Unpredictable hypersecretion of cortisol in Cushing's disease: detection by daily salivary cortisol measurements

A 70-year-old man with mild signs and symptoms of Cushing's syndrome due to an ACTH-secreting pituitary adenoma is described. He had a completely unpredictable pattern of urinary excretion of cortisol; 24 h urine for determination of cortisol excretion was collected daily at home on 725 consecutive days. During this period there were eight episodes in which urinary cortisol excretion exceeded the upper limit of normal. Within these episodes the pattern of cortisol secretion was extremely unpredictable, with cortisol excretion ranging from normal to highly elevated. Using a Cluster Analysis Program 61 pulses of cortisol excretion were detected within the eight periods of cortisol hypersecretion. The interval between two pulses varied from 2 to 12 days. Between the periods of cortisol hypersecretion, urinary cortisol excretion was completely normal, lasting from 4 to 102 days. There was no difference in the clinical expression of Cushing's syndrome between the periods of elevated and normal urinary cortisol excretion. During the last 439 days of the observation, cortisol was also measured in saliva collected at home at 09.00 after an overnight fast. The salivary cortisol pattern closely resembled that of urinary cortisol excretion and there was a significant correlation between salivary cortisol levels and 24 h urinary cortisol excretion in the 24 h after (r = 0.42, p < 0.0001, Spearman) and before saliva collection (r = 0.44, p < 0.0001). On 71% of occasions cortisol peaks in saliva, as detected by the Cluster Analysis Program, coincided with urinary cortisol peaks. We conclude that daily measurement of cortisol in saliva, collected at home, is a convenient and reliable method for detecting intermittent hypercortisolism in patients with Cushing's syndrome.