B. Klinger

Effects of insulin-like growth factor on linear growth, head circumference, and body fat in patients with Laron-type dwarfism

Patients with Laron-type dwarfism are clinically indistinguishable from those with isolated growth hormone (GH) deficiency, yet have high circulating GH concentrations associated with an inability to generate endogenous insulin-like growth factor I (IGF-I). Biosynthetic IGF-I was administered subcutaneously once daily for 3 to 10 months to 5 children with Laron-type dwarfism aged 3.3 to 14.5 years. There was a rapid stimulation of linear growth in body limbs, with a striking increase in head circumference, increased body weight, and a reduction in subcutaneous fat. Administration of IGF-I to patients with Laron-type dwarfism seems to have a beneficial effect on growth similar to that observed with long-term administration of GH in children with GH deficiency.

EFFECT OF ACUTE ADMINISTRATION OF INSULIN-LIKE GROWTH FACTOR I IN PATIENTS WITH LARON-TYPE DWARFISM

Biosynthetic insulin-type growth factor I (IGF-I) was given as an intravenous bolus of 75 micrograms/kg to 9 patients with Laron-type dwarfism. Rapid onset of hypoglycaemia (-45% of basal level) was associated with a reduction in plasma insulin (-55% of basal level); thus, the lack of growth hormone receptors in this condition does not apply to IGF-I receptors and post-receptor pathways. Long-term treatment may therefore be beneficial in Laron-type dwarfism.

Biochemical and hormonal changes induced by one week of administration of rIGF-I to patients with Laron type dwarfism.

Summary. objective The purpose of this investigation was to evaluate the effectiveness of short‐term administration of recombipant bfosynthetfc IGF‐I on patients with an hereditary inability to generate this hormone.

Intranasal administration of the GHRP hexarelin accelerates growth in short children

OBJECTIVE Hexarelin is a recently synthesized small growth hormone releasing peptide (GHRP) (His‐D‐methyl‐Trp‐Ala‐Trp‐D‐Phe‐Lys‐NH2). It Is actlve by intra‐venous, oral and intranasal administration In animals and man. The aim of this study was to find out whether longterm administration of this peptlde would promote growth In short chlldren.

Body Fat in Laron Syndrome Patients: Effect of Insulin-Like Growth Factor I Treatment

Changes in body fat mass were studied in 25 untreated patients with Laron syndrome from childhood into adulthood. It was found that these patients, characterized by marked dwarfism, high plasma hGH and low serum insulin-like growth factor I (IGF-I), develop progressive and marked obesity and have a tendency for elevated serum cholesterol levels. Long-term treatment of 8 children and 5 adults with this syndrome with IGF-I (50-150 micrograms/kg/day s.c.) resulted in a significant decrease in subcutaneous fat in all patients and a lowering of the serum cholesterol and triglycerides, mainly in the adults. As in Laron syndrome the GH receptors are inactive, it is hypothesized that IGF-I exerts a direct effect on adipose tissue metabolism.

Laron Syndrome: Clinical Features, Molecular Pathology and Treatment

Primary growth hormone (GH) insensitivity (Laron syndrome) is a hereditary disease due to polymorphic defects in the GH receptor, or in the postreceptor mechanisms, leading to an inability to generate IGF-1. The clinical features and biochemical profiles are indistinguishable from isolated GH deficiency. A diagnostic feature is the lack of rise of serum IGF-1 in response to GH. In most patients growth hormone binding protein is low. Treatment of children with Laron syndrome by biosynthetic IGF-1 accelerates linear growth velocity and head circumference, reduces body fat, and stimulates kidney function.

Carbohydrate metabolism in primary growth hormone resistance (Laron syndrome) before and during insulin-like growth factor-I treatment

Among 43 patients with Laron syndrome followed in our clinic, we were able to study the carbohydrate metabolism from infancy into adult age in 30 patients. During infancy, fasting blood glucose levels were in the hypoglycemic range (mean +/- SD, 3.5 +/- 1.2 mmol/L) and increased at the end of a delayed puberty to 4.6 +/- 0.6 mmol/L. Fasting plasma insulin was higher than expected for concomitant glucose levels, and several of the 20 patients who underwent an oral glucose tolerance test (OGTT) had glucose intolerance and relatively high insulin levels. In adult patients, insulinopenia developed and one 38-year-old patient developed non-insulin-dependent diabetes mellitus (NIDDM) with subsequent need for insulin therapy. Continuous insulin-like growth factor-I (IGF-I) treatment of a pubertal patient with glucose intolerance and hyperinsulinemia normalized both responses. In conclusion, long-term IGF-I deficiency leads to insulin resistance, which is reversed by exogenous IGF-I administration.

IGF-I treatment of adult patients with Laron syndrome: preliminary results.

OBJECTIVE Laron syndrome is a genetic disease due to a defect in the GH receptor or in the pod‐receptor mechanism which leads to an inability to generate IGF‐I. Biosynthetic IGF‐I treatment given to dwarfed children with this syndrome, produced a significant acceleration of growth velocity and reduction in obesity. In view of the known metabolic disturbances in untreated adult patients, the present clinical trial was performed to define the usefulness of IGF‐I treatment in LS adults.

IGF binding protein 3 in patients with Laron type dwarfism: effect of exogenous rIGF‐I

objective The aim of the study was to investigate the serum levels of IGFBP‐3, the major IGF‐I binding protein, in patients with Laron type dwarfism (LTD) before and after IGF‐I treatment

Muscle Force and Endurance in Untreated and Human Growth Hormone or Insulin-Like Growth Factor-l-Treated Patients with Growth Hormone Deficiency or Laron Syndrome

Muscle force and endurance of four muscle groups (biceps, triceps, hamstrings and quadriceps) were measured by a computerized device in three groups: (A) 4 boys with isolated growth hormone deficiencies (IGHD) examined before at 10 and 24 months of hGH treatment; (B) 5 children (2 F, 3 M) with Laron syndrome were examined 3.5-4 years after initiation of insulin-like growth factor-I (IGF-I) treatment, and (C) comprised 8 untreated adults (5 F, 3 M) with Laron syndrome. For each patient, 2 matched controls, by age, sex, physical activity and height below the 50th percentile, were examined. GH- or IGF-I-deficient patients before treatment revealed reduced muscle force and endurance. GH treatment (0.6 U/kg/week) restored muscle force and endurance, progressively, mainly in the boys with puberty. Three to 4 years of IGF-I treatment (150 micrograms/kg/day) in patients with Laron syndrome proved to have a weaker effect than GH in restoring muscle force. The difference in effectiveness between hGH and IGF-I in restoring muscle force may be due to either the more marked muscle underdevelopment in Laron syndrome patients than in patients with IGHD or a difference in action potential between the two hormones.