Susceptibility to Adrenal Crisis Is Associated With Differences in Cortisol Excretion in Patients With Secondary Adrenal Insufficiency

Objective: To compare cortisol pharmacokinetics and pharmacodynamics mapped through several glucocorticoid sensitive pathways in patients on hydrocortisone substitution with or without an adrenal crisis. Design: A post-hoc analysis of a previously conducted randomized controlled trial in patients with secondary adrenal insufficiency examining the effects of 2 weight-adjusted hydrocortisone doses. Methods: Comparisons were primarily made on a hydrocortisone dose of 0.2-0.3 mg/kg/day for plasma cortisol and cortisone, 24-hour urinary steroid profile, the glucocorticoid sensitive tryptophan-kynurenine pathway, the renin-angiotensin-aldosterone system and aspects of quality of life. Variables of interest were also analyzed on the hydrocortisone dose of 0.4-0.6 mg/kg/day. Results: Out of 52 patients, 9 (17%) experienced at least one adrenal crisis (AC+ group) and 43 did not develop an adrenal crisis (AC- group) during an observation period of 10 years. 24-hour urinary excretion of cortisol and cortisone were lower in the AC+ group (0.05 [IQR 0.03; 0.05] vs. 0.09 [0.05; 0.12] µmol/24h, P=0.01and 0.13 [0.10; 0.23] vs. 0.24 [0.19; 0.38] µmol/24h, P=0.04, respectively). No differences in pharmacokinetics of cortisol were observed. Kynurenine concentrations were higher in the AC+ group (2.64 [2.43; 3.28] vs. 2.23 [1.82; 2.38] µmol/L, P=0.03) as was general fatigue (Z-scores 1.02 [-0.11; 1.42] vs. -0.16 [- 0.80; 0.28], P=0.04). On the higher hydrocortisone dose urinary excretion of cortisol and cortisone was still significantly lower between the AC- and AC + group. The differences in glucocorticoid sensitive variables disappeared. Conclusion: Patients susceptible to an adrenal crisis demonstrated differences in cortisol and cortisone excretion as well as in pharmacodynamics when compared to patients who did not experience an adrenal crisis, suggesting a biological predisposition in certain patients for the development of an adrenal crisis

The Diagnostic Value of 18F-FDG PET/CT Scan in Characterizing Adrenal Tumors

CONTEXT: Imaging plays an important role in the characterization of adrenal tumors, but findings might be inconclusive. The clinical question is whether 18F fluodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is of diagnostic value in this setting.OBJECTIVE: This meta-analysis was aimed at the diagnostic value of 18F-FDG PET/CT in differentiating benign from malignant adrenal tumors discovered either as adrenal incidentaloma or during staging or follow-up of oncologic patients.DATA SOURCES: PubMed, EMBASE, Web of Science, and Cochrane Library were searched to select articles between 2000 and 2021.STUDY SELECTION: We included studies describing the diagnostic value of 18F-FDG PET/CT in adult patients with an adrenal tumor. Exclusion criteria were 10 or fewer participants, insufficient data on histopathology, clinical follow-up, or PET results. After screening of title and abstract by 2 independent reviewers, 79 studies were retrieved, of which 17 studies met the selection criteria.DATA EXTRACTION: Data extraction using a protocol and quality assessment according to QUADAS-2 was performed independently by at least 2 authors.DATA SYNTHESIS: A bivariate random-effects model was applied using R (version 3.6.2.). Pooled sensitivity and specificity of 18F-FDG PET/CT for identifying malignant adrenal tumors was 87.3% (95% CI, 82.5%-90.9%) and 84.7% (95% CI, 79.3%-88.9%), respectively. The pooled diagnostic odds ratio was 9.20 (95% CI, 5.27-16.08; P &lt; .01). Major sources of heterogeneity (I2, 57.1% [95% CI, 27.5%-74.6%]) were in population characteristics, reference standard, and interpretation criteria of imaging results.CONCLUSIONS: 18F-FDG PET/CT had good diagnostic accuracy for characterization of adrenal tumors. The literature, however, is limited, in particular regarding adrenal incidentalomas. Large prospective studies in well-defined patient populations with application of validated cutoff values are needed.</p