sermorelin and Dwarfism--Pituitary

Growth hormone releasing factor (GRF) is one of two main releasing hormones which control pituitary hGH production and release. This activity is retained even when the length of the GRF polypeptide is reduced to the 29 N-terminal residues. This 29-residue polypeptide has been chemically synthesized, and testing in healthy volunteers elicited secretion of hGH to a maximum level of about 40 ng/ml. In a trial of children with various disorders, the maximum hGH response was reached within 60 minutes; those children with hGH deficiency showed much lower responses than those with other disorders not related to hGH deficiency. The frequency of false-positive tests was low, and it is proposed that GRF testing could provide a useful additional tool in the diagnosis of hGH deficiency.

Topics: Child; Clinical Trials as Topic; Diagnostic Errors; Dwarfism, Pituitary; Female; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Hypothalamus; Male; Peptide Fragments; Pituitary Gland; Sermorelin

18 prepubertal growth-hormone (GH)-deficient children were treated with twice-daily subcutaneous injections of a growth-hormone-releasing hormone analogue, GHRH (1-29) NH2. In 12 of the children the height velocity rose on GHRH treatment, and 8 were judged to have shown a worthwhile response to therapy in that their height velocities during the first 6 months of treatment increased by greater than 2 cm/yr (range 2.7-11.2 cm/yr). These 8 children have now been treated for 6 to 18 months and their increase in height velocity has been maintained. In the 14 patients who had previously received human GH (hGH) height velocity on hGH correlated with that on GHRH. 4 of these patients showed growth deceleration with GHRH, for unknown reasons. A pretreatment peak serum GH response of above 30 mU/l during an intravenous GHRH test was predictive of a good growth response to GHRH but a lower peak did not preclude a growth response. There was no consistent evidence of a priming or desensitisation effect of therapy on the GH responses to GHRH. Although anti-GHRH antibodies developed in 14 patients, these did not seem to have adverse effects on either growth or the GH responses to GHRH. GHRH (1-29) NH2 therapy is an alternative to conventional hGH in the treatment of some GH-deficient children. Ideal dose regimens need to be established.

Topics: Adolescent; Antibodies; Body Height; Child; Drug Evaluation; Dwarfism, Pituitary; Female; Growth; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Injections, Subcutaneous; Insulin-Like Growth Factor I; Male; Radioimmunoassay; Sermorelin; Time Factors

A good response after an intravenous bolus of GRF-1-29 NH2 in patients with hypopituitary dwarfism localities the site of the GH-deficiency in the hypothalamus (GRF deficiency). These patients could be treated with GH and GRF. Never the less some patients with hypothalamic responses after TRH don't respond after GRF. Probably these non responders need GRF in pulsatile or prolonged administration and T4 substitution before and during the test if TSH is also deficient. At least some cases without GRF response can be accepted as pure pituitary only GH would be effective.

Topics: Adolescent; Adult; Child; Child, Preschool; Diagnosis, Differential; Dwarfism, Pituitary; Female; Gonadotropin-Releasing Hormone; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Hypopituitarism; Hypothalamic Diseases; Hypothalamo-Hypophyseal System; Male; Peptide Fragments; Secretory Rate; Sermorelin; Thyrotropin-Releasing Hormone