DHEAS and Differential Blood Counts as Indirect Signs of Glucocorticoid Excess in Adrenal Non-Producing Adenomas

2021 ◽  
Vol 53 (08) ◽  
pp. 512-519
Author(s):  
Eliza P. Winzinger ◽  
Hana Jandikova ◽  
Matthias Haase ◽  
Andreas Knauerhase ◽  
Tudor Winzinger ◽  
...  

AbstractThe majority of incidentally discovered adrenal tumors are later characterized as non-producing adrenocortical adenomas (NPA). We asked whether laboratory abnormalities in parameters that reflect glucocorticoid action can be found in patients with NPA despite their nature of being clinically unapparent. Since glucocorticoids are potent immunosuppressants we studied blood counts and differential blood counts along with corticotropin and dehydroepiandrostenedione sulfate (DHEAS) blood concentrations, as well as cortisol values before and after an overnight 1 mg dexamethasone suppression test. We compared the results of normal individuals, of patients with adrenal adenomas and normal hormone profiles and with subclinical autonomous glucocorticoid hypersecretion, as well as overt cortisol excess. We found that almost all indices of the blood counts were significantly different between the patients groups. In particular, patients with adrenal non-producing adenomas already showed signs of glucocorticoid excess, including relative lymphocytopenia, lowered DHEAS, and ACTH concentrations than control individuals. We also found that the extent of lymphocytopenia correlated with the concentrations of DHEAS and ACTH, and DHEAS correlated well with ACTH. We conclude that the basal ACTH and DHEAS values along with the differential blood counts give good information on the extent of glucocorticoid excess and that silent adrenal adenomas seem to oversecrete glucocorticoids at concentrations that already alter these parameters.

2003 ◽  
Vol 88 (7) ◽  
pp. 3113-3116 ◽  
Author(s):  
Eleni V. Dimaraki ◽  
Craig A. Jaffe

After evaluating a patient who appeared to have a falsely abnormal response to the dexamethasone suppression test while taking troglitazone, we examined the effects of troglitazone on the activity of hepatic CYP3A4 and the screening tests for Cushing’s syndrome. We studied five healthy women and three healthy men, aged 25 ± 2 yr, before and after treatment with troglitazone (600 mg daily) for 28 d. Baseline 0800 h cortisol and corticosterone were similar before and after troglitazone treatment. Before troglitazone treatment, all subjects suppressed 0800 h cortisol below 1.8 μg/dl (mean, 0.66 ± 0.08 μg/dl) during the 1-mg overnight dexamethasone suppression test (DST), whereas during troglitazone treatment none of the subjects suppressed 0800 h cortisol below 1.8 μg/dl (mean, 9.0 ± 1.8 μg/dl). Serum dexamethasone levels decreased by 66 ± 4%, and the erythromycin breath test measurements increased by 27 ± 8%, indicating increased CYP3A4 activity during troglitazone treatment. The hydrocortisone suppression test (HST) was performed by administering 50 mg hydrocortisone at 2300 h. Using the criterion of suppression of 0800 h plasma corticosterone by more than 50%, the specificity of the HST was 100% both before and after troglitazone treatment. In conclusion, troglitazone induced the activity of CYP3A4 leading to falsely abnormal DST. HST is a useful alternative to the DST in patients taking medications that increase the activity of CYP3A4.


1983 ◽  
Vol 58 (1) ◽  
pp. 129-132 ◽  
Author(s):  
Lucille W. King ◽  
Kalmon D. Post ◽  
Israel Yust ◽  
Seymour Reichlin

✓ Pituitary-adrenal function in a patient with classical features of Cushing's disease, increased urinary excretion of cortisol, and documented pituitary adenoma was found to be suppressed by dexamethasone in doses even less than those required to inhibit secretion in normal individuals. This response was shown to be due to inappropriately high levels of dexamethasone in plasma, presumed to be the consequence of decreased peripheral clearance. Because the dexamethasone suppression test is so widely used for diagnosis of Cushing's disease, it is important to recognize that this situation can occasionally occur.


1991 ◽  
Vol 3 (1) ◽  
pp. 8-13
Author(s):  
M. Maes ◽  
C. Vandervorst ◽  
E. Suy ◽  
M. Martin ◽  
B. Minner ◽  
...  

SummaryThe dexamethasone suppression test has been carried out in 111 depressed inpatients. Fasting, 8 a.m. plasma levels of Cortisol and adrenocorticotropic hormone (ACTH) were determined before and after administration of 1 mg dexamethasone. In 64 subjects multisequential (1-17,1-24,1-39) ACTH, and in 47 subjects intact (1-39) ACTH has been determined. Patients with melancholia exhibited significantly higher postdexamethasone Cortisol and intact ACTH values as compared with minor and simple major depressives. Severity of illness was significantly and positively related to postdexamethasone intact ACTH - but not to multisequential ACTH. Cortisol nonsuppressors showed higher postdexamethasone (only intact) ACTH values than Cortisol suppressors. Both postdexamethasone ACTH values were significantly and positively related with the postdexamethasone Cortisol values. We have established that Cortisol nonsuppression during melancholia is determined by an augmented escape of ACTH from suppression by dexamethasone. Intact ACTH showed the most significant clinical relevance for depression and Cortisol nonsuppression. In the clinical practice we advize the use of postdexamethasone intact ACTH in stead of plasma Cortisol or multisequential ACTH.


1983 ◽  
Vol 17 (4) ◽  
pp. 350-353
Author(s):  
Geoffrey D. Schrader ◽  
Timothy C. Durbridge

A review of case notes before and after the introduction of the DST into clinical psychiatric practice revealed considerable changes in diagnosis and management. Specifically there were increases in the diagnosis of biological depression and treatment with somatic antidepressant therapy. There was no association between DST results and particular management plans. There was a strong association between requesting the DST and management with antidepressants. It is suggested that the introduction of laboratory tests for psychiatric disorders may firm the belief of psychiatrists in the biological basis of some forms of depression and thus alter their diagnostic and treatment practice.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Catherine D Zhang ◽  
Elizabeth J Atkinson ◽  
Sara J Achenbach ◽  
Andreas Ladefoged Ebbehøj ◽  
Dingfeng Li ◽  
...  

Abstract Background: Benign adrenal tumors are frequently diagnosed on imaging and may pose health risks to patients regardless of functional status. Both non-functioning adrenal tumors (NFAT) and tumors with mild autonomous cortisol secretion (MACS) have been associated with increased cardiovascular events and risk factors. However, limited data exist on the association of adrenal adenomas with cardiometabolic outcomes in the population-based setting. Aim: 1) To determine the prevalence of cardiovascular co-morbidities and events and 2) to assess mortality in a population-based cohort of patients with adrenal adenomas. Methods: We identified adult patients living in the community diagnosed with an adrenal tumor from 1995-2017 using a medical records linkage system. Adrenal tumors were classified as MACS if cortisol was ≥1.8mcg/dL after 1 mg dexamethasone suppression test, NFAT if cortisol was <1.8 mcg/dL, and adenoma with unknown cortisol secretion (AUCS) if dexamethasone suppression test was not performed. Cardiovascular co-morbidities and events were assessed at baseline. Patients were then followed until death, migration out of the community, or through December 31, 2018. Results were compared to age and sex matched reference subjects without adrenal tumors and adjusted for tobacco use and BMI. Results: A total of 1,003 patients had adrenal adenomas with 136 (14%) NFAT, 86 (9%) MACS, and 781 (78%) AUCS. The median age of diagnosis was 63 years (range, 20-96) and 581 (58%) were women. At baseline, patients with adrenal adenomas were more likely to have hypertension (92% vs 81%, p<0.001), overweight/obesity (89% vs 82%, p<0.001), pre-diabetes/diabetes (82% vs 70%, p<0.001), dyslipidemia (89% vs 82%, p<0.001), and chronic kidney disease (11% vs 7%, p=0.004) than age and sex matched reference subjects. Myocardial infarctions (13% vs 8%, p <0.001), coronary intervention (9% vs 6%, p= 0.007), heart failure (12% vs 6%, p<0.001), peripheral vascular disease (26% vs 15%, p<0.001), and thromboembolic disease (7% vs 3%, p<0.001) were more prevalent in patients with adrenal adenomas, whereas overall survival was lower compared to reference subjects (60% vs 65%, p value = 0.013). Subgroup analysis (adjusted for age, sex, BMI, and smoking) demonstrated prevalence of cardiovascular events including peripheral vascular disease was highest in those with MACS (44.7%), followed by AUCS (40.1%), and then NFAT (36.6%), although differences between groups were not significant. Overall survival was lower in patients with MACS (62%) and AUCS (59%) compared to NFAT (71%), p<0.001. Conclusions: Adrenal adenomas are associated with significantly higher prevalence of cardiovascular risk factors and morbidity at the time of diagnosis and with increased morality during follow-up. Results are potentially related to abnormal cortisol secretion but are limited by suboptimal evaluation for hormone excess.


1990 ◽  
Vol 157 (5) ◽  
pp. 713-717 ◽  
Author(s):  
Isaac Schweitzer ◽  
George I. Szmukler ◽  
Kay P. Maguire ◽  
Leonard C. Harrison ◽  
Virginia Tuckwell ◽  
...  

When 20 female anorexic in-patients were investigated with weekly DSTs, 10 had an abnormal result at initial testing. There was no identifiable relationship between severity of weight loss and DST status; % ideal body weight was no different between suppressors and non-suppressors. There was no consistent relationship between normalisation of the DST response and weight gain. Depressive symptoms were common, with half the patients scoring 20 or more on the HRSD. Plasma ACTH concentrations before and after the DST were normal. There was a significant negative correlation between plasma dexamethasone concentrations and pre- and post-dexamethasone plasma Cortisol concentrations.


1987 ◽  
Vol 150 (4) ◽  
pp. 459-462 ◽  
Author(s):  
Alec Coppen ◽  
Maryse Metcalfe

The response to the dexamethasone suppression test (DST) was examined in 543 patients suffering from major depressive illness and 246 healthy controls, from 13 research centres, representing 12 different countries, in a World Health Organization Collaborative Study. In almost all the centres, the post-dexamethasone plasma Cortisol concentration was significantly higher in the patients than in the controls. Although there is variation between centres, this abnormal response to the DST was shown to be frequent in patients from widely different geographical areas.


2003 ◽  
Vol 88 (6) ◽  
pp. 2634-2643 ◽  
Author(s):  
Gregory A. Kaltsas ◽  
Andrea M. Isidori ◽  
Blerina P. Kola ◽  
Rob H. Skelly ◽  
Shern L. Chew ◽  
...  

We studied 211 hyperandrogenic women with respect to clinical presentation, basal androgen levels, and the degree of cortisol and androgen suppression during a 48-h low-dose (2 mg) dexamethasone-suppression test (LDDST) to exclude ovarian and adrenal tumors. In 42 women with elevated testosterone levels, 21 of whom failed to suppress testosterone during the LDDST, the response of serum androgen levels during a 4-wk administration of 7.5 mg prednisolone in a reverse circadian regimen was also assessed. These results were compared with an additional 17 patients with histologically proven androgen-secreting tumors. Clinical presentation alone was suggestive of a virilizing tumor in 70% of patients with tumors. Serum testosterone, although occasionally only marginally elevated, was the sole androgen that was elevated in every patient with a tumor. After the LDDST, none of the patients with tumors obtained either a greater than 40% reduction or normalization of the previously elevated testosterone levels, whereas 88% of patients with nontumorous hyperandrogenism showed either normalization or suppression of more than 40%. With one exception, all of the patients with nontumorous hyperandrogenism who showed inadequate suppression of testosterone during the LDDST, and were treated with prednisolone, normalized the previously elevated androgens after 1 month of administration. In summary, in women presenting with hyperandrogenism, lack of testosterone suppression during the LDDST is associated with 100% sensitivity and 88% specificity in distinguishing patients with ovarian and adrenal androgen-secreting tumors from patients with nontumorous hyperandrogenism in this small series. The LDDST is an easy to perform screening test that can also identify causes of hyperandrogenism due to altered glucocorticoid secretion.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Alejandro L Arregger ◽  
Liliana N Contreras ◽  
Estela M L Cardoso ◽  
María E Céspedes

Abstract The subclinical Cushing′s syndrome (SCS) is found in 20% of incidental adrenal tumors (AI). The overnight 1 mg oral dexamethasone suppression test (DST) with the measurement of circulating cortisol (F) is a sensitive method to rule out SCS. The assessment of salivary cortisol (SAF) as a surrogate of F became a non-invasive methodological advance. There are few data on the functional evaluation of AI through SAF in DST (SAFdex). The aim of this retrospective study was to investigate the utility of SAFdex for the detection of SCS in patients with AI. Subjects and Methods: 20 subjects with AI (7 male and 13 women; 65.0 ± 11.0 y/o; BMI: 26.5 ± 1.4) were studied. Sixteen had unilateral and 4 bilateral tumors (size: 10.0 - 90.0 mm; density (UH) was <10.0 in 17 cases and ≥ 10.0 in 3). They were not on drugs that may affect the HPA axis. Eight patients (1 male and 7 women; 20.0–60.0 y/o; BMI: 27.0 ± 3.0) with overt non ACTH dependent Cushing Syndrome (CS) were included as the reference group of active hypercortisolism. CS had unilateral adrenal tumors in 6 cases and bilateral in 2 (size: 11.0 -200.0 mm; density (UH) <10.0: n= 7 and >10.0: n=1).All subjects collected 24-hour urine for urinary free cortisol (UFC). After the urine collection, they obtained whole saliva samples at 23 h for cortisol (SAF23). Subsequently, they received 1 mg oral dexamethasone. The following day at 8 h, simultaneous blood (Fdex) and saliva (SAFdex) samples were obtained. F, SAF and UFC were determined by RIA and ACTH by IRMA. Reference values ​​from our laboratory (n= 100): UFC ≤90.0 µg / 24hs; ACTH: 10.0–50.0 pg / ml, SAF23: 0.5–3.8 nM / l; SAFdex: 0.5–2.0 nM; Fdex: 13.8–50.0 nM. Statistics were performed by Mann-Whitney and Spearman tests, p <0.05 was considered significant. In AI: ACTH 22.0 ± 11.0 pg /ml; UF:C 47.0 ± 20.0 µg / 24hs; SAF23: 1.5 ± 0.9 nM); SAFdex: 1.0 ± 0.5 nM and Fdex: 35.6 ± 10.0 nM were normal and significantly different from CS: 5.6±1.8 pg /ml; 391.0 ± 406.0 µg / 24hs; 20.0 ± 32.0 nM; 27.0 ± 24.0 nM and 674.0 ± 339.0 nM, respectively; p <0.05 in all cases. A positive and significant correlation was demonstrated between SAFdex and Fdex in AI (r = 0.830) and CS (r = 0.905); p <0.05 in both. Interestingly, a woman with overt CS and moderate signs of hypercortisolism, had normal SAF23 (1.5 nM) and UFC (76.0 µg / 24hs), while SAFdex (3.0 nM) and Fdex (69.0 nM) showed absence of suppression. Surgical resection of the adrenal tumor (an adrenocortical adenoma) and postoperative hypocorticism confirmed the diagnosis of CS. Conclusion: SCS was excluded in all AI. The dexamethasone suppression test using saliva as a diagnostic fluid was a sensitive and practical method to rule out hypercortisolism in these patients.


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