Modern Management of Mild Autonomous Cortisol Secretion

Abstract

Incidentally discovered adrenal tumors are reported in ~ 5% of adults undergoing cross-sectional imaging. Mild autonomous cortisol secretion (MACS) from the adrenal mass is demonstrated in 5-48% of patients with adrenal tumors. The diagnosis of MACS represents a challenge due to limitations of the currently used diagnostic tests, differences in the definitions of the clinically relevant MACS, and heterogeneity in an individual's susceptibility to abnormal cortisol secretion from the adrenal mass. Patients with MACS present with increased risk of cardiovascular risk factors, cardiovascular events, metabolic bone disease, and mortality. Adrenalectomy improves or reverses MACS-associated comorbidities in selected patients. The current review will address diagnostic and management challenges in the care of patients with MACS, discuss data on emerging biomarkers, and suggest future directions in the field of MACS.

Prospective Evaluation of Late-Night Salivary Cortisol and Cortisone by EIA and LC-MS/MS in Suspected Cushing Syndrome

“…None of the salivary steroid methods provided an adequate sensitivity and positive predictive value for ACTH-independent (adrenal) CS considering that, in our study, 11 of 16 of these patients did not have any elevated salivary results. This is not surprising, since most studies have found that LNSC (regardless of assay method) has a poor sensitivity in patients with mild cortisol excess (formerly known as subclinical CS) [ 20 , 56 , 62-76 ]. Accordingly, other studies such as the overnight 1 mg dexamethasone suppression test (DST) should be the initial test in patients with adrenal nodular disease or adrenal incidentalomas [ 19 , 56 , 64 , 65 , 74 ].…”

A Target‐Mediated Drug Disposition Model to Explain Nonlinear Pharmacokinetics of the 11β‐Hydroxysteroid Dehydrogenase Type 1 Inhibitor SPI‐62 in Healthy Adults

“…In the 1, 3 and 10 mg cohorts, venous blood samples were collected at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72 hours after dose administration. In the 6 mg cohort, venous blood samples were collected at 0.5, 1, 1.5, 2, 3,4,6,8,10,12,18,24,36,48,72,96, 120 hours after dose administration.…”

“…In the 0.4 mg cohort, 4 subjects received SPI-62 0.4 mg once daily for 14 days (Days 1-14). PK samples in these two cohorts were collected at 0.5, 1, 1.5, 2, 3, 4, 8, 12, 16, and 24 hours after the first dose; 0.5, 1, 1.5, 2, 3,4,8,12,16,24,48,72,96,120,144, and 168 hours after the last dose.…”

“…11β-hydroxysteroid dehydrogenase type 1 (HSD-1) converts inactive cortisone to active cortisol in tissues, including liver, fat, brain, bone and eye 1 , in which cortisol regulates a range of physiological functions, including glucose and lipid metabolism, mood, memory, sleep, osteoblast turnover, and intraocular pressure 2 . Cushing's syndrome and autonomous cortisol secretion (ACS) are conditions of cortisol excess that are associated with considerable metabolic, cardiovascular, bone, and other morbidity as well as substantial mortality risk 3,4 . HSD-1 acts similarly on the corticosteroid medicines, for example, it converts inactive prednisone to active prednisolone 5 .…”

“…12 SPI-62 is in development as a treatment for Cushing's syndrome and ACS and as adjunctive therapy to prednisolone in patients with polymyalgia rheumatica. 3 mg loading dose on day 1, 0.2 mg once-daily dose on days 2-14 0.4 mg once-daily doses on days 1-14 0.5, 1, 1.5, 2, 3, 4, 8, 12, 16, and 24 hours after the first dose; 0.5, 1, 1.5, 2, 3,4,8,12,16,24,48,72,96,120,144, and 168 hours after the last dose for 0.2-and 0.4-mg cohorts 0.004 6 0.7 mg single dose on day 1, 0.7-mg once-daily doses on days 7-20 0.5, 1, 1.5, 2, 3,4,8,12,16,24,36,48,72,96,120, and 144 hours after the first dose and 0.5, 1, 1.5, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, 120, 144, and 168 hours after the last dose for 0.7-and 2-mg cohorts 6 2 mg single dose on day 1, 2 mg once-daily doses on days 7-20 SAD, single ascending dose; MAD, multiple ascending dose; LLOQ, lower limit of quantification. a More doses were evaluated in the original clinical trials.…”