Adult height in patients treated for isolated growth hormone deficiency: role of birth weight

To evaluate the effect of growth hormone (GH) administration on adult height (AH) in two groups of isolated GH-deficient (IGHD) children born either small (birth weight below -2 SD) or appropriate (birth weight above -2 SD) for gestational age (GA). Out of 35 prepubertal IGHD children, 14 small for GA (SGA, group A) and 21 appropriate for GA (AGA, group B) were examined. All patients received continuous GH treatment at a median dose of 0.028 mg/kg/day (range 0.023-0.032) in group A and 0.024 (range 0.023-0.028) in group B. GH treatment was administered for a period of 67.0 months (range 42.37-96.05) in group A and 54.31 months (range 47.14-69.31) in group B. All children were measured using a Harpenden stadiometer every 6 months until they reached AH (growth velocity <1 cm/year). The patients underwent a retesting a few months after stopping GH therapy. A significant difference was found between group A and B as expected for birth weight SD, -2.70 (range -2.87 to -2.29) and -0.73 (range -1.30 to 0.14) respectively (p < 0.000001) and interestingly also for body mass index SDS (BMI SDS) at retesting, 0.08 (range 0.30 to -1.51) and 0.61 (range 0.73 to -1.10) respectively (p < 0.04). We observed no significant differences between groups A and B in height (expressed as the SDS for chronological age, height SDS) at diagnosis (p = 0.75), height SDS at start of puberty (p = 0.51), height SDS at retesting (p = 0.50), target height SDS (TH SDS) (p = 0.47), AH SDS (p = 0.92), corrected height SDS (height SDS - TH SDS) (p = 0.60), BMI SDS at diagnosis (p = 0.25), GH dosage (p = 0.34) and therapy duration (p = 0.52). GH treatment with a standard dose in short IGHD children leads to a normalization of AH without any significant difference between SGA and AGA patients.     

Experience with growth hormone therapy in Turner syndrome in a single centre: low total height gain, no further gains after puberty onset and unchanged body proportions

The experience gained since 1987, through observation of 85 girls with Turner syndrome under growth hormone (GH) treatment, has enabled the analysis of one of the largest cohorts. Our results show that age, karyotype and height reflect the heterogeneity of the patients examined at our growth centre. In 47 girls, followed over 4 years on GH (median dose 0.72 IU/kg/week), the median age was 9.4 years and mean height SDS was -3.55 (Prader) and -0.14 (Turner-specific), while height and other anthropometrical parameters [weight, body mass index, sitting height (SH), leg length (LL) SH/LL, head circumference, arm span] were documented and compared to normative data as well as to Turner-specific references established on the basis of a larger (n = 165) untreated cohort from Tübingen. The latter data are also documented in this article. Although there was a trend towards normalization of these parameters during the observation period, no inherent alterations in the Turner-specific anthropometric pattern occurred. In 42 girls who started GH treatment at a median age of 11.8 years, final height (bone age >15 years) was achieved at 16.7 years. The overall gain in height SDS (Turner) from start to end of GH therapy was 0.7 (+/- 0.8) SD, but 0.9 (+/- 0.6) SD from GH start to onset of puberty (spontaneous 12.2 years, induced 13.9 years) and -0.2 (+/- 0.8) from onset of puberty to end of growth. Height gain did not occur in 12 patients (29%) and a gain of > 5 cm was only observed in 16 patients (38%). Height gain correlated positively with age at puberty onset, duration, and dose of GH, and negatively with height and bone age at the time GH treatment started. Final height correlated positively with height SDS at GH start and negatively with the ratio of SH/LL (SDS). We conclude that, in the future, GH should be given at higher doses, but oestrogen substitution should be done cautiously, owing to its potentially harmful effect on growth. LL appears to determine height variation in Turner syndrome and the potential to treat short stature successfully with GH.     

Comparison of final height in monozygotic twins,one with idiopathic and isolated growth hormone deficiency treated with low dose of growth hormone

OBJECTIVE: We report final heights in a pair of monozygotic twins, one unaffected and the other affected with idiopathic and isolated growth hormone (GH) deficiency treated with human GH, and discuss the effect of GH dosage on the attainment of the genetic height potential in GH deficiency. PATIENTS: Male monozygotic twins were born at 35 weeks of gestation; birth weights were 1,876 g in the unaffected and 1,510 g in the affected twin. At 4.9 years of age, the affected twin was studied for short stature (-3.38 SD) and was diagnosed as having idiopathic and isolated GH deficiency, whereas the unaffected twin was normal in height (+/- 0 SD). GH treatment was started at the age of 5.7 years and continued throughout childhood and adolescence. The average dose of GH administered during the treatment period was 0.35 IU (0.12 mg)/kg/week. The affected twin appeared to grow normally without other hormone replacement and achieved a final height of 165.6 cm (-0.86 SD) compared with that of 166.4 cm (-0.71 SD) in the unaffected twin at 17.5 years of age. CONCLUSION: Our results indicate that a relatively low dose of GH treatment started at an early age may preserve genetic height potential in patients with isolated GH deficiency.     

Final height after growth hormone therapy in peripubertal boys with a subnormal integrated concentration of growth hormone.

The aim of this study was to test the effect of growth hormone (GH) therapy on final height in peripubertal boys with idiopathic short stature in whom a subnormal integrated concentration of GH (< 3.2 micrograms/l) was found. Twenty-eight peripubertal children were studied. Height was below 2 SD for age, growth velocity was < 4.5 cm/year, bone age was more than 2 SD below mean for age and GH response to provocative tests was more than 10 micrograms/l. Eleven subjects (group B) were treated with recombinant GH 0.75 unit/kg/week, divided into 3 weekly doses for 2 years, and then the same weekly dose divided into daily injections was administered until final height was attained. Seventeen untreated children (group A) who were followed until cessation of growth served as controls. The GH-treated patients reached their target heights (-2.1 +/- 0.5, mean +/- SD in SDS) and predicted heights (-1.8 +/- 0.8) determined by the Bayley and Pinneau method, while the final heights of the untreated patients were significantly lower than their target heights and their predicted final heights (-2.7 +/- 0.7, -1.8 +/- 1.0 and -2.7 +/- 0.7, respectively). The main effect of GH was observed during the 1st year of treatment when height velocity was significantly higher in the GH-treated group than in the untreated one (9.3 +/- 2.1 vs. 5.3 +/- 1.1, respectively, p < 0.001). The high cost of the treatment in this specific age group should be weighed against the results.     

Short-term growth response to GH treatment and considerations upon the limits of short-term growth predictions

OBJECTIVES: To investigate the impact of short-term growth measurements on predicting the individual growth response to GH treatment, and to elucidate the possible reasons for the limited accuracy of current growth prediction models for GH-treated children. METHODS: Short-term growth measurements by knemometry and stadiometer in 99 short, GH-treated children (27 girls, 72 boys), aged 10.3 +/- 2.3 years, from the Children's University Hospital, Leipzig, Germany. RESULTS: GH treatment significantly accelerated the mean height velocity (HV) from 4.3 +/- 1.0 to 8.1 +/- 1.8 cm/year during the first year of treatment, the average height standard deviation score (SDS) shifted by +0.52 SD. The variation in HV also increased, from S(2) = 1.0 before to S(2) = 3.4 cm(2)/year(2) during treatment. Lower leg length (LLL) velocity accelerated from 1.6 +/- 0.7 before treatment to 3.4 +/- 1.0 cm/year during the first 8 weeks of treatment. Four coefficients of correlation appeared clinically meaningful: (1) LLL velocity vs. body HV during the first year of GH treatment (r = 0.87), indicating that GH acts simultaneously on leg and rump growth; (2) early (first 8 weeks) LLL velocity vs. 1-year body HV during treatment, with r = 0.61 (R(2) = 0.38), indicating that 38% of the variation in HV during the first year of treatment is already predictable by an initial 8-week period of knemometry; (3) early (first 8 weeks) LLL velocity vs. 1-year LLL velocity during treatment, with r = 0.63 (R(2) = 0.39), and (4) early (first 8 weeks) LLL velocity vs. later LLL velocity, up to the end of the first year, with r = 0.53 (R(2) = 0.28) indicating that the early response on lower leg growth persists for at least 1 year of GH treatment. CONCLUSIONS: (1) Thirty-eight percent of the variation in HV during the first year of GH treatment is predictable by an initial 8-week period of knemometry. This parallels early changes in biochemical markers of bone turnover after GH treatment. (2) There is evidence for a baseline variability in HV both in healthy children and in children with growth disorders that make growth prediction difficult.     

Growth hormone normalises height, prediction of final height and hand length in children with Prader-Willi syndrome after 4 years of therapy

BACKGROUND: Based on the reported favourable effects of growth hormone (GH) treatment on growth and body composition in Prader-Labhart-Willi syndrome, we studied age dependency and the long-term effects on growth dynamics to elucidate the assumed hypothalamic GH deficiency. METHODS: We examined 23 children treated with hGH (24 U/m(2)/week) during a median of 4 (range 1.5-5.5) years; group 1: 10 young underweight (age 0.3-4.1 years), group 2: 8 prepubertal overweight (age 3.7-9.5 years) and group 3: 5 pubertal overweight children (age 9.0-14.6 years). RESULTS: After 4 years of therapy, height gain amounted to 1.8 SD; height (0.0 SD) and hand length (-0.2 SD) were normalised in the 2 prepubertal groups; in children above 6 years, height prediction approached parental target height. Weight for height rose in group 1 (to 0.64 SD) and decreased in group 2 (to 0.71 SD) to normal levels. Bone maturation of the pubertal children was too advanced to show a clear growth response to GH (height gain 0.42 SD). Even in this group, weight for height was reduced, but remained supernormal. CONCLUSION: Under exogenous GH, growth and body proportions are normalised in prepubertal children. With early institution of treatment, final height prediction reaches the parental target height range after 3 years. Such a growth-promoting effect of exogenous GH has so far only been described in children with GH deficiency.     

A randomized, double-blind study to assess the efficacy and safety of valtropin, a biosimilar growth hormone, in children with growth hormone deficiency

Valtropin is a recombinant human GH (rhGH) manufactured using a novel yeast expression system, classed as a 'biosimilar'. Valtropin was compared with Humatrope in children with GH deficiency (GHD). Treatment-naive, prepubertal children with GHD were randomized to Valtropin (n = 98) or Humatrope (n = 49) for 1 year. Standing height was measured 3-monthly and height velocity (HV) calculated. Serum IGF-I, IGFBP-3 and GH antibodies were determined centrally. HV at 1 year was 11.3 +/- 3.0 cm/year with Valtropin and 10.5 +/- 2.8 cm/year with Humatrope. Treatment difference was 0.09 cm/year with 95% confidence limits of -0.71, 0.90, within the preset non-inferiority limit of -2.0 cm/year. Height standard deviation (SD) scores were increased in both treatment arms with no acceleration of bone maturation. IGF-I and IGFBP-3 were increased comparably for both treatments. Adverse events showed no clinically relevant differences between treatment groups. Anti-GH antibodies were detected in 3 (3.1%) Valtropin and 1 (2.0%) Humatrope patients and the growth pattern was indistinguishable from the rest of the cohort. The 1-year efficacy and safety profile of Valtropin, a new biosimilar rhGH, are equivalent to the comparator rhGH, Humatrope. Valtropin can be used for the treatment of children with GHD and longer term data will fully establish its efficacy and safety profile.     

Assessing short-statured children for growth hormone deficiency

AIM: To optimize the workup of short-statured children by defining the most appropriate tools for diagnosing growth hormone (GH) deficiency. METHODS: Patients were assigned to prepubertal (n = 113) or pubertal (n = 112, including 25 boys primed with testosterone) age groups. Mean plasma GH concentration during sleep, GH peak after provocative test, and insulin-like growth factor I (IGF-I) were measured in a single evaluation. RESULTS: The mean GH concentration during sleep was more often normal (n = 155) than the GH peak after provocative tests (n = 105) or the IGF-I concentration (n = 88). Prepubertal patients with a normal body mass index (BMI) had mean GH concentrations during sleep that correlated positively with height, growth rate, GH peak after provocative tests, and IGF-I (p < 0.0005 for all) and negatively with the difference between target and patient heights (p = 0.01) and BMI (p < 0.05). Pubertal patients with a normal BMI had a mean GH concentration during sleep that correlated positively with GH after provocative tests (p < 0.0001) and IGF-I (p < 0.005). Mean GH concentration during sleep and IGF-I concentration for boys primed with testosterone were more often normal (n = 23) than the GH peak after provocative tests (n = 14). All 9 patients with pituitary stalk interruption had low IGF-I concentrations; 1 patient had a normal GH peak after provocative test, and 2 patients had normal mean GH concentrations during sleep. CONCLUSIONS: Measuring the GH concentration during sleep and priming boys with pubertal delay can help to exclude idiopathic GH deficiency. Magnetic resonance imaging is needed to exclude anatomic abnormalities when GH and/or IGF-I concentrations are low.     

Growth hormone and neurofibromatosis

Data collected from 102 neurofibromatosis (NF) children with growth hormone (GH) deficiency (GHD) who were receiving GH replacement therapy were reviewed to assess the efficacy and safety of GH therapy in this condition. GH was administered at a mean dose of 0. 18 mg/kg/week. During the 1st year the median height velocity increased significantly from 4.2 cm/year before treatment to 7.1 cm/year, and the median height standard deviation score increased from -2.4 to -1.9. The response to therapy, however, was not as good as that observed in patients with idiopathic GHD. GH therapy did not influence the progression of any of the features of NF, including intracranial tumours, and was not associated with an excess of other adverse events. We conclude that GH treatment of NF patients with GHD is beneficial in terms of improved growth rate and is well tolerated.     

Acromegaly induced by growth hormone replacement therapy

Recombinant human growth hormone (GH) has been shown to be efficacious and safe in the treatment of various growth disorders and GH deficiency. We here report a 61-year-old man with idiopathic hypopituitarism in whom clinically active acromegaly developed. Complete GH deficiency had been diagnosed earlier by arginine stimulation testing, and therapy with recombinant human GH (maintenance dose 2 IU/day) was implemented at the age of 54 years. At presentation, the patient's insulin-like growth factor 1 (IGF-1; 439 ng/ml) and insulin-like growth factor binding protein 3 (4.3 mg/l) levels were highly elevated. Endogenous GH production and pituitary adenoma were excluded. Retrospectively, IGF-1 levels up to 621 ng/ml had been documented (but not appreciated) in the preceding 7 years. Upon GH dose reduction, the IGF-1 serum levels returned to normal, and the patient's clinical status stabilized. No GH receptor polymorphisms were identified in the patient's genomic DNA. This observation demonstrates that the indiscriminate use of recombinant GH bears the risk of active acromegaly, emphasizing the need for long-term patient monitoring programs as integral part of GH therapy.     

Subcutaneous treatment with growth hormone-releasing hormone for short stature

In the present study we report the effects of therapy with growth hormone-releasing factor (1-29)NH2 (GRF) on growth rate, plasma levels of insulin growth factor I (IGF-I) and growth hormone (GH) secretion in 11 children who were selected solely on the basis of their short stature and normal GH secretion on standard provocative tests. All children received GRF for 6 months (5 micrograms/kg body weight subcutaneously) each evening. The 24-hour GH secretory profile was studied before and after 6 months of treatment. Simultaneously, GH secretory responses to single intravenous bolus GRF (1.5 micrograms/kg body weight) were also studied before, during, and 6 months off therapy with GRF(1-29)NH2. Plasma levels of IGF-I were measured before, during (1, 2 and 6 months), and after 6 months off therapy with GRF. Statural growth was measured at 3-month intervals. The peak plasma GH level in response to GRF was 56.04 +/- (SD) 24.46 ng/ml before treatment, and similar results were found after therapy. The 24-hour GH secretory profile did not show differences before, during, and after treatment. Comparably, no differences were found in GH pulse frequency, pulse amplitude, pulse height, pulse increment, pulse area and total area before, and 6 months off therapy with GRF. The increments in serum IGF-I achieved were not significantly different at all intervals studied. All patients increased growth velocities (mean +/- SD, cm/year) in response to GRF therapy. Our results demonstrate that GRF administration was effective in accelerating growth velocity in 11 children without GH deficiency.     

Skeletal dysplasia, growth hormone treatment and body proportion: comparison with other syndromic and non-syndromic short children

Skeletal dysplasias comprise a diverse group of conditions that usually compromise both linear growth and body proportions. It is of theoretical interest to evaluate the effect of GH treatment on linear growth, body proportion and final height in the different skeletal dysplasias. Reported experience of GH treatment in short children with skeletal dysplasia is sparse and often limited to short treatment periods and knowledge of its effects on final height and body proportion is generally lacking. Formal studies are almost all confined to achondroplasia as the most common entity. First-year response is typically a 2-3 cm increase in growth velocity in prepubertal children, or a gain of about 0.5 SDS or less in relative height from a baseline level of -4 to -5 SDS. GH treatment for up to 5 years in achondroplasia can produce a total height gain of about 1 SDS. Apart from achondroplasia, treatment of hypochondroplasia and dyschondrosteosis with GH has been reported in a small number of patients. Long-term data are, however, lacking. Of theoretical interest is that in many syndromic or non-syndromic short-statured children body proportion, i.e. trunk to leg length ratio, does not seem to be dependent on the degree of GH sufficiency and does not seem to be changed by GH treatment. GH treatment, at least in the prepubertal period, does seem to influence degree of disproportion.     

Comparison of growth hormone sleep release and responses to pharmacological tests

The spontaneous release of growth hormone (GH) during nocturnal sleep was studied at age 5-19 years in 44 male and 15 female patients with severe growth retardation (-2.1 to -6.5 SD) among whom 43 were prepubertal and 16 pubertal. Comparison with the results of classical stimulation tests with ornithine, arginine and/or insulin showed good agreement in cases of classical hypopituitarism (n = 14) as in patients who seemed to be endocrinologically normal (n = 27). In 18 patients (31%) there was a discrepancy between sleep release and responses of GH to stimulation test: treatment with hGH was available in only 4 of these children and enhanced sharply their growth rate. It is suggested that a large span of intermediary situations exists between normal GH secretion and complete GH deficiency, deserving a controlled therapeutic trial with hGH.     

Growth hormone treatment in short Japanese children born small for gestational age

Recent reports have shown that high-dose growth hormone (GH) treatment in short children born with small for gestational age (SGA) resulted in a pronounced acceleration of linear growth. We describe the results of multicenter trials of recombinant human GH (rhGH) treatment in short SGA children in Japan. Two clinical studies were performed and the results were combined. Study 1 comprised 104 SGA children and study 2 comprised 61 SGA children. The patients were divided into three groups: group 1 consisted of 20 patients (13 boys and 7 girls) who received rhGH 25 microg/kg per day six or seven times per week in the first year and 50 microg/kg per day in the second year and thereafter; group 2 consisted of 48 patients (28 boys, 20 girls) who received rhGH 45/50 microg/kg per day; group 3 consisted of 44 patients (28 boys, 16 girls) who received 90/100 microg/kg per day. The mean increments in height SDS were 0.46, 0.67 and 0.94 SD in boys and 0.49, 0.79 and 0.93 SD in girls in groups 1, 2 and 3, respectively. The mean increment in height SDS at 2 years in group 3 was significantly greater than that in group 1, but it was not significantly different from that in group 2 in boys and girls. Our data demonstrated that high-dose GH administration significantly improved height velocity and height SDS in short SGA children. Additional studies are necessary to optimize a long-term GH treatment regimen and combined luteinizing hormone releasing hormone analog treatment for final height. Careful observation is also necessary to assess the metabolic effects of high-dose GH, especially on carbohydrate metabolism.     

Early diagnosis and early treatment of growth hormone deficiency

In the past, growth hormone (GH) deficiency has usually been diagnosed too late in dwarfed children, so that substitution therapy was not able to obtain a final height in the normal range for most of them. Complete catch-up of growth in hypopituitary patients needs early diagnosis and early treatment. This requires: (1) that full attention be paid to any insufficiency of length or height increment in infants and young children; (2) that evaluation of GH secretion be performed in spite of the practical difficulties encountered in small patients, and (3) that the interpretation of hormonal measurements be carefully discussed. Though the overall results obtained to date in treating very young GH-deficient children have not been completely satisfactory, it is certain that those whose height was within or near the limits of -2 SD at the onset of treatment maintained a normal height. The relationship of end results with the doses of GH used remains to be investigated. Future results will probably be improved more by earlier diagnosis and by using daily injections than by an increase in the annual dose of GH.     

Influence of growth hormone on accretion of bone mass

Growth hormone (GH) exerts important influences on bone metabolism during lifespan. During childhood, GH is a major determinant of acquisition of bone mass and in adult life, GH partly determines the rate of bone remodelling and therefore influences maintenance of bone mineral density (BMD). Insights into the importance of GH in these respects may be obtained by studies of BMD and indices of bone remodelling in GH deficiency (GHD) of adult-onset and childhood-onset. Adult-onset GHD, usually accompanied by other features of hypopituitarism, may be associated with osteopenia and an increased fracture risk. Postulated mechanisms include GHD and gonadal steroid deficiency of unknown duration; glucocorticoid and thyroxine replacement do not appear to exert a major role. GH replacement in adult-onset GHD results in an early increment in indices of bone remodelling which persists for up to 5 years; BMD increases by 0.5-1.0 SD in males and stabilizes in females over this time period. In adolescents with GHD who traditionally discontinue GH at completion of linear growth, BMD is substantially lower than peak bone mass for a young adult population. Studies addressing the effects of continuation of GH after achievement of final height are currently underway and will provide insights into the possible need to continue GH into adult life. Such studies may confirm a role for GH in promoting continued accrual of bone mass and thereby demonstrate that cessation of GH at achievement of final height, by limiting peak bone mass, may predispose to clinically significant osteoporosis in later life. In addition to the potential importance of GH for achievement of peak bone mass, there may be a superimposed accelerated loss of BMD with advancing age similar to the situation observed in adult-onset GHD. To date, this has been difficult to assess in adult GHD of childhood-onset because the relative contributions of low peak bone mass and increased loss of bone in later life could not be distinguished.     

Final height in children with idiopathic growth hormone deficiency treated with recombinant human growth hormone: the Belgian experience

BACKGROUND: The growth response to recombinant hGH (rhGH) treatment and final height of 61 Belgian children (32 boys) with idiopathic growth hormone deficiency (GHD) were studied. PATIENTS/METHODS: Two patient groups were compared: Group 1 with spontaneous puberty (n = 49), Group 2 with induced puberty (n = 12). The patients were treated with daily subcutaneous injections of rhGH in a dose of 0.5-0.7 IU/kg/week (0.17-0.23 mg/kg/week) from the mean +/- SD age of 11.9 +/- 3.1 years during 5.1 +/- 2.1 years. RESULTS: rhGH treatment induced a doubling of the height velocity during the first year and resulted in a normalisation of height in 53 (87%) patients. Final height was -0.7 +/- 1.1 SDS, being 170.4 +/- 7.2 cm in boys and 158.0 +/- 6.4 cm in girls. Corrected for mid-parental height, final height was 0.0 +/- 1.1 SDS. Ninety-two percent of the patients attained an adult height within the genetically determined target height range. Although height gain during puberty was smaller in the patients with induced puberty (boys: 17.1 +/- 7.0 cm vs. 27.5 +/- 6.6 cm (p < 0.005); girls: 9.6 +/- 7.4 cm vs. 22.2 +/- 6.1 cm (p < 0.005)), no differences in final height after adjustment for mid-parental height were found between patients with spontaneous or induced puberty. CONCLUSIONS: We conclude that patients with idiopathic GHD treated with rhGH administered as daily subcutaneous injections in a dose of 0.5-0.7 IU/kg/week reach their genetic growth potential, resulting in a normalisation of height in the majority of them, irrespective of spontaneous or induced puberty.     

Growth hormone treatment downregulates serum leptin levels in children independent of changes in body mass index

The changes in serum leptin levels during growth hormone (GH) treatment were studied in 27 children, 17 with GH deficiency (GHD), 10 with idiopathic short stature (ISS), and 9 with Prader-Willi syndrome (PWS). Within 1 month of GH treatment, serum leptin levels decreased by 40% in the GHD children (p < 0.01). There was no significant change in serum leptin level in the children with ISS. In children with PWS, the mean serum leptin level decreased by almost 60% after 3 months of treatment (p < 0.001). Thereafter, no further decline was observed in any of the 3 groups. Changes in body composition became evident first after the 3 months of treatment. In the GHD children, the BMI was unchanged while the mean body fat percentage was 2.7% lower after 1 year of GH treatment (p < 0.05). In the ISS children, neither BMI nor body fat percentage were significantly changed during treatment. The PWS children exhibited a significant decrease in BMI after 6 months of GH treatment without any further change during the remaining period of treatment. In this group, the mean body fat percentage decreased from 42 +/- 2.4 to 28 +/- 2.2% after treatment (p < 0.001). The finding that the fall in leptin occurs before changes in body composition become detectable suggests a direct effect of GH on leptin production, metabolism, or clearance.     

Normal progression of testicular size in boys with idiopathic short stature and isolated growth hormone deficiency treated with growth hormone: experience from the KIGS

BACKGROUND: The aim of this retrospective analysis was to evaluate the effects of growth hormone (GH) treatment on testicular development in boys with idiopathic short stature (ISS) and isolated GH deficiency (IGHD) followed in the KIGS (Pharmacia International Growth Database). METHODS: For inclusion in the study, the patients had to have received more than 1 year of prepubertal GH treatment, at least 4 consecutive years of GH treatment in total, and to have attained their final height, defined as a height velocity of less than 2 cm/year. Data on 107 boys in the KIGS database have been analyzed. RESULTS: No significant differences in duration of GH treatment and testicular volume at the start of treatment or at final height were found between the boys with ISS and those with IGHD. The progression of testicular volume in boys with ISS or IGHD during GH treatment did not differ from the reference population. CONCLUSIONS: This analysis shows that GH treatment does not alter testicular growth in boys with ISS or IGHD. However, prospective controlled studies are needed to rule out moderate attenuating or stimulating effects.