Height Velocity SDS Research Articles

One-year Growth Hormone (GH) Treatment in Children with Non-endocrine Short Stature

The effect of one year of human growth hormone (hGH) treatment on height velocity, height SDS, height velocity SDS and bone age was studied in 71 children with non-endocrine short stature. At the start of hGH treatment, mean chronological age (CA) was 8.75 yr, mean bone age (BA) 6.63, mean height SDS -3.09SD, mean height velocity 4.4 cm/yr, mean height velocity SDS for CA -1.66SD and mean height velocity SDS for BA was -2.19SD. Subjects were divided into four groups: 22 cases with familial short stature (M 14, F 8). 16 cases with SFD short stature (M 11, F 5), 5 cases with both familial and SFD short stature (M 5), and 28 cases with idiopathic short stature (M 20, F 8). There was no significant difference in height SDS, height velocity, mean peak GH and mean sleep GH before treatment among these four groups. The children received rhGH at a dose of 0.5U/kg/week 6-7 times a week subcutaneously.During hGH treatment, 8 cases developed pubertal sign. Since there was no significant difference in the effect hGH treatment between prepubertal group and pubertal group, both group were analyzed together. After one-year hGH treatment, mean height SDS increased significantly to -2.63SD (+0.44SD), mean height velocity to 7M5 cm/yr (+2.63cm/yr), height velocity SDS for CA to+ L62 SD (+3.84SD) and height velocity SDS for BA to +1.63SD (+ 3.845D). There was no significant difference in these values among four groups. During hGH treatment, plasma IGF- I levels increased significantly, but serum osteocalcin levels remained at the same level. Bone age advanced 1.57 years and height age advanced 1.20 years during one-year hGH treatment. The mean ratio of δ bone age/δ height age was 1.34. The effectiveness judged by δheight velocity ≥2cm was 67.6% and that was 62.0% judged by Aheight velocity SDS≥2.5SD. There was no significant difference in these effectiveness among four groups.Short-term hGH treatment was useful in children with non-endocrine short stature. However, long-term effects remained to be clarified.

Growth hormone treatment in children with preterminal chronic renal failure: no adverse effect on glomerular filtration rate.

Impaired growth and stunting remains a major therapeutic problem in children with chronic renal failure (CRF). Recombinant human growth hormone (rhGH) treatment may be beneficial, but concern has been raised about possible side-effects, i.e. deterioration of renal function and glucose intolerance. We have treated 10 prepubertal children with CRF (median age 7.5 [1.7-10.0] years) with 4 IU rhGH/m2 per day s.c. over a period of 1 year. Height velocity increased significantly (P less than 0.03) from basal 4.6 (2.0-14.0) cm/year to 9.7 (6.8-17.6) cm/year. Height velocity SDS for chronological age and for bone age increased in all children from basal median -2.3 to +3.8 (P less than 0.005). Median glomerular filtration rate (GFR) measured by single injection inulin clearance at onset was 18 (11-66) ml/min per 1.73 m2 and did not change significantly during the treatment year. The loss of GFR as estimated by creatinine clearance was similar during the treatment year (median loss 1.3 ml/min per 1.73 m2) compared to the year before treatment (median loss 3.7 ml/min per 1.73 m2). Serum glucose levels during an oral glucose tolerance test did not change, but fasting as well as stimulated insulin levels increased significantly with time during the study period. It is concluded that the rhGH regimen employed was remarkably effective in improving growth velocity in children with CRF without adversely affecting GFR. Glucose homeostasis remained stable, but at the expense of increased serum insulin levels.

Rate of change (modulation) of serum growth hormone concentrations is a more important factor in determining growth rate than duration of exposure.

To determine whether duration of exposure to GH and/or rate of change of serum GH concentration are important factors in determining the growth rate of short children. An analysis of parameters of occupancy percentage and rate of change of serum GH concentration was performed as part of a prospective study investigating the relationship between growth and GH in childhood. Sixty-four short prepubertal children (48 male, 16 female) aged between 4.7 and 11.9 years were studied. Thirty-one children were growing with a height velocity standard deviation score between 0 and -0.8 and were defined as short normal. Thirty-three children were growing with a height velocity standard deviation score less than -0.8 and were defined as short slowly growing. Twenty-four hour serum GH concentration profiles were constructed by withdrawing samples at 20-minute intervals. Analysis of occupancy percentage was performed on each data array by determining cumulative distributions and plotting these as linear probits against log serum GH concentration. Estimates of peak (OC95), intermediate (OC50) and trough (OC5) occupancies were calculated. A first-order derivative of the concentration-time data array was determined for each profile as a measure of rate changes. First-order derivative values were significantly greater in the short normal group than in the short slowly growing children (short normal median 1.41 mU/l/min; short slowly growing median 0.72 mU/l/min; P less than 0.001). OC95 values were significantly higher in the short normal group (median 19.31 mU/l) than the short slowly growing group (median 7.69 mU/l) (P less than 0.001). There was no difference in OC50 values. OC5 values were lower in short normal children (median 0.20 mU/l) than in the short slowly growing children (0.55 mU/l) (P less than 0.003). The most important factor in determining growth rate was the rate of change in serum GH concentration (FOD). Occupancy percentage played no part in the relationship. The regression equation was Height velocity SDS = 1.16 (In FOD) - 1.03; r = 0.75; P less than 0.001 These data suggest that the pattern of presentation of GH in the circulation is an important factor in determining target organ response. Although occupancy percentages at differing serum GH concentrations differ between short slowly growing and short normal children, it is the rate of change of the hormone in the circulation which appears to be the more important 'signal' in terms of modulating growth.

Noonan's Syndrome: Abnormalities of the Growth Hormone/IGF‐I Axis and the Response to Treatment with Human Biosynthetic Growth Hormone

Auxological and endocrine data from 6 children (3 male, 3 female) aged 8.5-12.8 years with Noonan's syndrome and the results of treatment with human biosynthetic growth hormone (hGH) are presented. All the children were short (Ht SDS -3.5 to -2.3) and height velocity SDS ranged between -1.76 and +0.03. The maximum plasma growth hormone (GH) response to standard provocation tests ranged from 17 to 52 mU/l, yet, plasma insulin-like growth factor I (IGF-I) concentrations were low or low normal. Overnight GH secretory profiles were normal in all but 2 children who had disordered pulsatility with high trough concentrations. In 5 children who have completed one year of hGH therapy mean height velocity increased from 4.8 to 7.4 cm/year and the height velocity SDS ranged from +0.2 to +3.75. This improvement was associated with an increase in plasma IGF-I in three subjects. These results suggest that a defect of the GH/IGF-I axis may be present in some children with Noonan's syndrome and hGH therapy may have a role in the management of the short stature in these children.

Recombinant Human Growth Hormone Treatment in Short Children with Chronic Renal Disease, before Transplantation or with Functioning Renal Transplants: an Interim Report on Five European Studies

Growth retardation is common in children with chronic renal disease. Final adult height is often reduced, even in children with a functioning renal transplant. The five European studies considered here aim to investigate the efficacy and safety of recombinant human growth hormone therapy (rhGH) in two groups of short children with chronic renal disease. The first group comprises 29 prepubertal children with preterminal chronic renal failure (i.e. before renal transplantation), and the second group comprises 39 prepubertal and pubertal children with functioning renal transplants. The median bone age retardation in the groups at the start of treatment was between 2.2 and 3.7 years; this did not change during the first year of treatment. This interim report concentrates on patients who have been treated for at least 1 year (i.e. 22 children from the first group, and 28 children from the transplant group (15 prepubertal and 13 pubertal children). The median height velocity increased from 4.8 cm/year to 10.0 cm/year in the first group (the chronic renal failure group), from 2.6 cm/year to 6.2 cm/year in prepubertal children with renal transplants and from 3.8 cm/year to 6.7 cm/year in pubertal children with renal transplants. The corresponding changes in height velocity SDS were from -1.3 to 5.1 for the chronic renal failure group and -2.8 to 2.3 for the prepubertal children with renal transplants. Renal function declined in the chronic renal failure group but this decline corresponded to expected progression of the disease. Some of the children with renal transplants showed a decreased renal function, which in most cases was explained by non-compliance or chronic rejection.

Growth and Growth Hormone Secretion in Children Following Treatment of Brain Tumours with Radiotherapy

We have studied the growth of 144 children after treatment of brain tumours distant from the hypothalamo-pituitary axis. All had cranial irradiation and 87 spinal irradiation. In 56 patients observed without intervention for 3 years, height SDS in the cranial (CR) group (n = 20) declined from 0.02 to -0.44 and in the craniospinal (CS) group (n = 36) from -0.28 to -1.11. Failure of spinal growth had a marked effect in the CS group. The onset of puberty was slightly but not significantly advanced; median ages at onset of puberty were 10.3 years in girls and 12.1 years in boys. Of the total group 86.4% had clinical and biochemical evidence of growth hormone insufficiency. Fifty-two children, 33 (28 CS; 5 CR) of whom were prepubertal, received biosynthetic human growth hormone, in a dose of 15 mU/m2/week by daily injection for a period of one year. Height velocity SDS increased significantly in both groups from -2.74 to +1.90 (CS) and from -1.0 to +4.26 (CR). Spinal response to GH treatment was restricted in the craniospinal group.

Biosynthetic Human Growth Hormone in the Treatment of Growth Hormone Deficiency

A total of 309 previously untreated children with growth hormone deficiency (GHD) (219 boys, 90 girls; mean age 8.4 +/- 3.9 years, range 1.5-19 years) were treated for up to 3 years in an ongoing trial designed to examine the long-term efficacy and safety of biosynthetic somatropin (rhGH). The children were treated with rhGH, 0.06 mg/kg (0.16 IU/kg) three times weekly. In the prepubertal children, the mean height velocity increased during the first year from 3.8 +/- 1.8 cm/year to 8.9 +/- 2.2 cm/year (n = 188). During the second and third years, their height velocities were 7.1 +/- 1.1 (n = 147) and 6.3 +/- 1.2 cm/year (n = 64), respectively. The height velocity SDS increased from -2.5 +/- 1.9 before treatment to 3.1 +/- 2.6 during the first year of treatment in the prepubertal children. The mean pretreatment height velocity in those with idiopathic GHD (3.8 +/- 1.6 cm/year) did not differ from that in children with organic GHD (3.8 +/- 2.3 cm/year). In addition, the height velocities during the first year of therapy did not differ significantly with respect to the aetiology of GHD. For the children who entered puberty during the study, the mean height velocity increased from 3.0 +/- 1.7 cm/year before treatment to 8.4 +/- 2.3 cm/year during the first year of rhGH therapy. In the first year, the height velocity of children with a bone age of less than 5 years (9.4 +/- 2.3 cm/year) was significantly greater than that in children with a bone age of 5-10 years (8.4 +/- 1.8 cm/year) or greater than 10 years (7.8 +/- 2.2 cm/year: p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Growth Hormone Treatment in Non‐Growth Hormone‐Deficient Children: Effects of Stopping Treatment

Overnight physiological growth hormone (GH) secretion was evaluated in 95 short, prepubertal children (73 boys, 22 girls). All the children were below the 3rd centile for height and achieved GH levels greater than 15 mU/l following pharmacological stimulation. The mean average GH level was 7.1 mU/l and the mean sum of pulse amplitudes 80.4 mU/l. No relationship was found between age, height or height velocity and any of the parameters of GH secretion. The group was randomized to receive placebo, GH or remain under observation for the first 6 months and then all patients received GH treatment for a further 6 months. Those treated with GH, 0.27 IU/kg (0.1 mg/kg) three times weekly, in the first phase, demonstrated a mean increase in height velocity SDS of 3.24. There was no difference in growth response between the placebo or observation groups. In the second 6-month period, all children received GH according to the same dose regimen; they were then observed for a further 6 months following its discontinuation. In the 6 months following withdrawal of GH, all groups showed a significant fall in height velocity SDS, which returned to pretreatment levels, without demonstrating 'catch-down' growth. Repeat sampling of overnight GH secretion within 3 days of discontinuing GH showed normal secretory patterns with a small reduction in mean peak amplitude. These results suggest that short children without classic GH insufficiency respond well to exogenous GH in the short term and return to pretreatment height velocities afterwards. Consequently, it may be possible to increase final adult height in such children by GH treatment.

Effects of 3 Years of Growth Hormone Therapy in Short Normal Children

The effect of 3 years of growth hormone (GH) treatment on growth rate, predicted height, carbohydrate and metabolic status, and thyroid function was studied in 16 short prepubertal children growing with a normal pretreatment growth rate. The height velocity SDS increased from a pretreatment value of -0.44 +/- 0.33 (mean +/- SD) to a value of +2.20 +/- 1.03 during the first year of treatment. It was maintained at a value above zero over the subsequent 2 years. By the end of the third year of treatment, the predicted final height had increased by 6.8 cm in the boys and by 4.2 cm in the girls (p less than 0.001 and p less than 0.01, respectively). Increasing the dose of GH on a body surface area basis reduced the deceleration of growth observed during the second year of treatment, leading to an improvement in height prognosis over that year. Glucose homoeostasis was achieved initially at the expense of an elevation in fasting serum insulin concentration, but this had returned to pretreatment values by the end of the second year of therapy.

100 PROSPECTIVE RANDOMISED STUDY OF LOW DOSE ETHINYL-OESTRADIOL AND OXANDROLONE IN TURNER SYNDROME (TS)

30 patients with TS. aged 4.6-12.6 years were randomly allocated to receive oral ethinyl oestradiol (EE2) (0.5-2.0ug/day) or oxandrolone (OX) (0.625-1.25mg/day). Groups were matched for age, karyotype, pre-treatment height SDS for TS and height velocity SDS for TS (HV SDS) (Ranke).HV SDS results (SD) after 0.5-1.0 yrs were as follows:Response to EE2 was slightly less consistent than to OX (p < 0.05), with 2 non-responders.Both treatments were well tolerated. Cliteromegaly was noted in 2 on OX; 3 on EE2 had early breast development.24 hr growth hormone (GH) profiles were performed in 10 of each group before and during treatment. The sum of GH pulse amplitudes (SPA) was calculated using a computer algorithm (PULSAR). GH SPA was not changed by either treatment.Used in appropriate dosage, both agents are safe, simple and effective agents in Turner syndrome. Neither appears to work via increased CH secretion.

52 GROWTH AND PUBERTY IN SURVIVORS OF CHILDHOOD LEUKAEMIA

Childhood leukaemia is often associated with impaired growth and disorders of puberty. To see how common this is we re-examined all 13 survivors (9f, Am) of acute lymphoblastic leukaemia treated during childhood in our hospital 1964-1981. At diagnosis, aged 0.8 to 13.7 years, their mean height SDS was +0.9. They were given various chemotherapy, glucocorticoids and 11 had cranial irradiation (1600-2600 rad). During the first year after diagnosis the mean height velocity SDS was -1.4 (SD 1.2), and 6 of 13 lost >0.5 of their height SDS. By the end of therapy (7 years in 2, 3 to 3.6 years in 11) the mean height SDS was was +0.3 (SD 1.3) and 7 had lost >0.5 of their height SDS. After cancer therapy (follow-up 3 to 13 years) an improvement of height SDS >0.5 SD was seen in 4 and a deterioration in 1, due to scoliosis after paraplegia as a treatment complication. Of those 7 who had reached their final height, 4 were >1SD shorter than their midparert height SDS, 1 was 1 SD taller. Of those 6 still growing (aged 7.6 to 12.5 years) 3 were >1SD taller than their midparent height SDS and none was short. Five were obese with a relative weight for height of >120%, 2 were lean <90%. None of the girls had abnormal timing of puberty, and 2 had children. One boy was early in his puberty (G2 at 9.0 years). In conclusion, childhood leukaemia had impaired the growth of some of our patients, but their height deficit was not severe. Abnormal puberty was seen in only one of 13.

CONTRIBUTION OF GROWTH HORMONE PULSE AMPLITUDE AND PERIODICITY TO MID CHILDHOOD GROWTH - AN ASSESSMENT BY THE SEQUENCE ANALYSIS

Mid childhood growth has been studied in 21 short children (14M, 7F) aged 5.2-11.9 years growing with height velocity (HV) SDS between O and -0.8 (Group A) and 29 short children (21M,7F) growing with HV SDS < -0.8 (Group B). 24 hr GH profiles were analysed by an iterative method of pulse detection and subjected to time sequence analysis to determine dominant periodicities within the data array. Children aged <7 years from Group A had a dominant periodicity of 5 hours but after this age there was a shift to a 3 hour periodicity. In the whole sample (Groups A and B), differences between growth rate could be explained entirely by pulse amplitude. The modulation of childhood growth by GH pulse amplitude persisted into puberty in 14 tall pubertal girls in whom the periodicity of GH secretion remained unchanged. 6 children from Croup B had a similar sum of GH pulse amplitudes to the Group A children but a faster pulse frequency (11-14 pulses/24 hours) with a dominant periodicity of 2.3 hours. This led to a HV SDS -1.1- -3.0. We define this codition as neurosecretory dysfunction. To grow at a normal velocity a child needs 6 - 9 GH pulses/24 hours. We conclude that mid childhood and pubertal growth is GH pulse amplitude modulated with a periodicity of 3 hours. The major cause of poor growth velocity is low GH pulse amplitude but a sub group exists in which disturbance of pulse frequency is the major contributor.

THE LONGTERM EFFECTS OF GROWTH HORMONE THERAPY

The growth of 73 patients treated continuously with growth hormone (GH) for up to 5 years has been analysed. Catch-up growth in the sense of an improvement in height velocity SDS was induced in all patients regardless of age and pubertal status at start of treatment. There was improvement in height SDS for BA over the first year of therapy but overall, there was no change in height SDS for CA or BA compared to the start of treatment indicating that the deficit induced by poor growth velocity at any age irrecoverable.

SHORT SUBNORMALLY GROWING CHILDREN WITH NORMAL GH RESPONSE TO PHARMACOLOGICAL STIMULI: PHYSIOLOGICAL GH SECRETION AND RESPONSE TO GH TREATMENT

We have investigated 16 (3F, 13M) prepubertal children, mean age 8.65 years (range, 4.76 - 10.95) who had a mean height SDS of -2.90 (range, -4.61 to - 1.83). Mean height velocity SDS was -1.19 (range, -2.13 to-0.41). None had evidence of psychosocial disturbance. Patients were selected because they had normal responses (peak GH > 20 mU/l) to pharmacological stimuli of either glucagon, clonidine or insulin induced hypoglycacemia; mean peak GH attained to pharmacological stimuli was 27. 5 mu/l ( range, 20.1 - 40).All patients had an overnight serum GH profile, with blood drawn from an indwelling intravenous cannula at 15 minute intervals between 1800 - 0800 hrs. GH secretory dynamics were analysed using PULSAR computer programme. All children (except one) produced adequate spontaneous nocturnal pulsatile GH secretion. None of the children had fast frequency “neurosecretory dysfunction”. 15 (3F, 12M) were treated with bio-synthctic methionyl human GH in a regimen of 2 units subcutaneously daily. All have been treated for periods in excess of 6 months, and have responded by an increased height velocity SDS, mean +3.31 (range, -0.21 to + 6.27).This study points to the difficulty of interpreting pharmacologic and physiologic testing of GH secretion and re-emphasises the importance of anthropometric data in distinguishing those children who will respond to GH therapy.

CONTRIBUTION OF DOSE AND FREQUENCY TO THE THERAPEUTIC EFFECT OF CH

We treated 42 GH insufficient prepubertal children aged 3-12 years with 12 iu biosynthetic GH per week for 1 year after pretreatment observation of 1 year. Group 1 (n=13) received 4 iu GH 3 days per week, Group 2 (n=21) 2 iu GH 6 days per week and Group 3 (n=8) 1 iu GH twice daily 6 days per week. Between groups, pretreatment age (CA), bone age (BA) and auxological parameters were Identical.Height velocity improved (p<0.001) in all groups with a positive trend in the higher frequency regimens. Changes in height velocity (HV) SDS were +3.8 (sd 1.7) in Grp 1, +5.3 (sd 2.6) in Grp 2 and +5.9 (sd 2.7) in Grp 3. Height for BASDS improved equally in all groups.Of CA, BA, height SDS, height BASDS, HVSDS, frequency and dose/m2/wk only pretreatment HVSDS significantly determined response in the 42 children (r=-0.64). A significant difference was observed between the response of children receiving more or less than 15iu/m2/wk. If children were divided on the basis of pretreatment HVSDS, dose/m2/wk of GH received within each division affected outcome as follows:These data showed that GH dose and frequency of administration are relevant to the response to treatment with GH, but pretreatment HVSDS is the dominant factor in predicting its magnitude.

GROWTH AND GROWTH HORMONE (GH) TREATMENT FOLLOWING RADIOTHERAPY OF BRAIN TUMOURS

Of a cohort of 132 children alive and well following treatment of brain tumours remote from the hypothalamus or pituitary with radiotherapy, 96% had evidence of GH abnormality. 32 had completed their growth. 14 who had received craniospinal irradiation, had final height SDS -2.03 (range, -3.7 to +0.09), sitting height (SH) SDS -3.22 and subischial leg length (SILL) SDS -0.61. 18 treated with cranial irradiation alone had final height SDS -0.93 (range, -2.8 to +2.07), SH SDS -1.24 and STLL SDS -0.53. Thus the effect of spinal irradiation on final height was considerable.40 children were treated with GH for periods of 1-4 years. 32 had received craniospinal irradiation and 8 cranial irradiation alone. 17 children who had received craniospinal irradiation were treated with GH when prepubertal. Over the first 12 months of treatment mean height velocity SDS increased +2.52 (range -0.9 to +4.84). Mean height SDS for CA increased +0.27 (range -0.3 to +1.55) and height SDS for DA +0.09 (-0.89 to +0.99). Mean SILI. SDS increased +0.33 (-0.41 to +1.13) but SH SDS was not improved. GH giver, to 23 children in puberty was without significant effect on growth.We conclude: 1. Spinal irradiation adversely affected spinal growth and this did not respond to GH in the doses used. 2. After craniospinal irradiation, GH could only normalise leg growth and must therefore be instituted before puberty. 3. After cranial irradiation alone GH maintained height SDS. 4. Delay in instituting GH treatment leads to an irrevesible loss of final height prognosis.

PHYSIOLOGICAL GH SECRETION IN CHILDREN WITH SHORT STATURE DUE TO LOW BIRTHWEIGHT/RUSSELL-SILVER SYNDROME

We have studied 24 prepubertal children (7F, 17M) with short stature, mean height SDS -2.8 (range, -5.2 to -1.7) as a consequence of intrauterine growth retardation. Mean age at assessment was 6.3 yrs (range, 1.6-9.6). Mean birthweight SDS, allowing for gestational age, was -2.9 (range, -5.0 to -2.0). Mean height velocity SDS was -0.9 (range, -2.6 to + 1.0). Mean bone age delay was 0.6 “yrs”. Patients were divided into 2 groups; 11(3F, 8M) had dysmorphic features of the Russell-Silver syndrome (RSS group) and 13 (4F, 9M) did not (non RSS group). All children had an overnight serum GH profile from 1900-0800 hrs via an indwelling intravenous cannula with blood drawn at 15 minute intervals. A PULSAR computer programme was used for GH pulse analysis. GH pulse frequency, area under the GH pulses and sum of the GH peaks were calculated. All children had a maximum GH peak >20 mU/l except one boy who only attained a peak GH of 14mU/l. One boy in the non RSS group had high frequency “neurosecretory dysfunction”. The most pronounced abnormality in 6 of the 11 children with RSS was that only one large GH pulse during the night was observed with a mean value of 37 mU/l (range, 27-65). GH secretion remained detectable between pulses in 6 of the children in the non RSS group. It is probable that more than one endogenous GH pulse during the night is required for normal growth. Although growth failure in RSS is multi-factoral and end-organ insensitivity is probably important, abnormal GH secretion may be contributory.

SINGLE AND MULTIPLE PULSES OF GROWTH HORMONE (GH) IN THE TREATMENT OF GH DEFICIENCY

We have compared subcutaneous (s.c.) pulsed administration of hGH 0.6 IU 3 hourly at night with hGH 2 IU administered s.c. and 4 ID administered i.m. in 6 GH deficient children aged 5.9-11.6 years. Five had received hGH 4 IU i.m. for 3.6 years (range 2.5-4). Each of these children and one new patient received hGH 2 IU s.c. and 0.6 IU 3 times each night via a mini infusion pump for 6 months in random order. Serum GH profiles were obtained on all treatment regimens.Peak GH concentrations and areas under the GH curves were dose related. The time to attain the GH peaks was similar using i.m. (3.6h) or s.c. (3.9h) routes. A single injection did not mimic physiological GH pulses but these were more closely attained using pulsed administration.Four children completed the entire study; 3 grew equally at all times but height velocity fell in one on the pulsed regimen. Following cessation of all GH treatment, mean height velocity SDS (−4.0) was significantly lower than before all treatments (−2.1).Pulsatile hGH administration is effective but had no significant advantage. A post treatment velocity must not be used to measure the effects of a treatment.

Normal growth despite abnormalities of growthhormone secretion in children treated for acute leukemia

We have studied the relationship between abnormalities of the growth hormone-somatomedin axis and growth in 26 children previously treated for acute lymphatic leukemia. Each child had previously received cranial irradiation, was in complete clinical and hematologic remission, and off all drugs. The mean standing height SDS of the 26 children was significantly less than normal. There was no significant difference between the mean standing height SDS, height velocity SDS, somatomedin activities, and degree of bone age retardation between the 17 children who received the higher dose of cranial irradiation (Group 1) and the nine who had the lower dose of cranial irradiation (Group II). Furthermore, there was no significant reduction in mean height velocity SDS, somatomedin activity, or bone age in either group when compared to normal age-matched controls. The peak GH responses to both insulin hypoglycemia and an arginine test were significantly lowered in Groups I and II when compared to a control group of children. We conclude that only a minority of children, who previously received cranial irradiation for ALL were clinically GH deficient and, therefore, likely to benefit from GH therapy despite the finding that the majority of these children had reduced GH responses to pharmacologic stimuli.

Steroid interrelationships in congenital adrenal hyperplasia (CAH)

17-Hydroxyprogesterone (17P), testosterone (T), androstenedione (A), progesterone (P), 17-ketosteroids (17KS) and prenanetriol (p'triol) were measured serially in 31 CAH patients. Infants and adolescent girls showed significant correlations between 17P and T, A, P, respectively (p 1000ng/dl (30nmol/l), other steroid levels were high (particularly p'triol). There was no correlation between 17P and T in adolescent males (p>0.25). In infants, there was a significant correlation between mean 17P and T and height velocity SDS (p < 0.01). First year height velocity showed a significant negative correlation with hydrocortisone dose (p < 0.01). The results show the benefit of serial 17P and T measurements in the longer term management of CAH.