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B Klinger

Publications and source records attributed to B Klinger.

At least 19 recordsLinked to original sources
PubMed2000

Comparison of the growth-promoting effects of insulin-like growth factor I and growth hormone in the early years of life.

AIMS: Four infants with isolated growth hormone deficiency (IGHD) and five with Laron syndrome (LS) were studied. Birth length ranged from -2.5 to -4.5 SDS in both groups. RESULTS: Untreated IGHD children decreased in length from -2.5 to -5.2 SDS at 1 y and to -5.7 SDS at 2 y. Human growth hormone (hGH) treatment (0.07 U/kg/d) increased height by 1.2-2.4 SDS in 3 y. Untreated children with LS decreased in length from -3.5 to -6.5 SDS. Insulin-like growth factor (IGF)-I treatment (150-200 microg/kg/d) in 3 LS patients increased height by 0.5-1.5 SDS in 3 y. All untreated infants had borderline or below normal head circumferences. Both treatments induced a rapid catch-up in head size. In the two untreated LS patients, head circumference remained subnormal. CONCLUSIONS: Despite similar birth length, infants with IGHD responded better to hGH in terms of linear growth than did infants with LS to IGF-I, whereas the response in brain growth was similar.

Age Factors↗
PubMed1998

Development of hyperandrogenism during treatment with insulin-like growth factor-I (IGF-I) in female patients with Laron syndrome.

OBJECTIVE: Patients with Laron syndrome (LS) can now be treated with recombinant IGF-I. We describe the development of androgenization during IGF-I treatment of female LS patients. PATIENTS: Six female patients with LS--two clinically prepubertal (11.6 and 13.8 years of age) and four young adults (30 to 39 years old)--underwent long-term replacement treatment with recombinant IGF-I. The daily doses were 150 micrograms/kg/day by subcutaneous (s.c.) injection in the girls and 120 micrograms/kg/day in the adult women. METHODS: Testosterone, delta 4-androstenedione, LH, FSH, insulin and IGF-I were determined by radioimmunoassay. Blood samples were obtained after an overnight fast before the IGF-I injection. Serum IGF-I was also determined 4 hours after the s.c. injections. RESULTS: During IGF-I treatment, four out of the six patients (two girls and two adults) developed progressive clinical symptoms and signs of hyperandrogenism (oligo/amenorrhoea and acne). Laboratory determinations showed a significant elevation in serum testosterone, delta 4-androstenedione and LH/FSH ratio. The hyperandrogenism occurred concomitantly with an increase in IGF-I serum and a decrease in serum insulin concentrations. Reduction in IGF-I dose or interruption in IGF-I treatment restored androgen levels to normal values. At the same time, the acne and oligomenorrhoea resolved. CONCLUSIONS: Overdosage of IGF-I can lead to androgenization, a previously undescribed undesirable effect of IGF-I. Long-term IGF-I treatment necessitates progressive adjustment of the IGF-I dose to avoid overtreatment.

Adolescent↗
PubMed1998

Effect of insulin-like growth factor-I treatment on serum androgens and testicular and penile size in males with Laron syndrome (primary growth hormone resistance).

Serum gonadotrophins. androgens, insulin and insulin-like growth factor-I (IGF-I) were determined before and during long-term treatment with recombinant IGF-I of seven males with Laron syndrome, and the changes correlated with changes in testicular volume and penile size. The subjects were four boys below the age of 5, two boys aged 10 and 14 but prepubertal and one 28-year-old fully sexually developed adult. IGF-I was administered by a once daily subcutaneous injection of 150 microg/kg per day to the boys and 120 microg/kg per day to the adult patient. In the very young boys no change in serum gonadotrophins, androgens, gonads or genitals was registered. In the two older boys and the adult patient, there was a progressive rise in luteinizing hormone, follicle-stimulating hormone and testosterone. Concomitantly, there was an increase in size of the testes and penile length. The two boys started puberty. As very high serum IGF-I levels were registered in the adult patient, the daily dose was progressively decreased to 70 microg/kg per day. Stopping the IGF-I administration in this patient, according to the protocol, led to a return to pretreatment serum levels and testicular and penile size. This report shows for the first time a direct effect of IGF-I on sex hormones and sex organs in the male.

Adolescent↗
PubMed1997

Muscle force and endurance in untreated and human growth hormone or insulin-like growth factor-I-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.

Adolescent↗
PubMed1997

Growth hormone increases and insulin-like growth factor-I decreases circulating lipoprotein(a)

BACKGROUND: Elevated serum lipoprotein(a) (Lp(a)) is a strong risk factor for coronary artery disease (CAD). Genetic factors appear to account for the major variance in Lp(a) levels but the contribution hormones make in modulating Lp(a) levels is not yet clear. In the present investigation we determined the effects of human growth hormone (hGH) and insulin-like growth factor-I (IGF-I) on circulating Lp(a). METHODS: Four groups of patients were studied. Group a: adults with GH deficiency (n = 7) treated with hGH (0.05 U/kg/day, s.c.); group b: girls with Turner syndrome (n = 7) treated with hGH (0.1 U/kg/day, s.c.); group c: prepubertal boys with idiopathic short stature (n = 6) treated with the GH secretagogue (GHRP) hexarelin (60 micrograms t.i.d. intranasally); group d: Laron syndrome patients (n = 10) treated with IGF-I (100-200 micrograms/kg/day, s.c.). Following overnight fasting, serum was sampled before the initiation of treatment and during 6-9 months treatment. RESULTS: Serum IGF-I rose significantly in all the subjects in all four groups. In the first three groups in which IGF-I was elevated by exogenous or endogenous GH stimulation, serum Lp(a) increased significantly (119 +/- 35%, P < 0.01; 126 +/- 44%, P < 0.05; 102 +/- 29%, P < 0.01 for groups a, b, and c respectively). By contrast, serum Lp(a) levels decreased in group d to whom exogenous IGF-I was administered (-66 +/- 5%, P < 0.001). The differential effect of endogenous vs exogenous IGF-I on serum Lp(a) paralleled the behaviour of serum insulin. Insulin was significantly increased in all the subjects receiving hGH or GHRP (65.2 +/- 31%, P = 0.109; 93.7 +/- 53%, P = 0.062; 353.8 +/- 52.7%, P < 0.01 for groups a, b, and c respectively) whereas insulin levels were reduced following exogenous administration of IGF-I (-34.1 +/- 9.1%, P < 0.01). CONCLUSIONS: We conclude that long-term GH treatment increases and IGF-I decreases circulating levels of Lp(a). These findings may have clinical relevance in view of the increasing use of hGH in children and adults and the role of Lp(a) as a CAD risk factor.

Adult↗
PubMed1997

Long-term effects of insulin-like growth factor (IGF)-I on serum IGF-I, IGF-binding protein-3 and acid labile subunit in Laron syndrome patients with normal growth hormone binding protein.

A minority of patients with Laron syndrome have normal serum GH binding protein (GHBP), indicating that the defect is elsewhere than in the extracellular domain of the GH receptor. We have evaluated the effect of long-term IGF-I treatment on serum IGF-binding protein (IGFBP)-3 and the acid-labile subunit (ALS) in three sibling with Laron syndrome caused by a GH post-receptor defect and with normal GHBP. The children (a boy aged 3 years, a girl aged 4 years and a boy aged 10 years) were treated by daily s.c. injection of IGF-I in a dose of 150 micrograms/kg. IGFBP-3 was measured by RIA and Western ligand blotting, ALS by RIA. Based values of IGFBP-3 and ALS were low. During IGF-I treatment, the IGFBP-3 concentrations in the girl gradually increased, whereas in the boys there was a 60% decrease during the first week, followed by gradual increase towards baseline. The ALS concentrations followed a similar pattern. We conclude that IGF-I treatment induces and initial suppression and then an increase in the IGFBP-3 and ALS concentrations, confirming data from animal experiments that IGFBP-3 synthesis is not solely under GH control. The differences in responsiveness between the female and male siblings may reflect genetic differences, or lower circulating concentrations of IGF-I in the boys compared with the girl.

Carrier Proteins↗
PubMed1997

Specific detection of his-tagged proteins with recombinant anti-His tag scFv-phosphatase or scFv-phage fusions.

Using a cell-bound immunogen, we have generated a monoclonal antibody, 3D5, that recognizes carboxy-terminal oligo-histidine tags (His tags) on a wide variety of proteins. From this monoclonal antibody, we have generated a single-chain fragment of the variable domains (scFv), a dimeric scFv-alkaline phosphatase fusion and an oligovalent scFv-display phage. The antibody in its various formats is an effective tool used in fluorescence-activated cell sorting analysis, the BIAcore method, Western blots and enzyme-linked immunosorbent assay (ELISA). Western blots and ELISAs can be developed directly by using crude extracts of E.coli cells that produce the scFv-alkaline phosphatase fusion, thus providing an inexhaustable and convenient supply of detection reagent. Alternatively, oligovalent scFv-displaying phage can be used directly from culture supernatants for this purpose. The dissociation constants, KD of the peptide KGGHHHHH (KD = 4 x 10(-7) M) and of imidazole (KD = 4 x 10(-4) M) were determined. Molecular modeling of the Fv fragment suggests the occurrence of two salt bridges between the protonated histidine side chains of the peptide and the acidic groups in the antibody, explaining why the antibody or the substrate may be eluted under mildly basic conditions.

Antibodies, Monoclonal↗
PubMed1996

Insulin-like growth factor-I decreases serum lipoprotein (a) during long-term treatment of patients with Laron syndrome.

An increased circulating level of lipoprotein(a) [Lp(a)] is a well-recognized risk factor for coronary artery disease. While much remains to be understood about its regulation and physiological functions, we explored the effect of recombinant insulin-like growth factor-I (IGF-I) administration on circulating Lp(a) levels in 10 Laron syndrome (LS) patients (five children and five adults) with inherited IGF-I deficiency. There was no relationship between pretreatment or posttreatment Lp(a) levels and age and sex of the patients. With IGF-I treatment for 6 to 12 months, there was a significant reduction in Lp(a) (65.7% +/- 15.5%, P < .0001) from the pretreatment level of 76 +/- 45 mg/L to the posttreatment level of 29 +/- 26 mg/L. This decrease was dosage-dependent on the IGF-I administered (r = .685, F = 0.708, P = .029) and correlated more strongly with the dosage ratio of the end to the beginning of treatment (r = .78, F = 12.23, P = .008). The higher the IGF-I dose and the higher the dose ratio, the greater the Lp(a) decrease and the lower the Lp(a) at the end of treatment. In conclusion, we observed a dose-dependent relationship between IGF-I administration and Lp(a) reduction in patients with LS. Further studies are needed to elucidate the mechanism of the effect, but our findings suggest a possible metabolic link between these two and shed more light on the regulation of apolipoprotein(a) [apo(a)] expression. It could also open an avenue for additional therapeutic usage of IGF-I.

Adolescent↗
PubMed1996

Insulin-like growth factor-I raises serum procollagen levels in children and adults with Laron syndrome.

OBJECTIVE: Recombinant IGF-I is now available for the treatment of GH insensitivity (Laron syndrome). We have determined the effects of IGF-I on soft connective tissue and bone metabolism in a group of patients with this disorder. PATIENTS AND DESIGN: Thirteen patients with Laron syndrome (LS) (8 children and 5 adults) were included in the study. The children with LS were treated with IGF-I for 3 years with daily doses of 150-200 micrograms/kg. The adult LS patients were treated for 9 months with daily doses of 50-120 micrograms/kg. Blood samples for procollagens were collected before, during and at the end of IGF-I treatment. MEASUREMENTS: Serum levels of the carboxyterminal propeptide of type I procollagen (PICP), the aminoterminal propeptide of type III procollagen (PIIINP) and of the pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) were determined before and during IGF-I administration. RESULTS: Untreated patients with LS had lower than normal serum levels of PICP and PIIINP for age. IGF-I treatment increased significantly the PIIINP levels in children from 7.2 +/- 2.8 (SD) to 12.5 +/- 2.2 micrograms/l (P < 0.001), and in adults from 2.7 +/- 1.0 to 8.4 +/- 3.6 micrograms/l (P < 0.001); serum PICP increased from 243 +/- 123 to 384 +/- 190 micrograms/l (P < 0.087) in children, and in adults from 43.4 +/- 8.1 to 135.8 +/- 41.9 micrograms/l (P < 0.001). ICTP levels in children increased from 9.7 +/- 3.7 to 14.3 +/- 5.9 micrograms/l (P < 0.001) and in adult patients levels increased from 3.6 +/- 0.9 to 5.5 +/- 2.2 micrograms/l (P < 0.001) during treatment and returned to basal values after stopping IGF-I administration. CONCLUSIONS: Low procollagen levels in untreated Laron syndrome patients and their rise during replacement therapy with IGF-I provide evidence that IGF-I plays an important role in bone and soft connective tissue metabolism and that serum procollagen may serve as a marker to reflect some of the biochemical changes induced by IGF-I in connective tissue in the initial periods of treatment.

Adolescent↗
PubMed1996

Desensitization from long-term intranasal treatment with hexarelin does not interfere with the biological effects of this growth hormone-releasing peptide in short children.

A clinical, prospective experiment was carried out to determine whether long-term intranasal administration of the growth hormone-releasing peptide hexarelin (His-D-2-methyl-Trp-Ala-Trp-D-Phe -Lys-NH2) affects pituitary growth hormone secretion. Hexarelin (60 micrograms/kg t.i.d.) was administered to seven prepubertal constitutionally short children (mean age +/- SD = 7.6 +/- 2.4 years). Serum human growth hormone (hGH) response to an intranasal (20 micrograms/kg) and i.v. (1 mircogram/kg) bolus of hexarelin before, during and after 6-10 months of treatment was measured. The mean ( +/- SD) peak rise of hGH to the intranasal bolus before treatment was 70.6 +/- 28.2 mU/l. After 7 days of hexarelin treatment, mean peak values dropped to 34.1 +/- 15.7 mU/l (p < 0.002) and thereafter remained constant for 6 months of treatment at 37.5 +/- 10.3 mU/l (p < 0.03). The pretreatment peak to th i.v. hexarelin bolus was 84.8 +/- 52.5 mU/l, and at the end of the treatment period it was 19.8 +/- 10.9 mU/l (p < 0.05). Three months after stopping treatment the mean ( +/- SD) hGH response rose to 42.1 +/- 4.7 mU/l (p < 0.005). Growth velocity increased from 5.3 +/- 0.9 cm/year (before treatment) to 7.4 +/- 1.6 cm/year at 6-10 months of treatment (p < 0.005). In conclusion, teh partial suppression of pituitary hGH responsiveness to long-term intranasal hexarelin treatment, probably due to desensitization, does not affect the observed increase in growth velocity.

Administration, Intranasal↗
PubMed1995

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.

Blood Glucose↗
PubMed1995

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-2-methyl-Trp-Ala-Trp-D-Phe-Lys- NH2). It is active by intravenous, oral and intranasal administration in animals and man. The aim of this study was to find out whether long-term administration of this peptide would promote growth in short children. DESIGN AND PATIENTS: Intranasal hexarelin was administered in a dose of 60 micrograms/kg thrice daily to 8 prepubertal short children aged 4-11.6 years for periods of up to 8 months. RESULTS: Hexarelin treatment stimulated insulin-like growth factor-I (IGF-I) secretion raising the level from 10.4 +/- 3.9 (SD) to 14.1 +/- 4.6 nmol/l (P < 0.004). The rise in IGF-I led to a significant increase in the mean (+/- SD) linear growth velocity from 5.3 +/- 0.8 to 8.3 +/- 1.7 cm/year (P < 0.0001). There was also a significant decrease in skinfold thickness despite increase in body weight and an increase in head circumference. Additional findings were a rise in serum phosphate from 1.5 +/- 0.1 to 1.8 +/- 0.1 mmol/l (P < 0.004) and of alkaline phosphatase from 219 +/- 74 to 261 +/- 75 U/l (P < 0.05). CONCLUSIONS: The long-term GH/IGF-I stimulating, anabolic and growth promoting effects achieved by intranasal administration of this hexapeptide, seemingly without undesirable side-effects, suggests clinical potential for this new class of drugs.

Administration, Intranasal↗
PubMed1994

Renal function in Laron syndrome patients treated by insulin-like growth factor-I.

Eight children with Laron syndrome (5 males, 3 females) aged 3-14.5 years received daily subcutaneous injections of 150 micrograms/kg recombinant insulin-like growth factor-I (IGF-I) for 5 months. The children were examined weekly for the 1st month and then once monthly. At each visit, overnight fasting blood was drawn for serum IGF-I and blood chemistry measurements and a 24-h urine collection was performed for the determination of calcium, phosphorus, creatinine and nitrogen. The main effects related to kidney function were: an initial weight gain with a mild transitory reduction in the urinary volume, an increase in serum electrolyte concentrations and a decrease in urinary electrolyte excretion. The lower than normal mean (+/- SEM) basal creatinine clearance (76.7 +/- 15.8 ml/min per 1.73 m2) increased towards the normal range during treatment to 124.9 +/- 13 ml/min per 1.73 m2, with a mean increment of 73.4 +/- 28% (P < 0.02) from basal values after 2 months of treatment, without changes in the serum creatinine. Initially an increase in blood urea nitrogen was observed together with a reduction in urinary nitrogen excretion. During the IGF-I therapy the urinary calcium excretion increased from 0.7 +/- 0.2 nmol/day to 1.5 +/- 0.3 nmol/day and the tubular reabsorption of phosphate increased from 1.24 +/- 0.06 to more than 1.38 +/- 0.04 nmol/l (P < 0.002), resulting in a significant increase in serum phosphate levels from 1.51 +/- 0.06 to more than 1.63 +/- 0.04 nmol/l (P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

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 post-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. PATIENTS AND DESIGN: Five patients (1 male, 4 females) aged 28-40 years were treated during 9 months by daily administration of IGF-I (120 micrograms/kg), and followed for 6 months after its discontinuation. METHODS: At each visit, a complete physical examination was performed and blood was drawn for biochemical and hormone determinations. Twenty-four-hour urinary samples were collected at various intervals during treatment. Bone densitometry was performed before and after 6-9 months of therapy. RESULTS: The main findings were a reduction in subscapular skinfold thickness (from 27.5 +/- 1.4 (mean +/- SEM) to 19.5 +/- 1.0 mm; P < 0.002), a decrease in total cholesterol (from 6.78 +/- 0.28 (mean +/- SEM) to 5.80 +/- 0.36 mmol/l) and in LDL cholesterol (from 4.86 +/- 0.23 to 3.76 +/- 0.35 mmol/l), an increase in creatinine clearance (from 71.2 +/- 8.4 to 86.8 +/- 4.3 ml/min/1.73 m2, P < 0.04), an increase in phosphate reabsorption (from 0.89 +/- 0.06 to 1.14 +/- 0.06 mmol%; P < 0.02) leading to an increase in serum phosphate (from 1.08 +/- 0.06 to 1.27 +/- 0.03 mmol/l; P < 0.03), a rise in alkaline phosphatase (from 80.8 +/- 5.0 to 100.7 +/- 7.0 U/l) and in procollagen I-PICP (from 44.2 +/- 4.0 to 171.0 +/- 19.2 micrograms/l; P < 0.0001) and in procollagen III-PIIINP (from 2.68 +/- 0.45 to 10.10 +/- 1.4 micrograms/l; P < 0.005). There was a transient retention of water, sodium and chloride. Pretreatment serum IGFBP-3 levels were low, but increased progressively during treatment. This permitted a reduction in the IGF-I dose. There were no adverse effects other than pain and slight erythema at the injection site during the first weeks of treatment. All the anthropometric and metabolic changes reversed upon discontinuation of IGF-I. CONCLUSIONS: IGF-I treatment is beneficial in adults, as well as in children, with resistance to GH.

Adult↗
PubMed1994

Comparative effects of GH, IGF-I and insulin on serum sex hormone binding globulin.

OBJECTIVE: The serum level of sex hormone binding globulin (SHBG) changes inversely with that of both insulin and insulin-like growth factor (IGF-I), during several nutritional conditions, as well as in response to GH treatment. However, with exogenous IGF-I administration, endogenous IGF-I increases, while insulin decreases. In order to study the separate roles of these hormones in controlling SHBG metabolism, we compared SHBG levels in patients treated with IGF-I and GH. DESIGN AND PATIENTS: Serum levels of IGF-I, insulin and SHBG were measured before and during the treatment of patients with IGF-I or GH. Blood samples were drawn in the fasting state, prior to and during therapy, 24 hours after drug administration. Sixteen children and adults with Laron syndrome (LS) received daily s.c. injections of IGF-I (120-150 micrograms/kg) for up to 5 months. Three adults with isolated GH deficiency (IGHD) received daily s.c. injections of GH (0.03-0.06 U/kg) for 16 months. Two groups of nine prepubertal children with constitutional short stature (CSS) received GH (0.1 U/kg/day) for 3 months. MEASUREMENTS: Serum levels of insulin and acid extractable IGF-I were determined by RIA, and that of SHBG by IRMA. RESULTS: Basal insulin and SHBG levels were within normal range in the LS, IGHD and CSS patients. IGF-I levels were low in LS and IGHD patients, and normal in the CSS children. The mean peak response to chronic therapy was as follows: in LS patients, IGF-I administration decreased insulin levels to 62%, and increased SHBG levels by 64% above basal values. Chronic GH therapy in IGHD caused a marked rise in both IGF-I levels (473%), and insulin levels (96%), and a gradual decline of SHBG to 75% of the basal concentration. In GH treated CSS patients, serum IGF-I peaked at 80% and insulin levels at 102% above the respective basal levels, while SHBG decreased to 83% after 5 days of treatment. CONCLUSION: The results obtained in Laron syndrome, isolated GH deficiency and constitutional short stature patients treated with IGF-I or GH, indicate that serum insulin had consistently an inverse relation with the levels of circulating SHBG. No relation was found between IGF-I and SHBG levels.

Adult↗
PubMed1994

Growth hormone releasing activity by intranasal administration of a synthetic hexapeptide (hexarelin).

OBJECTIVE: Hexarelin is a new synthetic growth hormone releasing peptide. We have tested the efficacy of intranasal (i.n.) administration of hexarelin to stimulate plasma GH and have compared this to the intravenous (i.v.) administration of the peptide. PATIENTS: Ten children with familial short stature (FSS) aged 5.5-15.5 years and two known GH deficient patients aged 24 and 28 years without GH treatment. METHODS: All 12 subjects were submitted to i.v. (1 microgram/kg) and i.n. (20 micrograms/kg) hexarelin tests with a one-week interval between tests. Blood samples for GH, TSH, fT4 and T3 were obtained at 0, 15, 30, 60, 90 and 120 minutes. The hormone determinations were made by standard radio-immunoassays (RIA). RESULTS: Both the i.n. and i.v. administration of hexarelin induced a large GH response, the mean (+/- SD) being 72.2 +/- 35.5 mU/l for the i.n. test and 79.6 +/- 53.0 mU/l for the i.v. test. The peak GH in the i.v. test occurred at 15-30 minutes and in the i.n. test between 30 and 60 minutes. The GH deficient patients showed no GH response in either test. Plasma TSH decreased in the FSS children from a mean (+/- SD) of 1.0 +/- 0.26 to 0.64 +/- 0.2 mU/l (P < 0.005) during the i.n. test and from 1.0 +/- 0.3 to 0.7 +/- 0.3 mU/l (P < 0.05) during the i.v. test. In the isolated GH deficient patient, plasma TSH decreased from 1.06 +/- 0.38 mU/l to 0.86 +/- 0.17 during the i.v. test and from 1.60 +/- 0.01 to 1.11 +/- 0.06 mU/l during the i.n. test. There were no significant changes in plasma fT4 or T3 in any of the tests. CONCLUSIONS: The synthetic hexapeptide hexarelin is a potent pituitary GH stimulator when administered intranasally. The GH response was similar to that observed after intravenous hexarelin. Simultaneously, there was a significant decrease in plasma TSH but the concentrations remained in the normal range. These findings appear to be of theoretical and practical relevance to the investigation and management of short children.

Administration, Intranasal↗