LAUSR

Abstract Disclosure: J.G. Kallet: None. W. Hover: None. A.D. Krein: None. J.L. Crooks: None. G.L. Kinney: None. M.F. Slovick: None. U. Christians: None. B. Schniedewind: None. S. Majka: None. M.T. McDermott: None. E.A. Regan: None. Adrenal insufficiency (AI) has multiple causes including: infection, injury, surgical removal of the adrenal gland, impairment of pituitary or hypothalamus, genetic disorders and autoimmune disease. It results in a wide range of symptoms that are sometimes only partially relieved by replacement of the hormone cortisol. Cortisol secretion is circadian and also produced in response to stress. Many patients continue to experience disabling symptoms including fatigue, confusion, weakness, and others, and remain at risk for adrenal crisis under current replacement strategies. Previous work has shown that there is significant individual variation in absorption and metabolism of hydrocortisone (HC). Pharmacokinetic studies show HC has an average half life of only 90 minutes. Methods: We studied 18 individuals with adrenal insufficiency, pre and post morning HC dose for a total of 5 hours, and measured saliva cortisone and plasma cortisol in each pre-dose, and 1, 2, 3, 4, 5 hours post usual AM dose. Diagnosis of AI was confirmed by medical record review. Usual HC dose was recorded. Samples were analyzed using a quantitative high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. Results: Age range was 25-75, mean 51.2 (SD 15.7), sex: 4 males, 14 females. Six people reported that they were normally asymptomatic and 12 were symptomatic. AddiQoL = 100.1 (higher better) in the asymptomatic group and 75.5 in the symptom group, p=0.003. Morning dose was 10 mg for 10 people and 15 mg for 8. AddiQoL showed a non-significant trend to higher in the 15 mg group (90 vs 79). Both plasma cortisol and saliva cortisone showed distinct pattern over the time period with a peak at 1 hour post dose and steep decline by five hours post dose. Mean (SD) values for plasma cortisol of the time studied were T0 2.9 (4.4), T1 22.6 (5.4), T2 18.0 (5.7), T3 13.1 (5.3), T4 8.4 (4.4), 6.8 (7.2) mcg/dL. Correlation between plasma cortisol and saliva cortisone was high at 0.89, (p<0.0001). Of the 18 people, 11 had first morning cortisol levels below 1.0 mcg/dL, and four had levels above 5 mcg/dL. Discussion: Pre dose cortisol levels were very low in most of the adrenal insufficient people suggesting inadequate replacement during critical overnight hours. Plasma cortisol and saliva cortisone using mass spectrometry as a measurement technique are highly correlated and offer a means to monitor replacement hormone in symptomatic patients. There is large variation in the pattern of absorption and metabolism of cortisol between people that may result in inadequate symptom control. Some AI patients may have residual secretion of cortisol allowing them to be less symptomatic with lower doses of replacement. The established half-life of hydrocortisone dosed twice a day does not provide a match to the normal circadian secretion and may result in both symptoms and increased risk of adrenal crisis. Presentation: Monday, July 14, 2025