Hypocortisolemia in children undergoing evaluation for growth hormone deficiency

The group of children who have clinical manifestations of GH deficiency may potentially contain a large number of patients with secretory defects of cortisol. We assessed physiological cortisol secretion by measuring the 24-h integrated concentration of cortisol (IC-F) in a series of 105 patients, aged 7-19 yr, undergoing endocrinological evaluation for growth impairment possibly due to GH deficiency. The reference value for IC-F, established from 30 normal stature, normal weight children (controls), aged 7-18 yr, was 157 +/- 41 nmol/L (mean +/- 1 SD). There was no effect of age, gender, or pubertal status on IC-F in controls. The IC-F of patients was 150 +/- 72 nmol/L. Twelve patients (11%) had IC-F values more than 2 SD below the mean (i.e. less than 75 nmol/L) of the controls (P less than 0.001). An IC-F below 75 nmol/L was associated with a blunted peak cortisol response to insulin-induced hypoglycemia (367 +/- 160 nmol/L compared to 464 +/- 155 nmol/L in the other patients; (P less than 0.05). None of the patients had obvious clinical symptoms of hypocortisolemia at the time of testing. In general, IC-F levels were not correlated with IC-GH. However, 10 patients who had subnormal IC-F values also had laboratory evidence of GH secretory defects; 7 had subnormal IC-GH levels but normal stimulated GH responses, and 3 had both subnormal responses to stimulation as well as subnormal IC-GH. The long term prognosis and management implications of hypocortisolemia diagnosed in this patient group require further evaluation.