Low insulin, IGF-I and IGFBP-3 levels in children with Prader-Labhart-Willi syndrome

It is well established that insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and insulin are low in growth hormone deficiency, but due to their dependence on nutrition, they are elevated in healthy obese children. As the presence of growth hormone deficiency in Prader-Labhart-Willi syndrome (PWS) is still controversial, we studied insulin, IGF-I and IGFBP-3 levels in 19 children with PWS (age range 0.5–14.6 years). Serum concentrations of insulin (SDS: −0.7±0.9, P=0.01) and IGF-I (SDS: −0.7±0.8,P=0.002) were low, but IGFBP-3 (SDS: −0.3±1.2, P=0.2) was normal compared to normal weight age-matched children. Since children with PWS are typically obese, insulin, IGF-I and IGFBP-3 levels should be compared to normal obese children who present increased levels of these hormones. In comparison to data of healthy obese children reported in the literature, not only IGF-I, but also IGFBP-3 levels are low and fasting insulin levels even very low, suggesting a growth hormone deficiency. Received: 19 November 1997 / Accepted in revised form: 2 March 1998     

Arm span, serum IGF-1 and IGFBP-3 levels as screening parameters for the diagnosis of growth hormone deficiency in patients with myelomeningocele – preliminary data

Short stature is a common problem in patients with myelomeningocele (MMC) and hydrocephalus. We evaluated auxological and laboratory parameters to differentiate short stature due to neurological defect from short stature additionally caused by growth hormone deficiency (GHD). In a group of 38 prepubertal patients with MMC and hydrocephalus aged 3.8–11.0 years, auxological parameters, including arm span and bone age, and serum insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels were measured. Patients with normal supine length (n = 15) had normal arm span. Serum IGF-1 and IGFBP-3 levels were normal (≥ 10th percentile) in 14/15 patients. Twenty-three MMC patients had short stature (height SDS < −2), 11/23 patients had reduced arm span (SDS < −2), and 12/23 had normal arm span. Serum IGF-1 and IGFBP-3 levels were normal in 10/12 of short statured patients with normal arm span, but low (<10th percentile) in those patients with reduced arm span (IGF-1: 8/11 patients, P<0.05; IGFBP-3: 9/11 patients, P<0.005). In 7/11 short statured MMC patients with reduced arm span and low serum IGF-1 and IGFBP-3 levels, growth hormone secretion was investigated. All had a disturbed growth hormone secretion (GHD: n = 4; neurosecretory dysfunction: n = 3). Conclusion Arm span, serum IGF-1 and IGFBP-3 levels are estimated to be appropriate screening parameters for GHD in patients with MMC. Initiating growth hormone therapy should be considered not only according to endocrine findings but also with respect to neurological and orthopaedic anomalies. Received: 27 March 1997 / Accepted: revised form 18 September 1997     

Good growth despite very low levels of insulin-like growth factors

A 12.5-year-old girl presented with short stature. Insulin-like growth factor 1(IGF-I) and insulin- like growth factor binding protein (IGFBP-3) were below the 0.1 percentile. Growth hormone provocation tests disclosed normal responses to l-arginine and insulin-induced hypoglycaemia. A huge benign mesenteric cyst was discovered by abdominal ultrasound and completely removed. Subsequently, the girl showed a marked catch-up growth; however, IGF-I and IGFBP-3 remained below the 0.1 percentile. Conclusion These observations imply that growth may take place even with very low levels of insulin-like growth factors. The interpretation of low IGF-I and IGFBP-3 levels in short children still requires good clinical judgement and basic knowledge of their biological action. Received: 24 September 1997 / Accepted in revised form: 16 March 1998     

Auxological and endocrinological evaluation of children with hydrocephalus and /or meningomyelocele

Short stature and precocious puberty are frequently found in children with hydrocephalus and/or meningomyelocele (MMC). However, aetiology and pathophysiology have not been well characterized. In this study, 108 patients aged between 3 and 17.8 years were evaluated. Growth was documented on the basis of arm span measurements. Short arm span was found in 47 (43.5%) children with hydrocephalus and/or MMC. Mean arm span was −2.0 standard deviation score (SDS) (−6.4 to +0.8) in 43 girls and −1.4 SDS (−5.6 to +1.3) in 65 boys. When growth deficiency (more than −2.0 SDS) was diagnosed by arm span measurement (24 F, 23 M) or when early sexual maturation was found (6 F, 9 M), endocrine evaluation followed. Levels of serum insulin-like growth factor and insulin-like growth factor binding protein-3 were low in 22 of 62 (33.8%) patients. In 9 of 62 (14.5%) patients, insulin-like growth factor-1 and insulin-like growth factor binding protein-3 levels were found to be increased. Growth hormone (GH) deficiency was diagnosed by means of two different stimulation tests (clonidine and arginine) in 7 of 62 (11.3%) patients. In another 3 of 62 (4.8%) children, 12 h night time GH sampling showed low maximum peak levels and decreased area under the curve values, suggesting neurosecretory GH dysfunction. Precocious puberty or early onset of puberty associated with elevated luteinising hormone and follicle stimulating hormone concentrations after stimulation with luteinising hormone releasing hormone was found in 13 of 108 (12.0%) patients (age 7–9 years). Free thyroxine was abnormally low in 2 of 62 (3.2%) patients. Cortisol was within the normal range in all 62 (100%) tested patients. Conclusions Short arm span in children with hydrocephalus and/or MMC is frequently accompanied by GH deficiency or neurosecretory GH dysfunction. Early onset of puberty is another frequent finding. Both hormonal disorders may be the consequence of damage to the hypothalamus or the pituitary gland caused by increased intracerebral pressure or increased mass of cerebrospinal fluid. Received: 31 May 1996 / Accepted: 21 October 1996     

Growth, puberty and hypothalamic-pituitary function in children with suprasellar arachnoid cyst

A suprasellar arachnoid cyst may cause disorders of growth, puberty and hypothalamic-pituitary function, due to the proximity of the cyst to the hypothalamic-pituitary area. A total of 30 patients (17 boys) with cyst diagnosed at 4.3 ± 1 years were routinely evaluated at 5.4 ± 1 years; 24 of them had one or multiple cyst derivations. Some 23 cases had an abnormal height, weight or puberty: short (<−2SD, 5 cases) or tall (>2SD, 10 cases) stature, overweight (body mass index, BMI, >2SD, 6 cases), central precocious puberty (10 cases) and/or no progression of pubertal development (3 cases). The growth hormone (GH) peaks after pharmacological stimulation test were low (<10 μg/l) in 16 patients, confirmed by a second evaluation in 8/11 of them. The plasma free thyroxine was low in five patients, prolactin was high in two and the cortisol and concomitant plasma and urinary osmolalities were normal. BMI was correlated negatively with the GH peaks (r=−0.37, P < 0.01) and positively with the plasma leptin concentrations (r=0.55, P < 0.01). The plasma fasting insulin concentrations were also correlated negatively with the GH peaks (r=−0.55, P < 0.02) and positively with the plasma insulin-like growth factor I concentrations (r=0.64, P < 0.002). The adult height (12 cases) was at 4SD in 1 and <−2SD in 4 patients, two of whom had precocious puberty untreated with gonadotropin releasing hormone (GnRH) analogue, and two had untreated GH deficiency. The adult height of those treated was normal. One girl had primary amenorrhoea and two boys had low plasma testosterone, despite a normal gonadotropin response to a GnRH test. Conclusion Suprasellar arachnoid cysts may cause deficiencies of growth hormone and thyrotropin, stimulation of the hypothalamic-pituitary-gonadal axis, tall stature and/or overweight. These last two disorders may be due to hyperinsulinism, itself due to suprasellar arachnoid cyst. Received: 5 May 1999 / Accepted: 28 October 1999     

Short stature in children with an apparently normal male phenotype can be caused by 45,X/46,XY mosaicism and is susceptible to growth hormone treatment

Girls with unexplained short stature are routinely screened for the presence of Ullrich-Turner syndrome by clinical examination, laboratory tests, and karyotyping. In this study, we performed chromosomal analysis in boys to explore the role of 45,X/46,XY mosaicism for short stature in males. Short-term effects of growth hormone treatment in male 45,X/46,XY individuals were compared retrospectively to those in female patients. We report six boys with a normal-appearing male phenotype and 45,X/46,XY mosaicism, four of whom were diagnosed postnatally because of short stature. Two boys were diagnosed prenatally by amniocentesis. Five boys were short and were treated with growth hormone (0.04–0.05 mg/kg per day) in analogy to girls with Ullrich-Turner syndrome and gonadal dysgenesis. With the exception of one patient in whom treatment was initiated only at the age of 14.6 years, the male patients with 45,X/46,XY mosaicism responded to short-term growth hormone treatment similarly to females with an increasing height SDS. Conclusion:45,X/46,XY mosaicism remains undetected in some short boys because this group is not routinely karyotyped. We recommend chromosomal analysis of boys with otherwise unexplained short stature who are short for their families. Growth hormone treatment should be offered to short boys with 45,X/46,XY mosaicism and a predicted adult height below the mid-parental range within clinical trials.Abbreviations FSH follicle stimulation hormone - GH growth hormone - IGF-I insulin-like growth factor 1 - IGFBP-3 insulin-like growth factor binding protein-3 - LH luteinising hormone - MPH mid-parental height     

Growth hormone therapy

Growth hormone (GH) therapy has revolutionized treatment of children with growth hormone deficiency (GHD). Improved height outcome with final height in the target height range has been achieved in these children. Identification of Creutzfeldt-Jakob disease, a deadly prion mediated disorder, in recipients of pituitary GH accelerated the transition from pituitary derived GH to recombinant GH. Once daily subcutaneous administration of the freeze-dried preparation at evening is the recommended mode of GH therapy. Studies have led to use of higher dose of GH for improving height outcome (0.33 mg/kg/week or 0.14 IU/kg/day) albeit at a significantly high cost. Growth velocity increases from 3–4 cm/year before therapy to 10–12 cm/year during the first two years of therapy and is maintained at 7–8 cm/year after a period of two years. Close follow-up with regular clinical and laboratory monitoring is essential for achieving a desirable height outcome. A theoretical unlimited supply has led to wide spread use of GH in a variety of disorders other than GHD. Initially started in children with Turner syndrome, GH has now been used in chronic renal failure, idiopathic short stature and intrauterine growth restriction besides a wide array of newly emerging indications.     

The role of recombinant insulin-like growth factor I in the treatment of the short child

PURPOSE OF REVIEW: Commercial preparations of recombinant human insulin-like growth factor I became available in 2005. Off-label use has been promoted because of the paucity of patients having approved indications; I review the background and rationale for such use. RECENT FINDINGS: Attempts to identify growth hormone unresponsiveness in children with idiopathic short stature have been nonproductive. Treatment with insulin-like growth factor I for unequivocal growth hormone insensitivity improves but does not correct growth failure, in contrast to the typical experience with growth hormone replacement of growth hormone deficiency. This emphasizes the importance of direct effects of growth hormone at the growth plate, which cannot be duplicated by administration of recombinant insulin-like growth factor I. Adverse effects testify to the more than adequate delivery of administered recombinant human insulin-like growth factor I to other tissues, including lymphoid hyperplasia, coarsening of the facies, and increased body fat. SUMMARY: In view of the risk profile, the limited ability of endocrine insulin-like growth factor I to restore normal growth, and the suppression of endogenous growth hormone (and therefore local effects on growth) that occurs with insulin-like growth factor I administration, the use of recombinant insulin-like growth factor I should be limited to those with well-documented growth hormone unresponsiveness and severe short stature.     

Effect of growth hormone therapy on bone metabolism of growth hormone deficient children

The effects of human growth hormone (hGH) therapy on biochemical markers of bone metabolism were studied in 17 children (10 boys and 7girls, aged 3.7–13.1 years old) with idiopathic GH deficiency, before and 1 and 6 months after GH therapy (0.5–0.7 IU/kg weekly, SC). Serum levels of calcium, phosphate, alkaline phosphatase, osteocalcin, parathyroid hormone, 1,25 dihydroxyvitamin D, insulin-like growth factor I (IGF-I) and renal phosphate per 100 ml glomerular filtrate (TPO₄/GFR) were assessed. During therapy with hGH, a significant decrease of serum calcium levels and increases of phosphate, osteocalcin, parathyroid hormone 1,25 dihydroxyvitamin D and IGF-I were observed. TPO₄/GFR was also significantly increased. Growth response (increment in HV) was positively related with changes in alkaline phosphatase and IGF-I levels after 6 months of hGH therapy. There was also a significant positive correlation between increment in HV and increment in TPO₄/GFR after 1 month of GH therapy, whereas no correlation between HV and changes in osteocalcin levels was found. Conclusion GH treatment significantly influences mineral metabolism and the measurement of TPO₄/GFR after 1 month of GH therapy may serve as a useful predictor of growth response to hGH therapy in GH-deficient children. Received: 16 August 1996 / Accepted: 5 February 1997     

Growth hormone secretion, puberty and adult height after cranial irradiation with 18 Gy for leukaemia

The dose of prophylactic cranial irradiation given to patients for acute lymphoblastic leukaemia has been decreased from 24 to 18 Gy, but the beneficial effect of this decrease on growth is controversial. This study compares the growth hormone (GH) secretion and growth of 35 patients (20 boys) given 18 Gy at 3.7 ± 0.3 (SE) years, and routinely evaluated 5.4 ± 0.4 years after irradiation to define the indications for GH treatment in these patients. Of these, 63% had a low GH peak (<10 μg/l) after one (22 cases) or two (17 cases) stimulation tests. The plasma concentrations of insulin-like growth factor I and its GH-dependent binding protein were normal for age in all but two cases. The height changes between irradiation and evaluation were correlated with the GH peaks (P < 0.03) and were concordant, except in patients with early puberty. This occurred in 16 patients including all 12 girls irradiated before 4 years of age. A significant (P < 0.03) reduction in height (SD) between irradiation and adult height occurred in untreated GH-deficient patients (−1 ± 0.3, n = 6), but not in GH-deficient patients given GH (−0.6 ± 0.3, n = 8) or in those with normal GH peak (−0.4 ± 0.3, n = 7). Conclusion In children irradiated for acute lymphoblastic leukaemia, GH deficiency is frequent after 18 Gy but its impact on adult height is smaller than after higher doses. We suggest that the indications for gonadotropin releasing hormone analogue therapy should be broad in patients with early or rapidly progressing puberty and those for GH therapy in those patients with a below average constitutional height before irradiation. Received: 17 November 1997 / Accepted: 9 February 1998     

Growth hormone treatment increases CO2 response, ventilation and central inspiratory drive in children with Prader-Willi syndrome

We studied whether the beneficial effects of growth hormone (GH) treatment on growth and body composition in PWS are accompanied by an improvement in respiratory function. We measured resting ventilation, airway occlusion pressure (P_0.1) and ventilatory response to CO₂ in nine children, aged 7–14 years, before and 6–9 months after the start of GH treatment. During GH treatment, resting ventilation increased by 26%, P_0.1 by 72% and the response to CO₂ by 65% (P < 0.002, <0.04 and <0.02, respectively). This observed increase in ventilatory output was not correlated to changes in body mass index. Conclusion Treatment of children with Prader-Willi syndrome (PWS) seems to have a stimulatory effect on central respiratory structures. The observed increase in ventilation and inspiratory drive may contribute to the improved activity level reported by parents of PWS children during growth hormone therapy. Received: 28 April 1998 / Accepted: 6 April 1999     

一个Laron 综合征家系患者临床特点和生长激素受体基因突变分析

Laron 综合征是一种常染色体隐性遗传病,生长激素受体（GHR）基因缺陷是导致Laron 综合征的主要病因。Laron 综合征主要临床特征为生后严重的生长落后伴特殊面容,血生化特点为高生长激素(GH)、低胰岛素样生长因子- (IGF-I) 和低胰岛素样生长因子结合蛋白- (IGFBP-3)。该研究报道一家系2例Laron 综合征患者的临床特点及GHR基因突变。这两个病人为同胞姐弟。弟弟8岁,身高80.0 cm (-8.2 SDS),姐姐11岁,身高96.6 cm (-6.8 SDS)。他们出生体重和身长无特殊,自生后出现生长落后,身高明显落后于同龄正常儿童,并均呈现了典型Laron 综合征外貌特征：身材矮、肥胖、前额突出、大眼睛、塌鼻梁、头发稀软。这两个病人空腹血清GH值均明显高于正常儿童,空腹血清IGF-I明显低于同年龄同性别正常儿童,血浆IGFBP-3和生长激素结合蛋白（GHBP）低于检测线。其中1例（8岁男孩）胰岛素和可乐定刺激后GH峰值大于350 ng/mL,给予重组人生长激素治疗1年,身高由治疗前的80.0 cm 增加至83.3 cm。GHR基因序列测定结果显示2例患者均存在外显子4上第65位氨基酸的纯合突变S65H(TCA → CCA),为新发现的突变。Laron 综合征患者存在特殊的面貌特征,结合血GH、IGF-I、IGFBP-3和GHBP测定可以明确诊断。GHR基因外显子4上S65H突变可能是这两位Laron 综合征患者的致病原因。［中国当代儿科杂志,2007,9（4）：335-338］     

Comparison of growth hormone releasing hormone therapy and growth hormone therapy in growth hormone deficiency

Seven children with growth hormone deficiency of hypothalamic origin responded to an i.v. bolus of growth hormone releasing hormone (GHRH) (1–29)-NH2 with a mean serum increase of 10.7 ng/ml growth hormone (GH) (range 2.5–29.3 ng/ml). Continuous s.c. administration of GHRH of 4–6 g/kg twice daily for at least 6 months did not improve the growth rate in five of the patients. One patient increased his growth rate from 1.9 to 3.8 cm/year and another from 3.5 to 8.2 cm/year; however, the growth rate of the latter patient then decreased to 5.4 cm/year. When treatment was changed to recombinant human growth hormone (rhGH) in a dose of 2 U/m² daily, given s.c. at bedtime, the growth rate improved in all patients to a mean of 8.5 cm/year (range: 6.2 to 14.6). Presently GHRH cannot be recommended for the routine therapy of children with growth hormone deficiency since a single daily dose of rhGH produced catch-up growth which GHRH therapy did not.Abbreviations GH growth hormone - GHD growth hormone deficiency - GHRH growth hormone releasing hormone - hGH human growth hormone - rhGH recombinant human growth hormone - SM C/IGF I somatomedin C/insulin-like growth factor I On the occasion of the 85th birthday of Prof. Dr.Dr.h.c. mult. Adolf Butenandt     

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

ABSTRACT. 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.     

Magnetic resonance images of 91 children with different causes of short stature: pituitary size reflects growth hormone secretion

In order to validate an association between pituitary size and severity of growth hormone deficiency (GHD) we evaluated the magnetic resonance images (MRI) of 107 children with different causes of short stature. Ninety-one MRIs were evaluable (64 male, 27 female; age: 9.1 ± 3.9 years). The levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3), and tests of GH stimulation and spontaneous secretion, led to the following sub-groups: severe isolated GHD (SIGHD) (GH < 7 ng/ml) (n = 21); partial, isolated GHD (GH 7–10 ng/ml) (n = 22); multiple pituitary hormone deficiency (MPHD) (n = 13); neurosecretory dysfunction (n = 10); non-classifiable diagnosis (NC) (n = 13); idiopathic short stature (n = 9); and intra-uterine growth retardation (n = 3). Pituitary height (PHT) was measured and hypoplasia was assumed when PHT was <−2 SDS. An ectopic posterior pituitary with missing stalk and a hypoplastic anterior pituitary was present in 12 (57%) SIGHD cases, 12 (92%) MPHD cases and 1 patient from the NC group. An isolated hypoplastic anterior pituitary was observed in 15%−33% of the other groups. PHT (mm; mean, SD) in MPHD (1.7 ± 0.5) was lower than in SIGHD (2.7 ± 1.0, P < 0.05), with PHT of both groups being lower than in all the other groups (3.8 ± 0.9, P < 0.0001). PHT SDS correlates with IGF-I SDS (r = 0.48, P < 0.0001), IGFBP-3 SDS (r = 0.46, P < 0.0001) and the highest peaks in tests of GH stimulation and GH spontaneous secretion (r = 0.36, P < 0.0001). In contrast to all the other groups, no correlation with age was observed in MPHD and SIGHD. Breech delivery was recorded in up to 26% of patients in all seven groups. Surprisingly, only 1 out of 23 patients with an ectopic posterior pituitary was born by breech delivery, suggesting that ectopia of the posterior lobe is not necessarily related to breech delivery. Conclusion PHT is significantly correlated with GH secretion in several types of short stature. Patients with␣ectopic posterior pituitary, missing stalk and hypoplastic␣anterior pituitary either suffer from SIGHD or MPHD, and this anatomical defect is not necessarily related to breech delivery. Received: 1 December 1996 and in revised form: 8 February 1997 / Accepted: 18 February 1997     

Screening for growth hormone deficiency using urinary growth hormone measurement

The diagnostic approach in growth hormone deficiency (GHD) is complicated. Two or more provocative tests are essential for definitive diagnosis of GHD. However, such testing cannot be carried out routinely on all subjects with short stature because of the need for hospitalization and blood sampling. A simple screening method for GHD would be of great value. Human growth hormone (hGH) levels were measured in the early morning urine of 192 children aged 7–15 years with height 2.0 s.d. below the mean for their ages. Sixty-eight subjects were selected because they showed a urinary hGH level < 10 ng/g creatinine. They were further examined in terms of bone age and plasma insulin-like growth factor (IGF-I) levels. In 30 subjects, the ratio of bone age: chronological age was < 0.8 and/or plasma IGF-I level was < 0.7 U/mL. Finally 24 of these subjects were examined with provocative tests and other endocrinological tests. Eleven subjects proved to have poor growth hormone secretion and one subject was diagnosed as having Turner syndrome. In conclusion, 11 patients with GHD were diagnosed from 192 children with short stature using urinary hGH measurement as the first screening method. These findings suggests that urinary hGH measurement could be a useful and simple method for detecting GHD.     

Correlation between pituitary growth hormone reserve and degree of growth failure in children with short stature

The correlation between a releasable pituitary growth hormone (GH) pool and degree of growth failure was examined in 30 children with GH deficiency (group I) and 19 children with normal short stature (group II). Based on the responsiveness of GH to GH-releasing hormone (GHRH), group I, with low GH responses (below 7 ng/ml) to both insulin and arginine, was classified into three subgroups; I_a (peak value less than 10 ng/ml, n=19), I_b (10–20 ng/ml, n=5) and I_c (above 20 ng/ml, n=6). Group II, with a GH response above 10 ng/ml to either insulin or arginine, was also divided into II_a (below 20 ng/ml, n=5) and II_b (above 20 ng/ml, n=14). Body length and growth velocity in I_a and I_b were significantly reduced vs I_c; bone age in I_a was retarded vs I_c; plasma somatomedin C (Sm-C) levels in I_a and I_b were decreased vs I_c, who had almost normal levels (0.90±0.55 U/ml). The incidence of other combined pituitary hormone deficiencies and previous perinatal distress was definitely high in I_a and I_b, but zero in I_c. In group II also, body length and growth velocity were significantly decreased in II_a vs II_b (P<0.01). These results indicate that [1] the pituitary reserve of GH estimated by GHRH is a good reflection of the degree of growth failure in GH-deficient children as well as in those of normal short stature, [2] hypothalamic GHRH deficiency tends to have a milder effect on growth retardation than pituitary GH deficiency, and [3] normal short children with a diminished GH reserve may be potential candidates for the GH treatment.Abbreviations ACTH adrenocorticotropin - LH luteinizing hormone - LH-RH luteinizing hormone-releasing hormone - GH growth hormone - GHRH growth hormone-releasing hormone - Sm-C somatomedin C - TRH thyrotropin-releasing hormone - TSH thyrotropin     

Magnetic resonance and the diagnosis of short stature of hypothalamic-hypophyseal origin

Magnetic resonance imaging was performed in 23 patients with short stature (7 had multiple pituitary hormone defect, 11 had isolated growth hormone deficiency and 5 had normal variant short stature) to investigate if there is a relation between magnetic resonance findings and results of endocrine tests. Magnetic resonance imaging of patients with multiple pituitary hormone deficiency or with serious isolated growth hormone deficiency (growth hormone < 3 μg/l) revealed an interrupted pituitary stalk and ectopic neurohypophysis or a mass. In patients with less serious isolated growth hormone deficiency (growth hormone > 3 μg/l) or with normal variant short stature, the technique revealed a normal or hypoplastic hypophysis. Magnetic resonance appears to be a useful second-level diagnostic tool in defining the type of alteration in growth defects of endocrine origin.     

Growth Hormone Therapy of Short Stature1

ABSTRACT. Considerable progress has been made in the diagnosis and treatment of growth hormone-related short stature. Knowledge about growth hormone releasing factor (GRF) and somatomedin C has provided the possibility of distinguishing between hypothalamic and pituitary growth hormone deficiency and growth hormone resistance. It has been shown that treatment with GRF may stimulate growth in certain cases of growth hormone deficiency. Recombinant DNA techniques may, in the near future, provide sufficient amounts of GRF, growth hormone and possibly somatomedin C for clinical use. At present, many countries have prohibited the use of human pituitary growth hormone due to a possible risk of transmission of Creutzfeldt-Jakob disease. It has become increasingly clear that several short children without classical growth hormone deficiency, may increase their growth velocity during growth hormone treatment. There are many medical, psychological, ethical and economical implications involved in the extended treatment of children with short stature. It is necessary to maintain a restricted approach towards the treatment of children with short stature, and such treatment should be prescribed and controlled by a limited number of well-trained paediatric endocrinologists. This article reviews some of the present knowledge in this rapid developing field of paediatric endocrinology.     

A rational approach to short stature: Focus on use and abuse of growth hormone

The abundant supply of recombinant growth hormone has raised interesting possibilities of several new applications. While supplementation of the missing hormone in patients with growth hormone deficiency is still the undisputed primary indication for its use, there is now convincing evidence of its usefulness in the therapy of short stature due to Turner syndrome and pre-transplant chronic renal failure in childhood. Numerous studies on patients with other causes of short stature have failed to show any significant benefit in final adult height. Social pressures notwithstanding, it is still premature to advocate the use of this expensive therapy for indications other than the three stated above especially since our understanding of potential long-term complications from such treatment is far from complete.