Is the 1mg-dexamethasone suppression test a precise marker of glucocorticoid excess and cardiometabolic risk in patients with adrenal incidentalomas?

AIM: To analyze if the 1mg-dexamethasone suppression test (DST) is a reliable marker of glucocorticoid excess and cardiometabolic risk in patients with adrenal incidentalomas (AIs). METHODS: Cross-sectional study of patients with nonfunctioning adrenal incidentalomas (NFAIs, defined by cortisol post-DST ≤ 1.8 µg/dL) and patients with autonomous cortisol secretion (ACS, defined by cortisol post-DST > 1.8 µg/Dl). The urinary steroid profile (USP) was determined by gas chromatography coupled to mass spectrometry. Both groups were matched by sex, age and body mass index. RESULTS: Forty-nine patients with AIs (25 with ACS and 24 with NFAI) were included. As a whole, AIs showed a high excretion of ß-cortolone, tetrahydro-11-deoxycortisol (THS), α-cortolone, α-cortol, tetrahydrocortisol (THF) and tetrahydrocortisone (THE). A positive yet modest correlation between post-DST cortisol and total excretion of glucocorticoid metabolites (r = 0.401, P = 0.004) was observed, with the stronger being observed with total THS (r = 0.548, P < 0.001) and THF (r = 0.441, P = 0.002). Some of the metabolites that were elevated in patients with AIs, were higher in patients with ACS-related comorbidities than in those without comorbidities. Post-DST cortisol showed a fair diagnostic accuracy for the prediction of ACS-related comorbidities (AUC 0.767 [95% CI 0.634-0.882]). However, post-DST diagnostic accuracy improved when combined with urinary cortisone, α-cortol, THS and serum DHEAS (0.853 [0.712‒0.954]). CONCLUSION: The DST has a positive, but modest, correlation with urinary glucocorticoid excretion. Similarly, the diagnostic accuracy of the DST for the prediction of ACS-related comorbidities is only fair, but it may be improved if combined with the results of the USP and serum DHEAS. SIGNIFICANCE STATEMENT: This is the first study aimed to evaluate if 1mg-dexamethasone suppression test (DST) is a reliable marker of glucocorticoid excess and cardiometabolic risk in patients with adrenal incidentalomas (AIs) and if urinary steroid profile was measured by GS-MS could improve such a prediction. We found a positive yet modest correlation between post-DST cortisol and total excretion of glucocorticoid metabolites, with the stronger being observed with total tetrahydro-11-deoxycortisol (THS) and tetrahydrocortisol. Post-DST cortisol showed a fair diagnostic accuracy for the prediction of ACS-related comorbidities (AUC 0.767). However, post-DST diagnostic accuracy improved when combined with urinary cortisone, α-cortol, THS and serum DHEAS (0.853).

Evaluation of Body Composition in Patients With and Without Adrenal Tumors and Without Overt Hypersecretory Syndromes.

OBJECTIVE: To compare body composition between patients with autonomous cortisol secretion (ACS), those with nonfunctioning adrenal incidentalomas (NFAIs), and control subjects without adrenal tumors. METHODS: A cross-sectional study was performed, incluidng the following 3 groups: patients with ACS (cortisol post-dexamethasone suppression test [DST] >1.8 µg/dL), NFAIs (cortisol post-DST ≤ 1.8 µg/dL), and patients without adrenal tumors (control group). Patients of the 3 groups were matched according to age (±5 years), sex, and body mass index (±5 kg/m2). Body composition was evaluated by bioelectrical impedance and abdominal computed tomography (CT) and urinary steroid profile by gas chromatography mass spectrometry. RESULTS: This study enrolled 25 patients with ACS, 24 with NFAIs, and 24 control subjects. Based on CT images, a weak positive correlation between the serum cortisol level post-DST and subcutaneous fat area (r = 0.3, P =.048) was found. As assessed by bioelectrical impedance, lean mass and bone mass were positively correlated with the excretion of total androgens (r = 0.56, P <.001; and r = 0.58, P <.001, respectively); visceral mass was positively correlated with the excretion of glucocorticoid metabolites and total glucocorticoids (r = 0.28, P =.031; and r = 0.42, P =.001, respectively). Based on CT imaging evaluation, a positive correlation was observed between lean mass and androgen metabolites (r = 0.30, P =.036) and between visceral fat area, total fat area, and visceral/total fat area ratio and the excretion of glucocorticoid metabolites (r = 0.34, P =.014; r = 0.29, P =.042; and r = 0.31, P =.170, respectively). CONCLUSION: The urinary steroid profile observed in adrenal tumors, comprising a low excretion of androgen metabolites and high excretion of glucocorticoid metabolites, is associated with a lower lean mass and bone mass and higher level of visceral mass in patients with adrenal tumors.

Characterisation of the urinary steroid profile of patients with nonfunctioning adrenal incidentalomas: A matched controlled cross-sectional study.

AIM: To identify alterations in steroid metabolism in patients with nonfunctioning adrenal incidentalomas (NFAIs) through the analysis of their urinary steroid profile (USP). METHODS: Cross-sectional study with one study group (NFAIs, cortisol post dexamethasone suppression test [DST] ≤ 1.8 µg/dl [49.7 nmol/L]) and 2 control groups: patients with autonomous cortisol secretion (ACS group, cortisol post-DST > 1.8 µg/dl (49.7 nmol/L) and patients without adrenal tumours (healthy-adrenal group). Twenty-four-hour urine collections for USP measurement (total and free fraction of 51 24 h-urine specimens) were obtained from 73 participants (24 with NFAIs, 24 without AIs, and 25 with ACS). USP was determined by gas chromatography coupled to mass spectrometry. Patients of the three groups were matched according to sex, age (±5 years-old) and body mass index (±5 kg/m2 ). RESULTS: Compared to healthy-adrenal controls, patients with NFAIs had a lower excretion of androgen metabolites (230.5 ± 190.12 vs. 388.7 ± 328.58 µg/24 h, p = .046) and a higher excretion of urinary free cortisol (UFC) (54.3 ± 66.07 vs. 25.4 ± 11.16 µg/24 h, p = .038). UFC was above the reference range in 20.8% of patients in the NFAI, compared to 0% in the healthy-adrenal group (p = .018). Patients with ACS had a higher prevalence of hypertension, dyslipidemia, and diabetes than patients with NFAIs or the control group. A lower excretion of androgen metabolites (218.4 ± 204.24 vs. 231 ± 190 µg/24 h, p = .041) and a nonsignificant higher excretion of glucocorticoid metabolites (2129.6 ± 1195.96 vs. 1550.8 ± 810.03 µg/24 h, p = .180) was found in patients with ACS compared to patients with NFAIs. CONCLUSION: NFAIs seem to secrete a subtle, yet clinically relevant, excess of glucocorticoids. Future studies are needed to confirm our findings; and to identify metabolic alterations associated with an increased cardiometabolic risk.

The Beneficial Changes on Inflammatory and Endothelial Biomarkers Induced by Metabolic Surgery Decreases the Carotid Intima-Media Thickness in Men.

Obesity increases cardiovascular risk in men through several mechanisms. Among them, low-grade chronic inflammation and obesity-associated hypogonadism have been described. We aimed to study the effects of metabolic surgery on the carotid-intima media thickness through changes in inflammatory, endothelial biomarkers, and testosterone. We included 60 men; 20 submitted to laparoscopic Roux-en-Y gastric bypass (RYGB), 20 to sleeve gastrectomy (SG), and 20 to lifestyle modification (controls). Several inflammatory and endothelial biomarkers and total testosterone (TT) were measured at baseline and six months after surgery. Free testosterone (FT) was calculated, and carotid intima-media thickness (cIMT) was measured by ultrasonography. Compared to controls, cIMT decreased after surgery concomitantly with CRP, PAI-1, sICAM-1, and IL-18 (p < 0.01) and with an increase in sTWEAK (p = 0.027), with no differences between RYGB and SG. The increase in TT and FT after surgery correlated with the changes in cIMT (p = 0.010 and p = 0.038, respectively), but this association disappeared after multivariate analysis. Linear regression showed that sTWEAK (ß = -0.245, p = 0.039), PAI-1 (ß = 0.346, p = 0.005), and CRP (ß = 0.236, p = 0.049) were associated with the changes in cIMT (R2 = 0.267, F = 6.664, p = 0.001). In conclusion, both RYGB and SG induced improvements in inflammation and endothelial biomarkers that drove a decrease in cIMT compared to men with obesity who submitted to diet and exercise.

The Role of Adiponectin in the Resolution of Male-Obesity-Associated Secondary Hypogonadism after Metabolic Surgery and Its Impact on Cardiovascular Risk.

Male-obesity-associated secondary hypogonadism (MOSH) is a very prevalent entity that may resolve after marked weight loss. Adiponectin (APN) is an adipokine with anti-inflammatory properties that regulates metabolism. Low-circulating APN is associated with obesity, diabetes, and cardiovascular risk, along with circulating testosterone. We aimed to evaluate APN changes in men with MOSH (low circulating free testosterone (FT) with low or normal gonadotropins) and without it after metabolic surgery. We look for their possible association with cardiovascular risk measured by carotid intima-media thickness (cIMT). We included 60 men (20 submitted to lifestyle modification, 20 to sleeve gastrectomy, and 20 to gastric bypass) evaluated at baseline and 6 months after. The increase in APN at follow-up was reduction in patients with persistent MOSH (n = 10) vs. those without MOSH (n = 30) and MOSH resolution (n = 20), and the former did not achieve a decrease in cIMT. The increase in APN correlated positively with FT (r = 0.320, p = 0.013) and inversely with cIMT (r = -0.283, p = 0.028). FT inversely correlated with cIMT (r = -0.269, p = 0.038). In conclusion, men without MOSH or with MOSH resolution showed a high increase in APN after weight loss with beneficial effects on cIMT. Those without MOSH resolution failed to attain these effects.