Insulin-like growth factor-I treatment in two children with growth hormone gene deletions.

Two unrelated Brazilian patients had homozygous 6.7 kb deletions in the GH-1 gene (girl and boy, 1.8 and 3.3 yr, heights -7.9 and -6.0 SDS, respectively). Desensitization using small amounts of exogenous GH (0.033 IU/kg body weight/week, divided into daily s.c. injections) was attempted, but anti-GH antibodies appeared. Replacement with usual doses of hGH induced only transient increase in growth. IGF-I therapy with increasing doses resulted in catch-up growth without side-effects. Growth velocity was 7.5 cm/yr in the first year and 8.4 cm/yr in the next 6 months in patient 1, and 6.7 cm/yr in the first year, 5.9 cm/yr in the second year and 7.9 cm/yr in the third year of IGF-I treatment in patient 2, when the daily dose of 240 micrograms/kg was divided into three injections. IGFBP-3 levels were low (0.55 and 0.40 mg/I) and did not increase after IGF-I treatment, suggesting that this GH effect is not mediated by IGF-I, and injected IGF-I had a rapid disappearance rate. We conclude that IGF-I promotes growth by endocrine mechanisms and constitutes an effective treatment for patients with GH insensitivity secondary to GH antibodies.     

Use of growth hormone and gonadotropin releasing hormone agonist in addition to L-thyroxine to attain normal adult height in two patients with severe Hashimoto's thyroiditis

AIM: We report two patients with severe acquired juvenile hypothyroidism who presented with compromised predicted adult height (PAH), and the successful use of growth hormone (GH) and gonadotropin releasing hormone agonist (GnRHa) in addition to L-thyroxine to attain normal adult height. PATIENTS AND RESULTS: Patient 1: 13 year-old girl who presented with pubertal delay, short stature (height SDS -4), and marked bone age retardation (BA 8 yr). Serum T4 was undetectable and TSH level was 1,139 mIU/l. After 1 year of treatment with L-thyroxine, growth rate improved from 1.0 cm/yr to 9.8 cm/yr but puberty progressed (Tanner 3 breast) and BA accelerated by 4 years, compromising predicted adult height (PAH) (144 cm vs mid-parental target height [MTH] of 163 cm). Combined use of GH and GnRHa for one year slowed BA progression, and catch-up growth (10.4 cm/yr) continued to attain a final height (FH) of 155 cm. Patient 2: 14 year-old boy with undetectable T4, TSH of 811 mIU/l in mid-puberty with poor growth rate (1.0 cm/yr), without any bone age delay (BA 14 years) but compromised PAH (163.8 cm vs MTH 174 cm). Because of the advanced puberty and poor growth rate, treatment with GH and GnRHa was initiated. Treatment for 2 years led to improvement of growth velocity (10.6 cm/yr), slowed BA progression to attain a FH equal to MTH. CONCLUSION: Combined use of GH and GnRHa improved the FH of two patients, with Hashimoto's thyroiditis: one with pubertal and bone age delay and the other with normal onset of puberty and normal bone age.     

Biosynthetic growth hormone therapy in children with growth hormone deficiency: Experience at AIIMS,New Delhi

A total of 20 previously untreated children with growth hormone deficiency (GHD) were treated for one year with biosynthetic human growth hormone (hGH). The mean chronologic age was 9.43±3.52 years with a height age of 5.02 years, and bone age 9.43±3.52 (TW2-RUS) 6.42 years. The mean pretreatment growth velocity was 2.43±0.90 cm/year. Of these 14 children had complete GHD (peak GH levels less than 5 ng/ml) and 6 had partial GHD. They were treated with recombinant GH in a dose of 0.5 IU/kg/week divided into 6–7 injections per week subcutaneously at night. The mean growth velocity increased to 8.88±2.10 cm/yr at the end of 6 months and 8.00±2.21 cm/yr at 12 months. The actual gain ranged from 6–11 cm in a year. There were no local adverse reactions. One child developed vitiligo of the face and another transient hyperglycemia.     

Therapy in short children with subnormal integrated concentrations of growth hormone

We evaluated the effect of growth hormone (GH) therapy on the posttreatment growth of 11 poorly growing children who had normal GH response to provocative stimuli but subnormal integrated concentrations of GH. Patients received 0.1 U/kg of GH three times per week. Their mean (+/- SD) growth rate increased from 3.3 +/- 1.0 cm/y before treatment to 6.5 +/- 1.4 cm/y after eight months of treatment. The growth rates of five patients declined to below 4.5 cm/y four months after treatment. Three of these patients resumed GH therapy and again responded with increased growth velocity (8.0 +/- 1.2 cm/y). After therapy, the growth rate of five remaining patients continued to be greater than 4.5 cm/y (6.8 +/- 1.4 cm/y). Two of these patients had entered puberty and their posttreatment growth rate might have been due to a pubertal growth spurt. The three prepubertal patients in this group had a gradual decline in growth velocity to 3.8 +/- 1.0 cm/y by the end of 12 posttreatment months. We conclude that maintenance of normal growth in patients with this pattern of GH deficiency is dependent on GH replacement therapy.     

Long-term treatment with GHRH [1-44] amide in prepubertal children with classical growth hormone deficiency.

A cohort of 20 GH deficient prepubertal patients were treated with GHRH [1-44] 10 micrograms/kg or 20 micrograms/kg twice daily for up to four years (5 patients). GHRH treatment resulted in sustained improvement in height velocity. The mean prepubertal height velocity was 3.57 +/- 1.05 cm/yr pretreatment; 8.49 +/- 1.45 cm/yr at year 1; 6.86 +/- 1.45 cm/yr at year 2; 6.22 +/- 0.74 cm/yr at year 3; and 6.16 +/- 0.97 cm/yr at year 4. IGF-I levels increased and remained within normal range. The difference between the children's and the parents' Ht SD scores significantly diminished from a pretreatment difference of -2.43 to -0.48 after four years of treatment. No adverse effects were noted during treatment. We conclude that twice-daily GHRH [1-44] treatment in a small group of prepubertal GH deficient children resulted in sustained improvement in height and growth velocity, and achieved height SDS approaching closely those of their parents.     

Predictors of growth response to growth hormone in otherwise normal short children.

Sixty prepubertal short children (39 boys) with heights less than 2 SD for age and gender were treated daily for 1 year with recombinant human growth hormone (GH), either 0.1 IU/kg (group 0.1, n = 32) or 0.05 IU/kg (group 0.05, n = 28). Reserve of GH was determined by at least one GH provocative stimulus and 24-hour continuous blood withdrawal to determine the integrated concentration of GH (IC-GH). All participants had a GH response to provocative tests greater than 10 micrograms/L. The height velocity (mean +/- SD) of the group as a whole increased from 4.46 +/- 1.02 to 7.59 +/- 1.65 cm/yr (p less than 0.001). The growth velocity of group 0.1 was significantly greater than that of group 0.05 (8.1 +/- 1.5 vs 7.0 +/- 1.65 cm/yr; p less than 0.01). Bone age did not advance more than 1 year during the treatment period. Growth velocity after 1 year of GH therapy was inversely correlated with the IC-GH in both groups, as was the pretreatment height velocity. We found no correlation of growth velocity during GH therapy with other measures such as parental heights, bone age/chronologic age ratio, maximal GH response to provocative tests, chronologic age, or pretreatment insulin-like growth factor I levels. We conclude that the best predictors for the 1-year growth outcome of short children with a normal GH response to provocative tests are the pretreatment growth velocity and the IC-GH. The short-term benefit from GH therapy in children with a normal growth velocity and a normal IC-GH is poor, whereas marked growth acceleration is noted in children with a low growth velocity and a low 24-hour IC-GH.     

Results and side-effects of treating children with growth hormone after kidney transplantation – a preliminary report

The effect of growth hormone (GH) therapy on renal function was investigated in 203 children who had undergone kidney transplantation. In addition, the efficacy of GH in stimulating growth as well as other aspects of safety were assessed. The patients were randomized to receive either GH, 1 IU/kg/week, administered subcutaneously once daily, or no treatment during the first year (controls). During the second year, all patients received GH. The change in growth velocity and A height SD score during the first year of GH treatment was statistically significant compared with controls ( p < 0.0001). During the second year, those patients who received GH during the first year continued to show an increased rate of growth compared with that during the pretreatment period; however, the mean growth rate was lower than that in the first year of treatment. The mean change in glomerular filtration rate did not differ between the treated and control groups during the first year of the study. However, acute rejection episodes tended to be more frequent during GH treatment, particularly in those patients who had a history of more than one episode. Close monitoring of renal function is therefore recommended.     

Accelerated growth after recombinant human growth hormone treatment of children with chronic renal failure

We studied the effect of recombinant human growth hormone treatment on five boys, aged 4.6 +/- 1.8 years, who had chronic renal failure secondary to congenital renal diseases (mean creatinine clearance (+/- SD): 18.3 +/- 6.3 ml/min/1.73 m2 (0.32 +/- 0.11 ml/sec/1.73 m2]. Patients received 0.125 mg/kg of growth hormone three times per week for 1 year. Before beginning treatment, the children had a mean annual growth velocity of 4.9 +/- 1.4 cm/yr (range 3.0 to 6.3 cm/yr), with a mean standard deviation score for a height of -2.98 +/- 0.73 (range -2.16 to -3.59). At the end of therapy, the mean growth velocity had increased to 8.9 +/- 1.2 cm/yr (range 7.5 to 10.7 cm/yr), and the mean height standard deviation score improved to -2.36 +/- 0.83 (range -1.15 to -3.18). Bone age advancement was consistent with the period of growth. Routine laboratory determinations, including results of glucose tolerance testing, did not vary significantly from pretreatment levels. These preliminary data indicate that growth-retarded children with chronic renal failure can respond to exogenous growth hormone therapy with a marked acceleration in growth velocity.     

One-year treatment with recombinant human growth hormone of children with meningomyelocele and growth hormone deficiency: a comparison of supine length and arm span.

Growth retardation and precocious puberty are frequently found in children with meningomyelocele (MMC). Lower limb contractions, spasticity and kyphoscoliosis may lead to disproportionate short stature. Most of these patients have structural brain defects or hydrocephalus which can cause growth hormone deficiency. In this study, 19 children aged between 3.5 and 12.8 years with MMC and growth hormone (GH) deficiency were treated with recombinant human GH for a period of 12 months. Supine length, arm span and growth velocity were compared before, and after 6 and 12 months of treatment with rhGH (daily dose 2.0 IU/m2 BSA s.c.). Mean supine length standard deviation score (SDS) increased by +0.8 SDS after 6 months and +1.2 SDS after 12 months of therapy. Mean arm span standard deviation score increased by +0.9 SDS and +1.3 SDS. Growth velocity increased in supine length from 3.3 cm/yr (-2.1 SDS) to 8.4 cm/yr (+2.4 SDS) and in arm span from 4.8 cm/yr (-1.3 SDS) to 8.6 cm/yr (+3.1 SDS) in the first 6 months and was 8.1 cm/yr (+2.4 SDS) and 8.3 cm/yr (+2.6 SDS) after 12 months of therapy. Linear correlation between SDS growth velocity supine length and SDS growth velocity arm span during one year of treatment was excellent (r = 0.65, p < 0.0025). We surmise that body proportions do not deteriorate when growth velocity is stimulated in MMC patients. Both supine length and arm span measurements are necessary to document growth in children with spinal dysraphism.     

Evaluation of clinical and laboratory parameters during 2 years of growth hormone treatment in prepubertal children with chronic renal failure

Twelve prepubertal children with chronic renal failure (CRF) were treated with human growth hormone (GH) (1.2 IU/kg/week) for 2 years. High doses of GH clearly increased growth velocity, from 3.8±1.3 to 9.6±1.5 (P=0.0001) and 6.9 ±0.8 cm/year (P=0.0001) after the 1 st and 2nd year of treatment, respectively, leading to a mean height gain of 1.4 SD. During the 1 st year of treatment the height increment, expressed in SDS, correlated negatively with chronological age (P=0.003). Basal insulin-like growth factor 1 (IGF 1) levels were normal or elevated (7/12 patients) and correlated positively with the overnight integrated GH concentration (r=0.68,P<0.001). Basal insulin-like growth factor binding protein 3 (IGF-BP3) levels were elevated in 8/12 patients. GH induced a significant increase in IGF 1 and IGF-BP3 levels; IGF 1 peaked after 6 months (when growth velocity was optimal) and IGF-BP3 peaked after 12 months. The mean glomerular filtration rate, measured by inulin clearance and corrected for body surface area, fell after the 1st year of treatment, and significantly so at the end of the 2nd year (P=0.02).     

Combined therapy with GnRH analog plus growth hormone in central precocious puberty

GnRH analogues (GnRHa) arrest pubertal development, and slow growth velocity (GV) and bone maturation, thus improving adult height in central precocious puberty (CPP). In some patients, however, GV decreases to such an extent that it compromises the improvement in predicted adult height (PAH) and therefore the addition of GH is suggested. Of 20 patients with idiopathic CPP (treated with GnRHa [depot-triptorelin] at a dose of 100 microg/kg every 21 days i.m. for at least 2-3 yr) whose GV fell below the 25th percentile for chronological age (CA), ten received, in addition to the GnRHa, GH at a dose of 0.3 mg/kg/wk, s.c. 6 days weekly, for 2-4 yr. Ten patients matched for BA, CA, and duration of GnRHa treatment who showed the same growth pattern but refused GH treatment, served to evaluate the efficacy of the addition of GH. No patient showed classical GH deficiency. Both groups discontinued treatment at a comparable BA (mean +/- SEM): 13.2 +/- 0.2 yr in GnRHa + GH vs 13.0 +/- 0.1 yr in the control group. At the conclusion of the study all the patients had achieved adult height. Adult height was considered to be attained when the growth during the preceding year was less than 1 cm, with a BA of over 15 yr. Patients of the group treated with GH + GnRHa showed an adult height significantly higher (p<0.001) than pretreatment PAH (160.6 +/- 1.3 vs 152.7 +/- 1.7 cm). Height SDS for BA significantly increased from -1.5 +/- 0.2 at start of GnRHa to -0.21 +/- 0.2 at adult height (p<0.001). Target height was significantly exceeded. The GnRH alone treated group reached an adult height not significantly higher than pretreatment PAH (157.1 +/- 2.5 vs 155.5 +/- 1.9 cm). Height SDS for BA did not change (from -1.0 +/- 0.3 at start of GnRHa to -0.7 +/- 0.4 at adult height). Target height was just reached but not significantly exceeded. The gain in centimeters obtained calculated between pretreatment PAH and final height was 7.9 +/- 1.1 cm in patients treated with GH combined with GnRH analogue while in patients treated with GnRH analogue alone the gain was just 1.6 cm +/- 1.2 (p=0.001). Furthermore, no side effects, bone age progression, or ovarian cysts, were observed in GnRHa + GH treated patients. In conclusion, a gain of 7.9 cm in adult height represents a significant improvement which justifies the addition of GH for 2-3 yr to conventional treatment with GnRH analogues in patients with central precocious puberty, and with a decrease in growth velocity so marked as to impair predicted adult height to below the third percentile.     

Zinc deficiency: a contributing factor of short stature in growth hormone deficient children

Zinc is an essential trace element which affects growth by promoting DNA and RNA synthesis and cell division. Zinc deficiency causes growth retardation and its frequency is high in developing countries. It could contribute to the effect of growth hormone (GH) treatment in GH deficient children. In this study, we investigated zinc deficiency in GH children. Twenty-four GH deficient children (treated with GH for 2.2 +/- 1.6 years) were recruited for the study. Intracellular erythrocyte zinc levels were measured. Eleven (45.9 per cent) were found to be zinc deficient (Group 1), while 13 patients (54.1 per cent) had normal zinc levels (Group 2). The mean growth velocity was 5.98 +/- 0.8 cm/year in Group 1 and 6.9 +/- 1.4 cm/year in Group 2. Group 2 was given oral zinc supplementation with a resultant growth velocity of 7.51 +/- 0.5 cm/year. During GH treatment in GH deficient children, zinc status should be evaluated as severe zinc deficiency could affect the response to GH treatment.     

Rheumatoid arthritis and growth retardation in children: Treatment with human growth hormone

Twenty patients with rheumatoid arthritis or Still's disease associated with growth failure were treated with human growth hormone, 7.5 to 17 U/m² body surface per week.Five patients did not respond with better growth. In the remainder the mean growth rate increased from 1.9 cm/year (range: 0 to 3.3) to 6.2 cm/year (range: 3.6 to 12) over 5 to 7 months. Twelve patients treated for longer periods increased their mean growth rate from 2.3 cm/year (range: 0.7 to 5.7) to 6.3 cm/year (range: 2.4 to 9.7) and continued to grow during a second year of treatment. Growth velocity decreased in 6 patients when the hGH therapy was discontinued.The causes for this improvement in growth are possibly multifactorial: the growth rate is depressed by the severity of the disease and high-dose glucocorticoid therapy. Increases of growth rate occured during improvements in the disease, reduction of steroid medication, as a result of therapy with human growth hormone, and because of puberty in some patients.Human growth hormone seemed to improve the underlying condition of four of the patients but had no influence on the disease in the remaining children.On the occasion of the 75th birthday of Prof. Dr. Dr. h. c. Adolf Butenandt     

Growth-stimulating effects of human growth hormone therapy in patients with Turner syndrome

We determined the effect of pituitary human growth hormone treatment on the growth rate of 52 children with Turner syndrome. The pretreatment growth rate was 3.2 +/- 0.8 cm/yr. Growth hormone treatment (0.2 IU/kg three times per week) resulted in enhancement of the growth rate to 5.9 +/- 1.4 cm/yr for the first year of therapy. The bone age advanced approximately 1 year during the year of therapy. The growth hormone therapy was discontinued at 12 months, and the mean growth rate decreased to pretreatment levels, 3.1 +/- 1.9 cm/yr; 26 of 41 patients actually had post-treatment growth rates that were less than the pretreatment rate. Glucose tolerance tests at 6-month intervals did not indicate an effect of hGH treatment on glucose intolerance. Several patients had glucose intolerance that preceded hGH treatment, but this remained stable during treatment; glucose intolerance likely was related to obesity in this group of patients. Basal and hGH-stimulated somatomedin C levels (32 patients) correlated with age of the patient but not with growth rate during therapy. We conclude that hGH therapy can accelerate the growth rate of patients with Turner syndrome. The growth rate increased to "normal" levels and was dependent on continued treatment with hGH. If the response continues, long-term treatment of Turner syndrome may result in increased adult height.     

Growth Hormone Treatment in Short Children -Short-Term and Long-Term Effects on Growth

Short children with normal GH responses to arginine-insulin provocation testing and various amounts of spontaneously secreted GH over 24 hours participated in an ongoing study with GH, 0.1 IU/kg/day. A total of 40 prepubertal children have been treated for 1 year. Their mean height velocity increased from 4.6 to 7.5 cm/year. The children with the slowest pretreatment height velocity showed the best increment. An inverse relationship was found between the endogenous GH secretion and the increment in growth; 80% of the children had an endogenous GH secretion of less than 300 milliunits/litre/24 hours, estimated as area under the curve above the calculated baseline. They all showed an increment in height above 2 cm. The remaining 20% all had an endogenous GH secretion of more than 300 milliunits/litre/24 hours, estimated as area under the curve above the calculated baseline, Twenty-four of the children were prepubertal for the following 4 years, and their GH therapy continued. Their Deight velocity changed from 4.2 cm/year before therapy to 8.1,6.7,6.0 and 4.9 cm/year for the 1st, 2nd, 3rd and 4th years on treatment. Many of them have passed their expected final height, but have still not stopped growing. Those children who were in early puberty when GH treatment started went into a rapid growth spurt and have now stopped growing. They have all reached but not improved their expected final height. In 15 of the children GH treatment was stopped after 1-3 years. Their mean height velocity for the first post-treatment year was 5.1 cm/year; thus, for the group as a whole no'catch down'was observed. Of the 15 children, only 4 decreased in height velocity despite increasing age. Further studies on the long-term results of GH treatment in larger groups of short children are needed to verify the findings in this study.     

Growth hormone deficiency impedes the rise in plasma insulin-like growth factor I levels associated with precocious puberty

We tested the hypothesis that growth hormone (GH) mediates the rise in insulin-like growth factor I (IGF-I) concentrations in children with precocious puberty. We studied three groups of patients. Group 1 included six children with GH deficiency and precocious puberty (precocious GH-deficient); group 2 included 10 GH-sufficient patients with idiopathic true precocious puberty (precocious GH-sufficient); and group 3 included 9 prepubertal children with GH deficiency (prepubertal GH-deficient). Growth rates, pubertal status, and plasma IGF-I concentrations were determined at regular intervals. The precocious children with GH deficiency had a mean (+/- SD) growth rate of 7.2 +/- 2.1 significantly below that of the precocious GH-sufficient patients (10.5 +/- 2.5 cm/yr, p less than 0.05) but above that of the prepubertal GH-deficient children (3.9 +/- 1.4 cm/yr, p less than 0.05). The mean IGF-I concentration in the precocious GH-deficient children was 0.77 +/- 0.39 U/ml, significantly lower than the mean level of 2.2 +/- 0.67 U/ml in the precocious GH-sufficient patients (p less than 0.01). However, precocious GH-deficient patients had significantly higher IGF-I values than the prepubertal GH-deficient children (0.24 +/- 0.10 U/ml, p less than 0.05). IGF-I values did not rise with the onset of precocious puberty in four of the precocious GH-deficient children evaluated before and after the development of precocious puberty. However, three patients who began GH treatment did have a rise in plasma IGF-I concentrations to levels of 1.2, 3.4, and 3.7 U/ml, respectively. These findings are compatible with the concept that sex steroids increase IGF-I levels in precocious puberty primarily by increasing GH production. A small but direct effect of sex steroids on IGF-I production may also exist. The onset of precocious puberty in children with organic GH deficiency may mask the abnormal growth pattern of these children and delay diagnosis; determinations of plasma IGF-I concentrations may be helpful in assessing the GH status of these patients.     

A controlled trial of methionyl growth hormone therapy in prepubertal children with short stature, subnormal growth rate and normal growth hormone response to secretagogues. Dutch Growth Hormone Working Group

Thirty short and slowly growing children with normal plasma growth hormone (GH) responses to standard provocation tests were randomly assigned to either a group (n = 20) undergoing treatment with methionyl GH (somatrem), 2 IU per m2 body surface s.c. daily, or a control group (n = 10). Twelve out of 18 children who completed the first year of treatment showed a height velocity increment of more than 2 cm/year. The mean (SD) growth velocity of the treatment group increased by 3.0 (1.9) cm/year over the first year, compared with -0.2 (0.7) cm/year in the control group. Neither parameters of endogenous GH secretion nor plasma IGF-I levels showed a significant correlation with the growth response. Of the auxological variables studied, pre-treatment growth velocity (r = -0.8) and the short-term height velocity increment (r = 0.7-0.9) showed significant correlations with the growth response in the first year of treatment. Somatrem therapy was without side effects, except in one child who developed anti-GH antibodies in combination with a poor growth response.     

Treatment of patients with Ullrich-Turner syndrome with conventional doses of growth hormone and the combination with testosterone or oxandrolone: Effect on growth,IGF-I and IGFBP-3 concentrations

Thirty-nine girls with Ullrich-Turner syndrome (UTS) (median age 9.5 years) were treated with growth hormone (GH) with either 12 or 18 IU/m² per week for 12 months followed by combination therapy with either oxandrolone (Ox) (0.0625 mg/kg/day po) or low-dose testosterone (T) (5 mg im every 2 weeks). Growth velocity improved significantly after 12 IU/m² per week (6.4±1.7 cm/year vs 4.0±1.3 cm/year, x±SD,P<0.001) and 18 IU/m² per week of GH (6.5±1.3 cm/year vs 4.5±1.4 cm/year,P<0.001). Ox, but not T was effective in maintaining growth velocity during the 2nd year of therapy (6.9±1.3 vs 5.3±1.5 cm/year). Basal insulin-like growth factor-I (IGF-I) concentrations were in the lower normal range and increased significantly in patients treated with 18 IU/m² per week (357±180 ng/ml vs 160±84 ng/ml) and 12 IU/m² per week (273±121 ng/ml vs 140±77 ng/ml). IGF-I concentrations increased further after addition of Ox (533±124 ng/ml,P<0.001) or T (458±158,P<0.05). IGFBP-3 concentrations were in the upper normal range before therapy and increased only moderately in both GH dosage groups. However, IGF binding protein-3 (IGFBP-3) concentrations were not affected by additional Ox or T treatment.Conclusions 1. Conventional GH doses are effective in increasing growth velocity in UTS, especially, when combined with Ox. This additive effect is not evident when GH is combined with low dose T. 2. Changes in growth velocity are accompanied by an increase of the IGF-I/IGFBP-3 ratio. 3. Ox obviously acts by increasing IGF-I levels independent of the GH status.     

Growth hormone state after completion of treatment with growth hormone.

After completion of treatment with growth hormone (GH) 19 patients with isolated ''idiopathic'' GH deficiency and 15 with post-irradiation GH deficiency underwent retesting of GH secretion with an insulin tolerance test or an arginine stimulation test, or both. Patients with post-irradiation GH deficiency comprised 13 patients with central nervous system tumours distant from the hypothalamo-pituitary axis and two with acute lymphoblastic leukaemia, who had received cranial or craniospinal irradiation. All 15 patients with post-irradiation GH deficiency remained GH deficient (peak GH response less than 7 mU/l (n = 10) and 7-15 mU/l (n = 5)). Of the 19 retested patients with idiopathic GH deficiency, however, five (26%) had peak GH responses of greater than 15 mU/l (regarded now as transient or false idiopathic GH deficiency) and were indistinguishable from the remainder (permanent or true idiopathic GH deficiency, peak GH responses less than 7 mU/l (n = 12) and 7-15 mU/l (n = 2)), by pretreatment anthropometry and post-treatment height standard deviation score, but had a lower first year height velocity (mean (SD) velocity 5.6 (0.5) cm/year for false idiopathic deficiency v 8.7 (1.75) cm/year for true idiopathic deficiency, p less than 0.01) and height increment on treatment (mean (SD) increment 2.2 (1.5) cm/year for false idiopathic deficiency v 5.2 (2.3) cm/year for true idiopathic deficiency, p less than 0.05). By current practices two patients with false idiopathic deficiency may have been distinguished by sex steroid priming. Thus post-irradiation GH deficiency seems to be permanent, but errors in diagnosis in idiopathic GH deficiency are common.     

Evaluation of growth hormone secretion after completion of therapy

BACKGROUND: Growth hormone (GH) reserve in young adults previously diagnosed as having GH insufficiency, who were treated with human (h)GH replacement in childhood needs confirmation in adulthood. METHODS: Nine patients (seven males, two females; two empty cella, one hypoplasia of the hypophysis and six with idiopathic GH deficiency) diagnosed as having GH insufficiency by the insulin tolerance test (ITT) and dopamine stimulation test in childhood (mean age 12.8+/-2.6 years) were retested at completion of linear growth (mean age 21.0+/-3.0 years), 4.6+/-1.6 years after discontinuation of hGH therapy. RESULTS: At the initial diagnosis, seven had complete and two had partial GH deficiency. At diagnosis, the mean peak GH response to ITT and dopamine was 4.8+/-4.08 and 3.4+/-2.9 mU/L, respectively. At retesting, the mean GH response to ITT and dopamine stimulation was 3.5+/-2.5 and 3.3+/-3.1 mU/L, respectively (P=0.91 and 0.96, respectively). During hGH therapy, mean height velocity increased from 3.5+/-1.9 cm/year at diagnosis to 9.9+/-3.64 cm/year during the first year (P=0.002). One of nine children diagnosed as having GH insufficiency who was treated with hGH replacement had normal growth hormone secretion at completion of linear growth. CONCLUSIONS: All GH-insufficient children should be retested after completion of their hGH treatment and linear growth to identify those who are truly GH insufficient and who may benefit from GH therapy in adulthood.