GH/IGF-I axis in familial short stature
4. Shalet S.M., Toogood A., Rahim A., Brennan B.M. The di-
agnosis of growth hormone deficiency in children and
adults. Endocr. Rev. 1998, 19: 203-223.
may show enhanced spontaneous and stimulated GH
secretion and this seems contradictory with the pres-
ence of IGF-I levels overlapping with those in NHC. In
fact, there is agreement that IGF-I is the best marker
of GH status (12, 29-33) though IGF-I synthesis and
release are also under the important influence of the
nutritional status (34-36).
5. GH Research Society. Consensus guidelines for the diag-
nosis and treatment of growth hormone (GH) deficiency
in childhood and adolescence: summary statement of the
GH Research Society. J. Clin. Endocrinol. Metab. 2000, 85:
3990-3993.
To explain the uncoupling between GH and IGF-I se-
cretion in children with FSS, a slight reduction in pe-
ripheral GH sensitivity could be hypothesized. In fact,
there is already evidence showing that in a subgroup
of children with ISS the pathophysiological mecha-
nism underlying short stature is likely to include reduc-
tion in peripheral sensitivity to GH (17, 18, 20). Thus,
in our present study IGF-I levels in FSS could have
been maintained normal as an effect of enhanced GH
secretion needed to overcome a slight impairment
of peripheral GH sensitivity. This hypothesis could be
confirmed only by molecular evaluation (37, 38).
Independently of pathophysiological mechanisms,
our present findings further confirm that, testing
with GHRH+ARG distinguishes hypopituitaric chil-
dren with organic GHD from children with normal
growth. However, FSS children as well as children
with GHNSD (23) are not distinguished by NHC.
This evidence agrees with previous studies (4, 21,
27) indicating that single testing with GHRH+ARG
reliably evaluates the pituitary GH releasable pool
but normal GH response to this test does not rule
out the existence of GH insufficiency.
6. Hopwood N.J., Hintz R.L., Gertner J.M. et al. Growth re-
sponse of non-growth hormone deficient children with
marked short stature during three years of growth hor-
mone therapy. J. Pediatr. 1993, 123: 215-222.
7. McCoughey E.S., Mulligan J., Voss L.D., Betts P.R.
Randomised trial of growth hormone in short normal girls.
Lancet 1998, 351: 940-944.
8. Hintz R.L., Attie K.M., Baptista J., Roche A., for the
Genentech Collaborative Group. Effect of growth hormone
treatment on adult height of children with idiopathic short
stature. N. Engl. J. Med. 1999, 340: 502-507.
9. Johnston L.B., Savage M.O. Partial growth hormone insen-
sitivity. J. Pediatr. Endocrinol. Metab. 1999, 12: 251-257.
10. Ranke M.B. The Kabi Pharmacia International Growth
Study; aetiology classification list with comments. Acta
Paediatr. Scand. 1991, 379: 55-57.
11. Ranke M.B. Towards a consensus on the definition of id-
iopathic short stature. Horm. Res. 1996, 45: 64-66.
12. Underwood L.E., Van Wik J.J. Normal and aberrant
growth. In: Wilson J.D., Forster D.W. (Eds.), Williams text-
book of endocrinology, ed. 8. W.B. Saunders, Philadelphia,
p. 1079-1183, 1992.
13. Rosenfeld R.L., Cuttler L. Somatic growth and maturation.
In: De Groot L.J., Jameson J.L. Endocrinology. ed. 4, p.
477-502, 2001.
In conclusion, this study shows that FSS is character-
ized by enhanced secretory capacity of somatotroph
cells but IGF-I levels overlap with those in NHC; this
evidence fits well with the hypothesis that slight pe-
ripheral GH resistance could play a role in the patho-
genesis of some forms of ISS and FSS.
14. Kamp G.A., Wit J.M. High-dose growth hormone therapy
in idiopathic short stature. Horm. Res. 1998, 49: 67-72.
15. Kelnar C.J.H., Albertsson-Wikland K., Hintz R.L., Ranke
M.B., Rosenfeld R.G. on behalf of the Faculty. Should we
treat children with idiopathic short stature? Horm. Res.
1999, 52: 150-157.
ACKNOWLEDGEMENTS
16. Rudman D., Kutner M.H., Blackston R.D., Jansen R.D.,
Patterson J.H. Normal variant short stature: subclassifica-
tion based on responses to exogenous human growth hor-
mone. J. Clin. Endocrinol. Metab. 1979, 39: 92-99.
This study was supported by a grant from University of Turin and
SMEM Foundation (Turin).
17. Lesage C., Walker J., Landier F. Chatelain P., Chaussain
J.L., Bougneres P.F. Near normalization of adolescent
height with growth hormone therapy in very short children
without growth hormone deficiency. J. Pediatr. 1991, 119:
29-34.
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