Are “Non-Functioning” Adrenal Incidentalomas Actually Quiescent Masses?
Presentation Number: SUN 396
Date of Presentation: April 2nd, 2017
Martha Katherine Huayllas*1, Ravinder J. Singh2, Brian Netzel3 and Claudio E. Kater4
1Universidade Federal de São Paulo - UNIFESP, São Paulo, Brazil, 2Mayo Clinic, 3Mayo Clinic, Rochester, MN, 4Federal University of São Paulo, São Paulo, SP, Brazil
Introduction: AI occurs in nearly 5% of the adult population. After excluding malignancy and overt steroid overproduction, AI must be investigated for subclinical hypercortisolism (SCH) that is present in up to 30% of cases. Lack of cortisol (F) suppression after 1mg overnight dexamethasone (1mgDST) indicates SCH, in addition to reduced ACTH and/or DHEAS levels. Metabolic disorders, as obesity (OB), hypertension (HT), diabetes (DM) and dyslipidemia (DLP), are highly prevalent among SCH and are associated with increased cardiovascular mortality (CVM). “Non-functioning” adenomas (NFA) represent 90% of AI and are also associated with increased CVM. Aim: to investigate whether NFA may be active, secreting increased amounts of adrenal steroids that could be associated with a similar outcome. Patients and Methods: We studied 73 patients with AI (52 unilateral, 66% female, 18-87y [median 59y]) and 34 sex and age-matched controls (CS) whose adrenal imaging were unremarkable. All underwent an ACTH stimulation test (SynacthenÒ, 0.25mg IV bolus) and a 1mgDST and had blood samples drawn before and after the procedures for LC/MS-MS determinations of 10 steroids, mainly: F, corticosterone (B), 11-deoxycortisol (S), and Deoxycorticosterone (DOC) (done at Mayo Clinic). Results: Based on F responses to DST, AI was classified in SCH (F >2.5mg/dL, n=21) or NFA (F <2.5 mg/dL, n=52). DM, HT, and DLP were present in 38%, 75%, and 56% of SCH and 32%, 62%, and 62% of NFA, and in 6%, 63%, and 27% of CS. Basal F (12.3±0.9 and 10.0±0.5mg/dL; mean±SE) and B (343±51 and 243±23ng/dL) were increased in SCH and NFA, respectively, as compared do CS (7.6±0.6 mg/dL and 146±32ng/dL), and both were resistant to DST (4.9±0.6 and 1.4±0.1 vs 0.9±0.07 mg/dL, and 125±22 and 37±3 vs 26±3 ng/dL, for SCH, NFA and CS, respectively and overstimulated by ACTH (31±2 and 29±1 vs 24±1mg/dL, and 4057±359 and 3590±184 vs 2360±183 ng/dL, for SCH, NFA and CS, respectively). S and DOC follow a similar, although less evident pattern. Overall, bilateral AI disclosed worse profiles, both for SCH and NFA. Early precursors (pregnenolone [Preg] and 17-Preg] did not show significant differences. ACTH was <10pg/mL in 74.1% of SCH, 31.2% of NFA and 25% of CS. Discussion: Basal steroid profile (mainly terminal products, F and B) and their responses to suppression and stimulation were clearly abnormal in SCH as compared to CS; in presence of suppressed ACTH, it confirms secretory autonomy. Remarkably, NFA behave similarly to SCH, although in an intermediate fashion; still, NFA are quite different from CS. Conclusion: our data show that so-called NFA are not quiescent masses, as generally stated. NFA can autonomously secrete higher than normal steroid mixtures that may cause major metabolic abnormalities and increased CVM, as previously reported. Thus, special therapeutic considerations must be given at least to selected cases of NFA.
Nothing to Disclose: MKH, RJS, BN, CEK