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Nocturnal pulsatile growth hormone releasing hormone treatment in growth hormone deficiency
Insights
Pulsatile growth hormone-releasing hormone (GHRH) effectively stimulated GH secretion and improved growth velocity in some children with GH deficiency. Optimal GHRH dosage and administration require further study.
Area of Science:
- Pediatric Endocrinology
- Hormone Therapy
Background:
- Growth hormone (GH) deficiency in children impacts growth.
- Growth hormone-releasing hormone (GHRH) stimulates GH release from the pituitary.
Purpose of the Study:
- To evaluate the efficacy of pulsatile GHRH1-40 administration in prepubertal children with GH deficiency.
- To assess the impact of different GHRH dosages on GH secretion and growth velocity.
Main Methods:
- Five prepubertal children with GH deficiency received subcutaneous GHRH1-40 at 1 mcg/kg/pulse for 3 months, then 2 mcg/kg/pulse for 6 months.
- 24-hour GH profiles were measured before treatment; nocturnal profiles were monitored serially.
- Pituitary responsiveness to intravenous GHRH was assessed before treatment and at 3 and 6 months.
Main Results:
- Three of five children showed pulsatile GH secretion and increased growth velocity, from 3.7 cm/year to 5.5 cm/year (3 months) and 7.2 cm/year (9 months).
- One child responded only at the higher GHRH dose, while one child did not respond.
- GH secretion augmented with time and higher GHRH dosage, indicating a self-priming effect.
Conclusions:
- Pulsatile GHRH1-40 administration can effectively induce GH secretion and accelerate growth in some children with idiopathic GH deficiency.
- The optimal dose and administration strategy for GHRH in pediatric GH deficiency require further investigation.
Abstract:
We have treated five GH-deficient prepubertal children (4 M, 1 F) with GH releasing hormone 1-40 (GHRH1-40) in two dosage regimens over 9 months. Profiles of serum GH concentrations were obtained over 24 hours before treatment and nocturnal profiles were obtained serially throughout the study. GHRH was administered subcutaneously at night for four pulses using 1 microgram/kg/pulse in the first 3 months and 2 micrograms/kg/pulse for a further 6 months. All subjects demonstrated pituitary responsiveness to i.v. GHRH before treatment and at 3 and 6 months. GH secretion was induced in a pulsatile fashion in response to subcutaneous GHRH in three children from the first night of treatment. A self priming effect to successive GHRH pulses was evident and the response augmented with time and with the higher dose regimen. The growth velocity of these three children increased from a mean of 3.7 cm/year (range 3.7-3.8) before treatment to 5.5 cm/year (range 4.1-7.2) over the first 3 months and to 7.2 cm/year (range 4.8-9.2) over the following 6 months. In one subject entrainment of GH secretion to GHRH did not occur until the higher dose regimen and this was associated with a modest increase in growth velocity. One subject did not respond to treatment. Pulsatile administration of GHRH1-40 is effective in inducing GH secretion and promoting growth acceleration in some children with idiopathic GH deficiency. The optimal dose and mode of administration of GHRH have yet to be established.