MIFEPRISTONE TREATMENT FOR MILD AUTONOMOUS CORTISOL SECRETION DUE TO ADRENAL ADENOMAS: A PILOT STUDY.

Objective: Adrenal incidentalomas are increasingly detected with the widespread use of thoracic and abdominal imaging. The most common secretory syndrome in adrenal nodules is autonomous cortisol secretion (ACS). Recent data show that even mild cortisol excess is associated with adverse outcomes. The glucocorticoid receptor antagonist mifepristone has been used in patients with overt Cushing syndrome and hyperglycemia. The purpose of our study was to determine the effect of mifepristone on metabolic parameters in patients with ACS and concomitant prediabetes or diabetes. Methods: Eight patients with either unilateral or bilateral adrenal nodules with ACS were included in the study. Fasting laboratory tests including glucose and insulin levels to calculate homeostatic model assessment for insulin resistance (HOMA-IR) were performed at baseline and again after either 3 months (3 patients) or 6 months (5 patients) on mifepristone 300 mg daily treatment. Patients also completed several validated surveys on mood and quality of life at baseline and follow-up. Results: There were significant reductions in fasting glucose measurements and insulin resistance as measured by HOMA-IR in the 6 of 8 study patients in whom these measurements were available (P = .03). Conclusion: This pilot study demonstrates that mifepristone treatment of ACS is associated with a significant decrease in fasting glucose and insulin resistance as measured by HOMA-IR scores. Mifepristone treatment of ACS may be considered as a medical option for patients with ACS due to adrenal adenomas with concomitant abnormal glucose parameters in whom surgical removal is not being considered. Abbreviations: ACS = autonomous cortisol secretion; ACTH = adrenocorticotropic hormone; AI = adrenal incidentaloma; DHEAS = dehydroepiandrosterone sulfate; GR = glucocorticoid receptor; HbA1c = hemoglobin A1c; HOMA-IR = homeostatic model assessment for insulin resistance; ODT = overnight dexamethasone suppression test; QoL = quality of life; STAI = state trait anxiety inventory; TSH = thyroid stimulating hormone; UFC = urinary free cortisol.

Genetic basis of bilateral macronodular hyperplasia.

OBJECTIVE: To review the genetic basis of bilateral macronodular hyperplasia (BMAH). METHODS: Case presentation, review of literature, table, and bullet point conclusions. RESULTS: BMAH, also known as adrenocorticotropic hormone (ACTH)-independent macronodular hyperplasia (AIMH), can cause Cushing syndrome or mild hypercortisolism. Recent studies have demonstrated that hyperplastic tissue reproduces ectopic ACTH, implying that BMAH is the more proper term, as the syndrome is not ACTH-independent. BMAH was thought to be sporadic, but recent data have shown that there is likely a genetic component in the majority of cases. Mutations in ARMC5, a putative suppressor gene, have been found in many familial cases of BMAH and are thought to be responsible for the disorder. As these nodules inefficiently produce cortisol, large nodules are required to produce a clinical syndrome. ARMC5 likely requires a second somatic mutation to become clinically apparent. Clinical manifestations are not generally noted until the fifth to sixth decades of life. CONCLUSION: BMAH is an underrecognized genetic condition that can lead to Cushing syndrome and should be screened for in patients and susceptible family members.

Uncontrolled diabetes mellitus increases risk of infection in patients with advanced cirrhosis.

BACKGROUND: Diabetes mellitus (DM) is common in patients with cirrhosis and is associated with increased risk of infection. AIM: To analyze the impact of uncontrolled DM on infection and mortality among inpatients with advanced cirrhosis. METHODS: This study utilized the Nationwide Inpatient Sample from 1998 to 2014. We defined advanced cirrhosis using a validated ICD-9-CM algorithm requiring a diagnosis of cirrhosis and clinically significant portal hypertension or decompensation. The primary outcome was bacterial infection. Secondary outcomes included inpatient mortality stratified by elderly age (age≥70). Multivariable logistic regression analyzed outcomes. RESULTS: 906,559 (29.2%) patients had DM and 109,694 (12.1%) were uncontrolled. Patients who had uncontrolled DM were younger, had less ascites, but more encephalopathy. Bacterial infection prevalence was more common in uncontrolled DM (34.2% vs. 28.4%, OR 1.33, 95% CI 1.29-1.37, p<0.001). Although uncontrolled DM was not associated with mortality, when stratified by age, elderly patients with uncontrolled DM had a significantly higher risk of inpatient mortality (OR 1.62, 95% CI 1.46-1.81). CONCLUSIONS: Uncontrolled DM is associated with increased risk of infection, and when combined with elderly age is associated with increased risk of inpatient mortality. Glycemic control is a modifiable target to improve morbidity and mortality in patients with advanced cirrhosis.

Adrenal mild hypercortisolism.

Adrenal incidentalomas have become detected more often as the use of abdominal imaging has increased. Up to one-third of these may be secreting low levels of cortisol, known as mild hypercortisolism or subclinical Cushing syndrome. These low levels of cortisol have been found to be associated with an increased in the metabolic syndrome, osteoporosis, cardiovascular events, and mortality. This article discusses in detail the epidemiology, diagnosis, clinical associations, and treatment options of mild hypercortisolism.