Serum levels of somatomedin (SM)/insulin-like growth factor (IGF) and IGF carrier (IGF CP) have been determined in 49 patients with Cushing's syndrome before and/or after treatment and in 11 subjects under glucocorticoid therapy.Serum samples were gel filtered in acetic acid in order to separate IGFs from their carriers. IGF content was measured by a competitive protein-binding assay using the specific IGF CP produced by rat liver in culture and human IGF ([ 125 I]IGF I as tracer and a partially purified IGF preparation as standard). IGF CP concentration was assessed in terms of IGF CP binding to labeled IGF, compared to a reference IGF CP preparation obtained from human serum. Results are expressed in comparison with a pool of normal adult serum arbitrarily assigned values of 1 U IGF and 1 U IGF CP per milliliter.The mean IGF level for 39 untreated patients with Cushing's syndrome was 0.99 ± 0.06 (SEM) U/ml, which does not differ from normal adult values (1.05 ± 0.03). Nevertheless, 9 of these patients had subnormal values. For the 14 children or adolescents included in this group, the values observed fell within the range of the controls of the same age, although the growth rate determined for 10 of these patients averaged 1.4 cm/yr.The mean IGF CP level for the untreated patients was 0.78 ± 0.64 U/ml, which is significantly lower than that ol controls.(1.03 ± 0.05; P < 0.001).No correlation was found between IGF or IGF CP levels and parameters reflecting the severity of the hypercortisolism. In the 23 patients investigated after treatment, IGF and IGF CP levels fell within the range of normal values.For the 11 subjects under glucocorticoid therapy the mean IGF and IGF CP levels were no different from control values.Sulfation assays were carried out on the same serum samples as those used for the IGF determinations in 21 of the untreated patients with Cushing's syndrome. The mean SM activity (0.65 ± 0.06 U/ml) was significantly lower than that of controls (0.91 ± 0.04; P < 0.001), which suggests that factors other than IGF are responsible for the depressed SM activity.The conclusion that can be drawn from these findings is that the stunted growth associated with hypercortisolism cannot be attributed to an IGF deficiency. (J Clin Endocrinol Metab 54: 885, 1982) R ETARDED growth associated with either endogenous or exogenous hypercorticism is a well known phenomenon (1, 2) and constitutes one of the signs by which Cushing's syndrome may be diagnosed in young subjects.There have been conflicting reports concerning the secretion of GH in such cases, both normal and subnormal responses of plasma GH to provocative tests having been observed (3-10). Simultaneous treatment with glucocorticoids during GH therapy stunts growth if the doses are too high (11) and human GH administration has no effect on the retarded growth of children treated with large doses of glucocorticoid (6,12,13).A number of studies have demonstrated that glucocorticoids have a direct action on cartilage in addition to inhibiting the stimulatory ...