A longitudinal analysis of the growth of limb segments in adolescence.

The growth of upper and lower-limb segments of 96 adolescent boys and girls from the Royal Hospital School Longitudinal Study was analysed. Preece-Baines Model 1 curves were fitted to the longitudinal data to obtain, for each measurement, age at peak velocity and the magnitude of this velocity. Mean-constant peak velocities were between 1-0 and 2-5 cm/yr in all segments. They were in all cases greater than the values obtained from fitting the P-B curve to the cross-sectional means at successive ages. Boys had greater peak velocities than girls in all measurements (sex ratio 1-1 to 1-4). On average distal segments preceded more proximal segments in the ages at which peak velocity occurred. Considerable individual differences, however, occurred in the order for the upper limb segments. These differences seemed to be related to the individual's tempo of growth; late developers had a significantly different order to early developers.

Radiographically determined widths of bone muscle and fat in the upper arm and calf from age 3-18 years.

In the Harpenden Growth Study arm and calf radiographs were taken on 280 boys and 225 girls twice a year over varying periods. Widths of bone, muscle and fat halfway down the arm and at maximum calf diameter were measured, with widths of bone cortex and medulla where possible. Mean distance and velocity curves are given for chronological age 3-18 years together with curves based on time from peak-height velocity (PHV) and time from peak muscle velocity over the pubertal period. Muscle widths have their peak velocity more nearly coincident with the sitting height peak than with PHV; in the average child the whole muscle spurt lasts two years from start to finish. Calf muscle is much more pronounced in girls in comparison with boys than is arm muscle; this is true at all ages, with sex differences at maturity amounting to 10% for calf and 20% for arm. Humerus cortex has a marked spurt in both sexes, with the peak contemporaneous with the muscle peak. Both humerus and tibia medulla widths have a spurt in boys, but none in girls, where the means do not change from age 11 onwards. The average girl actually loses fat in the arm for a year at puberty, a result which contrasts with the velocity curve derived from mass cross-sectional data. Correlations between widths of bone in arm and calf average 0.5 during the pre-adolescent years and 0.4 at maturity; those between muscle widths in arm and calf 0.4 in pre-adolescence and 0.4 again at maturity. Between-tissue correlations are very low at all ages.

Comparative rapidity of response of height, limb muscle and limb fat to treatment with human growth hormone in patients with and without growth hormone deficiency.

The widths of muscle and fat in the upper arm and calf have been measured radiologically before treatment and at intervals of 1, 3. 6 and 12 months during administration of human growth hormone in 41 pre-pubertal patients with "isolated" growth hormone deficiency and in 22 patients with multiple deficiencies following gross CNS lesions. Height was also measured. The curves of response of muscle and fat on the one hand and height on the other were strikingly dissimilar. A very rapid increase of muscle took place in the first month; but after 6 months the increments had fallen to normal values for size and bone age. Decrements in fat followed the same pattern. Height, however, showed a smaller increment in the first month than in the period 1 to 3 months in the "isolated" deficiency cases, and much slower fall back towards normal. The first-year height increment was not at all correlated with the first-month height increment in the "isolated" deficiency cases, though it had a correlation coefficient of 0.46 with the first-month muscle increment. Nine cases of short stature not due to GH deficiency were similarly studied. There was considerable overlap between deficient and non-deficient in all responses in the first 3 months, though children in the top half of the responder's distribution could be distinguished. A 1-month radiological test of responses to hGH in doubtful cases is proposed, using in all only 40 IU of hormone. It is emphasised that a small response of muscle and fat may occur in cases who do nevertheless respond in height to hGH administration; a large response in muscle and fat, however, is indivative that treatment will be effective, though it does not well predict the precise amount of height that may be gained.

Relative importance of growth hormone and sex steroids for the growth at puberty of trunk length, limb length, and muscle width in growth hormone-deficient children.

We have followed the growth of stature, sitting height, skinfolds, muscle widths measured radiologically, and skeletal maturity in growth hormone-deficient patients in whom hGH was given and withheld in alternating three-month periods throughout puberty (referred to as "off-hGH" and "on-hGH" periods). Six boys and four girls had true isolated GH deficiency and developed puberty spontaneously. Two boys had gonadotrophin deficiency plus GH deficiency, and five boys had multiple deficiencies; in these boys the signs of puberty were induced by hormone treatment. Boys with true isolated deficiency grew about two-thirds as much in height in the off-hGH periods as in the on-hGH periods; their total gain in height during the adolescent spurt would have been about 20 cm, instead of 30 cm, if hGH had been discontinued at the beginning of puberty. The effect of hGH was entirely on growth in leg-length, however, which virtually ceased during the off-hGH periods. Growth in sitting height altered little when hGH was withdrawn. Growth in limb muscles, however, was GH dependent throughout puberty; during the majority of periods when hGH was withheld, muscle was actually lost; this occurred in the boys who were receiving large doses of testosterone as well as in those producing their own normal amounts. Subcutaneous fat diminished when hGH was given and increased when it was withdrawn; this occurred independently of administration of testosterone. There was little evidence that growth of pubic and axillary hair progressed faster during on-hGH periods, except perhaps in patients with multiple deficiencies. There was some evidence, however, that bone age progressed less rapidly during on-hGH periods than during off-hGH periods in the patients with isolated deficiency. The results in the girls agreed with those in boys so far as stature was concerned, but the relationship with sitting height and leg length appeared to be different; the reasons for this are discussed. We conclude that all children with GH deficiency should continue on treatment with hGH throughout puberty, ideally until growth ceases.

The adolescent growth spurt of boys and girls of the Harpenden growth study.

Logistic curves have been fitted to the growth during puberty of the 55 boys and 35 girls of the Harpenden Growth Study who were measured every three months during puberty and thereafter until growth ceased. Very good fits were obtained for stature, sitting height, subischial leg length, biacromial and bi-iliac diameters from approximately six months after the beginning of the adolescent spurt. This beginning, called "take-off", was determined graphically as the point of minimum velocity. The total height gained from take-off point to cessation of growth averaged 28 cm in boys and 25 cm in girls with standard deviations of about 4 cm. The adult sex difference in height was due much more to the later take-off in boys than to a greater male adolescent spurt. A sex difference in the spurt occurred in sitting height but not in leg length. Mean-constant curves for the four measurements are presented. In each measurement size at take-off and total adolescent gain were nearly independent, the average correlation coefficient being --0-2. The correlations between adolescent gains in different measurements averaged only 0-47, and between peak velocities of different measurements only 0-27. This implies considerable shape change at adolescence. In contrast the average correlation between ages at which the peak velocities were reached was 0-87. Ages at take-off, at peak velocity, and at menarche were independent of mature size, though correlated with percentage of adult size reached at the ages in question, a measure of somatic maturity. Relationships with the development of breasts, pubic hair and genitalia were examined; ages at take-off and at peak velocity correlated to the extent of 0-6 to 0-8 with ages of B2 and PH2 but both these parameters and also peak velocities were uncorrelated with the rapidity with which sex characters developed.

Dose dependence of growth response to human growth hormone in growth hormone deficiency.

A trial of the relative effect on growth of 20 IU/week and 10 IU/week of human growth hormone has been made in 38 patients with "isolated" growth hormone deficiency over 1 year of treatment, 18 patients over 2 years and 10 over 3 years, and in 17 patients with surgically treated craniopharyngiomata over 1 year. The velocity of height growth in the first year of treatment, compared with a full year of pre-treatment control, was 1.3 times as great in both groups of patients on the larger dose as it was in those on the smaller one. Second-degree equations fitted to the treatment catch-up curve gave estimates of 1.7 cm more height gained on the larger dose by the end of the first year, 2.7 cm by the end of the second, and 3.4 cm by the end of the third. Adjusting treatment increment by covariance for bone age at the beginning of treatment, pre-treatment velocity, and body surface area did not alter these mean differences. Bone age velocity during treatment was the same in both treatment groups (mean 1.09 "years"/year in the first year); thus we anticipate a gain in final adult height of the order of 10 cm from employing the larger dose. The decrease in skin folds occurring on treatment, however, was no different with the larger than with the smaller dose. This reinforces previous observations that the short-term metabolic and longer-term auxologic effects of hGH are not necessarily related.

Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty.

New charts for height, weight, height velocity, and weight velocity are presented for clinical (as opposed to population survey) use. They are based on longitudinal-type growth curves, using the same data as in the British 1965 growth standards. In the velocity standards centiles are given for children who are early- and late-maturing as well as for those who mature at the average age (thus extending the use of the previous charts). Limits of normality for the age of occurrence of the adolescent growth spurt are given and also for the successive stages of penis, testes, and pubic hair development in boys, and for stages of breast and pubic hair development in girls.

Relationship of radial metaphyseal band width to stature velocity.

A relatively radiodense metaphyseal band is present at the distal end of the radius in normally growing children. The width of this band is related to the velocity of stature growth. Though individual growth rates in height cannot be closely predicted from the width of the band in normal children and adolescents, in certain clinical conditions the band width may be a useful guide as to whether or not growth is proceeding normally. Examples are given of the effect of human growth hormone treatment on the band width in a case of isolated growth hormone deficiency and of the effect of thyroid treatment on the band width in a case of hypothyroidism.

A note on the bone age at which patients with true isolated growth hormone deficiency enter puberty.

Nineteen boys with true isolated growth hormone deficiency developed the first stages of puberty at an average bone age of 12.0"years" (Tanner Whitehouse Method 2, RUS score). The average chronological age was 15.0 years. Seven similar girls entered puberty at 10.9"years" in bone age and 13.7 years in chronological age. The means and ranges of bone age at beginning of puberty of these patients are very close to those of normal children.

Revised standards for triceps and subscapular skinfolds in British children.

Revised centile standards are given for triceps and subscapular skinfold measurements in boys and girls aged from one month to 19 years. The school age data are based on London measurements made in 1966, and the infant data on Midland Infant Welfare Clinic figures in 1966-67. All centiles are above those given in the earlier standards published in 1962, and particularly so in infancy. It is emphasized that the standards represent what is, not what ought to be.

Prediction of adult height from height, bone age, and occurrence of menarche, at ages 4 to 16 with allowance for midparent height.

Multiple regression equations for predicting the adult height of boys and girls from height and bone age at ages 4 and upwards are presented. There is a separate equation for each half year of chronological age; and for pre- and postmenarcheal girls at ages 11 to 14. These are based on longitudinal data from 116 boys and 95 girls of the Harpenden Growth Study and the London group of the International Children's Centre longitudinal study. The bone age used is the revised version of the Tanner-Whitehouse standards, omitting the score for carpal bones (RUS age, TW 2 system). Boys aged 4 to 12 are predicted in 95% of instances to within plus or minus 7 cm of true height, and at ages 13 and 14 to within plus or minus 6 cm. Girls ages 4 to 11 are predicted to within plus or minus 6 cm; premenarcheal girls aged 12 and 13 to within plus or minus 5 and plus or minus 4 cm, respectively; and postmenarcheal girls aged 12 and 13 to within plus or minus 4 and plus or minus 3 cm, respectively. Prediction can be somewhat imporved by allowing for midparent height. One-third of the amount that midparent height differs from mean midparent height is added or subtracted. An alternative system of equations which are based on initial classification by bone age rather than chronological age is given. These have about the same accuracy as the equations based on initial classification by chronological age, but allowance for bone age retardation is less. It is not clear which system is preferable. The equations probably apply to girls complaining of tall stature and boys or girls complaining of shortness and needing reassurance as to normality. In clearly pathological children, such as those with endocrinopathies, they do not apply.

Diurnal variation in stature and sitting height in 12-14-year-old boys.

1. Measurements of stature and sitting height were made at 0930 and 1400 h on 19 boys aged 12-14 years with the "stretching upward" technique. 11 different boys were similarly measured at 1000 and 1700 h. 2. The average decrease in stature from 0930 to 1400 h was 2.0 mm and from 1000 to 1700 h was 4.6 mm. The corresponding values for sitting height were 2.0 mm and 2.8 mm. 3. No strong evidence for individual differences in diurnal change was found. 4. The standard error of stature measurement, estimated from duplicate measurements taken five minutes apart by the same observer in the afternoon sessions, was +/- 1.8 mm.