Serum ghrelin concentrations are increased in children with growth hormone insensitivity and decrease during long-term insulinlike growth factor-I treatment.

Abstract

BACKGROUND:

Ghrelin increases food intake, body weight, and growth hormone (GH) secretion. Serum concentrations of ghrelin are low in obese hyperinsulinemic persons, are reduced by infusion of insulin into normal-weight subjects, and are increased in underweight hypoinsulinemic patients with anorexia nervosa. Laron syndrome is an autosomal recessive disorder of GH insensitivity that results in decreased insulinlike growth factor-I (IGF-I) synthesis and growth failure. These patients have elevated GH levels, excess adipose tissue, and are insulin resistant. Because IGF-I has insulinlike actions and patients with GH insensitivity syndrome (GHIS) exhibit excess adiposity, we sought to determine whether ghrelin levels were elevated in these patients and potentially regulated by IGF-I replacement.

METHODS:

Thirteen children with GHIS and 20 normal control children matched for age, sex, and body mass index underwent complete physical examination and a fasting blood draw at baseline. The GHIS subjects then underwent follow-up fasting blood draws during therapy with human recombinant IGF-I (80-120 mug/kg, given subcutaneously twice daily). Fasting glucose, insulin, and IGF-I concentrations were measured at the time of collection. Fasting total ghrelin levels were measured on stored serum samples.

RESULTS:

The GHIS subjects had 2-fold higher fasting ghrelin levels (2926 +/- 1869 pg/mL) compared with the normal control children (1492 +/- 493 pg/mL; P = 0.009), and mean ghrelin values were reduced 56% during 6.4 +/- 0.2 years of IGF-I replacement (P < 0.05).

CONCLUSIONS:

Growth hormone resistance and low IGF-I levels are associated with elevated ghrelin levels, which may potentiate GH secretion and adiposity in these children. Suppression of ghrelin during IGF-I treatment suggests a novel mechanism potentially regulating ghrelin levels.

• Authors: Aysin Uckun-Kitapci, Andrea M Haqq, Jonathan Q Purnell, Kenneth Newcomb, Hakan Gulkesen, Louis E Underwood
• Journal: Journal of investigative medicine : the official publication of the American Federation for Clinical Research (J Investig Med) Vol. 56 Issue 1 Pg. 26-31 (Jan 2008) ISSN: 1081-5589 [Print] England
• PMID: 18317425 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Ghrelin
• Recombinant Proteins
• Human Growth Hormone
• Insulin-Like Growth Factor I

Topics

• Adolescent
• Biomarkers (blood)
• Child
• Child, Preschool
• Disease Progression
• Female
• Follow-Up Studies
• Ghrelin (blood, drug effects)
• Growth Disorders
• Human Growth Hormone (deficiency)
• Humans
• Insulin-Like Growth Factor I (therapeutic use)
• Male
• Recombinant Proteins
• Time Factors
• Treatment Outcome