year old boy with delayed puberty.

'... I often get very upset, but I find it verydifficult to release my tension. When I do, thisresults in huge arguments, often over pettyinconsequential things. I do not wish to be toldto leave pubs, and 'X' certificate films when Iam 18. I lose a great deal of my confidence withgirls-I feel fine talking to them normally, butasking to go out with someone is something I

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wouldn't consider, as I can't understand many17 year olds wishing to go out with someonewho looks like a 14 year old. It is certainlydifficult for me to convey how I feel, but all Ican say is that I feel utterly powerless, and Ioften feel quite depressed over this matter.This, I fear, will begin to affect my work whichis very important as I am approaching my 'A'Level examinations'.

This summarises many of the difficulties that suchboys commonly experience, although it is unusual tohave such depth of insight. Many boys with CDGPare subject to bullying and some develop antisocialbehaviour such as shoplifting or vandalism, whichmay bring them into conflict with the authorities.They require therapeutic help and not unnecessaryinvestigation. It is surprising that when boys withCDGP are asked whether growth or puberty is theirprimary concern, most indicate the former and it isto this aspect that the therapeutic approach shouldbe aimed.

Treatment of constitutional delay of growth andpuberty

The most important decision is whether, rather thanhow, to treat a boy with CDGP. This is onlyindicated when such a boy is experiencing psycholo-gical distress. It is important to have the parentspresent at the initial interview as events such asbullying are more likely to be alluded to by theparents because the admission of this by an adoles-cent boy may be considered as a sign of weakness.Often the attendance of the adolescent and thediscussion about such delicate problems, as per-ceived by the adolescent, at a clinic appointment is asignificant sign in itself.

It is important to emphasise that this condition isjust a variation of the normal timing of puberty, andis not an illness. This also indicates the necessity foran effective but safe treatment. Misconceptionsabout future fertility and manhood may requirereassurance. It is unlikely that treatment willimprove final height, although this is theoreticallypossible using growth hormone treatment, but it willallow the boy to achieve final height at an earlierage.Two therapeutic approaches in the treatment of

CDGP are possible. Either the growth spurt can beinduced using a low dose of an anabolic steroid orpossibly growth hormone, with little alteration inthe progress of sexual maturation, or puberty can beinduced along with its associated growth spurt by theadministration of testosterone or human chorionicgonadotrophin.

ANABOLIC STEROIDSThese have been extensively used for the past threedecades in North America but unfortunately theirinitial use was in high dose regimens for long periodswhich resulted in side effects of hepatotoxicity,18suppression of the hypothalamo-pituitary-gonadalaxis,19 20 and inappropriate advance of epiphysealmaturation.18 Sobel noted that virilisation is dosedependent, whereas the growth acceleration wasnot.21 Low doses of anabolic steroid22 23 adminis-tered orally in a daily regimen induce a growth spurtthat is not a placebo effect.24 At the attainment of a4 ml testicular volume this growth acceleration issustained, and therefore only relatively shortcourses are required.22 23 At the cessation of treat-ment this induced growth spurt continues andeventually becomes indistinguishable from the spon-taneous growth spurt of puberty at the attainment ofa 10 ml testicular volume (fig 2). Such low doseregimens do not cause inappropriate advance inepiphyseal maturation and do not alter final heightprognosis.22 23 There is a normal advance in secon-dary sexual characteristics during such short course,low dose regimens of anabolic steroids and testicularvolume is not suppressed. Unfortunately, despitethe usefulness of anabolic steroids in the treatmentof constitutional delay and other growth disorders,fluoxymesterone is now unavailable and oxandro-lone can only be prescribed on a 'named patientbasis' as it has no product licence in the UnitedKingdom.

TESTOSTERONE AND HUMAN CHORIONICGONADOTROPHINAn alternative approach is to induce secondarysexual characteristics and thereby their associatedgrowth acceleration by using either testosterone orhuman chorionic gonadotrophin. Testosterone isusually administered by deep intramuscular injec-tion of a depot preparation at monthly intervals ororally, as testosterone undecanoate, during theevening. Unfortunately such oral preparations havevariable absorption from the gastrointestinal tractthat limit their usefulness. Depot testosterone estersare certainly effective,25 although unfortunatelythey are often used in excessive doses, but the2yprobably do not reduce final height attainment.Although testosterone administration suppressesthe hypothalamo-pituitary-gonadal axis, withreduction in testicular volume, this is only tem-porary. Testosterone treatment often produces arapid rise in serum testosterone concentrations andalso wide fluctuations in concentrations betweeninjections which can, in themself, produce emo-tional lability and may become counterproductive tothe indications for treatment. An alternative and



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Age (years)

Fig 2 Growth data from a boy with constitutional delay ofgrowth and puberty. Bone age is shown by the solid squares.Parental centiles are indicated on the right hand border. His expected pattern ofgrowth is indicated by the dotted line. At theage of14 years, he was treated with a three month course ofoxandrolone (1 -25 mg daily), and the induced, sustained growthacceleration became indistinguishablefrom the growth spurt ofpuberty at the attainment ofa 10 ml testicular volume.

more physiological treatment is human chorionicgonadotrophin, but this has to be administered intwo to three injections a week, which limits its use.Both testosterone and human chorionic gona-dotrophin need to be given for a minimum of threemonths in order to attain a sustained growth spurt.Of course, unlike anabolic steroids, both test-osterone esters and human chorionic gonadotrophinhave to be given by injection.For girls who require treatment low dose oestro-

gen, such as ethinyl oestradiol 2 [ig daily, can beadministered as this induces a growth acceleration.When an advance in puberty has occurred which isinappropriate for the dose of exogenous oestrogen,then the medication can be withdrawn with theprobability that spontaneous puberty has started.Human chorionic gonadotrophin cannot be adminis-

tered in girls because of the likelihood of ovarianhyperstimulation syndrome.

GROWTH HORMONEFrom the discussion about the mechanism of thegrowth spurt of puberty, it is not surprising that theadministration of growth hormone can improveshort term growth in boys with CDGP27 and thiscould theoretically improve their final height prog-nosis. Because of the increase in growth hormonesecretion which occurs during puberty, however,larger doses may have to be used than are adminis-tered in the treatment of growth hormone deficiencyin prepubertal children.28 From experience of themanagement of children with hypopituitarism,growth hormone treatment has little effect duringlate prepuberty. Treatment is expensive and may


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have to be continued for a long period of timebecause of the possibility of 'catchdown' growth.29Growth hormone is certainly not the primary choiceof treatment for children with CDGP; as they havephysiological growth hormone insufficiency it seemsmore appropriate to use an androgen in boys or anoestrogen in girls to induce increased endogenousgrowth hormone secretion.

A practical regimen

The normal harmony of puberty is the characteristicof CDGP. Indeed, endocrine investigations indelayed puberty are notoriously difficult to interpretand are more often misleading than they are helpful.Most -patients with psychological distress due toCDGP require an effective safe treatment, ratherthan investigations. If puberty is disordered or ifthere is an inappropriate anthropometric responseto treatment,3' however, then the patient shouldhave neuroradiological and endocrine assessment ofthe hypothalamo-pituitary axis.Once the diagnosis has been made then

reassurance should be given and treatment onlyoffered if there is inappropriate psychological dis-tress. For boys with CDGP for whom short stature isthe predominant symptom, then treatment shouldbe given with an anabolic steroid such as oxandro-lone 1.25-2.5 mg daily for three to four months.This will induce a growth spurt which, after theattainment of a 4 ml testicular volume, will be sus-tained. If growth deceleration does occur on cessa-tion of anabolic steroid treatment, then a furtherthree to four month course can be administered.Once a sustained growth spurt is achieved thengrowth and development should continue withoutrequiring any further treatment. It is important toexplain that this treatment is only advancing thetiming of the growth spurt without altering finalheight attainment. In the more unusual case whereinadequate sexual development is the predominantsymptom then treatment with testosterone esters(such as Sustanon 50) should be administered atmonthly intervals for three to four months. Usually,this is sufficient to induce an advance in pubertalmaturation with concomitant growth acceleration.Growth delay can often be recognised many years

before puberty and the growth pattern ofCDGP canbe anticipated and effectively prevented. In the pre-pubertal years and before the attainment of a 4 mltesticular volume, low dose anabolic steroids willinduce a growth spurt but this will not be sustained.A course of anabolic steroids, such as oxandrolone1-25 mg daily, can be administered for a period ofabout a year without inducing sexual developmentor inappropriate epiphyseal maturation. This

regimen will improve short term growth, allowingthe boy to attain a higher centile on a 'distance'chart.Growth hormone and human chorionic gona-

dotrophin have little place in the management ofCDGP, particularly as both have to be administeredby frequent injection and the former is very expen-sive.

Conclusion

Constitutional delay of growth and puberty shouldbe recognised clinically and not require endocrineinvestigation. Treatment by either anabolic steroidsor testosterone should only be given when psycho-logical distress is encountered, but the treatment canbe administered by either a paediatrician or com-munity paediatrician without the necessity for refer-ral to a specialised growth centre. However, assess-ment of epiphyseal maturation is essential in themanagement of children with delayed puberty.Rarely, when inadequate growth acceleration withtreatment is observed, referral to a specialist centreis indicated.

We are grateful to Professor HS Jacobs, Middlesex Hospital,London, for allowing us to use clinical data from one of hispatients.

References

Prader A. Delayed adolescence. Clin Ettdocrinol Metab1975;4:143-55.

2 Tanner JM. Developmental age, and the problems of early andlate maturers. Foetus inito man. London: Open Books, 1978:78-86.

3 Boyar RM, Finkelstein R. Roffwarg H, Kapen S, Weitzman E,Hellman L. Synchronisation of augmented luteinizing hormonesecretion with sleep during puberty. N Engl J Med1972;287:582-6.

4 Stanhope R, Brook CGD. An evaluation of hormonal changesat puberty in man. J Endocrinol 1988;116:301-5.Stanhope R, Brook CGD, Pringle PJ, Adams J, Jacobs HS.Induction of puberty by pulsatile gonadotrophin-releasing hor-mone (GnRH). Lancet 1987;ii:552-5.

6 Brook CGD, Hindmarsh PC, Stanhope R. Growth and growthhormone secretion. J Endocritiol 1988 (in press).Eastman CJ, Lazarus L, Stuart MC, Casey JH. The effect ofpuberty and growth hormone secretion in boys with shortstature and delayed adolescence. Aust NZ J Med 1971;1:154-9.

x Stanhope R, Pringle PJ, Brook CGD. The mechanism of theadolescent growth spurt induced by low-dose GnRH treatment.Clin Endocrinol 1988;28:83-91.

9 Peters H, Byskov AG, Grinster J. The development of theovary in childhood in health and disease. Coutts JRT, ed. Funic-tional morphology of the humnan ovary. Lancaster: MTP Press,1981:26-34.Stanhope R, Adams J, Jacobs HS, Brook CGD. Ovarian ultra-sound assessment in normal children, idiopathic precociouspuberty and during low-dose GnRH therapy of hypo-gonadotrophic hypogonadism. Arch Dis Child 1985;60:116-9.



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Marshall WA, Tanner JM. Variation in the pattern of pubertalchanges in girls. Arch Dis Child 1969;44:291-303.

12 Marshall WA, Tanner JM. Variation in the pattern of pubertalchanges in boys. Arch Dis Child 1970;45:13-23.

3 Tanner JM. Growth at adolescence. 2nd ed. Oxford: Black-well, 1962.

14 Prader A. Paediatric endocrinology, past and future. In: RankeMB, Bierich JR, eds. Paediatric endocrinology past and future.Munich: MD Verlag, 1986:13-21.

'5 Stanhope R, Brook CGD. The effect of gonadtrophin releasinghormone (GnRH) analogue on height prognosis in growthhormone deficiency and normal puberty. Eur J Pediatr 1988 (inpress).

6 Stanhope R, Brook CGD. The clinical diagnosis of disorders ofpuberty: the loss of consonance. Br J Hosp Med 1986;35:57-8.

7 Preece MA, Law CM, Davies PSW. The growth of children withchronic paediatric disease. Clin Entdocritiol Metab 1985:15:453-77.

lx Geller J. Oxandrolone effect on growth and bone-age inidiopathic growth failure. Acta Endocrinol (Copenih)1968;59:307-16.

9 Hopwood NJ, Kelch RP, Zipf WB, Hernandez RJ. The effect ofsynthetic androgens on the hypothalamo-pituitary-gonadal axisin boys with constitutional delayed growth. J Pediatr1979;94:657-62.

211 Marti-Henneberg C, Niirianen AK, Rappaport R. Oxandrolonetreatment of constitutional short stature in boys during adole-scence. Effect on linear growth, bone-age, pubic hair and testi-cular development. J Pediatr 1975;86:783-8.

2' Sobel EH. Anabolic steroids. In: Astwood EB, Cassidy CE,eds. Clinical endocrinology 11. New York: Grune and Stratton,1968:789-97.

22 Stanhope R, Bommen M, Brook CGD. Constitutional delay ofgrowth and puberty in boys. The effect of a short course of treat-

ment with fluoxymesterone. Acta Paediatr Scand 1985;74:390-3.

23 Stanhope R, Brook CGD. Oxandrolone in low dose for con-stitutional delay of growth and puberty in boys. Arch Dis Child1985;60:379-81.

24 Stanhope R, Buchanan CR, Fenn GC, Preece MA. Doubleblind placebo controlled trial of oxandrolone in the treatment ofboys with constitutional delay low dose of growth and puberty.Arch Dis Child 1988;63:501-5.

25 Wilson DM, Kei J, Hintz RL, Rosenfeld RG. Effects of testo-sterone therapy for pubertal delay. Am J Dis Child 1988;142:96-9.

26 Zachmann M, Studer S, Prader A. Short-term testosteronetreatment at bone-age of 12-13 years does not reduce adultheight in boys with constitutional delay of growth and adole-scence. Helv Paediatr Acta 1987;42:21-8.

27 Bierich JR. Treatment by hGH of constitutional delay of growthand adolescence. Acta Paediatr Scand [Suppli 1986;325:71-5.

2' Vanderschueren-Lodeweyckx M, Van Den Broeck J, Volter R,Malvaux P. Early initiation of growth hormone treatment: influ-ence on final height. Acta Paediatr Scand [Suppli 1987;337:4-11.

29 Preecc MA, Tanner JM. Results of intermittent treatment ofgrowth hormone deficiency with human growth hormone. J ClinEndocrinol Metab 1977;45:169-70.

3 Stanhope R, Hindmarsh P, Pringle PJ, Holownia P, Honour J,Brook CGD. Oxandrolone induces a sustained rise in GH secre-tion in boys with constitutional delay of growth and puberty.Pediatrician 1988 (in press).

Correspondence to Dr R Stanhope, Department of Growth andDevelopment, Institute of Child Health, 30 Guilforl Street,London WC1N 1EH.



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of growth and puberty - Archives of Disease in Childhoodadc.bmj.com/content/archdischild/63/9/1104.full.pdf · Archives of Disease in Childhood, 1988, 63, 1104-1110 Personal practice