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PubMed1993

Standards for ovarian volume in childhood and puberty.

OBJECTIVE: To examine the growth of the ovary and the prevalence of polycystic ovaries in childhood and to compare the ovarian volumes of girls with growth disorders. DESIGN: A retrospective study of ovarian volume measurements made with ultrasound. SETTING: Paediatric Endocrine Outpatient service at The Middlesex Hospital. PATIENTS: The control group consisted of girls with no endocrine defect. The study group consisted of girls with GH insufficiency, treated and untreated; skeletal dysplasia (and no endocrine defect) on a trial of recombinant human GH; and tall stature. METHODS: The prevalence of polycystic appearance ovaries in the control group was noted. Centiles were calculated for the volumes of normal appearance ovaries in the control group (428 scans from 358 girls). Standard deviation scores were calculated for the ovarian volumes in the study groups. RESULTS: There was continuous growth of the ovaries throughout childhood. There was an increase in the prevalence of polycystic ovaries from 6% at 6 years of age, until 26% of the scans showed polycystic ovaries at 15 years of age. The ovarian volume SD score of untreated GH insufficient girls was less than controls but did not achieve statistical significance. It was significantly less than that of GH-insufficient girls on GH, girls with skeletal dysplasia on GH, and girls with tall stature. Tall girls had significantly greater ovarian volume than either of the GH-treated groups. CONCLUSIONS: Growth hormone appears to influence ovarian growth. Most women who have polycystic ovarian appearance develop this appearance during childhood and puberty.

Body Height↗
PubMed1990

Results of long-term growth hormone replacement therapy in children: when and how to treat?

Up to now, the end results of treatment in GH deficiency (GHD) have not been as good as expected. Probably the main cause has been the delay in diagnosing GHD in short children, resulting in a very insufficient height at the onset of puberty. The need for early diagnosis and treatment must be emphasized. This agrees with the well-documented data demonstrating (1) that catch-up growth obtained in any treatable growth disorder has a limited duration, and (2) that the effect of GH replacement, whatever the doses and modes of therapy, is maximal during the first year and wanes during the following years. There are still many questions regarding the appropriate GH replacement dose. The height gain during the first year of treatment has been correlated with the logarithm (decimal or natural) of the dose in several groups of patients receiving GH 3 times/week. The initial dose-response relationship is better with GH 6 times/week. For the following years, no dose/response ratio has been demonstrated, and the final height-to-dose relations are still to be investigated. A dose increase after 2 years or more may improve the growth rate, but also with secondary waning. Thus, long-term prospective dose-response studies are needed. The first period of one such study is presented.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗
PubMed2002

Effect of intratracheal adenoviral vector administration on lung development in newborn rats.

Local overexpression of genes that promote lung defense or repair may be helpful in protecting the immature neonatal lung from injuries, but whether the vectors used to administer these genes affect physiological postnatal lung growth has not been investigated. We explored the effect on alveolarization of E1-deleted Adnull vector (Ad5-LMP-null) given intratracheally to 3-day-old rats. Three Adnull doses were evaluated 10(8), 5 x 10(8), and 10(9) TCID(50). Lung morphometry on day 21 showed significant growth disorders with the two higher doses. With 5 x 10(8) TCID(50), absolute lung volume increased significantly (+16%), as did absolute (+20%) and specific (+32%) alveolar airspace volumes, whereas alveolar surface density decreased by 13% (p < 0.009 for all parameters). Lung inflammation was mild, nonsignificant, and occurred mainly with the highest Adnull dose, indicating that it was unlikely to contribute to our results. Adnull instillation induced a significant#10; decrease in terminal bronchiolar cell proliferation as evaluated by proliferating cell nuclear antigen immunostaining (p = 0.02), as well as a 23% decrease in absolute parenchyma elastic fiber length (p = 0.02). Furthermore, lung tropoelastin mRNA content decreased by 25% (p < 0.02). In conclusion, E1-deleted adenoviral vectors can induce lung growth disorders when instilled into the airways of neonatal rats. Interactions with lung matrix turnover may be the main explanation to these deleterious effects.

Adenovirus E1A Proteins↗
PubMed1987

Physiological assessment of growth hormone secretion in the diagnosis of children with short stature.

Many advances characterize the research into the diagnosis of short stature in children. Increasing evidence shows a continuous spectrum of growth hormone (GH) output among GH-deficient patients and short normal children. Although biosynthetic human GH could theoretically offer the chance of treating most slowly growing children, it is not certain that all short normal children with a poor height velocity could benefit from therapy. Indeed, besides auxological findings, the assessment of GH secretion remains essential in selecting candidates for therapy. In this respect the evaluation of GH secretion by means of tests that can explore the physiological pathways involved in the hormone output appears important. Moreover some clinical evidence suggests that pharmacological stimuli cause the pituitary release of stored GH perhaps unavailable in physiological conditions. Among the classical physiological tests, the exercise test, the standardization of which has been debated, is commonly used in clinical practice. The sleep test, i.e. the evaluation of sleep-associated GH secretion, is the most important. It has no side effects and does not require the administration of exogenous stimuli. Several studies have demonstrated its reliability in diagnosing growth disorders in childhood, mainly if performed with EEG monitoring. Among the new physiological diagnostic approaches the most reliable test is the evaluation of 24-hour GH secretion. Knowledge of the integrated hormone concentrations appears particularly important in studying children who may have more subtle disturbances in GH secretion. These cases show normal GH response to provocative stimuli but show a reduced hormone output over 24 h. Indeed they respond well to human GH treatment.

Adolescent↗
PubMed1989

Pulmonary hypertensive vasculopathy--no indication for corrective operation of isolated ventricular septum defect in babyhood.

The frequency of surgical closure of a ventricular septum defect (VSD) in the first year of life has risen from 10% to 30% in the last seven years in West Germany. Whereas there was a decrease of mortality in older children, mortality has stagnated at 8% for correction at age 12 months or less (early correction). Development of an irreversible pulmonary hypertensive vasculopathy (PHVP) and recurrent heart failure with growth disorders are given as reasons for operation in the first year of life. In the last six years, we have operated on 31 infants for isolated VSD with pulmonary hypertension (PH) and closed the VSD. In approximately equal preoperative pressure in the two ventricles with a pressure ratio of 0.88 +/- 0.16, there was an immediate fall in pressure in the right ventricle with pressure ratios of 0.43 +/- 0.24. Three patients (9.7%) died perioperatively. In the same period, a primary VSD closure was carried out in 120 children even after over 12 months with three deaths (2.5%). Pulmonary tissue removed in this operation did not show any PHVP in four patients (13%), grades 0 to I and I to II in 10 patients each (total 33%) and a PHVP grade II to III in six patients (20%). This PHVP is capable of full regression. An irreversible PHVP does not develop up to the end of the first year of life in isolated VSD with PH, so that the correction can be safely postponed to the beginning of the second year of life provided that recurrent heart failure with growth disorders does not compel earlier correction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

Variability in the urinary excretion of growth hormone in children: a comparison with other urinary proteins.

As a basis for assessment of the clinical validity of urinary GH (uGH) measurements in children, the day-to-day variability in renal handling of GH has been compared with that of albumin, N-acetylglucosaminidase (NAG) and creatinine. Five overnight urine specimens were collected over a 2-week period from 78 healthy children (aged 5-16 years), 20 of normal stature and 58 with growth disorders; ten children were classified as GH-deficient (GHD) and 48 were designated short normal (SN). The variability of excretion of each substance was expressed as a coefficient of variation (C.V.) which was not influenced by expressing the urine results as total mass excreted, concentration, excretion rate or as a ratio to creatinine. There was considerable night-to-night variability in the excretion of all substances (mean C.V. values for all groups: 56% for albumin, 41% for GH, 33% for NAG and 27% for creatinine). No differences were found in the variability of GH excretion between males and females, nor between prepubertal and pubertal subjects. The mean C.V. for uGH excretion ranged from 37% in normal and 35% in SN children to 52% in those with GHD (P < 0.05). Assay variation rather than a change in renal protein handling accounted for the large variations in uGH concentrations of < 5 pg/ml, thus contributing to the high uGH C.V. of the GHD group.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗
PubMed1982

Radioimmunoassay for somatomedin C: comparison with radioreceptor assay in patients with growth-hormone disorders, hypothyroidism, and renal failure.

We raised an antiserum (Tr4) in rabbits against a basic somatomedin C-like peptide preparation. Using high-immunoreactivity somatomedin C tracer, we compared the performance of radioimmunoassays in which we used the Tr4 antiserum and a well-characterized somatomedin C antiserum distributed by the National Pituitary Agency (NPA) with that of the human placental-membrane somatomedin radioreceptor assay (RRA). In their cross reactivity toward various somatomedin-like and unrelated peptides, the two radioimmunoassay methods were almost identical, although NPA antiserum, with about fourfold higher titer than Tr4 antiserum, showed a slightly greater sensitivity for most peptides tested. Radioimmunoassay of acid-ethanol-extracted plasma samples from normal persons and acromegalic, hypopituitary, hypothyroid, and renal-failure patients revealed no analytical differences between the antisera (for 122 samples, r = 0.979 between methods). Somatomedin values for acromegalic and hypopituitary samples showed no overlap with normals. Values for hypothyroid and pre-dialysis renal-failure samples were significantly lower than normal. By comparison, the RRA showed greater cross reactivity toward some somatomedin-like peptides and gave significantly lower values than radioimmunoassay for acromegalic and hypothyroid plasma extracts, and significantly higher value for hypopituitary and renal-failure samples. We conclude that the radioimmunoassay methods clearly are of greater diagnostic value than RRA for clinical somatomedin measurement.

Acromegaly↗
PubMed1986

Determination of insulin-like growth factor-I in normal subjects and in patients with growth hormone disorders by radioimmunoassay using biosynthetic homologous peptide.

A highly sensitive and specific RIA for IGF-I has been developed using recombinant DNA-derived IGF-I of very high purity and specific antiserum to it. This assay system could detect IGF-I at as low concentrations as 20-30 ng/ml. The intra-assay and interassay coefficients of variation at various concentrations of IGF-I were 4.9 to 6.5% and 5.4 to 8.0%, respectively. The recovery rate of pure IGF-I added to plasma was 77.0 +/- 3.7%. The antiserum did not cross-react with porcine insulin, biosynthetic human insulin, hGH, hEGF, the synthetic C-domain of IGF-I or that of IGF-II, but reacted equally with an analog, Thr59-IGF-I. Plasma IGF-I was extracted by the acid-ethanol method before assay to separate IGF-I from its binding protein. When plasma IGF-I was assayed without extraction, the inhibition curves of serial dilution of plasma samples from several individuals were not parallel to the standard curve of IGF-I. The plasma concentration of IGF-I was 147 +/- 49 ng/ml (mean +/- SD) in 156 normal adults aged from 20-59 years. As reported by others, the IGF-I levels were low in cord plasma (41.8 +/- 23.5 ng/ml) and plasma of patients with GH deficiency (64.6 +/- 42.0 ng/ml), while its levels were high in normal children of pubertal ages (12-13 yr, 365 +/- 126 ng/ml) and in patients with active acromegaly (562 +/- 115 ng/ml). This RIA system is a simple and useful method for determining plasma IGF-I in normal and diseased states.

Acromegaly↗
PubMed1993

Disorders of growth hormone resistance in childhood.

This review describes the recent developments in the diagnosis and treatment of states of resistance to growth hormone based mainly on the studies performed on patients with an inborn molecular defect of the growth hormone receptor, ie, Laron syndrome. Use of the polymerase chain reaction technique has facilitated the study of the defect, which in the large majority of patients resides in the extracellular domain of the growth hormone receptor. This recessively transmitted hereditary disease, characterized clinically by dwarfism and obesity and biochemically by high levels of serum human growth hormone accompanied by low serum concentrations of insulin-like growth factor I, is diagnosed mainly in inbred societies of Asian Jews, Arabs, Iranians, Italians, and Spaniards or their descendants. Isolated mutations have been found in many countries all around the world. The recent biosynthesis of insulin-like growth factor I has enabled the successful treatment of these patients, accelerating their growth, reducing their obesity, and normalizing their metabolic abnormalities resultant from the insulin-like growth factor I deficiency. The Pygmies are an inbred population in Africa, Asia, and Oceania who seemingly also have a defect in the growth hormone receptor. Acquired states of growth hormone resistance are also discussed.

Drug Resistance↗
PubMed1997

Anthropometry and body composition in children.

Changes in body fat, fat-free mass and extracellular water occur in many disorders, and during normal growth in children. Thus, body composition is an increasingly important measurement in paediatric clinical practice, and is used for diagnostic purposes, for decisions for treatment and for monitoring improvement. A number of different methods exist for determining body composition in children; however, their use is complicated by the absence of a gold standard and the lack of validity data in children both with and without growth disorders. In this report, validity and usefulness are compared among anthropometric methods and weighted against other techniques used in children. Recent recommendations of a number of expert committees are discussed.

Adipose Tissue↗
PubMed2002

Low amplitude and disorderly spontaneous growth hormone release in obese women with or without polycystic ovary syndrome.

Obesity is associated with considerably reduced plasma GH concentrations, which may contribute to anovulation in (obese) women with polycystic ovary disease (PCOS). This clinical investigation was undertaken to establish whether the GH release process is deranged in obese women with PCOS and, if so, whether the observed anomalies are features of the syndrome or a sequel of body fat accretion. To this end we sampled 24-h plasma GH concentration profiles at 10-min intervals in 15 obese PCOS patients [mean age, 29 yr (range, 20-38); percent body fat, 47 +/- 5.2%], 15 equally obese controls with regular menstrual cycles [age, 34 yr (range, 20-44); percent body fat, 48 +/- 4.9%], and 15 healthy age-matched lean controls [age, 34 yr (range, 21-45); percent body fat, 29 +/- 9.0%]. Compared with lean controls, obese PCOS patients exhibited a greater than 60% reduction in basal and a greater than 75% reduction in pulsatile and total daily GH secretion due to a 2.7-fold attenuation of burst mass and a lesser (1.4-fold) slowing of GH pulse frequency. The mean +/- SEM number of statistically significant GH peaks was 13.9 +/- 1.2/24 h, the endogenous GH half-life was 14.1 +/- 0.4 min, basal GH secretion was 5.0 +/- 0.7 mU/liter.24 h, and total secretion was 61.4 +/- 9.6 mU/liter.24 h in obese women with PCOS. None of these parameters differed from those in the body mass index-matched controls. The approximate entropy ratio was significantly increased in obese women (both PCOS and controls), indicating greater irregularity of the GH release process. Total GH secretion in patients and the two control groups correlated strongly and negatively with percent body fat (r = -0.775; P < 10(-8)). Serum concentrations of IGF-I and IGF-binding protein-3 were higher in patients with PCOS than in obese controls (P = 0.03 and P = 0.02, respectively), but the IGF-1/IGF-binding protein-3 ratio was equivalent in all three study groups. In conclusion, the profoundly reduced and irregular GH release in obese women with PCOS appears to be a corollary of body fat accretion and not of the syndrome per se.

Adult↗