The utility of IGF1 in the evaluation of pediatric patients with endogenous hypercortisolemia

Cushing Disease (CD) is a rare endocrine disorder associated with impaired growth hormone (GH) and short stature. Insulin-like growth factor-1 (IGF-1) is a marker of GH secretion.

Patients with young onset CD (<21 years old) and available IGF-1 levels at diagnosis and/or follow-up were studied (total = 194, diagnosis = 174, follow-up = 104). IGF-1 was reported as z-score (IGF1z).

IGF1z was lower than expected in the general population (median IGF1z: -0.92 [-1.54, 0.07], p < 0.0001) at diagnosis and remained low at follow-up (median: -1.13 [-1.78, -0.66], p < 0.0001). There was no correlation of IGF1z at diagnosis with BMI; there was a weak correlation with height (r_s = 0.19, p = 0.035). IGF1z was inversely correlated with markers of hypercortisolemia, including morning (r_s = -0.31, p < 0.0001) and midnight cortisol (r_s = -0.30, p < 0.0001), and with insulin resistance (Homeostatic Model Assessment for Insulin Resistance, HOMA-IR, r_s = -0.27, p < 0.01).

IGF-1 levels in CS are on the lower side of the normal range during active disease and remain low at one year after treatment. IGF-1 levels correlated mainly with markers of hypercortisolemia rather than the short stature of patients and should not be used in the assessment of growth in this population.

We report that IGF-1 levels in childhood during active hypercortisolemia and up to 1 year after resolution are on the lower side of the normal range. Our results demonstrate that IGF-1 levels during active hypercortisolemia correlate mainly with markers of Cushing syndrome. This report adds data to the current literature where reports of IGF-1 in Cushing syndrome have shown variable results. Understanding the lack of utility of IGF-1 in assessing growth parameters in the pediatric Cushing syndrome population is important for physicians caring for these patients who should not use IGF-1 for diagnostic or treatment decisions.